Hyperparathyroidism - parathryoid adenoma; Overactive parathyroid gland - parathyroid adenoma ... Parathyroid adenomas are the most common cause of hyperparathyroidism (overactive parathyroid glands), which leads to an increased ...
Debiec-Rychter, M; Van Valckenborgh, I; Van den Broeck, C; Hagemeijer, A; Van de Ven, W J; Kas, K; Van Damme, B; Voz, M L
Pleomorphic adenoma gene 1 (PLAG1), a zinc finger transcription factor gene, is consistently rearranged and overexpressed in human pleomorphic adenomas of the salivary glands with 8q12 translocations. In this report, we describe the immunohistochemical localization of PLAG1 protein in pleomorphic adenomas of the salivary gland and corresponding normal tissue, in relation to cytokeratin, vimentin, and BCL-2 expression. Normal salivary gland tissue was not immunoreactive for PLAG1. In primary pleomorphic adenomas, cells strongly immunoreactive for PLAG1 were detected in the outer layer of tubulo-ductal structures, which are thought to be the origin of cells with bi-directional, epithelial, and mesenchymal phenotypes. In contrast, epithelial cells with abundant cytokeratin in the inner tubulo-ductal structures only sporadically expressed PLAG1. BCL-2 immunoreactivity was found mainly in the cells surrounding the tubulo-ductal structures and in the solid undifferentiated cellular masses, within the areas that had moderate PLAG1 immunoreactivity. The variability of PLAG1 expression in neoplastic cells seemed to reflect the morphologic heterogeneity that correlated with the stage of differentiation of the tumor cells. Immunohistochemical/cytogenetic evaluation of two pleomorphic adenomas with t(3;8)(p21;q12) or t(5;8)(p13;q12) translocations demonstrated the clonal nature of immunophenotypically diverse cells. This finding confirms the theory that pleomorphic adenoma cells share a common single-cell origin, most likely from the epithelial progenitor basal duct cells.
Carditello, Antonio; Milone, Antonino; Paparo, Domenica; Anastasi, Giuliana; Mollo, Francesco; Stilo, Francesco
Adenomas of the rectum are frequently found during endoscopic examination. We report on our 30 years of experience with the treatment of tubulo-villous adenomas based on histotype. Between 1971 and 2001, 104 villous tumours of the rectum were treated surgically. The patients' average age was 65 years. These were sessile tumours in 69% of cases, pedunculated in 17.5% and flowing tumours in 13.5%. The mean tumour size was 3 cm. They were associated with colon cancer in 15% of cases and with polyadenoma in 10%. They were located in the rectum within 0 to 6 cm of the anal margin in half the cases. These tumours were treated by local excision in 74 cases and by wide excision in 30 cases. The malignant potential of the tumours was 30%, including 10% invasive malignancy. There were no surgical fatalities, but a 6% medical fatality rate was registered. There was a 20% complication rate related to the surgical technique. Twenty patients were lost to follow-up. Out of 84 villous tumours, monitored over a mean survival period of 6.5 years, there were 24 recurrences: 18 underwent endoscopic excision and in 6 cases a wide resection. The various tumour resection techniques and the operative indications of variable difficulty are presented. It would seem, at present, that total resection of the rectum with a colo-anal anastomosis is the best treatment for large flowing villous tumours occupying almost the entire rectum. Thorough preoperative examination and the mastering of various surgical procedures should allow the most suitable choice of treatment for each individual case.
Giuffrè, G; Barresi, G; Sturniolo, G C; Sarnelli, R; D'Incà, R; Tuccari, G
The immunohistochemical distribution pattern of metallothionein, a low molecular weight protein with strong affinity for divalent heavy metal ions, has been investigated in normal and neoplastic conditions of the large bowel. Utilizing a monoclonal mouse antibody the following formalin-fixed paraffin-embedded surgical or biopsy samples were studied: tubulo-villous adenomas (8 cases); adenocarcinomas with various degree of differentiation (85), nine of which were mucinous-type; synchronous tubular or tubulo-villous adenomas separate from carcinomas (30); transitional mucosa (45); metastases in lymph nodes (43); and distant metastases (45). Twenty biopsies from the right and left colon of 10 patients affected by irritable bowel syndrome were also analyzed. Normal colonic mucosa as well as transitional mucosa showed metallothionein immunopositivity in enterocytes at the luminal surface and crypts. Evident nuclear and cytoplasmic staining was encountered in tubulo-villous adenomas; the same reactivity was noted in the basal glandular component of colorectal carcinomas-synchronous adenomas, while less intense staining was noted in the apical villous portions. A variable metallothionein immunostaining was observed in adenocarcinomas (62.3%), in lymph node (55.8%) and distant hepatic (17.2%) and omental (43.8%) metastases, although it was not always concordant with that reported in the corresponding primary tumour. Whether the metallothionein positivity observed in normal and neoplastic cells is the result of expression of a stable form of the protein or an accumulation in the nucleus and cytoplasm remains to be clarified.
Well circumscribed areas consisting of cuboidal to columnar cells lining alveoli. The size is usually less than 5 mm in diameter. These lesions retain preexisting alveolar structure and tend to be multiple in existing mouse models. Absence of pronounced fibrovascular stroma, as well as more "plump" shape of epithelial cells, may be the reason for different appearance of mouse adenomas, as compared to their human counterparts. Differentiation between a small adenoma and focal hyperplasia can be very difficult. At the same time, no absolute criteria exist for distinguishing a large adenoma from a well-differentiated adenocarcinoma. Among features indicating benign character are a small size, and absence of vascular invasion. Well delineated demarcation and absence of lepidic growth are considered by some as indicators of a benign character. Bland character of nuclei is a main feature of human adenomas. By this criterion many mouse adenomas could be assigned to adenocarcinomas. However, unlike in humans, mouse tumors rarely metastasize during the time of their observation.
McNeil, P E
Acute tubulo-interstitial nephritis was diagnosed post mortem when a dog died four days after surgery for a femoral head resection. Possible causative factors associated with halothane anaesthesia, flunixin meglumine analgesia and prophylactic antibiotic therapy with trimethoprim-sulphadiazine are discussed. It is concluded that death was due to renal failure associated with tubulo-interstitial nephritis as a result of a combination of ischaemic and toxic events.
van Wessel, Steffi; Van Kerrebroeck, Helena; Van Bogaert, Valerie; Tummers, Philippe; Van den Broecke, Rudy
► An extremely rare neoplasm, especially in the absence of DES ► It's important to distinguish it from an adenocarcinoma from another location ► Little is known about the aetiology, several explanations have been postulated.
Ketabchi, S; Massi, D; Franchi, A; Vannucchi, P; Santucci, M
Middle ear adenoma (MEA) is a rare tumor postulated to take origin from the lining epithelium of the middle ear cavity. The authors report on a case of MEA arising in a 53-year old woman suffering from a sensation of fullness in her left ear, otalgia, and light left-sided hearing loss. Histopathologically, the lesion was composed of cuboidal and polygonal cells displaying a trabecular, tubulo-glandular, and solid pattern of growth. Immunohistochemically, neoplastic cells diffusely stained with anti-vimentin antibodies and were focally positive for chromogranin A, neuron-specific enolase, lysozyme, and cytokeratins AE1/AE3. The majority of tumor cells showed weak and diffuse staining with both anti-PP and anti-ACTH antibodies and intense positivity with anti-glucagon and anti Leu-7 antibodies. Ultrastructural investigation revealed both mucinous-glandular and neuroendocrine differentiation. The authors suggest that the appropriate terminology would be adeno-carcinoid or amphicrine tumor of the middle ear rather than "adenoma," a term that does not reflect its dual nature.
Sousa, Vítor; Pinto, Eugénia; Franca, Teresa; Carvalho, Lina
Adenomas of solitary gland type together with papillomas are the true benign tumours in or around the bronchial tree. Alveolar adenoma and papillary adenoma are more frequently observed in peripheral parenchime although this group of tumours is very rare and often incidentally diagnosed. Presenting usually as solitary nodules in adults after 45 years, are easily recognized because of distinct morphology but alveolar adenomas may be difficult to evaluate in frozen sections. Two cases of pleomorphic adenoma and alveolar adenoma are presented and a review of literature is made.
Jha, S; Kumar, S
Thyrotropin (TSH) secreting pituitary adenomas are a very rare cause of hyperthyroidism. They typically present with signs and symptoms of hyperthyroidism and rarely can be asymptomatic. TSH secreting tumors account for 1 percent of all pituitary adenoma. They are a rare cause of thyrotoxicosis in which adenomas completely or partially lose feedback regulation of thyroid hormones and lead to sustained stimulation of thyroid gland. The most definitive treatment of thyrotropin (TSH)-secreting pituitary adenomas is transsphenoidal removal of tumor after restoring euthyroidism. We report a case of pituitary adenoma associated with elevated serum free thyroid hormones and non-suppressed TSH levels.
Hofmann, W; Edel, H; Guder, W G
Determination of marker proteins like albumin and alpha 1-microglobulin allows to differentiate various types of proteinuria in kidney diseases. In the present communication we calculate the degree of tubulointerstitial involvement by quantitation of the tubular marker alpha 1-microglobulin in urine in relation to albuminuria. A mathematical relation between minimal tubular proteinuria with the degree of albumin excretion was observed. Cases forming this line did not exhibit interstitial fibrosis when analyzed histologically. In contrast most cases exhibiting higher excretion rates of the tubular marker showed various degrees of tubulointerstitial involvement. In order to differentiate interstitial contribution from overload tubular proteinuria in patients with an albumin excretion rate above 3000 mg/g creatinine alpha 1-microglobulin (measured) is suggested to be corrected by the "glomerular" component of alpha 1-microglobulin using the following equation: "tubulo-interstitial alpha 1-microglobulin" = alpha 1-microglobulin (measured) -4.7 exp (2.2 x 10(-4)) [albumin]. Alternatively the correction can be performed graphically. This procedure may be of considerable help in preventing misinterpretations of urinary protein patterns in patients with nephrotic proteinuria.
Initially, the distinction between "functional" and "non-functional" adenomas was a purely clinical notion. A "non-secreting" adenoma was not considered to cause acromegaly nor Cushing's syndrome nor amenorrhea-galactorrhea syndrome. The term "chromophobe adenoma" has been used since the advent Herlant tetrachrome. More recently immunocytochemistry methods have demonstrated that most of the "clinically non functional" adenomas (chromophobe with classical histology) are actually gonadotrophin secreting adenomas or gonadotroph adenomas. Due to progress in immunocytochemistry applied to operated adenomas, it is now known that gonadotroph tumors account for 15 to 20% of all pituitary adenomas. Gonadotroph adenomas are monoclonal but their pathogenesis, unlike somatotroph adenomas causing acromegaly and despite numerous molecular studies, remains unknown. Gonadotroph adenomas are most always discovered in patients presenting a pituitary syndrome (half to three-quarters consult for a visual field disorder). Pituitary imaging almost always demonstrates a macroadenoma: two-thirds of the macroadenomas are enclosed. Anterior pituitary insufficiency is much more frequent than gonad hyperstimulation whether testicular (macro-orchidia) or ovarian (ovarian hyperstimulation similar to that observed in ovulation induction). A careful analysis of hormone assay results shows that baseline concentrations of gonadotrophin or their free sub-units is elevated in 30 to 50% of cases (especially FSH in men, and the free a sub-unit in premenopausal women). Dynamic tests contribute little to diagnosis: the GnRH test is positive in 75 to 100% of cases, the TRH test in 60 to 70% for FSH (or alpha) and when there is already a baseline hypersecretion of FSH (or a) in 20 to 30% of the cases for the LH when the baseline LH concentration is high. The immunocytochemistry of gonadotroph adenomas is slightly different from that of other adenomas: generally, only 5 to 10% of the cells, grouped in
Ali, Syed Rizwan; Arrossi, Andrea Valeria; Mehta, Atul C.; Frye, Laura; Mazzone, Peter; Almeida, Francisco
Pleomorphic adenomas are the most common tumors of the salivary glands. Rarely, they occur as benign lesions in the lungs in both the central airways and the lung parenchyma. Herein, we present a case of a 60-year-old smoker who was incidentally found to have an endobronchial mass while undergoing evaluation for a lung nodule. During bronchoscopy, a smooth globular nodule was identified at the main carina and removed using electrocautery snare. Histopathology examination revealed this to be a pleomorphic adenoma. PMID:28031854
Glezer, Andrea; Jallad, Raquel S; Machado, Marcio C; Fragoso, Maria C; Bronstein, Marcello D
Infertility is frequent in patients harboring pituitary adenomas. The mechanisms involved include hypogonadism secondary to hormonal hypersecretion (prolactin, growth hormone and cortisol), stalk disconnection and pituitary damage. With the improvement of clinical and surgical treatment, pregnancy in women harboring pituitary adenomas turned into a reality. Pituitary hormonal hyper- and hyposecretion influences pregnancy outcomes, as well as pregnancy can interfere on pituitary tumors, especially in prolactinomas. We review literature about specific follow-up and management in pregnant women harboring prolactinomas, acromegaly, or Cushings disease and the impact of clinical and surgical treatment on each condition.
Maawy, Ali A; Oh, Deborah K; Bouvet, Michael
Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical exploration in patients with persistent primary hyperparathyroidism. A 43-year-old woman with no significant medical or family history presented with fatigue and was diagnosed with primary hyperparathyroidism; however, preoperative imaging including sestamibi scan and ultrasound was unable to identify the hyperfunctioning gland. She underwent a neck exploration and hemithyroidectomy and partial parathyroidectomy with failure of resolution of her disease. Subsequent work up including a CT of the neck demonstrated a 1.9 cm mass adjacent to the left submandibular gland. This was removed with postoperative normalisation of the patient's serum calcium and parathyroid hormone levels. PMID:25737222
RECOMMENDED TREATMENTS: The different therapeutic strategies proposed for pituitary adenomas are relatively well-known thanks to numerous studies evaluating their effect on outcome. Unfortunately, large comparative clinical trials are difficult to construct due to the small number of cases of this rare condition. Therapeutic recommendations are thus generally based on the opinion of recognized experts. MICROADENOMA: Small (< 10 mm) prolactin-secreting adenomas should be treated surgically, generally by transsphenoidal adenomectomy, or medically by dopaminergic agonists: bromocriptin, quinagolide or cabergolin (the two latter drugs are more effective and better tolerated than their parent compound bromocriptin). MACROADENOMA: The expected success rate for surgical treatment of macroadenomas is low and dopaminergic agonists is generally recommended (including cases with visual impairment since the effect can be very rapid). Prolactin levels can be lowered and tumor volume reduced (in > 70% of cases). ACROMEGALY: Surgery is the firs intention treatment for acromegaly. In case of unsuccessful surgery (the criteria for "cure" are much more strict in 1998 than previously), somatostatin analog and/or hypothalamo-hypophyseal radiotherapy are recommended. Slow release formulations of somatostatin analogs can now be given by monthly (octreotide LP) or biweekly (lanreotide LP) injections. CUSHING'S DISEASE: Cure can be achieved in > 80% of cases with surgery, the first intention treatment of choice. If surgery is unsuccessful, radiotherapy can be proposed associated with anticortisol drugs (mitotane), if needed, while waiting for the late effect of radiotherapy. CLINICALLY SILENT ADENOMAS: Non-functional adenomas should be operated. Some propose adjuvant radiotherapy in all cases and others only if residual tissue persists post-operatively.
Mezosi, Emese; Nemes, Orsolya
According to epidemiological studies, the prevalence of pituitary adenomas is 16.5% and the majority of them are "incidentalomas". The symptoms of pituitary disorders are often non-specific; disturbances of pituitary function, compression symptoms, hypophysis apoplexy or accidental findings may help the diagnosis. The hormonal evaluation of pituitary adenomas is different from the algorithm used in the disorders of peripheral endocrine organs. The first-line therapy of prolactinomas are the dopamine agonists, and the aims of the treatment are to normalize the prolactin level, restore fertility in child-bearing age, decrease tumor mass, save or improve the residual pituitary function and inhibit the relapse of the disease. The available dopamine agonists in Hungary are bromocriptine and quinagolide. In case of tumors with good therapeutic response, medical therapy can be withdrawn after 3-5 years; hyperprolactinemia will not recur in 2/3 of these patients. Neurosurgery is the primary therapy of GH-, ACTH-, TSH-producing and inactive adenomas. In the last decades, significant improvement has been reached in surgical procedures, resulting in low mortality rates. Acromegalic patients with unresectable tumors have a great benefit from somatostatin analog treatment. The growth hormone receptor antagonist pegvisomant is the newest modality for the treatment of acromegaly. The medical therapy of Cushing's disease is still based on the inhibition of steroid production. A new, promising somatostatin analog, pasireotide is evaluated in clinical trials. The rare TSH-producing tumor can respond to both dopamine agonist and somatostatin analog therapy. The application of conventional radiotherapy has decreased; radiotherapy is mainly used in the treatment of invasive, incurable or malignant tumors. Further studies are needed to elucidate the exact role of radiosurgery and fractionated stereotaxic irradiation in the treatment of pituitary tumors.
Sim, Da Woon; Oh, In Jae; Kim, Kyu Sik; Choi, Yoo Duk; Kwon, Yong Soo
Endobronchial pleomorphic adenoma is an extremely rare condition. A 32-year-old woman with exertional dyspnea and cough presented with a carinal mass on chest CT scan. The tumor was successfully removed by rigid bronchoscopy using argon plasma coagulation. Biopsy confirmed the diagnosis of pleomorphic adenoma.
Can, Nuray; Çelik, Mehmet; Bülbül, Buket Yilmaz; Süt, Necdet; Özyilmaz, Filiz; Aytürk, Semra; Güldiken, Sibel; Sarikaş, Nurtaç; Puyan, Fulya Öz; Yalta, Tülin Deniz; Kutlu, Ali Kemal
Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TERT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TERT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TERT expression is related to clinicopathological features of pituitary adenomas. The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. Nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TERT antibody was performed. Both the nuclear and cytoplasmic expression of TERT antibody was noted, and total combined TERT staining was evaluated according to nuclear and cytoplasmic stainings. TERT expression did not differ between neoplastic and nonneoplastic pituitary tissues. Neither total (combined nuclear and cytoplasmic) TERT nor nuclear TERT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TERT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). This study introduces the notion that immunohistochemical expression of TERT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TERT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TERT in pituitary adenomas.
Wehrmann, M; Bohle, A; Bogenschütz, O; Eissele, R; Freislederer, A; Ohlschlegel, C; Schumm, G; Batz, C; Gärtner, H V
A retrospective long-term study (average follow-up time 5.2 years) of 334 patients with idiopathic membranous glomerulonephritis (MGN) was carried out with the following results: 1) MGN was found to have a relatively good prognosis when all cases were considered together: 5-year kidney survival rate (KSR) -88%, and 10-year KSR -77%. 2) Univariate survivorship analysis showed the following morphological and clinical parameters to be associated with an increased risk of terminal renal insufficiency or death from renal disease: a) tubulo-interstitial changes; b) glomerular stage III as opposed to stages I and II; c) elevation of serum creatinine concentration at the time of the biopsy; d) arterial hypertension at the time of the biopsy. 3) Multivariate analysis showed that only tubulo-interstitial changes (interstitial fibrosis and/or acute renal failure) found at the time of the biopsy and their clinical correlate, serum creatinine concentration, were significant and therefore of definite prognostic importance. 4) Unsystematic therapy with steroids and/or cytostatic agents does not improve the long-term prognosis of MGN. 5) The cause of disease in the tubulo-interstitial system in MGN is discussed. Interstitial fibrosis is considered to develop possibly as a consequence of unresorbed interstitial edema which can develop during an episode of acute renal failure. Coexisting T-cell-mediated disease in the region of the intertubular capillaries is also considered as a possible factor in the development of interstitial fibrosis.
Ebner, Florian Heinrich; Hauser, Till K; Honegger, Juergen
The rare case of a patient with SIADH following pituitary adenoma apoplexy is reported. Since apoplexy did not exert any mass effect on surrounding structures, the patient was treated conservatively and the anterior pituitary gland insufficiency has been substituted adequately. Seven days after the apoplexy the patient again showed low serum-Na(+) levels despite cortisol substitution. Diagnosis of SIADH was made. It is essential to be aware of this rare syndrome in patients with pituitary adenoma apoplexy.
Kalimuthu, Sangeetha N; Chelliah, Adeline; Chetty, Runjan
It is well established that colorectal cancer develops from a series of precursor epithelial polyps, including tubular adenomas, villous/tubulovillous adenomas (VA/TVA), sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA). Of these, TSAs are least common and account for only 5% of all serrated polyps. TSAs are characterised by the presence of a “pinecone-like” architecture, granular eosinophilic cytoplasm, luminal serrations, ectopic crypt foci (ECF) and elongated, pencillate nuclei. However, the distinct slit-like luminal serrations, reminiscent of small bowel mucosa, appear to be the most unique and reproducible feature to distinguish TSAs from other polyps. There is a contention that TSAs are not inherently dysplastic and that the majority do not show cytological atypia. Two types of dysplasia are associated with TSA. Serrated dysplasia is less well recognised and less commonly encountered than adenomatous dysplasia. In addition, it is now becoming increasingly evident that TSAs can be admixed with HP, SSA and VA/TVA. At a genetic level, polyps may switch phenotype as they accumulate genetic changes, evolving from a serrated pathway to a more conventional one, which could be the basis for a spectrum theory starting out with a TSA with serration and ECF evolving into a TSA with conventional dysplasia and, eventually, to a well-developed conventional adenoma. Nevertheless, there is an exigency for future studies to provide further illumination and bridge the gaps in our present understanding. PMID:28035250
Taylor, J V; Thomas, M G; Kelly, S; Sutton, R
Villous adenoma confined to the distal appendix has not been previously reported in conjunction with acute apendicitis. The presence of an adenoma indicates a need for further investigation due to an association with neoplasia elsewhere.
Hattori, N; Imakado, S; Kikuchi, K; Murakami, T; Furue, M
We report a case of papillary tubular adenoma, arising on the knee joint. The overall histologic structure of the tumor is consistent with that of papillary tubular adenoma with slight interluminal papillary changes, but most of the tumor cells present vacuolization outlined by carcinoembryonic antigen staining, suggesting that this adenoma may have resulted from microlumen formation. This is, to our knowledge, the first reported case of a papillary tubular adenoma with marked tubular vacuolization.
Rabade, Nikhil R; Goel, Naina A
Pleomorphic adenoma is the most common epithelial neoplasm of lacrimal gland. A clear cell myoepithelial carcinoma arising in the background of pleomorphic adenoma is common in the salivary glands but very rare in the lacrimal glands. We report the case of a 27 year old man whose lacrimal gland pleomorphic adenoma recurred several times over a period of four years and ultimately evolved into a clear cell myoepithelial carcinoma ex pleomorphic adenoma.
TSH-secreting pituitary adenomas represent 0.5 to 1% of all pituitary adenomas. They are recognized with increasing frequency due to the measurement of TSH level in patients with hyperthyroidism, the ultra sensitive TSH assays and the improvement in pituitary imaging. Patients present mild or moderate signs of hyperthyroidism. Hormonal evaluation shows increased free thyroid hormone concentration with detectable, normal or increased serum TSH level, raising the differential diagnosis with pituitary resistance to thyroid hormone syndrome. Magnetic resonance imaging reveals pituitary adenomas in most patients. Transphenoidal surgery remains the treatment of choice in patients with TSH-secreting pituitary microadenomas, while long-acting somatostatin analogs seem to be an alternative medical treatment to surgery in patients with macroadenomas or invasive pituitary tumors.
Clinical and experimental data have indicated that heavy proteinuria in renal glomerular diseases is associated with the formation of tubulo-interstitial fibrosis and contributes to the progression of renal failure. Albumin in glomerular ultrafiltrate does not appear to cause this sequelae, rather than compounds that are associated with ultrafiltered plasma proteins. One such protein-bound factor could be insulin-like growth factor I (IGF-I). The present studies show that in nephrotic rats, IGF-I is ultrafiltered in conjunction with IGF-binding protein-2 and is present in proximal tubular fluid at 1.35 nM. Proximal tubular fluid from nephrotic rats autophosphorylates IGF-I receptors in cultured proximal tubular cells. Nephrotic, but not control, rat proximal tubular fluid increases the [3H]thymidine incorporation in cultured tubular cells, and neutralizing IGF-I-receptor antibodies partially inhibit this activity. Incubation of cultured proximal tubular cells with an extract that was prepared from nephrotic rat urine increases the secretion of collagen types I and IV. Secretion of the two collagens is in part ameliorated by neutralizing IGF-I-receptor antibody. In concert, these findings suggest that the IGF-I present in nephrotic rat tubular fluid is bioactive and may contribute to the development of tubulo-interstitial fibrosis in chronic nephrotic glomerular diseases. PMID:8690782
Barco Nebreda, Israel; Vidal, M Carmen; Fraile, Manel; Canales, Lydia; González, Clarisa; Giménez, Nuria; García-Fernández, Antonio
Lactating adenoma is an uncommon breast palpable lesion occurring in pregnancy or lactation. Although it is a benign condition, it often requires core biopsy or even surgery to exclude malignancy. As with other solid lesions in pregnancy and lactation, lactating adenoma needs an accurate evaluation in order to ensure its benign nature. Work-up must include both imaging and histologic findings. Ultrasound evaluation remains the first step in assessing the features of the lesion. Some authors consider magnetic resonance imaging as a useful tool in cases of inconclusive evaluation after ultrasound and histologic exam in an attempt to avoid surgery. Most lactating adenomas resolve spontaneously, whereas others persist or even increase in size and must be removed. The authors present a case of a 35-year-old woman at 6 months postpartum with a lactating adenoma in her right breast. After surgical removal, breastfeeding was perfectly continued within the next 24 hours, which highlights the fact that breast surgery is most often compatible with breastfeeding. © The Author(s) 2016.
Youssef, A Samy; Agazzi, Siviero; van Loveren, Harry R
Although the transsphenoidal approach is the preferred approach to the vast majority of pituitary tumors with or without suprasellar extension, the transcranial approach remains a vital part of the neurosurgical armamentarium for 1 to 4% of these tumors. The transcranial approach is effective when resection becomes necessary for a portion of a pituitary macroadenoma that is judged to be inaccessible from the transsphenoidal route because of isolation by a narrow waist at the diaphragma sellae, containment within the cavernous sinus lateral to the carotid artery, projection anteriorly onto the planum sphenoidale, or projection laterally into the middle fossa. The application of a transcranial approach in these circumstances may still be mitigated by response to prolactin inhibition of prolactinomas, the frequent lack of necessity to remove asymptomatic nonsecretory adenomas from the cavernous sinus, and the lack of evidence that sustained chemical cures can be reliably achieved by removal of secretory adenomas (adrenocorticotropic hormone, growth hormone) from the cavernous sinus. Cranial base surgical techniques have refined the surgical approach to pituitary adenomas but have had less effect on actual surgical indications than anticipated. Because application of the transcranial approach to pituitary adenomas is and should be rare in clinical practice, it is useful to standardize the technique to a default mode with which the surgical team is most experienced and, therefore, most comfortable. Our default mode for transcranial pituitary surgery is the frontotemporal-orbitozygomatic approach.
Kraas, Jonathan; Clark, Paige B; Perrier, Nancy D; Morton, Kathryn A
Approximately 5 to 10% of parathyroid adenomas are located within the thin, fibrous capsule of the thyroid gland. These subcapsular adenomas can complicate minimally invasive parathyroidectomy. The small incision used in this procedure limits the view of the surgical bed. Palpation is less sensitive when the adenoma is covered by the thyroid capsule. If a subcapsular parathyroid adenoma can be identified on preoperative parathyroid scintigraphy, nuclear medicine physicians can recommend exploration of the thyroid capsule early, leading to an easier, more efficient operation. The objective of this observational study was to identify the scintigraphic appearance of subcapsular parathyroid adenomas. A total of 109 patients with primary hyperparathyroidism underwent preoperative dual-phase Tc-99m sestamibi parathyroid scintigraphy at our tertiary care center from October 2002 to March 2004. Tc-99m pertechnetate was used as a supplemental technique when deemed necessary for optimal interpretation. Retrospective chart review identified 16 surgically proved subcapsular parathyroid adenomas. Parathyroid scintigraphy was reviewed. Subcapsular parathyroid adenomas tend to conform to the expected shape of the thyroid gland. In this small series, subcapsular parathyroid adenomas followed 1 of 3 patterns on lateral images: (1) focal convex distortion of the posterior wall of the thyroid, (2) polar lentiform configuration, and (3) compression of the posterior thyroid parenchyma. Subcapsular parathyroid adenomas often have a distinct appearance on scintigraphy. Preoperative identification of this type of parathyroid adenoma can direct a subcapsular surgical approach, optimizing the efficiency of the minimally invasive parathyroidectomy.
Kissiedu, Juliana O; Prayson, Richard A
We report a case of a 60-year-old man who presented with weight gain, headaches, dizziness, erectile dysfunction and decreased libido. He was found to have elevated adrenocorticotropic hormone (ACTH) and prolactin serum levels. The imaging studies revealed a 1.4 cm sella/suprasellar mass which was compressing the optic chiasm. Histologic slides of the lesion showed a pituitary adenoma, marked by a proliferation of biphenotypic appearing cells, associated with a gangliocytoma, and marked by a proliferation of atypical appearing neuronal cells arranged against a glial-appearing background. Pituitary adenoma-gangliocytomas are benign combination tumors that rarely occur in the sellar region. Adenomas in this setting are sometimes functional, and rare patients with mixed adenomas (adenomas secreting more than one hormone) have been reported. To our knowledge, there has been only one other report of a combined ACTH and prolactin-producing adenoma with gangliocytoma, reported in a patient who also had acromegaly. In our patient, the immunohistochemical stains demonstrated that the bulk of the adenoma cells stained with prolactin antibody, and scattered clusters of cells within the adenoma stained positively for ACTH. The adenoma did not stain with antibodies to any of the other anterior pituitary hormones. Postoperatively, the elevated prolactin and ACTH levels returned to normal levels and there was no evidence of residual tumor. Adequate sampling and immunohistochemistry are important in rendering a correct diagnosis and in identifying the hormone status of mixed adenoma-gangliocytomas.
Calderwood, Audrey H; Lasser, Karen E; Roy, Hemant K
AIM To review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer (CRC)]. METHODS We performed a literature search using the National Library of Medicine through PubMed from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms (colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words (surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined non-advanced adenomas as 1-2 adenomas each < 10 mm in size and advanced adenomas as any adenoma ≥ 10 mm size or with > 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC. RESULTS Our search strategy identified 592 candidate articles of which 8 met inclusion criteria and were relevant for assessment of histology (low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma. CONCLUSION Data on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification. PMID:28035253
Karaçavuş, Seyhan; Kula, Mustafa; Cihan Karaca, Züleyha; Ünlühızarcı, Kürşad; Tutuş, Ahmet; Bayram, Fahri; Çoban, Ganime
The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB) and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive Conflict of interest:None declared. PMID:23487397
Dopamine agonists are able to restore ovulatory cycles in 80-90% of hyperprolactinemic patients and to reduce tumoral volume (often dramatically) in 80% of macroprolactinomas. Their side-effects will be reduced with the use of parenteral forms or new agonists currently in preparation. Somatostatin analogues administered either subcutaneously by three daily injections (octreotide) or intramusculary with a long-acting formulation every 10-15 days (lanreotide) are able to "normalize" GH levels in 70% of acromegalic patients and to shrink tumor in half of the patients. Side effects are generally minor but an increased incidence of gallstones has been reported. These somatostatin analogs are also very effective in the treatment of TSH-secreting adenomas. Medical treatment of other pituitary adenomas is much more disappointing.
Shi, T.; Farrell, M.A.; Kaufmann, J.C.
Eight years after radiation therapy (5000 rads of 60Co) for a pituitary adenoma, a patient developed a sellar fibrosarcoma. The tumor had an aggressive growth pattern: it infiltrated the optic nerve, sphenoidal air sinus, hypothalamus, and both cavernous sinuses, where compression of the left internal carotid artery resulted in a massive hemispheric infarction. Surgery was ineffective in arresting rapid growth of the lesion; death occurring 5 months after onset of symptoms.
Mortensen, L S; Rungby, J
Very little is known about the pathogenesis of tuberous sclerosis. Over the past 10 years, however, increasing numbers of reports on adenomatous diseases in association with tuberous sclerosis have been published. A case of hypercalcaemia and parathyroid adenoma in association with tuberous sclerosis is presented, of which there has been one such report published previously. This association might be another manifestation of this complex disease: it is therefore recommended that plasma calcium concentrations should be measured in such patients. PMID:1752991
Sharma, Yogesh; Maria, Anisha; Chhabria, Amit
Pleomorphic adenoma (PA) is the most common salivary gland tumor, accounting for about 40–70% of all major and minor salivary gland tumors. The commonest sites for intraoral PA are palate, buccal mucosa and lips. Palatal PA presents clinically as a painless, slow-growing mass found on posterior lateral aspect. The aim of this article is to present a case of palatal PA, which was treated successfully by surgical excision. PMID:22639506
Küçük, Ulkü; Tan, Serdar
Pleomorphic adenoma is the most common neoplasm of the salivary glands and is most commonly located in the parotis followed by the submandibular glands. Its localization in the minor salivary glands is mostly reported in the palate. Few publications report pleomorphic adenoma cases located in the lip. We present a 35-year-old male patient with a pleomorphic adenoma located in the upper lip.
Sajid, Muhammad; Rehman, Sajid; Misbah, Junaid
Salivary gland tumours are a relatively rare entity. Pleomorphic adenoma is the most common amongst these, comprising 60 - 70% of all parotid tumours. Pleomorphic adenomas are benign and tend to increase in size slowly. Here we are presenting a case of giant pleomorphic adenoma of the parotid, being the largest in size to be excised in Pakistan in recorded literature measuring 24 x 22 x 12 cm and weighing 1.8 kgs. Superficial parotidectomy was done with an excellent cosmetic outcome.
Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A
Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively.
Colorectal Adenoma With Mild Dysplasia; Colorectal Adenoma With Severe Dysplasia; Colorectal Adenomatous Polyp; Colorectal Low Grade Intraepithelial Neoplasia; Colorectal High Grade Intraepithelial Neoplasia
Kim, Joo Pyung; Kim, Sung Bum; Lim, Young Jin
Cause of pituitary apoplexy has been known as hemorrhage, hemorrhagic infarction or infarction of pituitary adenoma or adjacent tissues of pituitary gland. However, pituitary apoplexy caused by pure infarction of pituitary adenoma has been rarely reported. Here, we present the two cases pituitary apoplexies caused by pituitary adenoma infarction that were confirmed by transsphenoidal approach (TSA) and pathologic reports. Pathologic report of first case revealed total tumor infarction of a nonfunctioning pituitary macroadenoma and second case partial tumor infarction of ACTH secreting pituitary macroadenoma. Patients with pituitary apoplexy which was caused by pituitary adenoma infarction unrelated to hemorrhage or hemorrhagic infarction showed good response to TSA treatment. Further study on the predisposing factors of pituitary apoplexy and the mechanism of infarction in pituitary adenoma is necessary. PMID:19096606
Kim, Joo Pyung; Park, Bong Jin; Kim, Sung Bum; Lim, Young Jin
Cause of pituitary apoplexy has been known as hemorrhage, hemorrhagic infarction or infarction of pituitary adenoma or adjacent tissues of pituitary gland. However, pituitary apoplexy caused by pure infarction of pituitary adenoma has been rarely reported. Here, we present the two cases pituitary apoplexies caused by pituitary adenoma infarction that were confirmed by transsphenoidal approach (TSA) and pathologic reports. Pathologic report of first case revealed total tumor infarction of a nonfunctioning pituitary macroadenoma and second case partial tumor infarction of ACTH secreting pituitary macroadenoma. Patients with pituitary apoplexy which was caused by pituitary adenoma infarction unrelated to hemorrhage or hemorrhagic infarction showed good response to TSA treatment. Further study on the predisposing factors of pituitary apoplexy and the mechanism of infarction in pituitary adenoma is necessary.
During the last three decades liver cell adenoma and liver cell adenomatosis have emerged as new clinical entities in hepato-logical practice due to the widespread use of oral contraceptives and increased imaging of the liver. On review of published series there is evidence that 10% of liver cell adenomas progress to hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision biopsy, and the preferred treatment modality is resection of the liver cell adenoma to prevent bleeding and malignant transformation. In liver cell adenomatosis, the association with oral contraceptive use is not as high as in solitary liver cell adenomas. The risk of malignant transformation is not increased compared with solitary liver cell adenomas. Treatment consists of close monitoring and imaging, resection of superficially located, large (>4 cm) or growing liver cell adenomas. Liver transplantation is the last resort in case of substantive concern about malignant transformation or for large, painful adenomas in liver cell adenomatosis after treatment attempts by liver resection. PMID:18333188
Terzi, F; Burtin, M; Hekmati, M; Federici, P; Grimber, G; Briand, P; Friedlander, G
The role of EGF in the evolution of renal lesions after injury is still controversial. To determine whether the EGF expression is beneficial or detrimental, we generated transgenic mice expressing a COOH-terminal-truncated EGF-R under the control of the kidney-specific type 1 gamma-glutamyl transpeptidase promoter. As expected, the transgene was expressed exclusively at the basolateral membrane of proximal tubular cells. Under basal conditions, transgenic mice showed normal renal morphology and function. Infusion of EGF to transgenic animals revealed that the mutant receptor behaved in a dominant-negative manner and prevented EGF-signaled EGF-R autophosphorylation. We next evaluated the impact of transgene expression on the development of renal lesions in two models of renal injury. After 75% reduction of renal mass, tubular dilations were less severe in transgenic mice than in wild-type animals. After prolonged renal ischemia, tubular atrophy and interstitial fibrosis were reduced in transgenic mice as compared with wild-type mice. The beneficial effect of the transgene included a reduction of tubular cell proliferation, interstitial collagen accumulation, and mononuclear cell infiltration. In conclusion, functional inactivation of the EGF-R in renal proximal tubular cells reduced tubulo-interstitial lesions after renal injury. These data suggest that blocking the EGF pathway may be a therapeutic strategy to reduce the progression of chronic renal failure.
Scelzi, Sabino; Giubilei, Gianluca; Bartoletti, Riccardo; Di Loro, Filippo; Mondaini, Nicola; Crisci, Alfonso
Nephrogenic adenoma is an infrequent benign lesion of the urinary system that occurs in patients with a history of genitourinary surgery, stone disease, trauma, chronic urinary tract infection, or renal transplantation. We report the first case of nephrogenic adenoma of the bladder in a 53-year-old man with a 5-year history of ibuprofen abuse for chronic arthritis. We stress the importance of investigating the analgesic abuser for nephrogenic adenoma if microhematuria and/or irritative lower urinary tract symptoms are present.
Galland, Françoise; Chanson, Philippe
Pituitary adenomas are benign tumors that can be classified according to the type of hormone they produce, immunocytochemical characteristics (which generally confirm the clinical classification) or, as proposed by WHO in 2004, specific differentiation markers of the various ligneages. The pathophysiology of pituitary adenomas is largely unknown. Although a clonal origin is very likely, no univocal molecular abnormality (except for gsp mutations, found in 40% of somatotropic adenomas) has yet been found. Studies of cell cycle proteins, growth factors and oncogenes are beginning to shed light on the complex underlying mechanisms.
Lee, Chang Geun; Hahn, Suk Jae; Song, Min Keun; Lee, Jun Kyu; Kim, Jae Hak; Lim, Yun Jeong; Koh, Moon-Soo; Lee, Jin Ho; Kang, Hyoun Woo
Although epidemiologic and animal studies suggest a vegetarian diet protects against the development of colorectal cancer, the relationship between vegetarian diet and incidence of colorectal adenoma is not yet conclusive, especially for Asians. The purpose of this study was to examine the protective effect of a vegetarian diet against colorectal adenoma and advanced adenoma. This cross-sectional study compared the prevalence of colorectal adenoma among Buddhist priests, who are obligatory vegetarians, with that among age and sex-matched controls. All the subjects underwent health checkups in a health-promotion center in Korea. Colorectal adenoma and advanced adenoma were both more prevalent in the general population group than in the Buddhist priest group (25.2 vs. 17.9 %, 6.7 vs. 2.0 %). However, the prevalence of metabolic syndrome, high body mass index, and waist circumference were higher in the Buddhist priest group. According to univariate analysis, non-vegetarian diet (general population) significantly increased the prevalence of colorectal adenoma and advanced adenoma compared with a vegetarian diet (Buddhist priests) (OR 1.54, 95 % CI 1.08-2.21, P = 0.018; OR 3.60, 95 % CI 1.53-8.48, P = 0.003). In a conditional regression analysis model, non-vegetarian diet was also a significant risk factor for colorectal adenoma and advanced adenoma (OR 1.52, 95 % CI 0.75-2.07, P = 0.043; OR 2.94, CI 0.97-7.18, P = 0.036). Vegetarianism may be effective in preventing both colorectal adenoma and advanced adenoma in Asians.
Pokhrel, S M; Badu, B P; Lavaju, P; Shrestha, B G; Pant, A R; Agarwal, M
The pleomorphic adenoma of lacrimal gland presents as a painless, progressive, slowly growing supero-temporal swelling with variable proptosis. This tumor is usually found in adults and extremely rare in teenage. We report a case of a 15-year-old boy with pleomorphic adenoma of lacrimal gland which mimicked pseudotumor of orbit due to its presentation as an orbital inflammatory disease and the age distribution. Neuroimaging also suggested pseudotumor and oral steroid was started. But, there was no improvement on steroids and ultrasound guided Fine Needle Aspiration Cytology (FNAC) was performed which suggested Pleomorphic adenoma of the lacrimal gland. En-bloc excision of the mass through antero-lateral orbitotomy was done with satisfactory final outcome The histopathological evaluation was consistent with pleomorphic adenoma of the lacrimal gland.
Caimari, Francisca; Korbonits, Márta
Recently, a number of novel genetic alterations have been identified that predispose individuals to pituitary adenomas. Clinically relevant pituitary adenomas are relatively common, present in 0.1% of the general population. They are mostly benign monoclonal neoplasms that arise from any of the five hormone-secreting cell types of the anterior lobe of the pituitary gland, and cause disease due to hormonal alterations and local space-occupying effects. The pathomechanism of pituitary adenomas includes alterations in cell-cycle regulation and growth factor signaling, which are mostly due to epigenetic changes; somatic and especially germline mutations occur more rarely. A significant proportion of growth hormone- and adrenocorticotrophin-secreting adenomas have activating somatic mutations in the GNAS and USP8 genes, respectively. Rarely, germline mutations predispose to pituitary tumorigenesis, often in a familial setting. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and McCune-Albright syndrome. Pituitary tumors have also been described in association with neurofibromatosis type 1, DICER1 syndrome, and SDHx mutations. Pituitary adenomas with no other associated tumors have been described as familial isolated pituitary adenomas. Patients with AIP or GPR101 mutations often present with pituitary gigantism either in a familial or simplex setting. GNAS and GPR101 mutations that arise in early embryonic age can lead to somatic mosaicism involving the pituitary gland and resulting in growth hormone excess. Senescence has been suggested as the key mechanism protecting pituitary adenomas turning malignant in the overwhelming majority of cases. Here we briefly summarize the genetic background of pituitary adenomas, with an emphasis on the recent developments in this field. Clin Cancer Res; 22(20); 5030-42. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS
Oldfield, Edward H; Merrill, Marsha J
Pituitary adenomas occasionally undergo infarction, apoplexy, which often destroys much of the tumor. It is well known that apoplexy can be precipitated by several acute factors, including cardiac surgery, other types of surgery, trauma, insulin infusion, and stimulation with administration of hypothalamic releasing factors. The prior focus on mechanisms underlying pituitary apoplexy has been on these acute events. Less attention has been given to the endogenous features of pituitary tumors that make them susceptible to spontaneous infarction, despite that most pituitary apoplexy occurs in the absence of a recognized precipitating event. The authors examine intrinsic features of pituitary adenomas that render them vulnerable to apoplexy-features such as high metabolic demand, paucity of angiogenesis, and sparse vascularity, qualities that have previously not been linked with apoplexy-and argue that it is these features of adenomas that underlie their susceptibility to spontaneous infarction. The sensitivity of freshly cultured pituitary adenomas to hypoglycemia is assessed. Adenomas have high metabolic demand, limited angiogenesis, and reduced vessel density compared with the normal gland. Pituitary adenoma cells do not survive in the presence of reduced or absent concentrations of glucose. The authors propose that the frequent ischemic infarction of pituitary adenomas is the product of intrinsic features of these tumors. These endogenous qualities create a tenuous balance between high metabolic demand and marginal tissue perfusion. Thus, the tumor is vulnerable to spontaneous infarction or to acute ischemia by any event that acutely alters the balance between tumor perfusion and tumor metabolism, events such as acute systemic hypotension, abruptly decreased supply of nutrients, hypoglycemia with insulin administration, or increase in the tumor's metabolic demand due to administration of hypothalamic releasing factors. It may be possible to take advantage of these
De Kerangal, X; Poirrier, P; Soulard, R; Dot, J M; Ségneuric, J B; L'Her, P; Jancovici, R; Saint-Blancart, P
We report a new case of pleomorphous adenoma of the submaxillary glands with multiple lung metastases. Histological proof was obtained on the thoracoscopic surgical specimen. Clinically, this benign tumor presents as a malignant tumor. Diagnosis has been a subject of debate; surgical resection is indicated. Diagnosis is achieved by elimination in a patient with one or several nodules occurring in a context of recurrent pleomorphous adenoma.
Kajiya, Hanako; Takei, Mao; Egashira, Noboru; Tobita, Maya; Takekoshi, Susumu; Teramoto, Akira
This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology. PMID:18688636
Voorham, Quirinus J. M.; Carvalho, Beatriz; Spiertz, Angela J.; Claes, Bart; Mongera, Sandra; van Grieken, Nicole C. T.; Grabsch, Heike; Kliment, Martin; Rembacken, Bjorn; van de Wiel, Mark A.; Quirke, Philip; Mulder, Chris J. J.; Lambrechts, Diether; van Engeland, Manon; Meijer, Gerrit A.
Background Flat adenomas are a subgroup of colorectal adenomas that have been associated with a distinct biology and a more aggressive clinical behavior compared to their polypoid counterparts. In the present study, we aimed to compare the mutation spectrum of 14 cancer genes, between these two phenotypes. Methods A consecutive series of 106 flat and 93 polypoid adenomas was analyzed retrospectively for frequently occurring mutations in “hot spot” regions of KRAS, BRAF, PIK3CA and NRAS, as well as selected mutations in CTNNB1 (β-catenin), EGFR, FBXW7 (CDC4), PTEN, STK11, MAP2K4, SMAD4, PIK3R1 and PDGFRA using a high-throughput genotyping technique. Additionally, APC was analyzed using direct sequencing. Results APC mutations were more frequent in polypoid adenomas compared to flat adenomas (48.5% versus 30.3%, respectively, p = 0.02). Mutations in KRAS, BRAF, NRAS, FBXW7 and CTNNB1 showed similar frequencies in both phenotypes. Between the different subtypes of flat adenomas (0-IIa, LST-F and LST-G) no differences were observed for any of the investigated genes. Conclusion The lower APC mutation rate in flat adenomas compared to polypoid adenomas suggests that disruption of the Wnt-pathway may occur via different mechanisms in these two phenotypes. Furthermore, in contrast to previous observations our results in this large well-defined sample set indicate that there is no significant association between the different morphological phenotypes and mutations in key genes of the RAS-RAF-MAPK pathway. PMID:22848674
Morita, Ken; Nakamura, Fumihiko; Kamikubo, Yasuhiko; Mizuno, Naoaki; Miyauchi, Masashi; Yamamoto, Go; Nannya, Yasuhito; Ichikawa, Motoshi; Kurokawa, Mineo
Lymphoma occurring in the pituitary gland is an exceedingly infrequent event. Here, we describe a case of pituitary lymphoma complicating recurrent pituitary adenoma. A 56-year-old male with a history of pituitary adenoma was diagnosed with diffuse large B-cell lymphoma (DLBCL) of the left ocular adnexa, which was successfully treated by standard chemotherapy and local radiotherapy. Eight months later, he complained of diplopia and bitemporal hemianopia. Brain magnetic resonance imaging detected a suprasellar tumor. Transsphenoidal biopsy of the mass was performed, and histopathological examination revealed DLBCL admixed with pituitary adenoma. On a review of the literature, we found that pituitary lymphoma developing within adenoma is a recurrent phenomenon. The composite tumor is likely to be characterized by suprasellar involvement and presentation of visual disturbances. Moreover, in the present case, the suprasellar tumor remained visible after autologous peripheral stem cell transplant, likely due to the residual pituitary adenoma. We therefore recommend that refractory pituitary lymphoma should be vigorously biopsied in search of possibly underlying adenoma.
Park, Yeong Mi; Cho, Chang Ho; Kim, Sung Hi; Lee, Jung Eun
Colorectal cancer is the third most common cancer in Korea. Because colorectal adenoma is a precursor lesion of colorectal cancer, primary prevention of colorectal adenomas may be important for reducing morbidity and mortality from the disease. The aim of this study is to examine the association of alcohol consumption and cigarette smoking in relation with colorectal adenoma in a cross-sectional study of Korean adults. A total of 366 participants who underwent colonoscopy were included (113 cases and 255 controls) in this study. Information on alcohol intake and cigarette smoking was collected from structured questionnaires. The odds ratio (ORs) and 95% confidence intervals (CIs) were calculated using the multivariate logistic regression models. Alcohol intake was associated with a higher prevalence of colorectal adenoma in men; compared to non-drinkers, ORs (95% CIs) were 11.49 (2.55-51.89) for 10-20 g/day of alcohol intake and 14.15 (3.31-60.59) for â 20 g/day of alcohol intake (P for trend = 0.003). There was a weaker association of alcohol intake for women than men; however, there was a suggestive increase in the prevalence of colorectal cancer in women. Cigarette smoking was not associated with colorectal adenoma, but we cannot rule out the possibility that this was due to low statistical power. Our study provides evidence to suggest that alcohol intake may contribute to colorectal adenoma in the Korean population. Our study results demonstrate that a larger epidemiologic study is needed.
Abulí, Anna; Castells, Antoni; Bujanda, Luis; Lozano, Juan José; Bessa, Xavier; Hernández, Cristina; Álvarez-Urturi, Cristina; Pellisé, Maria; Esteban-Jurado, Clara; Hijona, Elizabeth; Burón, Andrea; Macià, Francesc; Grau, Jaume; Guayta, Rafael; Castellví-Bel, Sergi; Andreu, Montserrat
Common low-penetrance genetic variants have been consistently associated with colorectal cancer risk. To determine if these genetic variants are associated also with adenoma susceptibility and may improve selection of patients with increased risk for advanced adenomas and/or multiplicity (≥ 3 adenomas). We selected 1,326 patients with increased risk for advanced adenomas and/or multiplicity and 1,252 controls with normal colonoscopy from population-based colorectal cancer screening programs. We conducted a case-control association study analyzing 30 colorectal cancer susceptibility variants in order to investigate the contribution of these variants to the development of subsequent advanced neoplasia and/or multiplicity. We found that 14 of the analyzed genetic variants showed a statistically significant association with advanced adenomas and/or multiplicity: the probability of developing these lesions increased with the number of risk alleles reaching a 2.3-fold risk increment in individuals with ≥ 17 risk alleles. Nearly half of the genetic variants associated with colorectal cancer risk are also related to advanced adenoma and/or multiplicity predisposition. Assessing the number of risk alleles in individuals within colorectal cancer screening programs may help to identify better a subgroup with increased risk for advanced neoplasia and/or multiplicity in the general population.
Bolar, Nikhita Ajit; Golzio, Christelle; Živná, Martina; Hayot, Gaëlle; Van Hemelrijk, Christine; Schepers, Dorien; Vandeweyer, Geert; Hoischen, Alexander; Huyghe, Jeroen R; Raes, Ann; Matthys, Erve; Sys, Emiel; Azou, Myriam; Gubler, Marie-Claire; Praet, Marleen; Van Camp, Guy; McFadden, Kelsey; Pediaditakis, Igor; Přistoupilová, Anna; Hodaňová, Kateřina; Vyleťal, Petr; Hartmannová, Hana; Stránecký, Viktor; Hůlková, Helena; Barešová, Veronika; Jedličková, Ivana; Sovová, Jana; Hnízda, Aleš; Kidd, Kendrah; Bleyer, Anthony J; Spong, Richard S; Vande Walle, Johan; Mortier, Geert; Brunner, Han; Van Laer, Lut; Kmoch, Stanislav; Katsanis, Nicholas; Loeys, Bart L
Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) encompasses a group of disorders characterized by renal tubular and interstitial abnormalities, leading to slow progressive loss of kidney function requiring dialysis and kidney transplantation. Mutations in UMOD, MUC1, and REN are responsible for many, but not all, cases of ADTKD. We report on two families with ADTKD and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. Ultrasound and kidney biopsy revealed small dysplastic kidneys with cysts and tubular atrophy with secondary glomerular sclerosis, respectively. Exclusion of known ADTKD genes coupled with linkage analysis, whole-exome sequencing, and targeted re-sequencing identified heterozygous missense variants in SEC61A1-c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly)-both affecting functionally important and conserved residues in SEC61. Both transiently expressed SEC6A1A variants are delocalized to the Golgi, a finding confirmed in a renal biopsy from an affected individual. Suppression or CRISPR-mediated deletions of sec61al2 in zebrafish embryos induced convolution defects of the pronephric tubules but not the pronephric ducts, consistent with the tubular atrophy observed in the affected individuals. Human mRNA encoding either of the two pathogenic alleles failed to rescue this phenotype as opposed to a complete rescue by human wild-type mRNA. Taken together, these findings provide a mechanism by which mutations in SEC61A1 lead to an autosomal-dominant syndromic form of progressive chronic kidney disease. We highlight protein translocation defects across the endoplasmic reticulum membrane, the principal role of the SEC61 complex, as a contributory pathogenic mechanism for ADTKD.
Fesenko, Irina; Franklin, Danielle; Garnett, Paul; Bass, Paul; Campbell, Sara; Hardyman, Michelle; Wilson, David; Hanley, Neil; Collins, Jane
The kidney has an intrinsic ability to repair itself when injured. Epithelial cells of distal tubules may participate in regeneration. Stem cell marker, TRA-1-60 is linked to pluripotency in human embryonic stem cells and is lost upon differentiation. TRA-1-60 expression was mapped and quantified in serial sections of human foetal, adult and diseased kidneys. In 8- to 10-week human foetal kidney, the epitope was abundantly expressed on ureteric bud and structures derived therefrom including collecting duct epithelium. In adult kidney inner medulla/papilla, comparisons with reactivity to epithelial membrane antigen, aquaporin-2 and Tamm-Horsfall protein, confirmed extensive expression of TRA-1-60 in cells lining collecting ducts and thin limb of the loop of Henle, which may be significant since the papillae were proposed to harbour slow cycling cells involved in kidney homeostasis and repair. In the outer medulla and cortex there was rare, sporadic expression in tubular cells of the collecting ducts and nephron, with positive cells confined to the thin limb and thick ascending limb and distal convoluted tubules. Remarkably, in cortex displaying tubulo-interstitial injury, there was a dramatic increase in number of TRA-1-60 expressing individual cells and in small groups of cells in distal tubules. Dual staining showed that TRA-1-60 positive cells co-expressed Pax-2 and Ki-67, markers of tubular regeneration. Given the localization in foetal kidney and the distribution patterns in adults, it is tempting to speculate that TRA-1-60 may identify a population of cells contributing to repair of distal tubules in adult kidney.
The kidney has an intrinsic ability to repair itself when injured. Epithelial cells of distal tubules may participate in regeneration. Stem cell marker, TRA-1-60 is linked to pluripotency in human embryonic stem cells and is lost upon differentiation. TRA-1-60 expression was mapped and quantified in serial sections of human foetal, adult and diseased kidneys. In 8- to 10-week human foetal kidney, the epitope was abundantly expressed on ureteric bud and structures derived therefrom including collecting duct epithelium. In adult kidney inner medulla/papilla, comparisons with reactivity to epithelial membrane antigen, aquaporin-2 and Tamm–Horsfall protein, confirmed extensive expression of TRA-1-60 in cells lining collecting ducts and thin limb of the loop of Henle, which may be significant since the papillae were proposed to harbour slow cycling cells involved in kidney homeostasis and repair. In the outer medulla and cortex there was rare, sporadic expression in tubular cells of the collecting ducts and nephron, with positive cells confined to the thin limb and thick ascending limb and distal convoluted tubules. Remarkably, in cortex displaying tubulo-interstitial injury, there was a dramatic increase in number of TRA-1-60 expressing individual cells and in small groups of cells in distal tubules. Dual staining showed that TRA-1-60 positive cells co-expressed Pax-2 and Ki-67, markers of tubular regeneration. Given the localization in foetal kidney and the distribution patterns in adults, it is tempting to speculate that TRA-1-60 may identify a population of cells contributing to repair of distal tubules in adult kidney. PMID:20853169
Dikmen, Kursat; Bostanci, Hasan; Yildirim, Ali Cihat; Sakrak, Omer; Kerem, Mustafa
Serous cystadenomas are rare tumors comprising 1-2% of exocrine pancreas tumors. They are mostly known as benign conditions but malign transformation as serous cystadenocarcinoma is also reported. It is usually seen in females. Non-specific symptoms, such as abdominal pain or symptoms due to mass affect, are usually seen. A 64-year old female patient was investigated for abdominal pain. Physical and laboratory findings were normal. Abdomen ultrasonography confirmed an 11×9.5 cm solid cystic lesion and abdomen computed tomography scan confirmed a 12×11 cm lobulated cystic solid lesion which had central cystic necrotic areas extending from liver hilus inferiorly. Fine needle biopsy confirmed benign cytology and trucut biopsy of the pancreatic mass reported chronic inflamation. Nevertheless, this mass could have malignant contents and transformation potential. A laparatomy was decided due to patient's symptoms and mass effect. Due to vascular invasion of the tumor, Whipple procedure was performed. The pathology report confirmed serous microcystic adenoma. These rare tumors are usually benign but pre-operative malignity criterias are not identified. There are few differential diagnostic tools for excluding malignity. We suggest surgical resection as best treatment approach for selected cases.
Azizi, Ghobad; Piper, Kelé; Keller, James M; Mayo, Michelle L; Puett, David; Earp, Karly M; Malchoff, Carl D
This study prospectively determines the shear wave elastography characteristics of parathyroid adenomas using virtual touch imaging quantification, a non-invasive ultrasound based shear wave elastography method. This prospective study examined 57 consecutive patients with biochemically proven primary hyperparathyroidism and solitary parathyroid adenoma identified by ultrasound and confirmed by at least one of the following: surgical resection, positive Technetium-99m Sestamibi Scintigraphy (MIBI) scan, or fine needle aspiration biopsy with positive PTH washout (performed only in MIBI negative patients). Vascularity and shear wave elastography were performed for all patients. Parathyroid adenoma stiffness was measured as shear wave velocity in meters per second. The median (range) pre-surgical value for PTH and calcium were 58pg/mL (19, 427) and 10.8mg/dL (9.5, 12.1), respectively. 37 patients had positive MIBI scan. 20 patients had negative MIBI scan but diagnosis was confirmed with positive PTH washout. 42 patients underwent parathyroidectomy, and an adenoma was confirmed in all. The median (range) shear wave velocity for all parathyroid adenomas enrolled in this study was 2.02m/s (1.53, 2.50). The median (range) shear wave velocity for thyroid tissue was 2.77m/s (1.89, 3.70). The shear wave velocity of the adenomas was independent of adenoma size, serum parathyroid hormone concentration, or plasma parathyroid hormone concentration. Tissue elasticity of parathyroid adenoma is significantly lower than thyroid tissue. B-mode features and distinct vascularity pattern are helpful tools in diagnosing parathyroid adenoma with ultrasound. Shear wave elastography may provide valuable information in diagnosing parathyroid adenoma. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.
Williams, Lindsay; Chiosea, Simion I
Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas.
Guaraldi, Federica; Prencipe, Nunzia; di Giacomo, Valentina; Scanarini, Massimo; Gasco, Valentina; Gardiman, Marina Paola; Berton, Alessandro M; Ghigo, Ezio; Grottoli, Silvia
Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical, laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.
Ramia, José Manuel; Bernardo, Carmen; Valdivieso, Andrés; Dopazo, Cristina; Jover, José María; Albiol, M Teresa; Pardo, Fernando; Fernandez Aguilar, José Luis; Gutierrez Calvo, Alberto; Serrablo, Alejandro; Diez Valladares, Luis; Pereira, Fernando; Sabater, Luis; Muffak, Karim; Figueras, Joan
Hepatic adenomas (HA) are benign tumours which can present serious complications, and as such, in the past all were resected. It has now been shown that those smaller than 3 cm not expressing β-catenin only result in complications in exceptional cases and therefore the therapeutic strategy has been changed. Retrospective study in 14 HPB units. patients with resected and histologically confirmed HA. 1995-2011. 81 patients underwent surgery. Age: 39.5 years (range: 14-75). Sex: female (75%). Consumption of oestrogen in women: 33%. Size: 8.8 cm (range, 1-20 cm). Only 6 HA (7.4%) were smaller than 3 cm. The HA median was 1 (range: 1-12). Nine patients had adenomatosis (>10HA). A total of 51% of patients displayed symptoms, the most frequent (77%) being abdominal pain. Eight patients (10%) began with acute abdomen due to rupture and/or haemorrhage. A total of 67% of the preoperative diagnoses were correct. Surgery was scheduled for 90% of patients. The techniques employed were: major hepatectomy (22%), minor hepatectomy (77%) and one liver transplantation. A total of 20% were performed laparoscopically. The morbidity rate was 28%. There were no cases of mortality. Three patients had malignisation (3.7%). The follow-up period was 43 months (range 1-192). Two recurrences were detected and resected. Patients with resected HA are normally women with large lesions and oestrogen consumption was lower than expected. Its correct preoperative diagnosis is acceptable (70%). The major hepatectomy rate is 25% and the laparoscopy rate is 20%. There was a low morbidity rate and no mortality. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.
Zukic, Dženan; Egger, Jan; Bauer, Miriam H. A.; Kuhnt, Daniela; Carl, Barbara; Freisleben, Bernd; Kolb, Andreas; Nimsky, Christopher
The most common sellar lesion is the pituitary adenoma, and sellar tumors are approximately 10-15% of all intracranial neoplasms. Manual slice-by-slice segmentation takes quite some time that can be reduced by using the appropriate algorithms. In this contribution, we present a segmentation method for pituitary adenoma. The method is based on an algorithm that we have applied recently to segmenting glioblastoma multiforme. A modification of this scheme is used for adenoma segmentation that is much harder to perform, due to lack of contrast-enhanced boundaries. In our experimental evaluation, neurosurgeons performed manual slice-by-slice segmentation of ten magnetic resonance imaging (MRI) cases. The segmentations were compared to the segmentation results of the proposed method using the Dice Similarity Coefficient (DSC). The average DSC for all datasets was 75.92%+/-7.24%. A manual segmentation took about four minutes and our algorithm required about one second.
Berkmann, Sven; Fischer, Ingeborg; Sonderegger, Beat; Fischli, Stefan; Fandino, Javier
Sellar toxoplasmosis is associated with congenital infections or immunodeficiency. The finding of Toxoplasma bradycysts in a pituitary adenoma is very unusual. An otherwise healthy 27-year-old woman presented with secondary amenorrhea and moderately elevated prolactin levels. A macroprolactinoma was suspected on magnetic resonance imaging, and cabergoline was initiated. Although dopamine levels decreased, the tumor did not show significant shrinkage; after 2 years, transsphenoidal resection was indicated to clarify the diagnosis and to cure hyperprolactinemia. Histology showed an inactive pituitary adenoma and Toxoplasma bradycysts. Seropositivity for Toxoplasma gondii, but neither immunodeficiency nor intracerebral spread, was found. During a postoperative follow-up period of 15 months, the patient did not show any recurrence. Sellar toxoplasmosis in conjunction with pituitary adenoma is extremely rare. Nonfunctioning lesions should be suspected in cases of sellar masses and moderate hyperprolactinemia. Copyright © 2015 Elsevier Inc. All rights reserved.
Neumann, Helmut; Nägel, Andreas; Buda, Andrea
Advanced endoscopic imaging is revolutionizing our way on how to diagnose and treat colorectal lesions. Within recent years a variety of modern endoscopic imaging techniques was introduced to improve adenoma detection rates. Those include high-definition imaging, dye-less chromoendoscopy techniques and novel, highly flexible endoscopes, some of them equipped with balloons or multiple lenses in order to improve adenoma detection rates. In this review we will focus on the newest developments in the field of colonoscopic imaging to improve adenoma detection rates. Described techniques include high-definition imaging, optical chromoendoscopy techniques, virtual chromoendoscopy techniques, the Third Eye Retroscope and other retroviewing devices, the G-EYE endoscope and the Full Spectrum Endoscopy-system. PMID:25789092
Mouton, F; Faivre-Defrance, F; Cortet-Rudelli, C; Assaker, R; Soto-Ares, G; Defoort-Dhellemmes, S; Blond, S; Wemeau, J-L; Vantyghem, M-C
TSH-secreting adenomas are rare tumors, representing only 0.5 to 2.5% of pituitary adenomas. Their main clinical characteristics include signs of thyrotoxicosis, diffuse goiter and a compressive syndrome. Biologically, free T4 and T3 serum levels are elevated, contrasting with inadequate serum TSH levels and increased alpha chains. Magnetic resonance (MR) imaging shows a pituitary tumor, the main differential diagnosis being resistance to thyroid hormones. Treatment is based on surgery, possibly associated with somatostatin analogs and radiotherapy. Though the long-term evolution of this rare pathology seems to have improved, some clinical situations are still a challenge to treat. We report one such case that was resistant to both stereotactic radiotherapy and somatostatin analogs, but surprisingly improved with cabergoline. We suggest that cabergoline should be considered as an alternative treatment in cases of pituitary adenomas that resist traditional treatments.
