Hilus Cell Hyperplasia Research Articles

Ovarian Hilus Cell Hyperplasia and Sertoli-Leydig Cell Tumor in a Patient with Postmenopausal Virilization: a Rare Case Report

Objective; We present a case report regarding a 71-year-old woman with postmenopausal virilization caused by ovarian hilus cell hyperplasia and Sertoli-Leydig cell tumor who was suffered from hair loss, clitoromegaly and hirsutism. Case Report; The patient’s plasma testosterone levels were high. In the MRI examination, a nodular formation of 20x26mm in size was observed in the right ovary. At the transvaginal ultrasound, a cystic mass of 28x28mm was seen in the right ovary. Then we performed a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. The final pathology showed a poorly differentiated Sertoli Leydig cell tumor at the right ovary and hilus cell hyperplasia at the left ovary. Sertoli-Leydig cell tumors, which are relatively less common, are extremely rare to be seen in the postmenopausal period. Conclusion; What distinguishes this case from others is that Sertoli-Leydig cell tumor and hilus cell hyperplasia may cause virilization symptoms together, in addition to its prevalence in advanced age.

SAT-223 Insights into Ovarian Hyperandrogenism: Lessons from Two Unusual Cases

Introduction: The majority of cases with postmenopausal hyperandrogenism have a benign etiology such as ovarian hyperthecosis, hilus cell hyperplasia, ovarian or adrenal tumors. Determining adrenal versus ovarian OR tumorous versus nontumorous causes of hyperandrogenism can be tricky. Here we report two very different cases associated with ovarian hyperthecosis. Case 1: The 73 year old obese female with a history of prediabetes, hysterectomy and breast cancer presented with severe hirsutism and virilization over 5 years. Testosterone levels per LC/MS were between 200-350 ng/dL and rose further during a 2d LDDST (Low Dose Dexamethasone Suppression Test), while cortisol and DHEA-S suppressed appropriately. Imaging was negative for an adrenal or ovarian mass. Based on the biochemical data, we suspected a tumorous ovarian source of androgen excess despite negative imaging findings. The patient underwent salpingo-oophorectomy which revealed small bilateral steroid cell tumors (0.7-0.9 cm) in the setting of bilateral focal hyperthecosis and hilus cell hyperplasia. Postoperative testosterone levels fell to 14 ng/dL. Case 2: The 53 year old obese female with a history of diabetes and PCOS presented with progressive male pattern hair loss, acne and acanthosis nigricans over 3-5 years. Her testosterone levels per LC/MS were between 100-150 ng/dL. During LDDST, cortisol and DHEA-S suppressed appropriately, testosterone increased further. Imaging was again negative for an adrenal or ovarian mass. Following this workup, the patient was treated with a GnRH analogue which resulted in complete testosterone suppression, regression of acanthosis nigricans and scalp hair regrowth. She later underwent salpingo-oophorectomy which showed only a few scattered, minute clusters of luteinizing theca cells in both ovaries, no tumor was identified. Lessons: These cases illustrate that imaging often fails to detect small ovarian tumors, stressing the need for additional diagnostic markers such as LDDST. Based on their case series, Kaltsas et al. suggested that lack of testosterone suppression during LDDST ruled out a nontumorous androgen source (1). However, this was not true for case 2 presented here: Testosterone remained non-suppressed during LDDST, yet she did not have an androgen-producing tumor, but mild hyperthecosis. Notably, her testosterone levels were <150 ng/dL. In summary, we propose that testosterone levels >150 ng/dL PLUS absent testosterone suppression during LDDST might be suggestive of androgen-producing tumors. Furthermore, therapy with GnRH can be an alternative to surgery in cases with ovarian hyperandrogenism.

Hilus Cell Hyperplasia of Fallopian Tubes: A Rare and Incidental Finding with Uterine Leiomyomas

Hilus cells are ovarian counterpart of testicular leydig cells seen at hilar region of ovary. We present an interesting case of hilus cell hyperplasia in fallopian tube associated with multiple leiomyomata of uterus in a postmenopausal woman. To our knowledge very few cases reported the existence of hilus cells outside the ovary. We received a specimen of hysterectomy with bilateral salpingooopherectomy. On gross examination both the tubes showed multiple small yellowish nodules. Microscopic examination showed aggregation of hilus cells beneath a normal tubal epithelium. Hilus cell hyperplasia was not seen in the ovaries. On immunohistochemistry, hilus cell showed positivity for vimentin and calretinin. Co-existence of hilus cell hyperplasia of fallopian tube and leiomyoma is very rare and may be subjected to further research.

