CASE REPORT: Recurrent maternal virilization during pregnancy associated with polycystic ovarian syndrome: a case report and review of the literature

Maternal virilization in pregnancy is associated, in most benigncases, with luteoma of pregnancy and hyperreactio luteinalis.Only a few reports relate this phenomenon to hyperthecosis orpolycystic ovarian syndrome (PCOS). A case of recurrent maternalvirilization during two consecutive pregnancies in a patientwith PCOS is presented. In both pregnancies, the deepening ofher voice, facial hirsutism and scalp hair loss began at theend of the first trimester and regressed 3–4 months post-partum.The patient underwent ovarian venous catheterization, and androgensecretion from both ovaries was found to be markedly high butsimilar, therefore ruling out an ovarian androgen-secretingtumour. Reviewing the English literature of similar cases, wefound reports of only seven cases of maternal virilization duringpregnancy associated with PCOS. Here, we present a case of recurrentmaternal virilization in pregnancy associated with PCOS.     

Pathogenetic factors of menstrual function disturbances in women with pathological puberty

A correlation is shown between the peculiarities of puberty and clinical and laboratory parameters during reproductive period. Differences in the state of receptor apparatus in ovaries of examined patients attest to different pathogenesis of menstrual function disturbances with and without mild virilization in anamnesis. The patients with mild virilization and changed pattern of menstrual disturbances probably reflecting desensitization of the endometrium to hormone stimulation have the worst prognosis. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 4, pp. 449–451, April, 1997     

Bilateral virilizing sclerosing stromal tumours of the ovary in a pregnant woman with Gorlin''s syndrome: implications for pathogenesis of ovarian stromal neoplasms

A woman with Gorlin's syndrome who had become pregnant following clomiphene therapy presented in early pregnancy with bilateral ovarian sclerosing stromal tumours which were associated with profound virilization. Pre- and post-operative hormone profiles indicated androgen production by the tumours. Ovarian sclerosing stromal tumours have not previously been reported as occurring bilaterally or in association with Gorlin's syndrome. We discuss the questions raised by this unusual case regarding the pathogenesis of ovarian stromal neoplasms.     

Pubertal development in ALG6 deficiency (congenital disorder of glycosylation type Ic)

Information on the hypothalamic pituitary ovarian axis in congenital disorders of glycosylation (CDG) females is scarce. Varying hormonal profiles and degrees of virilization in CDG females suggest a spectrum of yet unidentified mechanisms affected by impaired N-glycosylation. We describe an ALG6D woman who completed puberty with normal gonadotropins and testosterone levels, no virilization, and regular menses. Hormonal follow-up of CDG females is necessary to improve our understanding of the role of glycosylation in pubertal development.     

Mature ovarian cystic teratoma with combined squamous cell carcinoma and malignant melanoma

 In a mature ovarian cystic teratoma (MOCT) in a 67-year-old woman we found associated invasive squamous cell carcinoma and nodular amelanotic malignant melanoma. The finding of foci of typical and atypical melanocytic proliferation at the junctional level of the dermal component together with the absence of other possible sources supports an ovarian origin of the melanoma. A comparative analysis of the reported MOCT-associated malignant melanomas emphasizes the singularity of our case in the amelanotic character of the melanoma, its lymphotropism and the coexistence of invasive squamous cell carcinoma. Received: 23 October 1997 / Accepted: 30 December 1997     

Ovarian Adrenal Rest Tumors Undetected by Imaging Studies and Identified at Surgery in Three Females with Congenital Adrenal Hyperplasia Unresponsive to Increased Hormone Therapy Dosage

Patients with congenital adrenal hyperplasia have a predisposition for developing adrenal rest tumors. In contrast to testicular adrenal rest tumors, ovarian adrenal rest tumors are less common, and only a few cases have been reported in the literature. This report presents three Chinese female congenital adrenal hyperplasia patients (9 to 15 years of age) with small ectopic adrenal cortical nodules that were not detected by imaging but were diagnosed at surgery. All three patients developed virilization with elevation of 17- hydroxyprogesterone, androstenedione, and androgen levels despite receiving maximum adrenal hormone replacement therapy. Ultrasound and magnetic resonance imaging of the abdomen and pelvis suggested bilateral expansion of the adrenal glands, but no lesions of the ovaries were observed. Laparoscopy and/or laparotomy revealed small nodular lesions surrounding the pelvic gonad in all three cases. Histopathological examination of the resected tissue in all cases revealed hyperplasic nodules of cells surrounded by fibrous tissue. The cells were arranged as nests with abundant cytoplasm, which were partially lightly stained with a small centered nucleus. Immunohistochemistry staining revealed the cells to be synaptophysin positive, melan-A positive, and chromogranin A negative, indicating the cells were adrenocortical tissue and not adrenal medullary cells. Thus, the findings of the histopathological examination were consistent with ovarian adrenal rest tumors. Female congenital adrenal hyperplasia patients with virilization who showed an inadequate response to hormone therapy and had negative imaging results may benefit from laparoscopic examination or laparotomy in order to confirm the diagnosis of ovarian adrenal rest tumors while receiving unilateral subtotal adrenalectomy or subtotal bilateral adrenalectomy.     