Rembao-Bojórquez, Daniel; Vega, Rosalba; Bermúdez-Maldonado, Luis; Gutiérrez, Ramón; Salinas, Citlaltepetl; Tena-Suck, Martha
Mucus-secreting adenomas or acinar adenoma of the choroid plexus are very rare. We report the case of a 79-year-old male with a 3-year history of occipital headaches with vomiting, ataxia and cerebellar signs. He was first seen due to difficulty while walking. He was admitted to the hospital with significant tumor expansion and clinical deterioration. CT and MRI revealed obstructive hydrocephalus secondary to a large fourth ventricular cyst mass, which enhanced markedly on contrast administration. Pathological findings were consistent with an acinar choroid plexus adenoma. The tumor was attached to the ependymal lining and was strongly adhered to the walls and floor of the IV ventricle. Post-operative bleeding complicated partial removal of this tumor. The patient died 6 h after surgery.
Ng, Siew C; Lau, James Y W; Chan, Francis K L; Suen, Bing Yee; Tse, Yee Kit; Hui, Aric J; Leung-Ki, En Ling; Ching, Jessica Y L; Chan, Anthony W H; Wong, Martin C S; Ng, Simon S M; To, Ka Fai; Wu, Justin C Y; Sung, Joseph J Y
The risk of colorectal neoplasms among siblings of patients with advanced adenomas is not clear. We determined the prevalence of advanced adenomas in the siblings of patients with advanced adenomas and compared it with that of siblings of individuals without these lesions. In a blinded, cross-sectional study, colonoscopies were performed (from 2010 through 2014), at 2 hospitals in Hong Kong on 200 asymptomatic siblings of patients with advanced adenomas (exposed; mean age, 58.2 ± 6.3 years; adenomas ≥10 mm, high-grade dysplasia, villous, or tubulovillous) and 400 age- and sex-matched siblings of subjects with normal findings from colonoscopies and no family history of colorectal cancer (unexposed; mean age, 58.1 ± 6 years). We recruited 1 sibling per family. The primary outcome was prevalence of advanced adenomas. Baseline demographics (ie, aspirin use, smoking, body mass index, and metabolic diseases) did not differ significantly between exposed and unexposed individuals. The prevalence of advanced adenoma was 11.5% among the exposed subjects and 2.5% among the unexposed subjects (matched odds ratio [mOR] = 6.05; 95% confidence interval [CI]: 2.74-13.36; P < .001). The prevalence of adenomas ≥10 mm was higher among exposed than unexposed siblings (10.5% vs 1.8%; mOR = 8.59; 95% CI: 3.44-21.45; P < .001), as was the prevalence of villous adenomas (5.5% vs 1.3% in unexposed; mOR = 6.28; 95% CI: 2.02-19.53; P = .001) and all colorectal adenomas (39.0% vs 19.0% in unexposed; mOR = 3.29; 95% CI: 2.16-5.03; P < .001). Two cancers were detected in exposed siblings and none in unexposed siblings. In a cross-sectional study of subjects undergoing colonoscopy in Hong Kong, siblings of individuals with at least 1 advanced adenoma had a 6-fold increased odds of advanced adenoma compared with subjects who had a sibling with a screening colonoscopy with no identified neoplasia. ClinicalTrials.gov, Number: NCT01593098. Copyright © 2016 AGA Institute. Published by Elsevier
Ahmed, Sartaj; Campbell, Ross M; Li, Jin Hong; Wang, Li Juan; Robinson-Bostom, Leslie
Adenomas in the anogenital region are uncommon. There has been debate about the origin, including ectopic breast tissue, cutaneous apocrine gland, and most recently anogenital mammary-like gland. An anogenital mass in a 36-year-old woman was excised, and histopathologic examination and immunostaining were performed. Microscopic tissue sections showed a morphologic pattern similar to that of a mammary fibroadenoma, and immunostaining demonstrated the presence of estrogen receptors and progesterone receptors. The possibility of adenomas of anogenital mammary-like glands should be considered when evaluating patients with a mass in this area with confirmation by tissue biopsy or aspiration cytology.
Glazer, Daniel Victor; Rømeling, Frans
Pleomorphic adenoma located in the soft palate is extremely rare. We report a 42-year-old woman, who presented to the ear nose & throat department with a mucosal swelling of the right soft palate mimicking a peritonsillar abscess. Drainage was attempted several times without significant results. Emergency tonsillectomy was carried out, which showed a tumour intraorally beside the right tonsil. The tumour and the tonsil were radically excised. Histological analysis of the tumour revealed a pleomorphic adenoma. At three-month follow-up the patient was doing well and MRI scan revealed a residual tumour of 6 mm.
Wang, Jiping; Carvajal-Carmona, Luis G.; Chu, Jen-Hwa; Zauber, Ann G.; Kubo, Michikai; Matsuda, Koichi; Dunlop, Malcolm; Houlston, Richard S.; Sieber, Oliver; Lipton, Lara; Gibbs, Peter; Martin, Nicholas G.; Montgomery, Grant W.; Young, Joanne; Baird, Paul N.; Ratain, Mark J.; Nakamura, Yusuke; Weiss, Scott T.; Tomlinson, Ian; Bertagnolli, Monica M.
Purpose Identification of single nucleotide polymorphisms (SNPs) associated with development of advanced colorectal adenomas. Experimental Design Discovery Phase: 1,406 Caucasian patients (139 advanced adenoma cases and 1,267 controls) from the Adenoma Prevention with Celecoxib (APC) trial were included in a genome-wide association study (GWAS) to identify variants associated with post-polypectomy disease recurrence. Genome-wide significance was defined as false discovery rate < 0.05, unadjusted p=7.4×10−7. Validation Phase: Results were further evaluated using 4,175 familial colorectal adenoma or CRC cases and 5,036 controls from patients of European ancestry (COloRectal Gene Identification consortium, Scotland, Australia and VQ58). Results Our study identified eight SNPs associated with advanced adenoma risk in the APC trial (rs2837156, rs7278863, rs2837237, rs2837241, rs2837254, rs741864 at 21q22.2, and rs1381392 and rs17651822 at 3p24.1, at p<10–7 level with odds ratio – OR>2). Five variants in strong pairwise linkage disequilbrium (rs7278863, rs2837237, rs741864, rs741864 and rs2837241, r2=0.8–1) are in or near the coding region for the tight junction adhesion protein, IGSF5. An additional variant associated with advanced adenomas, rs1535989 (minor allele frequency 0.11; OR 2.09; 95% confidence interval 1.50–2.91), also predicted CRC development in a validation analysis (p=0.019) using a series of adenoma cases or CRC (CORGI study) and 3 sets of CRC cases and controls (Scotland, VQ58 and Australia, N=9,211). Conclusions Our results suggest that common polymorphisms contribute to the risk of developing advanced adenomas and might also contribute to the risk of developing CRC. The variant at rs1535989 may identify patients whose risk for neoplasia warrants increased colonoscopic surveillance. PMID:24084763
Xiao, Deyong; Wang, Shousen; Huang, Yinxing; Zhao, Lin; Wei, Liangfeng; Ding, Chenyu
Objectives: This study is to summarize the clinical manifestations, imaging findings, treatment and prognosis of pituitary apoplexy caused by ischemic infarction. Methods: From January 2010 to March 2014, 412 patients with pituitary adenoma were admitted in the Department of Neurosurgery at Fuzhou General Hospital, with 9 cases being diagnosed with ischemic infarction stroke. Imaging examinations were performed, including computed tomography and magnetic resonance imaging. Pituitary adenomas were evaluated according to suprasellar, infrasellar, parasellar, anterior and posterior classification. Hematoxylin and eosin staining and immunohistochemical staining were used for identifying pituitary adenoma. Results: Tumor height was 1.3-3.3 cm, with an average of 2.27 cm. Eight patients had typical clinical stroke symptoms. Preoperatively, high blood growth hormone concentration was presented in 6 cases, full hypopituitarism in 2 cases, dysfunction of corticosteroids and gonads in 4 cases, and single gonadal dysfunction in 2 cases. Ring enhancement was presented in 8 cases on constructed computed tomography or magnetic resonance images, and sellar settlement in 7 cases. Eight patients were conducted with transsphenoidal resection, and secondary transsphenoidal after craniotomy in 1 case. During surgery, poor tumor blood supply was found in 7 cases, cheese-like or tofu-like necrotic tissues in 5 cases, and few dark blood clots in 2 cases. Conclusions: Pituitary ischemic infarction stroke is clinically rare, but can be correctly diagnosed before surgery by imaging examinations. The pathological characteristics of the tumor are necrosis and fibrosis, which are easy for resection. Therefore, pituitary adenoma usually has good prognosis. PMID:26221291
Inomoto, Chie; Sato, Haruhiro; Kanai, Genta; Hirukawa, Takashi; Shoji, Sunao; Terachi, Toshiro; Kajiwara, Hiroshi; Osamura, Robert Yoshiyuki
Functioning black adrenal adenoma (BAA) rarely causes preclinical Cushing's syndrome (CS). In the present case, a 46-year-old Japanese Peruvian woman presented with left flank pain and hypertension. Abdominal computed tomography showed that she had a 15-mm in diameter, round, left adrenal adenoma. She had no physical features of CS, such as moon face, buffalo hump, truncal obesity, or purple striae. Endocrinological examination showed that the plasma adrenocorticotropic hormone (ACTH) level was below the detectable level, despite a serum cortisol level within the normal range. A normal cortisol circadian rhythm was not present. Dexamethasone (1 mg and 8 mg) suppression testing did not decrease serum cortisol levels to the reference levels. These findings were compatible with preclinical CS. The left adrenal adenoma was laparoscopically removed. Examination of the surgical specimen revealed unilateral double adrenal adenomas of the left adrenal gland, one of which was a BAA. The BAA measured 20 × 11 × 10 mm. Microscopically, the BAA showed proliferation of compact cells containing numerous brown-pigmented granules. There were also foci of myelolipomatous degenerative changes in the tumor. The compact cell zones remained in the adrenal cortex adjacent to the BAA showed atrophic change. These findings indicated that BAA appeared to have caused preclinical CS in this patient.
Xiao, Deyong; Wang, Shousen; Huang, Yinxing; Zhao, Lin; Wei, Liangfeng; Ding, Chenyu
This study is to summarize the clinical manifestations, imaging findings, treatment and prognosis of pituitary apoplexy caused by ischemic infarction. From January 2010 to March 2014, 412 patients with pituitary adenoma were admitted in the Department of Neurosurgery at Fuzhou General Hospital, with 9 cases being diagnosed with ischemic infarction stroke. Imaging examinations were performed, including computed tomography and magnetic resonance imaging. Pituitary adenomas were evaluated according to suprasellar, infrasellar, parasellar, anterior and posterior classification. Hematoxylin and eosin staining and immunohistochemical staining were used for identifying pituitary adenoma. Tumor height was 1.3-3.3 cm, with an average of 2.27 cm. Eight patients had typical clinical stroke symptoms. Preoperatively, high blood growth hormone concentration was presented in 6 cases, full hypopituitarism in 2 cases, dysfunction of corticosteroids and gonads in 4 cases, and single gonadal dysfunction in 2 cases. Ring enhancement was presented in 8 cases on constructed computed tomography or magnetic resonance images, and sellar settlement in 7 cases. Eight patients were conducted with transsphenoidal resection, and secondary transsphenoidal after craniotomy in 1 case. During surgery, poor tumor blood supply was found in 7 cases, cheese-like or tofu-like necrotic tissues in 5 cases, and few dark blood clots in 2 cases. Pituitary ischemic infarction stroke is clinically rare, but can be correctly diagnosed before surgery by imaging examinations. The pathological characteristics of the tumor are necrosis and fibrosis, which are easy for resection. Therefore, pituitary adenoma usually has good prognosis.
Keramidas, Evangelos G; Miller, Gavin; Revelos, Kyriakos; Kitsanta, Panagiota; Page, Robert E
Aggressive digital papillary adenocarcinoma and aggressive digital papillary adenoma are rare tumours of the sweat glands. They are most common in the most distal part of the fingers and are locally aggressive with a 50% local recurrence rate; 14% of tumours metastasize. We present two cases.
We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenici...
We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenici...
Yao, Kun; Duan, Zejun; Bian, Yu; Wang, Mengyang; Qi, Xueling
Suprasellar salivary gland-Like pleomorphic adenoma is not a common disease and seldom reported so far. We are reporting a case of a 23-year-old man with recurrent suprasellar salivary gland-like pleomorphic adenoma, who underwent an operation of subtotal, subfrontal resection under the wrong pathology diagnosis of benign teratoma in another hospital 4-year-ago. Four years later, he was admitted to our hospital for additional visual loss of the right eye (left, 1.0; right, 0.4) resulting from tumor regrowth. Magnetic resonance imaging revealed that suprasellar extension and compressed optic chiasm resulted in visual disturbance of the patient. The tumor was totally excised and histological examination evidenced the pathological features of intrasellar salivary gland-like pleomorphic adenoma. The patient did not receive any further treatment and he is free from tumor recurrence for 30 months after the operation. From this point of view, clinical prognosis of intrasellar salivary gland-like pleomorphic adenoma was good after total surgical resection.
Witt, Robert L; Eisele, David W; Morton, Randall P; Nicolai, Piero; Poorten, Vincent Vander; Zbären, Peter
The objective of this review study was to encompass the relevant literature and current best practice options for this challenging, sometimes incurable problem. The source of the data was Ovid MEDLINE from 1946 to 2014. Review methods consisted of articles with clinical correlates. The most important cause of recurrence is enucleation with rupture and incomplete tumor excision at operation. Incomplete pseudocapsule, extracapsular extension, pseudopods of pleomorphic adenoma tissue, and satellite pleomorphic beyond the pseudocapsule are also likely linked to recurrent pleomorphic adenoma. Most recurrent pleomorphic adenoma are multinodular. Magnetic resonance imaging is the imaging study of choice for recurrent pleomorphic adenoma. Nerve integrity monitoring may reduce morbidity for recurrent pleomorphic adenoma. Treatment of recurrent pleomorphic adenoma must be individualized. Total parotidectomy, given the multicentricity of recurrent pleomorphic adenoma, is appropriate in many patients, but may be inadequate to control recurrent pleomorphic. There is accumulating evidence from retrospective series that postoperative radiation therapy results in significantly better local control.
Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Adjadj, Elisabeth; Thomas-Teinturier, Cecile; Oberlin, Odile; Veres, Cristina; Pacquement, Helene; Jackson, Angela; Munzer, Martine; N'Guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Bridier, Andre; Lefkopoulos, Dimitri; Schlumberger, Martin; Rubino, Carole; Diallo, Ibrahima; Vathaire, Florent de
Purpose: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. Methods and Materials: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose received at other anatomical sites of interest. Results: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. Conclusions: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma.
Cao, Y; Keum, N N; Chan, A T; Fuchs, C S; Wu, K; Giovannucci, E L
Background: Prolonged TV watching, a major sedentary behaviour, is associated with increased risk of obesity and diabetes and may involve in colorectal carcinogenesis. Methods: We conducted a cross-sectional analysis among 31 065 men with ⩾1 endoscopy in the Health Professionals Follow-up Study (1988–2008) to evaluate sitting while watching TV and its joint influence with leisure-time physical activity on risk of colorectal adenoma. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Prolonged sitting while watching TV was significantly associated with increased risk of colorectal adenoma (n=4280), and adjusting for physical activity or a potential mediator body mass index did not change the estimates. The ORs (95% CIs) across categories of TV watching (0–6, 7–13, 14–20, and 21+ h per week) were 1.00 (referent), 1.09 (1.01–1.17), 1.16 (1.06–1.27), and 1.10 (0.97–1.25) (OR per 14-h per week increment=1.11; 95% CI: 1.04–1.18; Ptrend=0.001). Compared with the least sedentary (0–6 h per week of TV) and most physically active (highest quintile) men, the most sedentary (14+ h per week) and least active (lowest quintile) men had a significant increased risk of adenoma (OR=1.25; 95% CI: 1.05–1.49), particularly for high-risk adenoma. Conclusions: Prolonged TV viewing is associated with modest increased risk of colorectal adenoma independent of leisure-time physical activity and minimally mediated by obesity. PMID:25590667
Seo, Ji Yeon; Choi, Seung Ho; Chun, Jaeyoung; Choi, Ji Min; Jin, Eun Hyo; Hwang, Sung Wook; Im, Jong Pil; Kim, Sang Gyun; Kim, Joo Sung
Background/Aims The efficacy and safety of endoscopic resection of colorectal cancer derived from sessile serrated adenomas or traditional serrated adenomas are still unknown. The aims of this study were to verify the characteristics and outcomes of endoscopically resected early colorectal cancers developed from serrated polyps. Methods Among patients who received endoscopic resection of early colorectal cancers from 2008 to 2011, cancers with documented pre-existing lesions were included. They were classified as adenoma, sessile serrated adenoma, or traditional serrated adenoma according to the baseline lesions. Clinical characteristics, pathologic diagnosis, and outcomes were reviewed. Results Overall, 208 colorectal cancers detected from 198 patients were included: 198 with adenoma, five with sessile serrated adenoma, and five with traditional serrated adenoma. The sessile serrated adenoma group had a higher prevalence of high-grade dysplasia (40.0% vs. 25.8%, P<0.001) than the adenoma group. During follow-up, local recurrence did not occur after endoscopic resection of early colorectal cancers developed from serrated polyps. In contrast, two cases of metachronous recurrence were detected within a short follow-up period. Conclusions Cautious observation and early endoscopic resection are recommended when colorectal cancer from serrated polyp is suspected. Colorectal cancers from serrated polyp can be treated successfully with endoscopy. PMID:27433150
Beck-Peccoz, Paolo; Persani, Luca; Mannavola, Deborah; Campi, Irene
Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of all pituitary adenomas. In the last years, the diagnosis has been facilitated by the routine use of ultra-sensitive TSH immunometric assays. Failure to recognise the presence of a TSHoma may result in dramatic consequences, such as improper thyroid ablation that may cause the pituitary tumour volume to further expand. The diagnosis mainly rests on dynamic testing, such as T3 suppression tests and TRH, which are useful in differentiating TSHomas from the syndromes of thyroid hormone resistance. The first therapeutical approach to TSHomas is the pituitary neurosurgery. The medical treatment of TSHomas mainly rests on the administration of somatostatin analogues, such as octreotide and lanreotide, which are effective in reducing TSH secretion in more than 90% of patients with consequent normalisation of FT4 and FT3 levels and restoration of the euthyroid state.
Wilkins, G. E.; Schmidt, N.; Lee-Son, L.
A 56-year-old woman had a 22-year history of hypertension. Investigation showed hypokalemia and kaliuresis without pronounced suppression of plasma renin activity or elevation of urinary aldosterone excretion. There was biochemical evidence of catecholamine metabolite excess but the usual clinical features of pheochromocytoma were absent. Laparotomy revealed a pheochromocytoma and adrenal adenoma in the right adrenal gland. Excision of the tumours was followed by resolution of the hypertension and metabolic abnormalities. Images FIG. 2 FIG. 3 PMID:844017
Chang, Brent A; Sharma, Anil; Anderson, Donald W
Ectopic parathyroid adenomas can occur in numerous anatomic locations. While ectopic parathyroid adenomas can rarely occur in the pharyngeal region, this has not previously been described in the soft palate. We report the first case of ectopic parathyroid adenoma within the soft palate. A 59 year old woman presented with hyperparathyroidism. She remained persistently hyperparathyroid after initial parathyroidectomy. Repeat exploration for a lesion suspicious on PET-CT for an ectopic parathyroid adenoma in the parapharyngeal region was unsuccessful in treating the hyperparathyroidism. An ectopic adenoma in the soft palate was eventually discovered. Removal through a transoral approach was successful in treating the hyperparathyroidism. Ectopic parathyroid adenomas can occur in various anatomical locations that may be missed even with the use of the various imaging modalities. The soft palate should be added to the list of possible ectopic locations high in the neck.
Nimsky, Christopher; Kikinis, Ron
In this study, we present pituitary adenoma volumetry using the free and open source medical image computing platform for biomedical research: (3D) Slicer. Volumetric changes in cerebral pathologies like pituitary adenomas are a critical factor in treatment decisions by physicians and in general the volume is acquired manually. Therefore, manual slice-by-slice segmentations in magnetic resonance imaging (MRI) data, which have been obtained at regular intervals, are performed. In contrast to this manual time consuming slice-by-slice segmentation process Slicer is an alternative which can be significantly faster and less user intensive. In this contribution, we compare pure manual segmentations of ten pituitary adenomas with semi-automatic segmentations under Slicer. Thus, physicians drew the boundaries completely manually on a slice-by-slice basis and performed a Slicer-enhanced segmentation using the competitive region-growing based module of Slicer named GrowCut. Results showed that the time and user effort required for GrowCut-based segmentations were on average about thirty percent less than the pure manual segmentations. Furthermore, we calculated the Dice Similarity Coefficient (DSC) between the manual and the Slicer-based segmentations to proof that the two are comparable yielding an average DSC of 81.97±3.39%. PMID:23240062
Bansal, M.; Fenoglio, C. M.; Robboy, S. J.; King, D. W.
Five thousand seven hundred seventy-eight adenomas or adenomas containing carcinoma from 3215 patients were examined by routine histologic methods for the presence of epithelial metaplasias. Three forms of epithelial metaplasia were encountered: squamous cell metaplasia (0.44%), Paneth cell metaplasia (0.20%), and melanocytic metaplasia (0.017%). In several instances multiple forms of metaplasia were encountered in the same polyp. In those cases in which the paraffin blocks were available, a Grimelius stain was performed. Grimelius-positive cells were present in 63% of the adenomas containing a metaplastic cell type. All cases with Paneth cell differentiation were immunoreactive for lysozyme; all lesions containing areas of squamous differentiation were immunoreactive for keratin except 2. The histopathologic features of these cases are discussed, and it is concluded that rather than representing a true metaplastic process, Paneth cell, squamous cell, and melanocyte differentiation represent the full range of cellular differentiation that endodermally derived tissues can exhibit, particularly when they undergo neoplastic alterations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:6202148
Doster, A R; Armstrong, D L; Bargar, T W
A seminoma and parathyroid adenoma were diagnosed in an aged snow leopard. The ultrastructural appearance of the seminoma was similar to that described in the dog and in man. The lack of significant amounts of rough endoplasmic reticulum, Golgi complexes and free ribosomes in the parathyroid adenoma suggested that it was non-functional. Parathyroid adenoma has not been previously described in a large wild feline.
Lynch, H T; Smyrk, T C; Lanspa, S J; Lynch, P M; Watson, P; Strayhorn, P C; Bronson, E K; Lynch, J F; Priluck, I A; Appelman, H D
Clinical, pathologic, and genetic studies on two colorectal cancer-prone families have disclosed right-sided colonic flat adenomas and colorectal cancer. Adenomatous polyp counts exceeded those found in hereditary nonpolyposis colorectal cancer (HNPCC) but were fewer than in familial adenomatous polyposis (FAP). Colon cancer occurred at a later age than in HNPCC or FAP and showed right-sided predominance. The older age of patients with colonic cancer, the right-sided predominance of colon cancer, and the paucity of rectal adenomas make FAP unlikely. Vertical transmission of polyps and colon cancer fit the pattern of autosomal dominant inheritance. A characteristic feature of this phenotype is the predominance of flat adenomas. Molecular genetic studies, with careful description of phenotype, should help clarify classification.
Kaur, Milanjeet; Bhogal, Jasmine
Pleomorphic adenoma is the most common benign salivary gland tumor, accounting for almost three-fourths of all such tumors. Cells with oncocytic change are a common finding in salivary glands and in salivary gland tumors. When found within pleomorphic adenomas, cells with oncocytic changes may be perceived as evidence of malignancy, and lead to a misdiagnosis of carcinoma ex-pleomorphic adenoma. A case of pleomorphic adenoma arising de novo in the minor salivary glands with oncocytic changes is discussed here. PMID:26392734
Eytan, Shira; Kim, Ki-Yoon; Bleich, David; Raghuwanshi, Maya; Eloy, Jean Anderson; Liu, James K
We report a 27-year-old woman with amenorrhea and galactorrhea with mildly elevated serum prolactin levels. Her MRI demonstrated a cystic macroadenoma in the left aspect of the sella and a small microadenoma in the right aspect of the sella. Endoscopic transsphenoidal resection of the tumors revealed two histologically distinct tumors. The left tumor was consistent with a silent corticotroph macroadenoma and the right tumor was a prolactin producing microadenoma. Isolated double pituitary adenomas that are clearly separated by normal pituitary gland tissue are extremely rare. The incidence is approximately 0.37-2.6%. The coexistence of double adenomas can pose diagnostic and management challenges for the pituitary neuroendocrine team.
Chanson, P; Salenave, S
Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specific stimulation and suppression tests for pituitary hormones are performed in selected situations for detecting the type of hypersecretion or the response to treatment. Imaging procedures (mainly magnetic resonance imaging, MRI, nowadays) determine the presence, size and extent of the lesion. The classification of pituitary tumors is based on the staining properties of the cell cytoplasm viewed by light microscopy and immunocytochemistry revealing the secretory pattern of the adenoma. Treatment of pituitary adenomas consists of surgery (performed in more than 99% of cases via a transphenoidal route) and radiotherapy, generally fractionated or, in selected cases, using stereotactic techniques such as gamma-knife. The availability of medical treatment (dopamine, DA, agonists, somatostatin analogs, GH-receptor antagonists...) has profoundly modified the indications of radiotherapy, drugs being now generally used as a second-line treatment, after surgery (or even as first-line treatment). Based on the results of the different treatment modalities for each type of pituitary adenoma, recommendations will be proposed. They may be summarized as follows. For treatment of GH-secreting adenomas, trans-sphenoidal surgery is the first-line therapy except when the macroadenoma is giant or if surgery is contra-indicated; postoperative radiation therapy (fractionated, or by gamma-knife) is
Su, Timothy; Washington, M. Kay; Ness, Reid M.; Rex, Douglas K.; Smalley, Walter E.; Ulbright, Thomas M.; Cai, Qiuyin; Zheng, Wei; Shrubsole, Martha J.
It is unclear if proximal and distal traditional adenomas present with differences in molecular events which contribute to cancer heterogeneity by tumor anatomical subsite. Participants from a colonoscopy-based study (n=380) were divided into subgroups based on the location of their most advanced adenoma: proximal, distal, or “equivalent both sides”. Eight biomarkers in the most advanced adenomas were evaluated by immunohistochemistry (Ki-67, COX-2, TGFβRII, EGFR, β-catenin, cyclin D1, c-Myc) or TUNEL (apoptosis). After an adjustment for pathological features, there were no significant differences between proximal and distal adenomas for any biomarker. Conversely, expression levels did vary by other features, such as their size, villous component, and synchronousness. Large adenomas had higher expression levels of Ki-67(P<0.001), TGFβRII (P<0.0001), c-Myc (P<0.001), and cyclin D1 (P<0.001) in comparison to small adenomas, and tubulovillous/villous adenomas also were more likely to have similar higher expression levels in comparison to tubular adenomas. Adenoma location is not a major determinant of the expression of these biomarkers outside of other pathological features. This study suggests similarly important roles of Wnt/β-catenin and TGF-β pathways in carcinogenesis in both the proximal and distal colorectum. PMID:27479195
Su, Timothy; Washington, M Kay; Ness, Reid M; Rex, Douglas K; Smalley, Walter E; Ulbright, Thomas M; Cai, Qiuyin; Zheng, Wei; Shrubsole, Martha J
It is unclear if proximal and distal traditional adenomas present with differences in molecular events which contribute to cancer heterogeneity by tumor anatomical subsite. Participants from a colonoscopy-based study (n = 380) were divided into subgroups based on the location of their most advanced adenoma: proximal, distal, or "equivalent both sides." Eight biomarkers in the most advanced adenomas were evaluated by immunohistochemistry (Ki-67, COX-2, TGFβRII, EGFR, β-catenin, cyclin D1, c-Myc) or TUNEL (apoptosis). After an adjustment for pathological features, there were no significant differences between proximal and distal adenomas for any biomarker. Conversely, expression levels did vary by other features, such as their size, villous component, and synchronousness. Large adenomas had higher expression levels of Ki-67(P < 0.001), TGFβRII (P < 0.0001), c-Myc (P < 0.001), and cyclin D1 (P < 0.001) in comparison to small adenomas, and tubulovillous/villous adenomas also were more likely to have similar higher expression levels in comparison to tubular adenomas. Adenoma location is not a major determinant of the expression of these biomarkers outside of other pathological features. This study suggests similarly important roles of Wnt/β-catenin and TGF-β pathways in carcinogenesis in both the proximal and distal colorectum. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Song, Yoon Kyung; Seon, Choon Sik; Lim, Hye Jin; Son, Byung Kwan; Ahn, Sang Bong; Jo, Young Kwan; Kim, Seong Hwan; Jo, Yun Ju; Lee, Ji Hyun; Kim, Seung Chan
Background/Aims Age, sex, gene and life style are modulating risks for colon cancer. Although alcohol intake may impact on colorectal adenoma, clear association has not been established yet. We aimed to investigate effects of alcohol consumption on the characteristics of colorectal adenoma. Methods Patients who underwent colonoscopic polypectomy of colorectal adenoma in the department of gastroenterology of Eulji hospital through 2005 to 2012, having both blood tests and ultrasound or abdominal CT examination were enrolled. The alcohol drinking patients were subdivided into normal or abnormal laboratory group, and alcoholic liver diseases group. Results 212 patients with colorectal adenoma were analyzed; advanced adenoma and multiple adenoma were found in 68 (32.0%) and 79 (37.2%) patients. When compared to the nondrinker group (120/212 patients), the alcohol drinker group (92/212 patients) represented significantly high odds ratios (ORs) for advanced adenoma (OR, 2.697; P=0.002), and multiple adenoma (OR, 1.929; P=0.039). Among alcohol drinker (92 patients), the ORs of advanced adenoma were 6.407 (P=0.003) in alcoholic liver diseases group (17 patients), 3.711 (P=0.002) in the alcohol drinker with abnormal lab (24 patients), and 2.184 (P=0.034), in the alcohol drinker with normal lab (51 patients) compared to nondrinker group. Conclusions This study showed that alcohol drinking may influence on the development of advanced colorectal adenoma and multiplicity. Especially in the group with alcoholic liver diseases and with abnormal lab presented significantly higher ORs of advanced adenoma. PMID:25691846
Pekic, S; Stojanovic, M; Popovic, V
Pituitary adenomas are common benign monoclonal neoplasms accounting for about 15% of intracranial neoplasms. Data from postmortem studies and imaging studies suggest that 1 of 5 individuals in the general population may have pituitary adenoma. Some pituitary adenomas (mainly microadenomas which have a diameter of less than 1 cm) are exceedingly common and are incidentally diagnosed on magnetic resonance imaging (MRI) performed for an unrelated reason (headache, vertigo, head trauma). Most microadenomas remain clinically occult and stable in size, without an increase in tumor cells and without local mass effects. However, some pituitary adenomas grow slowly, enlarge by expansion and become demarcated from normal pituitary (macroadenomas have a diameter greater than 1 cm). They may be clinically silent or secrete anterior pituitary hormones in excess such as prolactin, growth hormone (GH), or adrenocorticotropic hormone (ACTH) causing diseases like prolactinoma, acromegaly, Cushing's disease or rarely thyroid-stimulating hormone (TSH) or gonadotropins (LH, FSH). The incidence of the various subtypes of pituitary adenoma varies but the most common is prolactinoma. Clinically non-functioning pituitary adenomas (NFPAs), which do not secrete hormones often cause local mass symptoms and represent one-third of pituitary adenomas. Given the high prevalence of pituitary adenomas and their heterogeneity (different tumor subtypes), it is critical that clinicians have a thorough understanding of the potential abnormalities in pituitary function and prognostic factors for behavior of pituitary adenomas in order to timely implement specific treatment modalities. Regarding pathogenesis of these tumors genetics, epigenetics and signaling pathways are the focus of current research yet our understanding of pituitary tumorigenesis remains incomplete. Although several genes and signaling pathways have been identified as important factors in the development of pituitary tumors, current
Sey, Michael Sai Lai; Liu, Andy; Asfaha, Samuel; Siebring, Victoria; Jairath, Vipul; Yan, Brian
Adenoma detection rate (ADR) is an important measure of colonoscopy quality, as are polyp, advanced ADR, and adenocarcinoma detection rates. We investigated whether performance report cards improved these outcome measures. Endoscopists were given report cards comparing their detection rates to the institutional mean on an annual basis. Detection rates were evaluated at baseline, 1 year after report cards (Year 1), and 2 years after report cards (Year 2). Endoscopists were unaware of the study and received no other interventions. The primary outcome was ADR and secondary outcomes were polyp detection rate (PDR), advanced ADR, and adenocarcinoma detection rate. Multivariate regression was performed to adjust for temporal trends in patient, endoscopists, and procedural factors. Seventeen physicians performed 3,118 screening colonoscopies in patients with positive FOBT or family history of colon cancer. The ADR increased from 34.5 % (baseline) to 39.4 % (Year 1) and 41.2 % (Year 2) ( P = 0.0037). The PDR increased from 45 % (baseline) to 48.8 % (Year 1) and 51.8 % (Year 2) ( P = 0.011). There was no significant improvement in advanced ADR or adenocarcinoma detection rates. On multivariate analysis, the ADR increased by 22 % in Year 1 ( P = 0.03) and 30 % in Year 2 ( P = 0.008). Among physicians with a baseline ADR < 25 %, improvement in ADR was even greater, increasing 2.2 times by the end of the study ( P = 0.004). Improvements in ADR were not correlated with specialty although gastroenterologists were 52 % more likely to find an adenoma than general surgeons. Annual performance report cards increased adenoma detection rates, especially among physicians with low ADR < 25 %.
Altmann, H W
Nodular hyperplasias ("hyperplasiomas") are new formations whose development as a required and regulated response can be traced either to compensatory reactions to the loss of cells (regeneration in a narrow sense) and to decreased cellular performance, or to primary growth impulses. Included in this group are: the "macroregenerative nodules" after extensive cell losses; solitary nodules of uncertain etiology; and the minute foci of "micronodular transformation" whose origin can be traced to a particular disturbance of the hepatic blood supply. The so-called "adenomatous hyperplasias" of the cirrhotic liver that have a tendency towards carcinomatous change are not included in this group and are perhaps better considered as "hyperplasiogenic adenomas". The so-called "focal nodular hyperplasia" too, it must be stressed, should be separated from the simple hyperplasias, for it is more closely related to the adenomas, but represents a new formation of limited growth potential. Morphologically it is conspicuously subdivided by multiple connective tissue bands and scars, but it is above all characterized by metaplastically derived neoductuli, and hence it is appropriately designated as a "combined nodule". Among the true uninodular adenomas there are several variants differing in their morphology,--the so-called "atypical" or "intermediate" forms, that can give rise to carcinomas. The hepatocellular carcinoma, that may arise in a variety of ways, presents multiple cytological and histological variants, but only the so-called "fibrolamellar carcinoma" presents also a clinical peculiarity. "Hepatoblastomas" differ from the common hepatocellular carcinomas by their origin in early childhood from immature early precursor cells and, in the later phases of life, from redifferentiated cells that can even give rise to mesenchymal elements. There is no evidence of the existence of particular pluripotential stem cells.
Hilal, Mohammed Abu; Fabio, Francesco Di; Wiltshire, Robert David; Hamdan, Mohammed; Layfield, David M; Pearce, Neil William
AIM: To investigate the role of laparoscopy in the surgical management of hepatocellular adenoma (HA). METHODS: We reviewed a prospectively collected database of consecutive patients undergoing laparoscopic liver resection for HA. RESULTS: Thirteen patients underwent fifteen pure laparoscopic liver resections for HA (male/female: 3/10; median age 42 years, range 22-72 years). Two patients with liver adenomatosis required two different laparoscopic operations for ruptured adenomas. Indications for surgery were: symptoms in 12 cases, need to rule out malignancy in 2 cases and preoperative diagnosis of large HA in one case. Symptoms were related to bleeding in 10 cases, sepsis due to liver abscess following embolization of HA in one case and mass effect in one case (shoulder tip pain). Five cases with ruptured bleeding adenoma required emergency admission and treatment with selective arterial embolization. Laparoscopic liver resection was then semi-electively performed. Eight patients (62%) required major hepatectomy [right hepatectomy (n = 5), left hepatectomy (n = 3)]. No conversion to open surgery occurred. The median operative time for pure laparoscopic procedures was 270 min (range 135-360 min). The median size of the excised lesions was 85 mm (range 25-180 mm). One patient with adenomatosis developed postoperative bleeding requiring embolization. Mortality was nil. The median hospital stay was 4 d (range 1-18 d) with a median high dependency unit stay of 1 d (range 0-7 d). CONCLUSION: The laparoscopic approach represents a safe option for the management of HA in a semi-elective setting and when major hepatectomy is required. PMID:21860698
Namysłowski, G; Misiołek, M; Kubik, P; Misiołek, H; Morawski, K
The case of big size pleomorphic adenoma of the partoid gland was presented. Attention was paid on the necessity of the surgical treatment of pleomorphic adenomas by superficial or total parotidectomies. Possibility of the post operative complications avoidance, even in such big cases was emphasized.
Virapongse, C.; Bhimani, S.; Sarwar, M.; Greenberg, A.; Jung, K.
The authors describe 2 diffusely invasive prolactin-secreting pituitary adenomas which produced marked destruction of the base of the skull thought to be diagnostic of chordoma on computed tomography (CT). Failure to recognize this pattern led to biopsy, which was diagnostic. The authors emphasize the need to recognize this rare growth pattern of diffusely invasive pituitary adenoma on CT.
Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Ben-Shlomo, Anat; Wawrowsky, Kolja; Toledano, Yoel; Tong, Yunguang; Kovacs, Kalman; Scheithauer, Bernd; Melmed, Shlomo
Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth. PMID:21464964
Karkar, Ami M.; Tang, Laura H.; Kashikar, Nilesh D.; Gonen, Mithat; Solomon, Stephen B.; DeMatteo, Ronald P.; D' Angelica, Michael I.; Correa-Gallego, Camilo; Jarnagin, William R.; Fong, Yuman; Getrajdman, George I.; Allen, Peter; Kingham, T Peter
Introduction Hepatocellular adenoma (HA) is an uncommon benign hepatic tumour with the potential for malignant change or spontaneous haemorrhage. Resection has been the recommended treatment, but outcomes with other approaches are ill defined. Methods Demographic and outcomes data were retrospectively collected on patients diagnosed with HA at a tertiary hepatobiliary centre from 1992–2011 whom underwent resection, bland embolization or observation. Results In total, 52 patients with 100 adenomas were divided into single HA (n = 27), multiple HA (n = 18), and adenomatosis (n = 7) groups. Eighty-seven per cent were female and 37% had a history of hormone use. Median sizes of resected, embolized and observed adenomas were 3.6 cm, 2.6 cm and 1.2 cm, respectively. Forty-eight adenomas were resected as a result of suspicion of malignancy (39%) or large size (39%); 61% of these were solitary. Thirty-seven were embolized for suspicion of malignancy (56%) or hsemorrhage (20%); 92% of these were multifocal. Two out of three resected adenomas with malignancy were ≥10 cm and recurred locally [4%, confidence interval (CI) 1–14%]. Ninety-two per cent of the embolized adenomas were effectively treated; three persisted (8.1%, CI 2–22%). Most observed lesions did not change over time. Conclusions While solitary adenomas are often resected, multifocal HAs are frequently embolized. Small adenomas can safely be observed. Given low recurrence rates, select HAs can be considered for embolization. PMID:23374365
Cassani, Lisa S; Lanke, Gandhi; Chen, Hsiang-Chun; Wang, Xuemei; Lynch, Patrick; Lee, Jeffrey H
Nonampullary duodenal adenomas are either sporadic or associated with a hereditary syndrome such as familial adenomatous polyposis (FAP). The aim of this study is to compare characteristics and outcomes of sporadic and FAP-associated duodenal adenomas. We retrospectively collected clinical, endoscopic, and pathologic data in patients diagnosed with duodenal adenomas at our institution and included all available follow-up. Two hundred thirteen subjects were identified; 118 had FAP and 95 had sporadic adenomas. FAP subjects were more likely to have multifocal disease. Initial size was not significantly associated with dysplasia. Fourteen (12%) with FAP and 33 (35%) with sporadic adenomas underwent EMR. Among those subjects who did not undergo EMR or surgery, there was no difference between the FAP and sporadic groups with progression to new dysplasia or cancer. However, the FAP group was significantly more likely to have dysplasia at follow-up (P = .05). There was a significant difference in overall survival between the FAP and sporadic groups (log-rank test, P < .001). In the subgroup of patients aged 40 years old and older who did not undergo intervention, the FAP group had a shorter time to pathology progression compared with the similar sporadic subgroup. Range of time to progression to cancer was 3 to 161 months. FAP subjects were more likely to be younger and have multifocal disease. Progression of pathology was more likely in the older FAP group compared with the sporadic group. Time to progression to cancer was widely variable and, therefore, unpredictable. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.
Nanba, Kazutaka; Chen, Andrew X.; Omata, Kei; Vinco, Michelle; Giordano, Thomas J.; Else, Tobias; Hammer, Gary D.
Context: The use of next-generation sequencing has resulted in the identification of recurrent somatic mutations underlying primary aldosteronism (PA). However, significant gaps remain in our understanding of the relationship between tumor aldosterone synthase (CYP11B2) expression and somatic mutation status. Objective: The objective of the study was to investigate tumor CYP11B2 expression and somatic aldosterone-driver gene mutation heterogeneity. Methods: Fifty-one adrenals from 51 PA patients were studied. Immunohistochemistry for CYP11B2 was performed. Aldosterone-producing adenomas with intratumor CYP11B2 heterogeneity were analyzed for mutation status using targeted next-generation sequencing. DNA was isolated from CYP11B2-positive, CYP11B2-negative, and adjacent normal areas from formalin-fixed, paraffin-embedded sections. Results: Of 51 adrenals, seven (14 %) showed distinct heterogeneity in CYP11B2 by immunohistochemistry, including six adenomas with intratumor heterogeneity and one multinodular hyperplastic adrenal with both CYP11B2-positive and -negative nodules. Of the six adrenocortical adenomas with CYP11B2 heterogeneity, three had aldosterone-regulating mutations (CACNA1D p.F747C, KCNJ5 p.L168R, ATP1A1 p.L104R) only in CYP11B2-positive regions, and one had two different mutations localized to two histologically distinct CYP11B2-positive regions (ATP2B3 p.L424_V425del, KCNJ5 p.G151R). Lastly, one adrenal with multiple CYP11B2-expressing nodules showed different mutations in each (CACNA1D p.F747V and ATP1A1 p.L104R), and no mutations were identified in CYP11B2-negative nodule or adjacent normal adrenal. Conclusions: Adrenal tumors in patients with PA can demonstrate clear heterogeneity in CYP11B2 expression and somatic mutations in driver genes for aldosterone production. These findings suggest that aldosterone-producing adenoma tumorigenesis can occur within preexisting nodules through the acquisition of somatic mutations that drive aldosterone
Dey, Subrata; Beawarwala, Aziz; Gupta, Saikat
Parathyroid adenoma is a rare disease which is known to present with protean manifestations, leading to misdiagnosis in the initial stage of the disease. It is known to pose a diagnostic dilemma to the clinician, in which a high index of suspicion alone often leads to a proper diagnosis and timely management. We encountered two such cases who presented to us with varied presentation, in which nuclear scintigraphy along with intraoperative parathyroid hormone assay played a major role in diagnosis and management. PMID:28082776
Özgül, M. Akif; Seyhan, Ekrem Cengiz; Özgül, Güler; Çetinkaya, Erdoğan; Büyükkale, Songul; Ünver, Nurcan; Çakır, Tansel; Sayar, Adnan
Primary benign tumors of the trachea are uncommon. These tumors may cause tracheal occlusion and lead to a misdiagnosis of asthma. Ectopic parathyroid adenoma (EPA) can be seen anywhere between the mandibular angle and the mediastinum. The distal part of the trachea is a rare location for EPA, and EPA obstructing the endotracheal lumen has not been reported in the literature. We herein describe a 52-year-old female with a several-year history of asthma treatment who presented with progressive dyspnea. Computed tomography revealed a mass that was obstructing the tracheal lumen. Total mass excision was performed via endobronchial treatment, and pathologic examination revealed EPA. PMID:26029555
Zhang, Qui-Hang; Liu, Hai-Sheng; Yang, Da-Zhang; Cheng, Jing-Yu
To assess the role of neuronavigation in assisting endoscopic transsphenoidal surgery for pituitary adenomas. Ten endoscopic endonasal transsphenoidal reoperations for pituitary adenomas were selected. Clinical records were reviewed retrospectively. Five of 10 patients had gigantic adenoma, 3 microadenoma, 2 large adenoma. The mean setup time was 5 minutes, and the operative time was 50 minutes in image-guided procedures. In all cases, the system worked well without malfunction. Continuous information regarding instrument location and trajectory was provided to the surgeon. Measurements of intraoperative accuracy in the axial, coronal, and.sagittal planes indicated a mean verified system error of 1.5 mm. for pituitary adenomas. After operation, the symptoms relieved in all patients. Neuronavigation can be applied during endonasal transsphenoidal endoscopic surgery and requires a minimal amount of time. It makes reoperation easier, faster, and safer.
Ali, R; Noma, U; Jansen, M; Smyth, D
Ectopic pituitary adenomas are extremely rare. We report a case of ectopic pituitary adenoma in the midline of the nasopharynx. This adenoma probably arose from the pharyngeal remnant of Rathke's pouch. We discuss a case of a lady who presented to our unit with 2 months history of dryness and sensation of lump in her throat and a long standing history of hypothyroidism. Examination of nasopharynx revealed a smooth and fluctuant midline mass. CT scan of nose and paranasal sinuses confirmed the midline mass with small defect communicating with the sphenoid sinus. An initial diagnosis of Thornwaldt's cyst was made and she underwent upper aerodigestive tract endoscopy and marsupialization of the mass. Histopathological examination revealed ectopic pituitary adenoma. Ectopic pituitary adenoma is an important differential diagnosis for a midline nasopharyngeal mass. It is recommended that prior to surgical resection of midline nasopharyngeal mass biopsy is taken and MRI is performed.
Strub, Graham M; Georgolios, Alexandros; Graham, Robert S; Powers, Celeste N; Coelho, Daniel H
Pleomorphic adenoma, also known as benign mixed tumor, is the most common tumor affecting the parotid gland and can reach massive size; however, intracranial invasion is rare. Recurrence of pleomorphic adenoma after excision is a well-known phenomenon and can present decades after resection of the primary tumor. Here we present the case of a 53-year-old man who presented to our clinic with ear fullness, otalgia, and hearing loss 30 years after undergoing total parotidectomy and external beam radiotherapy for pleomorphic adenoma. Magnetic resonance imaging revealed a massive transcranial tumor invading the mastoid cavity, the dura of the posterior fossa, the fallopian and semicircular canals, the jugular foramen, the lateral infratemporal fossa skull base, the sigmoid and transverse sinuses, and the superior parapharyngeal region. Gross examination and histopathological studies confirmed that the mass was a recurrent pleomorphic adenoma. Here we discuss the features of recurrent pleomorphic adenoma and review the current literature.
Knappe, Ulrich J; Jaspers, Christian; Buschsieweke, Desirée; Reinbold, Wolf-Dieter; Alomari, Ali; Saeger, Wolfgang; Ehlenz, Klaus; Mann, W Alexander; Kann, Peter Herbert; Feldkamp, Joachim
The diagnosis of Cushing disease is based on endocrinological pa-rameters, with no single test being specific. In some patients, dynamic thin-slice sellar magnetic resonance imaging fails to detect a pituitary tumor. The purpose of this study is to investigate the role of ectopic pituitary adenoma in this situation. In a retrospective chart review, 5 patients (6%) with ectopic adenomas were identified in 83 consecutive patients undergoing transsphenoidal surgery for adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas by 1 surgeon. In all 5 patients (all female, 32-41 years of age), an exclusively extrasellar ACTH-secreting adenoma was excised. Three adenomas were located in the cavernous sinus, 1 in the sphenoid sinus, and 1 in the ethmoidal cells. Histologically, none of the tumors showed signs of aggressiveness. Three of the 5 adenomas specifically expressed somatostatin receptor 5. In 4 patients with Cushing disease, postoperative remission was obtained, with 1 recurrence after 14 months. In the patient with Nelson syndrome, ACTH decreased from >800 to <80 pg/mL. Three patients underwent previous surgery elsewhere, including 1 hypophysectomy. In this case, the ectopic adenoma (positive for somatostatin receptor 5) in the ethmoidal cells turned out to be positive on gallium 68 DOTATATE positron emission tomography/computed tomography. The incidence of primarily ectopic ACTH-secreting adenomas in this series was 6%. In cases of negative MRI findings, an ectopic ACTH-secreting adenoma should be taken into account. 68 Ga DOTATATE positron emission tomography/computed tomography may identify ectopic pituitary adenomas. Hypophysectomy should always be avoided in primary surgery for CD.
Kobayashi, M; Enzan, H; Araki, K; Kawai, S; Kitagawa, N
We report a case of spontaneous hepatocellular adenoma with marked cystic degeneration in the non-cirrhotic liver. A 36 year-old Japanese woman with neither history of liver diseases nor use of oral contraceptives and steroids, complained of a 6 kg weight loss over 6 months. Barium meal study revealed an extramural compression along the fornix of the stomach. Abdominal ultrasonography (UC) and computed tomography (CT) demonstrated a mass in the left lateral segment of the liver that measured 11.6x9.5 cm with cystic lesions. Laboratory data on admission showed no significant findings. Celiac angiography revealed a hyper-vascular mass. Surgical exploration revealed a soft mass arising and protruding from the left lateral segment of the liver. Partial resection of the left lateral segment was performed. Histologically, the tumor was surrounded by a thin fibrous pseudocapsule. The neoplastic cells resembling normal hepatocytes around the tumor were large, pale and arranged in thick, irregular cords. Neither mitotic figures nor foci of dysplasia were present. The central portions of the tumor showed marked cystic degeneration. The tumor was histologically diagnosed as hepatocellular adenoma (HCA). HCA with cystic degeneration has been rarely reported.
Brand, Eelco C; Wallace, Michael B
The adenoma detection rate (ADR), i.e., the proportion of average risk patients with at least one adenoma detected during screening colonoscopy, is inversely associated with the development of interval colorectal cancer. Increasing the ADR is therefore an important proxy for increase in quality and efficacy of (screening) colonoscopy. Several potentially modifiable factors, such as, procedural and technological factors, and quality improvement programs, and their effect on the ADR will be reviewed. Procedural factors, such as, bowel preparation, withdrawal time, and position changes of the patient are associated with the ADR. While the relation of others, such as inspection during insertion, use of antispasmodic agents, and second inspection in the proximal colon, with the ADR is not completely clear. Many new colonoscopy technologies have been evaluated over recent years and are still under evaluation, but no unequivocal positive effect on the ADR has been observed in randomized trials that have mostly been performed by experienced endoscopists with high baseline ADRs. Several quality improvement programs have been evaluated and seem to have a positive effect on endoscopists' ADR. Increase in ADR is important for the protective benefit of colonoscopy. There are now extensive methods to measure, benchmark, and improve ADR but increased awareness of these is critical. We have provided an overview of potential factors that can be used to increase personal ADRs in every day practice.
Imran, Syed Ali; Ur, Ehud; Clarke, David B.
OBJECTIVE To determine an appropriate approach to managing prolactin-secreting adenomas of varying severity in pregnant women. SOURCES OF INFORMATION MEDLINE was searched using the key words “hyperprolactinemia,” “prolactinoma,” “pregnancy,” and “management.” Experience from a multidisciplinary tertiary care centre was also reviewed. Recommendations are based on mostly levels II and III evidence. MAIN MESSAGE With appropriate management, most women with hyperprolactinemia can achieve pregnancy. Although most women with prolactin-secreting adenomas during pregnancy need only careful observation, others might require medical treatment or even surgical evacuation. Ideally, such patients should be managed by multidisciplinary teams. In the absence of such teams, most pregnant women with small tumours can be managed safely by their primary physicians. Those with large tumours should be referred to specialists. CONCLUSION Family physicians play an important role in managing women with prolactinomas during pregnancy. Knowledge of current approaches to management is crucial in determining when and how to refer these patients. PMID:17872715
Khan, Mohammad Naeem; Raza, Syed Shahmeer; Hussain Zaidi, Syed Aizaz; Haq, Ihtisham Ul; Hussain, Amer Kamal; Nadeem, Muhammad Daniyal; Farid, Khayyam
Pleomorphic adenoma is the most common benign tumour of salivary glands which is Known for its wide pleomorphic architecture. It accounts for 45-75% of all salivary gland neoplasm. It can involve major as well as minor salivary glands. Among minor salivary glands (5-10% of cases) the palate lip, nasal cavity, pharynx, larynx and trachea are the most common sites. Diagnosis is made with biopsy along with histopathology. Wide excision with biopsy and removal of underlying extension of tumour is the treatment of choice. Sixty years old farmer presented with painless swelling in the upper lip for the last 8 years. History revealed recurrent mass in the midline of upper lip with no other complaints. He was operated 3 times for this complaint in the past. Belonging to poor socioeconomic status no biopsy records were found. On examination 3×4 cm hard and mobile mass was found. Lymph nodes of head and neck and parotid gland revealed no enlargement. Surgery by wide excision was planned. After baseline investigation surgery was done and the mass sent for histopathology. Biopsy reports showed pleomorphic adenoma on unusual site. Dissection of salivary gland tumour is important as they have propensity to metastasize. Wide local excision along with biopsy is the method of choice. Proper surgical techniques are required to avoid recurrence.
Takano, Shingo; Akutsu, Hiroyoshi; Hara, Takuma; Yamamoto, Tetsuya; Matsumura, Akira
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in solid tumors. However, its role in angiogenesis in pituitary adenoma is controversial. Angiogenesis in solid tumors including pituitary adenoma is commonly evaluated by microvascular density (MVD). Here, we evaluated MVD and the role of VEGF in vascular architecture in 51 pituitary adenomas (24 nonfunctioning, 13 prolactin-secreting, 10 growth hormone-secreting, 3 adrenocorticotropic hormone-secreting, and 1 thyroid-stimulating hormone-secreting). Paraffin sections were stained with CD34 and VEGF. MVD and vascular architecture parameters (vessel area, diameter, perimeter, and roundness) were evaluated in CD34-stained sections. Immunohistochemistry showed 27/51 tumors (53%) were VEGF-positive. There were no significant differences in MVD, any vascular parameter, or adenoma volume between VEGF-positive and VEGF-negative tumors. VEGF mRNA expression was significantly higher in VEGF-positive tumors. There were no significant correlations between VEGF mRNA expression and MVD or vascular parameters. However, vessel diameter and perimeter were significantly larger in prolactin-secreting than nonfunctioning and growth hormone-secreting macroadenomas. The difference in vessel diameter was observed among both VEGF-positive and all adenomas (micro- and macroadenoma). Thus, VEGF may have limited roles in the development of vascular architecture and tumor angiogenesis in pituitary adenomas, but the differences in vessel architecture by histotype (i.e., larger vessel diameter and perimeter in prolactin-secreting adenomas) suggest the hormonal regulation of vessel architecture rather than angiogenesis.
Molmenti, Christine L. Sardo; Hibler, Elizabeth A.; Ashbeck, Erin L.; Thomson, Cynthia A.; Garcia, David O.; Roe, Denise; Harris, Robin B.; Lance, Peter; Cisneroz, Martin; Martinez, Maria Elena; Thompson, Patricia A.; Jacobs, Elizabeth T.
Purpose The association between physical activity and colorectal adenoma is equivocal. This study was designed to assess the relationship between physical activity and colorectal adenoma recurrence. Methods Pooled analyses from two randomized, controlled trials included 1,730 participants who completed the Arizona Activity Frequency Questionnaire at baseline, had a colorectal adenoma removed within 6 months of study registration, and had a follow-up colonoscopy during the trial. Logistic regression modeling was employed to estimate the effect of sedentary behavior, light-intensity physical activity, and moderate-vigorous physical activity on colorectal adenoma recurrence. Results No statistically significant trends were found for any activity type and odds of colorectal adenoma recurrence in the pooled population. However, males with the highest levels of sedentary time experienced 47% higher odds of adenoma recurrence. Compared to the lowest quartile of sedentary time, the ORs (95% CIs) for the second, third, and fourth quartiles among men were 1.23 (0.88, 1.74), 1.41 (0.99, 2.01), and 1.47 (1.03, 2.11) respectively (P trend=0.03). No similar association was observed for women. Conclusions This study suggests that sedentary behavior is associated with a higher risk of colorectal adenoma recurrence among men, providing evidence of detrimental effects of a sedentary lifestyle early in the carcinogenesis pathway. PMID:25060482
Cha, Jae Myung; Lee, Joung Il; Joo, Kwang Ro; Shin, Hyun Phil; Jeun, Jung Won; Lim, Jun Uk
Type 2 diabetes mellitus is associated with an increased risk of colorectal neoplasia. However, association between prediabetes and colorectal adenoma has not been reported. The aim of this study was to evaluate the relationship between prediabetes and the presence of colorectal adenomas. Consecutive prediabetic subjects who underwent screening colonoscopy were enrolled at Kyung Hee University Hospital in Gangdong, Seoul, Korea, between June 2006 and May 2012. Non-prediabetic subjects were separately pooled from the database of the Center for Health Promotion between January 2012 and May 2012. Prediabetes was defined according to the recommendations of the American Diabetes Association. The prevalence of colorectal adenomas and their characteristics were compared between prediabetic and non-prediabetic groups. The prevalence of colorectal adenoma was higher in prediabetic subjects than in non-prediabetic subjects (39.6 vs. 30.6 %, respectively, p = 0.019). Prediabetic subjects had more multiple and high-risk adenomas than the control group in non-matched analysis (p = 0.000, respectively). In age-matched analysis, the prevalence of multiple and high-risk adenomas were significantly higher in a prediabetic group than those in a control group (44.4 vs. 28.4 %, p = 0.034; 51.9 vs. 34.6 %, p = 0.026, respectively). Furthermore, prediabetes (odds ratio = 2.198; 95 % confidence interval = 1.042-4.637; p = 0.039) was found to be an independent risk factor for a high-risk adenoma by multivariate analysis. The prevalence of multiple and high-risk colorectal adenomas is significantly higher in the prediabetic subjects than those in the control group. Furthermore, prediabetes was found to be an independent risk factor for a high-risk colorectal adenoma.
Pashtan, Itai; Oh, Kevin S; Loeffler, Jay S
Radiation therapy in the form of fractionated treatment or radiosurgery has an important role in the management of pituitary adenomas. Radiation is a reliable way of gaining local control for radiographically progressing pituitary adenomas. For functioning adenomas that are biochemically recurrent or persistent, radiation therapy is less consistent in offering biochemical normalization and often requires a latency period of years or decades. The decision of when to use radiation therapy is a delicate balance between its benefits and late sequelae, especially in the context of benign disease. Recent technological advances in radiation oncology hold the potential to minimize dose to uninvolved normal tissue and therefore reduce the risk of toxicity.
Lee, Jun Haeng; Kim, Jeong Wook; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik; Cho, Eun Yoon
Nonpolypoid adenomas, which can be important precursors of colorectal cancers, are difficult to find during routine colonoscopy. The aim of this study was to evaluate the usefulness of routine chromoendoscopy in Korea, where the incidence of colorectal cancer is low compared with western countries. Colonoscopy with chromoendoscopy was performed in 74 consecutive patients (48 men, 26 women; mean age 53.0 yr). After a careful examination of the whole colon, a defined segment of the sigmoid colon and rectum (0-30 cm from the anal verge) was stained with 20 ml of 0.2% indigocarmine solution with a spraying catheter. Nonpolypoid lesions were classified as flat or depressed types. Biopsies were taken from all lesions detected before or after staining with indigocarmine. Indications for colonoscopy included routine check-up (21 patients), diarrhea or loose stool (14 patients), abdominal pain (12 patients), constipation (7 patients), bleeding (6 patients), and others (14 patients). Before staining, 58 lesions were found in 30 patients (43.2%). Histology showed tubular adenoma in 41 lesions, hyperplastic or inflammatory changes in 14 lesions, adenocarcinoma in 2 lesions, and villous adenoma in 1 lesion. After indigocarmine staining for normal-looking distal 30 cm colorectal mucosa, 176 lesions were found in 46 patients (62.2%). Histologically, 158 lesions were hyperplastic or inflammatory in nature, and 17 lesions (from 11 patients) were tubular adenomas. There was one serrated adenoma. Eighteen adenomas seen only after spraying indigocarmine were 2.6 +/- 0.6 mm in diameter, and all of them were classified as flat adenomas. There was no depressed-type adenoma. No adenoma with high grade dysplasia, villous histology, or cancer was found after staining. Presence of macroscopic adenomatous lesions or carcinoma before staining could not predict the existence of adenoma after staining. In a large proportion of patients, flat or depressed adenomas could be found after spraying
Yan, Mao-Lin; Pan, Jun-Yong; Bai, Yan-Nan; Lai, Zhi-De; Chen, Zhong; Wang, Yao-Dong
Familial adenomatous polyposis (FAP) or Gardner's syndrome is often accompanied by adenomas of the stomach and duodenum. We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis. Only 8 cases of adenomas or adenocarcinoma of the common bile duct have been reported in the literature in patients with FAP or Gardner's syndrome. Those patients presented with acute cholangitis or pancreatitis. Local excision or Whipple procedure may be the reasonable surgical option.
Rex, Douglas K; Ponugoti, Prasanna; Kahi, Charles
Classification schemes for differentiation of conventional colorectal adenomas from serrated lesions rely on patterns of blood vessels and pits. Morphologic features have not been validated as predictors of histology. The aim of this study was to describe the prevalence of the "valley sign" and validate it as a marker of conventional adenomas. Three experts judged the prevalence of the valley sign in 301 consecutive small adenomas. Medical students were taught to recognize the valley and were tested on their recognition of the valley sign. Consecutive diminutive polyps were video-recorded and used to validate the association of the valley sign with conventional adenomas. The prevalence of the valley sign in 301 consecutive adenomas <10 mm in size, determined by 3 experts, ranged from 35% to 50%. Kappa values for agreement among the 3 experts were 0.557, 0.679, and 0.642. Ten medical students were taught to interpret the valley sign and recognized it with accuracy of 96% or higher in 50 selected photographs of diminutive polyps. Four medical students evaluated video-recordings of 170 consecutive diminutive polyps for the presence of the valley sign. Kappa values for the interpretation of the valley sign ranged from 0.52 to 0.68 among the students. The sensitivity of the valley sign for adenoma ranged from 40.2% to 54.9%, and specificity ranged from 90.2% to 91.7%. The valley sign was strongly associated with adenomas (P < .0001). The valley sign is insensitive but highly specific for conventional adenoma in diminutive polyps. It may enhance classification schemes for differentiation of adenomas from serrated lesions based on vessels and pits. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.
Otto, C.A.; Marshall, J.C.; Lloyd, R.V.; Sherman, P.S.; Wieland, D.M.
Prolactin-secreting pituitary adenomas are the most common type of pituitary tumors. Detection currently depends on physical symptoms, elevated serum prolactin levels and CT scans. An imaging agent which specifically localized in prolactinomas based on some functional characteristic of the tumor would be of considerable clinical value not only for early detection but also for monitoring of therapy. Tritiated spiroperidol (/sup 3/H-Sp) was selected for evaluation based on 1) the presence of D-2 receptors in normal anterior pituitary and adenoma tissue and 2) the high affinity of spiroperidol for D-2 receptors. Recent data have established that implantation of diethylstilbestrol (DES) in Fischer F344 rats induced prolactin-secreting tumors in the pituitary. /sup 3/HSp was evaluated in pituitary tissue of both control and DES-treated rats. /sup 3/HSp concentration in normal female anterior pituitary tissue was found to be about 0.27% kg dose/g from 5 min to 4hrs. This value was about 10 times levels in cortex, cerebellum and striatum. In DES-treated rats the % kg dose/g values remained approximately the same. A 5-fold increase in serum prolactin was associated with a 6-fold increase in both pituitary weight and % dose/organ. The data suggests that although total pituitary weight has increased due to tumor growth (reflected in increased values for % dose/organ), the relative number of receptors per g of tissue has remained constant. This result is in agreement with observations of others on D-2 receptor concentration in prolactinomas.
Budhathoki, Sanjeev; Iwasaki, Motoki; Yamaji, Taiki; Sasazuki, Shizuka; Tsugane, Shoichiro
Coffee is a commonly consumed beverage which contains several potential anticarcinogenic and chemopreventive compounds, and has been hypothesized to have protective effects in colorectal neoplasia. However, the limited available data on coffee consumption in relation to colorectal adenoma (CRA), a precursor lesion to most colorectal cancers, remain largely inconsistent. In this study, we evaluated the association of coffee intake with the risk of CRA in a middle-aged Japanese population. Study subjects were selected from examinees who underwent total colonoscopy as part of a cancer screening program and responded to self-administered dietary and lifestyle questionnaires. A total of 738 patients with adenoma and 697 controls were included in the study. Coffee intake was assessed with a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) of CRA, with adjustment for potential confounding factors. High coffee consumption was associated with a reduced risk of CRA, with a multivariate-adjusted OR for the highest versus lowest quartile of coffee intake of 0.67 (95% CI = 0.48-0.93; ptrend = 0.02). The inverse association of coffee intake was limited to proximal (OR = 0.64; 95%CI = 0.44-0.95; ptrend = 0.04) and distal colon adenoma (OR = 0.62; 95%CI = 0.39-0.99; ptrend = 0.06), and appeared to be more evident with small (OR = 0.68; 95%CI = 0.49-0.96; ptrend = 0.04) and single adenomas (OR = 0.65; 95%CI = 0.44-0.95; ptrend = 0.02). Green tea intake was not found to be associated with CRA risk. This study provides support for the protective effect of coffee drinking on colon adenomas, a precursor of colon cancer. © 2014 UICC.
