Positivity For Inhibin Research Articles

Rare Diagnoses and Diagnostic Pitfalls in Female Genital Tract Neoplasms: A Case Series

There is a wide spectrum of disorders that may originate from different parts of the female genital tract. They are often unique and rare, posing a diagnostic challenge for reporting pathologists. Their uniqueness lies in the rare histomorphologic picture and challenging clinical scenarios, accentuated by a paucity of available literature. Sometimes, histomorphology alone may not be sufficient for diagnosis, and ancillary studies like Immunohistochemistry (IHC) may help arrive at a definitive diagnosis. Present article represents a series of six unique cases. The first case presented with virilising features and menstrual irregularities. Gross examination of the adnexal neoplasm showed solid yellowish-orange areas, which were diagnosed as Steroid Cell Tumour (SCT), Not Otherwise Specified (NOS) based on histomorphology. This diagnosis was further substantiated by diffuse and strong Inhibin positivity on IHC. The second case presented with huge abdominal distention and markedly raised CA-125 levels. It was diagnosed as mucinous carcinoma with a focus of Benign Brenner Tumour. The third case presented with postmenopausal bleeding and underwent radical hysterectomy. Gross examination revealed simultaneous involvement of the unilateral adnexa, and it was finally diagnosed as endometrioid carcinoma with adnexal metastasis, International Federation of Gynaecology and Obstetrics (FIGO) stage IIIA. The fourth case was a cervical carcinoma with histomorphology suggestive of high-grade, but it did not fit into any of the known subtypes of adenocarcinoma. Therefore, it was reported as Adenocarcinoma NOS with focal mucinous differentiation. The fifth case was a rare cervical Adenosquamous Carcinoma (ASCC) with both malignant squamous and glandular components. The sixth case was of mesenchymal origin in the vulva, namely Aggressive Angiomyxoma (AA). All these cases highlight the fact that pathologists should be well aware of these entities to make an appropriate diagnosis.

Unusual case of infrarenal pheochromocytoma developed on ectopic adrenal tissue: An autopsy case report

Abstract Introduction: Pheochromocytomas are catecholamine-secreting tumors arising from the chromaffin cells of the adrenal medulla. We describe an unusual case of pheochromocytoma located in the infrarenal area and associated with bilateral adrenal hyperplasia. Case presentation: A 70-year-old patient was admitted for syncope, diaphoresis, and high blood pressure. Computed tomography showed a 73×70×72 mm retroperitoneal mass of the left infrarenal area. High levels of metanephrine and noradrenaline were found in the urine. A tumor resection was performed. A few days after surgery, the blood pressure suddenly decreased and could not be restored, resulting in the death of the patient. Histopathological examination of the surgical specimen revealed a proliferation of monotonous cells, with eosinophilic cytoplasm, round nuclei with prominent nucleoli arranged in clusters, and capsular and vascular invasion. The tumor cells expressed synaptophysin and chromogranin, without positivity for inhibin A or S100 protein. At the autopsy, both adrenal glands showed hyperplasia but unrelated to the tumor mass. The histological aspect, location, and immunophenotype indicated an ectopic infrarenal pheochromocytoma. Conclusions: In patients with pheochromocytoma developed on ectopic adrenal tissue, clinical management might be difficult, and diagnosis can be sometimes established only based on post-mortem histopathological examination. Autopsy can be extremely useful in such cases with unexplained evolution.

SUN-931 Characterization of an Ovarian Steroid Cell Tumor in a VHL Patient

Most ovarian steroid cell tumors arise sporadically. However, they can also be observed as a rare manifestation of von Hippel Lindau disease. Here, we present a clinical, pathological and molecular characterization of a steroid cell tumor in a VHL patient. A 14 year old girl with molecularly confirmed diagnosis of VHL developed hirsutism and amenorrhea. Initial clinical hormonal evaluation was notable for elevated 17-OHP of 406ng/dl, androstenedione 275ng/dl, and testosterone 102ng/dl. In order to exclude congenital adrenal hyperplasia as a common cause of hirsutism in adolescents, ACTH stimulation was performed, but no increase in 17-OHP was observed. Anti Muellerian hormone, inhibin (INH) A and INH B were normal. Imaging revealed a bilobed 6cm left adnexal mass. The mass was resected en bloc via a left oophorectomy. Pathological evaluation showed multinodular steroid cell tumor with clear cytoplasm and delicate vascular meshwork. Immunoprofiling demonstrated positivity for inhibin and calretinin; while renal cell carcinoma markers were negative. All laboratory values normalized post-surgery. In addition to clinical measurements pre- and post-surgery, steroid profiles were evaluated by LC-MS/MS. Quantitative RT-PCR analysis showed robust tumor expression of enzymes facilitating the production of androgens, but not estrogens. Further preliminary analysis by exome sequencing confirmed the known germline pathogenic variant in VHL, but no additional obvious somatic driver mutations were identified. Interestingly, the NGS analysis of different specimens from the same tumor revealed multiple different single base pair variants in the VHL gene as a second hit. In summary, hirsutism in VHL patients should raise the suspicion for unusual ovarian tumors. In contrary to the usual theory of a monoclonal expansion after loss of the wt VHL allele, this tumor appeared to be oligoclonal as evidenced by different somatic VHL mutations. This could be either explained by initial parallel occurrence of several clones or that the VHL second hit is not an initial event, but the mutation instead supports tumor expansion following initial steps of tumorigenesis.