Pathology of Struma Ovarii: A Report of 96 Cases.

Thyroid tissue is a relatively frequent component of mature teratoma and can occur in 5-20 % of cases. Struma ovarii is defined as ovarian goiter which comprises either entirely or predominantly thyroid tissue (>50 %). This also includes cases of mature teratoma with less than 50 % thyroid tissue but harboring thyroid-associated malignancy. A total of 118 patients with mature teratoma containing thyroid tissue were identified at our institution (1989 to 2014). Ninety-six cases were diagnosed struma ovarii, including 10 cases of papillary thyroid carcinoma, 1 case of highly differentiated follicular carcinoma of ovarian origin (HDFCO), 5 cases of strumal carcinoid, and 80 cases of struma ovarii (53 cases of thyroid-only struma ovarii). Six cases had diffuse adenomatous hyperplasia, and seven cases had focal adenomatous hyperplasia. There was no recurrence on follow-up except one of the papillary thyroid carcinomas. Concurrent primary ovarian lesions included: serous cystadenoma--3, mucinous cystadenoma--4, Brenner tumor--3, thecoma--2, ovarian fibroma--1, and focal hilus cell hyperplasia--4 cases. In this series, papillary thyroid carcinoma and strumal carcinoid were the most common well-differentiated neoplasm/malignancies arising in struma ovarii; these demonstrate a minimal or no aggressive clinical behavior.

Ovarian hemangiomas with associated hilus cell hyperplasia

Ovarian hemangiomas with associated hilus cell hyperplasia

Ovarian hilus cell hyperplasia as the cause of virilization in 45,X Turner’s syndrome

To describe a rare case of 45,X Turner's syndrome with elevated T and clitoromegaly caused by ovarian hilus cell hyperplasia. Case report. Tertiary care pediatric hospital. An 11-and-a-half-year-old girl with 45,X karyotype showed signs of accelerated growth and clitoromegaly and was found to have elevated serum T. Fluorescence in situ hybridization was used to confirm her karyotype as monosomy X and absence of the SRY gene. Elevated gonadotropins indicated absence of ovarian function. Laparoscopic bilateral gonadectomy. Serum T level. Pathology showed ovarian hilus cell hyperplasia within the removed gonads. Serum T levels returned to normal after gonadectomy. Ovarian hilus cell hyperplasia is an extremely rare cause of virilization in Turner's syndrome. Gonadectomy should be considered for patients with confirmed 45,X karyotype who exhibit virilization.

Ovarian Pathology in Risk-reducing Salpingo-oophorectomies From Women With BRCA Mutations, Emphasizing the Differential Diagnosis of Occult Primary and Metastatic Carcinoma

Risk-reducing salpingo-oophorectomy (RRSO) is an effective prophylactic procedure for women with mutations in BRCA1 or BRCA2 genes, both of which confer an increased lifetime risk for ovarian, tubal, peritoneal, and breast cancer. In addition to lowering this risk, RRSO also offers the opportunity to detect occult early-stage fallopian tube or ovarian carcinoma. The differential diagnosis of occult tubal/ovarian cancer includes a spectrum of benign tubal and ovarian alterations and also occult metastatic breast cancer, although only rare cases of the latter have been reported in RRSO. Neoadjuvant breast cancer chemotherapy may contribute to diagnostic difficulty due to treatment-induced cytologic alterations. With the aim of elucidating features which may help with differential diagnosis, this study reports the incidence and pathologic features of benign ovarian alterations, benign ovarian tumors, and occult primary and metastatic malignancies in prophylactic oophorectomies from 108 women with a BRCA mutation and from 35 women with other strong risk factors for hereditary breast/ovarian carcinoma. We direct particular emphasis on morphologic features of primary ovarian lesions that may mimic occult metastatic breast cancer. We also evaluate histologic alterations due to neoadjuvant breast cancer chemotherapy in the ovary and fallopian tube of patients who received such treatment immediately preceding RRSO. Comparison is made to ovarian metastases of breast cancer in our hospital-based population of breast cancer patients, none of whom underwent RRSO. Overall, 69% of RRSO patients had a personal history of breast cancer. Neoadjuvant breast cancer chemotherapy was administered in 15%. Occult primary carcinoma occurred in 7 (6.5%) BRCA patients (5 in fallopian tube, 1 in fallopian tube and ovary, 1 in ovary). Ovarian metastasis of breast cancer occurred in 1 (1%) BRCA patient undergoing RRSO and in up to a similar proportion (0.8%) of the hospital-based population of breast cancer patients. The metastasis in the RRSO patient was clinically occult, unilateral, 0.2 cm, and demonstrated mild atypia without mitoses. Abundant foamy, vacuolated cytoplasm due to neoadjuvant chemotherapy exposure was notable. In contrast, ovarian metastases in the non-RRSO population were all clinically detected, bilateral, large, and exhibited well-developed malignant cytologic features. None of the normal cell types in the ovary or tube demonstrated any cytologic alterations in RRSO patients who received neoadjuvant chemotherapy. The main morphologic mimics of metastasis with superimposed chemotherapy-induced alterations in RRSO were stromal hyperthecosis (n=8), nodular hyperthecosis (n=2), adrenal rests (n=3), hilus cell nodules (n=43), and hilus cell hyperplasia (n=4). Occult primary ovarian carcinoma was reliably distinguished from ovarian metastases of breast cancer by WT-1+, p53+, mammaglobin-, GCDPF-immunoprofile. These results demonstrate that evaluation of RRSO specimens requires awareness of a spectrum of ovarian lesions which may mimic occult primary or metastatic carcinoma; awareness of the masquerading effects of neoadjuvant chemotherapy; and awareness of the potential morphologic differences between occult metastatic breast cancer in RRSO and non-RRSO specimens.