Castillo-Lancellotti, C; Tur Marí, J A; Uauy Dagach, R
Observational studies show that folate levels may be associated with the development of adenomas and colorectal cancer, suggesting that folic acid supplementation may have a preventive effect. Systematic review of scientific evidence from randomized placebo-controlled clinical studies to identify the effects of folic acid supplementation on the recurrence of colorectal adenomas. Medline via Pubmed systematic review of randomized clinical trials, double-blind and placebo-controlled and references, specifically to evaluate the effect of acid supplementation on the recurrence of colorectal adenomas. Seven randomized clinical trials that met the inclusion criteria were selected and evaluated for analysis based on pre established criteria. The selected studies do not support that folic acid supplementation is beneficial in recurrence of colorectal adenomas. We observed in some studies differences in risk by type of folate suggesting to review the criteria and levels of supplementation in some population subgroups with higher risks.
Kogan, M I; Kireev, A Iu
Blood levels of total PSA and testosterone, size of the prostatic gland, Qmax were measured in 40 patients with prostatic adenoma symptoms treated with alfusozine in a dose 10 mg/day before the treatment, on the treatment week 4, 12 and 24. At the same time the examinees were questioned using IPSS, MSHQ, IIEF questionnaires. The sexuality phenotype was estimated according to the Rostov Questionnaire of Integral Male Sexuality. It was found that sexuality phenotypes (hypo-, normo- and hypersexuality) occur with the same frequency in males with prostatic adenoma symptoms. Hypersexual men with prostatic adenoma have more definite lower urinary tract symptoms, worse erection and ejaculation, more frequent signs of hypogonadism. The highest alfusozine efficacy was observed in normo- and hyposexual men with prostatic adenoma who achieved better results in improvement of Qmax, symptoms of the lower urinary tract, erectile and ejaculation function. The treatment efficacy in the hypersexual men is low.
Feng, Qiang; Liang, Suisha; Jia, Huijue; Stadlmayr, Andreas; Tang, Longqing; Lan, Zhou; Zhang, Dongya; Xia, Huihua; Xu, Xiaoying; Jie, Zhuye; Su, Lili; Li, Xiaoping; Li, Xin; Li, Junhua; Xiao, Liang; Huber-Schönauer, Ursula; Niederseer, David; Xu, Xun; Al-Aama, Jumana Yousuf; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Arumugam, Manimozhiyan; Tilg, Herbert; Datz, Christian; Wang, Jun
Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.
Polat, Kerem; Doğan, Mansur; Yüce, Salim; Uysal, Ismail Önder; Müderris, Suphi
Parapharyngeal space tumors are rare, accounting for 0.5% of head and neck neoplasms. Most of them are benign and originate in the salivary glands, especially the pleomorphic adenoma. We presented a 47-year-old man with parotid tail pleomorphic adenoma extending to the parapharyngeal space. The patient applied to our clinic with the complaints of a painless mass on his neck and in his mouth for 3 months. After fine needle aspiration biopsy, the mass was diagnosed as pleomorphic adenoma. The patient was hospitalized and operated in our clinic. As we see in literature review, parapharyngeal space tumors are rare, and most of them are pleomorphic adenomas arising from the deep lobe of the parotid gland and extend into the PPS.
Herman, V.; Drazin, N.Z.; Gonskey, R.; Melmed, S. )
Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. The authors studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K-, and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7 and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact on GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including, PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRl-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site. 31 refs., 5 figs., 2 tabs.
Gogichaev, Z Kh; zolotarev, I I
The authors have gained minimum blood losses when suturing with provisional catgut ligature through the urinary bladder bottom between interureteral fold and internal urethral orifice yet before dessection of adenoma surgical capsule and tumor enucleation. Depending on the functional state of the upper urinary tract, the bladder tonus and adenoma size, the method of postoperative drainage of the urinary bladder is selected: cystostomy, microirrigation, active suction, etc.
Jacobs, Elizabeth T.; Martínez, María Elena; Alberts, David S.; Jiang, Ruiyun; Lance, Peter; Lowe, Kimberly A.; Thompson, Patricia A.
Background and Aims Obesity has been associated with increased risk for colorectal adenoma, though its role as a risk factor after polypectomy for successive events is unclear. Therefore, we sought to evaluate the effect of anthropometric measures of obesity on adenoma after polypectomy. Methods Subjects with baseline adenomas (n=2465) and follow-up colonoscopy data were drawn from two randomized trials designed to prevent adenoma recurrence. Results Presence of a BMI ≥ 30 kg/m2 was associated with a non-significant 17% increase in the odds for any adenoma recurrence among all subjects (OR=1.17; 95% CI=0.92–1.48). This result was confined to men (OR= 1.36; 95% CI=1.01–1.83), and not observed for women (OR=0.90; 95% CI= 0.60–1.33). Results for waist circumference did not reach statistical significance, though trends were similar to those for BMI. Analyses of the effects of obesity on more clinically significant lesions demonstrated that high BMI was a slightly stronger risk factor for advanced adenoma recurrences in men (OR=1.62; 95% CI=1.04–2.53) when compared to non-advanced lesions (OR= 1.26; 95% CI= 0.91–1.75). Additionally, we observed an association for obesity and odds of adenoma recurrence among participants reporting a family history of colorectal cancer (OR=2.25; 95% CI= 1.32–3.84), but not for those without (OR=1.00; 95%= CI-0.77–1.31; pint = p=0.008). Conclusions Our results support obesity as a risk factor for subsequent short-interval development of colorectal adenomas, particularly among men and persons with a family history of colorectal cancer. Further, obesity in men appears to be strongly associated with the development of clinically advanced lesions. PMID:17553754
Yin, Wu; Mo, Xiang-lan; Wen, Zong-hua; Zhou, Xiang-zhen; Zhou, Min-yan; Wei, Hai-ming
To explore the clinicopathological features, immunophenotype, differential diagnosis, pathogenesis and prognosis of villous adenoma with poorly differentiated adenocarcinoma of the urinary tract. Clinical and pathologic findings of 3 cases of villous adenoma with poorly differentiated adenocarcinoma of the urinary tract were analyzed by gross examination, microscopic investigation and immunohistochemical staining. The related literatures were reviewed. All of the three cases were middle-aged or elderly patients. Three cases all presented with hematuria and mucusuria. Endoscopic examination identified that case 1 had a polyp with broad attachment in the dome of bladder, case 2 had a solid mass in the ureter, and case 3 had a exophytic fungating tumor in the renal pelvis. Microscopically, case 1 revealed a papillary lesion with finger-like processes lined by pseudostratified columnar epithelium with abundant goblet cells. The cells demonstrated moderate degree dysplasia. In case 2 and case 3, both villous adenomas and poorly differentiated adenocarcinoma were observed, the adenoma cells arranged in a cribriform pattern, and the tumor cells showed severe atypia, mitotic activity, and transition with invasive poorly differentiated adenocarcinoma. Immunohistochemically, the tumor cells in three cases were positive for CK20, CEA,EMA and MUC-1; none of them expressed cdx-2 and PSA; In case 2 and 3, the same immunophenotype of villous adenomas and their associated adenocarcinomas was observed, but the number of the positive cells of p53 and Ki-67 staining were significantly increased in the area of adenocarcinomas than in that of the villous adenomas. Villous adenoma of the urinary tract is rare. It can occur in the urinary bladder, urachus, renal pelvis, ureter and urethra. These lesions may have malignant potential and frequently coexist with other malignant tumors. So, villous adenoma of the urinary tract should be removed completely and sampled thoroughly to avoid
Quillo, Amy R; Grant, Clive S; Thompson, Geoffrey B; Farley, David R; Richards, Melanie L; Young, William F
Historically, treatment of confirmed primary aldosteronism has been adrenalectomy for unilateral adenoma; bilateral hypersecretion is treated medically. Increasingly, we use adrenal venous sampling (AVS) to define unilateral hypersecretion. Histology of glands resected based on AVS often reveals multiple nodules or hyperplasia. The aim of this study was to compare patients with multiple nodules or hyperplasia with those with single adenoma with regard to cure, preoperative imaging, AVS ratio, and biochemical evaluation to determine if a nonsingle adenoma (NSA) process could be predicted to impact extent of adrenalectomy. This was a retrospective study reviewing a single-institutional surgical experience at a tertiary academic center from 1993 to 2008, during which 215 patients with primary aldosteronism underwent unilateral adrenalectomy based on imaging of a single adenoma (normal contralateral gland) or AVS ratios. Histology included single adenoma versus NSA; cure was defined as normal immediate postoperative plasma or urine aldosterone level, normal aldosterone:renin ratio, or normotension without antihypertensive medications. Follow-up (mean 13 months, range 0 to 185 months) was available for 167 patients: 132 (79%) single adenoma and 35 (21%) NSA. All 35 patients with NSA and 128 patients (97%) with single adenoma were cured. Imaging studies correctly predicted NSA in 29% and 57% when combined with AVS. Identifying patients with NSA preoperatively was impossible biochemically: mean serum and urinary aldosterone levels and AVS ratios were not different than those of the single adenoma group. Twenty-one percent of patients had NSA, all cured by unilateral adrenalectomy. No preoperative evaluation reliably predicted NSA. Therefore, total unilateral adrenalectomy was safest given the potential for incomplete resection with partial adrenalectomy. Accurate AVS is highly predictive of cure irrespective of the unilateral adrenal histology. Copyright © 2011 American
Chew, Yok Kuan; Brito-Mutunayagam, Sushil; Chong, Aun Wee; Prepageran, Narayanan; Chandran, Patricia Ann; Khairuzzana, Baharudin; Lingham, Omkara Rubini
Pleomorphic adenoma is the most common type of benign salivary gland tumor. It can also be found in the larynx, ear, neck, and nasal septum. It is rarely found in the maxillary sinus, and it has never been reported in the frontal sinus. We report a case of pleomorphic adenoma of the frontal sinus that masqueraded as a mucocele. We discuss the clinical presentation, diagnosis, and treatment of this patient, and we review the literature.
Keerthi, R; Raut, Rohan P; Vaibhav, N; Ghosh, Abhishek
Carcinoma ex pleomorphic adenoma (CXPA) is a carcinoma arising from a primary or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to clinicians and pathologists. The entity is difficult to diagnose preoperatively. Pathological assessment is the gold standard for making the diagnosis. Treatment for CXPA often involves an ablative surgical procedure, which may be followed by radiotherapy. We report a case of a 65-year-old lady with a history of recurrent swelling in the left preauricular region and a history of surgery 10 years back, in the same region. Preoperatively, a diagnosis of pleomorphic adenoma of the parotid gland metastasizing to the cervical lymph node was made, but postoperatively it was reported as CXPA adenoma of the parotid gland. A radical parotidectomy involving en bloc resection of the facial nerve along with deep and superficial lobes of the parotid was performed followed by radiotherapy. The fact that pleomorphic adenomas are classified as benign tumors should not overshadow the wide range of biological behaviors associated with these tumors. On account of the potential for malignant transformation, surgical treatment must be properly performed. Surgery followed by radiotherapy should be considered as the standard care for a patient with carcinoma ex pleomorphic adenoma.
Zoli, Matteo; Faustini-Fustini, Marco; Mazzatenta, Diego; Marucci, Gianluca; De Carlo, Eugenio; Bacci, Antonella; Pasquini, Ernesto; Lanzino, Giuseppe; Frank, Giorgio
OBJECT Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon. METHODS The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. RESULTS Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18-51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma "shifted" to a functioning adenoma and then regressed back to a silent form with spontaneous
Moore, Patrick S.; Zamboni, Giuseppe; Brighenti, Antonietta; Lissandrini, Daniele; Antonello, Davide; Capelli, Paola; Rigaud, Gildas; Falconi, Massimo; Scarpa, Aldo
Pancreatic serous microcystic adenomas (SCAs) are rare, benign tumors with a striking female preference. Virtually no information is available about chromosomal or genetic anomalies in this disease. We performed extensive molecular characterization of 21 cases of formalin-fixed, paraffin-embedded sporadic SCAs consisting in genome-wide allelic loss analysis with 79 microsatellite markers covering all 22 autosomes, assessment of microsatellite instability, and mutational analysis of the VHL, K-ras, and p53 genes in nine cases for which frozen tissue was available. Although no case showed microsatellite instability of the type seen in mismatch repair-deficient tumors, a relatively low fractional allelic loss of 0.08 was found. Losses on chromosome 10q were the most frequent event in SCAs (50% of cases), followed by allelic losses on chromosome 3p (40% of cases). Moderately frequent losses (>25% of cases) were found on chromosomes 1q, 2q, and 7q. The VHL gene, located on chromosome 3p, had somatic inactivating mutations in two of nine cases (22%), whereas no mutations were found in either K-ras or p53, in agreement with the finding that all 21 cases stained negative for p53 by immunohistochemistry. Our study indicates that the involvement of chromosomal arms 10q and 3p is characteristic of SCAs and that the VHL gene is involved in a subset of sporadic cases. PMID:11141506
Imaizumi, Katsuichi; Harada, Yoshinori; Wakabayashi, Naoki; Yamaoka, Yoshihisa; Dai, Ping; Tanaka, Hideo; Takamatsu, Tetsuro
Recently autofluorescence imaging (AFI) endoscopy, visualizing tissue fluorescence in combination with reflected light, has been adopted as a technique for detecting neoplasms in the colon and other organs. However, autofluorescence colonoscopy is not infallible, and improvement of the detection method can be expected to enhance the performance. Colonic mucosa contains metabolism-related fluorophores, such as reduced nicotinamide adenine dinucleotide, which may be useful for visualizing neoplasia in autofluorescence endoscopy. We examined sliced cross-sections of endoscopically resected tubular adenomas under a microscope. Fluorescence images acquired at 365-nm excitation (F365ex) and 405-nm excitation (F405ex), and reflectance images acquired at 550 nm (R550) were obtained. Fluorescence ratio (F365ex/F405ex) images and reflectance/fluorescence ratio (R550/F405ex) images were calculated from the acquired images. The fluorescence ratio images could distinguish adenomatous mucosa from normal mucosa more clearly than the reflectance/fluorescence ratio images. The results showed that the autofluorescence ratio imaging is a potential technique for increasing the diagnostic power of autofluorescence endoscopy.
Naunheim, Molly; Wu, Xin; Ryan, William R; Wang, Steven J; Heaton, Chase M
Surgery for recurrent pleomorphic adenoma (PA) can be challenging and may increase the risk of operative complications, particularly facial nerve weakness. As observation may be a viable alternative to surgery for slow-growing tumors, our objective was to assess the growth rate of recurrent PAs. This study is a case series of patients at our tertiary academic medical center with recurrent PA. Two magnetic resonance images (MRI) were compared; total volume (TV) of recurrent tumor on both studies was calculated to obtain our main outcomes of percent change in TV and tumor growth rate. Fourteen patients with recurrent PA had a median interval time between MRI of 12.8 months. Though growth rates were variable, the median continuous compound growth per year was 10.2%. Notably, 3 patients (21%) had no growth, and 2 patients (14%) had a reduction in TV. The median growth rate for enlarging tumors is estimated at 10.2% per year. Due to variability, tumor growth rate should be estimated on an individual patient basis. For slow-growing tumors, physicians may weigh the risk of this slow growth with the morbidity of reoperation.
Zaidi, Hasan A; Cote, David J; Dunn, Ian F; Laws, Edward R
Despite formal pathological criteria, not all atypical pituitary adenomas display clinically aggressive behavior. We set out to determine which factors predict a clinically aggressive phenotype among a cohort of atypical pituitary adenomas. Medical records were retrospectively reviewed from April 2008 to July 2015. Of 569 pituitary adenomas, 47 (8.3%) patients were surgically treated for atypical adenomas as defined by the WHO criteria. Clinically aggressive adenomas were defined as occurring in those patients who necessitated additional therapeutic intervention after the index (first) surgery, including additional surgery, medical therapy, or radiosurgery. Forty-seven patients with histopathological and immunohistochemical confirmation of atypical adenomas were identified and of these, 23 were noted to have a clinically aggressive course. Among the remaining 24 patients, the disease remained quiescent after the index surgery. On univariate analysis, clinically aggressive lesions were more likely to have a larger axial diameter on MRI (2.9±1.9cm vs. 1.9±0.7cm, p=0.02), greater incidence of cavernous sinus invasion (65.2% vs. 20.8%, p<0.01), and greater incidence of clival extension (60.9% vs. 0, p<0.01) on preoperative imaging. The two groups were equivalent with regard to immunohistochemical staining for ACTH, HGH, LH, FSH, PRL, and TSH. Clinically aggressive lesions, however, trended towards a greater average MIB-1 proliferative index (7.5%±4.9 vs. 6.0%±3.6, p=0.03). On multivariate analysis, the MIB-1 proliferative index trended towards statistical significance (p=0.06) as an independent predictor of clinical aggressiveness. Atypical pituitary adenomas are defined by a rigid set of immunohistochemical markers, but not all necessarily demonstrate an aggressive clinical phenotype.
Cugat, E.; Veloso, E.; Marco, C.
Introduction: Duodenal villous adenoma arising from the ampulla of Vater has a high risk of malignant development. Excluding associated malignant disease prior to resection of an adenoma of the ampulla is not always possible. Therefore, the surgical procedure of choice to treat this rare tumour is still controversial. Objective: To evaluate retrospectively results of treatment of villous adenoma arising from ampulla of Vater with dysplasia or associated carcinoma limited to the ampulla. Patients and Methods: From 1985 to 1996, eight patients have been diagnosed with ampullary villous adenoma suitable for resection. We have reviewed treatment, morbidity, mortality, follow-up and final outcome. Results: Pancreatoduodenectomy (PD) was performed in 4 patients. Transduodenal ampullectomy and endoscopic resection was performed in 2 patients each. There was no perioperative mortality. None of the patients had biliary, pancreatic or intestinal leakage but two patients who underwent PD had minor postoperative complications. The mean follow-up was 44 (range: 6–132) months. Villous adenoma was associated with adenocarcinoma in 50% of the cases (4/8 patients). During the followup both patients who underwent transduodenal ampullectomy developed recurrent disease. All patients initially treated by PD are alive without evidence of recurrent disease. Conclusions: Treatment of villous adenoma of the ampulla must be individualized within certain limits. In our series, PD achieve good results and it appears to be the procedure of choice in order to treat villous adenomas with proved presence of carcinoma, carcinoma in situ or severe dysplasia. Endoscopic or local resection may be appropriate for small benign tumours in high risk patients. PMID:10674748
Ferlitsch, Monika; Reinhart, Karoline; Pramhas, Sibylle; Wiener, Caspar; Gal, Orsolya; Bannert, Christina; Hassler, Michaela; Kozbial, Karin; Dunkler, Daniela; Trauner, Michael; Weiss, Werner
Although some studies have shown that men are at greater age-specific risk for advanced colorectal neoplasia than women, the age for referring patients to screening colonoscopy is independent of sex and usually recommended to be 50 years. To determine and compare the prevalence and number needed to screen (NNS) for adenomas, advanced adenomas (AAs), and colorectal carcinomas (CRCs) for different age groups in men and women. Cohort study of 44,350 participants in a national screening colonoscopy program over a 4-year period (2007 to 2010) in Austria. Prevalence and NNS of adenomas, AAs, and CRCs in different age groups for men and women. The median ages were 60.7 years (interquartile range [IQR], 54.5-67.5 years) for women and 60.6 years (IQR, 54.3-67.6 years) for men, and the sex ratio was nearly identical (51.0% [22,598] vs 49.0% [21,572]). Adenomas were found in 19.7% of individuals screened (95% CI, 19.3%-20.1%; n = 8743), AAs in 6.3% (95% CI, 6.1%-6.5%; n = 2781), and CRCs in 1.1% (95% CI, 1.0%-1.2%; n = 491); NNS were 5.1 (95% CI, 5.0-5.2), 15.9 (95% CI, 15.4-16.5), and 90.9 (95% CI, 83.3-100.0), respectively. Male sex was significantly associated with a higher prevalence of adenomas (24.9% [95% CI, 24.3%-25.4%] vs 14.8% [95% CI, 14.3%-15.2%]; P < .001; unadjusted odds ratio [OR], 1.9 [95% CI, 1.8-2.0]), AAs (8.0% [95% CI, 7.6%-8.3%] vs 4.7% [95% CI, 4.4%-4.9%]; P < .001; unadjusted OR, 1.8 [95% CI, 1.6-1.9]), and CRCs (1.5% [95% CI, 1.3%-1.7%] vs 0.7% [95% CI, 0.6%-0.9%]; P < .001; unadjusted OR, 2.1 [95% CI, 1.7-2.5]). The prevalence of AAs in 50- to 54-year-old individuals was 5.0% (95% CI, 4.4%-5.6%) in men but 2.9% (95% CI, 2.5%-3.4%) in women (adjusted P = .001); the NNS in men was 20 (95% CI, 17.8-22.6) vs 34 in women (95% CI, 29.1-40; adjusted P = .001). There was no statistical significance between the prevalence and NNS of AAs in men aged 45 to 49 years compared with women aged 55 to 59 years (3.8% [95% CI, 2.3%-6.1%] vs 3.9% [95% CI, 3.3%-4.5%] and
Boehnert, M; Hensen, J; Henig, A; Fahlbusch, R; Gross, P; Buchfelder, M
Severe hyponatremia has been described after elective surgery with subsequent permanent brain damage. Other authors, however, have noted that morbidity and mortality rates of severe hyponatremia have been greatly overestimated. We retrospectively examined 19 patients (8 male, 11 female) who developed severe hyponatremia (100 to 124 mmol/liter) after transsphenoidal surgery for pituitary adenomas. Eight patients had hormonally inactive adenomas, 5 ACTH-secreting adenomas, 2 GH-secreting adenomas and 4 prolactin-secreting adenomas. The mean age of the patients was 47.5 years, with a range from 16 to 71 years. The mean preoperative serum sodium level was 137.8 mmol/liter. The timing of hyponatremia showed two different patterns. Five patients developed early postoperative hyponatremia (mean 114.0 mmol/liter +/- 4.85) and 14 patients showed the lowest mean serum level one week after surgery (118.1 mmol/liter +/- 6.86). Patients with early hyponatremia had fewer and less severe symptoms than patients with delayed hyponatremia. None of the patients developed seizures or a demyelination syndrome. Despite severe degree of hyponatremia for most of our patients treatment with water restriction and oral sodium supplementation was sufficient.
Lu, Yingying; Chen, Jing; Zheng, Junyuan; Hu, Guoyong; Wang, Jingjing; Huang, Chunlan; Lou, Lihong; Wang, Xingpeng; Zeng, Yue
Recent reports have suggested that the gut microbiota is involved in the progression of colorectal cancer (CRC). The composition of gut microbiota in CRC precursors has not been adequately described. To characterize the structure of adherent microbiota in this disease, we conducted pyrosequencing-based analysis of 16S rRNA genes to determine the bacterial profile of normal colons (healthy controls) and colorectal adenomas (CRC precursors). Adenoma mucosal biopsy samples and adjacent normal colonic mucosa from 31 patients with adenomas and 20 healthy volunteers were profiled using the Illumina MiSeq platform. Principal coordinate analysis (PCoA) showed structural segregation between colorectal adenomatous tissue and control tissue. Alpha diversity estimations revealed higher microbiota diversity in samples from patients with adenomas. Taxonomic analysis illustrated that abundance of eight phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Chloroflexi, Cyanobacteria, Candidate-division TM7, and Tenericutes) was significantly different. In addition, Lactococcus and Pseudomonas were enriched in preneoplastic tissue, whereas Enterococcus, Bacillus, and Solibacillus were reduced. However, both PCoA and cluster tree analyses showed similar microbiota structure between adenomatous and adjacent non-adenoma tissues. These present findings provide preliminary experimental evidence supporting that colorectal preneoplastic lesion may be the most important factor leading to alterations in bacterial community composition. PMID:27194068
Nugent, Julia L; McCoy, Amber N; Addamo, Cassandra J; Jia, Wei; Sandler, Robert S; Keku, Temitope O
Several studies have linked bacterial dysbiosis with elevated risk of colorectal adenomas and cancer. However, the functional implications of gut dysbiosis remain unclear. Gut bacteria contribute to nutrient metabolism and produce small molecules termed the "metabolome", which may contribute to the development of neoplasia in the large bowel. We assessed the metabolome in normal rectal mucosal biopsies of 15 subjects with colorectal adenomas and 15 nonadenoma controls by liquid chromatography and gas chromatography time-of-flight mass spectrometry. Quantitative real-time PCR was used to measure abundances of specific bacterial taxa. We identified a total of 274 metabolites. Discriminant analysis suggested a separation of metabolomic profiles between adenoma cases and nonadenoma controls. Twenty-three metabolites contributed to the separation, notably an increase in adenoma cases of the inflammatory metabolite prostaglandin E2 and a decrease in antioxidant-related metabolites 5-oxoproline and diketogulonic acid. Pathway analysis suggested that differential metabolites were significantly related to cancer, inflammatory response, carbohydrate metabolism, and GI disease pathways. Abundances of six bacterial taxa assayed were increased in cases. The 23 differential metabolites demonstrated correlations with bacteria that were different between cases and controls. These findings suggest that metabolic products of bacteria may be responsible for the development of colorectal adenomas and CRC.
Korbonits, Márta; Storr, Helen; Kumar, Ajith V
Familial Isolated Pituitary Adenomas (FIPA), an autosomal dominant disease with low penetrance is being increasingly recognized. FIPA families can be divided into two distinct groups based on genetic and phenotypic features. Patients with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are characterized by young-onset somatotroph or lactotroph macroadenomas, while in the other, larger group of FIPA patients with typically adult-onset disease and more varied adenoma types, no causative gene(s) has been identified. Young-onset macroadenoma patients can also be identified with germline AIP mutation without an apparent family history. Further data and longer follow-up are necessary to establish formal guidelines, but the current data suggest genetic screening of the AIP gene in patients with a pituitary adenoma and no other associated features who have (i) a family history of pituitary adenoma, (ii) childhood-onset pituitary adenoma or (iii) a pituitary somatotroph or lactotroph macroadenoma diagnosed before the age of 30 years.
Nascimento, Luiz Augusto; Vilela, Thais Gonçalves Pinheiro
Introduction Pleomorphic adenoma, also known as mixed tumor, is the most common benign tumor of the major and minor salivary glands. The occurrence of pleomorphic adenoma of the tongue base is very rare, and very few cases have been reported in the literature. Objective The authors present a rare case of pleomorphic adenoma of the tongue base and a review of the literature. Case Report A 55-year-old woman had an extensive cervical mass, with little pain, from the submental level to the level below the hyoid bone. Fiberoptic endoscopic examination showed an extensive mass at the base of the tongue with considerable reduction in the airway. Magnetic resonance image scan revealed a contrast-enhancing mass of heterogeneous density over the base of the tongue of 8 × 8 × 7 cm and a reduction of the hypopharyngeal airway. Biopsy of the lesion was performed along with a tracheostomy due to the bulging tongue base and acute respiratory failure. Histologic examination with an immunohistochemistry study revealed a diagnosis of pleomorphic adenoma. The excision of the tumor was performed by a lateral pharyngotomy approach and the total mass was excised. Conclusion The authors consider the rarity of this case and show that this is the 11th and the largest pleomorphic adenoma reported in the English-language medical literature.
de Ridder, Mischa; Smeele, Ludi E; Balm, Alfons J M
The importance of complete excision of a benign pleomorphic adenoma is illustrated by two patients' histories. A 28-year-old man underwent a local excision of a nodule under the left ear without histological confirmation. Ten years later he returned to our institute with a large multilocular process and subcutaneous nodules. Cytology showed pleomorphic adenoma. Patient was treated with total facial nerve preserving parotidectomy and radiotherapy. An 81-year-old male underwent a surgical removal of a swelling under his left ear eight years before admission for a large diffusely infiltrating tumor in the neck. Repeated cytology showed carcinoma ex pleomorphic adenoma. This tumor was inoperable and he was treated by palliative irradiation. In case of incomplete resection, pleomorphic adenoma cells are spilled with an increasing chance of local recurrence. Also degeneration into carcinoma ex pleomorphic adenoma is possible after incomplete resection, with impact on survival. These risks of residual disease determine the need of centralization of diagnosis and treatment of this benign parotid tumor.
Kessoku, Hisashi; Yoshimura, Tsuyoshi; Iino, Takashi; Tanaka, Yasuhiro
In January 2011, a 64-year-old woman who had undergone tumor resection for pleomorphic adenoma of the left parotid gland four times since her first operation in 1996 visited an orthopedist in our hospital complaining of pain in her right lower limb. Computed tomography (CT) of the whole body showed multiple tumors on the left parotid gland, right kidney, the sacrum, and both lungs. Biopsy of the sacral region and right nephrectomy were performed based on a clinical diagnosis of sacral and pulmonary metastases from renal cell carcinoma, and palliative radiation therapy was immediately begun on the sacral region. Given the definitive pathological diagnosis of metastasis of pleomorphic adenoma of the parotid gland, the recurrent tumor of the left parotid gland and the surrounding lymph nodes were first removed. Postoperative findings demonstrated that the pleomorphic adenoma had metastasized to the lymph nodes. The lung tumors were resected subsequently, and postoperative findings led to the diagnosis of pleomorphic adenoma. Metastasis of pleomorphic adenoma is known to be extremely rare, and to our knowledge this case of metastasis to a kidney is the first reported in Japan.
Hulsmans, F H; Tio, T L; Mathus-Vliegen, E M; Bosma, A; Tytgat, G N
Exclusion of focal infiltrating malignancy in colorectal villous adenoma is a prerequisite when nonsurgical treatment is considered. In a study of 81 patients with endoscopically identified colorectal villous adenoma screened for malignancy with transrectal ultrasonography (US), 15 patients were excluded because of incomplete follow-up. Twelve carcinomas were present, confirmed with either histopathologic examination after surgical resection (n = 9) or biopsies during laser treatment (n = 3). Nine of them were detected with transrectal US on the basis of disruption of the anatomic wall layers (sensitivity, 75%). In 46 of the 54 adenomas transrectal US helped confirm the benign nature of the lesion (specificity, 85%). Seven of the eight false-positive cases happened to be previously treated with surgery or coagulation. Treatment-associated inflammatory changes in the wall layers seemed responsible for this misinterpretation. Because of the high predictive value for a negative result (benign adenoma, 94%), transrectal US is recommended for the evaluation of villous adenomas to detect malignancy, especially when nonsurgical treatment is considered. Transrectal US should be performed before diagnostic polypectomy.
Kalipatnapu, Sasank; Samuel, Vimalin; Johnson, Martha; Perookavil Daniel, Koshy
Tubular adenomas are rare benign epithelial tumors of the breast. Only a handful of cases have been reported in literature. We describe a very rare case of a giant tubular adenoma with a concurrent fibroadenoma in a young woman.
Joo, K.G.; Baeumler, G.R.
A case of a parathyroid cyst with adenoma was seen on Tl-201/Tc-99m subtraction imaging. The literature regarding parathyroid cysts and the subtraction technique for parathyroid adenoma imaging was reviewed.
Dhillon, Manu; Tomar, Divya; Sharma, Manu; Goel, Samta; Srivastava, Siddharth
Pleomorphic adenoma originally called the mixed tumour is a neoplasm commonly involving major salivary glands. The spectrum of malignancy in pleomorphic adenoma comprises three distinct entities - Carcinoma ex pleomorphic adenoma, carcinosarcoma and benign metastasising pleomorphic adenoma. Carcinoma ex pleomorphic adenoma consists of pleomorphic adenoma with a malignant epithelial component. Occasionally, carcinomas ex pleomorphic adenoma develops metastasis. Here we are reporting here a case of benign pleomorphic adenoma arising in parotid gland which turned into malignancy after four years. The patient developed facial nerve paralysis suggesting malignant transformation. Along the course of the disease, the patient developed regional metastasis to lymph nodes and neck and distant metastasis to liver. This case report emphasises the role of advanced imaging modalities in the early diagnosis of the condition and evaluation of metastasis. The patients with this condition should be treated early for favorable outcome and investigated for distant metastasis.
Landeiro, José Alberto; Fonseca, Elissa Oliveira; Monnerat, Andrea Lima Cruz; Taboada, Giselle Fernandes; Cabral, Gustavo Augusto Porto Sereno; Antunes, Felippe
Background: We report our surgical series of 35 patients with giant nonfunctioning pituitary adenomas (GNFPA). We analyzed the rule of Ki-67 antigen expression in predicting recurrence. Methods: Thirty-five patients were operated between 2000 and 2010. Suprassellar extension of the tumors were classified according to Hardy and Mohr based on magnetic resonance (MR) studies. Pituitary endocrine function and MR scans were assessed preoperatively and at 1, 6, and 12 months postoperatively. Immunohistochemical studies were based in regard to the expression of the proliferative Ki-67 index and the hormonal receptor for luteinizing hormone, follicle stimulating hormone, growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, and prolactin. Tumors specimens were obtained from 35 patients with GNFPA. Endoscopic transsphenoidal surgery was the approach of choice. Results: Thirty-five patients were submitted to 49 surgeries, 44 (89.8%) were transsphenoidal and 5 (10.2%) were transcranial. The most frequent preoperative complaints were visual acuity impairment and visual field defect in 25 (71.2%) and 23 (65.7%) cases, respectively. Improvement of visual acuitiy and visual field deficit after surgery was seen in 20 (80%) and 17 (73.9%) patients, respectively. Endocrinological deficits were encountered in 20 patients (57.1%). After surgery, 18 patients (51.4%) required hormonal replacement. Three patients had visual symptoms related to pituitary apoplexy and recovered after surgery. The Ki-67 labeling index (LI) ranged from <1% to 4.8%. The rate of recurrence in tumors with Ki-67 <3% was 7.7% (2 patients), Ki-67 >3% was present in 5 patients and the recurrence committed 3 patients. Conclusion: In our series, regardless the improvement of visual function and compressing symptoms, 5 patients with expression of Ki-67 LI more than 3% experienced a recurrence. PMID:26674325
Kinoshita, Yasuyuki; Tominaga, Atsushi; Usui, Satoshi; Arita, Kazunori; Sugiyama, Kazuhiko; Kurisu, Kaoru
Advanced magnetic resonance imaging (MRI) and optical instruments for surgery frequently demonstrate subclinical haemorrhage in pituitary adenomas; however, the effects of subclinical haemorrhage on pituitary glands remain unclear. We sought to clarify the pituitary function in patients with subclinical pituitary adenoma haemorrhage (SPAH). Between January 2006 and December 2012, we retrospectively reviewed 328 consecutive patients who underwent surgery for pituitary adenoma. SPAH was defined as an intratumoral haemorrhage based on both 3 tesla MRI and operative findings, with no clinical symptoms of acute pituitary adenoma apoplexy. The pituitary dysfunction assessed using pre- and postoperative provocative tests was investigated in patients categorized into three groups: nonapoplectic adenoma, adenoma with SPAH and adenoma with clinical apoplexy. The main outcome measure was the incidence of pituitary dysfunction. The overall incidence of nonapoplectic adenomas, adenomas with SPAH and adenomas with clinical apoplexy was 82·3%, 14·3% and 3·4%, respectively. Clinical pituitary apoplexy frequently occurred in male patients with large nonfunctioning adenomas, causing pituitary dysfunction. Contrastingly, the incidence of SPAH was significantly higher in the patients with prolactinoma (P = 0·0260), including those with relatively small adenomas (P = 0·0007). No medications, such as dopamine agonists or somatostatin analogues, were observed to affect the occurrence of SPAH. No deterioration of the pituitary function was observed in the SPAH patients in comparison with the patients with nonapoplectic adenoma, and the size of the haematoma occupying the pituitary adenoma did not exhibit any relationships with the deterioration of the pituitary function. Furthermore, SPAH caused no deterioration of the pituitary function after a surgery based on the postoperative provocation tests. Subclinical pituitary adenoma haemorrhage does not cause any added dysfunction in
Peper, Johannes Gerrit Karel; Srbljin, Sandra; van der Zant, Friso Martijn; Knol, Remco Johannes Jacob; Wondergem, Maurits
Radioisotope-labeled prostate-specific membrane antigen (PSMA) tracers have been proven accurate for detection of prostate cancer localizations. Uptake of those tracers in other malignant and benign lesions has been reported, including faint accumulation of Ga-PSMA-HBED-CC in adrenal adenoma. A 77-year-old man with prostate carcinoma was scanned with F-DCFPyL, a promising F-labeled PSMA ligand, for prostate-specific antigen progression while on luteinizing hormone-releasing hormone agonist therapy. The PET/CT shows F-DCFPyL uptake in bilateral enlarged adrenals. Non-contrast-enhanced CT scan indicated left adrenal adenoma. Regarding the high positive predictive value of multiphase contrast-enhanced CT (98%), presence of right adrenal adenoma is also likely.
de Brito, Beatriz Samara; Gaspar, Natália Giovanelli; Egal, Erika Said Abu; Sanchez-Romero, Celeste; Martins, Antonio Santos; Tincani, Álfio José; de Oliveira Gondak, Rogério; de Almeida, Oslei Paes; Kowalski, Luiz Paulo; Altemani, Albina; Mariano, Fernanda Viviane
The proto-oncogene (pleomorphic adenoma gene 1 (PLAG1)) is immunohistochemically overexpressed in pleomorphic adenoma (PA). Its expression in recurrent pleomorphic adenoma (RPA), however, has not been investigated. Since complex mechanisms are involved in tumor recurrence, the aim of this study was to investigate whether PLAG1 overexpression occurs in RPA. We studied PLAG1 protein expression in 40 PAs and 36 RPAs by immunohistochemistry. Cases with immunopositive cells were classified into two categories, between 10 and 50 % and >50 %. In both groups, PLAG1 expression was observed in both epithelial and myoepithelial cells. Of PAs, 37 cases (93 %) were positive, while this was the case in 34 RPA cases (94 %). Our findings suggest that in addition to morphological similarity, PA and RPA express PLAG1, which might play a role in tumor recurrence. Furthermore, as for PA, expression of PLAG1 can be considered a valuable diagnostic marker for RPA.
Pingarrón-Martín, Lorena; Arias-Gallo, L. J.; Demaría-Martínez, G.; Chamorro Pons, M.
The objective of this article is to present the first case reported in the literature of metachronous pleomorphic adenoma of bilateral parotid glands and submaxillary gland. The authors report the case of a 27-year-old female with metachronous mixed tumors in her right parotid and submandibular glands. The patient has no history of previous radiotherapy. All three lesions were diagnosed by fine-needle aspiration. The histopathologic evaluation of all three major salivary gland masses demonstrated pleomorphic adenomas, with no occult malignancy observed on serial sections. The presentation of pleomorphic adenomas in the parotids and submandibular glands probably represents three unrelated primary sites of tumor, yet the possibility of metastasis from one gland to the other cannot be excluded. PMID:26000084
Safaei, Akbar; Farzaneh, Mohamad Reza; Amin Sharifi, Ali Reza
Nephrogenic adenoma is a rare benign lesion of bladder that may be confused with malignant lesions. There is a strong relation with urinary tract irritation and intravesicle instrumentations. Nephrogenic adenoma was initially thought to originate from urothelial metaplasia; however, no solid proof is available. We present a case of 55-year-old lady with urinary problem. Cystocopic examination showed a sessile mass, and biopsy revealed circumscribed proliferation of tubules, cysts, and papillae that were lined by low cuboidal to columnar epithelial cells. Nephrogenic adenoma can be a significant diagnostic pitfall due to the presence of certain histological features such as the presence of enlarged nuclei with prominent nucleoli. Immunohistochemistery study was strongly positive for CK7, P504S, CD10, and EMA, but negative for CK20, PSA, and P63.
Hamano, H; Abiko, Y; Hashimoto, S; Inoue, T; Shimono, M; Takagi, T; Noma, H
Basal cell adenoma of the parotid gland was studied with immunohistochemical methods. We observed cells in the tumor with positive reaction to polyclonal keratin, prekeratin, monoclonal PKK-1, polyclonal S-100 protein, monoclonal S-100 protein (alpha), secretory component, actin and laminin. However, no cells which stained positively with monoclonal KL-1, amylase, carcinoembryonic antigen, or epithelial membrane antigen were recognized. From these immunohistochemical results and our ultrastructural observations reported previously, we conclude that the cells constituting the basal cell adenoma are ductal, myoepithelial, and squamous cells but not secretory ones. It is also suggested that the origins of basal cell ademona as well as those of pleomorphic and clear cell adenoma are undifferentiated cells of intercalated duct.
Casado, A; Sánchez-Gutiérrez, V; Barrancos, C; Albandea, A
The case is presented of 48 year-old male complaining of a painful left upper eyelid and swelling of the lacrimal gland, with a suspicion of dacryoadenitis. Removal was decided after dacriops suspicion. Histopathology diagnosed a pleomorphic adenoma of the lacrimal gland, with areas of necrosis. Lacrimal gland pleomorphic adenoma usually presents as a slowly progressive painless mass. However, painful presentation in this case might be related with necrotic foci found in the histopathological examination. Although not described in lacrimal glands, pleomorphic adenomas have already been reported in the major and minor salivary glands, and these patients also presented with a painful mass. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
Soler, R.; Bargiela, A.; Cordido, F.; Aguilera, C.; Argueeso, R.; Cao, I.
Primary hyperparathyroidism is a common disorder that results from an increased secretion of parathyroid hormone, most often due to a solitary and solid parathyroid adenoma usually found in the inferior group of parathyroid glands. Parathyroid gland is ectopic in approximately 10 to 20% of the cases, and the retrosternal and prevascular mediastinum is the most common location. Most mediastinal parathyroid adenomas are solid and <3 cm, but mediastinal parathyroid cysts are very uncommon and rarely cause hyperparathyroidism. We know of 18 cases of mediastinal parathyroid cysts that have been previously reported and only four of them presented with hyperparathyroidism. We report an unusual case of hyperparathyroidism due to a large cystic parathyroid adenoma located in the anterior mediastinum diagnosed by MRI. 2 refs., 1 fig.
Ogawa, Yoshikazu; Tominaga, Teiji; Ikeda, Hidetoshi
Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma accounts for 1% of pituitary adenoma and often manifests as invasive macroadenoma. If the TSH value is not high enough to cause clinical symptoms presenting as inappropriate secretion of TSH, the tumor may be missed or misdiagnosed as Graves disease. Some of these patients receive inadequate treatment with the antithyroid agent, radioiodine treatment, and thyroidectomy. This tumor is also known as a tough and firm tumor because of the significant interstitial fibrosis. We report two cases of TSH-secreting pituitary adenomas which were comparatively small. Although a tough and difficult operation was expected, actual tumor dissection was easy and gross total removal was achieved within less than 3 hours. We discuss the relationship between the intraoperative findings and histopathology, as well as the ultrastructure and endocrinology.
Berker, Dilek; Isik, Serhat; Aydin, Yusuf; Tutuncu, Yasemin; Akdemir, Gokhan; Ozcan, Hatice Nursun; Guler, Serdar
Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors manifested as hyperthyroidism with goiter in the presence of elevated TSH. We present a case with pituitary adenoma secreting both TSH and growth hormone (GH) with the prominent clinical findings of hyperthyroidism but without clinical findings of acromegaly. Pituitary magnetic resonance imaging revealed a macroadenoma. Transsphenoidal surgery was performed twice. The immunohistochemical staining showed that tumor cells were strongly reactive to GH and relatively mildly reactive to TSH. Control pituitary imaging revealed a residual macroadenoma, and long acting octreotide treatment was administered. After two years of the treatment, tumor size remained the same while thyroid function tests and insulin-like growth factor 1 (IGF-I) values returned to normal ranges. In conclusion, we always recommend hormonal examinations for all patients who have pituitary adenoma without signs and symptoms of acromegaly.
Traxer, Olivier; Mouton, Albert; Abbecassis, Rémy; Tassard, Marc; Vigneau, Cécile; Gattegno, Bernard; Thibault, Philippe
Primary hyperparathyroidism (PHPT) is not a rare disease. Renal stones are the most frequent complication of PHPT The authors report the case of a patient with giant parathyroid adenoma responsible for early recurrence of renal stones. Ultrasound examination of the neck, parathyroid MRI and Technetium99m-Sestamibi scintigraphy confirmed the parathyroid adenoma. Surgical exploration allowed resection of a giant adenoma (6.5 x 2.5 x 1.5 cm weighing 17 g). In the light of this case, the authors describe the characteristics of HPT define the place of preoperative imaging and emphasize the need for systematic aetiological work-up looking for HPT in all patients with a first episode of renal stones.
Arik, Deniz; Dündar, Emine; Yilmaz, Evrim; Sivrikoz, Cumhur
Water-clear cell adenoma of the parathyroid gland is a rare neoplasm that consists of cells with abundant clear-pink cytoplasm. There have only been 19 cases reported in the English literature. Here we report a case of water-clear cell adenoma of the mediastinal parathyroid gland. A 70-year-old male patient presented to the hospital with back pain and a mediastinal mass 6 cm in size was detected. After excision and microscopic evaluation, uniform, large clear cells with fine cytoplasmic vacuolization, without nuclear atypia, and arranged in solid and acinar patterns were revealed. The cells formed nests that were separated by fine fibrovascular septae and stained positively with anti-parathyroid hormone. To the best of our knowledge, this has not been previously reported in this location. In the differential diagnosis of clear cell lesions of the mediastinum, water-clear cell parathyroid adenoma should be considered.
Arik, Deniz; Dündar, Emine; Yilmaz, Evrim; Sivrikoz, Cumhur
Water-clear cell adenoma of the parathyroid gland is a rare neoplasm that consists of cells with abundant clear-pink cytoplasm. There have only been 19 cases reported in the English literature. Here we report a case of water-clear cell adenoma of the mediastinal parathyroid gland. A 70-year-old male patient presented to the hospital with back pain and a mediastinal mass 6 cm in size was detected. After excision and microscopic evaluation, uniform, large clear cells with fine cytoplasmic vacuolization, without nuclear atypia, and arranged in solid and acinar patterns were revealed. The cells formed nests that were separated by fine fibrovascular septae and stained positively with anti-parathyroid hormone. To the best of our knowledge, this has not been previously reported in this location. In the differential diagnosis of clear cell lesions of the mediastinum, water-clear cell parathyroid adenoma should be considered.
Lung, T; Juncar, M
Pleomorphic adenoma is one of the most frequent tumors that involve the parotid gland. The tumor constantly increases in dimension if not cured in due time and may become malignant. A case of a patient suffering from a carcinoma ex-pleomorphic adenoma that had a 20-year-evolution and reached impressive dimensions is presented. The tumor holds the second place worldwide among the largest carcinoma ex-pleomorphic adenoma in terms of size and the ninth place worldwide among the most voluminous parotid tumors ever surgically excised, as far as we know. Nevertheless, the regional invading character of the tumor in this particular case has been limited, without generating local lymph node invasion or metastases.
Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza
Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.
Aaltonen, Lauri A.; Daly, Adrian F.
Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses
Beckers, Albert; Aaltonen, Lauri A; Daly, Adrian F; Karhu, Auli
Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses
Emy, P; Combe, H; Marchand, J P; Villeneuve, A; Sicre, G; Chadenas, D
Mediastinal parathyroid adenoma located on the 5th ectopic gland is rare. We report here two new cases diagnosed by scintigraphy. In one case the adenoma was found to be located in the mediastinum prior to cervicotomy. The modern imaging methods capable of locating parathyroid adenomas are evaluated.
Sobrinho, L G; Duarte, J S; Paiva, I; Gomes, L; Vicente, V; Aguiar, P
It has been reported that women with prolactinoma were exposed, early in life, to an environment characterized by an absent or violent father. The present study was designed to evaluate whether paternal absence or violent paternal behavior were more prevalent in patients with pituitary adenomas (prolactinoma, acromegaly, non-secreting adenoma and Cushing's disease) compared to a control population. We conducted an observational case-control multicenter study. We interviewed 395 patients with prolactinoma (296 females and 99 males), 130 with acromegaly (87 females and 43 males), 237 with non-secreting adenoma (144 females and 93 males) and 68 with Cushing's disease (61 females and 7 males) and 365 patients from the same clinics with nodular thyroid disease or lymphocytic thyroiditis with euthyroidism as controls. Violent or absent fathers were significantly more prevalent in patients with prolactinoma or acromegaly than in controls (P = 0.001 and P = 0.002, respectively) but not in patients with non-secreting adenoma or corticotrophinoma. Absent fathers in prolactinoma and acromegaly versus controls: P = 0.001 and P = 0.119. Violent fathers in prolactinoma and acromegaly versus controls: P = 0.069 and P = 0.001. The prevalence of absent or violent fathers was also significantly higher in prolactinoma and acromegaly when compared to non-secreting adenoma (P = 0.039 and P = 0.033, respectively). Paternal deprivation before adolescence may be a risk factor for prolactinoma and acromegaly but not for non-secreting pituitary adenomas or Cushing's disease.
Mahta, Ali; Haghpanah, Vahid; Lashkari, Anahita; Heshmat, Ramin; Larijani, Bagher; Tavangar, Seyed Mohammad
Pituitary adenomas without clinically active hypersecretion are summarized under the term non-functioning pituitary adenoma (NFPA). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties. By using immunohistochemical methods we will have new insight into the nature and pathogenesis of these tumours. Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its labelling index (LI) is considered a marker of normal and abnormal cell proliferation. The aim of this study was to investigate the possible role of immunohistochemistry and MIB1-LI determination in NFPAs to predict tumoural behaviour and better management. In this clinicopathological study, 85 cases of NFPAs were analysed immunohistochemically. MIB1-LI was also determined in studied cases. Clinical presentation, treatment and follow-up data were also reviewed and the correlation between clinical and pathologic findings was established. Eighteen adenomas (21.2%) were immunoreactive to one or two adenohypophysial hormones of which 4 GH positive adenomas had aggressive behaviour (2 significant juxtasellar extensions and 2 recurrences). MIB-1 LI was more than 5% in only 5 cases including 2 invasive adenomas but with no evidence of recurrence. No significant statistical difference between clinical presentations in immunoreactive and non-immunoreactive NFPAs was observed except for unilateral temporal hemianopia which was more common in immunoreactive adenomas (P=0.022). NFPAs comprise several pathologically different types of tumours, some of which are potentially hormone producing, but some defects in hormone secretion or production of biologically inactive or insufficient amount of hormone may be the culprit in the lack of evidence of rising serum hormone levels. MIB-1 LI may be indicative of invasiveness but not a predictor of recurrence. Silent somatotropinomas may have more aggressive behaviour in comparison with other NFPAs.
Ortiz, Ana Patricia; Thompson, Cheryl L; Chak, Amitabh; Berger, Nathan A; Li, Li
Increasing evidence supports insulin resistance (IR) as the underpinning of the obesity-colorectal neoplasia link. The homeostasis model assessment-IR (HOMA-IR) is a widely accepted index of evolving hyperinsulinemia and early IR. Studies of the relation between HOMA-IR and colorectal adenomas are limited. Therefore, the authors sought to determine the associations of HOMA-IR and central obesity (waist to hip ratio [WHR]) with risk of colorectal adenomas in a screening colonoscopy-based study. The authors collected lifestyle information and fasting blood samples from 1222 participants (320 incident adenoma cases and 902 without adenomas) before their screening colonoscopies. Unconditional logistic regression models were used to assess risk associations. In multivariate analysis of participants (n = 1093) reporting no antidiabetic medication use, those in the top quartile of WHR were twice as likely (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.33-3.57; P-trend = .003) and those in the top quartile of HOMA-IR were 63% more likely (OR, 1.63; 95% CI, 1.09-2.44; P-trend = .01) to have adenomas compared with those in the bottom quartiles. Stratified analysis revealed a statistically significant interaction between HOMA-IR and sex (P-interaction = .04), with the association largely limited to men; compared with those in the bottom tertile, men in the top tertile of HOMA-IR were twice more likely to have adenomas (OR, 2.11; 95% CI, 1.18-3.78; P-trend = .01). The results support central obesity and insulin resistance, particularly in men, as important risk factors for the development of early colorectal neoplasia. Copyright © 2011 American Cancer Society.
Thyagarajan, Bharat; Guan, Weihua; Fedirko, Veronika; Barcelo, Helene; Tu, Huakang; Gross, Myron; Goodman, Michael; Bostick, Roberd M
Despite previously reported associations between peripheral blood mtDNA copy number and colorectal cancer, it remains unclear whether altered mtDNA copy number in peripheral blood is a risk factor for colorectal cancer or a biomarker for undiagnosed colorectal cancer. Though colorectal adenomas are well-recognized precursor lesions to colorectal cancer, no study has evaluated an association between mtDNA copy number and colorectal adenoma risk. Hence, we investigated an association between peripheral blood mtDNA copy number and incident, sporadic colorectal adenoma in 412 colorectal adenoma cases and 526 cancer-free controls pooled from three colonoscopy-based case-control studies that used identical methods for case ascertainment, risk factor determination, and biospecimen collection. We also evaluated associations between relative mtDNA copy number and markers of oxidative stress, including circulating F2 -isoprostanes, carotenoids, and fluorescent oxidation products. We measured mtDNA copy number using a quantitative real time polymerase chain reaction (PCR). We used unconditional logistic regression to analyze the association between mtDNA copy number and colorectal adenoma risk after multivariable adjustment. We found no association between logarithmically transformed relative mtDNA copy number, analyzed as a continuous variable, and colorectal adenoma risk (odds ratio = 1.02, 95%CI: 0.82-1.27; P = 0.86). There were no statistically significant associations between relative mtDNA copy number and other markers of oxidative stress. Our findings, taken together with those from previous studies, suggest that relative mtDNA copy number in peripheral blood may more likely be a marker of early colorectal cancer than of risk for the disease or of in vivo oxidative stress. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
Newey, Paul J.; Nesbit, M. Andrew; Rimmer, Andrew J.; Attar, Moustafa; Head, Rosie T.; Christie, Paul T.; Gorvin, Caroline M.; Stechman, Michael; Gregory, Lorna; Mihai, Radu; Sadler, Greg; McVean, Gil; Buck, David
Context: Genetic abnormalities, such as those of multiple endocrine neoplasia type 1 (MEN1) and Cyclin D1 (CCND1) genes, occur in <50% of nonhereditary (sporadic) parathyroid adenomas. Objective: To identify genetic abnormalities in nonhereditary parathyroid adenomas by whole-exome sequence analysis. Design: Whole-exome sequence analysis was performed on parathyroid adenomas and leukocyte DNA samples from 16 postmenopausal women without a family history of parathyroid tumors or MEN1 and in whom primary hyperparathyroidism due to single-gland disease was cured by surgery. Somatic variants confirmed in this discovery set were assessed in 24 other parathyroid adenomas. Results: Over 90% of targeted exons were captured and represented by more than 10 base reads. Analysis identified 212 somatic variants (median eight per tumor; range, 2–110), with the majority being heterozygous nonsynonymous single-nucleotide variants that predicted missense amino acid substitutions. Somatic MEN1 mutations occurred in six of 16 (∼35%) parathyroid adenomas, in association with loss of heterozygosity on chromosome 11. However, no other gene was mutated in more than one tumor. Mutations in several genes that may represent low-frequency driver mutations were identified, including a protection of telomeres 1 (POT1) mutation that resulted in exon skipping and disruption to the single-stranded DNA-binding domain, which may contribute to increased genomic instability and the observed high mutation rate in one tumor. Conclusions: Parathyroid adenomas typically harbor few somatic variants, consistent with their low proliferation rates. MEN1 mutation represents the major driver in sporadic parathyroid tumorigenesis although multiple low-frequency driver mutations likely account for tumors not harboring somatic MEN1 mutations. PMID:22855342
Dardick, I.; Kahn, H. J.; Van Nostrand, A. W.; Baumal, R.
Monomorphic adenoma of basal cell type is a salivary gland tumor believed to result from a proliferation of a single type of cell. However, ultrastructural and immunocytochemical investigations of 6 monomorphic adenomas (5 from parotid and 1 from intraoral minor salivary gland) indicate that there are two classes of these lesions, one composed of two types of tumor cells and the other wholly or predominantly made up of one type of cell (isomorphic). In the former group, the organization of the tumor cells closely mimicked that of normal and hyperplastic salivary gland intercalated ducts. Aggregates of tumor cells were arranged as an inner layer of luminal epithelial cells which were surrounded by an outer layer of cells that, in some cases, had ultrastructural and immunohistochemical features indicating myoepithelial cell differentiation. In some adenomas formed by two types of tumor cells, basal-lamina-lined extracellular spaces were identified ultrastructurally in relation to modified myoepithelial cells; such spaces had the same fine-structural features as those reported in pleomorphic adenoma and adenoid cystic carcinoma. Predominantly isomorphic adenomas were composed exclusively of luminal epithelial cells. These results indicate that despite the varied histologic patterns in the numerous subtypes of monomorphic adenoma, there is a central theme of differentiation and organization in this type of neoplasm which recapitulates the ductoacinar unit of normal salivary gland parenchyma. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:6375388
Hughes, Laura; Talha Khan, Muhammad; Khalid Hasan, Muhammad; Inayat, Irteza
KCNQ1 gene mutation has a well-known association with long QT syndrome (LQTS). However, recent studies suggest that it may be implicated in intestinal neoplasia. We present a 27-year-old Hispanic man with a known history of LQTS secondary to KCNQ1 mutation, who presented with painless jaundice. Endoscopic retrograde pancreatic cholangiography revealed a prominent ampulla, with histology consistent with ampullary adenoma with high-grade dysplasia. Further endoscopic studies did not suggest familial adenomatous polyposis. To date, this is the index case of duodenal ampullary adenoma in the setting of KCNQ1 mutation. PMID:27921062
Ogaki, Satoko; Suzuki, Seiji; Suzuki, Hiroaki; Suzuki, Masatsune; Shimano, Hitoshi; Toyoshima, Hideo; Sone, Hirohito; Okuda, Yukichi; Yamada, Nobuhiro
We report a case of cerebral hemorrhagic infarction after radiation for pituitary adenoma. A 55-year-old woman was hospitalized to check for aldosteronism, post-operative pituitary function, and recurrence of thyroid cancer. She had short-term memory disturbance beginning two months prior to admission. Brain MRI showed a T1 and T2 high intensity lesion of her left anterolateral thalamus. Brain MRA revealed a narrowing in her left middle cerebral artery. The abnormal brain lesion was diagnosed as cerebral hemorrhagic infarction. She had received radiation therapy for pituitary adenoma 20 years earlier. It was considered that her cerebral hemorrhagic infarction was caused by radiation therapy.
Corley, Douglas A; Jensen, Christopher D; Marks, Amy R; Zhao, Wei K; Lee, Jeffrey K; Doubeni, Chyke A; Zauber, Ann G; de Boer, Jolanda; Fireman, Bruce H; Schottinger, Joanne E; Quinn, Virginia P; Ghai, Nirupa R; Levin, Theodore R; Quesenberry, Charles P
The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas (the adenoma detection rate) is a recommended quality measure. However, little is known about the association between this rate and patients' risks of a subsequent colorectal cancer (interval cancer) and death. Using data from an integrated health care delivery organization, we evaluated the associations between the adenoma detection rate and the risks of colorectal cancer diagnosed 6 months to 10 years after colonoscopy and of cancer-related death. With the use of Cox regression, our estimates of attributable risk were adjusted for the demographic characteristics of the patients, indications for colonoscopy, and coexisting conditions. We evaluated 314,872 colonoscopies performed by 136 gastroenterologists; the adenoma detection rates ranged from 7.4 to 52.5%. During the follow-up period, we identified 712 interval colorectal adenocarcinomas, including 255 advanced-stage cancers, and 147 deaths from interval colorectal cancer. The unadjusted risks of interval cancer according to quintiles of adenoma detection rates, from lowest to highest, were 9.8, 8.6, 8.0, 7.0, and 4.8 cases per 10,000 person-years of follow-up, respectively. Among patients of physicians with adenoma detection rates in the highest quintile, as compared with patients of physicians with detection rates in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52 (95% confidence interval [CI], 0.39 to 0.69), for advanced-stage interval cancer, 0.43 (95% CI, 0.29 to 0.64), and for fatal interval cancer, 0.38 (95% CI, 0.22 to 0.65). Each 1.0% increase in the adenoma detection rate was associated with a 3.0% decrease in the risk of cancer (hazard ratio, 0.97; 95% CI, 0.96 to 0.98). The adenoma detection rate was inversely associated with the risks of interval colorectal cancer, advanced-stage interval cancer, and fatal interval cancer. (Funded by the Kaiser Permanente
Kanaan, I N
Pituitary adenomas are the third most common benign intracranial tumor seen in neurosurgical practice. They represent >or= 15 % of all primary intracranial tumors with 25 % prevalence as reported in autopsy series. Advances in biomedical assays, imaging studies support their diagnosis and tailor their management. The direct endonasal transsphenoidal surgery is the recommended intervention for adenoma resection in more than 95 %. The safety and efficacy of this intervention was enhanced by microsurgery and more recently by the introduction of neuronavigation, assisted endoscopy and intraoperative MRI. Anticipation of clinical, biochemical, radiological and surgical pitfalls by a multidisciplinary team is of paramount importance in improving treatment and preventing potential complications.
Sirek, A. M.; Corenblum, B.; Horvath, E.; Rewcastle, B.; Ezrin, C.; Kovacs, K.
Cases of seven different types of surgically resected pituitary adenoma are described. Included are tumours secreting prolactin or growth hormone or both, and nonfunctioning tumours--undifferentiated and oncocytic tumours, and one tumour with cells of the adrenocorticotropin-melanocyte-stimulating hormone type. The final interpretation of a case of pituitary adenoma should include an assessment of thorough morphologic studies, using not only routine staining and light microscopy but also immunostaining and electron microscopy, to complement the biochemical, radiologic and clinical evaluation. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 PMID:204403
Martínez-Sanchíz, Carlos; Martínez-Ruiz, Jesús; Anguita-Fernandez, Pedro J.; Giménez-Bachs, José M.; Atiénzar-Tobarra, Manuel; Rodríguez, Julio Antonio Virseda; Salinas-Sánchez, Antonio S.
Vesical nephrogenic adenoma is a rare, benign entity that appears most commonly in middle-aged males. Its etiology is unknown, but it has been linked to chronic irritating factors, such as infection, trauma, urological surgery, kidney stones, foreign bodies and chemical agents, such as Bacille Calmette-Guerin. We report 2 new cases with a history of transurethral resection of the bladder and the prostate and a history of prolonged voiding symptoms. In both cases, the findings of encysted tubular structures lined with flattened cuboidal cells without atypia were consistent with the diagnosis of vesical nephrogenic adenoma. PMID:21989174
McGinness, Sam; Coleman, Hedley; Varikatt, Winny; da Cruz, Melville
Neuroendocrine tumours occur throughout the body but are rare in the head and neck region and particularly rare in the middle ear. Clinical findings are often nonspecific and therefore pose a diagnostic challenge. Furthermore, the nomenclature of neuroendocrine tumours of the middle ear is historically controversial. Herein a case is presented of a middle ear adenoma in a 33-year-old patient who presented with otalgia, hearing loss, and facial nerve palsy. A brief discussion is included regarding the histopathological features of middle ear adenomas and seeks to clarify the correct nomenclature for these tumours. PMID:27429819
Assoufi, Naoufal; Bahadi, Nessrine; Omri, Nawal El; Sekkach, Youssef; Ameziane, Taoufiq; Ghafir, Driss
We report the case of Conn adenoma revealed by tetraparesis in a 33-year old pregnant woman at the 16(th)week of amenorrhea. The patient had a blood pressure of 147/87 mmHg, which was considered high-normal, hypokalemia at 1.1 mmol/l. The diagnosis was confirmed by hormone dosage which showed elevated plasma aldosterone levels and decreased plasma renin activity. MRI showed a left adrenal nodule, 1.5 cm in diameter, compatible with adrenal adenoma. Left adrenalectomy was performed with simple postoperative course and normalization of kalemia and blood pressure.
Parekh, Deval; Sengupta, Moumita; Das, Mou; Chatterjee, Uttara
Xanthogranulomatous pyelonephritis is an uncommon inflammatory condition accounting for 1% of chronic pyelonephritis cases. Clinically and radiologically it mimics other renal space occupying lesions. Hence, correct preoperative diagnosis is not possible in all cases and nephrectomy is done in most patients. Renal tubulopapillary adenomas are benign epithelial lesions of kidney found to be associated with papillary renal cell carcinoma, acquired renal cystic disease, long term hemodialysis, arteriosclerotic renal vascular disease, etc. Here, we report two cases of Xanthogranulomatous pyelonephritis associated with the rare finding of renal tubulopapillary adenomas.
Hassan, Cesare; Maselli, Roberta; Pontone, Paolo; Angelini, Rita; Brighi, Manuela; Patrizi, Gregorio; Pironi, Daniele; Magliocca, Fabio Massimo; Filippini, Angelo
Background The safety and diagnostic accuracy of colonoscopy depend on the quality of colon cleansing. The adenoma detection rate is usually used as a quality measurement score. Objective We aimed to introduce and evaluate three new parameters to determine polyps and adenomas segmental localization and their distribution in association with different bowel preparation levels during colonoscopy. We introduce the multiple adenoma detection rate (the percentage of patients with >2 adenomas diagnosed during colonoscopy), the zonal adenoma detection rate (the percentage of patients with >2 adenomas diagnosed during colonoscopy in different colon areas (rectum, sigmoid, descending, transverse, ascending and cecum colon)), and multi-zone adenoma detection rate (the percentage of patients with >2 adenomas diagnosed during colonoscopy in different colon areas with at least a segment between them with or without lesions (i.e. rectum and descending colon with or without lesions in the sigmoid)). Methods We prospectively enrolled outpatients who underwent colonoscopy from January 2013 to October 2014. The bowel preparation quality, according to the Aronchick modified scale, number and location of lesions, Paris classification and histology, were recorded. The multiple adenoma/polyp detection rate, zonal adenoma/polyp detection rate, and multi-zone adenoma/polyp detection rate were determined. Results In total, 519 consecutive patients (266/253 M/F; mean age 55.3 ± 12.8 years) were enrolled. The adenoma and polyp detection rates were 21% and 35%, respectively. Multiple adenomas were detected in 28 patients. Adenoma and polyp detection rate and new parameters were statistically significantly higher in the optimal as compared with the adequate bowel preparation. Conclusions An optimal level of bowel preparation was strongly associated not only with a higher adenoma detection rate, but also with a higher chance of detecting multiple clinically relevant lesions in adjacent or
Salman, Rida; Sebaaly, Mikhael G; Wehbe, Mohammad Rachad; Sfeir, Pierre; Khalife, Mohamad; Al-Kutoubi, Aghiad
Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.