"Dissecting Gonadoblastoma" of Scully: A Morphologic Variant That Often Mimics Germinoma.

Dr Robert E. Scully, who recognized and defined gonadoblastoma (GB), used the term "dissecting gonadoblastoma" (DGB) to describe variants with either an infiltrative type or diffuse pattern instead of the usual small nested arrangement. These patterns have not been emphasized in the literature. To investigate the features of DGB we examined 50 GBs microscopically and performed immunohistochemistry (IHC) in some. DGB was found in 38 (76%) GBs and was represented by 3 patterns. The most frequent was solid/expansile (n=26), consisting of large coalescent nests of germ cells, often (92%) interrupted by fibrovascular septa, with usually minor numbers of sex cord cells. Less frequent were small anastomosing nests (n=24) and cord-like arrangements (n=22) of germ cells irregularly distributed in a prominent stroma and with mostly inconspicuous sex cord cells. Most DGBs (24) showed >1 pattern and demonstrated the characteristic globular deposits of basement membrane, although these were often subtle. The germ cells in all patterns varied from spermatogonium-like to seminoma-like; OCT3/4 was positive only in the latter (7/7). The sex cord cells were small with dense, oval or angulated nuclei, inconspicuous nucleoli, and positivity for inhibin (9/9, strong), FOXL2 (9/9, strong), SF1 (8/9, strong), SOX9 (9/9, weak and focal), WT1 (5/7, variable), and calretinin (3/7, variable). Granulomas were present in 84% of germinoma foci, 13% of DGB foci, and 8% of classic GB foci. Twenty two of 38 DGBs had associated germinoma; 3 also had embryonal carcinoma, yolk sac tumor, and choriocarcinoma, respectively. Follow-up of 2 cases lacking an invasive tumor showed that both patients were disease free at 13 and 4.8 years after bilateral gonadectomy. We conclude that DGB is commonly seen with classic GB and displays identical IHC features, supporting it as a morphologic variant of GB. It appears likely that cord-like DGB is the earliest phase in a GB developmental continuum that may proceed successively into anastomosing, nested (classic GB), and solid/expansile patterns. DGB often mimics germinoma because of the large size of the nests, pseudoinfiltrative pattern of some cases, and inconspicuous sex cord cells. The presence of sex cord cells (identification aided by IHC for sex cord markers), the heterogenous morphology of the germ cells, and globules of basement membrane are useful differential features. The lack of a granulomatous reaction also favors DGB over germinoma. Mistaking DGB for GB with invasive germinoma may result in more aggressive therapy than warranted. The likely relationship of DGB to the relatively recently described concept of so-called "undifferentiated gonadal tissue" is discussed herein.

Cytomorphology and Clinicopathologic Correlation of the Recurrent and Metastatic Adult Granulosa Cell Tumor of the Ovary: A Retrospective Review.

Granulosa cell tumors (GCT) of the ovary are low grade tumor with a potential ability of late pelvic recurrences and distant metastases. However, there is sparse literature on the cytopathologic features of metastatic granulosa cell tumors (MGCT). Between 2000 and 2014, eight cases of MGCT were diagnosed by FNA. Clinical, cytologic, and histopathologic features were reviewed. The age ranged from 34 to 84 years. Metastases were found in abdominal wall (4 cases), pelvic mass (1 case), liver (2 cases), and lung (1 case). The time to metastasis ranged from 1 to 14 years. All cases were hypercellular, with both large and small overlapping cell clusters and individual cells. The cytologic features included: naked nuclei (8/8 cases), Call-Exner bodies (2/8 cases), and prominent metachromatic stroma (3/8 cases). Moderate cytoplasm (4/8 cases) to scant delicate cytoplasm (4/8 cases) was seen. Cytoplasmic vacuoles were also noted (6/8 cases). N/C ratios were high although lower than small round cell tumors like lymphoma. Prominent, central nucleoli were also present (6/8 cases) as well as nuclear grooves (2/8 cases). Cell block was available in 3/8 cases and all were positive for inhibin immunostain. Histologic examination of the metastatic tissue confirmed MGCT. The important cytologic features of GCT like uniformity of tumor cells, nuclear grooves and Call-Exner bodies are occasionally present in MGCT. Prominent nucleoli and many naked nuclei were frequent. Therefore, the accurate interpretation of cytologic findings of MGCT requires cytohistologic correlation and inhibin positivity to avoid unnecessary surgical interventions for diagnostic purposes. The possibility of late recurrence of GCT should be kept in mind. Diagn. Cytopathol. 2016;44:1058-1063. © 2016 Wiley Periodicals, Inc.