SRY Gene Increases the Risk of Developing Gonadoblastoma and/or Nontumoral Gonadal Lesions in Turner Syndrome

The presence of Y-chromosome material in patients with dysgenetic gonads increases the risk of gonadal tumors and/or nontumoral androgen-producing lesions. The patients' prognosis can vary, depending on their karyotype. The objective of this study was to investigate the presence of Y-chromosome mosaicism in Turner syndrome patients and its association with the development of gonadal tumors and/or nontumoral androgen-producing lesions. Eighty-seven Turner syndrome patients were studied. Genomic DNA was extracted from peripheral blood and genes SRY and TSPY and DYZ3 repeat of the Y chromosome were amplified by polymerase chain reaction. To the Y-positive patients, prophylactic gonadectomy was offered. The data disclosed hidden Y-chromosome mosaicism in 16 (18.5%) of the patients. SRY sequence was detected in all of the 16 patients, and 4 (4.6%) of them presented DYZ3 repeat region and TSPY gene. Eleven of the patients with Y-positive sequences agreed to undergo the prophylactic surgery. In 2 cases, bilateral gonadoblastoma was found and, in another case, the histopathologic study of the gonads revealed hilus cell hyperplasia. In a further case, there were hilus cell hyperplasia and a stromal luteoma. In conclusion, a systematic search for hidden Y-chromosome mosaicism, especially SRY, in Turner syndrome patients is justified by the possibility of preventing gonadal lesions.

Clinical implications of the detection of Y-chromosome mosaicism in Turner's syndrome: report of 3 cases

To determine the clinical implications of the presence of a Y chromosome in Turner's syndrome patients with karyotype abnormalities. To investigate the presence of Y-chromosome sequences in different tissue samples. Endocrinology outpatient clinic of a federal university in Brazil. Five Turner's syndrome patients with karyotype abnormalities such as marker chromosomes, additional material, or ring chromosomes. Peripheral blood, oral epithelial cells, and hair root samples were collected. The SRY gene and the DYZ3 repeat region were amplified by polymerase chain reaction followed by gel electrophoresis mobility of amplified genomic DNA, and ultraviolet visualization. Prophylactic gonadectomy was offered to the Y-positive patients. The analysis of the different tissues revealed that three of the five patients studied presented Y-chromosome mosaicism. These three patients underwent prophylactic gonadectomy, and in one of them, the histopathologic study of the gonads disclosed hilus cell hyperplasia and stromal luteoma with contralateral nodular hyperthecosis. A systematic search for Y-chromosome mosaicism in Turner's syndrome patients is justified by the risk of developing gonadal tumors or androgen-producing lesions.