Lasa, J S; Moore, R; Peralta, A D; Dima, G; Zubiaurre, I; Arguello, M; Senderovsky, M; Moretti, L; Avagnina, A; Soifer, L
There has been little reported experience in the Latin American hospital setting in relation to the impact of the endoscopic training process on colonoscopy quality. To determine the effect that training in the technique of colonoscopy has on adenoma detection in an Argentinian teaching hospital. Within the time frame of July 2012 and July 2013, 3 physicians received training in colonoscopy from 4 experienced endoscopists. The colonoscopies performed by the supervised trainees were compared with those carried out by the experienced endoscopists. A total of 318 colonoscopies performed by any one of the 3 supervised trainees and 367 carried out by any one of the experienced endoscopists were included. The univariate analysis showed a non-significant difference in the detection rate of adenomas (30.4 vs. 24.7%, P=.09). In the multivariate analysis, the detection rate of adenomas was significantly higher in the colonoscopies performed by one of the 3 trainees (odds ratio = 1.72 [1.19-2.48]). The supervised involvement of endoscopic trainees has a positive effect on adenoma detection. Copyright © 2013 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.
Hosoyama, Tohru; Nishijo, Koichi; Garcia, Melinda M.; Schaffer, Beverly S.; Ohshima-Hosoyama, Sachiko; Prajapati, Suresh I.; Davis, Michael D.; Grant, Wilmon F.; Scheithauer, Bernd W.; Marks, Daniel L.; Rubin, Brian P.; Keller, Charles
Pituitary adenomas are classified into functioning and nonfunctioning (silent) tumors on the basis of hormone secretion. However, the mechanism of tumorigenesis and the cell of origin for pituitary adenoma subtypes remain to be elucidated. Employing a tamoxifen-inducible mouse model, we demonstrate that a novel postnatal Pax7+ progenitor cell population in the pituitary gland gives rise to silent corticotroph macro-adenomas when the retinoblastoma tumor suppressor is conditionally deleted. While Pax transcriptional factors are critical for embryonic patterning as well as postnatal stem cell renewal for many organs, we have discovered that Pax7 marks a restricted cell population in the postnatal pituitary intermediate lobe. This Pax7+ early progenitor cell population is overlapping but ontologically downstream of the Nestin+ pituitary stem cell population, yet upstream of another newly discovered Myf6+ late progenitor cell population. Interestingly, the Pax7+ progenitor cell population is evolutionarily conserved in primates and humans, and Pax7 expression is maintained not only in murine tumors but also in human functioning and silent corticotropinomas. Taken together, our results strongly suggest that human silent corticotroph adenomas may in fact arise from a Pax7 lineage of the intermediate lobe, a region of the human pituitary bearing closer scientific interest as a reservoir of pituitary progenitor cells. PMID:20811506
Butler, Colin; Kulendra, Kevin N; Menon, Gopind; D’Souza, Alwyn R
The present report describes a case of an 85-year-old woman who underwent an excisional biopsy of a preauricular lesion centred over the zygoma and subsequently developed an immediate iatrogenic facial palsy. Histopathological diagnosis revealed a canalicular adenoma of the parotid gland. PMID:21686469
Suto, Yuji; Kodama, Fumiko; Kato, Takashi
I-123 IMP is now widely used as a radioactive material for cerebral blood flow scintigraphy. It is also known that this substance will accumulate in certain types of tumors. The authors present a case of a 47-year-old woman who showed accumulation of I-123 IMP in hepatic cell adenoma. 6 refs., 3 figs.
Lee, Min Ho; Lee, Ju Hee; Seol, Ho Jun; Lee, Jung-Il; Kim, Jong Hyun; Kong, Doo-Sik
Background Non-functioning pituitary adenomas (NFPA) are clinically challenging because they present at a late stage with local mass effects or hypopituitarism. Surgery for non-functioning pituitary adenoma requires a special strategic approach for both minimal morbidity and radical resection. However, the clinical predictive factors associated with recurrence are limited. Here, we investigated optimal treatment of non-functioning pituitary adenoma. Methods We enrolled 289 patients who presented with non-functioning pituitary adenoma between January 2000 and January 2012 and who had received follow-up for at least one year for this retrospective study. Of these patients, 152 were male and 137 were female, with a median age of 51 years (range 15.79 years) and a median follow-up of four years (range 1.12.6 years). Characteristics of patients and tumors were reviewed with electronic medical records and radiologic images, retrospectively. Results Of the tumors, 193 were gross-totally resected, 53 were near-totally resected, and 43 were sub-totally resected. The extent of resection and adjuvant radiotherapy were both statistically significant prognostic factors of recurrence. Immunohistochemistry of tumor specimens did not yield consistent results. Conclusion With a high rate of recurrence, NFPA should be closely followed-up over a long-term period. Improvement of surgical techniques with advanced surgical equipment and adjuvant radiosurgery would lead to reduce the recurrence rate and improve patients' outcome. PMID:27195254
Cahyanur, Rahmat; Setyawan, Wawan; Sudrajat, Dedy G; Setyowati, Susie; Purnamasari, Dyah; Soewondo, Pradana
Acromegaly is a rare disorder caused by excessive growth hormone. Majority of acromegaly are due to pituitary adenoma. It is estimated that 5% of pituitary adenoma become invasive and may grow to gigantic sizes (>4 cm in diameter). We would like to describe a man with giant invasive adenoma. We describe the case of 52-year-old man with acromegaly. The patient was presented to medical care because of hemichorea. He also had visual field defect, uncontrolled diabetes, and dyslipidemia. Hormonal profile showed increment of GH 2-hour after a standard 75-g oral glucose load and of high IGF-1 level with low level of FSH and LH. The next was performed by pituitary imaging. Magnetic resonance imaging showed a macroadenoma with diameter 2.3x3.5x6.6 cm3 that fills the sella tursica, and enlarges into suprasella, genu of corpus collosum, and invades third ventricle. This report describes a rare case of acromegalic patient with giant invasive adenoma. This could be a demonstrative case and lesson for diagnosis and manage acromegalic patient.
Al-Suhaili, A.R.; Lynn, J.; Lavender, J.P.
The authors report, probably for the first time, a successful pre-operative localization of 7 mm intrathyroidal parathyroid adenoma which was successfully removed by using parathyroid imaging using a dual tracer (T1-201 and Tc-99m) and subtraction technique.
Sharman, Mellora; FitzGerald, Louise; Kiupel, Matti
An 8-year-old, male neutered, domestic longhair cat was referred for investigation of insulin-resistant diabetes mellitus. Routine haematology, serum biochemistry, urinalysis (including culture), total T4 and urine creatinine:cortisol ratio were unremarkable, but markedly increased insulin-like growth factor-1 concentration was identified and a pituitary mass was subsequently documented. The cat was treated conservatively with the dopamine agonist L-deprenyl and was re-presented 16 months later for worsening polyuria, polydipsia, polyphagia, marked lumbar muscle atrophy, development of a pendulous abdomen and marked thinning of the abdominal skin. Hyperadrenocorticism was diagnosed based on abdominal ultrasonography, dexamethasone suppression testing and endogenous adrenocorticotropic hormone (ACTH). The cat was treated with trilostane (30 mg q24h PO) and showed some clinical improvement, but developed an opportunistic fungal infection and skin fragility syndrome 4.5 months after commencing treatment, and was euthanased. A double-pituitary adenoma comprising a discrete somatotroph adenoma and a separate plurihormonal adenoma (positive immunoreactivity for ACTH, melanocyte-stimulating hormone and follicle-stimulating hormone) was identified on post-mortem examination. These two pituitary adenomas were suspected to have arisen as independent neoplastic entities with the plurihormonal tumour either being clinically silent at the initial presentation or having developed over the subsequent 16 months.
Van Thong Ho; Rao, V.J.; Mikaelian, D.O.
A case of mixed type adenoma of the middle ear and mastoid is presented in which CT showed complete opacification of the middle ear and mastoid air cells with bulging of the tympanic membrane but without ossicular or bony destruction. 7 refs., 1 figs.
Binello, E; Cunliffe, C; Post, K D; Kleinman, G M
Signet-ring cell changes in the pituitary adenomas are extremely rare. To date, there have been only two reports documenting signet-ring cells in pituitary adenomas, one in a growth-hormone cell adenoma and the other in a nullcell adenoma. This report describes, for the first time, signet-ring cells in a prolactincell adenoma. The patient is a 46-year-old male who presented with severe headache and acute on chronic visual loss. Radiographic studies demonstrated a large cystic pituitary lesion with evidence of pituitary apoplexy. Laboratory values were consistent with a prolactin-cell adenoma. The patient underwent transsphenoidal resection of the prolactin-cell adenoma with significant post-operative improvement. The tumor was composed of sheets of monomorphic round cells with conspicuous nuclei and granular cytoplasm, consistent with pituitary adenoma. Many cells had eccentric, often crescentic-shaped nuclei, imparting a signet-ring appearance and immunostaining was positive for prolactin, denoting an atypical prolactin-cell adenoma. The MIB-1 labeling index was slightly elevated. Electron microscopy demonstrated the presence of vacuolated areas in the cytoplasm that were not membrane bound and did not have specific inclusions. This case augments the literature on pituitary adenomas with signet-ring cells. The clinical significance of signet-ring cells in pituitary adenomas is unknown. Accumulation of clinical cases, together with the advances in molecular techniques and experimental models, may yield further insight.
An intracapsular carcinoma ex pleomorphic adenoma with lung metastases composed exclusively of benign elements: histological evidence of a continuum between metastasizing pleomorphic adenoma and carcinoma ex pleomorphic adenoma.
Weissferdt, Annikka; Langman, Gerald
Malignant mixed tumors of the salivary glands, encompassing carcinoma ex pleomorphic adenoma (ca ex PA), carcinosarcoma and metastasizing pleomorphic adenoma (mPA), are rare neoplasms. Ca ex PA arises in a pre-existing pleomorphic adenoma (PA). When the malignant component does not breach the capsule of the parent PA, the lesion is termed intracapsular ca ex PA, a neoplasm which is thought to have no metastatic potential. Metastatic deposits of ca ex PA are composed exclusively of malignant elements or mixed benign and malignant components. We describe the case of a 62-year-old female with an intracapsular ca ex PA of the buccal mucosa with subsequent metastases to the lung. The metastatic deposits resembled benign PA with no histological evidence of malignancy. This pattern of spread is described with mPA, an entity that caused controversy in the past regarding its exact classification as a benign or malignant tumor. The possibility that ca ex PA originates from a mPA, with intracapsular ca ex PA representing an intermediate lesion in a histological continuum, is discussed.
Lan, Xiaolei; Gao, Hua; Wang, Fei; Feng, Jie; Bai, Jiwei; Zhao, Peng; Cao, Lei; Gui, Songbai; Gong, Lei; Zhang, Yazhuo
Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA) were sequenced by whole-exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas. A total of 15 identified variants were mainly associated with angiogenesis, metabolism, cell cycle phase, cellular component organization, cytoskeleton and biogenesis immune at a cellular level, including 13 variants that occurred as single nucleotide variants and 2 that comprised of insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline-rich protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2), PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F-actin binding protein and zinc finger protein 717 in IPA specimens were 50% decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and SPANXN2 mRNA levels in IPA specimens were approximately four-fold lower compared with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast, the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7 (EGFL7), low density lipoprotein receptor-related protein 1B and dynein, axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased PRDM2 expression was associated with tumor recurrence. The findings of the present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary adenomas are modifiers of
Thapar, Kamal; Yamada, Yukio; Scheithauer, Bernd; Kovacs, Kalman; Yamada, Shozo; Stefaneanu, Lucia
Assessment of mitotic activity represents one of the oldest and most routinely used histopathologic methods of evaluating the biological aggressiveness of human tumors. In the case of pituitary tumors, however, the relevance of this approach as a means of gauging tumor behavior remains ill-defined. In this article, the relationship between the mitotic index and biological aggressiveness of pituitary tumors was evaluated in a series of 54 pituitary adenomas and 6 primary pituitary carcinomas. All tumors were fully classified by immunohistochemistry and electron microscopy; adenomas were further stratified on the basis of their invasion status, the latter being defined as gross, operatively, or radiologically apparent infiltration of dura or bone. Mitotic figures were present in 11 tumors, 10 being either invasive adenomas or pituitary carcinomas. A significant association between the presence of mitotic figures and tumor behavior was noted, as evidenced by progressive increments in the proportion of cases expressing mitotic figures in the categories of noninvasive adenoma, invasive adenoma, and pituitary carcinoma (3.9, 21.4, and 66.7%, respectively; Fisher's exact test, two-tailed, p < 0.001). The mitotic index, however, appeared to be a less informative parameter, being extremely low in all cases (mean = 0.016% +/- 0.005 [+/- SEMI). Although the mean mitotic index in pituitary carcinomas (0.09% +/- 0.035) was significantly higher than the mean mitotic index of either noninvasive adenomas (0.002% +/- 0.002) or invasive adenomas (0.013% +/- 0.005), no practical threshold value capable of distinguishing these three groups was evident. Comparison of the mitotic index with Ki-67 derived growth fractions in these tumors revealed a significant but weak linear correlation (r = 0.41, p < 0.01). These data suggest that when, mitotic figures are present, they do provide some indication of the behavior and invasive potential of pituitary tumors. For routine diagnostic
Jin, L; Chandler, W F; Smart, J B; England, B G; Lloyd, R V
The distribution of chromogranin/secretogranin (Cg/Sg) mRNAs, determined by Northern and in situ hybridization, was analyzed in 14 cultured pituitary adenomas characterized by immunohistochemistry and hormone secretion in a defined medium in vitro. There were 5 functional GH adenomas, 1 silent GH adenoma, 7 null cell adenomas, and 1 oncocytoma. The null cell adenomas, oncocytoma, and silent GH adenomas were also analyzed by electron microscopy. Most null cell adenomas and the oncocytoma secreted FSH and LH into the culture medium. GH adenomas, which are examples of well differentiated tumors based on morphological examination, expressed significantly more SgIII mRNA compared to the null cell adenomas and oncocytoma (70 +/- 6% vs. 22 +/- 5%; P < 0.001). GH adenomas also expressed significantly less CgA mRNA compared to the less well differentiated null cell adenomas and oncocytoma (27 +/- 6% vs. 67 +/- 4%; P < 0.001), which could be considered less well differentiated based on ultrastructural morphological features. After treatment with phorbol 12-myristate 13-acetate (10(-7) M) for 7 days, there was an increase in the mRNA for CgB and SgII mRNAs in GH and null cell tumors, while dexamethasone treatment for 7 days increased CgA mRNA in GH and null cell adenomas. GnRH treatment for 7 days increased CgB mRNA in null cell adenomas. Phorbol 12-myristate 13-acetate also decreased the percentage of immunoreactive GH cells and GHm RNA, determined by in situ and Northern hybridization analyses. These results indicate that pituitary adenomas have a distinct pattern of Cg/Sg mRNA expression, which appears to be related to the degree of morphological differentiation of these neoplasms, and suggest that the effects of secretagogues on various Cg/Sg mRNA levels may be related to the stimulation of hormone secretion.
Thompson, Cheryl L; Larkin, Emma K; Patel, Sanjay; Berger, Nathan A; Redline, Susan; Li, Li
Short duration and poor quality of sleep have been associated with increased risks of obesity, cardiovascular disease, diabetes mellitus, and total mortality. However, few studies have investigated their associations with risk of colorectal neoplasia. In a screening colonoscopy-based case-control study, the Pittsburg Sleep Quality Index (PSQI) was administered to 1240 study participants before colonoscopy. Three hundred thirty-eight (27.3%) of the participants were diagnosed with incident colorectal adenomas. Although there was no appreciable difference in the overall PSQI score between cases and adenoma-free controls (5.32 vs 5.11; P = .37), the authors found a statistically significant association of colorectal adenoma with the PSQI component 3, which corresponds to sleep duration (P = .02). Cases were more likely to average less than 6 hours of sleep per night (28.9% vs 22.1% in controls, P = .01). In multivariate regression analysis adjusted for age, gender, race, smoking, family history of colorectal cancer, and waist-to-hip ratio, individuals averaging less than 6 hours per night had an almost 50% increase in risk of colorectal adenomas (OR = 1.47; CI = 1.05-2.06, P for trend = .02) as compared with individuals sleeping at least 7 hours per night. Cases were also more likely to report being diagnosed with sleep apnea (9.8% vs 6.5%, P = .05) and more likely to have worked alternate shifts (54.0% vs 46.1%, P = .01), although these differences were not significant in multivariate models. Shorter duration of sleep significantly increases risk of colorectal adenomas. The authors' results suggest sleep duration as a novel risk factor for colorectal neoplasia. Copyright © 2010 American Cancer Society.
Thompson, Cheryl L.; Larkin, Emma K.; Patel, Sanjay; Berger, Nathan A.; Redline, Susan; Li, Li
Background Short duration and poor quality of sleep have been associated with increased risks of obesity, cardiovascular disease, diabetes mellitus, and total mortality. However, few studies have investigated their associations with risk of colorectal neoplasia. Methods In a screening colonoscopy-based case-control study, the Pittsburg Sleep Quality Index (PSQI) was administered to 1,240 study participants prior to their colonoscopy. Results Three hundred and thirty eight (27.3%) of the participants were diagnosed with incident colorectal adenomas. Although there was no appreciable difference in the overall PSQI score between cases and adenoma-free controls (5.32 vs. 5.11; p=0.37), we found a statistically significant association of colorectal adenoma with the PSQI component 3, which corresponds to sleep duration (p=0.02). Cases were more likely to average less than 6 hours of sleep per night (28.9% vs. 22.1% in controls, p=0.01). In multivariate regression analysis adjusted for age, gender, race, smoking, family history of colorectal cancer, and waist-to-hip ratio, individuals averaging less than 6 hours per night had an almost 50% increase in risk of colorectal adenomas (OR=1.47, CI =1.05-2.06, p for trend=0.02) as compared with individuals sleeping at least 7 hours per night. Cases were also more likely to report of being diagnosed with sleep apnea (9.8% vs. 6.5%, p=0.05) and more likely to have worked alternate shifts (54.0% vs. 46.1%, p=0.01), although these differences were not significant in multivariate models. Conclusions Shorter duration of sleep significantly increases risk of colorectal adenomas. Our results suggest sleep duration as a novel risk factor for colorectal neoplasia. PMID:20936662
Snead, Felicia E. Amdur, Robert J. M.D.; Morris, Christopher G. M.S.; Mendenhall, William M.
Purpose: To evaluate long-term local control and toxicity for pituitary adenomas treated with fractionated radiotherapy (RT). Methods and Materials: The records of 100 patients with pituitary adenomas treated between 1983 and 2003 were retrospectively reviewed. Thirty-one patients had hormone-secreting tumors; 69 patients were treated with surgery and postoperative RT. Median follow-up was 6.7 years (range, 0.6-20.2 years) for all patients and 6.2 years (range, 2-20.2 years) for living patients. The mean dose delivered was 45 Gy (range, 43-50.4 Gy). Results: The 10-year actuarial local control rates for nonsecreting and secreting adenomas were 98% and 73%, respectively (p 0.0015). Actuarial 10-year cause-specific survival (CSS) rates were 95% and 88%, and overall survival rates were 66% and 79% for nonsecreting and secreting adenomas, respectively. Involvement of the sphenoid sinus was found to be significantly associated with decreased 10-year CSS (p = 0.0453). When compared with the two- or three-field techniques, stereotactic RT was associated with improved CSS (p = 0.0775). CSS was not significantly associated with hormone excretion, extent of surgery, or whether RT was administrated postoperatively or for salvage after a postsurgical recurrence. New cases of hypopituitarism occurred in 35 patients. One patient experienced vision loss, and one patient developed a post-treatment glioma. Conclusions: This is one of the most mature series in the literature that documents excellent results with fractionated RT for pituitary adenoma. We recommend 45 Gy at 1.8 Gy per fraction using stereotactic noncoplanar fields.
Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong
Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.
Rubio, Carlos A; Jónasson, Jón G
Iceland has a total population of 300,000 inhabitants. All patients consulting for symptoms of the lower digestive tract during a four-year period (2003-2006) were subjected to a colonoscopic examination; all polyps were endoscopically removed. Out of the total 3,037 colorectal adenomas (CRAs), 308 (10.2%) were traditional serrated adenomas (TSAs). TSAs were divided according the predominant histological phenotype (>50%) into those with ectopic crypt formations (ECF), and those with unlocked serrations (US). ECF-TSA accounted for 5.9% (178/3037) and US-TSA for 4.3% (130/3037). The majority of patients with ECF-TSA and US-TSA were ≥ 60 years of age (74.1% and 76.2%, respectively). Notwithstanding, when patients having advanced adenomas (with high-grade dysplasia, with or without intramucosal carcinoma) were listed by age, those with ECF-TSA were significantly younger than those with US-TSA (p<0.05). ECF-TSA were more frequently left-sided (71.8%), whereas US-TSA were more frequently right-sided (60.0%). Invasive carcinoma evolved more frequently in ECF-TSA (7.8%) and in US-TSA (7.7%) than in tubular adenomas and in villous/tubulovillous adenomas (0.1% and 4.4%, respectively). Comparative studies indicated that the incidence rates/year of ECF-TSA and US-TSA were significantly higher in Iceland than in Sweden or in Italy (p<0.05). Genetic and putative epigenetic (environmental) factor(s) might account for the high incidence rate/year of ECF-TSA and US-TSA in this country.
Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi
Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings. PMID:25077093
Kim, Sangmi; Keku, Temitope O.; Martin, Christopher; Galanko, Joseph; Woosley, John T.; Schroeder, Jane C.; Satia, Jessie A.; Halabi, Susan; Sandler, Robert S.
The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF-α in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF-α were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between levels of inflammatory cytokines, colorectal adenomas, and known risk factors. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines such as older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF-α, and to a lesser degree, with CRP. For IL-6, adjusted odds ratios for colorectal adenomas were 1.78 (95% confidence interval [CI]: 1.18–2.68) for the second highest plasma level, and 1.84 (95% CI: 1.24– 2.74) for the highest level compared with the reference level. A similar association was found with TNF-α, with adjusted odds ratios of 1.54 (95% CI: 1.02–2.33) and 1.65 (95% CI: 1.09–2.50), respectively. Our findings indicate that inflammation might be involved in the early development of colorectal neoplasia, and suggest that systemic inflammatory cytokines might be an indicator of obesity and other risk factors for colorectal neoplasia. PMID:18172326
Samalavicius, Narimantas Evaldas; Mikelis, Kipras; Samalavicius, Robertas
Introduction Transanal endoscopic microsurgery (TEM) is a method of choice for the local treatment of rectal adenomas. Though generally considered as a safe method, some authors have expressed skepticism about the anorectal function following TEM. Aim To review our experience in using TEM for removal of rectal adenomas. We focused on morbidity, local recurrence rates, and anorectal function following the operation. Material and methods The study included 72 patients who underwent TEM for rectal adenomas from December 2009 to November 2014 at the Department of Surgical Oncology, National Cancer Institute. Of the 72 patients, 31 (43.1%) were lost in the follow-up. We recorded the demographics, operative details, final pathology, post-operative length of stay, post-operative complications, recurrences and functional outcome for each of the 41 (56.9%) remaining participants. Results Of the 41 eligible patients, 19 (46.3%) were male and 22 (53.7%) were female. The mean age of our patients was 66.8 years. There were no intraoperative complications. In 4 (9.8%) cases, postoperative complications were observed – urinary retention (2 cases, 4.9%) and postoperative hemorrhage (2 cases, 4.9%). All complications were treated conservatively. There was a single case (2.4%) of adenoma recurrence during the follow-up period. The mean score of the FISI questionnaire was 7.6 ±9.2 (ranging from 0 to 36), and the mean Wexner score was 2.3 ±3.4 (ranging from 0 to 17). Conclusions Transanal endoscopic microsurgery in our experience demonstrated low complication and recurrence rates, and good functional results. We conclude that TEM is an effective and safe method for the treatment of rectal adenomas. PMID:28133497
Mathew, A; Sinha, R; Burt, R; Caan, B; Paskett, E; Iber, F; Kikendall, W; Lance, P; Shike, M; Weissfeld, J; Schatzkin, A; Lanza, E
A large multicenter randomized controlled trial was re-assessed to check whether meat intake and a reduction in its consumption are associated with recurrence of adenomatous polyps of the large bowel, which are precursors of most colorectal malignancies. All subjects (n = 1905; 958 interventions and 947 controls) had one or more histologically confirmed colorectal adenomas removed during a colonoscopy within 6 months before randomization. The subjects were followed-up for approximately 4 years after randomization and a colonoscopy for detecting adenomas was conducted at the 1st and 4th year after randomization. Dietary variables were assessed at baseline (T0) and in conjunction with annual visits at the end of the 1st (T1), 2nd (T2), 3rd (T3) and 4th (T4) years. Odds ratios using logistic regression models for meat variables were estimated based on the average intake at T0, T1, T2, T3 and T4 (prior to the T4 colonoscopy) as well as change (T0-T4) in intake. In the intervention group, the total reduction in median intake of red meat from T0 to T4 was observed by the end of 1st year itself (30 and 31% for men and women, respectively). The analysis provide no evidence to suggest that lower intake or reduction in total and in red meat consumption during a period of 4 years reduces the risk of adenoma recurrence (including multiple or advanced adenoma), whereas the data suggest that high intake of fish is associated with lower risk of adenoma recurrence.
Arakawa, Yoshiki; Mizowaki, Takashi; Ogura, Kengo; Sakanaka, Katsuyuki; Hojo, Masato; Hiraoka, Masahiro; Miyamoto, Susumu; Murata, Daiki
BACKGROUND: Radiation therapy is an available treatment modality for pituitary adenoma. In particular, it is effective for the case unable to be removed with surgery or repeating recurrence. However, hypopituitarism and optic nerve injury associated with radiation therapy become a problem. Novalis® (Brain Lab) is an equipment of radiation to establish the detailed irradiation area, fractionated stereotactic radiotherapy (fSRT) and intensity-modulated radiation therapy (IMRT). Retrospectively, we review local control and morbidity following fSRT with Novalis in pituitary adenoma. PATIENTS AND METHODS: Between 2007 and 2012, 29 patients with pituitary adenoma (9 functioning, 20 non-functioning) received fSRT with Novalis in our institute. Total radiation dose was 50.4-54Gy (1.8 Gy per fraction) and prescribed to the gross target volume + 2 mm. The effectiveness of fSRT was evaluated by tumor volume and clinical symptoms on pre- fSRT, and every 1-year. RESULTS: The median follow-up time was 59.1 months (20 to 83 months). Tumor regrowth was observed in 2 cases. Progression free survival rate was 93%. New visual field deficit was observed in 1 case, and new pituitary dysfunction were not observed in all patients. CONCLUSION: fSRT with Novalis is safe and effective in the treatment for pituitary adenoma. Although follow-up time is short, any problematic complications were not observed. In the future, fSRT is expected to make for safe and effective treatment in pituitary adenoma impossible to cure surgically.
ZHANG, HONGZHI; XU, CHUAN; SUN, NINGYANG; ZHOU, YINTING; YU, XIAOFEI; YAN, XUE; ZHANG, QIUJUAN
The present study aimed to screen potential genes associated with pituitary adenomas to obtain further understanding with regard to the pathogenesis of pituitary adenomas. The microarray GSE23207 dataset, containing 16 pituitary adenoma samples from multiple endocrine neoplasia syndrome-associated rats and 5 normal pituitary tissue samples, was downloaded from Gene Expression Omnibus. The Linear Models for Microarray Data package was used to identify the differentially-expressed genes (DEGs) with the cut-off criteria of a |log2fold change (FC)|>1 and adjusted P-values of <0.05. The potential functions of the DEGs were predicted by functional and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery. Furthermore, the interaction associations of the up- and downregulated DEGs obtained from the Search Tool for the Retrieval of Interacting Genes database were respectively revealed by the protein-protein interaction networks visualized with Cytoscape. A total of 391 upregulated and 238 downregulated DEGs in were screened in the pituitary adenoma samples. The upregulated DEGs with a higher degree in the protein-protein interaction network (e.g., CCNA2, CCNB1 and CDC20) were significantly involved in cell cycle and cell division. Notably, PTTG1 was enriched in every functional term. These DEGs interacted with each other. The downregulated DEGs (e.g., GABRA1, GABRA4 and GABRB1) also interacted with each other, and were relevant to neuroactive ligand-receptor interaction; the DEG POU1F1, interacting with POMC, was correlated with the development of the pituitary gland, adenohypophysis and endocrine system. Certain DEGs, including CCNB1, CCNA2, CDC20, GABRA1, GABRA4, GABRB1, POU1F1 and POMC, and particularly PTTG1, were shown to be closely involved in the pathogenesis of pituitary adenomas. PMID:26870179
Chlumská, A; Boudová, L; Zámecník, M
Sessile serrated adenoma (SSA) is a newly characterized type of the large bowel adenoma. It arises in hyperplastic polyp (HP) and represents a precursor lesion of colorectal carcinoma with microsatellite instability. SSAs differ from common HPs by abnormal proliferation of the crypt epithelium and by nuclear atypia. We examined 15 SSAs from 15 patients. The age range was 25-80 years (average 60 years). Six patients were females and 9 were males. For comparison, we examined 10 conventional tubular adenomas and 10 common HPs with vesicular cells. The sites of SSAs were as follows: 8 in rectum, 4 in rectosigmoid colon, 1 in transverse colon, 1 next to mucinous carcinoma of ascending colon, 1 in anastomosis after resection of the transverse colon adenocarcinoma. The diameter of the lesions ranged from 5 to 12 mm. Histologically, SSAs showed asymmetrical proliferation of the epithelium, irregular shape of the crypts with their branching and some crypt dilatations especially in the basal parts of the crypts. Cellular atypia (dysplasia) was usually low. In 5 cases the nuclei were focally stratified and localized in the lower part of the cells. High-grade dysplasia was found only in SSA adjacent to mucinous adenocarcinoma. Immunohistochemically, SSAs showed secretion of gastrointestinal mucin expressing MUC2 and MUC5A. Both MUC2 and MUC5A were also positive in mucinous carcinoma. In previous studies these expressions were considered specific for serrated type of carcinogenesis. However, our study found positivity of MUC2 and MUC5A also in conventional adenomas. Expression of p53 in SSAs was minimal. SSAs have malignant potential comparable with conventional adenomas and for this reason they must be distinguished from HPs.
Jogunoori, Wilma; Menon, Vipin; Majumdar, Avijit; Chen, Jiun-Sheng; Gi, Young Jin; Jeong, Yun Seong; Phan, Liem; Belkin, Mitchell; Gu, Shoujun; Kundra, Suchin; Mistry, Nipun A.; Zhang, Jianping; Su, Xiaoping; Li, Shulin; Lin, Sue-Hwa; Javle, Milind; McMurray, John S.; Rahlfs, Thomas F.; Mishra, Bibhuti; White, Jon; Rashid, Asif; Beauchemin, Nicole; Weston, Brian R.; Shafi, Mehnaz A.; Stroehlein, John R.; Davila, Marta; Akbani, Rehan; Weinstein, John N.; Wu, Xifeng; Mishra, Lopa
Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-β signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-β signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-β in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression. PMID:27100181
Lim, Chul-Hyun; Cho, Young-Seok
Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis (FAP), but nonampullary sporadic duodenal adenomas (SDAs) are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polyp-free duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAP-related polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas. PMID:26811631
Caretto, Amelia; Lanzi, Roberto; Piani, Cecilia; Molgora, Michela; Mortini, Pietro; Losa, Marco
Gonadotroph adenomas are pituitary adenomas with inefficient and variable secretory characteristics, that is why they are usually considered as a subgroup of nonfunctioning pituitary adenomas (NFPA) and are recognized only at immunohistochemistry. When gonadotroph adenomas secrete active hormones, they may cause spontaneous ovarian hyperstimulation syndrome (OHSS) in premenopausal women. Aim of our study is to describe three women with OHSS diagnosed before the removal of the adenoma and to calculate the prevalence of OHSS in premenopausal women with a clinical diagnosis of NFPA. We reviewed clinical records of premenopausal women that underwent neurosurgery for NFPA at our centre between 1993 and 2014. OHSS was diagnosed in patients with high levels of FSH, suppressed LH, hyperestrogenism, abdominal symptoms, polymenorrhea, enlarged ovaries with cysts or previous surgery for ovarian cysts. 171 women were included into the study; 62 (36.6%) had a gonadotroph adenoma diagnosed at immunohistochemistry. Two patients were retrospectively diagnosed as having OHSS due to gonadotroph adenoma and three had OHSS diagnosed before neurosurgery. The prevalence of OHSS was 2.9% in the overall group of patients with NFPA and 8.1% among patients with a gonadotroph adenoma detected at immunohistochemistry. Frequency of OHSS due to a gonadotroph adenoma is not negligible. Increased awareness of the characteristic clinical and hormonal picture should permit an early detection of this condition in premenopausal women with a pituitary adenoma.
Del Vecchio Blanco, G; Cretella, M; Paoluzi, O A; Caruso, A; Mannisi, E; Servadei, F; Romeo, S; Grasso, E; Sileri, P; Giannelli, M; Biancone, L; Palmieri, G; Pallone, F
First-degree relatives (FDRs) of patients with colorectal cancer (CRC) have an increased CRC risk. Few studies have addressed if adenoma and advanced adenoma risk is increased among individuals, 40-49 years of age, with a family history of CRC. Therefore, the aim of the study was to define the prevalence and location of adenoma, advanced adenoma and CRC, according to age, in asymptomatic individuals with a family history of CRC. Retrospective study of asymptomatic FDRs, 40 to ≥70 years of age undergoing first screening colonoscopy over a 3-year period, of CRC patients. Among 464 individuals studied, the prevalence of adenoma and advanced adenoma was 18.1% and 6.4%, respectively. According to age intervals, the prevalences of adenoma and advanced adenoma were 14% and 3.5%, respectively, in subjects 40-49 years of age; 14.4% and 6.3%, respectively, in subjects 50-59 years of age; 27% and 8%, respectively, in subjects 60-69 years of age; and 25% and 14%, respectively, in subjects ≥70 years of age; no significant difference was found among the four groups. No difference in lesion location was found, with similar numbers of preneoplastic lesions being present in the right colon and the left colon. CRC was diagnosed in three (0.64%) subjects, one of whom was in the 40-49 years age group. In our population of FDRs of CRC patients, 40-49 years of age, the prevalences of adenoma and advanced adenoma were similar to those observed in older subjects with the same CRC risk. Our data support the current indication to perform screening colonoscopy earlier than 45 years of age in subjects at high CRC risk. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.
Jackson, J.A.; Naul, L.G.; Montgomery, J.L.; Carpentier, W.R.; Roberts, J.W.
A 55-yr-old man presented with an atypical relapsing meningitis and was found to have intense unilateral adrenal uptake by /sup 67/Ga imaging. Computed tomography showed a 4-cm right adrenal mass which was hypointense on the T1-weighted images and mildly hyperintense on the T2-weighted images of a magnetic resonance (MR) scan. At surgery, a coincidental benign adrenocortical adenoma was found. Because /sup 67/Ga uptake is usually associated with inflammatory or malignant lesions and malignant adrenal lesions are hyperintense on T2-weighted MR images, these findings contributed to diagnostic uncertainty in this patient. Thus, a nonhyperfunctional adrenocortical adenoma may be associated with abnormal /sup 67/Ga uptake and atypical MR findings.
Martin, Nicole M; Abu Dayyeh, Barham K; Chung, Raymond T
Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.
Becker, Gerd; Kocher, Martin; Kortmann, Rolf-Dieter; Paulsen, Frank; Jeremic, Branislav; Müller, Rolf-Peter; Bamberg, Michael
Pituitary tumors are relatively uncommon, comprising 10-12% of all intracranial tumors. The treatment consisting of surgery, radiotherapy and drug therapy or a combination of these modalities is aimed at the control of tumor cell proliferation and--in endocrine active tumors--the reduction of hormone secretion. However, the slow proliferation characteristics of pituitary tumors necessitate long-term studies for the evaluation of the treatment results. In the last decade there has been continuous improvement in surgical procedures, radiotherapy techniques and drug generation. In this paper, literature will be reviewed to assess the role of modern radiotherapy and radiosurgery in the management of pituitary adenomas. Nowadays, magnetic resonance imaging for the definition of the target volume and a real three-dimensional (3-D) treatment planning with field conformation and the possibility for non-coplanar irradiation has to be recommended. Most groups irradiate these benign tumors with single doses of 1.8-2.0 Gy up to a total dose of 45 Gy or 50.4 Gy in extensive parasellar adenomas. Adenomas are mostly small, well circumscribed lesions, and have, therefore, attracted the use of stereotactically guided high-precision irradiation techniques which allow extreme focussing and provide steep dose gradients with selective treatment of the target and optimal protection of the surrounding brain tissue. Radiation therapy controls tumor growth in 80-98% of patients with non-secreting adenomas and 67-89% for endocrine active tumors. Reviewing the recent literature including endocrine active and non-secreting adenomas, irradiated postoperatively or in case of recurrence the 5-, 10- and 15-year local control rates amount 92%, 89% and 79%. In cases of microprolactinoma primary therapy consists of dopamine agonists. Irradiation should be preferred in patients with macroprolactinomas, when drug therapy and/or surgery failed or for patients medically unsuitable for surgery. Reduction
Lee, Jing-Sheng; Lau, Beng-Huat; Yeh, Ming-Lun; Lee, Chin-Cheng
A 12-year-old girl was admitted to ward because of persistent left flank pain, vomiting, and hematuria. A stone was located at the ureteropelvic junction of the left kidney, as determined by means of abdominal sonography. Metabolic investigation for a renal stone revealed that she had hypercalcemia, hypophosphatemia, and hypercalciuria. Hyperparathyroidism was diagnosed based on the hypercalcemia and inappropriately elevated serum parathyroid hormone level. A parathyroid adenoma was successfully diagnosed by using thallium/technetium subtraction parathyroid scanning. Extracorporeal shock wave lithotripsy was performed to treat the renal stone, and the parathyroid adenoma was successfully removed. The patient's postoperative course was uneventful. This case is presented because urolithiasis and hyperparathyroidism are rare in children. Metabolic evaluation is mandatory in children with a renal stone. Further investigation for the hyperparathyroidism should be performed if hypercalcemia associated with hypercalciuria is documented.
Cooper, B. T.; Mountford, R. A.; McKee, C.
A 49-year-old woman presented with a one month history of headaches, loss of libido and galactorrhoea. She had been taking metoclopramide for the previous 3 months for reflux oesophagitis. She was found to have substantially elevated serum prolactin levels and a pituitary adenoma, which have not been previously described in a patient taking metoclopramide. The drug was stopped and the serum prolactin level fell progressively to normal with resolution of symptoms over 4 months. This suggested that contrary to our original impression that she had a prolactin-secreting pituitary adenoma which had been stimulated by metoclopramide, she had metoclopramide-induced hyperprolactinaemia and an incidental pituitary tumour. ImagesFig. 1 PMID:7202198
Martin, Nicole M; Dayyeh, Barham K Abu; Chung, Raymond T
Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks. PMID:18680242
Theodros, Debebe; Patel, Mira; Ruzevick, Jacob; Lim, Michael; Bettegowda, Chetan
Pituitary adenomas are among the most common central nervous system tumors. They represent a diverse group of neoplasms that may or may not secrete hormones based on their cell of origin. Epidemiologic studies have documented the incidence of pituitary adenomas within the general population to be as high as 16.7%. A growing body of work has helped to elucidate the pathogenesis of these tumors. Each subtype has been shown to demonstrate unique cellular changes potentially leading to tumorigenesis. Surgical advancements over several decades have included microsurgery and the employment of the endoscope for surgical resection. These advancements increase the likelihood of gross-total resection and have resulted in decreased patient morbidity. PMID:26497533
Rodríguez-Gutiérrez, René; Bautista-Medina, Mario Arturo; Teniente-Sanchez, Ana Eugenia; Zapata-Rivera, Maria Azucena; Montes-Villarreal, Juan
Pure androgen-secreting adrenal adenoma is very rare, and its diagnosis remains a clinical challenge. Its association with resistant hypertension is uncommon and not well understood. We present an 18-year-old female with a 10-year history of hirsutism that was accidentally diagnosed with an adrenal mass during the evaluation of a hypertensive crisis. She had a long-standing history of hirsutism, clitorimegaly, deepening of the voice, and primary amenorrhea. She was phenotypically and socially a male. FSH, LH, prolactin, estradiol, 17-hydroxyprogesterone, and progesterone were normal. Total testosterone and DHEA-S were elevated. Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonclassic congenital adrenal hyperplasia were ruled out. She underwent adrenalectomy and pathology reported an adenoma. At 2-month followup, hirsutism and virilizing symptoms clearly improved and blood pressure normalized without antihypertensive medications, current literature of this unusual illness and it association with hypertension is presented and discussed. PMID:23819074
Rodríguez-Gutiérrez, René; Bautista-Medina, Mario Arturo; Teniente-Sanchez, Ana Eugenia; Zapata-Rivera, Maria Azucena; Montes-Villarreal, Juan
Pure androgen-secreting adrenal adenoma is very rare, and its diagnosis remains a clinical challenge. Its association with resistant hypertension is uncommon and not well understood. We present an 18-year-old female with a 10-year history of hirsutism that was accidentally diagnosed with an adrenal mass during the evaluation of a hypertensive crisis. She had a long-standing history of hirsutism, clitorimegaly, deepening of the voice, and primary amenorrhea. She was phenotypically and socially a male. FSH, LH, prolactin, estradiol, 17-hydroxyprogesterone, and progesterone were normal. Total testosterone and DHEA-S were elevated. Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonclassic congenital adrenal hyperplasia were ruled out. She underwent adrenalectomy and pathology reported an adenoma. At 2-month followup, hirsutism and virilizing symptoms clearly improved and blood pressure normalized without antihypertensive medications, current literature of this unusual illness and it association with hypertension is presented and discussed.
Liao, Po-Wu; Chen, Yen-Lin; Chen, Jeng-Wen
Abstract Background: A carcinoma ex pleomorphic adenoma (CXPA) is an epithelial malignancy arising in or from a benign pleomorphic salivary adenoma. The parotid gland is the most common location of CXPAs. Minor salivary gland CXPAs of the nasal cavity are exceedingly rare, with only 6 documented in the literature. Methods and Result: We present a 7th case: an unusual pedunculated intranasal CXPA, which had a favorable outcome after a wide endoscopic excision and the longest follow-up period reported to date. The clinical features, immunohistochemical characteristics, treatment choices, and disease outcomes of the intranasal CXPAs reported in previous studies are also reviewed. Conclusion: This case demonstrates the importance of considering the possibility of CXPA in the differential diagnosis of minor salivary gland malignancies in the nasal cavity. PMID:27684860
Tran, Fiona; Koo, Jenn Hian
To examine the impact of the patient's birthplace on the prevalence of colonic polyps and histopathological subtypes. This is a retrospective audit of the colonoscopy practice of one Gastroenterologist in a tertiary-referral hospital from 2008 to 2011. Data collected include demography, birthplace, language spoken, details of the colonoscopy including indications, completion rates, complications, results including prevalence and histopathology of polyps. Statistical methods used were binary logistic regression, χ(2) and Mann-Whitney U. A total of 623 patients (48% male, 67% aged over 50 years) were recruited and categorised according to birthplace: Australia/New Zealand 42%, European 20%, Asian 15%, Middle Eastern/African 11%, South American 9% and Pacific Islander 3%. The median age of the cohort was 56.3 years (range: 17-91 years), median body mass index 27.3 kg/m(2) (range: 16-51 kg/m(2)), 25% were smokers, 25% had hypercholesterolemia, 20% had diabetes mellitus 16% were on aspirin and 7% were on non-steroidal anti-inflammatory drugs. A total of 651 colonoscopies were performed for standard indications. The prevalence of polyps varied according to patient's birthplace: Europe 45.1%, Australia and New Zealand 39.5%, Pacific Islands 33.3%, Asia 30.3%, Middle East and Africa 26.9% and South America 24.5% (P = 0.027, df = 6). However, multivariate analysis revealed that birthplace was not an independent predictor of developing polyps, including adenomas and advanced adenomas after correcting for age and male sex. Birthplace is not a predictor for developing colorectal neoplasia, including adenomas and advanced adenomas; hence, should not influence the recommendations for colorectal cancer screening.
Ostrosky, Alejandro; Klurfan, Federico Juan; Gonzalez, Maximiliano Jorge; Camaly, Diego; Villa, Diego
Lacrimal gland tumors are rare. We present a case of a 69 year old male patient with a one year history of an orbital tumor (Pleomorphic Adenoma). The tumor was surgically enucleated and patient recovery was very satisfactory, with no signs of recurrence after one year of follow-up. A review of the clinical symptoms, radiologic features, treatment and histopathology of this kind of tumors is also made.
Diergaarde, Brenda; Tiemersma, Edine W; Braam, Hanneke; van Muijen, Goos N P; Nagengast, Fokko M; Kok, Frans J; Kampman, Ellen
Inactivating mutations in APC are thought to be early, initiating events in colorectal carcinogenesis. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors and the occurrence of these mutations in a Dutch case-control study of sporadic colorectal adenomas (278 cases; 414 polyp-free controls). Direct-sequencing was used to screen adenomas for mutations in the mutation cluster region of APC; truncating mutations were detected in 161 (58%) of the adenomas. Red meat consumption was significantly differently related to polyps with truncating APC mutation (APC(+) polyps) compared to polyps without truncating APC mutation (APC(-) polyps) (highest vs. lowest tertile, odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.3-1.0). High intake of red meat and fat seemed to increase the risk of APC(-) polyps only (APC(+) vs. controls: red meat, OR = 1.0, 95% CI = 0.6-1.6; fat, OR = 1.1, 95% CI = 0.6-1.9; APC(-) vs. controls: red meat, OR = 1.8, 95% CI = 1.0-3.1; fat, OR = 1.9, 95% CI = 1.0-3.7). Intake of carbohydrates was inversely associated with both polyp groups, most noticeably with APC(-) polyps. Most other evaluated dietary factors were not distinctively associated with a specific APC status. None of the dietary factors was specifically associated with a particular type of truncating APC mutation. Our data suggest that red meat and fat may increase the risk of APC(-) polyps in particular, whereas carbohydrates may especially decrease the risk of APC(-) polyps. However, most examined dietary factors do not appear to be specifically associated with the occurrence of truncating APC mutations in colorectal adenomas but seem to affect both pathways equally.
Casillas-Enríquez, José D; Álvarez-Maldonado, Pablo; Salguero-Cruz, Luís; Navarro-Reynoso, Francisco; Cicero-Sabido, Raúl; Núñez-Pérez Redondo, Carlos
We present the case of a 33-year-old woman who was being treated for bronchial asthma for 4 years. A tracheal tumor was evident on a computed tomography of the thorax and removed with argon plasma coagulation. It was diagnosed as pleomorphic adenoma of the trachea. It is a rare tracheal tumor without definite treatment guidelines. Our endoscopic approach to this rare lesion is discussed.
Dik, Vincent K; Moons, Leon MG; Siersema, Peter D
Up to a quarter of polyps and adenomas are missed during colonoscopy due to poor visualization behind folds and the inner curves of flexures, and the presence of flat lesions that are difficult to detect. These numbers may however be conservative because they mainly come from back-to-back studies performed with standard colonoscopes, which are unable to visualize the entire mucosal surface. In the past several years, new endoscopic techniques have been introduced to improve the detection of polyps and adenomas. The introduction of high definition colonoscopes and visual image enhancement technologies have been suggested to lead to better recognition of flat and small lesions, but the absolute increase in diagnostic yield seems limited. Cap assisted colonoscopy and water-exchange colonoscopy are methods to facilitate cecal intubation and increase patients comfort, but show only a marginal or no benefit on polyp and adenoma detection. Retroflexion is routinely used in the rectum for the inspection of the dentate line, but withdrawal in retroflexion in the colon is in general not recommended due to the risk of perforation. In contrast, colonoscopy with the Third-Eye Retroscope® may result in considerable lower miss rates compared to standard colonoscopy, but this technique is not practical in case of polypectomy and is more time consuming. The recently introduced Full Spectrum Endoscopy™ colonoscopes maintains the technical capabilities of standard colonoscopes and provides a much wider view of 330 degrees compared to the 170 degrees with standard colonoscopes. Remarkable lower adenoma miss rates with this new technique were recently demonstrated in the first randomized study. Nonetheless, more studies are required to determine the exact additional diagnostic yield in clinical practice. Optimizing the efficacy of colorectal cancer screening and surveillance requires high definition colonoscopes with improved virtual chromoendoscopy technology that visualize the
Onyekaba, C O
Spontaneous thyroid micro-follicular adenoma was found in an 18-month-old nursing Swiss albino mouse. The lesion was first noted as a tiny bulge at the base of the neck. The tumor was solid, and within two months, had grown such an enormous size that movement, feeding and suckling of the litter were greatly hampered. The litter of seven mice later died due to improper nursing while their mother remained generally unaffected by the mass.
To treat pituitary adenomas, three modes of treatment are usually combined: neurosurgery, radiation and pharmacological. Prolactinomas are an exception with predominantly pharmacological management. Patients with acromegaly are usually diagnosed late and thus many neurosurgeries fail to completely remove the adenoma. Any residual tumour tissue is usually irradiated with the Leksell Gamma Knife, and dopamine agonists, somatostatine analogues or growth hormone receptor antagonists are used to normalize the hormonal hypersecretion until the complete effect of the radiation. The same surgical and Gamma Knife procedures are used in patients with the Cushing's disease and TSH-secreting adenomas. Ketoconazole, metyrapone and cabergoline are used until the radiation effect in the Cushing's disease is complete, similarly, somatostatine analogues are used in TSH-secreting adenomas. Nonfunctional adenomas are less responsive to pharmacological treatment. Proautophagic cytostatic temozolamide has been used in aggressive pituitary adenomas and carcinomas.
van der Vorst, Joost R.; Schaafsma, Boudewijn E.; Verbeek, Floris P.R.; Swijnenburg, Rutger-Jan; Tummers, Quirijn; Hutteman, Merlijn; Hamming, Jaap F.; Kievit, J.; Frangioni, John V.; van de Velde, Cornelis J.H.; Vahrmeijer, Alexander L.
Background Intraoperative identification of parathyroid adenomas can be challenging. We hypothesized that low-doses methylene blue (MB) and near-infrared fluorescence (NIRF) imaging could be used to identify parathyroid adenomas intraoperatively. Methods MB was injected intravenously after exploration at a dose of 0.5 mg/kg into 12 patients who underwent parathyroid surgery. NIRF imaging was performed using the Mini-FLARE™ imaging system. Results In 10 of 12 patients, histology confirmed a parathyroid adenoma. In 9 of these patients, NIRF could clearly identify the parathyroid adenoma during surgery. Seven of these 9 patients had a positive preoperative 99mTc-sestamibi SPECT scan. Importantly, in two patients, parathyroid adenomas could be identified only using NIRF. Conclusion This is the first study to show that low-dose MB can be used as NIRF tracer for identification of parathyroid adenomas, and suggests a correlation with preoperative 99mTc-sestamibi SPECT scanning. PMID:23720199
Ziaeean, Bizhan; Sohrabi-Nazari, Sahar
Parathyroid adenoma is a benign tumor of the parathyroid glands. The cause of most parathyroid adenomas is unknown. Parathyroid adenoma increases the secretion of parathyroid hormone and results in primary hyperparathyroidism. High amounts of parathyroid hormone in the blood cause the imbalance of calcium, which leads to various complications such as kidney stones, depression, lethargy, nausea, vomiting, abdominal pain, myalgia, bone and joint pain, hoarseness, etc. Oropharyngeal dysphagia is defined as having problem in swallowing due to abnormalities in the structure and function of oropharynx and other related organs. The exact prevalence of dysphagia caused by parathyroid adenoma is unknown, but since this complication can lead to increased mortality and morbidity, its diagnosis is important. It is difficult to distinguish parathyroid malignancies from parathyroid adenoma even after surgery. Therefore, the final diagnosis is possible through surgery and histopathological evaluation. Here, a case of parathyroid adenoma with first presentation of generalized weakness and dysphagia has been reported. PMID:27582595
Pramod Krishna, B
Salivary gland tumours are rare in childhood, and almost all of them occur in parotid gland. Minor salivary gland tumours are even rarer, pleomorphic adenoma being the most frequently found tumour. Only seventeen cases of pleomorphic adenoma arising in the minor salivary gland tumour have been reported in children and adolescents. Pleomorphic adenoma of minor salivary gland represents about 45% of all the tumours of the minor salivary glands. Pleomorphic adenoma is slowly enlarging tumour indistinguishable from adenoid cystic carcinoma clinically, except for pain and ulceration, which is more common in the latter. Carcinoma arising from pleomorphic adenoma has been reported in 3% cases amongst the minor salivary gland tumours. This report presents a case of pleomorphic adenoma of minor salivary gland in a 14 year old female patient with a brief review of literature.
Aver-De-Araujo, L M; Chaves-Tarquinio, S B; Neuzling-Gomes, A P; Etges, A
Pleomorphic adenoma is the most common neoplasm of the salivary glands, affecting mainly the parotid gland. The preferential intraoral site of this tumor is the palate. A case of a 31-year-old woman with an intraosseous pleomorphic adenoma located in the maxilla (left paramedian region), showing an approximate evolution of one year is reported. The present intraosseous case represents a rare location, with the tumor probably originating from glandular epithelial remnants captured during embryogenesis. In a review of the literature of 142 cases of intragnathic localization (24% in the maxilla) are identified. A slight predominance of women was observed (56%), with 55% of the patients being affected during the 5th to 7th decade of life. The tumors were malignant in 94% of the cases, with special predominance of mucoepidermoid carcinoma (65%). Intraosseous pleomorphic adenomas are rare, with the present patient being the 6th case reported in the literature and the second found in the maxilla. Mean age of the 5 previously reported cases was 58.8 years.
Cho, Hwa Jin; Kim, Hanna; Kwak, Yoon Jin; Seo, Jeong Wook; Paek, Sun Ha; Sohn, Chul-Ho; Yun, Jung Min; Kim, Da Seu Ran; Kang, Peter; Park, Peom; Park, Sung-Hye
Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.
Dusan, Ruzicic; Relja, Kovacevic; Marija, Mirkovic; Jelena, Radovanovic; Vesna, Krstevska; Milijana, Terzic; Vladimir, Pantelic; Irena, Matic; Dragan, Hrncic
Metanephric adenoma (MA) is a rare neoplasm that acounts for 0.2% of adult renal neoplasms. MAs are typically discover incidentally during detailed examinations for nonspecific symptoms such as abdominal or flank pain, hematuria, fever and palpable abdominal mass. Additionally, polycythemia has occasionally been reported as well. Herein we describe a case of metanephric adenoma which was an incidental finding in the course of a clinical autopsy in a patient with complete AV block and polycythemia. Histologically, the tumor was composed of small and uniform tubular structures reminiscent of renal tubuli, without signs of cellular atypia and pleomorphism. Such tumor histomorphology was consistent with the diagnosis of metanephric adenoma. Thrombosis is a common complication of polycythemia that often causes death. Polycythemia with an increasing number of blood cells causes hyperviscosity and, in 20-40% of cases, lethal thrombosis or hemorrhage. Hyperviscosity and coronary artery disease in our patient caused acute myocardial infarction with the subsequent rupture of posterior left ventricle wall and hemopericardium. PMID:27471365
Dusan, Ruzicic; Relja, Kovacevic; Marija, Mirkovic; Jelena, Radovanovic; Vesna, Krstevska; Milijana, Terzic; Vladimir, Pantelic; Irena, Matic; Dragan, Hrncic
Metanephric adenoma (MA) is a rare neoplasm that acounts for 0.2% of adult renal neoplasms. MAs are typically discover incidentally during detailed examinations for nonspecific symptoms such as abdominal or flank pain, hematuria, fever and palpable abdominal mass. Additionally, polycythemia has occasionally been reported as well. Herein we describe a case of metanephric adenoma which was an incidental finding in the course of a clinical autopsy in a patient with complete AV block and polycythemia. Histologically, the tumor was composed of small and uniform tubular structures reminiscent of renal tubuli, without signs of cellular atypia and pleomorphism. Such tumor histomorphology was consistent with the diagnosis of metanephric adenoma. Thrombosis is a common complication of polycythemia that often causes death. Polycythemia with an increasing number of blood cells causes hyperviscosity and, in 20-40% of cases, lethal thrombosis or hemorrhage. Hyperviscosity and coronary artery disease in our patient caused acute myocardial infarction with the subsequent rupture of posterior left ventricle wall and hemopericardium.
Introduction Lesions of the ampulla of Vater are rare histological entities with an incidence of between 0.1 and 0.2% of gastrointestinal tumors. Until recently the main response to this kind of lesion was duodenopancreatectomy, regardless of the cellular atypia and local edema. In this study, we propose the application of transduodenal local excision of the ampulla of Vater especially in recognized cases of nonmalignant adenomas. Case presentation In this case report we analyze the case of a 78-year-old Greek man who revealed symptoms such as icterus, abdominal pain without constipation and bloody stools. A physical examination showed painless swelling of the gallbladder (Courvoisier sign). No previous abdominal operations or hernias were identified. Blood tests, computed tomography scan analysis, gastroscopy and endoscopic retrograde cholangiopancreatography along with biopsies and cytological tests diagnosed nonmalignant adenoma of the ampulla of Vater with high-grade dysplasia. The treatment we followed was transduodenal local excision of his ampulla of Vater. Conclusions Transduodenal local excision of the ampulla of Vater has limited side effects and postoperative complications, suggesting this particular technique to be the proper treatment for nonmalignant cases of adenomas. PMID:24965285
Samar, María Elena; Avila, Rodolfo Esteban; Fonseca, Ismael Bernardo; Anderson, William; Fonseca, Gabriel M; Cantín, Mario
Canalicular adenoma (CA) is an uncommon benign neoplasia of salivary glands which is clinically difficult to recognise. Despite having an excellent prognosis, the histological diagnosis and clinical management of this entity can be troublesome. While the main differential diagnosis to consider is basal cell adenoma (BCA), similar histological patterns and multifocality have been observed in adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA), both locally-aggressive malignancies which require radically different treatment to CA. An emphasis has been placed on the value of immunohistochemistry in avoiding diagnostic and surgical errors. CA is positive for AE1/AE3, CD117 and S-100 protein, and negative for p63, α-SMA, Ki 67 and vimentin. Here we discuss the case of a 61-year-old female with CA in her right upper lip, showing multifocal growth histologically. The differential diagnosis with other adenomas is discussed in addition to the role of immunohistochemical studies that can confirm the clinical and surgical findings. PMID:25550873
Gana, Polycarp; Masterson, Liam
Introduction Pleomorphic adenomas are the most common benign tumour of the major salivary glands. In addition, they may also occur in the minor salivary glands of the hard and soft palate. Intranasal pleomorphic adenomas are unusual and may be misdiagnosed because they have greater myoepithelial cellularity and fewer myxoid stromata compared to those elsewhere. Case presentation We present the case of a 61-year-old man who presented with a 2-year history of left nasal obstruction, occasional epistaxis and facial pain. Radiological examination demonstrated well pneumatised paranasal sinuses and a soft tissue mass in the anterior aspect of the left nasal cavity. In this patient, an intranasal approach was used to achieve a wide local resection. Conclusion Pleomorphic adenomas are rare tumours of the nasal cavity and have been shown to be misdiagnosed in over half of cases leading to more aggressive treatment than is necessary. If unilateral nasal obstruction is the main presenting complaint, we suggest consideration of this diagnosis. In view of the potential for tumour recurrence, long-term follow-up and careful examination of the nose with an endoscope are necessary. PMID:19014678
Davidov, M I
A randomized trial of efficacy and safety of vitaprost plus and vitaprost forte has been made in 70 patients with prostatic adenoma comorbid with chronic bacterial prostatitis. The patients were randomized into two groups: group 1 patients received vitaprost plus in rectal suppositoria for 1 months, then vitaprost forte for 2 months; group 2 patients (control) received gentos and lomefloxacin per os. Short- and long-term results were evaluated in 3 and 6 months. By all parameters group 1 achieved better treatment results than controls. Immediate positive response was observed in 97.1% patients, long-term positive effects were observed in 85.7%. Total points of prostatic adenoma symptoms reduced by 37%, chronic prostatitis--by 55%, residual urine diminished by 66%, Qmax increased, quality of life improved by 45%, sexual function enhanced. Size of the prostate decreased by 7.4 cm3, leukocyte count in prostatic secretion fell 6-fold, eradication of prostatitis causing agent was achieved in 3 months in 80% patients. Side effects and complications were not registered. Thus, vitaprost plus and vitaprost forte are highly effective and safe for treatment of patients with combination of prostatic adenoma with chronic bacterial prostatitis.
Russo, D.; Arturi, F.; Filetti, S.
Forty-four thyroid autonomously hyperfunctioning adenomas were analyzed to assess the frequency of mutations occurring in the TSH receptor (TSHR). PCR-amplified fragments encompassing the entire exon 10 of the TSHR gene were obtained from the genomic DNA extracted from the tumors and their adjacent normal tissues and were examined by direct nucleotide sequencing. Point mutations were found in 9 of 44 adenomas examined (20%). One mutation occurred in codon 619 (Asp to Gly), four in codon 623 (three were Ala to Ser, one Ala to substitution), two in codon 632 (both Thr to Ile), and two in codon 633 (Asp to Tyr or His). All the alterations were located in a part of the gene coding for an area including the third intracellular loop and the sixth transmembrane domain of the TSH receptor. All mutations were somatic and heterozygotic, and none was simultaneous with alterations of ras or gsp oncogenes. Thus, our data show that in our series of 44 hyperfunctioning thyroid adenomas, a somatic mutation of the TSHR, responsible for the constitutive activation of the cAMP pathway, occurs in 20% of the tumors. 28 refs., 2 tabs.
Chanson, Philippe; Raverot, Gerald; Castinetti, Frédéric; Cortet-Rudelli, Christine; Galland, Françoise; Salenave, Sylvie
Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
For many years, it was generally accepted that the vast majority of the colorectal carcinomas (CRCs) evolved from conventional adenomas, via the adenoma–carcinoma sequence. More recently, serrated colorectal polyps (hyperplastic polyps, sessile serrated polyps and traditional serrated adenomas (TSAs)) have emerged as an alternative pathway of colorectal carcinogenesis. It has been estimated that about 30% of the CRC progress via the serrated pathway. Recently, TSAs were also detected in the upper digestive tract. In this work, we review the literature on TSA in the oesophagus, the stomach, the duodenum, the pancreatic main duct and the gallbladder. The review indicated that 53.4% (n=39) out of the 73 TSA of the upper digestive tract now in record showed a simultaneously growing invasive carcinoma. As a corollary, TSAs of the upper digestive tract are aggressive adenomas that should be radically excised, either endoscopically or surgically, to rule out the possibility of a synchronously growing invasive adenocarcinoma or to prevent cancer progression. The present findings substantiate a TSA pathway of carcinogenesis in the upper digestive tract. PMID:26468393
Singh, Kanika; Agarwal, Charu; Pujani, Mukta; Verma, Pragya; Chauhan, Varsha
Carcinoma ex pleomorphic adenoma (Ca ex PA) is a malignant neoplasm arising from primary or recurrent benign pleomorphic adenoma. It is rare with an annual incidence rate of 0.17 tumors per million. Histopathology remains the gold standard for the diagnosis of Ca ex PA, with only a handful of cases reported on cytology. In our case a 66-year-old male presented with the right parotid mass for 5 years rapidly increasing for the last 3 months. Fine needle aspiration cytology (FNAC) smears showed malignant tumor cells in clusters along with benign myoepithelial cells in chondromyxoid background. Histopathologically, highly pleomorphic malignant epithelial cells in sheets along with foci of comedonecrosis and areas corresponding to benign pleomorphic adenoma were observed on careful scrutiny. Immunohistochemistry revealed positivity for cytokeratin (CK 7) and gross cystic disease fluid protein 15 (GCDFP-15) while CK5/6 and high molecular weight CK (34 βE12) were negative in the malignant tumor cells. So, the final impression was Ca ex PA with salivary duct carcinoma as malignant component. We hereby report this case to highlight the significance of FNAC in the diagnosis of Ca ex PA which can be easily missed on cytopathology. However, it is important to corroborate the cytological findings with clinical suspicion of malignancy as well as radiology. Diagn. Cytopathol. 2017. © 2017 Wiley Periodicals, Inc.
Campobasso, Paolo; Fasoli, Lorella; Dante, Stefania
Nephrogenic adenoma is a rare, benign lesion of the bladder, occurring as an epithelial response to chronic infection or trauma, probably arising from nephrogenic metaplasia. In contrast to nephrogenic adenomas in adults, who present with this tumor in the entire ureteral tract, it has been observed exclusively in the bladder of children thus far. We report and discuss here the case of a 12-year-old boy with diffuse calculus-producing nephrogenic adenoma successfully treated with sodium hyaluronate.