Enxtraoviarian granulosa cell tumor: a case report

Extraovarian granulosa cell tumor (GCT) is a very unusually tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian granulosa cell tumor was encountered in a 60-year-old female patient who presented with a large intra-abdominal mass. Computerized tomography revealed a large retroperitoneal mass measuring 11 x 10 x 8cm in size. Her past medical history was irrelevant. She underwent exploration laparotomy and the mass was excised. Histopathological examination of the excised mass showed features of adult-type granulosa cell tumor.The tumor showed positivity for inhibin while epithelial membrane antigen was negative thus confirming the diagnosis of granulosa cell tumor. A diagnosis of extraovarian granulosa cell tumor can only be done after excluding any previous history of granulosa cell tumor of the ovary. Immunostains help to differentiate granulosa cell tumors from other neoplasms.

Extra - Ovarian Granulosa Cell Tumor : A Case Report

Extraovarian granulosa cell tumor is a very rare tumor, assumed to arise from mesenchymal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian granulosa cell tumor was encountered in a 73-year-old female patient who presented with a large intraabdominal mass. Computerized tomography revealed a large retroperitoneal mass measuring 9 cm x 6.5 cm. Her past medical history was irrelevant. She underwent exploration laparotomy and the mass was excised. Histopathological examination of the excised mass showed features of adult-type granulosa cell tumor. Because metastatic epithelial tumors, particularly from the ovaries, may show identical morphology, immunostains for inhibin and Epithelial Membrane Antigen (EMA) were performed. The tumor showed positivity for inhibin while epithelial membrane antigen was negative thus confirming the diagnosis of granulosa cell tumor. A diagnosis of extraovarian granulosa cell tumor can only be done after excluding any previous history of granulosa cell tumor of the ovary. Immunostains help to differentiate granulosa cell tumors from other neoplasms.

Inhibin-expressing clear cell neuroendocrine tumor of the ampulla: an unusual presentation of von Hippel–Lindau disease

von Hippel-Lindau (VHL) disease is a hereditary autosomal dominant disorder associated with deletions or mutations in the VHL tumor suppressor gene. Characteristically, up to 60% of neuroendocrine tumors (NETs) associated with VHL disease display a spectrum of clear cell morphology including multivacuolated lipid-rich cell change. Unlike neurofibromatosis type 1 and multiple endocrine neoplasia type 1 syndromes, ampullary NETs have not been described in association with VHL disease. In this report, we discuss the features of an incidental ampullary clear cell NET occurring in a patient with pancreatic VHL disease including multiple pancreatic NETs. The ampullary lesion consisted of epithelial cells resembling lipoblasts or signet ring cells. In our case, all NETs showing clear cell change were positive for inhibin. While the underlying mechanism of this finding is largely unknown, it is of note that positivity for inhibin has not been observed in clear cell NETs associated with multiple endocrine neoplasia type 1 syndrome. Our case proves that NETs can develop in the ampullary region in patients with VHL; clear cell change can occur in these lesions and can mimic signet ring cell carcinoma. This issue is of clinical significance especially in small biopsy samples; thus, positivity for keratin alone should not be taken as evidence of an adenocarcinoma. Moreover, demonstration of inhibin expression in a NET with clear cell change along with other clinical stigmata should alert the diagnostician to the possibility of VHL disease. However, further larger series examining inhibin expression in both syndrome-related and sporadic clear cell NETs are needed to confirm our findings.

Hemangioblastoma of the Gastrointestinal Tract

We present the first documented case of hemangioblastoma located in the left colon. A 75-year-old woman undergoing adjuvant chemotherapy for breast cancer experienced rectal bleeding. Colonoscopy revealed a roundish mass covered with normal mucosa in the sigmoid colon. Endoscopic ultrasound showed an isoechoic lesion originating from the third layer of the intestinal wall; underlying layers were normal. Endoscopic ultrasound features were not suggestive of either cancer or malignant stromal tumor. Left hemicolectomy was subsequently performed due to repeated episodes of lower gastrointestinal bleeding. Grossly, a circumscribed submucosal yellowish nodule (13 mm) was observed, which was not attached to any peripheral nerve. Histologically, the lesion was composed of large, atypical cells traversed by a network of blood vessels. Immunohistochemically, the cells showed positivity for inhibin and NSE and weak positivity for S-100. A diagnosis of hemangioblastoma was made. This case highlights that hemangioblastoma of the gastrointestinal tract can also occur.