Diffuse Stromal Leydig Cell Hyperplasia: A Unique Cause of Postmenopausal Hyperandrogenism and Virilization

A 60-year-old woman presented with diffuse scalp alopecia, hirsutism, and clitorimegaly, and the mean serum testosterone levels were greater than 200 ng/dL. Findings on computed tomography of both adrenal glands were normal. After bilateral oophorectomy, a unique histological picture consisting of diffuse stromal Leydig cell hyperplasia was found. Reinke crystals were present, but neither hilus cell hyperplasia nor stromal hyperthecosis was noted. Sequencing of the 11 exons of the gene for the luteinizing hormone receptor revealed no abnormality. Relevant data suggest that treatment of the postmenopausal woman with hyperandrogenism and virilization is bilateral laparoscopic oophorectomy if she has no pronounced ovarian enlargement or adrenal tumor on imaging. In this setting, an intensive endocrine evaluation or a search for metastatic disease seems to be unnecessary.

Y-chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y-mosaicism.

The frequency of gonadoblastoma is high in patients with Turner's syndrome bearing cells with Y or partial Y-chromosome. About 60% of patients with Turner's syndrome have a 45,X karyotype. In 30% of them a Y-sequence is disclosed by DNA analysis. To identify patients at risk of developing gonadoblastoma, a PCR based assay with SRY, ZFY and DYZ3 specific primers was carried out to detect different Y-sequences in the DNA of peripheral lymphocytes from patients with Turner's syndrome. Peripheral blood karyotypes from 36 patients with Turner's syndrome were studied. Patients with proven Y-chromosomal material were excluded. Genomic DNA was extracted from peripheral blood. SRY and ZFY genes and DYZ3 repetion of Y-chromosome were amplified by PCR. Patients with clinical signs of hyperandrogenism or with positive Y-sequences by PCR underwent gonadectomy. The gonadal tissues were examined for Y-sequences using PCR, morphology and immunohistochemical study. Turner's syndrome and signs of hyperandrogenism were evaluated both clinically and through laboratory tests. Haematoxylin and eosin staining was employed in gonadal morphology studies. The presence of testosterone was detected by immunohistochemistry using a monoclonal antibody. Two patients who had Y-positive blood samples and three hyperandrogenic (2 hirsutes, 1 virilized) Y-negatives underwent gonadectomy. PCR was carried out on their gonadal tissue. The tissue from the two patients without hyperandrogenism was Y-positive. The gonadal tissue from the three hyperandrogenics was Y-negative. Gonadal morphology disclosed hilus cell hyperplasia in the 3 hyperandrogenic Y-negatives and in one Y-positive patient; stromal luteoma and hyperthecosis in the virilized patient, cystadenofibroma in one hirsute patient and gonadoblastoma in one Y-positive. Testosterone was detected immunohistochemically in the hilus cell hyperplasia, stromal luteoma and hyperthecosis found in the hyperandrogenic patients. The molecular study was sensitive and useful in the evaluation of patients at risk of developing gonadoblastoma. Other nontumour, gonadotrophin-dependent and Y-independent mechanisms which deserve the same medical approach may be involved in the genesis of hyperandrogenic signs in Turner's syndrome.

Virilization in a postmenopausal woman as a result of hilus cell hyperplasia associated with a simple ovarian cyst

A 68-year-old woman who had virilization was found to have an androgen-secreting simple ovarian cyst at laparotomy. Histologic examination demonstrated hilus cell hyperplasia in the ovarian hilus and cyst wall. In the differential diagnosis of postmenopausal virilization, hilus cell hyperplasia, although rare, should be considered. (Am J Obstet Gynecol 1997;176:719-20.)

Tumor-Like Lesions of the Ovary Associated—with Pregnancy

Six nonneoplastic ovarian lesions (or alterations) are associated with pregnancy or the puerperium, each of which can simulate a neoplasm on clinical, gross, or microscopic examination. These lesions include pregnancy luteoma, hyperreactio luteinalis, large solitary luteinized follicle cyst of pregnancy and puerperium, intrafollicular granulosa cell proliferations, hilus cell hyperplasia, and ectopic decidua. Because these lesions involute spontaneously after termination of pregnancy or are adequately treated by a conservative surgical approach, unnecessarily radical operations can be avoided if the correct diagnosis is made by the pathologist.