Koestler, Devin C; Li, Jing; Baron, John A; Tsongalis, Gregory J; Butterly, Lynn F; Goodrich, Martha; Lesseur, Corina; Karagas, Margaret R; Marsit, Carmen J; Moore, Jason H; Andrew, Angeline S; Srivastava, Amitabh
Recent studies have shown two distinct non-CIMP methylation clusters in colorectal cancer, raising the possibility that DNA methylation, involving non-CIMP genes, may play a role in the conventional adenoma-carcinoma pathway. A total of 135 adenomas (65 left colon and 70 right colon) were profiled for epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip. A principal components analysis was performed to examine the association between variability in DNA methylation and adenoma location. Linear regression and linear mixed effects models were used to identify locus-specific differential DNA methylation in adenomas of right and left colon. A significant association was present between the first principal component and adenoma location (P=0.007), even after adjustment for subject age and gender (P=0.009). A total of 168 CpG sites were differentially methylated between right- and left-colon adenomas and these loci demonstrated enrichment of homeobox genes (P=3.0 × 10(-12)). None of the 168 probes were associated with CIMP genes. Among CpG loci with the largest difference in methylation between right- and left-colon adenomas, probes associated with PRAC (prostate cancer susceptibility candidate) gene showed hypermethylation in right-colon adenomas whereas those associated with CDX2 (caudal type homeobox transcription factor 2) showed hypermethylation in left-colon adenomas. A subgroup of left-colon adenomas enriched for current smokers (OR=6.1, P=0.004) exhibited a methylation profile similar to right-colon adenomas. In summary, our results indicate distinct patterns of DNA methylation, independent of CIMP genes, in adenomas of the right and left colon.
Borras, Ester; San Lucas, F. Anthony; Chang, Kyle; Zhou, Ruoji; Masand, Gita; Fowler, Jerry; Mork, Maureen E.; You, Y. Nancy; Taggart, Melissa W.; McAllister, Florencia; Jones, David A.; Davies, Gareth E.; Edelmann, Winfried; Ehli, Erik A.; Lynch, Patrick M.; Hawk, Ernest T.; Capella, Gabriel; Scheet, Paul; Vilar, Eduardo
Purpose The molecular basis of the adenoma to carcinoma transition has been deduced using comparative analysis of genetic alterations observed through the sequential steps of intestinal carcinogenesis. However, comprehensive genomic analyses of adenomas and at-risk mucosa are still lacking. Therefore, our aim was to characterize the genomic landscape of colonic at-risk mucosa and adenomas. Experimental Design We analyzed the mutation profile and copy number changes of 25 adenomas and adjacent mucosa from 12 familial adenomatous polyposis patients using whole-exome sequencing and validated allelic imbalances in 37 adenomas using SNP arrays. We assessed for evidence of clonality and performed estimations on the proportions of driver and passenger mutations using a systems biology approach. Results Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer-driver genes (APC, KRAS, FBXW7, TCF7L2) and allelic imbalances in chromosomes 5, 7 and 13. Moreover, 80% of adenomas had somatic alterations in WNT pathway genes. Adenomas displayed evidence of multiclonality similar to stage I carcinomas. Strong correlations between mutational rate and patient age were observed in at-risk mucosa and adenomas. Our data indicate that at least 23% of somatic mutations are present in at-risk mucosa prior to adenoma initiation. Conclusions The genomic profiles of at-risk mucosa and adenomas illustrate the evolution from normal tissue to carcinoma via greater resolution of molecular changes at the inflection point of premalignant lesions. Furthermore, substantial genomic variation exists in at-risk mucosa before adenoma formation, and deregulation of the WNT pathway is required to foster carcinogenesis. PMID:27221540
Slonim, S M; Haykal, H A; Cushing, G W; Freidberg, S R; Lee, A K
MR images of an ectopic pituitary adenoma have been published in only a single case, a suprasellar mass. We present a patient with Cushing's disease in whom MRI revealed a pituitary adenoma within the sphenoid sinus. Radiologic characteristics of ectopic pituitary adenomas are reviewed, with emphasis on MRI, which demonstrates a soft tissue mass, isointense with gray matter on T1-weighted images, which enhances in a heterogeneous manner.
Muto, T; Kamiya, J; Sawada, T; Konishi, F; Sugihara, K; Kubota, Y; Adachi, M; Agawa, S; Saito, Y; Morioka, Y
Thirty-three small "flat adenomas," not more than 1 cm in diameter, were collected from surgically and colonoscopically removed specimens, and their colonoscopic and histologic characteristics were described. There were 14 adenomas with mild atypia, five with moderate atypia, 14 with severe atypia (or focal carcinoma limited to the mucosa). The grade of atypia seems to increase with the size of lesions, and these lesions were assumed to play an important role in the adenoma-carcinoma sequence. The importance of recognizing the presence of these small "flat adenomas" in everyday practice is stressed.
Jia, Ruichao; Li, Mu; Chang, Binge; Chen, Laichao; Ma, Jingjian
The purpose of this study was to explore the role of neuropeptide Y (NPY) on molecular and histological changes in human pituitary adenomas. The localization of NPY and its expression at the protein, messenger RNA (mRNA), and receptor levels were investigated here in different subcategories of pituitary adenomas. Immunohistochemical staining was performed in all cases to assess expression of NPY. Reverse transcription-polymerase chain reaction (RT-PCR) was used to study the mRNA expression of NPY. NPY subcellular localization was observed using immunoelectron microscopy in cytoplasm, rough endoplasmic reticulum, and cell matrix in four of the six cases of pituitary adenoma. NPY protein expression was observed in 59.6% of 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. mRNA expression of NPY was observed in all 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. Significantly different levels of expression were observed across different subcategories of pituitary adenoma. mRNA expression of Y1R and Y2R was observed across all subcategories of pituitary adenomas, and a positive correlation was observed between NPY and Y2R. In conclusion, evidence is provided here for the expression of NPY and its receptors, Y1R and Y2R, in human pituitary adenoma, and the levels of expression were found to differ across different subcategories. Differences in expression of Y2R in human pituitary adenomas were found to have remarkable statistical significance.
Jacoby, R F; Marshall, D J; Kailas, S; Schlack, S; Harms, B; Love, R
Genetic instability related to defective DNA mismatch repair genes may be involved in the pathogenesis of carcinoma in hereditary nonpolyposis colon cancer (HNPCC). However, nonneoplastic tissues from patients inheriting defects in human MSH2 or human MLH1 do not show significant genetic instability. The aim of this study was to determine whether acquisition of genetic instability at the adenoma stage promotes malignant transformation by studying adenoma-carcinoma progression in HNPCC. Dinucleotide repeat loci were analyzed by polymerase chain reaction from microdissected adenoma and/or carcinoma stages from formalin-fixed paraffin-embedded HNPCC tumors. Although genetic instability was observed at some loci in almost all cases, the proportion of microsatellite loci altered was significantly less (P < 0.01) in completely benign adenomas (24%) than in benign areas of adenomas with malignancy (54%). Molecular fingerprints indicated intratumor heterogeneity, with evolution of related subclones of neoplastic cells. However, in all cases of tumor progression, at least one subclone from the adenoma stage was closely related to the carcinoma. Some genetic instability develops at the benign adenoma stage in most HNPCC tumors. Adenomas with a greater rate of genetic instability are more likely to progress to carcinoma. Topographic genotyping data provides evidence supporting the hypothesis of adenoma-carcinoma progression in HNPCC.
Daly, Adrian F; Beckers, Albert
The most frequent conditions that are associated with inherited/familial pituitary adenomas are familial isolated pituitary adenoma (FIPA) and multiple endocrine neoplasia type 1 (MEN1), which together account for up to 5% of pituitary adenomas. One important genetic cause of FIPA are inactivating mutations or deletions in the aryl hydrocarbon receptor interacting protein (AIP) gene. FIPA is the most frequent clinical presentation of AIP mutations. This article traces the current state of knowledge regarding the clinical features of FIPA and the particular genetic, pathologic, and clinical characteristics of pituitary adenomas due to AIP mutations.
Histopathological localization of lymphatic vessels has been hindered because of a lack of suitable immunocytochemical markers for lymphatic vessels. Using lymphatic vessels endothelial hyaluronan receptor-1 (LYVE-1) immunocytochemical staining, hyperplastic polyps, tubular adenomas to villous adenomas, were investigated for lymphatic vessels compared with immunostained blood vessels using factor-8. Four cases each of hyperplastic polyps, tubular adenomas to villous adenomas, were routinely fixed in formalin and embedded in paraffin and were immunostained using goat anti-LYVE-1 for lymphatic vessels and rabbit anti-factor-8 for blood vessels. In normal colon and hyperplastic polyps, slender lymphatic vessels were noted in muscularis mucosa, which spread into the base of colonic crypt, whereas round venous vessels, they extend into lamina propria. In tubular adenomas, small lymphatic and venous vessels were noted in broad fibrous stalks. In villous adenomas, smaller lymphatic and venous vessels were noted in fine intervillous stroma. In normal colon and hyperplastic polyps, slender, irregularly shaped lymphatic vessels were present in muscularis mucosa, spreading into the base of the colonic crypt. In tubular adenomas, small lymphatic and venous vessels were noted in fibrous stalks. In villous adenomas, smaller lymphatic and venous vessels were noted in intervillous stroma. There are no increased lymphatic and venous vessels in intermucosal stroma and stalks of adenomas compared with normal colon.
Skálová, A; Andrle, P; Hostička, L; Michal, M
Pleomorphic adenoma is the most common salivary gland tumor, characterized by a complex biphasic proliferation of epithelial and myoepithelial cells intermingled with a mezenchymal component with frequent metaplastic changes and protean histomorphology of the cells. This review describes several unusual histological findings in pleomorphic adenoma that may mimic malignancy, and therefore they represent a diagnostic pitfall. Intravascular invasion of tumor cells is generally suspicious of malignancy; however, intravascular tumor deposits may be rarely found within the capsule of clinically benign salivary pleomorphic adenomas. It is important not to render a malignant diagnosis in such neoplasms, in the absence of other evidence of malignancy. Pleomorphic adenomas, particularly of minor glands of palate, may contain large areas of squamous and mucinous metaplasia suspicious of mucoepidermoid carcinoma (MEC). In contrast to MEC, metaplastic pleomorphic adenomas do not harbour the distinctive translocations t(11;19) and t(11;15), they are not invasive, in contrast they reveal at least focally myxochondroid stroma. Cribriform structures in pleomorphic adenoma may mimic adenoid cystic carcinoma. Oncocytic metaplasia in cellular rich pleomorphic adenoma/myoepithelioma may be associated with significant nuclear polymorphism and hyperchromasia suspicious of malignancy. The most common pitfall in diagnosis of pleomorphic adenoma is so called "atypical PA" that must be distinguished from early malignant transformation to in situ-carcinoma ex pleomorphic adenoma.
Wang, Mingguang; Zhang, Huan; Heng, Xueyuan; Pang, Qi; Sun, Aigang
Background The aim of this study was to detect the expression of cold-inducible RNA-binding protein in pituitary adenoma and to determine its effects on tumor recurrence. Material/Methods We collected a total of 60 post-op samples collected from pituitary adenoma patients (including 20 cases of invasive pituitary adenoma, 20 cases of non-invasive adenoma, and 20 cases of non-invasive recurrent adenoma) admitted in our hospital. Both protein and mRNA levels of CIRP in 3 types of pituitary adenoma samples were quantified by Western blotting and real-time PCR, respectively. Results Western blotting revealed significantly elevated CIRP expression levels in invasive pituitary adenoma compared to non-invasive tumors, with statistical significance (p<0.05). Recurrent pituitary adenoma expressed significantly higher CIRP levels compared to non-recurrent tumors (p<0.05). Real-time PCR for CIRP mRNA obtained consistent results: transcript levels were significantly higher in invasive pituitary adenoma compared to non-invasive adenoma (p<0.05); recurrent adenoma also had significantly higher CIRP mRNA levels compared to non-recurrent tumors (p<0.05). Among all 3 types of pituitary adenoma, recurrent tumors had the highest levels of CIRP mRNA and protein. Conclusions The expression of CIRP in pituitary adenoma is closely related with tumor proliferation and invasion, and its significantly elevated expression level indicates post-op recurrence. PMID:25934796
Racho, Ronald G; Krishna, Murli; Coe, Susan G; Thomas, Colleen S; Crook, Julia E; Diehl, Nancy N; Wallace, Michael B
Sessile serrated adenomas/polyps (SSA/P) are an under-recognized disease with a unique malignant pathway. Improved endoscopic recognition and pathological interpretation is needed. To determine whether an educational intervention that improved adenoma detection rate (ADR) could improve SSA/P detection rate after reclassification of previously termed "hyperplastic" polyps. We reanalyzed data from a prospective randomized trial of an educational intervention aimed at increasing ADR. All hyperplastic polyps ≥6 mm reported in a previously published study were rereviewed and reclassified using standardized criteria for serrated lesions. Detection rates of sessile serrated adenomas/polyps and other clinically relevant serrated polyps were calculated in the baseline and post-training phases of the original study. Of 263 available for rereview, 33 (12.5%) were reclassified as SSA/P (N = 32) or traditional serrated adenoma (TSA) (N = 1). Reclassification was more common in the right colon (18 vs. 8%, p = 0.02). Baseline SSA/P detection rate was 0.7% in the untrained group and 1.3% in the trained group. Post-training, the SSA/P detection rate increased to 2.1 and 1.5%, respectively. The clinically relevant serrated polyp detection rate at baseline was 14.2% in the untrained group and 11.3% in the trained group. After the educational intervention, the clinically relevant serrated polyp detection rates increased to 16.5 and 14.8% in the untrained and trained groups, respectively. The estimated odds of an endoscopist detecting either a SSA/P or other clinically relevant serrated polyp during colonoscopy increased by only 3% with the educational intervention (OR 1.03, 95% CI 0.61-1.74, p = 0.91). Pathological re-interpretation of larger serrated polyps resulted in the reclassification of 12.5% of lesions. Quality improvement methods focused on adenoma detection did not impact SSA/P detection, and thus specific methods for serrated polyp detection are needed.
Rubio, Carlos A
A recent review of archived sections from early experiments in rats showed neoplasias exhibiting serrated configurations. The aim was to assess the frequency of serrated neoplasias in the colon and small intestine of carcinogen-treated rats. While reviewing archival sections from early experiments in Sprague-Dawley (SD) and Fisher-344 (F-344) rats, we recently detected colonic and intestinal traditional serrated adenomas (displaying serrated or microtubular patterns) and serrated carcinomas. SD rats were injected 1,2-dimethylhydrazine (DMH) for 27 weeks whereas F-344 rats were fed with a pyrolysate (GLU-1) for 24 months. Filed sections from 358 colonic and small intestinal neoplasias were re-evaluated. DMH-treated SD rats had 215 colonic neoplasias (1.4% were serrated adenomas, 7.9% microtubular adenomas, 2.8% serrated carcinomas and 2.8% microtubular carcinomas). GLU1-treated F-344 rats had 53 colonic neoplasias (1.9% were serrated adenomas and 20.8% microtubular adenomas), and 89 small intestinal neoplasias (1.1% were serrated adenomas, 42.7% microtubular adenomas and 6.7%, microtubular carcinomas). DMH/SD-rats develop serrated and microtubular adenomas and carcinomas in the colon, whereas GLU1/F-344 rats develop microtubular adenomas in the colon and microtubular adenomas and carcinomas in the small intestine. The two rat-settings emerge as suitable models to study the molecular attributes of serrated and microtubular neoplasias under the standard conditions of the laboratory. This study is the first showing that a substantial number of serrated and particularly microtubular adenomas and carcinomas develop in the colon and small intestine of experimental rats. Importantly, serrated and microtubular neoplasias in rats recreate the histology of duodenal and colonic traditional serrated neoplasias in human beings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Koestler, Devin C; Li, Jing; Baron, John A; Tsongalis, Gregory J; Butterly, Lynn F; Goodrich, Martha; Lesseur, Corina; Karagas, Margaret R; Marsit, Carmen J; Moore, Jason H; Andrew, Angeline S; Srivastava, Amitabh
Recent studies have shown two distinct non-CIMP methylation clusters in colorectal cancer, raising the possibility that DNA methylation, involving non-CIMP genes, may play a role in the conventional adenoma–carcinoma pathway. A total of 135 adenomas (65 left colon and 70 right colon) were profiled for epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip. A principal components analysis was performed to examine the association between variability in DNA methylation and adenoma location. Linear regression and linear mixed effects models were used to identify locus-specific differential DNA methylation in adenomas of right and left colon. A significant association was present between the first principal component and adenoma location (P = 0.007), even after adjustment for subject age and gender (P = 0.009). A total of 168 CpG sites were differentially methylated between right- and left-colon adenomas and these loci demonstrated enrichment of homeobox genes (P = 3.0 × 10−12). None of the 168 probes were associated with CIMP genes. Among CpG loci with the largest difference in methylation between right- and left-colon adenomas, probes associated with PRAC(prostate cancer susceptibility candidate) gene showed hypermethylation in right-colon adenomas whereas those associated with CDX2(caudal type homeobox transcription factor 2) showed hypermethylation in left-colon adenomas. A subgroup of left-colon adenomas enriched for current smokers (OR = 6.1, P = 0.004) exhibited a methylation profile similar to right-colon adenomas. In summary, our results indicate distinct patterns of DNA methylation, independent of CIMP genes, in adenomas of the right and left colon. PMID:23868178
Zibar Tomšić, Karin; Dušek, Tina; Kraljević, Ivana; Heinrich, Zdravko; Solak, Mirsala; Vučinović, Ana; Ozretić, David; Mihailović Marasanov, Sergej; Hršak, Hrvoje; Kaštelan, Darko
The aim of the study was to investigate the incidence of and risk factors for hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenoma. We conducted a retrospective analysis of the pituitary function of 90 patients who underwent GKRS for pituitary adenoma at the University Hospital Centre Zagreb between 2003 and 2014. Twenty seven of them met the inclusion criteria and the others were excluded from the study due to pituitary insufficiency which was present before GKRS. Eighteen patients had non-functioning and 9 patients had secretory adenomas. Median patients' age was 56 years (24-82). GKRS was performed using the Leksell gamma knife Model C. The median prescription radiation dose was 20 Gy (15-25) and the median tumor volume size was 3.4 cm(3) (0.06-16.81). New onset hypopituitarism was defined as a new deficit of one of the three hormonal axes (corticotroph, thyreotroph, or gonadotroph) ≥3 months following GKRS. SPSS was used for statistical analysis, with the significance level at P<0.05. During the median follow-up period of 72 months (range 6-144), 30% of patients developed new hypopituitarism after GKRS. This corresponds to incidence of one new case of hypopituitarism per 15 patient-years. Age, gender, tumor function, tumor volume, suprasellar extension, prescription dose of radiation, as well as dose-volume to the pituitary gland, stalk and hypothalamus were not predictive factors for the development of hypopituitarism. In our cohort of patients with pituitary tumors who underwent GKRS, 30% developed new hypopituitarism during the follow-up period.
Yao, Ruisheng; Wang, Yian; Lubet, Ronald A; You, Ming
Abstract Because of similarities in histopathology and tumor progression stages between mouse and human lung adenocarcinomas, the mouse lung tumor model with lung adenomas as the endpoint has been used extensively to evaluate the efficacy of putative lung cancer chemopreventive agents. In this study, a competitive cDNA library screening (CCLS) was employed to determine changes in the expression of mRNA in chemically induced lung adenomas compared with paired normal lung tissues. A total of 2555 clones having altered expression in tumors were observed following competitive hybridization between normal lung and lung adenomas after primary screening of over 160,000 clones from a mouse lung cDNA library. Among the 755 clones confirmed by dot blot hybridization, 240 clones were underexpressed, whereas 515 clones were overexpressed in tumors. Sixty-five clones with the most frequently altered expression in six individual tumors were confirmed by semiquantitative RT-PCR. When examining the 58 known genes, 39 clones had increased expression and 19 had decreased expression, whereas the 7 novel genes showed overexpression. A high percentage (>60%) of overexpressed or underexpressed genes was observed in at least two or three of the lesions. Reproducibly overexpressed genes included ERK-1, JAK-1, surfactant proteins A, B, and C, NFAT1, α-1 protease inhibitor, helix-loop-helix ubiquitous kinase (CHUK), α-adaptin, α-1 PI2, thioether S-methyltransferase, and CYP2C40. Reproducibly underexpressed genes included paroxanase, ALDH II, CC10, von Ebner salivary gland protein, and α- and β-globin. In addition, CCLS identified several novel genes or genes not previously associated with lung carcinogenesis, including a hypothetical protein (FLJ11240) and a guanine nucleotide exchange factor homologue. This study shows the efficacy of this methodology for identifying genes with altered expression. These genes may prove to be helpful in our understanding of the genetic basis of lung
Rocco, Alba; Borriello, Pasquale; Compare, Debora; Colibus, Patrizia De; Pica, Loredana; Iacono, Alessandro; Nardone, Gerardo
Brunner’s gland adenoma (BGA）is a very rare benign tumour of the duodenum, which is usually asymptomatic and discovered incidentally at endoscopy. Occasionally, this lesion may be large, causing upper gastrointestinal haemorrhage or intestinal obstruction. The case had a large Brunner’s gland adenoma, presenting melena that was managed by endoscopic excision. PMID:16610009
Villa, Chiara; Lagonigro, Maria Stefania; Magri, Flavia; Koziak, Maria; Jaffrain-Rea, Marie-Lise; Brauner, Raja; Bouligand, Jerome; Junier, Marie Pierre; Di Rocco, Federico; Sainte-Rose, Christian; Beckers, Albert; Roux, François Xavier; Daly, Adrian F; Chiovato, Luca
Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas require emergency neurosurgery; one patient had incipient pituitary apoplexy. Post-surgically, the patients were found to have silent somatotrope adenomas on pathological examination. Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumors of virtually identical characteristics. The adenomas were accompanied by multiple areas of pituitary hyperplasia, which stained positively for GH, indicating somatotrope hyperplasia. Genetic analyses of the FIPA kindred revealed a novel E216X mutation of the AIP gene, which was present in both the affected patients and the unaffected father. Molecular analysis of surgical specimens revealed loss of heterozygosity (LOH) in the adenoma but showed that LOH was not present in the hyperplastic pituitary tissue from either patient. AIP immunostaining confirmed normal staining in the hyperplastic tissue and decreased staining in the adenoma in the tumors from both patients. These results demonstrate that patients with AIP germline mutation can present with silent somatotrope pituitary adenomas. The finding of somatotrope hyperplasia unaccompanied by AIP LOH suggests that LOH at the AIP locus might be a late event in a potential progression from hyperplastic to adenomatous tissue.
Chaudhry, Nauman S; Raber, Michael R; Cote, David J; Laws, Edward R
Rathke's cleft cysts (RCC) are benign cystic lesions that originate from remnants of the epithelial lining of Rathke's pouch. RCC are known rarely to occur together with a concomitant pituitary adenoma. Here, we report a patient with a pituitary adenoma arising in the same location as a previously-resected RCC, 3 years post-operatively, and review the literature of "collision" sellar lesions. Consecutive transsphenoidal operations from a single-center between 2008 and 2016 were reviewed to identify patients with pituitary adenoma arising after surgical resection of RCC, and a systematic search of the literature was also performed to identify such patient reports, as well as reports of concomitant pituitary adenoma and RCC. Of 837 transsphenoidal operations from our own experience, one patient with pituitary adenoma occurring after RCC resection was identified and is reported here. A systematic review of the literature resulted in identification of 34 patients with concomitant RCC and pituitary adenoma and no incidents of pituitary adenoma occurring after resection of RCC. Concomitant occurrence of RCC and pituitary adenoma was more commonly diagnosed in women (61%), at a median age of diagnosis of 44 years. The RCC histological analysis in these patients consistently described ciliated columnar or cuboidal epithelium. Although rare, the presence of a new, pathologically-distinct lesions in the sella after prior surgical treatment, is possible. During post-operative monitoring, physicians should consider that what appears as a "recurrent" lesion may actually be growth of a new and entirely different lesion.
Chablani, Sumedha V; Jandorf, Lina; DuHamel, Katherine; Lee, Kristen K; Sriphanlop, Pathu; Villagra, Cristina; Itzkowitz, Steven H
Colorectal cancer (CRC) is the second leading malignancy diagnosed among US Latinos. Latinos in the USA represent a heterogeneous amalgam of subgroups varying in genetic background, culture, and socioeconomic status. Little is known about the frequency of CRC precursor lesions found at screening colonoscopy among Latino subgroups. The aim was to determine the prevalence and distribution of histologically confirmed adenomas found at screening colonoscopy among average-risk, asymptomatic US Latinos according to their subgroup and socio-demographic background. Cross-sectional analysis of pathological findings resulting from screening colonoscopy among average-risk, asymptomatic US Latinos aged ≥50 in two prospective randomized controlled trials at an academic medical center. Among the 561 Latinos who completed screening colonoscopy, the two largest subgroups were Puerto Ricans and Dominicans. The findings among both subgroups were: adenomas 30.6%, proximal adenomas 23.5%, advanced adenomas 12.0%, and proximal advanced adenomas 8.9%. These rates are at least as high as those found at screening colonoscopy among US whites. While Puerto Ricans were more likely than Dominicans to be born in the USA, speak English, be acculturated, have a smoking history, and be obese, there were no significant differences in adenoma rates between these subgroups. The prevalence of adenomas, advanced adenomas, and proximal neoplasia was high among both subgroups. These findings have implications for CRC screening and surveillance among the increasingly growing Latino population in the USA.
Kim, Jeehyun; Oh, Seung-Won; Kim, Young-Sun; Kwon, Hyuktae; Joh, Hee-Kyung; Lee, Ji-Eun; Park, Danbee; Park, Jae-Hong; Ko, Ah-Ryoung; Kim, Ye-Ji
Abstract The incidence of colorectal cancer is rapidly increasing in South Korea. It is important to clarify the association between colorectal cancer and diet, being one of the main modifiable risk factors, as such studies in the Korean population are lacking. A cross-sectional study was performed using data from participants who had undergone a screening colonoscopy and a nutritional assessment during a routine health check-up from January 2008 to December 2011. Dietary intake data were derived from 1-day food records; colorectal adenoma was histopathologically confirmed by biopsy during colonoscopy. Eventually, 2604 participants were included in the analysis. The risk of colorectal adenoma by quintile of dietary fat intake was analyzed using logistic regression. Subgroup analyses by degree of risk and by location of colorectal adenoma were additionally performed. In men, total fat intake was not associated with risk of colorectal adenoma. However, risk of colorectal adenoma increased with higher saturated fatty acid (SFA) intake. The adjusted odds ratio in the highest quintile was 1.71 (95% confidence interval, 1.01–2.91) compared with that in the lowest quintile. There was no significant association between fat intake and risk of colorectal adenoma characterized by subsite. In female participants, total fat and specific fatty acid intake were not associated with risk of colorectal adenoma. These data support that high SFA intake is associated with risk of colorectal adenoma in Korean men. PMID:28072719
Gupta, Mayank; Kandasamy, Subramaniam
Inflammatory lesions, particularly granulomas, involving adenoma of the parathyroid gland are rare. Ectopic thymic tissue is commonly associated with the thyroid and/or parathyroid gland due to their close embryonic relationship. We report a rare case of coexisting adenoma and granuloma of the parathyroid gland with adjacent ectopic thymic tissue. PMID:24957592
Teramoto, Akira; Sanno, Naoko; Tahara, Shigeyuki; Osamura, Yoshiyuki R
Thyrotropin (TSH)-secreting adenomas are rare and, as most adenomas are large, invasive and difficult to cure by surgery only, many require additional medical treatment. Many TSH-secreting adenomas cosecrete growth hormone (GH) and/or prolactin (PRL). We evaluated the relationship between pathology and the effect of dopamine agonist bromocriptine and somatostatin analogue octreotide in 20 operated patients with TSH-secreting adenomas. The four men and 16 women ranged in age from 23 to 62 years; three had clinically overt acromegaly; two manifested galactorrhea-amenorrhea. Endocrinologically, elevated serum GH, and/or IGF-1 were observed in six patients and elevated serum PRL was observed in eight. Immunohistochemically, 16 of the 20 adenomas were positive for GH and/or PRL (GH-positive, n=13; PRL-positive, n=9). Pituitary-specific transcription factor Pit-1 was demonstrated in the nuclei of all adenoma cells. Octreotide tests showed suppression of serum TSH (<50%) in ten of 14 patients. Preoperative octreotide treatment effectively reduced serum TSH and tumor size in two patients. Electron micrographs of octreotide-treated TSH-secreting adenomas showed shrinkage of the cytoplasm and diffuse distribution of secretory granules. Our study suggests that cosecretion of GH and/or PRL from TSH-secreting adenoma has no correlation with response of tumor cells to medical treatment.
PU, JIUJUN; WANG, ZHIMING; ZHOU, HUI; ZHONG, AILING; JIN, KAI; RUAN, LUNLIANG; YANG, GANG
Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas. PMID:27347184
Zhao, Yachao; Xiao, Zheng; Chen, Wenna; Yang, Jinsheng; Li, Tao; Fan, Bo
O6-methylguanine-DNA methyltransferase (MGMT) activity is responsible for temozolomide (TMZ) resistance in patients harboring aggressive pituitary adenomas. Recently, disulfiram (DSF) has been shown to induce the loss of MGMT protein and increase TMZ efficacy in glioblastoma cells, while CD133+ nestin+ cells isolated from the cell population have been implicated as pituitary adenoma stem-like cells. However, whether DSF is able to potentiate the cytotoxic effects of TMZ on human pituitary adenoma cells has not been investigated to date. In the present study, CD133+ nestin+ phenotype cells were isolated from primary cultured human pituitary adenoma cells using microbeads. It was found that DSF reduced MGMT protein expression and sensitized human pituitary adenoma cells and stem-like cells to TMZ in vitro, while the proteasome inhibitor PS-341 abrogated the inhibitory effect of DSF on MGMT in vitro. The sensitizing effect of DSF was also verified in primary cultured human pituitary adenoma cells in vivo. The results of the present study suggested that DSF can increase the efficacy of the anti-tumor effect of TMZ on human pituitary adenoma cells and CD133+ nestin+ stem like cells via the ubiquitin-proteasomal MGMT protein elimination route. DSF combined with TMZ may be an effective therapeutic strategy against aggressive pituitary adenomas.
Fiori, Enrico; Lamazza, Antonietta; De Masi, Ercole; Schillaci, Alberto; Crocetti, Daniele; Antoniozzi, Angelo; Sterpetti, Antonio V; De Toma, Giorgio
Metabolic syndrome has been identified as a risk factor for colorectal cancer and adenoma. The aim of our study was to assess the risk of colorectal cancer and adenoma in an adult Italian population with metabolic syndrome. Ninety patients with metabolic syndrome were prospectively compared against a matched population without the syndrome to assess the prevalence of colorectal adenoma. Another 1,500 patients undergoing screening colonoscopy were prospectively analyzed: 134 patients with metabolic syndrome and colorectal adenoma were compared against a group of 108 patients with colorectal adenoma without metabolic syndrome to assess the prevalence of cancer. The study was performed from January 2008 until December 2010. Data were analyzed from March to June 2011. The prevalence of colorectal adenoma was twice as high in patients with metabolic syndrome. The incidence of cancer was higher in patients with colorectal adenoma and metabolic syndrome. Associated obesity and liver steatosis were the only factors with independent statistical value. Metabolic syndrome is a risk factor for adenoma and cancer degeneration when obesity is present. Associated liver steatosis is a significant risk factor for colorectal cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Gupta, Mayank; Kandasamy, Subramaniam
Inflammatory lesions, particularly granulomas, involving adenoma of the parathyroid gland are rare. Ectopic thymic tissue is commonly associated with the thyroid and/or parathyroid gland due to their close embryonic relationship. We report a rare case of coexisting adenoma and granuloma of the parathyroid gland with adjacent ectopic thymic tissue. 2014 BMJ Publishing Group Ltd.
Teng, Cindy Y; Diego, Emilia J
Lactating adenomas are rare benign breast tumors, most commonly found during pregnancy and lactation. They are usually slow growing and smaller than 3cm in maximal diameter. Rare cases of giant lactating adenomas and rapid postpartum enlargement have been reported, but none have shown a giant lactating adenoma with rapid antepartum enlargement or antepartum surgical management. A 27 year-old pregnant woman presented at 28 weeks gestation with a 5cm left breast mass that doubled to 10cm within six weeks and was increasingly tender. Histopathologic examination of a core biopsy was consistent with a lactating adenoma. The mass was excised at 31 weeks gestation with no complications. Lactating adenomas are common during pregnancy and need to be distinguished from breast cancer, a commonly diagnosed malignancy in pregnancy. They can be distinguished from carcinoma and other benign tumors like fibroadenoma under histopathologic examination. Rare cases of giant lactating adenomas with rapid postpartum enlargement that were managed by postpartum excision have been reported. However, a giant lactating adenoma with rapid antepartum enlargement, managed by excision in the third trimester of pregnancy, has not been reported. Excision of a large, rapidly enlarging lactating adenoma in the third trimester of pregnancy is a safe and feasible management option. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Lee, Seungkoo; Bang, Seunghyun; Song, Kyuyoung; Lee, Inchul
The majority of colon cancers develop from pre-existing adenomas. We analyzed the expression profiles in the sequence of normal colon crypts, adenomas and early-stage carcinomas using microdissected cells from tubular adenomas with foci of malignant transformation. Differentially expressed genes were detected between normal-adenoma and adenoma-carcinoma, and were grouped according to the patterns of expression changes in the sequence. Down-regulated genes in the sequence included PLA2G2A, TSPAN1, PDCD4, FCGBP, AATK, EPLIN, FABP1, AGR2, MTUS1, TSC1, galectin 4 and MT1F. PLA2G2A has been shown to suppress colon tumorigenesis in mice, but the pathobiological role in humans has been controversial. Our data showed continuous down-regulation of PLA2G2A in the sequence supporting an implication in human colon cancer. Tumor suppressor and/ or proapoptotic activities have also been reported in other genes. Up-regulated genes included ribosomal proteins, IER3 and TPR. TGF-beta2 and matrix metalloproteinase 23B were up-regulated in carcinoma but not in adenoma, supporting the pathobiological roles in malignant transformation. Differentially expressed genes partly coincided with those in the adenoma-carcinoma sequence of the stomach, which was published previously, suggesting a partial overlap between the adenoma-carcinoma sequences of the colon and stomach.
Luan, Chunguang; Xie, Lingling; Yang, Xi; Miao, Huifang; Lv, Na; Zhang, Ruifen; Xiao, Xue; Hu, Yongfei; Liu, Yulan; Wu, Na; Zhu, Yuanmin; Zhu, Baoli
The fungal microbiota is an important component of the human gut microbiome and may be linked to gastrointestinal disease. In this study, the fungal microbiota of biopsy samples from adenomas and adjacent tissues was characterized by deep sequencing. Ascomycota, Glomeromycota and Basidiomycota were identified as the dominant phyla in both adenomas and adjacent tissues from all subjects. Among the 60 genera identified, the opportunist pathogens Phoma and Candida represented an average of 45% of the fungal microbiota. When analyzed at the operational taxonomic unit (OTU) level, however, a decreased diversity in adenomas was observed, and three OTUs differed significantly from the adjacent tissues. Principal Component Analysis (PCA) revealed that the core OTUs formed separate clusters for advanced and non-advanced adenomas for which the abundance of four OTUs differed significantly. Moreover, the size of adenomas and the disease stage were closely related to changes in the fungal microbiota in subjects with adenomas. This study characterized the fungal microbiota profile of subjects with adenomas and identified potential diagnostic biomarkers closely related to different stages of adenomas. PMID:25613490
Adachi, Yoshin; Nakamura, Hiroshige; Taniguchi, Yuji; Miwa, Ken; Fujioka, Shinji; Haruki, Tomohiro
We report a case of thoracoscopic resection of mediastinal parathyroid adenomas using methylene blue to localize the tumors during the operation. After methylene blue 4 mg/kg was injected intravenously, we easily identified methylene blue-stained parathyroid glands and successfully resected them with sufficient surgical margins. The use of methylene blue for detection of parathyroid adenoma is a useful technique.
Pu, Jiujun; Wang, Zhiming; Zhou, Hui; Zhong, Ailing; Jin, Kai; Ruan, Lunliang; Yang, Gang
Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas.
Gakidis, Ioannis; Mihos, Petros T; Chatziantoniou, Christos; Stamatelopoulos, Athanasios; Eftychiadis, Christos; Mantas, Constantinos
Primary pleomorphic adenomas of the lung are very rare tumors that have peculiar clinical and oncologic features. We report here on the diagnostic and therapeutic approach for a patient with a large neglected pulmonary pleomorphic adenoma that presented initially as pneumonia.
Mitnick, J.S.; Bosniak, M.A.; Megibow, A.J.; Naidich, D.P.
Eighteen patients with unilateral non-metastatic non-functioning adrenal masses were studied with computed tomography (CT). Pathological examination in cases revealed benign adrenal adenomas. The others were followed up with serial CT scans and found to show no change in tumor size over a period of six months to three years. On the basis of these findings, the authors suggest certain criteria of a benign adrenal mass, including (a) diameter less than 5 cm, (b) smooth contour, (c) well-defined margin, and (d) no change in size on follow-up. Serial CT scanning can be used as an alternative to surgery in the management of many of these patients.
Bacaj, Patrick; Borah, Gregory
Summary: A 38-year-old woman is described who presented with a slowly growing mass on the posterior aspect of the left ear. Excision and histopathologic evaluation revealed a pleomorphic adenoma (PA) originating from heterotopic salivary gland tissue. Many authors have presented cases of PAs originating from ceruminous glands in the external auditory canal or of so-called chondroid syringoma originating from apocrine and eccrine sweat glands. This is the only case in the recent literature of a PA originating from a heterotopic rest of salivary gland tissue in the retroauricular region. The 3 main sources of PAs, their embryologic derivation, and treatment are described. PMID:27757344
Grome, Luke; Bacaj, Patrick; Borah, Gregory
A 38-year-old woman is described who presented with a slowly growing mass on the posterior aspect of the left ear. Excision and histopathologic evaluation revealed a pleomorphic adenoma (PA) originating from heterotopic salivary gland tissue. Many authors have presented cases of PAs originating from ceruminous glands in the external auditory canal or of so-called chondroid syringoma originating from apocrine and eccrine sweat glands. This is the only case in the recent literature of a PA originating from a heterotopic rest of salivary gland tissue in the retroauricular region. The 3 main sources of PAs, their embryologic derivation, and treatment are described.
Laszewski, M J; Moore, S A
Pituitary adenomata are benign neoplasms which usually grow slowly and present with manifestations relating to an associated endocrinopathy or visual disturbance. Rarely these neoplasms will demonstrate a more aggressive behavior with extracranial extension and symptoms of upper airway obstruction or anosmia. Several reported cases suggest that although these neoplasms behave aggressively the overall survival and prognosis for these patients remains good. We present the clinical and postmortem findings of an occult invasive pituitary adenoma leading to the development of bacterial meningitis, coma and death. This communication stresses the necessity for the early diagnosis and treatment of the invasive adenomata to prevent the development of potentially fatal infectious sequelae.
Sold, Moritz; Kähler, Georg
Summary Background Endoscopic therapy of colorectal adenomas and early cancers is a standard method. Besides oncological criteria, the method is limited by polyp location, size, and texture. Method Based on the current literature, technical modifications and developments in endoscopic mucosal resection are described. Results Numerous approaches exist to improve the conditions of resection, including optimisation of mucosal elevation and modification of techniques, tools, and devices. Conclusion Endoscopic therapy of sessile and flat colorectal polyps remains a challenge. Some of the presented modifications can help to address this challenge. PMID:26286120
Mariano, Fernanda Viviane; Giovanetti, Karina; Saccomani, Luis Fernando Vidal; Del Negro, André; Kowalski, Luiz Paulo; Krepischi, Ana Cristina Victorino; Altemani, Albina
A key step of cancer development is the progressive accumulation of genomic changes resulting in disruption of several biological mechanisms. Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive neoplasm that arises from a pleomorphic adenoma. CXPA derived from a recurrent PA (RPA) has been rarely reported, and the genomic changes associated with these tumors have not yet been studied. We analyzed CXPA from RPAs and RPAs without malignant transformation using array-comparative genomic hybridization (array-CGH) to identify somatic copy number alterations and affected genes. DNA samples extracted from FFPE tumors were submitted to array-CGH investigation, and data was analyzed by Nexus Copy Number Discovery Edition v.7. No somatic copy number alterations were found in RPAs without malignant transformation. As for CXPA from RPA, although genomic profiles were unique for each case, we detected some chromosomal regions that appear to be preferentially affected by copy number alterations. The first case of CXPA-RPA (frankly invasive myoepithelial carcinoma) showed copy number alterations affecting 1p36.33p13, 5p and chromosomes 3 and 8. The second case of CXPA-RPA (frankly invasive epithelial-myoepithelial carcinoma) showed several alterations at chromosomes 3, 8, and 16, with two amplifications at 8p12p11.21 and 12q14.3q21.2. The third case of CXPA-RPA (minimally invasive epithelial-myoepithelial carcinoma) exhibited amplifications at 12q13.3q14.1, 12q14.3, and 12q15. The occurrence of gains at chromosomes 3 and 8 and genomic amplifications at 8p and 12q, mainly those encompassing the HMGA2, MDM2, WIF1, WHSC1L1, LIRG3, CDK4 in CXAP from RPA can be a significant promotional factor in malignant transformation. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.
Miuţescu, B; Sporea, I; Popescu, Alina; Bota, Simona; Iovănescu, Dana; Burlea, Amelia; Mos, Liana; Palaghia, Mădălina; Vasilescu, A; Miuţescu, E
The aim of the study was to evaluate the benefit of the immunochemical fecal blood test (FIT) for detection of advanced adenomas. We have conducted a screening study on a average-risk cohort of subjects, aged 50 -74 years. We used a rapid quantitative FIT to perform the screening. Colonoscopy was recommended in all participants with positive FIT. We assessed the participation rate and analyzed advanced adenomas detected in the screening examinations. Our study enrolled 1111 asymptomatic participants. Immunochemical test results were positive in 72 subjects (6.5%). Colonoscopy was performed by 50/72 (69.4%) subjects. The detection rate for advanced adenomas was 2.2%. A total number of 28 advanced adenomas were detected in 24 subjects, meaning 1.2 advanced adenoma/subject. Analyzing the 3 characteristics of advanced adenomas, we observed in our study that 25/28 adenomas (89.3%) had sizes > or = 10 mm, 11/28 adenomas (39.3%) were tubulovillous/villous and 19/28 adenomas (67.9%) had high dysplasia. The majority of advanced adenomas were found in the left colon as compared to the right colon: 71.4% vs. 28.6%. p = 0.0008. In our study was obtained a 2.2% detection rate for advanced adenomas, most of them (71.4%) being located in the left colon. The dominant feature of advanced adenomas detected was the size > or = 10 mm (89.3% of cases).
Ogando-Rivas, Elizabeth; Alalade, Andrew F; Boatey, Jerome; Schwartz, Theodore H
Double adenomas in the pituitary gland are a rare occurrence. The ability to cure a hormone-producing adenoma with surgery is dependent on the ability to identify and completely remove the correct adenoma. The relative frequency of each subtype of hormone-secreting adenomas confirmed with magnetic resonance image (MRI), surgery and immunohistochemistry is not defined. Following PRISMA guidelines, we performed a systematic review of PubMed Central, Google Scholar, Scopus Database, Cochrane database and Science Research, using the key-words: "double pituitary adenomas", "multiple pituitary adenomas" and only papers where multiple or truly separate double pituitary adenomas were identified pre-surgically by MRI and/or confirmed by pathology/immunohistochemistry staining were included. We reviewed papers from 1975 to 2016 and found 17 cases with two pituitary adenomas and 1 with three pituitary adenomas. The ages ranged from 22 to 67 years old, and there were twelve females and five males. Immunohistochemical staining showed that the most common double pituitary adenomas were growth hormone (GH)- followed by adrenocorticotropic (ACTH)-secreting. Double pituitary adenomas are rare but most commonly found with GH- or ACTH-producing tumors. It is critical to remove all identified possible adenomas to achieve biochemical cure and clinicians should have heightened sensitivity in patients with acromegaly or Cushing's Disease.
Tarakji, Bassel; Altamimi, Mohammed Alsakran; Baroudi, Kusai; Nassain, Mohammad Z; Alenzi, Faris Q
Objective: This study was aimed at characterizing alterations in the immunohistochemical expression of p16 in carcinoma ex-pleomorphic adenomas. Study Design: A selected series of 27 cases of carcinoma ex-pleomorphic adenomas were examined. Results: The results showed that p16 expression in non tumour duct cells was strongly positive nuclear staining in 23 (85%) cases out of 27 cases, that 3 (11.1%) had moderate staining, and that 1 (3.7%) had weak staining. p16 expression in carcinoma ex-pleomorphic adenomas was indicated as a negative nuclear staining in 22 (81.4%) cases out of 27cases, and 5 (18.5%) cases expressed moderate staining. Conclusion: This study suggests that alteration of p16 expression is detected in carcinoma ex-pleomorphic adenomas. p16 has a role in development of carcinoma ex-pleomorphic adenomas. PMID:24551726
Kroppenstedt, S N; Liebig, T; Mueller, W; Gräf, K J; Lanksch, W R; Unterberg, A W
The presence of an abscess in a pituitary tumor is a very rare finding. The authors report the case of a 69-year-old man with a pituitary adenoma confirmed by neuroimaging results, in whom a high fever, meningismus, and left-sided ophthalmoplegia developed 4 days after tooth extraction. The results of serial cranial magnetic resonance imaging were highly indicative of an abscess formation within the pituitary adenoma. During surgery the tumor was approached transsphenoidally and removed. Histological examination confirmed the presence of an abscess formation within the pituitary adenoma. It is most likely that the tooth extraction caused a bacteremia, which led to an inflammation with abscess formation within the pituitary adenoma. The authors conclude that invasive dental procedures should be avoided before planned resection of a pituitary adenoma.
Aiello, Aurora; Cassarino, Maria Francesca; Nanni, Simona; Sesta, Antonella; Ferraú, Francesco; Grassi, Claudio; Losa, Marco; Trimarchi, Francesco; Pontecorvi, Alfredo; Cannavò, Salvatore; Pecori Giraldi, Francesca; Farsetti, Antonella
The aim of this study was to generate immortalized human anterior pituitary adenoma cells. Reliable cell models for the study of human pituitary adenomas are as yet lacking and studies performed so far used repeated passaging of freshly excised adenomas, with the attendant limitations due to limited survival in culture, early senescence, and poor reproducibility. We devised a technique based upon repeated co-transfections of two retroviral vectors, one carrying the catalytic subunit of human telomerase, hTERT, the other SV40 large T antigen. This approach extended the lifespan of cells derived from a human growth hormone-secreting adenoma up to 18 months while retaining morphology of primary cells, growth hormone synthesis and growth hormone secretion. Our attempt represents the first demonstration of successful lifespan extension of human growth hormone-secreting pituitary adenoma cells via co-transfection of hTERT and SV40T and paves the way to future attempts to obtain stable cell lines.
Zheng, Jiangjiang; Zhu, Yin; Li, Changshui; Li, Yinya; Nie, Qianqian; Zhu, Ziling; Deng, Hong
Objective: To investigate the expression of CD10 in tumor-associated fibroblasts (TAF) in colorectal adenomas and its relation to cancerization and recurrence of adenoma. Methods: Tissue samples of low-grade adenoma (n=50), high-grade adenoma (n=50) and colorectal adenocarcinoma (n=50) were collected, and tissue samples at the distal margin of corresponding colorectal lesions were taken as controls. The expression of CD10 in the stromal TAFs, and the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells were detected by immunohistochemistry (Envision). The correlation of CD10 expression in stromal TAFs with the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells was analyzed by Spearmen. One hundred samples of low-grade colorectal adenoma were collected, including 57 non-recurrent cases and 43 recurrent cases (16 cases of recurrent adenoma and 27 cases of recurrent adenocarcinoma); the expression of stromal TAF CD10 were determined and compared among groups. Results: There was no TAF in normal colorectal mucosa. The expression rates of TAF CD10 in low-grade adenoma, high-grade adenoma and colorectal adenocarcinoma were 22%, 50% and 78%, respectively (all P<0.05). The expression of Ki-67 and β-catenin in low-grade adenoma, high-grade adenoma, colorectal adenocarcinoma was on a rising trend (all P<0.01). The expression of CyclinD1 in high-grade adenoma was higher than that in colorectal adenocarcinoma and low-grade adenoma (all P>0.05). The expression of p53 in colorectal adenocarcinoma and high-grade adenoma was higher than that in low grade adenoma (all P<0.01). The expression of TAF CD10 was correlated with the expression of p53, Ki-67 and β-catenin-nucleus(r=0.264、0.307、0.320, all P<0.01),but not correlated with CyclinD1 and β-catenin-membrane (r=0.012、-0.073, all P>0.05). The TAF CD10 level was significantly higher in low-grade adenoma with recurrence than that in those without recurrence (P<0.05).The expression of CD10 in
Vento, S I; Numminen, J; Kinnunen, I; Rautiainen, M; Tarkkanen, J; Hagström, J; Mäkitie, A A
The objective of the study was to investigate the nationwide occurrence of sinonasal pleomorphic adenoma in Finland. A retrospective study was conducted at The Departments of Otorhinolaryngology-Head and Neck Surgery, and Pathology at the five university hospitals in Finland. Data were obtained by searching for sinonasal pleomorphic adenoma cases in the clinical and histopathological registries at these institutions for the past two to four decades. All patients who had had a histologically proven pleomorphic adenoma in the sinonasal area were included as participants. Ten cases with pleomorphic adenoma of the nasal cavity were found. The majority of these tumours originated in the septum, and there were no malignant transformations. Pleomorphic adenomas of the nasal cavity were found to be extremely rare in this nationwide investigation.
Kwak, Ji Yeong; Kim, Kwang Min; Yang, Hae Jin; Yu, Kil Jong; Lee, Jae Gon; Jeong, Yeon Oh; Shim, Sang Goon
The prevalence of colorectal adenoma is increasing in the average-risk population. However, little research is available on colorectal adenoma in young adults under age 40. The aim of this study was to investigate the prevalence and risk factors of colorectal adenoma in 20- to 39-year-old adults. We evaluated 4286 asymptomatic young adults aged 20 to 39 years who underwent first colonoscopy screening as part of an employer-provided health wellness programme at the Health Promotion Centre of Samsung Changwon Hospital, Korea from January 2011 to December 2013. Logistic regression modelling was used to identify risk factors for colorectal adenoma in asymptomatic young adults. The prevalence of colorectal adenoma and advanced adenoma was 11.6% (497/4286) and 0.9% (39/4286), respectively. By age group, the prevalence of colorectal adenoma was 5.4% (33/608) in participants aged 20 to 29 years and 12.6% (464/3678) in participants aged 30 to 39. Colorectal adenoma was found in 13.1% (403/3072) of men and 7.7% (94/1214) of women. Increased risk of colorectal adenoma was associated with age over 30 years (OR, 2.37; 95% CI, 1.64-3.42), current smoker status (OR, 1.48; 95% CI, 1.14-1.91), and alcohol consumption (OR, 1.29; 95% CI, 1.03-1.63). Our findings indicate that even if the prevalence of colorectal adenoma was low in young adults aged 20 to 39, being over 30, cigarette smoking, and alcohol consumption can affect young adults who have no other CRC risks.
Sieber, Oliver M; Lipton, Lara; Crabtree, Michael; Heinimann, Karl; Fidalgo, Paulo; Phillips, Robin K S; Bisgaard, Marie-Luise; Orntoft, Torben F; Aaltonen, Lauri A; Hodgson, Shirley V; Thomas, Huw J W; Tomlinson, Ian P M
Germ-line mutations in the base-excision-repair gene MYH have been associated with recessive inheritance of multiple colorectal adenomas. Tumors from affected persons displayed excess somatic transversions of a guanine-cytosine pair to a thymine-adenine pair (G:C-->T:A) in the APC gene. We screened for germ-line MYH mutations in 152 patients with multiple (3 to 100) colorectal adenomas and 107 APC-mutation-negative probands with classic familial adenomatous polyposis (>100 adenomas). Subgroups were analyzed for changes in the related genes MTH1 and OGG1. Adenomas were tested for somatic APC mutations. Six patients with multiple adenomas and eight patients with polyposis had biallelic germline MYH variants. Missense and protein-truncating mutations were found, and the spectrums of mutations were very similar in the two groups of patients. In the tumors of carriers of biallelic mutations, all somatic APC mutations were G:C-->T:A transversions. In the group with multiple adenomas, about one third of patients with more than 15 adenomas had biallelic MYH mutations. In the polyposis group, no patient with biallelic MYH mutations had severe disease (>1000 adenomas), but three had extracolonic disease. No clearly pathogenic MTH1 or OGG1 mutations were identified. Germ-line MYH mutations predispose persons to a recessive phenotype, multiple adenomas, or polyposis coli. For patients with about 15 or more colorectal adenomas--especially if no germ-line APC mutation has been identified and the family history is compatible with recessive inheritance--genetic testing of MYH is indicated for diagnosis and calculation of the level of risk in relatives. Clinical care of patients with biallelic MYH mutations should be similar to that of patients with classic or attenuated familial adenomatous polyposis. Copyright 2003 Massachusetts Medical Society
Shih, I M; Yan, H; Speyrer, D; Shmookler, B M; Sugarbaker, P H; Ronnett, B M
Pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by mucinous ascites and peritoneal lesions composed of histologically bland to low-grade adenomatous mucinous epithelium within pools of extracellular mucin, often with an associated mucinous adenoma of the appendix. There is evidence that the peritoneal lesions in PMP are clonally derived from the associated appendiceal adenoma. Little is known about the molecular genetic alterations or hereditary factors involved in the development of appendiceal mucinous tumors and PMP. We report the only known example of appendiceal mucinous adenomas in identical twin brothers, one of whom developed PMP. We analyzed the status of the K-RAS and APC genes in these tumors using digital polymerase chain reaction and digital single nucleotide polymorphism (SNP) assay. Identical K-RAS mutations were detected in the appendiceal adenoma and peritoneal tumor from the twin with PMP, whereas the adenoma from the other twin harbored a different mutation. Digital SNP analysis demonstrated loss of heterozygosity of APC only in the adenoma from the twin without PMP but not from the appendiceal or peritoneal tumors of the twin with PMP. The adjacent normal tissue in each case retained both APC alleles. The K-RAS mutational analysis supports the view that PMP is clonally derived from the associated appendiceal mucinous adenoma. The lack of loss of heterozygosity of APC in the adenoma and peritoneal tumor from the twin with PMP suggests that loss of heterozygosity of APC is not necessarily involved in the development of all appendiceal adenomas or PMP. The different types of mutations in K-RAS and the different allelic status of the APC locus in the tumors from both twins suggest that mutation in K-RAS and loss of heterozygosity of APC occurs somatically in adenomas and is independent of the identical genetic background of the twins.
de Brito, Beatriz Samara; Giovanelli, Natália; Egal, Erika Said; Sánchez-Romero, Celeste; Nascimento, Juliana de Souza do; Martins, Antonio Santos; Tincani, Álfio José; Del Negro, André; Gondak, Rogério de Oliveira; Almeida, Oslei Paes de; Kowalski, Luiz Paulo; Altemani, Albina; Mariano, Fernanda Viviane
PLAG1 (pleomorphic adenoma gene 1) is frequently activated in pleomorphic adenoma (PA). Carcinoma ex pleomorphic adenoma (CXPA) arises in PA, and PLAG1 expression is believed to be maintained from PA to CXPA, as it can contribute to the carcinogenesis process. To evaluate if PLAG1 is a good marker of malignant transformation from PA to CXPA as well as to evaluate if PLAG1 expression is associated with progression and histopathologic subtype of CXPA. Forty PAs, 21 residual PAs (without malignant transformation), and 40 CXPAs were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according to histopathologic subtype and invasiveness degree. Thirty-seven PAs (92.5%), 15 residual PAs (71%), and 14 CXPAs (35%) were positive for PLAG1. In relation to the CXPA group, among the intracapsular cases, myoepithelial carcinoma and epithelial-myoepithelial carcinoma showed the highest level of PLAG1 expression. PLAG1 expression is lost when PA undergoes malignant transformation, possibly due to other pathway activation and different clone cells. In addition, PLAG1 expression seems to be present mainly in low-grade carcinomas and in cases with early phase of invasion, due to its regulation of oncogene-induced cell senescence. In CXPA, PLAG1 expression was most associated with myoepithelial differentiation. This way, loss of PLAG1 expression can be considered a hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation.
Misra, Somen; Bhandari, Akshay; Misra, Neeta; Gogri, Pratik; Mahajan, Shruti
Ectopic lacrimal gland, being one of the choristomas, is comprised of lacrimal gland tissue outside the lacrimal gland fossa in the fronto-lateral part of the orbital roof. Ectopic lacrimal gland is a rare condition where the gland may be found in the orbit, eyelids, ocular adnexa or within the globe. Neoplastic transformation of such tissue may occur. A sixty-two-year old male patient presented with right eye proptosis and slight nasal displacement of the globe. Computerized tomography scan revealed a well-defined hypodense lesion of size 19 x 18 x 20 mm supero-lateral to lateral rectus muscle, with mild proptosis and thinning of the right lateral orbital wall. Excisional biopsy was performed through a lateral orbitotomy approach. A well circumscribed globular mass was removed from the right orbit, well behind the fossa for the lacrimal gland in the retrobulbar space. Histopathology was suggestive of pleomorphic adenoma of lacrimal gland. Pleomorphic adenoma is an epithelial tumor of the lacrimal gland which is extremely rare from an ectopic lacrimal gland and only few cases have been reported in literature till date.
Matsuda, Takahisa; Ono, Akiko; Sekiguchi, Masau; Fujii, Takahiro; Saito, Yutaka
High-quality colonoscopy is mandatory to prevent adenoma recurrence and colorectal cancer. In the past few years, technical advances have been developed with the purpose of improving adenoma detection rate (ADR), one of the most important validated colonoscopy quality benchmarks. Several techniques or devices are used to optimize visualization: observation techniques; add-on devices; auxiliary imaging devices; colonoscopes with increased field of view; and colonoscopes with an integrated inflatable reusable balloon. Image-enhanced endoscopy (IEE) facilitates the detection and characterization of polyps and especially nonpolypoid colorectal neoplasms. Indigo carmine is the most frequently used dye in colonoscopy as it deposits in depressed areas, improving detection of flat and depressed lesions. Virtual chromoendoscopy has emerged as an effective contrast enhancement technology without the limitation of preparing dyes and applying them through the colonoscope working channel. Narrow-band imaging (NBI) enhances the capillary pattern and surface of the mucosa using optical filters, and second-generation NBI provides a twofold brighter image than the previous system, yielding promising ADR results. Moreover, a second-generation blue laser imaging system, LASEREO, has been reported to improve not only polyp detection rate but also ADR, becoming a promising IEE modality. Herein, we describe technical advances in colonoscopy imaging and their effect on ADR.
Chalkley, M D; Kiupel, M; Draper, A C E
Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama.
Nemoto, Yukako; Tokuhisa, Junya; Shimada, Nagasato; Gomi, Tatsuya; Maetani, Iruru
Endoscopic mucosal resection (EMR) allows the removal of flat or sessile lesions, laterally spreading tumors, and carcinoma of the colon or the rectum limited to the mucosa or the superficial submucosa. Acute appendicitis is the most common abdominal emergency requiring emergency surgery, and it is also a rare complication of diagnostic colonoscopy and therapeutic endoscopy, including EMR. In the case presented here, a 53-year-old female underwent colonoscopy due to a positive fecal occult blood test and was diagnosed with cecal adenoma. She was referred to our hospital and admitted for treatment. The patient had no other symptoms. EMR was performed, and 7 h after the surgery, the patient experienced right -lower abdominal pain. Laboratory tests performed the following day revealed a WBC count of 16000/mm(3), a neutrophil count of 14144/mm(3), and a C-reactive protein level of 2.20 mg/dL, indicating an inflammatory response. Computed tomography also revealed appendiceal wall thickening and swelling, so acute appendicitis following EMR was diagnosed. Antibiotics were initiated leading to total resolution of the symptoms, and the patient was discharged on the sixth post-operative day. Pathological analysis revealed a high-grade cecal tubular adenoma. Such acute appendicitis following EMR is extremely rare, and EMR of the cecum may be a rare cause of acute appendicitis.
Takahashi, H; Fujita, S; Okabe, H; Tsuda, N; Tezuka, F
Seven cases of basal cell adenomas of the salivary gland were analyzed by immunohistochemical methods with a broad panel of routinely used antibodies. Histologically the epithelial elements were classified as tubuloglandular, trabecular and solid patterns. The authors' results indicated the following: 1) The duct lining cells of tubuloglandular and trabecular patterns have distinct epithelial features with cytokeratins (KL 1, PKK 1, *PKK 2 and PKK 3), alpha-one-antichymotrypsin (alpha 1-ACT), carcinoembryonic antigen (CEA) and S-100 alpha subunit positivity. 2) The basaloid cells in the trabecular and solid patterns expressed two immunophenotypes: one had actin, neuron-specific enolase (NSE), S-100 protein and S-100 beta subunit patterns typical of myoepithelial cells in normal glands. The other basaloid cells had vimentin and S-100 protein patterns. The former cell type could be found in 4 of 7 cases and the latter was found in 7 cases. This represents a minor participation of the myoepithelial cells in the basal cell adenoma. 3) The basement membrane and stromal connective tissue around the neoplastic cells were positive for alpha-one-antitrypsin (alpha 1-AT). This antibody is a good marker in identifying the basement membrane-like material.
Rakha, Emad A; Aleskandarany, Mohammed A; Samaka, Rehab M; Hodi, Zsolt; Lee, Andrew H S; Ellis, Ian O
Pleomorphic adenoma (PA) of the breast is a rare tumour seen usually in postmenopausal women. Although PA of the salivary glands (SG) is recognized to be a benign tumour, the nature and biology of similar tumours seen in the breast remains to be defined. The aim of this study was to describe PA of the breast that was reported on core biopsy as an invasive matrix-producing metaplastic breast carcinoma (MBC). A core biopsy from a clinically malignant retroareolar mass showed mildly atypical polygonal cells with surrounding myxoid stroma. Immunohistochemistry showed expression of basal and luminal cytokeratins, but oestrogen receptor, human epidermal growth factor receptor 2 (HER2) and myoepithelial markers were negative. The excision specimen showed similar features, but in addition the stroma showed cartilage and bone. Also it was clear that the lesion was circumscribed and merged with a sclerosed papillary lesion consistent with what has been described as mammary PA. This lesion shows an overlap of morphology and immunophenotype with SG-PA and with MBC. The majority of mammary PAs have a benign behaviour, but local recurrence and development of carcinoma occur. We propose a new terminology of pleomorphic adenoma-like tumour of the breast to reflect the uncertain nature of these tumours and help guide management decisions. © 2015 John Wiley & Sons Ltd.
Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.
A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.
Hasegawa, Shin; Mitsuyama, Keiichi; Kawano, Hiroshi; Arita, Keiko; Maeyama, Yasuhiko; Akagi, Yoshito; Watanabe, Yasutomo; Okabe, Yoshinobu; Tsuruta, Osamu; Sata, Michio
Sessile serrated adenoma (SSA) is a proposed precursor of colorectal carcinogenesis. This study aimed to analyze the potential of endoscopy to discriminate SSA from other serrated lesions, specifically traditional serrated adenoma (TSA) and hyperplastic polyp (HP). Of 145 serrated lesions, 111 sessile serrated lesions including 32 TSAs, 25 SSAs and 54 HPs were analyzed for size, color, location and morphologic features using conventional endoscopy and magnifying chromoendoscopy. SSA was preferentially located in the right colon, whereas TSA and HP were located in the left colon. The sizes of SSA and TSA were larger than those of HP. The lesion color was indistinguishable among TSA, SSA and HP. Macroscopically, a pinecone-like or two-tier raised appearance were found more frequently in TSA than in SAA and HP. Under magnified chromoendoscopic observation, the stellar IIIL pit pattern and fern-like appearance were observed more frequently in TSA than in SAA and HP. In conclusion, endoscopic discrimination between SSA and other sessile serrated lesions based on morphological features was difficult. However, size and location of the lesions facilitated diagnosis. PMID:22866127
Babula, Daniel; Horecka, Anna; Luchowska-Kocot, Dorota; Kocot, Joanna; Kurzepa, Jacek
Nitric oxide (NO) is synthesized by the conversion of Arginine (Arg) into the NO and Citrulline (Cit). Although the NO is involved into the pathogenesis of several physiological and pathological processes, the role of NO in pituitary adenomas (PA) progres-sion is not determined. Our purpose was to evaluate the relationship between NO and PA as well as the effect of tumor resection on NO metabolites level in serum. The study group consisted of 21 patients with PA, 18 patients with macroade-nomas and 3 with microadenomas. Venous blood samples were collected at two time-points; 1) before the surgery and 2) 3-5 days after PA resection. Arg and Cit levels were determined by the automated ion-exchange chromatography with usage of Amino Acids Analyser (AAA 400). Commercially available kit for the evaluation of nitrate/nitrite serum levels was applied for indirect assessment of serum NO level. Significant decrease in NO concentration after the surgery was observed in com-parison with the time-point 1. Arg level did not significantly change during the study period. Cit level was ranged below the detection limit of applied method. The decrease of NO level after the pituitary adenoma resection indicates the relationship between NO synthesis and PA occurrence.
Amlashi, Fatemeh G; Tritos, Nicholas A
Inappropriate secretion of TSH was first described in 1960 in a patient with evidence of hyperthyroidism and expanded sella on imaging. It was later found that a type of pituitary adenoma that secretes TSH (thyrotropinoma) was the underlying cause. The objective of the present review article is to summarize data on the epidemiology, pathogenesis, diagnosis, and management of thyrotropinomas. The prevalence of thyrotropinomas is lower than that of other pituitary adenomas. Early diagnosis is now possible thanks to the availability of magnetic resonance imaging and sensitive laboratory assays. As a corollary, many patients now present earlier in the course of their disease and have smaller tumors at the time of diagnosis. Treatment also has evolved over time. Transsphenoidal surgery is still considered definitive therapy. Meanwhile, radiation therapy, including radiosurgery, is effective in achieving tumor control in the majority of patients. In the past, radiation therapy was used as second line treatment in patients with residual or recurrent tumor after surgery. However, the availability of somatostatin analogs, which can lead to normalization of thyroid function as well as shrink these tumors, has led to an increase in the role of medical therapy in patients who are not in remission after pituitary surgery. In addition, dopamine agonists have shown some efficacy in the management of these tumors. Better understanding of the molecular pathogenesis of thyrotropinomas may lead to rationally designed therapies for patients with thyrotropinomas.