Lipid-rich variant of pancreatic endocrine tumour with inhibin positivity and microscopic foci of microcystic adenoma-like areas: emphasis on histopathology

Pancreatic endocrine tumours (PETs) are uncommon tumours with typical morphology characterised by relatively uniform cuboidal cells arranged in nests and festoons, with distinctive nuclear salt-and-pepper chromatin. A lipid-rich variant poses diagnostic difficulties in the midst of other pancreatic tumours and metastatic goblet cell carcinoid. A 22-year-old man presented with symptoms of abdominal pain and jaundice. His liver function test and blood glucose level were normal, but computed tomography of the abdomen suggested the presence of a tumour in the head of the pancreas. Specimen obtained by pancreaticoduodenectomy revealed an infiltrating yellow-tan tumour composed of nests and a cribriform arrangement of polygonal vacuolated cells with pyknotic nuclei, along with focal classical areas of PET. Two foci of early serous microcystic adenoma were seen. Immunohistochemistry contributed to the arrival of a conclusive diagnosis. Von Hippel-Lindau disease was excluded in our patient, as other supportive classical features of the syndrome were absent.

Extraovarian granulosa cell tumor

Extraovarian granulosa cell tumor (GCT) is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian GCT was encountered in a 58-year-old female who presented with a large intraabdominal lump. Computerized tomography revealed one large retroperitoneal mass measuring 15 cm x 16 cm and another mesenteric mass of 8 cm x 5 cm size. The patient had a history of hysterectomy with bilateral salpingooophorectomy 20 years ago for uterine leiomyoma. Ultrasonography-guided aspiration smears revealed cytological features suggestive of GCT. Histopathological examination of the excised masses showed features of adult-type GCT. Because metastatic epithelial tumors, particularly from the ovaries, may show identical morphology, immunostains for inhibin and epithelial membrane antigen (EMA) were performed. The tumor showed positivity for inhibin while EMA was negative thus confirming the diagnosis of GCT. As this patient had no previous history of GCT and was oophorectomized 20 years ago, the tumor was considered as extraovarian. A diagnosis of extraovarian GCT should be carried out after excluding any previous history of GCT of the ovary. Immunostains help to differentiate GCTs from other neoplasms.

Uterine tumor resembling ovarian sex cord tumors treated by hysteroscopy

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) were first described in 1976 [1]. All reported cases were treated by abdominal hysterectomy. We present a case of UTROSCT managed by hysteroscopy and conservation of the uterus resulting in successful child bearing. A 28-year-old woman (gravida 0, para 0) presented with intermenstrual bleeding. Ultrasound revealed an endometrial polyp arising from the posterior uterine muscular layer. The polyp was removed at hysteroscopy. The histopathologic examination reported that the endometrium was normal. In the stroma there was focal periglandular condensation together with expanded areas demonstrating prominent ovarian sex cord-like architecture. Scattered mitotic figures were seen (up to 2 per 10 high power fields). The sex cord-like areas were positive for vimentin, the epithelial marker cytokeratin CAM 5.2, estrogen receptor (ER), and progesterone receptor (PR). Patchy positivity for inhibin and calretinin confirmed their sex cord stromal differentiation. The stroma between the sex cord-like areas was positive for actin and focally for desmin, but CD10 was only positive in the more normal areas of the endometrial stroma (Fig. 1).

Gonadoblastoma and Dysgerminoma Associated with XY Gonadal Dysgenesis in an Adolescent with Chronic Renal Failure: A Case of Frasier Syndrome

Study Objectives: To report a rare reason for primary amenorrhea, a Frasier syndrome, XY gonadal dysgenesis associated with renal failure with eventual development of gonadoblastoma. To study immunohistochemical analysis of gonadoblastoma and dysgerminoma. To analyze the possibility of androgen receptor mutation in this rare syndrome. Methods: We report a case of a 16-yr-old female with this syndrome. She underwent a laparoscopic bilateral gonadectomy and salpingectomy. A histopathological examination revealed gonadoblastoma with focal malignant dysgerminoma in the left dysgenetic gonad and an immunohistochemical of these fairly rare, malignant tumors. An androgen receptor was coded. Analysis was done. Results: Immunohistochemical analysis showed that inhibin was strongly positive in gonadoblastoma but negative in dysgerminoma. No mutations of the androgen receptor gene were found. Conclusions: Inhibin positivity in gonadal stroma and in gonadoblastoma may indicate hormonal activity causing advanced puberty in patients with XY gonadal dysgenesis.