Selective venous catheterization in the evaluation of hyperandrogenism

Retrograde bilateral ovarian-adrenal vein catheterization was carried out in 16 patients with plasma testosterone levels exceeding 1.4 ng/ml (4.85 nmol/l). While pelvic ultrasonography and computerized axial tomographic scan failed to locate the androgen-producing ovarian tumors, catheterization led to a diagnosis of occult ovarian tumor in 5 patients, based on the observation of an abnormally-high and unilateral ovarian-peripheral vein testosterone gradient, which was subsequently confirmed histopathologically. In one case, unilateral elevation of the adrenal-peripheral vein testosterone gradient was found, complementing the ultrasonographic finding of an adrenal mass and confirming the diagnosis of a virilizing adrenal tumor. In the other 10 patients, gradient analysis ruled out an androgen-producing tumor, leading to the identification of nontumoral hyperandrogeny, such as a severe form of the polycystic ovary syndrome in the 6 premenopausal patients and of ovarian stromal and hilus cell hyperplasia in the 4 menopausal patients. In conclusion, appropriate indication of selective catheterization may considerably reduce the need for exploratory surgery and may help in selecting the adequate surgical approach.

Hilus Cell Pathology and Hirsutism

SUMMARY Hilus cell abnormalities are uncommon causes of hirsutism with virilization. Although hilus cell tumours have been well described, hilus cell hyperplasia is rare and is poorly defined clinically. We describe three cases of hilus cell hyperplasia and compare them with a case of hilus cell tumour. Both pathologies were associated with increased testosterone and oestradiol secretion. Suppression of testosterone to the ‘normal range’in response to exogenous oestrogen was seen only in the cases with hyperplasia; only partial responsiveness was seen in the case with hilus cell tumour. Bilateral oophorectomy offers the potential for cure for both hilus cell hyperplasia and tumour.

HILUS CELL PATHOLOGY AND HIRSUTISM

Hilus cell abnormalities are uncommon causes of hirsutism with virilization. Although hilus cell tumours have been well described, hilus cell hyperplasia is rare and is poorly defined clinically. We describe three cases of hilus cell hyperplasia and compare them with a case of hilus cell tumour. Both pathologies were associated with increased testosterone and oestradiol secretion. Suppression of testosterone to the 'normal range' in response to exogenous oestrogen was seen only in the cases with hyperplasia; only partial responsiveness was seen in the case with hilus cell tumour. Bilateral oophorectomy offers the potential for cure for both hilus cell hyperplasia and tumour.

Nonneoplastic gonadal testosterone secretion as a cause of vaginal cell maturation in streak gonad syndrome.

Endocrine studies were carried out on 3 patients with streak gonad syndrome, 2 of whom had slight proliferative vaginal smear patterns, and the 3rd had slight hirsutism with increased muscle mass but an atrophic type vaginal smear pattern. Simultaneous sampling of peripheral, adrenal and streak gonadal venous blood revealed mildly increased testosterone secretion by the streaks in the 2 patients who had proliferative cytohormonal patterns. Histologic examination of their streak gonads showed hilus cell hyperplasia. It might be suggested that hilus cell hyperplasia was the source of the increased testosterone secretion in these 2 patients and thus resulted in slight maturation of the vaginal epithelium.

Ovarian Leiomyoma With Hilus Cell Hyperplasia That Caused Virilization

A 68-year-old woman had noted gradual virilization and depression for 3 years. Examination revealed a 10-cm right pelvic mass. Plasma testosterone was substantially elevated (1,082 ng/dl), but urinary ketosteroid and ketogenic steroid excretion was normal. Laparotomy revealed a 10-cm mass that replaced the right ovary and weighed 210 g. Histologic analysis revealed a leiomyoma and proliferation of hilus cells in the periphery of the mass. The plasma testosterone decreased postoperatively to 45 ng/dl. We believe that this is the first report of an ovarian leiomyoma associated with hilus cell hyperplasia that caused virilization.

Virilism with Hilus Cell Hyperplasia

Virilism with Hilus Cell Hyperplasia

Adenocarcinoma of the endometrium following radiation therapy and associated with hilus cell hyperplasia

The case history is presented concerning a 65-yr-old woman in whom a malignant uterine tumor was found 28 yr after pelvic x irradiation for a benign condition. The estimated mid-pelvis dose was 1350 r. The endometrial adenocarcinoma was accompanied by a proliferation of ovarian hilus cells. The patient had also developed a cecal adenocarcinoma 16 yr after radiotherapy. It is suggested that x irradiation may have been-primarily responsible for both tumors and that hilar hyperplasia may have provided endocrine stimulation acting as a secondary factor in the induction of the endometrial cancer. Thus, irradiation may have acted as the initiating stimulus and excessive hormone output as the promoting factor or cocarcinogen. An extensive review is made of the literature of cases of this type. (H.H.D.)