Zhan, Xianquan; Wang, Xiaowei; Cheng, Tingting
Pituitary adenoma (PA) is a common intracranial neoplasm that impacts on human health through interfering hypothalamus–pituitary–target organ axis systems. The development of proteomics gives great promises in the clarification of molecular mechanisms of a PA and discovery of effective biomarkers for prediction, prevention, early-stage diagnosis, and treatment for a PA. A great progress in the field of PA proteomics has been made in the past 10 years, including (i) the use of laser-capture microdissection, (ii) proteomics analyses of functional PAs (such as prolactinoma), invasive and non-invasive non-functional pituitary adenomas (NFPAs), protein post-translational modifications such as phosphorylation and tyrosine nitration, NFPA heterogeneity, and hormone isoforms, (iii) the use of protein antibody array, (iv) serum proteomics and peptidomics, (v) the integration of proteomics and other omics data, and (vi) the proposal of multi-parameter systematic strategy for a PA. This review will summarize these progresses of proteomics in PAs, point out the existing drawbacks, propose the future research directions, and address the clinical relevance of PA proteomics data, in order to achieve our long-term goal that is use of proteomics to clarify molecular mechanisms, construct molecular networks, and discover effective biomarkers. PMID:27303365
Lasio, Giovanni; Ferroli, Paolo; Felisati, Giovanni; Broggi, Giovanni
To assess the role that neuronavigation plays in assisting endoscopic transsphenoidal reoperations for recurrent pituitary adenomas. During a 45-month period, 19 endoscopic endonasal transsphenoidal reoperations were performed for recurrent pituitary adenomas. In 11 of 19 patients, the procedure was performed with the aid of an optically guided system. Clinical records were reviewed retrospectively, with attention to the following: comparison of baseline clinical data, the duration of surgery, and the postoperative course and complications of both image-guided and non-image-guided endoscopic reoperations. In addition, to test the reliability of the neuronavigation system, we made measurements of intraoperative accuracy in five additional transnasal endoscopic procedures in "virgin" noses and sphenoidal sinuses. In both groups studied, we found no difference with regard to either morbidity or mortality, which were null. The mean setup time was 13 minutes shorter in non-image-guided procedures (P = 0.021), and the operative time was 36 minutes shorter in image-guided procedures (P = 0.038). No other statistically significant differences were found between the two groups. In all cases, we found that the system performed without malfunction. Continuous information regarding instrument location and trajectory was provided to the surgeon. Measurements of the intraoperative accuracy in the axial, coronal, and sagittal planes indicated a mean intraoperatively verified system error of 1.6 +/- 0.6 mm. Neuronavigation can be applied during endonasal transsphenoidal endoscopic surgery and requires a minimal amount of time. It makes reoperation easier, faster, and probably safer.
Hong, Jae Won; Lee, Mi Kyung; Kim, Sun Ho; Lee, Eun Jig
The objective of this study was to evaluate characteristics that discriminate prolactinoma from non-functioning pituitary macroadenoma with hyperprolactinemia. We included 117 patients with hyperprolactinemic pituitary macroadenomas. Patients were divided into three groups according to treatment outcomes and pathologic results: (A) prolactinoma that responded to dopamine agonist (DA) treatment (PRDA); (B) prolactinoma requiring surgical treatment (PRS); and (C) non-functioning pituitary adenoma with hyperprolactinemia (NFPAH). Old age, low serum prolactin levels, and extrasellar extension were associated with NFPAH. Most patients with NFPAH had serum prolactin levels less than 100 ng/ml. Visual defects and GH deficiency were more common in patients with NFPAH compared with patients with PRS and PRDA, without difference of tumor size. Galactorrhea and amenorrhea were less frequent in patients with NFPAH than in patients with PRS and PRDA. Post-operative remission of hyperprolactinemia was achieved in 100% of patients with NFPAH and in 72.5% of patients with PRS. DA administration was required in 25.5% of patients with PRS; however, no patients with NFPAH required DA administration. In conclusion, old age, extrasellar tumor extension with relatively low prolactin levels, visual defect, and GH deficiency were considered suggestive of non-functioning pituitary adenoma rather than prolactinoma in hyperprolactinemic pituitary macroadenoma.
Sun, Zhulei; Kan, Shihai; Zhang, Leilei; Zhang, Yan; Jing, Hong; Huang, Gui; Yu, Qichun; Wu, Jiang
To assess the clinicopathological, immunohistochemical and molecular features of metanephric adenoma (MA). Clinicopathologic data were obtained for 5 cases of MA with follow-up information. Specimens from these patients were stained by HE and immunohistochemistry for the detection of WT1, vimentin, S-100 protein, CK7, P504s, CD10 and renal cell carcinoma marker (RCC). Fluorescence in situ hybridization (FISH) was performed on 4 tumors. The patients included 1 male and 4 females, aged from 30 to 49 (mean=39) years. Tumor diameters ranged from 3 to 5.5 cm. Histologically, the tumors had tubular, papillary, or glomeruloid architectures, and were composed of cells with uniform and round nuclei, inconspicuous nucleoli, and high ratio of nucleus to cytoplasm. Nuclear polymorphism and mitotic figures were not observed. Immunohistochemically, they expressed WT1 (5/5), vimentin (5/5), S-100 (4/5), CK7 (2/5), P504s (2/5), and CD10 (1/5) and not RCC. FISH study was carried out on 4 metanephric adenoma cases, and no abnormalities were observed in chromosomes 3, 7, 17, and P16 gene of chromosomes 9. MA is an uncommon renal tumor. Its diagnosis depends on morphological, immunohistochemical and molecular features. PMID:26261480
Zogheri, A; Di Mambro, A; Mannelli, M; Serio, M; Forti, G; Peri, A
Pituitary adenomas may be the cause of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), although few cases have so far been reported. We described a case of hypotonic hyponatremia in a 76-yr-old man with a pituitary macroadenoma. He had a recent history of two syncopal attacks which had occurred in the last two months. Baseline assessment demonstrated a sodium serum level of 114 mEq/l. Clinically, the patient appeared euvolemic. Thyroid and adrenal function testing did not show any abnormality. Plasma and urinary osmolality (238 and 186 mOsm/kg, respectively) were in agreement with the diagnosis of SIADH. Accordingly, 3% hypertonic saline solution was started, followed by water intake restriction when natremia reached 126 mEq/l. A computed tomography (CT) scan of the chest revealed the presence of a 2-cm lesion in the azygos-esophageal recess. Because the nature of the lesion appeared uncertain, antibiotic therapy was initiated. After one month, a new CT scan did not show any evidence of the mediastinic mass. Sodium serum level was within the normal range (141 mEq/l) and remained stable thereafter, without fluid restriction. This case very well demonstrates that, in the presence of hyponatremia due to SIADH, more frequently associated co-morbidities (ie mediastinic diseases) have to be searched, even in the presence of a possible, yet rare, cause of this syndrome (ie pituitary adenoma).
Bento, Patrícia Meira; Freitas, Roseana de Almeida; Pinto, Leão Pereira; de Souza, Lélia Batista
Objectives: To analyze the expression and distribution pattern of extracellular matrix components in pleomorphic adenomas of the major and minor salivary glands and to compare the morphological findings of these tumors with the immunohistochemical expression, considering the different types of stroma predominating in each case. Methods and Results: The expression of tenascin (TN) and fibronectin (FN) was analyzed in 23 cases of pleomorphic adenomas, 11 major and 12 minor salivary gland tumors, by the streptavidin-biotin method using anti-tenascin and anti-fibronectin antibodies. In addition, the immunohistochemical results were correlated with the morphological findings of the lesions. All cases analyzed were immunoreactive for the antibodies used. Fibronectin showed strong labeling in fibrous and chondroid stroma, while labeling was weak in hyaline and myxoid stroma. Tenascin expression was more intense in fibrous and chondroid stroma and moderate in hyaline and myxoid stroma. Conclusions: No difference in the expression of these proteins was observed between major and minor salivary gland tumors. PMID:19089073
Rondonotti, Emanuele; Andrealli, Alida; Amato, Arnaldo; Paggi, Silvia; Conti, Clara Benedetta; Spinzi, Giancarlo; Radaelli, Franco
Adenoma detection rate (ADR) is the most robust colonoscopy quality metric and clinical studies have adopted it as the ideal method to assess the impact of technical interventions. Areas covered: We reviewed papers focusing on the impact of colonoscopy technical issues on ADR, including withdrawal time and technique, second evaluation of the right colon, patient positional changes, gastrointestinal assistant participation during colonoscopy, water-aided technique, optimization of bowel preparation and antispasmodic administration. Expert commentary: Overall, technical interventions are inexpensive, available worldwide and easy to implement. Some of them, such as the adoption of split dose regimen and slow scope withdrawal to allow a careful inspection, have been demonstrated to significantly improve ADR. Emerging data support the use of water-exchange colonoscopy. According to published studies, other technical interventions seem to provide only marginal benefit to ADR. Unfortunately, the available evidence has methodological limitations, such as small sample sizes, the inclusion of expert endoscopists only and the evaluation of single technical interventions. Additionally, larger studies are needed to clarify whether these interventions might have a higher benefit on low adenoma detectors and whether the implementation of a bundle of them, instead of a single technical maneuver, might have a greater impact on ADR.
Di Palma, Silvana
Carcinoma ex pleomorphic adenoma (CXPA) is a broad category of carcinomas of the salivary glands which includes at least 2 clinically relevant categories; one is referred here as early CXPA (ECXPA), the other as widely invasive CXPA. The former includes several histological patterns ranging from non-invasive/in situ/intraductal/intratubular, early invasive/extratubular/intracapsular and extracapsular (up to 6 mm). The latter includes any CXPA with invasion of >6 mm. The clinical behaviour of ECXPA is not aggressive and tends to overlap that of a pleomorphic adenoma (PA) which makes the histological report of carcinoma contradictory. These early malignant changes in PA are known since the 1970s but it has been the use of immunohistochemical and molecular genetic analysis for HER-2 and TP53 gene in the last decade that has clarified the genuine malignant nature of the cells. HER-2 and TP53 gene and protein are involved in the early stages of malignant transformation of PA. Moreover the immunohistochemical over-expression HER-2, p53 protein and Mib-1 proliferation marker may be useful markers to identify malignant areas in PA.
Vantyghem, M C; Cortet, C; Bauters, C; Gevaert, M H; Dewailly, D; Lefebvre, J; Mazzucca, M
Glycoprotein hormone alpha subunit (alpha SU) is expressed in nearly all thyreotroph adenomas and most gonadotrophinomas, but is less well documented in plurisecreting adenomas. We therefore examined the immunohistochemical (IHC) expression of alpha SU in a generally accepted model of plurisecreting adenomas (somatoprolactinic type) by comparison to a series of pure monosecreting somatotroph tumors. Fifty patients (32 females, 18 males) aged 15 to 68 years with clinical and/or biological acromegaly requiring adenomectomy were studied. Forty-five had clinical acromegaly and 5 had isolated amenorrhea and/or galactorrhea syndromes. Forty-eight of the 49 patients who had baseline assessments of plasma GH had a mean concentration of 5 ng/ml or more (normal value < 5). Fifteen of the 46 patients who had baseline measurements of plasma PRL had a prolactinemia value greater than 20 ng/ml (normal value < 20) but below 100 ng/ml, except for one patient. All the adenomas studied were positive by GH immunohistochemistry; 21 were immunostained by an antiPRL antibody and formed the "somatoprolactinic" (GH-PRL) group. Five of these 21 patients were male. The 12 female patients younger than 50 years had amenorrhea or galactorrhea, and one male patient complained of impotence. Eleven patients (9 females, 2 males) in this GH-PRL group had hyperprolactinemia. Sixteen of these GH-PRL adenomas were immunolabeled by alpha SU antiserum. The remaining 29 adenomas, which were immunonegative with the PRL antibody and formed the "somatotroph adenoma" (GH) group, were more frequent in male patients (13/29; 45%) compared to GH-PRL group. Eight amenorrhea or galactorrhea syndromes occurred among the 14 women younger than 50 years, 3 of whom had hyperprolactinemia. Thirteen of these 29 adenomas (45%) were immunopositive with alpha SU antibody. Compared to the GH group, the GH-PRL group had a significant higher frequency of amenorrhea and/or galactorrhea syndromes among women under 50 years (100
Voss, Katherine; Peppas, Dennis
Nephrogenic adenoma is an uncommon urothelial lesion that has been associated with chronic inflammation and surgical manipulation of the urinary tract. Several cases of vesical nephrogenic adenoma in patients with a history of renal transplantation have been reported. The present case report reviewed the management of recurrent nephrogenic adenoma in a 6-year-old boy with history of renal transplantation 3 years before the diagnosis of nephrogenic adenoma. After multiple surgical resections for recurrent nephrogenic adenoma, the lesion finally resolved with long-term treatment with ibuprofen (Motrin) and trimethoprim and sulfamethoxazole (Septra). Copyright © 2013 Elsevier Inc. All rights reserved.
Bellan, Alberto; Cappellesso, Rocco; Lo Mele, Marcello; Peraro, Laura; Balsamo, Laura; Lanza, Cristiano; Fassan, Matteo; Rugge, Massimo
Among colorectal cancers, the prevalence of signet ring cell carcinoma (SRCC) is lower than 1%; to date, only 6 cases of early SRCCs arising in colonic adenoma have been reported. In spite of the well-established understanding of the phenotypic and genetic changes occurring in conventional colonic carcinogenesis, the molecular landscape of colon SRCC is still far to be elucidated. We describe the histologic and immunohistochemical phenotype and the molecular profile of a case of intramucosal SRCC developed within a 4.5-cm large sigmoid adenoma. The DNA sequencing of the 2 microdissected neoplastic components (adenomatous and SRCC) showed the same G12V KRAS mutation. Interestingly, although the adenomatous epithelium showed unequivocal p53 overexpression, no signet ring cancer cells featured p53 nuclear immunostain. This molecular pattern supports the unique histogenesis of the 2 coexisting neoplastic oncotypes, also suggesting that the signet ring cell component is derived from the molecular de-differentiation (p53 loss) of the preexisting adenomatous lesion. Copyright © 2015 Elsevier Inc. All rights reserved.
Heitman, Steven J; Ronksley, Paul E; Hilsden, Robert J; Manns, Braden J; Rostom, Alaa; Hemmelgarn, Brenda R
There is an extensive yet inconsistent body of literature reporting on the prevalence of adenomatous polyps (adenomas) and colorectal cancer among average risk individuals. The objectives of our study were to determine the pooled prevalence of adenomas and colorectal cancer, as well as nonadvanced and advanced adenomas, among average risk North Americans. Articles were obtained by searching electronic databases (MEDLINE: 1950 through March 2008 and EMBASE: 1980 through March 2008), bibliographies, major journals, and conference proceedings, with no language restrictions. Two reviewers independently selected cross-sectional studies reporting adenoma and colorectal cancer prevalence rates in average risk individuals and assessed studies for inclusion and quality, and extracted the data for analysis. Pooled adenoma and colorectal cancer prevalence rates were estimated using fixed and random effects models. Stratification and metaregression was used to assess heterogeneity. Based on 18 included studies, the pooled prevalence of adenomas, colorectal cancer, nonadvanced adenomas, and advanced adenomas was 30.2%, 0.3%, 17.7%, and 5.7%, respectively. Heterogeneity was observed in the pooled prevalence rates for overall adenomas, advanced adenomas, and colorectal cancer and was explained by the mean age (> or = 65 years vs < 65 years) with older cohorts reporting higher prevalence rates. None of the study quality indicators was found to be significant predictors of heterogeneity. The high prevalence of advanced adenomas and colorectal cancer, especially among older screen-eligible individuals, provides impetus for expanding colorectal cancer screening programs. Furthermore, the pooled prevalence estimates can be used as quality indicators for established programs.
Awad, Ahmed J; Rowland, Nathan Christopher; Mian, Matthew; Hiniker, Annie; Tate, Matthew; Aghi, Manish Kumar
Pituitary abscesses occurring in pre-existing pituitary pathology like Rathke's cleft cyst or adenomas (secondary pituitary abscesses) are rare and of unclear etiology. While surgery and antibiotics have been effective in some cases reported to date, leading to the suggestion that secondary pituitary abscesses are mostly indolent, we investigated the hypothesis that infected adenomas, given their propensity to invade the paranasal sinuses and subarachnoid space, could carry a worse prognosis than uninfected adenomas or secondary abscesses forming in other pituitary pathologies. We identified infected adenomas from our center through retrospective review. Given the rarity of this diagnosis at any single center, we also reviewed published cases of secondary pituitary abscesses occurring in pituitary adenomas to look for common features. Twenty-three cases (19 from the literature and four from our center) of infected adenomas were identified. The mean age at presentation was 46 years, with 65 % male. The most common presenting symptoms were visual disturbances (83 %) and headache (65 %), followed by infectious signs like fever (39 %) and meningitis (26 %). The sphenoidal sinus was the most common site of extrasellar invasion. While good outcome occurred in 74 % of patients, and most achieved vision improvement, the mortality was 26 %. Patients with infected pituitary adenomas commonly present with visual disturbances and headache, with symptoms of infection also occurring. Surgery and antibiotics are indicated for these lesions. While the infection is more indolent than other intracranial abscesses, it is associated with high mortality even after prompt operation and antibiotic treatment.
La Rosa, Stefano; Vigetti, Davide; Placidi, Claudia; Finzi, Giovanna; Uccella, Silvia; Clerici, Moira; Bartolini, Barbara; Carnevali, Ileana; Losa, Marco; Capella, Carlo
Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells.
Background The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas. Methods Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel. Results Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa. Conclusions The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection. PMID:21777459
Rifkin, Samara B; Shrubsole, Martha J; Cai, Qiuyin; Smalley, Walter E; Ness, Reid M; Swift, Larry L; Zheng, Wei; Murff, Harvey J
Dietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62, P trend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (P trend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.
Rhee, Je-Keun; Jung, Seung-Hyun; Lee, Sung Hak; Baek, In-Pyo; Kim, Min Sung; Lee, Sug Hyung; Chung, Yeun-Jun
Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four -stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a ‘parallel’ evolution of synchronous adenoma-to-carcinoma, rather than a ‘stepwise’ evolution. The abundance of indel (in MSU and MSS pairs) and microsatellite instability (in MSU pairs) was noted in the later adenoma- or carcinoma-specific mutations, indicating that the mutational processes and functional constraints operative in early and late colorectal carcinogenesis are different. All MSU cases exhibited clonal, truncating mutations in ACVR2A, TGFBR2, and DNA mismatch repair genes, but none were present in APC or KRAS. In three MSS pairs, both APC and KRAS mutations were identified as both early and clonal events, often accompanying clonal copy number changes. An MSS case uniquely exhibited clonal ERBB2 amplification, followed by APC and TP53 mutations as carcinoma-specific events. Along with the previously unrecognized clonal origins of synchronous colorectal adenoma-carcinoma pairs, our study revealed that the preferred sequence of mutational events during colorectal carcinogenesis can be context-dependent. PMID:26336987
Fajardo-Montañana, Carmen; Daly, Adrian F; Riesgo-Suárez, Pedro; Gómez-Vela, José; Tichomirowa, María A; Camara-Gómez, Rosa; Beckers, Albert
Clinically relevant pituitary adenomas occur 3-5 times more frequently than previously thought. The majority are isolated cases, but their presentation can be familial in the setting of known syndromes such as multiple endocrine neoplasia (MEN)-1 and Carney complex. When 2 or more cases of pituitary adenomas occur in the same family in the absence of the above-mentioned syndromes, a diagnosis of FIPA (familial isolated pituitary adenomas) is made, which accounts for 1-2% of all pituitary adenomas. Mutations of the gene AIP (aryl hydrocarbon receptor-interacting protein) may account for 15% of FIPA families (50% of familial acromegaly), and as such the genetic causes continue to be studied. Also mutations in AIP can be detected in sporadic adenomas among young populations (< 30 years of age). We describe the characteristics of FIPA, detailing the study of a spanish family, in this case AIP mutation negative. Also, the reported findings in sporadic adenomas in the young population are detailed, accompanied by the description of a 19- year old patient with an intronic AIP mutation. Multicenter studies have provided understanding of aspects such as mutations in AIP; however, further studies are necessary to identify other genes involved in FIPA and sporadic pituitary adenomas occurring at a young age.
Mehta, Gautam U.; Montgomery, Blake K.; Raghavan, Pooja; Sharma, Susmeeta; Nieman, Lynnette K.; Patronas, Nicholas; Oldfield, Edward H.; Chittiboina, Prashant
We report a patient with Cushing’s disease (CD) and two pituitary adenomas that demonstrated different imaging characteristics and therefore suggest an alternative imaging strategy for these patients. A 42-year-old woman presented with signs and symptoms of CD. Biochemical evaluation confirmed hypercortisolemia and suggested CD. On pituitary MRI with spoiled gradient recalled acquisition in the steady-state and T1-weighted spin echo protocols, a 5 mm hypoenhancing region typical for a pituitary adenoma was identified on the left. However, after surgical resection the patient remained hypercortisolemic and pathology revealed a nonfunctional adenoma. At early repeat surgical exploration a 10 mm adenoma was found in the right side of the gland. Postoperatively the patient became hypocortisolemic and pathology demonstrated an adrenocorticotropic hormone (ACTH)-staining adenoma. On review of the initial MRI this tumor corresponded to a region of contrast retention best visualized on delayed fluid attenuated inversion recovery (FLAIR) imaging. While the incidentaloma in this case demonstrated classical imaging characteristics of a pituitary adenoma the larger ACTH-secreting tumor was best appreciated by contrast retention. This suggests a role for delayed postcontrast FLAIR imaging in the preoperative evaluation of CD. ACTH-secreting tumors causing CD cause significant morbidity. Due to their small size, a pituitary adenoma is frequently not identified on imaging despite endocrinologic testing suggesting CD. Regardless of improvements in MRI, many tumors are only identified at surgical exploration. PMID:25827866
Rashid, Mamunur; Fischer, Andrej; Wilson, Cathy H; Tiffen, Jessamy; Rust, Alistair G; Stevens, Philip; Idziaszczyk, Shelley; Maynard, Julie; Williams, Geraint T; Mustonen, Ville; Sampson, Julian R; Adams, David J
Familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) are inherited disorders associated with multiple colorectal adenomas that lead to a very high risk of colorectal cancer. The somatic mutations that drive adenoma development in these conditions have not been investigated comprehensively. In this study we performed analysis of paired colorectal adenoma and normal tissue DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from each patient, and a further 63 adenomas by capillary sequencing (41 FAP, 22 MAP). With these data we examined the profile of mutated genes, the mutational signatures and the somatic mutation rates, observing significant diversity in the constellations of mutated driver genes in different adenomas, and loss-of-function mutations in WTX (9%; p < 9.99e-06), a gene implicated in regulation of the WNT pathway and p53 acetylation. These data extend our understanding of the early events in colorectal tumourigenesis in the polyposis syndromes. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Mehta, Gautam U; Montgomery, Blake K; Raghavan, Pooja; Sharma, Susmeeta; Nieman, Lynnette K; Patronas, Nicholas; Oldfield, Edward H; Chittiboina, Prashant
We report a patient with Cushing's disease (CD) and two pituitary adenomas that demonstrated different imaging characteristics and therefore suggest an alternative imaging strategy for these patients. A 42-year-old woman presented with signs and symptoms of CD. Biochemical evaluation confirmed hypercortisolemia and suggested CD. On pituitary MRI with spoiled gradient recalled acquisition in the steady-state and T1-weighted spin echo protocols, a 5mm hypoenhancing region typical for a pituitary adenoma was identified on the left. However, after surgical resection the patient remained hypercortisolemic and pathology revealed a non-functional adenoma. At early repeat surgical exploration a 10mm adenoma was found in the right side of the gland. Postoperatively the patient became hypocortisolemic and pathology demonstrated an adrenocorticotropic hormone (ACTH)-staining adenoma. On review of the initial MRI this tumor corresponded to a region of contrast retention best visualized on delayed fluid attenuated inversion recovery (FLAIR) imaging. While the incidentaloma in this case demonstrated classical imaging characteristics of a pituitary adenoma the larger ACTH-secreting tumor was best appreciated by contrast retention. This suggests a role for delayed postcontrast FLAIR imaging in the preoperative evaluation of CD. ACTH-secreting tumors causing CD cause significant morbidity. Due to their small size, a pituitary adenoma is frequently not identified on imaging despite endocrinologic testing suggesting CD. Regardless of improvements in MRI, many tumors are only identified at surgical exploration. Published by Elsevier Ltd.
Bello, M Josefa; De Campos, Jose M; Isla, Alberto; Casartelli, Cacilda; Rey, Juan A
The epigenetic changes in pituitary adenomas were identified by evaluating the methylation status of nine genes (RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1 and caspase-8) in a series of 35 tumours using methylation-specific PCR analysis plus sequencing. The series included non-functional adenomas (n=23), prolactinomas (n=6), prolactinoma plus thyroid-stimulating hormone adenoma (n=1), growth hormone adenomas (n=4), and adrenocorticotropic adenoma (n=1). All of the tumours had methylation of at least one of these genes and 40% of samples (14 of 35) displayed concurrent methylation of at least three genes. The frequencies of aberrant methylation were: 20% for RB1, 17% for p14(ARF), 34% for p16(INK4a), 29% for p73, 11% for TIMP-3, 23% for MGMT, 6% for DAPK, 43% for THBS1 and 54% for caspase-8. No aberrant methylation was observed in two non-malignant pituitary samples from healthy controls. Although some differences in the frequency of gene methylation between functional and non-functional adenomas were detected, these differences did not reach statistical significance. Our results suggest that promoter methylation is a frequent event in pituitary adenoma tumourigenesis, a process in which inactivation of apoptosis-related genes (DAPK, caspase-8) might play a key role.
Morita, T; Tamura, S; Miyazaki, J; Higashidani, Y; Onishi, S
The aim of this study was to reveal the clinical features of serrated colonic adenoma by investigating its endoscopic features using a magnifying videoscope. 68 colorectal serrated adenomas presented for colonoscopic examination were included in this study. A magnifying videoscope with a zoom ranging from x 1 to x 100 magnification was employed to observe the pit patterns of colonic lesions, and 39 of the serrated adenoma specimens were evaluated using this. Some pit patterns appeared as elongated oval and stellar-like orifices of the crypts; we termed these type which was detected III(SA) patterns. Other pit patterns showed a flower petal-like or pineal form, and this was termed a type IV(SA) pit pattern. In the entire sample of serrated adenomas, 53 were of the protruded type, and 15 were superficial, for a protruded/superficial ratio of 3.5 : 1. The protruded type of serrated adenoma predominated in the distal portion. The superficial type was preferentially located in the proximal portion of the colon (P < 0.0001). Among the 13 superficial types in which the magnifying videoscope was used, all 13 showed the type III(SA) basic pit pattern. In these serrated adenomas of the superficial type, an additional IV(SA) pit pattern was found in 23.1% (3/13), which was detected in 53.8% (14/26) in the protruded type. Small serrated adenomas measuring less than 10 mm in diameter were preferentially mild to moderate atypia (odd's ratio = 15.9, P = 0.0216). The pit pattern may prove useful for the endoscopic diagnosis of serrated adenoma. Furthermore, endoscopic treatment is indicated for serrated adenoma; in particular those of 10 mm or more in diameter should be treated because of the possibility of high-grade glandular intraepithelial neoplasia.
Yang, Moon Hee; Rampal, Sanjay; Sung, Jidong; Choi, Yoon-Ho; Son, Hee Jung; Lee, Jun Haeng; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Rhee, Jong Chul; Guallar, Eliseo; Cho, Juhee
Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans. Cross-sectional study of 19,372 consecutive participants aged 20 to 79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009. Among participants at average risk, those without a history of colorectal polyps or a family history of colorectal cancer, the prevalence of colorectal adenomas and advanced adenomas were 34.5% and 3.1%, respectively, in men and 20.0% and 1.6%, respectively, in women. The prevalence of adenomas increased with age in both men and women, with a more marked increase for advanced adenoma. Participants with a family history of colorectal cancer or with a history of colorectal polyps had significantly higher prevalence of adenomas compared with participants of average risk (36.9% vs. 26.9%; age- and sex-adjusted prevalence ratio = 1.16; 95% confidence interval, 1.09-1.22). The prevalence of adenomas increased annually in both men and women. In this large study of asymptomatic Korean men and women participating in a colonoscopy screening program, the prevalence of colorectal adenomas was comparable and possibly higher than previously reported in Western countries. Cost-effectiveness studies investigating the optimal age for starting colonoscopy screening and etiological studies to identify the reasons for the increasing trend in colorectal adenomas in Koreans are needed. ©2014 AACR.
Wong, Hui-Lee; Peters, Ulrike; Hayes, Richard B; Huang, Wen-Yi; Schatzkin, Arthur; Bresalier, Robert S; Velie, Ellen M; Brody, Lawrence C
While germline mutations in the adenomatous polyposis coli (APC) gene cause the hereditary colon cancer syndrome (familial adenomatous polyposis (FAP)), the role of common germline APC variants in sporadic adenomatous polyposis remains unclear. We studied the association of eight APC single nucleotide polymorphisms (SNPs), possibly associated with functional consequences, and previously identified gene-environment (dietary fat intake and hormone replacement therapy (HRT) use) interactions, in relation to advanced colorectal adenoma in 758 cases and 767 sex- and race-matched controls, randomly selected from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Cases had at least one verified advanced adenoma of the distal colon; controls, a negative sigmoidoscopy. We did not observe an association between genotypes for any of the eight APC SNPs and advanced distal adenoma risk (P(global gene-based)=0.92). Frequencies of identified common haplotypes did not differ between cases and controls (P(global haplotype test)=0.97). However, the risk for advanced distal adenoma was threefold higher for one rare haplotype (cases: 2.7%; controls: 1.6%) (odds ratio (OR)=3.27; 95% confidence interval (CI)=1.08-9.88). The genetic association between D1822V and advanced distal adenoma was confined to persons consuming a high-fat diet (P(interaction)=0.03). Similar interactions were not observed with HRT use. In our large, nested case-control study of advanced distal adenoma and clinically verified adenoma-free controls, we observed no association between specific APC SNPs and advanced adenoma. Fat intake modified the APC D1822V-adenoma association, but further studies are warranted.
Park, Jung Hun; Kim, Sang Jin; Hyun, Jong Hee; Han, Kyung Su; Kim, Byung Chang; Hong, Chang Won; Lee, Sang-Jeon; Sohn, Dae Kyung
The adenoma detection rate is commonly used as a measure of the quality of colonoscopy. This study assessed both the association between the adenoma detection rate and the quality of bowel preparation and the risk factors associated with the adenoma detection rate in screening colonoscopy. This retrospective analysis involved 1,079 individuals who underwent screening colonoscopy at the National Cancer Center between December 2012 and April 2014. Bowel preparation was classified by using the Aronchick scale. Individuals with inadequate bowel preparations (n = 47, 4.4%) were excluded because additional bowel preparation was needed. The results of 1,032 colonoscopies were included in the analysis. The subjects' mean age was 53.1 years, and 657 subjects (63.7%) were men. The mean cecal intubation time was 6.7 minutes, and the mean withdrawal time was 8.7 minutes. The adenoma and polyp detection rates were 28.1% and 41.8%, respectively. The polyp, adenoma, and advanced adenoma detection rates did not correlate with the quality of bowel preparation. The multivariate analysis showed age ≥ 60 years (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.02-1.97; P = 0.040), body mass index ≥ 25 kg/m(2) (HR, 1.56; 95% CI, 1.17-2.08; P = 0.002) and current smoking (HR, 1.44; 95% CI, 1.01-2.06; P = 0.014) to be independent risk factors for adenoma detection. The adenoma detection rate was unrelated to the quality of bowel preparation for screening colonoscopy. Older age, obesity, and smoking were independent risk factors for adenoma detection.
Nalbantoglu, ILKe; Watson, Rao; Goodwin, Jonathan; Safar, Elyas; Chokshi, Reena V.; Azar, Riad R.; Davidson, Nicholas O.
Background The presence of advanced adenomas in younger individuals is a criterion for Lynch syndrome (LS). However, the utility of screening advanced adenomas for loss of mismatch repair (MMR) protein expression to identify suspected LS remains unclear. Aims Determine the prevalence of MMR defects to understand whether these patients harbor a defined genetic risk for CRC. Methods The study cohort included adult patients ≤45 years of age with advanced adenomas (villous histology, ≥1 cm in diameter, ≥3 polyps of any size) endoscopically removed between 2001 and 2011. Clinical records were reviewed along with detailed pathological review and immunohistochemical MMR analysis. Results A total of 76 (40.1 % male, age 40.6 ± 5.4 years) patients met inclusion and exclusion criteria. Indications for colonoscopy were gastrointestinal (GI) bleeding 39 (51.3 %), CRC in a first-degree relative 17 (22.4 %) and somatic GI symptoms 20 (26.3 %). Index colonoscopy revealed a median of 1 adenoma (range 1–4), mean diameter of 12.9 ±7.1 mm, 40 (52.6 %) with villous histology. The mean follow-up duration was 3.3 ± 2 years. Recurrent adenomas developed in 24 (31.6 %), of which 8 (10.5 %) were advanced adenomas; none of these patients developed CRC. One of 66 (1.5 %) adenomas available for immunohistochemical (IHC) testing revealed loss of MLH1 and PMS2. Conclusions IHC screening of advanced adenomas from patients younger than 45 years of age identified potential LS in one of 64 patients. The low yield of IHC screening in this population suggests that universal IHC screening of advanced adenomas from patients younger than 45 years of age for MMR defects is not an efficient strategy for identifying LS subjects. PMID:24925148
Cooper, Odelia; Ben-Shlomo, Anat; Bonert, Vivien; Bannykh, Serguei; Mirocha, James
Silent corticotrophins adenomas (SCAs) are clinically silent and non-secreting but immunostain positively for ACTH. We hypothesize that SCAs comprise both corticotroph and gonadotroph characteristics. Cohort analysis from 1994–2008 with follow-up time ranging from 1–15 years in a tertiary referral center. We compared preoperative and postoperative clinical results and tumor cytogenesis in 25 SCAs and 84 nonfunctioning adenomas in 109 consecutive patients diagnosed pre-operatively with nonfunctioning pituitary adenomas. Clinical outcomes were radiologic and hormonal measures. Pathologic outcomes were expression of relevant pituitary hormones, tissue-specific transcription factors, and electron microscopy features. Preoperative SCA presentation was similar to that observed for nonfunctioning adenomas. However, SCAs recurred postoperatively at a median of 3 years vs. 8 years for nonfunctioning adenomas (p<0.0001). Fifty-four percent of patients with SCAs had new onset postoperative hypopituitarism vs. 17% of nonfunctioning adenomas (p<0.025). SCAs (n=18) were immunopositive for ACTH, cytoplasmic and nuclear SF-1, NeuroD1, DAX-1, and alpha-gonadotropin subunit, but Tpit negative, and co-expression of tumor ACTH with either SF-1 or LH was detected. In contrast, functional corticotroph adenomas (n=11) were immunopositive for ACTH, nuclear SF-1, NeuroD1, and Tpit, but negative for DAX-1, a gonadotroph cell transcription factor. Gonadotroph adenomas (n=23) were immunonegative for ACTH and Tpit but positive for nuclear SF-1, NeuroD1, and DAX-1. SCA electron microscopy demonstrated ultrastructural features consistent with corticotroph and gonadotroph cells. As SCAs exhibit features consistent with both corticotroph and gonadotroph cytologic origin, we propose a pathologic and clinically distinct classification of SCAs as silent corticogonadotroph adenomas. PMID:20717480
Thirlwell, Christina; Will, Olivia C C; Domingo, E; Graham, Trevor A; McDonald, Stuart A C; Oukrif, Dahmane; Jeffrey, Rosemary; Gorman, Maggie; Rodriguez-Justo, Manuel; Chin-Aleong, Joanne; Clark, Sue K; Novelli, Marco R; Jankowski, Janusz A; Wright, Nicholas A; Tomlinson, Ian P M; Leedham, Simon J
According to the somatic mutation theory, monoclonal colorectal lesions arise from sequential mutations in the progeny of a single stem cell. However, studies in a sex chromosome mixoploid mosaic (XO/XY) patient indicated that colorectal adenomas were polyclonal. We assessed adenoma clonality on an individual crypt basis and completed a genetic dependency analysis in carcinomas-in-adenomas to assess mutation order and timing. Polyp samples were analyzed from the XO/XY individual, patients with familial adenomatous polyposis and attenuated familial adenomatous polyposis, patients with small sporadic adenomas, and patients with sporadic carcinoma-in-adenomas. Clonality was analyzed using X/Y chromosome fluorescence in situ hybridization, analysis of 5q loss of heterozygosity in XO/XY tissue, and sequencing of adenomatous polyposis coli. Individual crypts and different phenotypic areas of carcinoma-in-adenoma lesions were analyzed for mutations in adenomatous polyposis coli, p53, and K-RAS; loss of heterozygosity at 5q, 17p, and 18q; and aneuploidy. Phylogenetic trees were constructed. All familial adenomatous polyposis-associated adenomas and some sporadic lesions had polyclonal genetic defects. Some independent clones appeared to be maintained in advanced adenomas. No clear obligate order of genetic events was established. Top-down growth of dysplastic tissue into neighboring crypts was a possible mechanism of clonal competition. Human colorectal microadenomas are polyclonal and may arise from a combination of host genetic features, mucosal exposures, and active crypt interactions. Analyses of tumor phylogenies show that most lesions undergo intermittent genetic homogenization, but heterotypic mutation patterns indicate that independent clonal evolution can occur throughout adenoma development. Based on observations of clonal ordering the requirement and timing of genetic events during neoplastic progression may be more variable than previously thought. 2010 AGA
Bunchorntavakul, C; Bahirwani, R; Drazek, D; Soulen, M C; Siegelman, E S; Furth, E E; Olthoff, K; Shaked, A; Reddy, K R
Hepatocellular adenoma is a benign tumour associated with bleeding and malignant transformation. Obesity has been linked to hepatic tumourigenesis. To evaluate the presentation of hepatocellular adenoma in obesity, and the impact of obesity on the clinical course. Records of 60 consecutive patients (between 2005 and 2010) with a diagnosis of hepatocellular adenoma from a single tertiary centre were analysed. Fifty six of 60 patients were women, median age was 36years, 75% had history of contraceptive use, 18% were overweight and 55% were obese (BMI ≥30kg/m(2) ). Majority (63%) were asymptomatic; seven patients presented with bleeding. Single (28%) and multiple adenomas (72%) were encountered; size ranged from 1 to 19.7cm. Obesity was more often associated with multiple adenomas (85% vs. 48%, P=0.005), bilobar distribution (67% vs. 33%, P=0.01), lower serum albumin (P=0.007) and co-morbidities of fatty liver (P=0.006), diabetes (P=0.003), hypertension (P=0.006) and dyslipidemia (P=0.03). During median follow-up of 2.6years, there were no instances of bleeding, malignant transformation or death. Thirty four patients underwent therapeutic intervention (17 surgical resection, nine transarterial embolization and eight both interventions sequentially). The rate of complete resection of adenoma(s) was significantly lower in obese patients (8% vs. 69%, P=0.004). In the 26 patients without intervention, tumour size progression was more frequently observed in obese patients (33% vs. 0%, P=0.05). Three of 15 obese patients (20%) lost ≥5% body weight and there was no progression in the liver lesions. Obesity and features of metabolic syndrome were frequently observed in hepatocellular adenoma. Multiple and bilobar adenomas were more frequent in obese patients. Among patients who were conservatively managed, tumour progression was more often associated with obesity. © 2011 Blackwell Publishing Ltd.
Brenner, Hermann; Altenhofen, Lutz; Kretschmann, Jens; Rösch, Thomas; Pox, Christian; Stock, Christian; Hoffmeister, Michael
The adenoma detection rate (ADR) is an important quality indicator of screening colonoscopy; it is inversely associated with risk of interval cancers and colorectal cancer mortality. We assessed trends in the ADR in the first 10 years of the German screening colonoscopy program. We calculated age-adjusted and age-specific detection rates of nonadvanced adenomas and advanced adenomas for each calendar year based on 4.4 million screening colonoscopies conducted from 2003 through 2012 and reported to the German screening colonoscopy registry. We observed a steady and strong increase in rate of detection of nonadvanced adenomas in both sexes and all age groups. Age-adjusted rates of detection of nonadvanced adenomas increased from 13.3% to 22.3% among men and from 8.4% to 14.9% among women. This increase was mostly due to an increase in detection rates of adenomas <0.5 cm, and it is partly explained by an innovation effect (higher ADRs among incoming colonoscopists than among leaving colonoscopists, and relatively stable ADRs among continuing colonoscopists). Only modest increases were observed in detection rates of advanced adenomas (from 7.4% to 9.0% among men, and from 4.4% to 5.2% among women) and colorectal cancer. In 2012, overall ADR reached 31.3% and 20.1% in men and women, respectively. We observed a strong increase in ADRs from 2003 through 2012 in Germany. Although we cannot exclude the effects of secular trends in colorectal neoplasm prevalence, the observed increase was mainly the result of a steady increase in detection of nonadvanced adenomas (especially adenomas <0.5 cm). Further research should address potential implications for defining screening and surveillance intervals. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
Lim, Yun Jeong; Kwack, Won Gun; Lee, Youg-Sup; Hahm, Ki Baik; Kim, Young-Kwon
The obese patients with diabetes or cardiovascular risk factors are associated with increased risk of colorectal cancer as well as adenomas under the shared pathogenesis related to atherosclerosis. Here we determined the association between increased arterial stiffness and colorectal adenomas incorporating parameters including age, gender, waist circumference, body mass index, lipid profiles, fasting glucose, and blood pressure. Subjects who simultaneously underwent colonoscopies and pulse wave velocity (PWV) determinations between July 2005 and September 2006 were analyzed, based on which the subjects were classified into two groups as patients group with colorectal adenomas (n = 49) and control group (n = 200) with normal, non-polypoid benign lesions or hyperplastic polyps. Uni- and multi-variate analyses were performed to calculate the odd ratio for colon adenomas. Based on uni-variate analysis, age, waist circumference, body mass index, heart-femoral PWV (hfPWV), and brachial-ankle PWV were significantly associated with adenomas (p<0.05) and multiple logistic regression analysis showed that the heart-femoral PWV, waist circumference, and the levels of LDL-C were significant risk factor for colorectal adenoma. However, arterial stiffness did not affect the progression of colon adenoma. The finding that hfPWV, reflecting aortic stiffness, was increased in patients with colorectal adenomas lead to conclusion that patients who have prominently increased arterial stiffness can be recommended to undergo colonoscopic examinations and at the same time we also recommend counseling about the risk for atherosclerosis in those who have colorectal adenomas. PMID:21103036
Dhaoui, Amen; Nfoussi, Haifa; Kchir, Nidhameddine; Haouet, Slim
Ectopic breast tissue is defined as glands located outside of the breast. Ectopic breast tissue should be excised because it may develop benign (fibroadenoma) or malignant pathologic processes. Less than forty cases of fibroadenomas have been reported in the literature. Although lactation changes can occur, lactating adenoma in the vulva are extremely rare. Only four cases have been reported. We report a case of a young woman who presented with vulvar mass during her lactation. The mass was excised, and histology confirmed vulvar lactating adenoma associated with fibroadenoma. This is the first case of vulvar heterotopic breast lesion associating lactating adenoma and fibroadenoma.
Jass, J R; Young, P J; Robinson, E M
Three hundred and thirty six forensic necropsy specimens of large bowel were examined in order to identify subject related variables that independently predicted the following adenoma characteristics: presence, size (largest), multiplicity and high grade dysplasia. The variables were age, gender, body mass index, race (European origin versus Maori/Polynesian) and presence of hyperplastic (metaplastic) polyp(s). Subjects included 303 New Zealanders of European origin (M = 185, F = 118) yielding 149 adenomas and 251 hyperplastic polyps and 33 Maori/Polynesians (M = 25, F = 8) yielding five adenomas and one hyperplastic polyp. Independent predictors of adenoma presence as determined by regression analysis were age (p = 0.0001), presence of hyperplastic polyps (p = 0.0001) and male gender (p = 0.05). Models were poor at explaining variation in size, multiplicity, and dysplasia. Larger adenomas occurred more frequently in subjects with multiple adenomas (p = 0.03) and multiple adenomas were probably associated with hyperplastic polyps (p = 0.09) and male gender (p = 0.09) in Europeans. High grade dysplasia was more frequent in women (p = 0.05) and possibly in subjects with hyperplastic polyps (p = 0.2). Body mass index and ethnicity did not predict any adenoma characteristics, but hyperplastic polyp prevalence was influenced by European origin (p = 0.04) and to a lesser extent by body mass index (p = 0.08) as well as presence of adenoma (p = 0.0002) and age ( = 0.005). The association of hyperplastic polyp with presence, multiplicity but not size of adenoma and with a high risk group for colorectal cancer (New Zealanders of European origin) suggests that the hyperplastic polyp serves as a marker for a factor which influences neoplastic evolution at the stages of initiation/transformation but not promotion. Fifty nine per cent of individuals with adenoma(s) did not have hyperplastic polyp(s) emphasising that the last would serve only as a marker of populations and not
Allgoewer, I; Grevel, V; Philipp, K; Schmidt, P; Brunnberg, L
A case of a 6.5-year-old castrated male European Shorthair Cat with an unilateral lesion of the oculomotor nerve is described. Nuclear magnetic resonance imaging revealed a mass in the area of the pituitary gland which could be identified as a somatotrope adenoma by immunochemistry. Unlike the feline somatotrope adenoma cases described in the literature this cat showed clinically no acromegalic features or hyperglycemia. An oculomotor nerve lesion in conjunction with a feline somatotropic pituitary adenoma has also not been described before.
Tarsitano, Achille; Foschini, Maria Pia; Farneti, Paolo; Pasquini, Ernesto; Marchetti, Claudio
Pleomorphic salivary adenomas are the most common benign neoplasms affecting the salivary glands. Very occasionally however, metastatic lesions are identified in patients with a history of PSA, which, on detailed pathological evaluation, are found to exhibit all the histological hallmarks of the preceding benign lesions. Diagnosis of benign metastasizing pleomorphic adenoma of the salivary gland is extremely rare and still under debate. We present the first case-report in literature of multiple metachronous nasal cavity, scalp and encephalic metastases of a pleomorphic adenoma of the parotid gland in a young girl.
Albores-Saavedra, Jorge; Chablé-Montero, Fredy; González-Romo, Marco Aurelio; Ramírez Jaramillo, Manuel; Henson, Donald E
We report 201 gallbladder adenomas from 91 patients most of whom were adult females. Fifty-three (58%) patients had gallstones. In 83 (91%) patients the adenomas were single. One gallbladder had 102 adenomas. Histologically, 165 (82%) of 201 adenomas were classified as pyloric, 28 (14%) as intestinal, 5 (2.4%) as foveolar, and 3 (1.4%) as biliary. Two patients had intestinal-type adenomas coexisting with biliary papillomatosis. Twenty-eight percent of pyloric gland adenomas contained squamoid morules. Two pyloric gland adenomas were composed predominantly of columnar oxyphil cells. High-grade dysplasia/carcinoma in situ was identified in 44 (27%) of 165 pyloric gland adenomas and low-grade dysplasia in 25 (15%) of 165. However, only 2 (1%) invasive adenocarcinomas, both of intestinal type, arose in pyloric gland adenomas. Both patients survived more than 5 years. Intestinal-type adenomas were classified as tubular, papillary, and tubulopapillary. High-grade dysplasia/carcinoma in situ was recognized in 13 (46%) of 28 intestinal adenomas. However, only 1 (3.5%) invasive adenocarcinoma with biliary phenotype arose in an intestinal-type adenoma. Foveolar adenomas showed low-grade dysplasia, and biliary adenomas were composed of columnar cells similar to the normal biliary cells of the gallbladder. None of these tumors progressed to adenocarcinoma. MUC5AC and MUC6 labeled 44 (95%) of 46 pyloric gland adenomas, whereas CDX2 was positive in 14 (78%) of 18 intestinal adenomas and MUC2 in 6 (33%) of 18. MUC5AC and MUC6 labeled 2 foveolar adenomas, and 2 biliary adenomas expressed only CK7. The immunophenotype of gallbladder adenomas justifies their classification into pyloric, intestinal, foveolar, and biliary. Our results indicate that adenomas of the gallbladder play a minor role in the pathway of gallbladder carcinogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.
Syro, Luis V.; Rotondo, Fabio; Ramirez, Alex; Di Ieva, Antonio; Sav, Murat Aydin; Restrepo, Lina M.; Serna, Carlos A.; Kovacs, Kalman
Pituitary adenomas are common neoplasms. Their classification is based upon size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment and recurrence. Although they are considered benign tumors, some of them are difficult to treat due to their tendency to recur despite standardized treatment. Functional tumors present other challenges for normalizing their biochemical activity. Novel approaches for early diagnosis, as well as different perspectives on classification, may help to identify subgroups of patients with similar characteristics, creating opportunities to match each patient with the best personalized treatment option. In this paper, we present the progress in the diagnosis and classification of different subgroups of patients with pituitary tumors that may be managed with specific considerations according to their tumor subtype. PMID:26124750
Syro, Luis V; Rotondo, Fabio; Ramirez, Alex; Di Ieva, Antonio; Sav, Murat Aydin; Restrepo, Lina M; Serna, Carlos A; Kovacs, Kalman
Pituitary adenomas are common neoplasms. Their classification is based upon size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment and recurrence. Although they are considered benign tumors, some of them are difficult to treat due to their tendency to recur despite standardized treatment. Functional tumors present other challenges for normalizing their biochemical activity. Novel approaches for early diagnosis, as well as different perspectives on classification, may help to identify subgroups of patients with similar characteristics, creating opportunities to match each patient with the best personalized treatment option. In this paper, we present the progress in the diagnosis and classification of different subgroups of patients with pituitary tumors that may be managed with specific considerations according to their tumor subtype.
Gao, Mingtong; An, Yanyan; Huang, Zhihong; Niu, Jianyi; Yuan, Xunhui; Bai, Yun'an; Guo, Liemei
Both of Pituitary adenoma (PA) and Rathke cleft cyst (RCC) are the most common and benign sellar lesions. Generally, the origin of RCC is considered to be derived from remnants of Rathke punch, while PA is formed by proliferation of the anterior wall of Rathke pouch. Although they have a possibility to share a common embryological origin, the coexistence of PA and RCC is extremely rare. Here, the authors report a 50-year-old male patient who was found to have a large cystic sellar lesion, and surgical resection revealed components of a RCC coexisting with a PA. This collision reminded us of the possibility of RCC coexisting with PA. Furthermore, a clinicopathologic relation of them were reviewed and investigated.
Bhagavan, B S; Tiamson, E M; Wenk, R E; Berger, B W; Hamamoto, G; Eggleston, J C
The histologic and ultrastructural features of nephrogenic adenomas of the urinary bladder and urethra were studied in multiple specimens obtained from eight patients. Three of these were studied by indirect immunofluorescence for Tamm-Horsfall uromucoprotein. The lesions are uncommon benign metaplastic proliferations of urothelium, occurring most frequently in males as small cystic, papillary, or nodular masses and most often presenting with hematuria. Typically the metaplastic tubules resemble nephronic tubules. A florid atypical and pseudoinfiltrative proliferation of these tubules may led to an erroneous diagnosis of adenocarcinoma. Ultrastructural features of proximal convoluted tubules were identified in some of the tubules, but resemblance to specific segments of distal tubules was less certain. The ultrastructural features combined with the absence of Tamm-Horsfall protein in tubular lumina or cells suggest a mesonephric rather than metanephric homology. The lesions are appropriately treated by transurethral resection or fulguration, but persistent lesions were present in three patients up to 18 yeas after initial treatment.
Silva, Sindeval José da; Costa Junior, Gabriel Tadeu; Brant Filho, Adalberto Caldeira; Faria, Paulo Rogério; Loyola, Adriano Mota
Bilateral salivary gland tumors are very rare, accounting for 3% of all parotid gland tumors. Although the most common tumor with bilateral development is the Warthin tumor, pleomorphic adenomas (PA) have been diagnosed simultaneously as well, but in a smaller incidence. Because of this, the prevalence, etiology, pathogenesis, and behavior of the PA in this context are poorly understood. We present a case of bilateral metachronous PA affecting the parotid gland in a 63-year-old woman. Clinically, the lesions presented with similar aspects as seen in cases of solitary PA with slow-growing asymptomatic nodule. Both lesions were diagnosed by fine-needle aspiration biopsy at an interval of 2 years between them. A total and superficial parotidectomy for left and right tumors, respectively, was performed. Only on the left side some facial nerve branches were removed that induced partial paralysis in the patient. A review of the pertinent literature is included.
Maksimov, V A; Khodyreva, L A; Dudareva, A A; Al'bitskaia, A Iu
Of late, we observe a trend to a progressive rise of overactive bladder (OB) morbidity with age. M-cholinolytic drugs are most effective in management of OB but old patients with prostatic adenoma (PA) and comorbid pathology have a risk of acute urinary retention and serious side effects. We have the experience in combined treatment of 30 old patients with PA and OB with M-cholinolytic and alpha-adrenoblocker. The results of the treatment show its efficacy and absence of complications in the control of residual urine for 3 months. Combination of M-cholinolytic with alpha-adreboblocker significantly reduced daily diuresis, improved an accumulation function of the bladder and life quality.
Mori, H; Kawai, T; Tanaka, T; Fujii, M; Takahashi, M; Miyashita, T
An electron microscopic observation on a pancreatic tumor removed from a 34-year-old woman revealed the fine structural morphology of a functional beta cell adenoma. Characteristic PAS positive crystalline structures were frequently observed in the cytoplasm of the tumor cells. They were not bounded by a membrane and had a rectangular or irregular hexagonal shape. Highly regular patterns were seen as such as lattice or honeycomb and parallel ripple structures. They are similar to the Reinke's crystal or crystalline structures reported in human hepatocytes suffering from several different diseases and considered as a protein-carbohydrate complex. Occasionally, small paracrystalline structures appeared to indicate an immature type of these structures in the opaque fine fibrillar mass. Crystalline or paracrystalline structures were not detected in the normal pancreatic tissue removed with the tumor from the patient.
Wang, Xian-Ling; Dou, Jing-Tao; Gao, Jiang-Ping; Zhong, Wen-Wen; Jin, Du; Hui, Lüzhao; Lu, Ju-Ming; Mu, Yi-Ming
Tumors originating from ectopic adrenal tissue are relatively rare. In this article, we describe a case with Cushing's syndrome caused by an ectopic adrenal adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2 years was diagnosed to have ACTH-independent Cushing's syndrome based on endocrinological evaluation. Mutiple radiological examinations detected bilateral adrenal atrophy. When the images were investigated in a more expanded scope, a 3.0×3.5×5.3 cm mass was detected in the anterior of left renal hilum and left renal vein. The mass was successfully resected with intraoperative endoscopy and pathological evaluation revealed an ectopic adrenal tumor. It is suggested that when the endocrinlogically confirmed adrenal neoplasm could not be well and definitely localized, the possibility of ectopic adrenal should be presumed and further radiography examinations should extend to the field where ectopic adrenal usually presents.
Charbonnel, B.; Chatal, J.F.; Ozanne, P.
An adrenal tumor was discovered fortuitously in a patient with no clinical features of Cushing's syndrome. On adrenal imaging, there was good uptake in the nodule but no visualization of the contralateral adrenal. The latter was seen, however, in a second scan performed under ACTH treatment. In the hormone assessment, basal cortisol and 17-hydroxycorticoids were normal and cortisol diurnal variation was near normal, but a dexamethasone suppression test and ACTH responses to metyrapone and insulin hypoglycemia were abnormal. Eight months after excision of a spongiocytic-type adenoma, the remaining adrenal was visible on scintigram and the hormonal tests were normal. This pattern suggests that the clinical Cushing's syndrome was enough to partially suppress ACTH and, consequently, visualization of the contralateral gland.
Abshirini, Hassan; Rashidi, Iran; Saki, Nader
The pattern of clinical presentation of primary hyperparathyroidism (pHPT) has changed dramatically from a severe disease to an asymptomatic condition in Western countries. The story is completely different in Eastern countries. Bone and joint related sign and symptoms like bone pain and multiple fractures are common in these patients. Imaging and nuclear medicine studies will be helpful specially in patient who candidate for surgical removal of the abnormal parathyroid gland. Here, we present a 48-year-old man with multiple typical fractures in long bones and a single adenoma in his right inferior parathyroid gland. pHPT is a severe, symptomatic disease with serious complications and high morbidity in Iran. Advanced skeletal disease is the most common pattern of presentation. PMID:21209742
Bond, Ashley; Sarkar, Sanchoy
Adenoma detection rate (ADR) is a key component of colonoscopy quality assessment, with a direct link between itself and future mortality from colorectal cancer. There are a number of potential factors, both modifiable and non-modifiable that can impact upon ADR. As methods, understanding and technologies advance, so should our ability to improve ADRs, and thus, reduce colorectal cancer mortality. This article will review new technologies and techniques that improve ADR, both in terms of the endoscopes themselves and adjuncts to current systems. In particular it focuses on effective techniques and behaviours, developments in image enhancement, advancement in endoscope design and developments in accessories that may improve ADR. It also highlights the key role that continued medical education plays in improving the quality of colonoscopy and thus ADR. The review aims to present a balanced summary of the evidence currently available and does not propose to serve as a guideline. PMID:26265990
Akahoshi, Kazuya; Kubokawa, Masaru; Gibo, Junya; Osada, Shigeki; Tokumaru, Kayo; Yamaguchi, Eriko; Ikeda, Hiroko; Sato, Takao; Miyamoto, Kazuaki; Kimura, Yusuke; Shiratsuchi, Yuki; Akahoshi, Kazuaki; Oya, Masafumi; Koga, Hidenobu; Ihara, Eikichi; Nakamura, Kazuhiko
AIM To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) using the clutch cutter (CC) (ESD-CC) for gastric adenoma (GA). METHODS From June 2007 to August 2015, 122 consecutive patients with histological diagnoses of GA from specimens resected by ESD-CC were enrolled in this prospective study. The CC was used for all ESD steps (marking, mucosal incision, submucosal dissection, and hemostatic treatment), and its therapeutic efficacy and safety were assessed. RESULTS Both the en-bloc resection rate and the R0 resection rate were 100% (122/122). The mean surgical time was 77.4 min, but the time varied significantly according to tumor size and location. No patients suffered perforation. Post-ESD-CC bleeding occurred in six cases (4.9%) that were successfully resolved by endoscopic hemostatic treatment. CONCLUSION ESD-CC is a technically efficient, safe, and easy method for resecting GA. PMID:28744346
Bae, Il-Hong; Pakhrin, Bidur; Jee, Hyang; Shin, Nam-Shik
A 7-year-old female Eurasian otter (Lutra lutra) at the Seoul Grand Park, Korea, died after displaying depression, anorexia, weight loss and rough skin for several days. At necropsy, a solitary friable round mass, which was approximately 12 × 9 × 5 cm and mottled dark red and yellow, was found bulging from the right hepatic lobe. Microscopically, the nonencapsulated, poorly circumscribed mass was composed of solid sheets of neoplastic hepatocytes. In addition, numerous small tan foci, ranging from 0.5 to 1.0 cm in diameter, were evenly scattered throughout the pancreatic tissue. These foci were found to be nonencapsulated, well-demarcated hyperplastic nodules of the exocrine pancreatic gland. We observed neither intrahepatic nor extrahepatic metastases. Based on the gross and microscopic changes, we diagnosed the animal as having a hepatocellular adenoma accompanied by exocrine pancreatic nodular hyperplasia. PMID:17322782
Chen, Chen; Zhou, Xiaoyu; Jing, Jing; Cheng, Jing; Luo, Yu; Chen, Jiachao; Xu, Xi; Leng, Fei; Li, Xiaomu; Lu, Zhiqiang
Abnormal global DNA methylation levels are associated with many diseases. In this study, we examined long interspersed nuclear elements-1 (LINE-1) methylation as a biomarker for abnormal global DNA methylation and aldosterone-producing adenoma (APA). Tissues from 25 APA and 6 normal adrenal glands (NAs) were analyzed for LINE-1 methylation by real-time methylation-specific polymerase chain reaction. The estimated LINE-1 methylation level was then tested for correlation with the clinicopathologic parameters of APA patients. The methylation index (MI) level for LINE-1 was 0.91 in NA samples and 0.77 in APA samples (P < 0.001). For the APA samples, there were no statistical correlations between the MI level and various clinicopathologic parameters such as gender (P = 0.07). LINE-1 methylation is significantly lower in APA samples than in NA samples. LINE-1 methylation is not correlated with the clinical characteristics of APA.
De Rosa, Nicolina; Maiorino, Alfonso; De Rosa, Ilaria; Curcio, Carlo; Sellitto, Carmine; Amore, Dario
The alveolar adenoma of the lung is a rare benign tumor characterized by a proliferation of both the alveolar epithelial cells and the mesenchymal septal cells. Immunohistochemically, the epithelial cells stain for cytokeratin (CK) AE1AE3, CK7, thyroid transcription factor 1 (TTF1), and surfactant apoprotein confirming the derivation by the type 2 pneumocytes. The stromal cells are negative for these markers but they show focally smooth muscle and muscle-specific actin positivity. We describe two cases that showed immunohistochemically a CD34 positivity of the mesenchymal septal cells. This aspect has been previously described in a two cases report, but not emphasized by the authors as a distinctive feature of the lesion. We consider this CD34 positivity as a marker of immaturity or stemness of the lesional septal spindle cells, that could be responsible of the different phenotypic and morphological profile of the interstitial cells, that could be, therefore, considered neoplastic and not reactive. PMID:23118769
Jardel, P; Fakhry, N; Makeieff, M; Ferrie, J-C; Milin, S; Righini, C; Lacout, A; Costes, V; Malard, O; Marcy, P-Y; Guevara, N; Odin, G; Bensadoun, R-J; Thariat, J
Parotid pleomorphic adenoma is the most frequent tumor of salivary glands. The prognosis depends on the recurrences because they could lead to iatrogenic events (facial paralysis). Moreover the risk of malignant transformation increases with the number of local relapses. This article aims at reviewing histological and radiological criteria and the surgical techniques. To improve local control, adjuvant irradiation (in first intention or after recurrence) may be useful but is still controversial for benign tumors in young patients with a risk of radio-induced cancer. We listed studies in which adjuvant radiotherapy was used so as to define its place in the treatment strategy. Prognostic factors were found by some authors. Other studies have to be done before strong evidence-based recommendations are issued.
Gao, Hua; Xue, Yake; Cao, Lei; Liu, Qian; Liu, Chunhui; Shan, Xiaosong; Wang, Hongyun; Gu, Yi; Zhang, Yazhuo
Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups. The effects of fulvestrant on cell proliferation and cell invasion were explored in the pituitary adenoma cell lines GH3 and JT1-1. The ESR1-positive cells rates of 191/289 cases were more than 50%. And ESR1 high level cases (age≥50) were 103/133, and 88/156 in cases (age<50) (X(2) = 14.17, p = 0.0001). The average weight of the pituitary gland in F344 rat tumor model induced by 17-β-estradiol was 38.6 ± 11.2 mg, almost 6 times higher than control group (6.2 ± 1.7 mg). Fulvestrant significantly reduced the weight of the pituitary and its inhibition rate was 68.4 ± 8.3%. TUNEL assay and Western blotting showed that fulvestrant induced apoptotic cell death in vivo and in vitro. PTEN/MAPK signaling pathways were activated in response to fulvestrant treatment in GH3 cells. U0126 partly rescued cell viability of GH3 cells after fulvestrant exposure. ESR1 can be a potential target for PAs, especially for elder GHomas and NFPAs. Fulvestrant may be a new choice for the treatment of PAs.
Barazeghi, Elham; Gill, Anthony J; Sidhu, Stan; Norlén, Olov; Dina, Roberto; Palazzo, F Fausto; Hellman, Per; Stålberg, Peter; Westin, Gunnar
Primary hyperparathyroidism is characterized by enlarged parathyroid glands due to an adenoma (80-85 %) or multiglandular disease (~15 %) causing hypersecretion of parathyroid hormone (PTH) and generally hypercalcemia. Parathyroid cancer is rare (<1-5 %). The epigenetic mark 5-hydroxymethylcytosine (5hmC) is reduced in various cancers, and this may involve reduced expression of the ten-eleven translocation 1 (TET1) enzyme. Here, we have performed novel experiments to determine the 5hmC level and TET1 protein expression in 43 parathyroid adenomas (PAs) and 17 parathyroid carcinomas (PCs) from patients who had local invasion or metastases and to address a potential growth regulatory role of TET1. The global 5hmC level was determined by a semi-quantitative DNA immune-dot blot assay in a smaller number of tumors. The global 5hmC level was reduced in nine PCs and 15 PAs compared to four normal tissue samples (p < 0.05), and it was most severely reduced in the PCs. By immunohistochemistry, all 17 PCs stained negatively for 5hmC and TET1 showed negative or variably heterogeneous staining for the majority. All 43 PAs displayed positive 5hmC staining, and a similar aberrant staining pattern of 5hmC and TET1 was seen in about half of the PAs. Western blotting analysis of two PCs and nine PAs showed variable TET1 protein expression levels. A significantly higher tumor weight was associated to PAs displaying a more severe aberrant staining pattern of 5hmC and TET1. Overexpression of TET1 in a colony forming assay inhibited parathyroid tumor cell growth. 5hmC can discriminate between PAs and PCs. Whether 5hmC represents a novel marker for malignancy warrants further analysis in additional parathyroid tumor cohorts. The results support a growth regulatory role of TET1 in parathyroid tissue.
Losa, Marco; Bogazzi, Fausto; Cannavo, Salvo; Ceccato, Filippo; Curtò, Lorenzo; De Marinis, Laura; Iacovazzo, Donato; Lombardi, Giuseppe; Mantovani, Giovanna; Mazza, Elena; Minniti, Giuseppe; Nizzoli, Maurizio; Reni, Michele; Scaroni, Carla
Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.
Saiki, Hirotsugu; Nishida, Tsutomu; Yamamoto, Masashi; Hayashi, Shiro; Shimakoshi, Hiromi; Shimoda, Akiyoshi; Amano, Takahiro; Sakamoto, Aisa; Otake, Yuriko; Sugimoto, Aya; Takahashi, Kei; Mukai, Kaori; Matsubara, Tokuhiro; Nakajima, Sachiko; Fukui, Koji; Inada, Masami; Yamamoto, Katsumi; Tokuda, Ryozo; Adachi, Shiro
Background and study aims: Sessile serrated adenoma/polyps (SSA/Ps) have a different potential than traditional adenomatous polyps for developing into malignant colorectal cancer. However, little is known about the coexistent cancer rate. Here, we evaluate the frequency of carcinoma in serrated polyps removed by endoscopic resection (ER). Patients and methods: This was a retrospective single-center cohort study of consecutive patients with colorectal polyps who underwent ER from March 2003 to October 2014. We determined the frequency of serrated polyps among all resected colorectal polyps and analyzed the clinicopathological findings as well as the frequency and characteristics of coexistent carcinoma in the serrated polyps resected by ER based on pathology reports. Results: A total of 21,048 polyps from 15,326 patients were identified, including 15,984 traditional adenomatous polyps (75.9 %), 621 SSA/Ps (3.0 %), 136 traditional serrated adenomas (TSAs) (0.6 %), 1,121 hyperplastic polyps (5.3 %), and 3,186 polyps of other types (15.1 %). The clinical and endoscopic findings of SSA/Ps revealed a male predominance (68.6 %), with 61.7 % of the polyps located in the proximal colon. Males accounted for 77.2 % of all patients with TSAs, and 77.2 % of these polyps were located in the distal colon. The mean sizes of the SSA/Ps and TSAs were 8.8 and 10.7 mm, respectively. Among the SSA/Ps, 8 (1.3 %) cases had coexistent carcinoma, and 1 (0.7 %) patient with TSA showed coexistent carcinoma. In the patients with SSA/Ps, female sex and a tumor size ≥ 10 mm were predictive factors for coexistent carcinoma. Conclusions: The frequency of SSA/Ps with carcinoma was lower than that for traditional adenoma. Female sex and tumor size ≥ 10 mm were significant predictive factors for coexistent carcinoma. PMID:27092327
Pereira, Michele Conceição; Pereira, Alessandro Antônio Costa; Hanemann, João Adolfo Costa
Canalicular adenoma is an uncommon benign salivary gland neoplasm that has a marked predilection for occurrence in the upper lip. It is composed of columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. This tumor has an excellent prognosis after conservative surgical treatment in all locations. In the present report we describe, using immunohistochemistry, the expression of cytokeratins (CK), S-100 protein and EMA in a canalicular adenoma that arose in the upper lip of a 55-year-old female. Cells of the canalicular adenoma showed an immunohistochemical profile that indicates an excretory duct origin: most of these cells positively expressed AE1/AE3 cytokeratins and S100 protein. A comparison of the immunohistochemical features of canalicular adenoma with other salivary gland neoplasms that share similar histological features is discussed.
Ismı, Onur; Vayısoğlu, Yusuf; Arpaci, Rabia Bozdogan; Eti, Can; Pütürgeli, Tuğçe; Gorur, Kemal; Ozcan, Cengiz
Carcinoma ex pleomorphic adenoma (CEPA) is the malignant salivary gland tumor originating from primary (de novo) or recurrent pleomorphic adenoma. Although parotid gland is the most common site, it can also be seen in submandibular gland or minor salivary glands. It can be seen rarely in head and neck region, such as oral cavity, trachea, nasal cavity and lacrimal gland. Although pleomorphic adenoma cases originating from ectopic salivary gland tissue in the neck region are present in the English literature, there is no published pleomorphic adenoma ex carcinoma case. In this case report we presented a CEPA as a 7.5 cm long neck mass in a 72-year-old woman originating from the submandibular region apart from submandibular gland. Difficulties in diagnosis and way to appropriate treatment are discussed with current literature.
González-García, Raúl; Nam-Cha, Syong H; Muñoz-Guerra, Mario F; Gamallo-Amat, C
Basal cell adenoma of the salivary glands is an uncommon type of monomorphous adenoma. Its most frequent location is the parotid gland. It usually appears as a firm and mobile slow-growing mass. Histologically, isomorphic cells in nests and interlaced trabecules with a prominent basal membrane are observed. It is also characterized by the presence of a slack and hyaline stroma and the absence of myxoid or condroid stroma. In contrast to pleomorphic adenoma, it tends to be multiple and its recurrence rate after surgical excision is high. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma is mandatory. We describe a case of basal cell adenoma of the parotid gland. We also review the literature and discuss the diagnosis and management of this rare entity.
Dou, Wanchen; Di, Xiao; Wang, Renzhi; Zhu, Huijuan; Yao, Yong; Deng, Kan; Feng, Ming; Li, Guilin; Wei, Junji
The feasibility of transsphenoidal approach under a guidance of neuronavigation was explored to remove pituitary adenomas for patients with McCune-Albright syndrome (MAS). From August, 2008 to July, 2010, there were 5 patients diagnosed with MAS associated with a pituitary adenoma in our department of Peking Union Medical College Hospital. All the patients underwent transsphenoidal surgery for the removal of pituitary adenomas with the assistant of neuronavigation and all the procedures went uneventfully. Four of the five patients have got cured radiologically by imaging and 3 of them have got cured based on endocrinological criteria. Transsphenoidal approach under the neuronavigational guidance is a safe and effective management for the MAS patients with pituitary adenomas.
Bakhtiar, Yuriz; Hanaya, Ryosuke; Tokimura, Hiroshi; Hirano, Hirofumi; Oyoshi, Tatsuki; Fujio, Shingo; Bohara, Manoj; Arita, Kazunori
Apart from the radiologic features regarding size and invasiveness, we had noticed some differences in morphology among types of pituitary adenomas. We conducted this study to verify the differences in radiologic morphology between growth hormone producing pituitary adenomas (GHoma) and nonfunctioning pituitary adenomas (NFoma). Pre-surgical magnetic resonance images (MRIs) were assessed in 50 cases of GHoma and 50 cases of NFoma. Geometric parameters on MRI were set in accordance with sellar anatomy. Intensity of T1-weighted image was not different between the two groups, but hypo-intensity of T2-weighted image was more frequently seen in GHoma. Predominant inferior extension of tumor was seen mostly in GHoma (88 vs. 38%). Extension of the tumor to the superior compartment of cavernous sinus was more frequent in NFoma. Pituitary gland was generally located superior to GHoma and postero-superior to NFoma. Growth characteristics of pituitary adenoma were confirmed to differ between GHoma and NFoma.
Wang, Qinying; Chen, Haihong; Wang, Shenqing
Basal cell adenoma is an uncommon benign salivary gland neoplasm, presenting isomorphic basaloid cells with a prominent basal cell layer. Basal cell adenoma arising from the nasal septum is exceptionally rare. Reports on positron emission tomography with 2-deoxy-2-fluorine-18-fluoro-D-glucose (18FDG-PET) imaging for basal cell adenoma are limited. Here, we present the case of a 49-year-old man who had the symptoms of intermittent repeated bleeding from the left nose for half a year. 18FDG-PET scanning showed increased accumulation of 18FDG with its characteristic benign pathology has a potential to malignancy. After removal of the mass, the patient became symptom free. Pathology showed basal cell adenoma. The evidence of active and growing cells was present in the specimen.
Background: Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis. Objective: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conduc...
Portinari, Mattia; Liboni, Alberto; Feo, Carlo V
Hepatic adenomas are uncommon benign tumours of the liver which may eventually present with acute onset following rupture of the lesion and haemorrhage. We present here a unique case of strangulated adenoma of the liver presenting as acute abdomen. A 27-year-old woman taking oral contraceptives, presented to the emergency department with abdominal pain, palpable abdominal mass, fever, and neutrophilia. An abdominal ultrasound showed a 3-cm hepatic nodule and an 11-cm mesogastric mass. Computed tomography of the abdomen revealed a 2.3-cm liver adenoma and a 13-cm pedunculated mass of the liver showing no contrast enhancement suggestive of pedicle torsion with ischemia of the mass. The patient underwent an emergent open resection of the strangulated liver mass, she recovered without complications, and was discharged home after three days. Final pathology confirmed an hepatocellular adenoma with areas of necrosis and hemorrhage. The clinical significance of the disease is discussed.
Tarsitano, A; Pizzigallo, A; Giorgini, F; Marchetti, C
Pleomorphic adenoma is the most common type of all salivary gland tumours. Although uncommon, cases of giant pleomorphic adenomas have been described in the medical literature, the majority involving the parotid gland. This paper describes an unusual case of a giant adenoma arising in the parotid gland. The patient underwent surgical resection of the giant tumour, which was one of the largest pleomorphic adenoma reported in recent literature. This case has prompted us to evaluate the behaviour of those benign tumours, which suggested that aesthetic and social morbidity is sufficient to justify, when possible, early tumour excision, despite the relatively low risk of malignant transformation. Management of this unusual tumour is discussed, and the literature on giant parotid tumours is reviewed.
Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc
Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751
Namysłowski, Grzegorz; Scierski, Wojciech; Misiołek, Maciej; Czecior, Eugeniusz; Lange, Dariusz
Ceruminous adenoma (ceruminoma) of the external auditory meatus is a rare neoplasm with benign clinical behavior. This tumor is mainly composed of the ceruminous gland cells (modified apocrine sweat glands). These glands are localized deep in the skin mostly in the cartilaginous part of the external auditory meatus. The most often symptom of the ceruminous adenoma of external auditory meatus is the unilateral conductive hearing loss. Occasionally symptoms of this tumor (pain, otorrhoea) can result from an otitis externa secondary to meatus obstruction. Ceruminous adenoma should be radical excised with adequate margins of the normal tissues. The prognosis of these tumors is good. The difficulties of nomenclature, histological structure of the auditory external meatus ceruminoma, as well as symptomatology, treatment and clinical behavior are discussed on the basis of the literature. A case of histologically confirmed ceruminoma (ceruminous adenoma) of the external auditory meatus in a surgically treated 53 years old men is presented.
Feng, Jie; Hong, Lichuan; Wu, Yonggang; Li, Chuzhong; Wan, Hong; Li, Guilin; Sun, Yilin; Yu, Shenyuan; Chittiboina, Prashant; Montgomery, Blake; Zhuang, Zhengping; Zhang, Yazhuo
Non-functioning pituitary adenomas (NFPAs) may be locally invasive. Surgery is a treatment option, but unlike the case for functional pituitary adenomas, there are almost no drug treatments available for NFPAs. Markers of invasiveness are needed to guide therapeutic decision-making and identify potential adjuvant drugs. Owing to the highly heterogeneous nature of NFPAs, little is known regarding the subtype-specific gene expression profiles associated with invasiveness. To identify important biomarkers of invasiveness, we selected 23 null cell adenomas and 20 oncocytomas. These tumors were classified as invasive or non-invasive adenomas based on magnetic resonance imaging, pathology slides and surgical findings. Firstly, we observed that there were significant differences in expression between invasive (n = 3) and non-invasive (n = 4) adenomas by gene expression microarray. A total of 1,188 genes were differentially expressed in the invasive and non-invasive adenomas. Among these 1,188 genes, 578 were upregulated and 610 were downregulated in invasive adenomas. Secondly, the expression of ENC1, which displayed the significant alterations, was further confirmed by qRT-PCR and Western blot analysis in all 43 tumor samples and three normal pituitary glands. Low levels of ENC1 were found in tumor samples, while high levels were detected in normal pituitary glands. Interestingly, the ENC1 expression level was low in invasive null cell adenomas compared with non-invasive adenomas, but this relationship was not observed in invasive oncocytomas. Immunohistochemistry also demonstrated that the staining of ENC1 was different between invasive and non-invasive null cell adenomas. In addition, bioinformatics studies, including gene ontology and protein interaction analyses, were also performed to better understand the critical role of ENC1 in the development and progression of null cell adenomas and oncocytomas. Consequently, ENC1 may be an important biomarker for null cell
Brand, Linda; Munding, Johanna; Pox, Christian P; Ziebarth, Wibke; Reiser, Markus; Hüppe, Dietrich; Schmiegel, Wolff; Reinacher-Schick, Anke; Tannapfel, Andrea
Endoscopic polypectomy significantly reduces the incidence of colorectal cancer, but recurrence rates are high, especially for adenomas with advanced histology. The present guidelines recommend re-colonoscopy 3 to 5 years later. Due to limited resources, more precise predictions of adenoma recurrence are required. Lesions from 109 patients with colorectal adenomas recruited into a randomized, placebo-controlled chemoprevention trial with mesalazine were included. Formalin-fixed paraffin-embedded tissue sections were stained for ß-catenin, cyclooxygenase-2 (Cox-2), and p53 and scored. Adenoma recurrence rates were recorded after 3 years and associated with clinical and immunohistochemical parameters by contingency table analysis. After 3 years, adenomas recurred in 51.4% of patients. Out of 109 adenomas, 95 met at least one criterion of advanced adenoma (size >1 cm, villous histology, high-grade intraepithelial neoplasia). There was no influence of age, sex, size or villous histology on adenoma reappearance, whilst the number of adenomas at baseline was positively associated with recurrence (p = 0.003). In contrast, ß-catenin nuclear localisation, Cox-2 expression and p53 nuclear expression were significantly associated with adenoma recurrence after 3 years (ß-catenin: p = 0.002; Cox-2: p = 0.001; p53: p = 0.001). Combining these three markers led to a negative predictive value of 88.5% and a sensitivity of 94.6%. (OR = 13.54) CONCLUSIONS: Scoring each single parameter and, more strongly, the combination of all three parameters of the expression of ß-catenin, Cox-2 and p53 in colorectal adenoma tissue may be a useful negative predictor for adenoma recurrence in patients with advanced colorectal adenomas.
Thomas, Laura Elizabeth; Hurley, Joanna J; Meuser, Elena; Jose, Sian; Ashelford, Kevin E; Mort, Matthew; Idziaszczyk, Shelley; Maynard, Julie; Leon Brito, Helena; Harry, Manon; Walters, Angharad; Raja, Meera; Walton, Sarah Jane; Dolwani, Sunil; Williams, Geraint T; Morgan, Meleri; Moorghen, Morgan; Clark, Susan K; Sampson, Julian R
Duodenal polyposis and cancer are important causes of morbidity and mortality in familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). This study aimed to comprehensively characterize somatic genetic changes in FAP and MAP duodenal adenomas to better understand duodenal tumorigenesis in these disorders.
Experimental Design: Sixty-nine adenomas were biopsied during endoscopy in 16 FAP and 10 MAP patients with duodenal polyposis. Ten FAP and 10 MAP adenomas and matched blood DNA samples were exome sequenced, 42 further adenomas underwent targeted sequencing and 47 were studied by array comparative genomic hybridization. Findings in FAP and MAP duodenal adenomas were compared to each other and to the reported mutational landscape in FAP and MAP colorectal adenomas.
Results: MAP duodenal adenomas had significantly more protein-changing somatic mutations (P = 0.018), truncating mutations (P = 0.006) and copy number variants (P = 0.005) than FAP duodenal adenomas, even though MAP patients had lower Spigelman stage duodenal polyposis. Fifteen genes were significantly recurrently mutated. Targeted sequencing of APC, KRAS, PTCHD2 and PLCL1 identified further mutations in each of these genes in additional duodenal adenomas. In contrast to MAP and FAP colorectal adenomas, neither exome nor targeted sequencing identified WTX mutations (P=0.0017).
Conclusions: The mutational landscapes in FAP and MAP duodenal adenomas overlapped with, but had significant differences to those reported in colorectal adenomas. The significantly higher burden of somatic mutations in MAP than FAP duodenal adenomas despite lower Spigelman stage disease could increase cancer risk in the context of apparently less severe benign disease. Copyright ©2017, American Association for Cancer Research.
Park, Sung Yoon; Park, Byung Kwan; Park, Jung Jae; Kim, Chan Kyo
The purpose of this study was to quantitatively differentiate adrenal hyperplasia from adenoma with the use of adrenal CT protocols. Between January 2004 and November 2012, a total of 156 patients (69 men and 87 women; mean age, 48.9 years) underwent unenhanced CT, early contrast-enhanced CT, and delayed contrast-enhanced CT before undergoing adrenalectomy. Of these patients, 142 had 144 adenomas and 14 had nodular (n = 12) or diffuse (n = 2) hyperplasia. An ROI was placed on 144 adenomas and 27 hyperplastic nodules that were 1 cm or larger or on the four thickest areas of both adrenal glands. The number of each type of lesion and the attenuation value, absolute percentage washout (APW), and relative percentage washout (RPW) associated with hyperplasia and adenoma were compared. The reference standard was pathologic examination. A mixed model and the Fisher exact test were used for statistical analysis. On unenhanced CT, the mean (± SD) attenuation value for hyperplasia and adenoma was 18.8 ± 10.8 HU and 13.7 ± 15.6 HU, respectively (p = 0.375). When a threshold of 10 HU or lower was used, 22.6% of hyperplastic lesions (7/31) were misdiagnosed as adenomas. The mean APW associated with hyperplasia and adenoma was 73.7% ± 9.3% and 67.3% ± 26.2%, respectively (p = 0.449), whereas the mean RPW for hyperplasia and adenoma was 61.2% ± 9.2% and 59.9% ± 23.0%, respectively (p = 0.625). When an APW threshold of 60% or higher or an RPW threshold of 40% or higher was used, 100% of hyperplastic lesions (31/31) were misdiagnosed as adenoma. Three or more nodules were detected in 33.3% of patients with nodular hyperplasia (4/12) but in none of the patients with adenoma (p < 0.001). Adrenal hyperplasia cannot be quantitatively differentiated from adenoma because there is significant overlap in findings from CT densitometry and assessment of percentage washout. However, the presence of three or more nodules increases the likelihood of nodular hyperplasia.
Wang, Junwen; Voellger, Benjamin; Benzel, Julia; Schlomann, Uwe; Nimsky, Christopher; Bartsch, Jörg W; Carl, Barbara
Invasion of tumor cells critically depends on cell-cell or cell-extracellular matrix interactions. Enzymes capable of modulating these interactions belong to the proteinase families of ADAM (a disintegrin and metalloprotease) and MMP (matrix metalloprotease) proteins. Our objective is to examine their expression levels and evaluate the relationship between expression levels and cavernous sinus invasion in pituitary adenomas. Tissue samples from 35 patients with pituitary adenomas were analyzed. Quantitative real-time polymerase chain reaction (qPCR) was employed to assess mRNA expression levels for ADAM and MMP genes. Protein levels were examined using immunohistochemistry and Western Blot. Correlation analyses between expression levels and clinical parameters were performed. By silencing ADAM12 and MMP-14 with siRNA in a mouse pituitary adenoma cell line (TtT/GF), their cellular effects were investigated. In our study, nine women and 26 men were included, with a mean age of 53.1 years (range 15-84 years) at the time of surgery. There were 19 cases with cavernous sinus invasion. The proteins ADAM12 and MMP-14 were significantly up-regulated in invasive adenomas compared to noninvasive adenomas. Both human isoforms of ADAM12 (ADAM12L and ADAM12s) were involved in tumor invasion; moreover, ADAM12L was found to correlate positively with Ki-67 proliferation index in pituitary adenomas. In TtT/GF pituitary adenoma cells, silencing of ADAM12 and MMP-14 significantly inhibited cell invasion and migration, respectively, whereas only silencing of ADAM12 suppressed cell proliferation. We conclude that ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas, which qualifies these proteins in diagnosis and therapy.
Figueiredo, Jane C; Mott, Leila A; Giovannucci, Edward; Wu, Kana; Cole, Bernard; Grainge, Matthew J; Logan, Richard F; Baron, John A
Observational data suggest that lower folate status is associated with an increased risk of colorectal neoplasia, implying that folate may be useful as a chemopreventive agent. We conducted a combined analysis of three large randomized trials of folic acid supplementation for the prevention of metachronous adenomas in patients with an adenoma history. Participants included 2,632 men and women who had a history of adenomas randomized to either 0.5 or 1.0 mg/day of folic acid or placebo and who had a follow-up endoscopy 6 to 42 months after randomization [mean = 30.6 (standard deviation = 8.1) months]. We used random-effects meta-analysis to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The RR comparing folic acid versus placebo was 0.98 (95% CI = 0.82-1.17) for all adenomas and 1.06 (95% CI = 0.81-1.39) for advanced lesions. Folic acid was associated with a nonsignificant decreased risk of any adenoma among subjects in the lowest quartile of baseline plasma folate (≤ 11 nmol/L) and no effect among individuals in the highest quartile (> 29 nmol/L, p for trend = 0.17). There was a nonsignificant trend of decreasing risk of any adenoma associated with folic acid supplements with increasing alcohol intake. During the early follow-up reported here, more deaths occurred in the placebo group than in the folic acid group (1.7% vs. 0.5%, p = 0.002). In conclusion, after up to 3.5 years of folic acid use, there is no clear decrease or increase in the occurrence of new adenomas in patients with a history of adenoma. Copyright © 2010 UICC.
Pieterse, S.; Dinning, T.A.; Blumbergs, P.C.
A case is reported in which a fibrosarcoma developed 20 years after irradiation of a pituitary chromophobe adenoma. This rare lesion, like most of the other documented postirradiation pituitary sarcomas, was a combination of fibrosarcoma and pituitary adenoma. These lesions tend to behave in a characteristic fashion, with onset after a long latent interval following irradiation, growth to a large size, and failure to metastasize.
Leese, G.; Jeffreys, R.; Vora, J.
A patient with a pituitary adenoma secreting follicle-stimulating hormone with co-existent primary hyperaldosteronism is described. After his second transsphenoidal surgery, the patient developed a Staphylococcus aureus pituitary abscess. Symptoms improved after abscess drainage. Subsequent cabergoline therapy arrested the deterioration of symptoms. and decreased serum follicle-stimulating hormone concentrations. Cabergoline may be a useful treatment for aggressively growing non-prolactin-secreting pituitary adenomas. PMID:9307745
Bălinişteanu, Bogdan; Cîmpean, Anca Maria; Ceauşu, Amalia Raluca; Corlan, Ana Silvia; Melnic, Eugen; Raica, Marius
Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study included 50 pituitary adenomas. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method. Additional paraffin sections from each tumor were immunostained using primary antibodies against the following pituitary hormones: somatotropin (STH), prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). To detect the expression of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The percentage of Ki-67 positive nuclei (Ki-67 labeling index) was assessed by counting approximately 1000 nuclei of the tumor cells at ×400 magnification. Out of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative activity, and the proliferation rate was variable in this group. The overall mean Ki-67 labeling index was 1.59 ± 1.47, ranging from 0.3% to 6.6%. In 5 cases, the Ki-67 index was >3%, all of them being prolactinomas. The Ki-67 index was higher in PRL-secreting adenomas (mean ± SD was 3.37 ± 1.80, range 0.9 - 6.6%). Our study provides the evidence that a higher Ki-67 value is associated with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL-secreting adenomas).
Yoshimitsu, Shinichiro; Morita, Makiko; Hamachi, Tadamichi; Tabata, Shinji; Abe, Hiroshi; Tajima, Osamu; Uezono, Kousaku; Ohnaka, Keizo; Kono, Suminori
Folate-mediated one-carbon metabolism has been implicated in colorectal carcinogenesis. We investigated associations of functional genetic polymorphisms of methionine synthase (MTR), MTR reductase (MTRR), and thymidylate synthase (TS) with colorectal adenomas. The study subjects were 455 cases of colorectal adenomas and 1052 controls with no polyp at colonoscopy. Genotypes were determined for MTR A2756G, MTRR A66G and two polymorphisms in the TS gene, 28-bp tandem repeat polymorphism in the promoter enhancer region (TSER) and 6-bp deletion polymorphism at position 1494 in the 3' untranslated region (TS 1494del6). We also examined the alcohol-genotype and gene-gene interactions on adenoma risk. The GG genotype of MTR A2756G was associated with an increased risk of colorectal adenomas; odds ratios for AG and GG versus AA genotype were 0.99 (95% confidence interval 0.78-1.26) and 1.72 (1.04-2.82), respectively. The increase in the risk associated with MTR 2756GG genotype was evident in men with high alcohol consumption (≥30 mL/d), but not in those with low alcohol consumption (interaction P = 0.03). Men who were homozygous for the TSER double-repeat allele had a slightly decreased risk of colorectal adenomas as compared with those homozygous for the TSER triple-repeat allele. Neither MTRR A66G nor TS 1494del6 was associated with colorectal adenomas. There was no measurable interaction either between MTR A2756G and MTRR A66G or between TSER and TS 1494del6. MTR A2756G appears to be associated with colorectal adenoma risk differently according to alcohol consumption. The MTR-catalyzed reaction may play an important role in the development of colorectal adenomas.
Mooney, Michael A; Simon, Elias D; Little, Andrew S
The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.
Skorić, T; Korsić, M; Zarković, K; Plavsić, V; Besenski, N; Breskovac, L; Giljević, Z; Paladino, J
A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.
Guilera, Magda; Connelly-Frost, Alexandra; Keku, Temitope O; Martin, Christopher F; Galanko, Joseph; Sandler, Robert S
Although both physical inactivity and obesity have been associated with an increased risk of colorectal adenomas, it is unclear whether physical activity modifies the relationship between obesity and colorectal adenomas or through what mechanism this might occur. The aim of this study is to evaluate whether physical activity modifies the relationship between body mass index (BMI) and colorectal adenomas and whether apoptosis is a plausible mechanism responsible for this effect modification. Study subjects were part of a large, cross-sectional study, the Diet and Health Study III. Consecutive patients underwent colonoscopy between August 1998 and March 2000. Apoptosis was measured by morphological evaluation of hematoxylin and eosin-stained sections obtained from rectal pinch biopsy samples. There were 226 patients with adenomas and 494 adenoma-free controls. When comparing overweight subjects with the referent group (high physical activity/normal BMI), the relative odds of having an adenoma decreased as physical activity increased: low (odds ratio, OR=1.6; 95% confidence interval, CI=0.7-3.4); moderate (OR=1.1; 95% CI=0.6-2.0); and high (OR=0.8; 95% CI=0.4-1.6). When comparing obese subjects with the referent group, relative odds of having an adenoma were increased regardless of physical activity level. Apoptosis was not associated with obesity or physical activity. Our results suggest that physical activity may modify the association between obesity and colorectal adenoma until a high level of obesity is achieved. Apoptosis does not appear to be associated with obesity or physical activity.
Losa, Marco; Spatola, Giorgio; Albano, Luigi; Gandolfi, Alessandra; Del Vecchio, Antonella; Bolognesi, Angelo; Mortini, Pietro
Gamma Knife radiosurgery is often used in pituitary adenomas. Aim of our study is to describe the characteristics and long-term outcome of patients with adenoma recurrence after Gamma Knife radiosurgery. We conducted a retrospective analysis of patients with pituitary adenoma treated by Gamma Knife radiosurgery between 1994 and 2014. Tumor recurrence was labeled as "in field" when the tumor growth occurred adjacent or within the prescribed isodose, whereas it was classified as "out of field" when the tumor growth occurred outside the prescribed isodose. Five hundred forty-three patients were included, 272 (50.1 %) had a nonfunctioning pituitary adenoma (NFPA) and 271 (49.9 %) patients had a hormone secreting-pituitary adenoma. The median follow-up after GKRS was 78 months (IQR, 36-125 months). Thirty-nine patients (7.2 %) had recurrence of disease and it was more frequent in patients with NFPA than in patients with hormone secreting adenomas (9.6 % vs. 4.8 %). The 10-yr progression-free survival in patients with NFPA was 78.7 % (95 % CI 69.5 - 87.9 %), as compared with 93.3 % (95 % CI 89.3 - 97.3 %; p < 0.01) in hormone secreting adenomas. Tumor recurrence was "in field" in 17 cases (43.6 %) and "out of field" in 22 cases (56.4 %). Seven of the 39 patients with recurrence died despite further treatments. Six of these patients had an "in field" recurrence. Recurrence of a pituitary adenoma after GKRS may occur several years after initial treatment. Distinction between "in field" and "out of field" tumor recurrence probably reflects two different pathophysiological mechanisms and may have prognostic importance.
Hashimoto, Luis; Dabbs, Andy; Sewell, Patrick; Doherty, Mike
A case of multiple hepatic adenomas associated with birth control pills in a 25-year-old female is presented. Her only complaint was abdominal pain, and an elevated alkaline phosphatase was the only laboratory abnormality. The largest adenoma was located in the caudate lobe and was resected. The other two were small, located deep in the right lobe, and treated with radiofrequency ablation. Currently, the patient is asymptomatic and her alkaline phosphatase has returned to normal levels.
Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.
The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036
Kim, Nam Hee; Suh, Jung Yul; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Choi, Kyuyong; Jung, Yoon Suk
Limited data are available regarding the associations between parameters of glucose and lipid metabolism and the occurrence of metachronous adenomas. We investigated whether these parameters affect the occurrence of adenomas detected on surveillance colonoscopy. This longitudinal study was performed on 5289 subjects who underwent follow-up colonoscopy between 2012 and 2013 among 62171 asymptomatic subjects who underwent an initial colonoscopy for a health check-up between 2010 and 2011. The risk of adenoma occurrence was assessed using Cox proportional hazards modeling. The mean interval between the initial and follow-up colonoscopy was 2.2±0.6 years. The occurrence of adenomas detected by the follow-up colonoscopy increased linearly with the increasing quartiles of fasting glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglycerides measured at the initial colonoscopy. These associations persisted after adjusting for confounding factors. The adjusted hazard ratios for adenoma occurrence comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, and triglycerides were 1.50 [95% confidence interval (CI), 1.26-1.77; p(trend)<0.001], 1.22 (95% CI, 1.04-1.43; p(trend)=0.024), 1.22 (95% CI, 1.02-1.46; p(trend)=0.046), 1.36 (95% CI, 1.14-1.63; p(trend)=0.004), and 1.19 (95% CI, 0.99-1.42; p(trend)=0.041), respectively. In addition, increasing quartiles of low-density lipoprotein-cholesterol and apolipoprotein B were associated with an increasing occurrence of adenomas. The levels of parameters of glucose and lipid metabolism were significantly associated with the occurrence of adenomas detected on surveillance colonoscopy. Improving the parameters of glucose and lipid metabolism through lifestyle changes or medications may be helpful in preventing metachronous adenomas.
Yu, ChuanTing; Li, JiXia; Sun, FengNan; Cui, JinPeng; Fang, HuaLi; Sui, GuoLang
Background Although pituitary adenoma is a malignant tumor, it can present as invasive growth in some cases. MicroRNA (miR)-26a has been found to be abnormally highly expressed in pituitary adenoma, indicating possible involvement in pathogenesis. As a known target gene of miR-26a, PLAG1 has abnormally low expression in pituitary adenoma. The correlation between miR-26a or PLAG1 expressional abnormality and occurrence of pituitary adenoma is still unknown, as is its association with invasiveness of pituitary adenoma. Material/Methods Pituitary adenoma tissues, including both invasive and non-invasive subtypes, were collected from our Neurosurgery Department, in parallel with normal pituitary tissues from postmortem autopsy. qRT-PCR was used to detect mRNA expression of miR-26a and PLAG1, while Western blotting was used to test PLAG1 protein expression. The correlation between miR-26a and PLAG1, and with pathological features, were analyzed. ROC analysis revealed the utility of miR-26a and PLAG1 in differential diagnosis of invasive/non-invasive pituitary tumors and in analyzing their effects on patient prognosis. Results MiR-26a was remarkably upregulated in pituitary tumors, while PLAG1 was downregulated, especially in invasive pituitary tumors. miR-26a and PLAG1 had higher diagnostic values for differentiating between invasive and non-invasive pituitary tumors (AUC=0.889 and 0.818, respectively). Those patients with miR-26 overexpression and PLAG1 downregulation had unfavorable prognosis. miR-26 and PLAG1 are independent factors affecting patient diagnosis. Conclusions MiR-26a can facilitate occurrence of pituitary tumor and invasiveness, probably via inhibiting PLAG1 expression. PMID:28012286
Xiao, Zhengzheng; Liu, Qin; Zhao, Boxi; Wu, Jun; Lei, Ting
The hypoxia inducible factor 1 α (HIF-1α) activity has been associated with various hemorrhagic events. The biological role of HIF-1α in the hemorrhagic transformation of pituitary adenomas remains unknown. We hypothesized that fast growing tumor cells tend to predispose themselves to sublethal hypoxia and activate the HIF-1α signaling pathway, leading to hemorrhagic transformation in pituitary adenomas. Here, we used apoplectic and non-apoplectic pituitary adenomas to determine the involvement of HIF-1α signaling in intratumoral hemorrhage. We employed HIF-1α overexpression/knockdown strategies to examine the association between HIF-1α signaling and hemorrhagic presentation in vitro and in vivo. In support of our hypothesis, compared with non-hemorrhagic pituitary adenomas, higher cellular proliferation was observed in hemorrhagic ones and it correlated with increased HIF-1α signaling. HIF-1α overexpression activated its downstream genes, vascular endothelial growth factor and the proapoptotic BNIP3, in MMQ pituitary adenoma cells and this up-regulation was attenuated by HIF-1 siRNA. In vivo studies using MMQ cell xenografts in nude mice showed that HIF-1α overexpression significantly promoted hemorrhagic transformation. Our study indicates that tumor hypoxia, following rapid tumor growth, may promote hemorrhagic transformation in pituitary adenomas via the HIF-1α signaling pathway.
Sekine, Shigeki; Yamashita, Satoshi; Tanabe, Taro; Hashimoto, Taiki; Yoshida, Hiroshi; Taniguchi, Hirokazu; Kojima, Motohiro; Shinmura, Kazuya; Saito, Yutaka; Hiraoka, Nobuyoshi; Ushijima, Toshikazu; Ochiai, Atsushi
The molecular mechanisms underlying the serrated pathway of colorectal tumourigenesis, particularly those related to traditional serrated adenomas (TSAs), are still poorly understood. In this study, we analysed genetic alterations in 188 colorectal polyps, including hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), TSAs, tubular adenomas, and tubulovillous adenomas by using targeted next-generation sequencing and reverse transcription-PCR. Our analyses showed that most TSAs (71%) contained genetic alterations in WNT pathway components. In particular, PTPRK-RSPO3 fusions (31%) and RNF43 mutations (24%) were frequently and almost exclusively observed in TSAs. Consistent with the WNT pathway activation, immunohistochemical analysis showed diffuse and focal nuclear accumulation of β-catenin in 53% and 30% of TSAs, respectively. APC mutations were observed in tubular and tubulovillous adenomas and in a subset of TSAs. BRAF mutations were exclusively and frequently encountered in serrated lesions. KRAS mutations were observed in all types of polyps, but were most commonly encountered in tubulovillous adenomas and TSAs. This study has demonstrated that TSAs frequently harbour genetic alterations that lead to WNT pathway activation, in addition to BRAF and KRAS mutations. In particular, PTPRK-RSPO3 fusions and RNF43 mutations were found to be characteristic genetic features of TSAs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Yan, Ye; Chen, Yi-Na; Zhao, Qian; Chen, Chao; Lin, Chun-Jing; Jin, Yin; Pan, Shuang; Wu, Jian-Sheng
AIM To explore the association between Helicobacter pylori (H. pylori) infection status, intestinal metaplasia (IM), and colorectal adenomas. METHODS We retrospectively reviewed 1641 individuals aged ≥ 40 years who underwent physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy, and an interview to ascertain baseline characteristics and general state of health. Histopathological results were obtained by gastric and colorectal biopsies. RESULTS The prevalence of H. pylori infection and adenomas was 51.5% (845/1641) and 18.1% (297/1641), respectively. H. pylori infection was significantly correlated with an increased risk of colorectal adenomas (crude OR = 1.535, 95%CI: 1.044-1.753, P = 0.022; adjusted OR = 1.359, 95%CI: 1.035-1.785, P = 0.028). Individuals with IM had an elevated risk of colorectal adenomas (crude OR = 1.664, 95%CI: 1.216-2.277, P = 0.001; adjusted OR = 1.381, 95%CI: 0.998-1.929, P = 0.059). Stratification based on H. pylori infection stage and IM revealed that IM accompanied by H. pylori infection was significantly associated with an increased risk of adenomas (crude OR = 2.109, 95%CI: 1.383-3.216, P = 0.001; adjusted OR = 1.765, 95%CI: 1.130-2.757, P = 0.012). CONCLUSION H. pylori-related IM is associated with a high risk of colorectal adenomas in Chinese individuals. PMID:28293091
Pappa, Theodora; Papanastasiou, Labrini; Markou, Athina; Androulakis, Ioannis; Kontogeorgos, George; Seretis, Andreas; Piaditis, George
Thyrotoxic Periodic Paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. Thyroid-Stimulating Hormone (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism. Even more rare is the occurrence of TPP as the first manifestation of a TSH-secreting pituitary adenoma. We report a 31-year-old Asian male patient suffering from TPP caused by a TSH-secreting adenoma, who was evaluated for persistent episodes of muscle paralysis. Laboratory investigation revealed hypokalemia as well as elevated levels of both thyroid hormones and TSH. The Magnetic Resonance Imaging (MRI) of the pituitary gland revealed a microadenoma, thus suggesting the presence of a TSH-secreting adenoma. The patient underwent transphenoidal resection and the pathological investigation confirmed the diagnosis of TSH-secreting pituitary adenoma. After the adenomectomy and the restoration of euthyroidism, the patient did not experience any episode of hypokalemic paralysis or weakness. Despite its rarity, TSH-secreting pituitary adenoma should be included in the differential diagnosis of TPP.
Azma, Roxana; Fallahi, Minoo; Khoddami, Maliheh; Shamsian, Bibi Shahin; Alavi, Samin
Introduction: Pleomorphic adenoma is a rare benign salivary gland neoplasm in children, which can be treated by simple excision. This tumor is rarely included in the differential diagnosis of solid submandibular masses in children. In the neonates, congenital pleomorphic adenoma usually presents in the nasopharynx. Surgical excision is the treatment of choice and recurrence is not expected. We report what appears to be the first case of congenital pleomorphic adenoma in the submandibular region in a one-day-old newborn. Case Report: The case of a one-day-old term baby is presented with a 5x2 cm left submandibualr mass with extension to the oral cavity. The mass was hard and non-mobile. During Ultrasonography and Contrast-enhanced Computed Tomography (CT) scan, the mass was solid with a heterogeneous internal structure. The tumor was completely excised and proved to be a pleomorphic adenoma during histopathological examination. Conclusion: Congenital pleomorphic adenoma rarely occurs in the nasopharynx and is treated by surgical excision. Our case is unique because the congenital pleomorphic adenoma is located in the submandibular gland of a newborn. PMID:27280103
Kim, Won; Clelland, Claire; Yang, Isaac; Pouratian, Nader
Despite advances in surgical techniques and medical therapies, a significant proportion of pituitary adenomas remain endocrinologically active, demonstrate persistent radiographic disease, or recur when followed for long periods of time. While surgical intervention remains the first-line therapy, stereotactic radiosurgery is increasingly recognized as a viable treatment option for these often challenging tumors. In this review, we comprehensively review the literature to evaluate both endocrinologic and radiographic outcomes of radiosurgical management of pituitary adenomas. The literature clearly supports the use of radiosurgery, with endocrinologic remission rates and time to remission varying by tumor type [prolactinoma: 20–30%, growth hormone secreting adenomas: ~50%, adrenocorticotrophic hormone (ACTH)-secreting adenomas: 40–65%] and radiographic control rates almost universally greater than 90% with long-term follow-up. We stratify the outcomes by tumor type, review the importance of prognostic factors (particularly, pre-treatment endocrinologic function and tumor size), and discuss the complications of treatment (with special attention to endocrinopathy and visual complications). We conclude that the literature supports the use of radiosurgery for treatment-refractory pituitary adenomas, providing the patient with a minimally invasive, safe, and effective treatment option for an otherwise resistant tumor. As such, we provide literature-based treatment considerations, including radiosurgical dose, endocrinologic, radiographic, and medical considerations for each adenoma type. PMID:22826820
Bendib, Mouna; Badescu, Alina; Handra-Luca, Adriana
Colorectal adenomas are the most frequent benign colorectal tumors. These tumors are characterized by dysplasia, low and high grade, the latter having the potential to evolve to adenocarcinoma. The aim of this study was to study the expression patterns of PTEN protein in a series of colorectal adenomas and the relationships to cell proliferation and CD133, marker of stem phenotype. Colorectal adenomas were studied for the immunohistochemical expression of PTEN on tissue microarrays. PTEN expression was analysed with regard to morphological features and with regard to the Ki67 and CD133-positive cell compartments by using the Kendall rank-correlation test. PTEN was expressed in 92% adenomas, either in a cytoplasmic or nuclear pattern. Cytoplasmic PTEN was correlated to cytoplasmic CD133 (p = 0.02, tau 0.191) while nuclear PTEN to decreased adenoma size and to tubular architecture (p = 0.01, τ-0.184 and p = 0.01, τ-0.183). Nuclear PTEN was also correlated to low grade intraepithelial neoplasia, while global PTEN (nuclear or cytoplasmic) was correlated to the presence of a decreased Ki67-positive component but with marginal significance (p = 0.06, τ-0.144 and p = 0.07, τ-0.213). The results of this study suggest a role for PTEN in colorectal adenoma morphogenesis and cell protein heterogeneity, being correlated to decreased size, tubular architecture and a high CD133-positive component. Copyright © 2014 Elsevier GmbH. All rights reserved.
Rubio, Carlos A
In the normal duodenum, Paneth cells migrate from the stem cells downwards, towards the bottom of the crypts of Lieberkuhn. The spatial position of Paneth cells within the profile of histological sections was investigated with hematoxilin and eosin (H&E) in 6 duodenal adenomas; 2 of them were also immonostained with lysozyme, an enzyme present in Paneth cells. In H&E stain sections, the numbers of mature Paneth cells/high power field varied from 2 to 7 (mean 4.5). In the two immunostained adenomas, the numbers of lysozyme-expressing cells/high power field were 15 and 42, respectively. The lysozyme-stained cells were present at all levels in the adenomas, including the luminal epithelial layer. In duodenal adenomas, not all Paneth cells detected by lysozyme immunostain are apparent in H&E-stained sections, suggesting that lysozyme immunostain also detects Paneth cells precursors. Since mature Paneth cells and their precursors are positioned underneath the stem cells, it is conceivable that the Paneth cells that had reached the luminal aspect of the adenomas, were preceded by stem cells. This possibility would imply that in duodenal adenomas, the stem cells would be subjected to the same laws that orchestrate the turnover of epithelial duodenal cells, including Paneth cells and their precursors.
Zhou, Cuiqi; Jiao, Yonghui; Wang, Renzhi; Ren, Song-Guang; Wawrowsky, Kolja; Melmed, Shlomo
Pituitary somatotroph adenomas result in dysregulated growth hormone (GH) hypersecretion and acromegaly; however, regulatory mechanisms that promote GH hypersecretion remain elusive. Here, we provide evidence that STAT3 directly induces somatotroph tumor cell GH. Evaluation of pituitary tumors revealed that STAT3 expression was enhanced in human GH-secreting adenomas compared with that in nonsecreting pituitary tumors. Moreover, STAT3 and GH expression were concordant in a somatotroph adenoma tissue array. Promoter and expression analysis in a GH-secreting rat cell line (GH3) revealed that STAT3 specifically binds the Gh promoter and induces transcription. Stable expression of STAT3 in GH3 cells induced expression of endogenous GH, and expression of a constitutively active STAT3 further enhanced GH production. Conversely, expression of dominant-negative STAT3 abrogated GH expression. In primary human somatotroph adenoma-derived cell cultures, STAT3 suppression with the specific inhibitor S3I-201 attenuated GH transcription and reduced GH secretion in the majority of derivative cultures. In addition, S3I-201 attenuated somatotroph tumor growth and GH secretion in a rat xenograft model. GH induced STAT3 phosphorylation and nuclear translocation, indicating a positive feedback loop between STAT3 and GH in somatotroph tumor cells. Together, these results indicate that adenoma GH hypersecretion is the result of STAT3-dependent GH induction, which in turn promotes STAT3 expression, and suggest STAT3 as a potential therapeutic target for pituitary somatotroph adenomas.
Schembre, Susan M; Cheng, Iona; Wilkens, Lynne R; Albright, Cheryl L; Marchand, Le Loïc
Genetic variants in bitter-taste receptor genes have been hypothesized to negatively impact health outcomes and/or influence dietary intake and, consequently, could increase the risk of colorectal neoplasia. Using a case-control study of 914 colorectal adenoma cases/1188 controls, we explored associations among colorectal adenoma risk, dietary intake, and genetic variation in 3 bitter-taste receptor genes: TAS2R38 (rs713598, rs1726866, rs10246939), TAS2R16 (rs846672), and TAS2R50 (rs1376251). Analysis of covariance was conducted to detect trends in dietary intake across TAS2R genotypes/haplotypes. Odds ratios and 95% confidence intervals were estimated by logistic regression to test gene-adenoma risk associations. No significant associations were observed between the TAS2R38 PAV/PAV diplotype or the TAS2R16 (rs846672) polymorphism with the selected diet variables. We observed weak inverse associations between the TAS2R50 (rs1376251) C allele and dietary fiber and vegetable intake (Ps < 0.015). Odds ratios for adenoma risk were not significantly different from the null. Our findings do not support a link between these TAS2R genotypes/haplotypes and dietary intake that could impact colorectal adenoma risk. However, given the paucity of data, we cannot dismiss the possibility that these genes may influence colorectal adenoma risk in other ways, such as through impaired gastrointestinal function, particularly in subgroups of the population.
Chen, Tang; Tang, Dongfang; You, Jinliang
Background Pituitary adenoma is one of the most common intracranial neoplasms, and its primary treatment is endoscopic endonasal transsphenoidal tumorectomy. Postoperative hypokalemia in these patients is a common complication, and is associated with morbidity and mortality. This study aimed to analyze the etiopathology of postoperative hypokalemia in pituitary adenomas after endoscopic transsphenoidal surgery. Methods and Materials This retrospective study included 181 pituitary adenomas confirmed by histopathology. Unconditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Repeated measures ANOVA was used to analyze change in serum potassium levels at different time points. Results Multiple Logistic regression analysis revealed that only ACTH-pituitary adenoma (OR = 4.92, 95% CI [1.18–20.48], P = 0.029) had a significant association with postoperative hypokalemia. Moreover, the overall mean serum potassium concentration was significantly lower in the ACTH versus the non-ACTH group (3.34 mmol/L vs. 3.79 mmol/L, P = 0.001). Postoperative hypokalemia was predominantly found in patients with ACTH-pituitary adenoma (P = 0.033). Conclusions ACTH-pituitary adenomas may be an independent factor related postoperative hypokalemia in patients despite conventional potassium supplementation in the immediate postoperative period. PMID:28560099
Rossi, Luigi; Giordani, Erika; Fontana, Antonella; Di Cristofano, Claudio; Cavallaro, Giuseppe; Bagni, Oreste; Filippi, Luca; Bianchi, Loredana; Rinaldi, Giulia; Congedi, Francesca Perrone; Papa, Anselmo; Caruso, Davide; Verrico, Monica; Silecchia, Gianfranco; Tomao, Silverio
Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands that spreads through direct extension, through the lymphatic vessels, and, rarely, hematogenously. When distant metastases have been found, they have been reported mainly in the lung. We present an unusual case of carcinoma ex pleomorphic adenoma of the parotid gland with splenic metastases. The patient presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland and he underwent a total parotidectomy with laterocervical lymphadenectomy ipsilateral and adjuvant radiation therapy to the right parotid area. One year later, the patient showed an ipsilateral supraclavicular lymph node recurrence, treated with surgery and radiation therapy. Two more years later, the patient developed lung and splenic lesions, detected through CT and PET. He underwent splenectomy and pathologic assessment of the specimen showed metastatic carcinoma ex pleomorphic adenoma. To our knowledge, there is no reported case of a carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated for carcinoma ex pleomorphic adenoma should be investigated for distant metastases with a long-term follow-up examination for local and distant metastases and new splenic lesions in these patients should be investigated.
van der Vorst, Joost R; Schaafsma, Boudewijn E; Verbeek, Floris P R; Swijnenburg, Rutger-Jan; Tummers, Quirijn R J G; Hutteman, Merlijn; Hamming, Jaap F; Kievit, Job; Frangioni, John V; van de Velde, Cornelis J H; Vahrmeijer, Alexander L
Intraoperative identification of parathyroid adenomas can be challenging. We hypothesized that low-doses methylene blue (MB) and near-infrared fluorescence (NIRF) imaging could be used to identify parathyroid adenomas intraoperatively. MB was injected intravenously after exploration at a dose of 0.5 mg/kg into 12 patients who underwent parathyroid surgery. NIRF imaging was performed using the Mini-FLARE imaging system. In 10 of 12 patients, histology confirmed a parathyroid adenoma. In 9 of these patients, NIRF could clearly identify the parathyroid adenoma during surgery. Seven of these 9 patients had a positive preoperative (99m) Tc-sestamibi single photon emission CT (SPECT) scan. Importantly, in 2 patients, parathyroid adenomas could be identified only using NIRF. This is the first study to show that low-dose MB can be used as NIRF tracer for identification of parathyroid adenomas, and suggests a correlation with preoperative (99m) Tc-sestamibi SPECT scanning. © 2013 Wiley Periodicals, Inc.
Adachi, M; Muto, T; Morioka, Y; Ikenaga, T; Hara, M
Two flat adenomas and a flat mucosal carcinoma of the colon were reported in patients with synchronous and metachronous colonic carcinomas. These lesions were almost flat and were not detected by preoperative endoscopic examinations. Colonoscopists should be aware of the presence of flat adenomas, which can be easily missed, and recognize them as lesions that play an important role in the "adenoma-carcinoma sequence."
Kogut, V V; Dzhuran, B V
Pilot results of prostatic adenoma treatment with diode laser (940 nm) in 94 patients showed high efficacy of laser vaporization of the prostate. The effect was achieved in all the patients in minimal number of complications and in satisfactory tolerance of the surgery. Laser vaporization has some advantages over standard treatment (TUR) and is a method of choice in small and middle-size adenomas. In large adenoma good results were obtained in combination of laser vaporization with bipolar TUR.
Zhang, Dagong; Xiao, Liu; Tian, Huan
We present an extremely rare case of pleomorphic adenoma of the nasal septum in a 24-year old woman who went to consultation because of right nasal neoplasm. The radiologic discoveries by computerized tomography showed a tumor in the right nasal septum. Incisional biopsy was done, with a histopathological report of pleomorphic adenoma. Later, nasal endoscopy was used to remove the neoplasm and histology revealed pleomorphic adenoma of the nasal septum.
Background The seroprevalence of IgG antibodies of Streptococcus gallolyticus subspecies gallolyticus, CIP 105428, was evaluated to investigate the controversial association of S. gallolyticus with colorectal carcinoma and adenoma in attempt to investigate the nature of such association if any, by exploring the mRNA expression of NF-κB and IL-8. Moreover, the serological behavior of S. gallolyticus IgG antibodies was compared to that of an indicator bacterium of bowel, Bacteroides fragilis. Methods ELISA was used to measure IgG antibodies of S. gallolyticus and B. fragilis in sera of 50 colorectal cancer, 14 colorectal adenoma patients, 30 age- and sex- matched apparently healthy volunteers (HV) and 30 age- and sex- matched colonoscopically-proven tumor-free control subjects. NF-κB and IL-8 mRNA expression was evaluated in tumorous and non-tumorous tissue sections of carcinoma and adenoma patients in comparison with that of control subjects by using in situ hybridization assay. Results Colorectal cancer and adenoma patients were associated with higher levels of serum S. gallolyticus IgG antibodies in comparison with HV and control subjects (P < 0.05) while no similar association was found with serum IgG antibodies of B. fragilis (P > 0.05). ELISA cutoff value for the seropositivity of S. gallolyticus IgG was calculated from tumor-free control group. The expression of NF-κB mRNA was higher in tumorous than non-tumorous tissue sections of adenoma and carcinoma, higher in carcinoma/adenoma sections than in control subjects, higher in tumorous sections of carcinoma than in adenoma patients, and higher in S. gallolyticus IgG seropositive than in seronegative groups in both tumorous and non-tumorous sections (P < 0.05). IL-8 mRNA expression in tumorous sections of adenoma and carcinoma was higher than in non-tumorous sections, higher in carcinoma/adenoma than in control subjects, and higher in S. gallolyticus IgG seropositive than in seronegative groups in tumorous
Woodson, Karen; Weisenberger, Daniel J; Campan, Mihaela; Laird, Peter W; Tangrea, Joseph; Johnson, Laura Lee; Schatzkin, Arthur; Lanza, Elaine
Hypermethylation of tumor suppressor and other regulatory genes is thought to play an important role in colorectal neoplasia and tumorigenesis. This study examined the association between gene methylation status in baseline adenomas and subsequent adenoma recurrence in a randomized dietary intervention study, the Polyp Prevention Trial. The methylation status of four genes [CDKN2A (p16), PTGS2 (COX2), ESR1 (ER-alpha), and PGR(PR)] was determined by MethyLight in 284 baseline adenomas from 196 trial participants. The association of gene methylation with recurrence was determined using logistic regression models. Gene methylation was evaluated as percent of methylated reference, a measure of methylation of each gene relative to control DNA. ESR1methylation status was inversely associated with adenoma recurrence, odds ratio = 0.36 (95% confidence interval, 0.15-0.88; P = 0.02) for the highest compared with the lowest quartile of the ESR1methylation. Further, ESR1 methylation status was inversely associated with the recurrence of multiple adenomas, advanced adenomas, and the recurrence of adenomas in the proximal but not distal bowel. No association between CDKN2A, PTGS2, or PGR methylation and adenoma recurrence was observed. These data suggest that ESR1 methylation may play a role in subsequent adenoma recurrence.
Sanno, N; Itoh, J; Teramoto, A; Itoh, Y; Hori, S; Osamura, R Y
Natural killer (NK) cells are specialized lymphocytes which are characterized as non-T and non-B cells, as they lack classic T and B cell surface markers. Recently, NK like immunoreactivity has been identified in endocrine and neuronal tissues as well as in the tumors derived from the neuroectoderm and neuroendocrine system. We examined the expression of NK-1 like immunoreactivity in 6 normal pituitary glands and in 55 cases of neoplastic pituitaries (16 growth hormone (GH) producing adenomas, 14 prolactin (PRL) producing adenomas, 4 thyrotropin (TSH) producing adenomas, 5 adrenocortocitropin (ACTH) producing adenomas and 16 non-functioning adenomas) immunohistochemically. The expression of the S-100 protein, which is a marker for folliclo-stellate (FS) cells, which have been reported to secrete cytokines as immuno-endocrine modulators, were also examined. In normal pituitary glands, NK-1 was detected in all 6 tissues in the cytoplasm of about 5-10% of the anterior pituitary cells. By serial sectioning and double immunostaining, NK-1 immunopositivity was frequently found to be localized in ACTH cells. The colocalization with other anterior pituitary hormones such as GH. PRL, the beta-subunit of luteinizing hormone (LH beta), follicle stimulating hormone (FSH beta). TSH beta and alpha-subunit of glycoprotein (alpha SU) was not observed. The S-100 immunopositive FS cells, which were scattered among hormone producing cells, were closely associated with NK-1 immunoreactive cells in the normal pituitaries. Among the 55 cases of pituitary adenomas, NK-1 was present in all the types of pituitary tumors, and a total of 33 (60.0%) contained NK-1 positive tumor cells. The frequency of NK-1 immunoreactivity in the individual adenoma types was; 14 of 16 GH producing adenomas (87.5%), 7 of 14 PRL producing adenomas (50%). 3 of 4 TSH producing adenomas (75%), 3 of 5 ACTH producing adenomas (60%), and 5 of 16 nonfunctioning adenomas (31.3%). By double immunostaining, NK-1 was
Flickinger, J.C.; Nelson, P.B.; Taylor, F.H.; Robinson, A.
The incidence of cerebral infarction was studied in 156 patients irradiated for treatment of pituitary adenomas. Seven patients experienced strokes at intervals of 3.2 to 14.6 years after irradiation. The observed incidence was not significantly greater than the expected value of 3.5 strokes (P = 0.078). Six strokes occurred in patients receiving equivalent doses (ED) of 1070 ret or more (observed to expected ratio 3.87, significantly elevated; P less than 0.001). Univariate log-rank analysis showed that the risk of stroke was significantly higher (P = 0.010) in patients receiving an ED of 1070 ret or more (4180 cGy/22 fractions) than those receiving lower doses. Multivariate analysis, however, demonstrated that the increased risk of stroke was associated only with increasing age (P less than 0.0001), not ED (P = 0.148). Due to these inconsistent statistical results, no definitive conclusions could be reached about the relationship between radiation dose to the pituitary and subsequent cerebral infarction.
Parikh, Neil D; Gibson, Joanna; Nagar, Anil; Ahmed, Ali A
Background and aims Sessile serrated adenomas/polyps (SSA/Ps) are difficult to differentiate from non-neoplastic tissue on white-light endoscopy. Confocal laser endomicroscopy (CLE) provides subcellular imaging and real-time “optical biopsy”. The aim of this study was to prospectively describe CLE features of SSA/Ps. Patients and methods Consecutive patients with SSA/Ps were prospectively evaluated with probe-based CLE imaging. CLE images and polyp histology were independently reviewed by three endoscopists and an expert gastrointestinal (GI) pathologist. Distinguishing CLE features of SSA/Ps were identified in conjunction with pathologic correlation. Results In total, 260 CLE images were generated from nine SSA/Ps evaluated in seven patients. Four consensus CLE features of SSA/P were identified: (1) a mucus cap with a bright, cloud-like appearance; (2) thin, branching crypts; (3) increased number of goblet cells and microvesicular mucin-containing cells; and (4) architectural disarray, with dystrophic goblet cells and lack of regular circular crypts Conclusion This is a novel description of characteristic CLE features of SSA/Ps. The four features we identified are easy to detect and may allow for CLE to serve as a diagnostic modality. PMID:27536371
Wassef, M; Kanavaros, P; Polivka, M; Nemeth, J; Monteil, J P; Frachet, B; Tran Ba Huy, P
Middle ear adenoma (MEA) is a distinctive, rare entity that appears to be derived from the lining epithelium of the middle ear mucosa. We report four cases of MEA displaying the typical histologic growth pattern. Two distinct tumor cell immunophenotypes were identified in all cases; the first type exhibited positivity with anti-epithelial membrane antigen and anti-keratin antibodies, and the second type showed immunoreactivity with anti-keratin, anti-vimentin, and anti-neuron-specific enolase antibodies. Ultrastructural studies revealed bidirectional mucinous and neuroendocrine differentiation, demonstrated by the presence of two distinct cell types containing apically located mucous granules and basally concentrated neuroendocrine granules, respectively. The presence of neuroendocrine differentiation was supported by the immunohistochemical detection of vasoactive intestinal polypeptide in the tumor cells in one case and neuron-specific enolase in three cases. These findings suggest that the potential for mixed mucinous/neuroendocrine differentiation described in other endodermally derived tumors also exists in middle ear mucosa. We also believe that the rare lesions diagnosed as primary carcinoid tumors of the middle ear might in fact be MEA with predominant or only neuroendocrine differentiation. The clinical course of our four cases and our review of the pertinent literature confirm the benign nature of MEA and indicate that these tumors should be treated by complete local excision without additional therapy.
Wynford-Thomas, V.; Wynford-Thomas, D.; Williams, E.D.
Neonatal inbred Wistar albino rats were given either 5 or 10 microCi radioiodine (/sup 131/I) within 24 hours of birth. After weaning, animals were placed on diets high, normal, or deficient in vitamin D3 (cholecalciferol) for periods up to 2 years. In animals aged 12 months and older, adenomas were found in 0 of 67 unirradiated controls, in 22 of 67 given 5 microCi /sup 131/I, and in 25 of 67 given to microCi /sup 131/I. The incidence of tumors in irradiated animals was highest (55%) in those on a low-vitamin D diet and lowest (20%) in those on a high-vitamin D diet. Plasma calcium levels were significantly increased by the high-vitamin D diet, but the low-vitamin D diet did not lead to any significant decrease as compared to the calcium levels of the normal vitamin D diet group. Small but significant calcium increases were found in tumor-bearing animals. These findings indicate that parathyroid tumors in the rat can be induced by radiation and that their incidence is strongly influenced by dietary vitamin D content. The possibility that metabolites of vitamin D3 may influence parathyroid growth and tumor formation directly is discussed.
Åkerström, Tobias; Maharjan, Rajani; Sven Willenberg, Holger; Cupisti, Kenko; Ip, Julian; Moser, Ana; Stålberg, Peter; Robinson, Bruce; Alexander Iwen, K.; Dralle, Henning; Walz, Martin K.; Lehnert, Hendrik; Sidhu, Stan; Gomez-Sanchez, Celso; Hellman, Per; Björklund, Peyman
Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5–10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling is mutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutations in a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of the tumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. All of the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3. The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. This report provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occur in APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation. PMID:26815163
Kistka, Heather M.; Kasl, Rebecca A.; Nayeri, Arash; Utz, Andrea L.; Weaver, Kyle D.; Chambless, Lola B.
Objectives To determine the cost of annual magnetic resonance imaging (MRI) surveillance after resection of nonfunctioning pituitary adenomas (NFPAs) and its effectiveness in reducing visual compromise due to tumor recurrence. Design Retrospective case series. Setting Vanderbilt University Medical Center (2003–2011). Participants A total of 120 patients underwent primary transsphenoidal resection and surveillance of NFPAs between 2003 and 2011. Main Outcome Measures Time from initial surgery to most recent imaging or progression. Surveillance MRI costs according to Centers for Medicare and Medicaid database and visual field deficits. Results Patients received 382 surveillance scans at a total cost of $218,477.30. The median follow-up was 47 months (interquartile range [IQR]: 26–76), and the median interval between scans was 357 days (IQR: 225–434). Overall, 50 scans (13%) revealed tumor growth. The cost per scan revealing growth was $4,369.55. The cost to identify 19 patients (16%) with clinically significant growth was $11,498.80 per patient. A total of 5 of 19 patients (26%) experienced new visual deficits prior to intervention. Patients with visual decline tended to have longer scan intervals than those with preserved vision (mean: 239 versus 794 days; p = 0.0584). No patient with annual surveillance imaging experienced visual decline. Conclusions Annual MRI scans are a sensitive and cost-conscious method to identify NFPA recurrence prior to visual decline. PMID:26401475
Ben-Shlomo, Anat; Liu, Ning-Ai; Melmed, Shlomo
Somatostatin and dopamine receptors are expressed in normal and tumoral somatotroph cells. Upon receptor stimulation, somatostatin and the somatostatin receptor ligands octreotide, lanreotide, and pasireotide, and to a lesser extent, dopamine and the dopamine analogs bromocriptine and cabergoline, suppress growth hormone (GH) secretion from a GH-secreting pituitary somatotroph adenoma. Somatostatin and dopamine receptors are Gαi-protein coupled that inhibit adenylate cyclase activity and cAMP production and reduce intracellular calcium concentration and calcium flux oscillations. Although their main action on somatotroph cells is acute inhibition of GH secretion, they also may inhibit GH production and possibly somatotroph proliferation. These receptors have been reported to create complexes that exhibit functions distinct from that of receptor monomers. Somatostatin suppression of GH is mediated mainly by somatostatin receptor subtype 2 and to a lesser extent by SST5. Human somatostatin receptor subtype 5 has also been shown to harbor mutations associated with GH levels, somatotroph tumor behavior, and somatostatin receptor ligand (SRL) responsiveness. Reviewing current knowledge of somatostatin and dopamine receptor expression and signaling in normal and tumoral somatotroph cells offers insights into mechanisms underlying SRL and dopamine agonist effectiveness in patients with acromegaly.
Pilati, Camilla; Amessou, Mohamed; Bihl, Michel P.; Balabaud, Charles; Van Nhieu, Jeanne Tran; Paradis, Valérie; Nault, Jean Charles; Izard, Tina; Bioulac-Sage, Paulette; Couchy, Gabrielle; Poussin, Karine
Inflammatory hepatocellular adenomas (IHCAs) are benign liver tumors. 60% of these tumors have IL-6 signal transducer (IL6ST; gp130) mutations that activate interleukin 6 (IL-6) signaling. Here, we report that 12% of IHCA subsets lacking IL6ST mutations harbor somatic signal transducer and activator of transcription 3 (STAT3) mutations (6/49). Most of these mutations are amino acid substitutions in the SH2 domain that directs STAT3 dimerization. In contrast to wild-type STAT3, IHCA STAT3 mutants constitutively activated the IL-6 signaling pathway independent of ligand in hepatocellular cells. Indeed, the IHCA STAT3 Y640 mutant homodimerized independent of IL-6 and was hypersensitive to IL-6 stimulation. This was associated with phosphorylation of tyrosine 705, a residue required for IL-6–induced STAT3 activation. Silencing or inhibiting the tyrosine kinases JAK1 or Src, which phosphorylate STAT3, impaired constitutive activity of IHCA STAT3 mutants in hepatocellular cells. Thus, we identified for the first time somatic STAT3 mutations in human tumors, revealing a new mechanism of recurrent STAT3 activation and underscoring the role of the IL-6–STAT3 pathway in benign hepatocellular tumorigenesis. PMID:21690253
Ponce Bravo, Santa; Ledesma Montes, Constantino; López Becerril, Uriel; Morales Sánchez, Israel
The aim of this study was to quantify by immunohistochemistry the number of myoepithelial cells (MyECs) in pleomorphic adenomas (PAs). We retrieved the paraffin cubes of 27 PAs, new slides were done and they were stained with anti-S100 protein antibody. The amount of S-100 protein positive cells was quantified, their morphology was recorded and comparison among MyEC number with age, gender and involved gland were also done. With S-100 protein, MyECs in normal salivary gland tissue were seen surrounding the ductual structures only. In the analysed PAs a mean of 27.4% of the neoplastic cells were positive to the antibody. With the exception of one PA, in all the analysed cases the plasmacytoid cells were the most commonly identified cells (48,6%). Results of this study suggest that MyECs do not constitute the main cellular component of the neoplastic compartment in PAs and corroborate the previously reported evidence by different authors, who studying the PAs suggested that MyECs does not comprise the main cellular neoplastic component of these entities.
Rioja, Paula; Mateu, Germán; Lorente-Poch, Leyre; Sancho, Juan J; Sitges-Serra, Antonio
Undescended glands are a rare cause of primary and secondary hyperparathyroidism (HPT), but they are more common, however, among patients with recurrent HPT or those who have undergone a failed initial cervical exploration. The currently development of more precise noninvasive imaging techniques has improved the results of preoperative diagnosis of these ectopic lesions. The operative reports of patients undergoing parathyroidectomy at our institution were reviewed to identify patients with an undescended parathyroid gland adenomas. Demographic, clinical, imaging and surgical variables were recorded. Three patients were included: 2/598 parathyroidectomies performed for primary HPT and 1/93 performed for secondary HPT. One case is presented as jaw tumor syndrome (JTS). All the patients had undergone at least one operation before the definitive focused surgery and represented 6% of our parathyroid reoperations. No significant complications and no recurrences were observed in the long-term follow up. Accurate preoperative localization of these lesions was possible with noninvasive studies. High cure rate is possible through selective approach when accurate preoperative localization. Thorough knowledge of parathyroid embryology and meticulous surgical technique are essential, particularly in patients with previous unsuccessful explorations.
Mateu, Germán; Lorente-Poch, Leyre; Sancho, Juan J.; Sitges-Serra, Antonio
Background Undescended glands are a rare cause of primary and secondary hyperparathyroidism (HPT), but they are more common, however, among patients with recurrent HPT or those who have undergone a failed initial cervical exploration. The currently development of more precise noninvasive imaging techniques has improved the results of preoperative diagnosis of these ectopic lesions. Methods The operative reports of patients undergoing parathyroidectomy at our institution were reviewed to identify patients with an undescended parathyroid gland adenomas. Demographic, clinical, imaging and surgical variables were recorded. Results Three patients were included: 2/598 parathyroidectomies performed for primary HPT and 1/93 performed for secondary HPT. One case is presented as jaw tumor syndrome (JTS). All the patients had undergone at least one operation before the definitive focused surgery and represented 6% of our parathyroid reoperations. No significant complications and no recurrences were observed in the long-term follow up. Conclusions Accurate preoperative localization of these lesions was possible with noninvasive studies. High cure rate is possible through selective approach when accurate preoperative localization. Thorough knowledge of parathyroid embryology and meticulous surgical technique are essential, particularly in patients with previous unsuccessful explorations. PMID:26312215
López, Ainhoa Abad; Fragueiro, Luz Martín; García, Nuria Palacios
The 85% of cases of primary hyperparathyroidism (PHPT) are due to parathyroid adenomas (PA) and less than 1% to parathyroid carcinomas (PC). The PA usually measure <2 cm, weigh <1 g and generate a mild PHPT, whereas the PC usually exceeds these dimensions and are associated with a severe PHPT. However, giant PA (GPA), which is defined as those larger than 3 g, has been documented. Those may be associated with very high levels of PTH and calcium. In these cases, their differentiation before and after surgery with PC is very difficult. We present a case of severe PHPT associated with a large parathyroid lesion, and we discuss the differential aspects between the GPA and PC. Learning points: In parathyroid lesions larger than 2 cm, the differential diagnosis between GPA and PC should be considered. Pre and postsurgical differentiation between GPA and PC is difficult; however, there are clinical, analytical and radiographic characteristics that may be useful. The depth/width ratio larger or smaller than 1 seems to be the most discriminatory ultrasound parameter for the differential diagnosis. Loss of staining for parafibromin has a specificity of 99% for the diagnosis of PC. The simultaneous presence of several histological characteristics, according to the classification of Schantz and Castleman, is frequent in PC and rare in GPA. PMID:28491324
Minniti, G.; Scaringi, C.; Amelio, D.; Maurizi Enrici, R.
Radiotherapy (RT) is often employed in patients with acromegaly refractory to medical and/or surgical interventions in order to prevent tumour regrowth and normalize elevated GH and IGF-I levels. It achieves tumour control and hormone normalization up to 90% and 70% of patients at 10–15 years. Despite the excellent tumour control, conventional RT is associated with a potential risk of developing late toxicity, especially hypopituitarism, and its role in the management of patients with GH-secreting pituitary adenomas remains a matter of debate. Stereotactic techniques have been developed with the aim to deliver more localized irradiation and minimize the long-term consequences of treatment, while improving its efficacy. Stereotactic irradiation can be given in a single dose as stereotactic radiosurgery (SRS) or in multiple doses as fractionated stereotactic radiotherapy (FSRT). We have reviewed the recent published literature on stereotactic techniques for GH-secreting pituitary tumors with the aim to define the efficacy and potential adverse effects of each of these techniques. PMID:22518123
Heaney, Anthony P.; Fernando, Manory; Melmed, Shlomo
Pituitary tumors cause considerable morbidity due to local invasion, hypopituitarism, or hormone hypersecretion. In many cases, no suitable drug therapies are available, and surgical excision is currently the only effective treatment. We show here abundant expression of nuclear hormone receptor PPAR-γ in all of 39 human pituitary tumors. PPAR-γ activating thiazolidinediones (TZDs) rosiglitazone and troglitazone induced G0-G1 cell-cycle arrest and apoptosis in human, rat somatolactotroph, and murine gonadotroph pituitary tumor cells, and suppressed in vitro hormone secretion. In vivo development and growth of murine somatolactotroph and gonadotroph tumors, generated by subcutaneous injection of prolactin-secreting (PRL-secreting) and growth hormone–secreting (GH-secreting) GH3 cells, luteinizing hormone–secreting (LH-secreting) LβT2 cells, and α-T3 cells, was markedly suppressed in rosiglitazone-treated mice, and serum GH, PRL, and LH levels were attenuated in all treated animals (P < 0.009). These results demonstrate that PPAR-γ is an important molecular target in pituitary adenoma cells and PPAR-γ ligands inhibit tumor cell growth and GH, PRL, and LH secretion in vitro and in vivo. TZDs are proposed as novel oral medications for managing pituitary tumors. PMID:12727930
Juaneda, R; Thanigasalam, R; Rizk, J; Perrot, E; Theveniaud, P E; Baumert, H
The aim of this study is to compare Holmium laser enucleation of the prostate with another minimally invasive technique, the laparoscopic simple prostatectomy. We compared outcomes of a series of 40 patients who underwent laparoscopic simple prostatectomy (n=20) with laser enucleation of the prostate (n=20) for large adenomas (>100 grams) at our institution. Study variables included operative time and catheterization time, hospital stay, pre- and post-operative International Prostate Symptom Score and maximum urinary flow rate, complications and economic evaluation. Statistical analyses were performed using the Student t test and Fisher test. There were no significant differences in patient age, preoperative prostatic size, operating time or specimen weight between the 2 groups. Duration of catheterization (P=.0008) and hospital stay (P<.0001) were significantly less in the laser group. Both groups showed a statistically significant improvement in functional variables at 3 months post operatively. The cost utility analysis for Holmium per case was 2589 euros versus 4706 per laparoscopic case. In the laser arm, 4 patients (20%) experienced complications according to the modified Clavien classification system versus 5 (25%) in the laparoscopic group (P>.99). Holmium enucleation of the prostate has similar short term functional results and complication rates compared to laparoscopic simple prostatectomy performed in large glands with the advantage of less catheterization time, lower economic costs and a reduced hospital stay. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.
Vanounou, Tsafrir; Groeschl, Ryan T; Geller, David A; Marsh, J Wallis; Gamblin, T Clark
For small asymptomatic hepatic adenomas (HA), available data are insufficient to establish the superiority of either observation or surgery. We sought to investigate the cost-effectiveness of two initial management strategies. We performed a comparative analysis of two theoretical cohorts of 100 patients with small (<5 cm), asymptomatic HA. Discounted cash flow (DCF) models compared the net present value (NPV) of both treatment options at year 10 under three distinct progression rate scenarios. A break-even (BE) analysis was used to determine the BE point at which the NPV for observation and immediate surgery intersect. The NPV for immediate surgery was $1,733,955. The NPV for observation varied between $2,065,315-$2,745,631 for computed tomography (CT), $2,264,575-$2,929,541 for magnetic resonance imaging (MRI), and $802,837-$1,580,413 for ultrasound (US). The BE point was between 6 and 8 years for CT and 5-7 years for MRI. The BE point for US was not reached except in the highest progression rate scenario (12 years). This study highlights the importance of the underlying progression rate and the cost of imaging when following patients with asymptomatic HA. Overall, US surveillance is the most cost-efficient approach to observing small asymptomatic HA. If cross-sectional imaging is utilized, then immediate surgery is the most cost-effective decision at 5-8 years. Copyright © 2012 Wiley Periodicals, Inc.
Louiset, Estelle; Gobet, Françoise; Libé, Rossella; Horvath, Anelia; Renouf, Sylvie; Cariou, Juliette; Rothenbuhler, Anya; Bertherat, Jérôme; Clauser, Eric; Grise, Philippe; Stratakis, Constantine A.; Kuhn, Jean-Marc; Lefebvre, Hervé
Context: Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing’s syndrome. Objective: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma. Design and Setting: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. Intervention: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. Main Outcome Measure: Detection of 17α-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes. Results: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17α-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway. Conclusion: This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing’s syndrome. PMID:19915020
Cao, Yin; Rosner, Bernard A.; Ma, Jing; Tamimi, Rulla M.; Chan, Andrew T.; Fuchs, Charles S.
Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective U.S. studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs 1.8% for men in the bottom decile (Odds Ratio[OR]=9.41), and 6.6% vs 2.1% for women (OR=3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the U.S. population that may provide guidance for first-time colorectal cancer screening. PMID:25820865
Cao, Yin; Rosner, Bernard A; Ma, Jing; Tamimi, Rulla M; Chan, Andrew T; Fuchs, Charles S; Wu, Kana; Giovannucci, Edward L
Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective US studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs. 1.8% for men in the bottom decile (Odds Ratio [OR] = 9.41), and 6.6% vs. 2.1% for women (OR = 3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the US population that may provide guidance for first-time colorectal cancer screening.
Eichholzer, Monika; Rohrmann, Sabine; Barbir, Aline; Hermann, Silke; Teucher, Birgit; Kaaks, Rudolf; Linseisen, Jakob
Colorectal adenoma (CRA) and colorectal cancer (CRC) risks have been linked to the intake of red and processed meat. Heterocyclic aromatic amines (HCA) formed herein during high temperature cooking, are metabolized by a variety of enzymes, and allelic variation in the coding genes could influence individual CRA risk. Associations of polymorphisms in NAT1, NAT2, GSTA1, SULT1A1, CYP1A2, UGT1A7, UGT1A9, GSTP1 genes with colorectal adenoma risk were investigated in a nested case-control study of the EPIC-Heidelberg cohort including 428 cases matched by age, sex and year of recruitment with one or two controls (n=828) with negative colonoscopy per case. Genoyping was preformed with the Sequenom MassArray system and the LightCycler 480. Conditional logistic regression was used to compute odds ratios (OR) and corresponding 95% confidence intervals (CI). For rs15561 (NAT1) and rs1057126 (NAT1), the rarer allel was significantly inversely associated with adenoma risk OR=0.80 (95% CI 0.65-0.97) and (OR=0.81 (95% CI 0.65-0.99) and, respectively). For the combined NAT2 alleles encoding for enzymes with medium (versus slow) activity we also observed a significantly inverse association with adenoma risk (OR=0.75; 95% CI 0.85-0.97). In addition, homozygous carriers of the A allele of rs3957357 (GSTA1), i.e., those with a decreased enzyme activity, had a decreased risk of colorectal adenoma with an OR of 0.68 (95% CI 0.50-0.92; AA versus GG/GA). Polymorphisms in the other tested genes did not modify the risk of colorectal adenomas. In conclusion, polymorphisms in NAT1, NAT2, and GSTA1 are related to colorectal adenoma risk in this German cohort. PMID:22724046
Adler, Andreas; Aminalai, Alireza; Aschenbeck, Jens; Drossel, Rolf; Mayr, Michael; Scheel, Mathias; Schröder, Andreas; Yenerim, Timur; Wiedenmann, Bertram; Gauger, Ulrich; Roll, Stephanie; Rösch, Thomas
Improvements to endoscopy imaging technologies might improve detection rates of colorectal cancer and patient outcomes. We compared the accuracy of the latest generation of endoscopes with older generation models in detection of colorectal adenomas. We compared data from 2 prospective screening colonoscopy studies (the Berlin Colonoscopy Project 6); each study lasted approximately 6 months and included the same 6 colonoscopists, who worked in private practice. Participants in group 1 (n = 1256) were all examined by using the latest generation of wide-angle, high-definition colonoscopes that were manufactured by the same company. Individuals in group 2 (n = 1400) were examined by endoscopists who used routine equipment (a mixture of endoscopes from different companies; none of those used to examine group 1). The adenoma detection rate was calculated on the basis of the number of all adenomas/number of all patients. There were no differences in patient parameters or withdrawal time between groups (8.0 vs 8.2 minutes). The adenoma detection rate was significantly higher in group 1 (0.33) than in group 2 (0.27; P = .01); a greater number of patients with least 1 adenoma were identified in group 1 (22.1%) than in group 2 (18.2%; P = .01). A higher percentage of high-grade dysplastic adenomas were detected in group 1 (1.19%) than in group 2 (0.57%), but this difference was not statistically significant (P = .06). The latest generation of wide-angle, high-definition colonoscopes improves rates of adenoma detection by 22%, compared with mixed, older technology endoscopes used in routine private practice. These findings might affect definitions of quality control parameters for colonoscopy screening for colorectal cancer. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
Marek, J; Malík, J; Fendrych, P
Surgery of pituitary adenomas is not quite satisfactory so far and in some patients it is associated with a high risk. Conventional radiotherapy is only partly successful. Only few hospitals have experience with treatment of pituitary adenomas with Leksell's gamma knife. The objective of the presented paper is to give an account of the authors' own results of treatment of pituitary adenomas by irradiation with Leksell's gamma knife. The treated group comprised 13 patients (6 women, 7 men, 25-72 years old, median 44 years) with a pituitary adenoma. Hormonally active acromegaly was recorded in 9 patients, a prolactinoma in one female patient, afunctional adenoma in 3 patients. Twelve patients had been operated already previously, 3 of them twice. For visualization of the pituitary magnetic resonance (NMR) was used on a Magnetom apparatus 1.5 Tesla, Siemens Co. before surgery and one year after surgery. As hormonal indicators the following were examined: growth hormone (GH) profile in the course of the day and during the thyroliberin test (TRH), insulin-like growth factor I (IGF I), the prolactin level, the thyrotropin level (TSH) during the thyrotropin releasing hormone test (TRH) test the thyroxine level (T4) and the triiodothyronine level (T3), the plasma concentration of adrenocorticotropin (ACTH), the cortisol level, plasma testosterone level and 17-beta estradiol level. Complete recovery was achieved only in one female patient with acromegaly 18 months after irradiation, and in one patient with a prolactinoma a partial decline of hormone levels was recorded without detectable changes in the size of the adenoma. Only one female patient developed hypopituitarism. No other complications were recorded. Stereotactic irradiation with Leksell's gamma knife is valuable for treatment of pituitary adenomas and it is well tolerated therapy. Its effect is manifested only after several months. Complications in the sense of hypopituitarism may occur.
Bourroul, Guilherme Muniz; Fragoso, Hélio José; Gomes, José Walter Feitosa; Bourroul, Vivian Sati Oba; Oshima, Celina Tizuko Fujiyama; Gomes, Thiago Simão; Saba, Gabriela Tognini; Palma, Rogério Tadeu; Waisberg, Jaques
ABSTRACT Objective To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. Methods Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student’s t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used. Results In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (p<0.001 and p<0.0001, respectively). The immunoreactivity of GSK3β, axin 1 and ubiquitin proteins was significantly higher (p=0.03, p=0.039 and p=0.03, respectively) in colorectal carcinoma than in the colonic adenoma and adjacent non-neoplastic mucosa. The immunohistochemistry staining of these proteins did not show significant differences with the clinical and pathological characteristics of colorectal cancer and colonic adenoma. Conclusions These results suggest that, in adenomas, the lower expression of the beta-catenin, axin 1 and GSK3β proteins indicated that the destruction complex of beta-catenin was maintained, while in colorectal carcinoma, the increased expression of beta-catenin, GSK3β, axin 1, and ubiquitin proteins indicated that the destruction complex of beta-catenin was disrupted. PMID:27462886
Ding, Dale; Starke, Robert M; Sheehan, Jason P
Pituitary adenomas represent one of the most common types of intracranial tumors. While their macroscopic appearance and anatomical location are relatively homogeneous, pituitary tumors have the potential to generate a wide variety of clinical sequelae. Treatment options for pituitary tumors include medical therapy, microscopic or endoscopic surgical resection, radiosurgery, radiation therapy, or observation depending on the biochemical profile and clinical status of the patient. Radiosurgery and external beam radiation therapy (EBRT) are most commonly as adjunctive treatments following incomplete surgical resection leaving residual tumor, tumor recurrence, or failure of medical therapy. We present a comprehensive literature review of the radiosurgery series for pituitary tumors including nonfunctioning adenomas, ACTH- and GH-secreting adenomas, and prolactinomas. While postradiosurgery radiographic tumor control for nonfunctioning adenomas is excellent, typically around 90 %, the rates of biochemical remission for functioning adenomas are lower than the tumor control rates. The highest endocrine remission rates are achieved patients with Cushing’s disease and the lowest in those with prolactinomas. Although EBRT has been largely supplanted by radiosurgery for the vast majority of pituitary adenomas cases, there remains a role for EBRT in select cases involving large tumor volumes in close proximity to critical neural structures. By far the most common complication after radiosurgery or EBRT is delayed hypopituitarism followed by cranial neuropathies. The effect of suppressive medications on radiosurgery outcomes remains controversial. Due to the rare but well-documented occurrence of late recurrence following endocrine remission, long-term and rigorous clinical and radiographic follow-up is necessary for all pituitary adenoma patients treated with radiosurgery or EBRT.
Gupta, Mamta; Lloyd, Ricardo V; Fischer-Colbrie, Reiner; Tischler, Arthur S; Dayal, Yogeshwar
Neuroendocrine secretory protein-55 (NESP-55) is a recently described member of the chromogranin family and appears to be a marker of the constitutive secretory pathway in certain neural, neuroendocrine, and endocrine cell types. It has been shown to be selectively expressed in tumors differentiating towards the adrenal chromaffin and pancreatic islet cell phenotypes. The highest levels of NESP-55 expression, at least in animals, appear to be in the adrenal medulla and the pituitary gland. However, very little is known about the status of NESP-55 expression in pituitary adenomas. We therefore studied the immunohistochemical profile of NESP-55 expression in a series of 30 well-characterized pituitary adenomas (five each of FSH/LH and ACTH, four GH, three TSH, seven prolactin, and six null cells). All tumors were positive for one or more generic marker(s) (chromogranin A, synaptophysin, neuron-specific enolase) of neuroendocrine differentiation. All pituitary adenomas selected for study were stained for NESP-55 with appropriate positive and negative controls. NESP-55 immunoreactivity, seen as brown finely granular cytoplasmic staining of the tumor cells with prominent perinuclear accentuation, was graded as focal (<10% tumor cells staining), moderate (10-50% tumor cells staining), and diffuse (>50% tumor cell staining). Four of seven prolactinomas were positive for NESP-55 (one focal, two moderate, and one diffuse). Two of four GH adenomas were also positive (one focal and one diffuse) while only 1/5 FSH tumors showed a moderately intense immunoreactivity. All other pituitary adenomas were completely negative for NESP-55. Our results indicate that, in human pituitary adenomas, NESP-55 has a more restricted pattern of expression than that of chromogranins A and B. Since immunohistochemical expression of NESP-55 is largely confined to prolactinomas and GH adenomas, it raises the possibility that NESP-55 may somehow be involved in the secretory pathways of these
Risio, Mauro; Hassan, Cesare; Sottile, Antonino; Saglia, Alberto; Segnan, Nereo; Senore, Carlo
The detection of advanced adenomas within organized screening programs using either immunochemical fecal occult blood test (FIT) or endoscopy has been associated with the prevention of colorectal cancer. The histological changes and pathogenetic mechanisms that lead to the detection of such lesions by either of these screening methods have not yet been addressed. The histological specimens of 50 advanced adenomas detected by FIT were compared with those of 50 advanced adenomas detected by primary endoscopy screening that were matched for size and histology. The following variables were systematically recorded: 1) histopathological changes compatible with luminal bleeding induced by ischemia; 2) hypoxia in the adenomatous tissue, assessed through the expression of carbonic anhydrase IX; and 3) microvessel quantitative analysis, evaluated by CD31 and CD105 immunostains. All specimens were reviewed blindly by an expert gastrointestinal pathologist. Histopathological changes associated with ischemia-related luminal bleeding were significantly more frequent in FIT-positive than in endoscopy-detected advanced adenomas (78 % vs. 14 %; P < 0.001). Carbonic anhydrase IX expression was also significantly higher in FIT-detected advanced adenomas (immunohistochemical score: 12.0 vs. 4.1; P < 0.001). Conversely, no differences were found in microvessel density. The detection of advanced adenomas by FIT screening appears to be related to ischemia-associated luminal bleeding, which, in turn, may be due to periods of hypoxia. The absence of such changes in endoscopy-detected advanced adenomas would suggest that the two screening methods may be complementary for the detection of advanced neoplasia within organized screening programs. © Georg Thieme Verlag KG Stuttgart · New York.
Georgitsi, Marianthi; Raitila, Anniina; Karhu, Auli; Tuppurainen, Karoliina; Mäkinen, Markus J.; Vierimaa, Outi; Paschke, Ralf; Saeger, Wolfgang; van der Luijt, Rob B.; Sane, Timo; Robledo, Mercedes; De Menis, Ernesto; Weil, Robert J.; Wasik, Anna; Zielinski, Grzegorz; Lucewicz, Olga; Lubinski, Jan; Launonen, Virpi; Vahteristo, Pia; Aaltonen, Lauri A.
Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause pituitary adenoma predisposition (PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. Typically, PAP patients were of a young age at diagnosis but did not display a strong family history of pituitary adenomas. To evaluate the role of AIP in pituitary adenoma susceptibility in other populations and to gain insight into patient selection for molecular screening of the condition, we investigated the possible contribution of AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP mutations were identified. Because many of the patients displayed no family history of pituitary adenomas, detection of the condition appears challenging. Feasibility of AIP immunohistochemistry (IHC) as a prescreening tool was tested in 50 adenomas: 12 AIP mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP. PMID:17360484
Xiao, Lan; Tu, Chaofeng; Chen, Shuai; Yu, Zhibin; Lei, Qianqian; Wang, Zeyou; Xu, Gang; Wu, Minghua; Li, Guiyuan
Pituitary adenoma results from accumulation of multiple genetic and/or epigenetic aberrations such as GNAS, MEN1, CNC, and FIPA. LRRC4 is relatively tissue-specific expressed gene in the normal brain and downregulated expression in glioma (87.5%), meningioma (80.9%), and pituitary adenoma (85.5%). It has been suggested that the aberrant expression of LRRC4 contributes to tumorigenesis in glioma. However, little is known yet about association between LRRC4 and risk of pituitary adenoma. In this study, we genotyped three LRRC4 haplotype-tagging SNPs (htSNP) by direct sequencing in case-control studies, which included 183 Han Chinese patients diagnosed with pituitary adenoma and 183 age-, gender-matched, and geographically matched Han Chinese controls. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of the htSNP. We observed statistically significant differences regarding the genotype TT + CT of rs6944446 in the NCA. Haplotype AC of rs3823994-rs6944446 is suggested to have a protective effect in the development of pituitary adenoma (OR 0.339; 95% CI 0.123-0.934). However, haplotype GT of rs3808058-rs6944446 (OR 1.575; 95% CI 1.048-2.368) and AGT of rs3823994-rs6944446-rs3808058 (OR 1.673; 95% CI 1.056-2.651) might be a risk factor for pituitary adenoma development. In a brief, the results support the hypothesis that polymorphisms or haplotypes in the LRRC4 may have important research significance and could be used to predict the risk of pituitary adenoma.
Cluster headache belongs to a group of primary headache entities: the trigeminal autonomic cephalalgias. Cluster headache is the most common variant. The headache is usually severe and it is also associated with autonomic symptoms. Secondary causes of cluster headache have been reported, such as intracranial artery aneurysms and tumors. The question of when to carry out neuroimaging in patients with cluster headache is yet unsettled. To the best of the author's knowledge, cluster headache associated with a clinically non-functioning pituitary adenoma (chromophobe adenoma) has not been described. This case report describes the case of a man with cluster headache where the evaluation showed a clinically non-functioning pituitary adenoma. This case involved a 49-year-old Caucasian man who presented with a one-month history of side-locked attacks of pain located in the right orbit. His symptoms fulfilled the criteria for cluster headache and a diagnosis of cluster headache was made. The patient responded to symptomatic treatment. Enhanced magnetic resonance imaging showed a pituitary adenoma. Further evaluations including hormonal screening revealed a clinically non-functioning pituitary adenoma (chromophobe adenoma). After surgery to remove the tumor, his headache attacks resolved totally. Tumors have been reported in patients with cluster headache whose clinical attacks are identical to genuine cluster headache. A clinically non-functioning pituitary adenoma can present as cluster headache. This case emphasizes the need of imaging procedures in patients with cluster headache. Contrast-enhanced magnetic resonance imaging including the sella turcica should always be done in patients with cluster headache.
Shen, Huafeng; Lipka, Seth; Kumar, Ambuj; Mustacchia, Paul
Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome (MetS) and the most common chronic liver disease worldwide. The association between NAFLD and colorectal adenoma has been investigated in multiples studies but the results have been conflicting. We performed a systematic review and meta-analysis to evaluate this in asymptomatic patients who underwent screening colonoscopy. We searched the literatures of all languages from PubMed, EMBASE and the Cochrane library from January 1, 1980 through July 15, 2014. Combined and subgroup analyses stratified by study designs, study locations, characteristics of adenoma (location, size, number, and advanced adenoma) were performed. Four cross-sectional and one cohort studies with a total of 6,263 subjects were included in the meta-analysis. NAFLD was significantly associated with colorectal adenoma [pooled odds ratio (OR) 1.74, 95% confidence interval (CI): 1.53-1.97]. The association was more significant in Asian population (pooled OR =1.77, 95% CI: 1.52-2.05, n=3 studies), compared to European/North American population (pooled OR =1.42, 95% CI: 0.75-2.67, n=2 studies). NAFLD was significantly associated with the number of colorectal adenoma (pooled OR =1.78, 95% CI: 1.10-2.86, n=2 studies), but not the location, size, or presence of advanced adenoma. Our results suggest NAFLD is significantly associated with the presence of colorectal adenoma in asymptomatic patients undergoing screening colonoscopy. This finding provides additional risk stratifications for applying colorectal cancer (CRC) screening strategies. However, more studies of western population are needed to further investigate the ethnic disparity.
Seol, Ju Eun; Cho, Chang Ho; Kim, Sung Hi; Lee, Jung Eun
Colorectal cancer in Korea has become more prevalent over the few last decades, and calcium is considered a preventive factor for colorectal cancer development. We examined the associations between total and dietary calcium intake and the prevalence of colorectal adenoma in Korean adults. This cross-sectional study included 112 colorectal adenoma cases and 252 adenoma-free non-cases, aged 45 to 71 years, who underwent colonoscopies at the Daegu Catholic University Medical Center from August 2011 to September 2012. Participants were asked about their diet using a validated food frequency questionnaire and about supplement use through interviews. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between total and dietary calcium intake and the prevalence of colorectal adenomas using multivariable logistic regression models. Increasing total calcium intake from foods and supplements was significantly associated with a decreased prevalence of colorectal adenoma in women; comparing the highest quartile with the lowest quartile, the OR (95% CI) was 0.35 (0.15-0.85; P for trend = 0.03). Likewise, high dietary calcium intake from foods was associated with a lower prevalence of colorectal adenoma in women; compared with the lowest quartile, the ORs (95% CIs) were 0.32 (0.13-0.82) for the 3rd quartile and 0.44 (0.19-1.03; P for trend = 0.13) for the 4th quartile. However, the association was not clear for either total or dietary calcium intake among men. A higher intake of calcium was associated with a reduction of colorectal adenoma prevalence in Korean women.
Composite intestinal tumors of adenoma-lymphoma type are rare. To our knowledge 1 tumor showing this association has been previously reported, the histologic diagnosis being made retrospectively. We report the case of an 80-year old male patient complaining for epigastric pain, rectorrhagia, diarrhea, and weight loss. At endoscopy, a rectal lesion (3 cm) of villous low-grade dysplasia adenoma type was detected. Due to persistence of symptoms, new gastro- and coloscopies were performed, the biopsies showing low-grade dysplasia adenomas (right colon, and rectum) and an abundant lymphoid infiltrate (gastroduodenal anastomosis, small intestine, sigmoid, right and left colon, transverse colon, and rectum) of mantle cell lymphoma type, the rectal polyp being composed of both tumor types. The muscularis mucosa was focally infiltrated by the lymphoma, the bulk of the lymphoma being submucosal. After the treatment of 8 mini-cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone cures, lymphoma persisted. On endoscopic ultrasound examination, after the 6 cures of bendamustine following the cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone treatment, the signal of the rectal villous lesion disappeared in the peripheral layers, including of the muscular layer, suggestive of an invasive lesion or persistence of lymphoma. Biopsies confirmed the persistence of the rectal adenoma with low and high-grade adenoma, without lymphoma. In conclusion, the biopsic diagnosis of composite intestinal tumors of adenoma-mantle cell lymphoma type may be challenging, the bulk of the lymphoma being submucosal as in the present case. Although the malignant tumor treatment is the priority in such cases, the effects of chemotherapy on the evolution of benign tumors such as adenomas should be carefully assessed.
Wang, Qing; Lu, Xiao-Jie; Sun, Jun; Wang, Jing; Huang, Ci You; Wu, Zhi Feng
Ectopic thyroid-stimulating hormone (TSH)-secreting pituitary adenomas are rare and can often be misdiagnosed as primary hyperthyroidism. We present a case of an ectopic suprasellar TSH-secreting pituitary adenoma. A literature review of previously reported ectopic TSH-secreting and suprasellar pituitary adenomas is included to illustrate the clinical characteristics of this disease entity and the diversity of operative approaches to treating ectopic suprasellar pituitary adenomas. A 46-year-old man presented with typical clinical signs of hyperthyroidism and a history of progressive visual field impairment and vision loss. Laboratory investigations revealed that the patient had elevated levels of free thyroxine and free triiodothyronine and a normal level of TSH. Neuro-ophthalmologic examination showed right eye/left eye = 1.0/0.6 and left temporal hemianopia. Magnetic resonance imaging revealed a mass located in the suprasellar space. The patient underwent preoperative short-term octreotide treatment followed by gross total resection of the tumor via the extended endoscopic endonasal transtuberculum sellar approach. At 6-month follow-up evaluation, the patient's endocrinologic function tests met the criteria for cure, and magnetic resonance imaging revealed a normal pituitary gland and stalk with no tumor recurrence. Histologic diagnosis confirmed the presence of a TSH-secreting pituitary adenoma. To the best of our knowledge, this is the first reported case of an ectopic suprasellar TSH-secreting pituitary adenoma. Preoperative preparation and complete resection are the keys to a cure. The extended endoscopic endonasal transtuberculum sellar approach is an alternative minimally invasive method for the removal of an ectopic suprasellar pituitary adenoma. Copyright © 2016 Elsevier Inc. All rights reserved.
Cohen, Jonah; Grunwald, Douglas; Grossberg, Laurie B; Sawhney, Mandeep S
Although colonoscopy with polypectomy can prevent up to 80% of colorectal cancers, a significant adenoma miss rate still exists, particularly in the right colon. Previous studies addressing right colon retroflexion have revealed discordant evidence regarding the benefit of this maneuver on adenoma detection with concomitant concerns about safety and rates of maneuver success. In this meta-analysis, we sought to determine the effect of right colon retroflexion on improving adenoma detection compared with conventional colonoscopy without retroflexion, as well as determine the rates of retroflexion maneuver success and adverse events. Multiple databases including MEDLINE, Embase, and Web of Science were searched for studies on right colon retroflexion and its impact on adenoma detection compared with conventional colonoscopy. Pooled analyses of adenoma detection and retroflexion success were based on mixed-effects and random-effects models with heterogeneity analyses. Eight studies met the inclusion criteria (N=3660). The primary analysis comparing colonoscopy with right-sided retroflexion versus conventional colonoscopy to determine the per-adenoma miss rate in the right colon was 16.9% (95% confidence interval, 12.5%-22.5%). The overall rate of successful retroflexion was 91.9% (95% confidence interval, 86%-95%) and rate of adverse events was 0.03%. Colonoscopy with right-sided retroflexion significantly increases the detection of adenomas in the right colon compared with conventional colonoscopy with a high rate of maneuver success and small risk of adverse events. Thus, reexamination of the right colon in retroflexed view should be strongly considered in future standard of care colonoscopy guidelines for quality improvement in colon cancer prevention.
Background Recent studies suggest that bacterial endotoxins may be associated with various chronic diseases, including colorectal adenomas and cancer. Given the evidence linking inflammation and colorectal cancer, we sought to determine if plasma endotoxin concentrations are associated with indicators of systemic or local inflammation and colorectal adenomas. Methods This cross-sectional study consisted of participants who underwent screening colonoscopies and included adenoma cases (n=138) and non-adenoma controls (n=324). Plasma concentrations of endotoxin were measured with Limulus Amebocyte Lysate (LAL) assay. We quantified concentrations of inflammatory cytokines, interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) in plasma by ELISA and mRNA expression levels in rectal mucosal biopsies by quantitative RT-PCR. Interleukin-17 was evaluated only in the rectal mucosa. Results Compared to subjects with low plasma endotoxin concentrations, those with higher concentrations were more likely to have adenomas (OR 1.4, 95% CI 1.0-2.1). Among subjects with adenomas, those with villous histology were more likely to have higher endotoxin concentrations (5.4 vs. 4.1EU/mL, p=0.05) and lower plasma IFN-γ (0 vs. 1.64 pg/mL, p=0.02) compared to those with only tubular adenomas. Cases showed a trend of having higher plasma TNF-α levels than controls (p=0.06), but none of the other plasma or rectal mucosal cytokine levels differed between cases and controls. Elevated mucosal IL-12 levels were associated with having multiple adenomas (p=0.04). Higher concentrations of plasma endotoxin predicted increased plasma IL-12 levels (OR 1.5, 95% CI 1.0-2.2) and rectal mucosal IL-12 (OR 1.9, 95% CI 1.0-3.7) and IL-17 gene expression (OR 2.2, 95% CI 1.0-4.6). Conclusions These findings suggest that interactions between elevated plasma endotoxin concentrations and inflammatory cytokines may be relevant to the development of
Sengul, Ilker; Sengul, Demet; Aribas, Duygu
Context: Pleomorphic adenoma is the most common neoplasm of the minor salivary glands which are uncommon among the entire salivary gland tumors. The lower lip is a very rare site of occurrence for pleomorphic adenoma. We intended to present a case of pleomorphic adenoma of the lower lip. Case Report: A 49-year-old Turkish man presented with the painless mass on his lower lip. A total excision was choiced for the mass by both we and the patient because of some cosmetic reasons. The histopathological evaluation revealed the diagnosis of pleomorphic adenoma and neither complication nor recurrence was observed during a clinical follow-up for 40 months. Conclusions: A clinician should be vigilant for the possibility of existence of a pleomorphic adenoma located on the lower lip even it is rare. Once it is diagnosed concisely, a wide excision is suggested in general if there is no cosmetic care and no risk of damage to functional structures of head and neck. PMID:22540103
Muhr, C; Bergström, M; Lundberg, P O; Bergström, K; Långström, B
Patients with pituitary adenomas were examined with positron emission tomography (PET) with the administration of the 11C-labelled dopamine-D2 antagonists N-methylspiperone and raclopride. The studies were repeated after protection of the D2-receptors with Haloperidol to enable a separation of specific and unspecific receptor binding. The receptor binding was evaluated by visual inspection and with the application of a kinetic model. The results showed marked specific dopamine-D2 receptor binding in the prolactinomas and minimal or no such binding in the hormonally inactive adenomas. The two tracers 11C-raclopride and 11C-N-methylspiperone showed qualitatively the same result although raclopride resulted in a higher tumor to normal brain ratio. In conclusion, PET is a valuable complement to other radiologic techniques like computed tomography and magnetic resonance imaging in the evaluation of pituitary adenomas. An assessment of the dopamine-D2 receptors in the adenomas has a direct influence on the choice of treatment because adenomas with high amounts of receptors are in most cases effectively treated with dopamine agonists like bromocriptine.
Mudd, Pamela A; Hohensee, Samantha; Lillehei, Kevin O; Kingdom, Todd T; Kleinschmidt-Demasters, Bette K
Ectopic pituitary adenomas usually occur within sphenoid sinus or nasopharynx, and seldom within the clivus. There is only a single reported example of ectopic adenoma with clinical apoplexy, albeit not from clivus. We report a 78-year-old male with known prostate carcinoma admitted with acute onset of blurred vision, suggestive of apoplexy. Work-up revealed unilateral cranial nerve VI palsy and neuroimaging showed a mass confined to the clivus; sellar region was normal. Preoperative considerations included chordoma, chondrosarcoma, or metastatic prostate carcinoma to bone. Resection was via endoscopic transsphenoidal approach to the clivus. An ectopic null cell pituitary adenoma with bland infarction was identified as the cause of the patient's clinical apoplexy. No antecedent precipitating factors for apoplexy were present; specifically the patient had not received leuprolide preoperatively, a known precipitant of pituitary apoplexy in prostate cancer patients who receive drug. We review the literature on ectopic clival pituitary adenomas, apoplexy in ectopic adenomas, and the link between apoplexy and leuprolide usage.
Zhu, J.; Leon, S.P.; Beggs, A.H.; Busque, L.; Gilliland, D.G.; Black, P.M.
The retinoblastoma tumor suppressor gene (RB1) is inactivated in hereditary and sporadic forms of retinoblastoma as well as in a number of other sporadic tumors. The majority of human pituitary tumors have been shown to be monoclonal neoplasms, suggesting that 1 or more somatic mutations are involved in the clonal expansion of a single progenitor cell. Recently, a high percentage of transgenic mice containing a disrupted RB1 allele have been shown to develop pituitary tumors. To investigate whether RB1 inactivation contributes to the development of human pituitary adenomas, the authors searched for loss of heterozygosity (LOH) within the RB1 gene locus in a variety of human pituitary adenomas. They screened 34 adenomas for LOH using a polymerase chain reaction (PCR)-based microsatellite polymorphic marker at the RB1 gene locus. In addition, a variable number of tandem repeat markers from within the RB1 gene was also used to search for LOH in 14 tumors. They found no LOH or microsatellite instability at the RB1 locus in any of the informative cases (30 of 34). Additionally, they showed that 4 representative adenomas from female patients are monoclonal in origin using a PCR-based clonality analysis assay. They conclude that the RB1 gene shows no LOH in a variety of human pituitary adenomas and that PCR-based microsatellite markers can serve as a useful tool for LOH analysis in human pituitary tumors. 42 refs., 3 figs., 1 tab.
He, Wei; Huang, Ling; Shen, Xiaoli; Yang, Yanlin; Wang, Dapeng; Yang, Yue; Zhu, Xingen
The RWD-containing sumoylation enhancer (RSUME) can stabilize hypoxia-inducible factor-1α (HIF-1α) which promotes vascular endothelial growth factor-A (VEGF-A) expression. RSUME plays an important role in promoting the invasion of pituitary adenoma. In this study, we compared the mRNA and protein levels of RSUME, HIF-1α, and VEGF-A in pituitary adenoma tissue and analyzed the correlation. We found that the expression levels of RSUME, HIF-1α, and VEGF-A in invasive pituitary adenoma were significantly higher than in noninvasive pituitary adenoma. Moreover, a positive correlation was found between RSUME and HIF-1α/VEGF pathways. RSUME and HIF-1α were treated with hypoxia-mimicking CoCl2 and transfected into AtT-20 and GT1.1 cell lines to determine the relationship between them. It was found that RSUME effects post-transcriptional expression of HIF-1α regulated VEGF-A secretion. Reducing RSUME expression using siRNA transfection resulted in a decrease of the invasion inhibition rate of AtT-20 cells, as determined using Transwell and MTT assays. Together, we found that RSUME silencing can inhibit the invasion of pituitary adenoma cells.
Oterdoom, Leendert H; Verweij, K Evelyne; Biermann, Katharina; Langeveld, Mirjam; van Buuren, Henk R
Glycogen storage diseases (GSDs) are a group of inherited metabolic disorders characterized by accumulation of abnormal glycogen in muscle or liver or both. Specific hepatic complications include liver adenomas and hepatocellular carcinoma (HCC). Hepatocellular carcinomas described in GSD type I are often due to the degeneration of liver adenomas. Hepatocellular carcinoma in GSD type III, however, is rare and is thought to be associated with underlying cirrhosis.We present the case of a 63-year old male who was admitted for assessment of suitability for liver transplantation because of development of recurrent HCC in the presence of multiple liver adenomas. A diagnosis of GSD type III was made in this patient without underlying cirrhosis or metabolic disturbances resembling GSD. This case report is the first documentation of HCC development in an asymptomatic, non-cirrhotic patient with GSD type III. This raises the possibility that in GSD type III, the adenoma - carcinoma sequence can occur as it is also seen in GSD type I. Physicians taking care of GSD patients should be aware of this and some form of surveillance for cirrhosis and HCC should be considered. Also male patients with adenomas should have a thorough workup to reveal any underlying disease such as GSD.
Gentilin, Erica; Minoia, Mariella; Molè, Daniela; delgi Uberti, Ettore C.; Zatelli, Maria Chiara
Magmas is a nuclear gene that encodes for the mitochondrial import inner membrane translocase subunit Tim16. Magmas is overexpressed in the majority of human pituitary adenomas and in a mouse ACTH-secreting pituitary adenoma cell line. Here we report that Magmas is highly expressed in two out of four rat pituitary adenoma cell lines and its expression levels inversely correlate to the extent of cellular response to staurosporine in terms of apoptosis activation and cell viability. Magmas over-expression in rat GH/PRL-secreting pituitary adenoma GH4C1 cells leads to an increase in cell viability and to a reduction in staurosporine-induced apoptosis and DNA fragmentation, in parallel with the increase in Magmas protein expression. These results indicate that Magmas plays a pivotal role in response to pro-apoptotic stimuli and confirm and extend the finding that Magmas protects pituitary cells from staurosporine-induced apoptosis, suggesting its possible involvement in pituitary adenoma development. PMID:24069394
Deshmukh, Ajinkya Amritrao; Deshmukh, Atul A.
A 65-year-old female patient reported with a chief complaint of swelling in the left lower region of the jaw since two years. On clinical examination, the swelling was present on the mandibular left posterior region and measuring approximately 6.2 cm antero-posteriorly × 6.2 cm mediolaterally × 8.7 cm superioinferiorly. Initially, it was non tender but eventually it became tender. Fine needle aspiration was done to rule out any salivary gland pathology and report obtained was carcinoma ex pleomorphic adenoma. Then, excisional biopsy was taken and tissue sent for histopathology. Histopathological diagnosis was benign adenoma with carcinoma. Later serial sections of tissue were studied and came to the conclusion of carcinoma ex pleomorphic adenoma which was non invasive type and showed bizarre cells with neoplastic changes. Benign part was composed of myxomatous area with partial capsule. Neoplastic cells showed invasion into capsule and few necrotic areas were also present. Overall interpretation was favoured Non invasive carcinoma ex pleomorphic adenoma. So here, we reported a case of Carcinoma ex Pleomorphic Adenoma (CAEXPA) which is a deadly and rare variant of salivary gland malignancy. PMID:28658924
Buva, Kirti Balkrishna; Deshmukh, Ajinkya Amritrao; Deshmukh, Atul A
A 65-year-old female patient reported with a chief complaint of swelling in the left lower region of the jaw since two years. On clinical examination, the swelling was present on the mandibular left posterior region and measuring approximately 6.2 cm antero-posteriorly × 6.2 cm mediolaterally × 8.7 cm superioinferiorly. Initially, it was non tender but eventually it became tender. Fine needle aspiration was done to rule out any salivary gland pathology and report obtained was carcinoma ex pleomorphic adenoma. Then, excisional biopsy was taken and tissue sent for histopathology. Histopathological diagnosis was benign adenoma with carcinoma. Later serial sections of tissue were studied and came to the conclusion of carcinoma ex pleomorphic adenoma which was non invasive type and showed bizarre cells with neoplastic changes. Benign part was composed of myxomatous area with partial capsule. Neoplastic cells showed invasion into capsule and few necrotic areas were also present. Overall interpretation was favoured Non invasive carcinoma ex pleomorphic adenoma. So here, we reported a case of Carcinoma ex Pleomorphic Adenoma (CAEXPA) which is a deadly and rare variant of salivary gland malignancy.
Brady, Paula C; Missmer, Stacey A; Laufer, Marc R
Endometriosis-ectopic implantation of endometrial-like tissue-affects 10% of female adolescents and adults. First-line treatment includes progesterone only (such as norethindrone acetate [NET-A]) or combined estrogen/progestin oral contraceptive pills. Estrogen-containing contraceptives confer increased risk of hepatic adenomas, whereas the association with NET-A is very rarely reported. Three adolescents with stage I to II endometriosis managed with NET-A (up to 15 mg/d for 28-78 months) were diagnosed with hepatic adenomas at ages 17-22 years. They previously received estrogen-containing medications, which were stopped 24 months or longer before diagnosis of hepatic adenoma. NET-A in a dose greater than 10 mg/d might be associated with increased risk for hepatic adenomas, likely due to peripheral conversion to ethinyl estradiol. Use of NET-A might not be advisable in patients with known hepatic adenomas. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.
Losa, M; Fortunato, M; Molteni, L; Peretti, E; Mortini, P
Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Patients with TSH-secreting adenoma usually present with signs and symptoms of hyperthyroidism milder than those in patients with hyperthyroidism of thyroid origin, in addition to symptoms secondary to mass effects of the pituitary tumour. Mixed pituitary tumours co-secrete growth hormone and prolactin. The characteristic biochemical abnormalities are normal or high serum TSH concentrations in the presence of elevated total and/or free thyroid hormones concentrations. Measurement of markers of peripheral thyroid hormone action and dynamic tests may aid in the differential diagnosis with the syndrome of resistance to thyroid hormone. Neuroimaging is fundamental to visualize the pituitary tumor. Therapy of TSH-secreting adenomas can be accomplished by surgery, radiation therapies, and medical treatment with somatostatin analogs or dopamine agonists. Nowadays, and in contrast with the first reports on this rare disease, most patients are well controlled by current therapies.
Ben, Qiwen; Wang, Lifu; Liu, Jun; Qian, Aihua; Wang, Qi; Yuan, Yaozong
The International Agency for Research on Cancer concluded that alcohol consumption was positively related to colorectal cancer. However, the association between alcohol consumption and colorectal adenoma (CRA), the established precancerous lesion of colorectal cancer, remains unclear. We identified studies from a literature search of MEDLINE, EMBASE, and ISI Web of Science through 31 October 2013, and by searching reference lists of pertinent articles. Summary relative risks with 95% confidence intervals were calculated using a random-effects model. A total of 30 studies with 26,145 incident CRA cases were included. Overall, an increase of 25 g (two drinks) per day of alcohol consumption was related to an increased risk of CRA (summary relative risk=1.27, 95% confidence interval: 1.17-1.37). There was considerable heterogeneity between studies not explained by study design, sex, geographic location, publication year, site or size of the lesions, type of adenoma, number of cases, endoscopic assessment, or adjustment for main confounders. The positive association was evident for both men and women and for colonic adenoma, but not for rectal adenoma. Increased alcohol consumption is associated with an increased risk of CRA for both men and women and for adenoma in the colon, but not in the rectum.
Galbraith, Rachel L.; Poole, Elizabeth M.; Duggan, David; Muehling, Jill; Hsu, Li; Makar, Karen; Xiao, Liren; Potter, John D.; Ulrich, Cornelia M.
The WNT/β-catenin signaling pathway upregulates transcription of genes involved in cell proliferation and cancer progression; it has been implicated in colorectal adenoma formation. To date, no studies have examined polymorphisms in WNT genes or WNT gene–environment interactions in relation to adenoma risk. Within a colonoscopy-based case-control study of 628 adenoma cases and 516 polyp-free controls, we analyzed two tagSNPs in WNT6 (rs6747776 G > C, rs6754599 G > C) and WNT10A (rs7349332 G > A, rs10177996 A > G). The WNT6 rs6747776 homozygous minor allele (CC) was associated with increased risk of colorectal adenoma (OR = 2.75, 95% CI: 1.03–7.31). We observed a statistically significant interaction between WNT6 rs6747776 and the proportion of calories from total fat (P-int = 0.02), where the highest risk was observed among those with minor alleles and lowest fat intake. We also detected a marginally significant (0.05 < P ≤ 0.10) interaction with fish intake (P-int = 0.09). Additionally, a marginally significant interaction was observed between proportion of calories from saturated fat and the WNT10A rs7349332 polymorphism. Our results suggest that genetic variability in the WNT pathway may play a role in colorectal adenoma formation or may partly mediate the increased risk of colorectal cancer associated with fat intake. PMID:21547848
Galbraith, Rachel L; Poole, Elizabeth M; Duggan, David; Muehling, Jill; Hsu, Li; Makar, Karen; Xiao, Liren; Potter, John D; Ulrich, Cornelia M
The WNT/β-catenin signaling pathway upregulates transcription of genes involved in cell proliferation and cancer progression; it has been implicated in colorectal adenoma formation. To date, no studies have examined polymorphisms in WNT genes or WNT gene-environment interactions in relation to adenoma risk. Within a colonoscopy-based case-control study of 628 adenoma cases and 516 polyp-free controls, we analyzed two tagSNPs in WNT6 (rs6747776 G > C, rs6754599 G > C) and WNT10A (rs7349332 G > A, rs10177996 A > G). The WNT6 rs6747776 homozygous minor allele (CC) was associated with increased risk of colorectal adenoma (OR = 2.75, 95% CI: 1.03-7.31). We observed a statistically significant interaction between WNT6 rs6747776 and the proportion of calories from total fat (P-int = 0.02), where the highest risk was observed among those with minor alleles and lowest fat intake. We also detected a marginally significant (0.05 < P ≤ 0.10) interaction with fish intake (P-int = 0.09). Additionally, a marginally significant interaction was observed between proportion of calories from saturated fat and the WNT10A rs7349332 polymorphism. Our results suggest that genetic variability in the WNT pathway may play a role in colorectal adenoma formation or may partly mediate the increased risk of colorectal cancer associated with fat intake.
Mishra, Ankur; Newman, David
Context. Severe hypercalcemia is a life-threatening condition. Atypical parathyroid adenoma and parathyroid carcinomas are uncommon causes which can be difficult to differentiate. Objective. We report a case of a 36-year-old male with very high serum calcium due to a possible atypical parathyroid adenoma versus parathyroid carcinoma. Case Illustration. A serum calcium level of 23.2 mg/dl was noted on admission. He was initially treated with IV hydration, pamidronate, and salmon calcitonin to lower his calcium levels. He also underwent a surgical en bloc resection of parathyroid mass. Pathology showed a mixed picture consistent with possible atypical adenoma versus parathyroid carcinoma. However, due to the possible involvement of the recurrent laryngeal nerve, parathyroid carcinoma was more likely. Also after operation the patient developed hungry bones syndrome and his calcium was replaced vigorously. He continues to be on calcium, vitamin D, and calcitriol supplementation. Results. A review of the literature was conducted to identify previous studies pertaining to parathyroid adenomas and parathyroid cancer. Conclusion. We thereby conclude that hypercalcemia requires very careful monitoring especially after operation. Also it can be very difficult to distinguish between atypical parathyroid adenomas and parathyroid carcinomas as in our case and no clear cut guidelines yet exist to differentiate the two based on histology. PMID:24959180
Félix, I A; Rodríguez Mendoza, L; Guinto, G; Torres Corzo, J; Wussterhaus, C A
Study of biopsies from 120 pituitary adenomas from the Hospital de Especialidades, Centro Médico Nacional, and the Hospital 20 de Noviembre, ISSSTE, were studied over a period of 55 months. 70 cases were female and 50 male. Ages varied between 18 and 67 years of age (with an average of 31 years). Histologically 41 tumors were chromophobes, 34 acidophilic, 37 mixed and 8 basophilic. 101 patients were operated by trans-sphenoidal (84.5%) and 19 were operated (15.5%) by trans-cranial approaches. 99 tumors were macroadenomas (81.1%) and 21 were microadenomas (18.9%). More than one hormone was found in the cytoplasm of 69 adenomas, although only 20 fulfilled the criteria of being plurihormonal. Those adenomas classified as "non-functional", mostly produced glycoprotein hormones corresponding to oncocytomas and null cell adenomas, from an ultrastructural point of view. 85 patients developed different degrees of visual impairment, with 30 tumoral relapses, of which 10 received radiotherapy. 40 adenomas produced prolactin, although only 29 patients developed clinical signs of hyperprolactinemia; 38 tumors contained growth hormone, of which only 25 had acromegaly; 8 tumors contained ACTH in the cytoplasm, although only 7 developed Cushing's Syndrome and 57 patients (47.5%) were classified as nonfunctional and did not show any endocrinological data. All the cases are studied with a light microscope, electron microscope, and they were all submitted to a complete set of adenohypophyseal hormone with immunoperoxidase technique.
Rooney, Sydney L; Robinson, Robert A
Basal cell predominant salivary gland neoplasms can be difficult to separate histologically. One of the most aggressive of basaloid salivary gland neoplasms is adenoid cystic carcinoma. MYB expression by immunohistochemistry has been documented in adenoid cystic carcinoma. Some investigators have suggested that using this expression can help in establishing the diagnosis of adenoid cystic carcinoma. Utilizing tissue microarrays, we studied a group of basal cell adenocarcinomas and basal cell adenomas to determine: (i) whether either tumor expressed MYB and (ii) the frequency of any expression in either tumors. Seventeen salivary gland basal cell adenocarcinomas and 30 salivary gland basal cell adenomas were used to construct microarrays. These tissue microarrays were used to assess for immunohistochemical MYB expression. Fifty-three percent (nine of 17) of salivary gland basal cell adenocarcinomas and 57% (17 of 30) of salivary gland basal cell adenomas showed MYB overexpression. For comparison, we studied 11 adenoid cystic carcinomas for MYB expression and found that 64% (seven of 11) overexpressed MYB. We found no relation to clinical course for basal adenomas or basal cell adenocarcinomas that overexpressed MYB vs those that did not. MYB expression does not help separate basal cell adenocarcinomas from basal cell adenomas, and our data suggest it does not differentiate between either of these neoplasms and adenoid cystic carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Mercado, Moises; Melgar, Virgilio; Salame, Latife; Cuenca, Dalia
Clinically non-functioning pituitary adenomas (NFPAs) are among the most common tumors in the sellar region. These lesions do not cause a hormonal hypersecretion syndrome, and are therefore found incidentally (particularly microadenomas) or diagnosed based on compressive symptoms such as headache and visual field defects, as well as clinical signs of pituitary hormone deficiencies. Immunohistochemically, more than 45% of these adenomas stain for gonadotropins or their subunits and are therefore called gonadotropinomas, while 30% of them show no immunostaining for any hormone and are known as null cell adenomas. The diagnostic approach to NFPAs should include visual field examination, an assessment of the integrity of all anterior pituitary hormone systems, and magnetic resonance imaging of the sellar region to define tumor size and extension. The treatment of choice is transsphenoidal resection of the adenoma, which in many instances cannot be completely accomplished. The recurrence rate after surgery may be up to 30%. Persistent or recurrent adenomas are usually treated with radiation therapy. In a small proportion of these cases, drug treatment with dopamine agonists and, to a lesser extent, somatostatin analogs may achieve reduction or at least stabilization of the tumor. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.
Yoshida, Daizo; Kim, Kyongsong; Ishii, Yudo; Tahara, Shigeyuki; Teramoto, Akira; Morita, Akio
Gremlin is an antagonist of bone morphogenetic protein (BMP) and a major driving force in skeletal modeling in the fetal stage. Several recent reports have shown that Gremlin is also involved in angiogenesis of lung cancer and diabetic retinopathy. The purpose of this study was to investigate the role of Gremlin in tumor angiogenesis in pituitary adenoma. Double fluorescence immunohistochemistry of Gremlin and CD34 was performed in pituitary adenoma tissues obtained during transsphenoidal surgery in 45 cases (7 PRLoma, 17 GHoma, 2 ACTHoma, and 2 TSHoma). Gremlin and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from tissue microarray analysis of 60 cases of pituitary adenomas (6 PRLoma, 23 GHoma, 22 NFoma, 5 ACTHoma, and 4 TSHoma). In tissue microarray analysis, MVD was significantly correlated with an increased Gremlin level (linear regression: P < 0.005, r 2 = 0.4958). In contrast, Gremlin expression showed no correlation with tumor subtype or Knosp score. The high level of expression of Gremlin in pituitary adenoma tissue with many CD34-positive vessels and the strong coherence of these regions indicate that Gremlin is associated with angiogenesis in pituitary adenoma cells. PMID:25834571
Jrebi, Nezar Y; Hefty, Matthew; Jalouta, Tarek; Ogilvie, James; Davis, Alan T; Asgeirsson, Theodor; Luchtefeld, Martin
The adenoma detection rate (ADR) is a quality indicator for colonoscopy. High-definition (HD) imaging has been reported to increase polyp detection rates. The primary objective of this study was to compare polyp detection rate (PDR) and adenoma detection rate (ADR) before and after the implementation of HD colonoscopy. A retrospective chart review was performed on patients aged 48-55 years old, who underwent first-time screening colonoscopy. The first group underwent standard-definition (SD) colonoscopy in the first 6 months of 2011. The second group underwent screening with HD colonoscopy during the first 6 months of 2012. We compared age, gender, PDR, ADR, and average sizes of adenomatous polyps between gastroenterologist and colorectal surgeon and among physicians themselves. Statistical analysis was performed with Fischer's exact test and Pearson Chi-square. A total of 1268 patients were involved in the study (634 in each group). PDR (35.6 vs. 48.2 %, p < 0.001) and ADR (22.2 vs. 30.4 %, p = 0.02) were higher in the HD group. The average size of an adenomatous polyp was the same in the two groups (0.58 vs. 0.57, p = 0.69). However, this difference was not seen among colorectal surgeons PDR (35.7 vs. 37 %, p = 0.789), ADR (22.9 vs. 24.5 % p = 0.513), but clearly seen among gastroenterologist, PDR (35.6 vs. 53.1 % p < 0.001) and ADR (21.9 vs. 32.9 % p < 0.001). When polyps were categorized into size groups, there was no difference in ADR between the two timeframes (<5 mm in size (41.5 vs. 35.4 %), 5-10 mm (49.3 vs. 60.1 %) and >10 mm (9.2 vs. 4.5 %), p = 0.07). Polyps were most commonly seen in the sigmoid colon (26.1 vs. 24.7 %). There was no difference in the rate of synchronous polyp detection between modalities (25.6 vs. 29 %, p = 0.51). Withdrawal time was the same in both procedure (9.2 vs. 8.5 min, p = 0.10). Screening colonoscopy with high-definition technology significantly improved both PDR and ADR. In addition
Sewda, Kamini; Coppola, Domenico; Enkemann, Steven; Yue, Binglin; Kim, Jongphil; Lopez, Alexis S; Wojtkowiak, Jonathan W; Stark, Valerie E; Morse, Brian; Shibata, David; Vignesh, Shivakumar; Morse, David L
Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.
Yang, B T; Chong, V F H; Wang, Z C; Xian, J F; Chen, Q H
Ectopic pituitary adenomas (EPAs) are rare lesions. The purpose of this study was to describe the CT and MRI features of sphenoid sinus EPAs. Eight patients with histology-proven EPAs in the sphenoid sinus, all of whom underwent CT and MRI, were reviewed retrospectively. The following imaging features were analysed: (i) size, (ii) margin, (iii) CT attenuation characteristics and (iv) MRI signal intensity. In addition, the involvement of adjacent structures and the time–intensity curve (TIC) of dynamic contrast-enhanced (DCE) MRI were analysed. All EPAs had well-defined margins and showed no relationship to the intrasellar pituitary gland. The mean size was 28 mm (range, 20–46 mm). On non-enhanced CT, the lesions appeared isodense to grey matter in 7 (88%) patients and hypodense in 1 (12%) patient. Only two patients underwent post-contrast CT, and they showed moderate enhancement. On T1 weighted images, EPAs appeared isointense in 6 (75%) patients and hypointense in 2 (25%). On T2 weighted images, the lesions appeared hyperintense in 2 (25%) patients and isointense in 6 (75%). EPAs showed mild to moderate heterogeneous contrast enhancement and exhibited a cribriform-like appearance. Two patients underwent DCE MRI; the TIC showed a rapidly enhancing and slow washout pattern. The following features were also seen: an empty sella, bone changes and involvement of the cavernous sinus (5 patients; 62.5%). In conclusion, a high index of suspicion for EPA and a familiarity with the imaging findings may help to diagnose this rare entity accurately. PMID:19651706
Doolittle, Derrick A; Atwell, Thomas D; Sanchez, William; Mounajjed, Taofic; Hough, David M; Schmit, Grant D; Kurup, A Nicholas
Given the recent classification of hepatic adenoma (HA) into subtypes and recognition of imperfect specificity of MRI to differentiate HA from focal nodular hyperplasia (FNH), there is a resurgent interest in the role of biopsy to diagnose HA. The purpose of this study was to determine the safety and outcomes of biopsy of HAs. A retrospective review of the electronic medical records of all patients who underwent hepatic mass biopsy revealing HA from 2000 through 2013 was performed. The biopsy procedure parameters were evaluated. Complications were graded using the Common Terminology Criteria for Adverse Events. Pathology-specific outcomes related to the diagnosis of HA were assessed. Sixty patients (52 women and eight men) were identified with a mean age of 42 ± 13 (SD) years and a mean follow-up of 2.3 ± 3.0 years after biopsy. One patient had two HAs biopsied during the same procedure, resulting in a total of 61 biopsy-proven HAs. Of the 60 patients, one patient (2%) had a single major complication, which involved bleeding that resulted in a blood transfusion, and six patients (10%) had a minor complication. A total of six (10%) discordant biopsy results were found: Four biopsy-proven HAs (7%) revealed FNH on surgical resection or repeat biopsy, one HA (2%) showed well-differentiated hepatocellular carcinoma (HCC) at subsequent biopsy, and one HA (2%) showed findings suggestive of HCC on follow-up imaging. Complications after biopsy of HAs are uncommon. Although uncommon, discordant pathology results between biopsy and surgical resection may occur.
Yadav, Yr; Sachdev, S; Parihar, V; Namdev, H; Bhatele, Pr
Endoscopic endonasal trans-sphenoid surgery (EETS) is increasingly used for pituitary lesions. Pre-operative CT and MRI scans and peroperative endoscopic visualization can provide useful anatomical information. EETS is indicated in sellar, suprasellar, intraventricular, retro-infundibular, and invasive tumors. Recurrent and residual lesions, pituitary apoplexy and empty sella syndrome can be managed by EETS. Modern neuronavigation techniques, ultrasonic aspirators, ultrasonic bone curette can add to the safety. The binostril approach provides a wider working area. High definition camera is much superior to three-chip camera. Most of the recent reports favor EETS in terms of safety, quality of life and tumor resection, hospital stay, better endocrinological, and visual outcome as compared to the microscopic technique. Nasal symptoms, blood loss, operating time are less in EETS. Various naso-septal flaps and other techniques of CSF leak repair could help reduce complications. Complications can be further reduced after achieving the learning curve, good understanding of limitations with proper patient selection. Use of neuronavigation, proper post-operative care of endocrine function, establishing pituitary center of excellence and more focused residency and endoscopic fellowship training could improve results. The faster and safe transition from microscopic to EETS can be done by the team concept of neurosurgeon/otolaryngologist, attending hands on cadaveric dissection, practice on models, and observation of live surgeries. Conversion to a microscopic or endoscopic-assisted approach may be required in selected patients. Multi-modality treatment could be required in giant and invasive tumors. EETS appears to be a better surgical option in most pituitary adenoma.
Yadav, YR; Sachdev, S; Parihar, V; Namdev, H; Bhatele, PR
Endoscopic endonasal trans-sphenoid surgery (EETS) is increasingly used for pituitary lesions. Pre-operative CT and MRI scans and peroperative endoscopic visualization can provide useful anatomical information. EETS is indicated in sellar, suprasellar, intraventricular, retro-infundibular, and invasive tumors. Recurrent and residual lesions, pituitary apoplexy and empty sella syndrome can be managed by EETS. Modern neuronavigation techniques, ultrasonic aspirators, ul