PCR detection of Y-specific sequences in patients with Ullrich-Turner syndrome: Clinical implications and limitations

Cytogenetic analysis of patients with Ullrich-Turner syndrome (UTS) may fail to detect low levels of Y chromosome mosaicism or Y-derived marker chromosomes. More sensitive polymerase chain reaction (PCR)-based tests have been developed; however, applicability of these data to prognosis of virilization and gonadoblastoma development has not been investigated adequately. We used a multiplex PCR-based method to detect two Y-specific sequences, SRY and AMGLY. Thirteen patients with UTS without cytogenetically detected Y chromosomes were studied. Y-specific sequences were detected in 5 patients by multiplex PCR. A cryptic translocation involving the Y chromosome was found in one patient with severe virilization of external genitalia and a male phenotype. Y chromosomal mosaicism was detected in peripheral blood and in both gonads of one patient, and only in the left gonad of another patient. Existence of a Y-derived marker was demonstrated in 2 patients, one of whom had no testicular tissue or virilization. Consistent with previous reports, we conclude that PCR is more sensitive than classical cytogenetic analysis and detects patients with Y-specific sequences in blood cells. However, the absence of Y-specific material in blood is not a sufficient reason to reject surgical treatment in case of virilization. Am. J. Med. Genet. 76:283–287, 1998. © 1998 Wiley-Liss, Inc.     

Selective ovarian vein sampling can be crucial to localize a Leydig cell tumor: an unusual case in a postmenopausal woman

Leydig cell tumors of the ovary are very rare, frequently associated with symptoms of virilization in postmenopausal patients. It is sometimes difficult to localize the tumor precisely even with modern imaging techniques. A 62-year-old patient presented with recent onset of rapidly progressive virilization including increased hirsutism, progressive balding, deepening voice and enlargement of the clitoris. Initial laboratory examination revealed a total serum testosterone level of 1330 ng/dL. Serum dehydroepiandrosterone sulfate, androstenedione and 17 hydroxyprogesterone levels were all within normal limits. Extensive pre-operative evaluations included transvaginal ultrasound, abdominal computed tomography and magnetic resonance imaging failed to localize the tumor. Therefore, selective ovarian venous hormonal sampling (SOVHS) was performed and they revealed that the total serum testosterone level was significantly higher in the left than in the right ovarian vein (7000 ng/dL vs. 225 ng/dL). A total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Microscopic examination of the left ovary revealed a Leydig cell tumor. In conclusion, when the precise location of the tumor is not determined pre-operatively, SOVHS may be valuable to make accurate diagnosis.     

Clinicopathologic features of ovarian Sertoli-Leydig cell tumors

Background: Ovarian Stertoli-Ledig cell tumor (SLCT) is a rare type of sex cord-stromal tumor of the ovary. The present study was to evaluate clinicalopahologic features and prognosis of patients with Sertoli-Leydig cell tumor treated by surgery and adjuvant chemotherapy during short term follow-up. Methods: A total of sixteen patients with ovarian Sertoli-Leydig cell tumor treated at the Obstetrics and Gynecology Hospital, Shanghai, China, between Jan 2001 and Dec 2011 were reviewed. The clinical data, treatment and prognosis were obtained from medical records. Results: The median age of the patients with ovarian Sertoli-Leydig cell tumor was about 27.5 years old in non-menopausal women, while the median age of menopausal women was about 63 years old. The most common complaint was with hormonal-related symptoms in the form of secondary amenorrhea and infinity, features of virilization, abdominal mass or irregular vaginal bleeding. All of sixteen patients underwent surgical staging and all were found to have stage I disease at the time of diagnosis. Eleven patients with intermediate and two patients with poorly differentiated tumors received adjuvant chemotherapy. There were differences found in operative time, blood loss and postoperative recovery time between laparotomy and laparoscopy. There were no disease-related deaths and all patients were under complete remission at the last follow-up. Conclusions: Ovarian Sertoli-Leydig cell tumors could happen in any period age of women. However, the tumors typically occur in the single side while still at the early stage, a favorable outcome could be achieved by surgery and adjuvant chemotherapy. Laparoscopy has similar surgical effects as laparotomy, but has a number of advantages.     

Steroid cell tumor of the ovary in a child

An 8-year-old girl exhibited severe, progressive virilization of 2 years' duration associated with markedly elevated circulating testosterone concentrations. Based on her initial clinical presentation and results of a chemical evaluation, she was originally thought to have non-classic 21-hydroxylase deficiency, but her condition did not respond to corticosteroid therapy. Further evaluation confirmed the presence of an ovarian neoplasm. The excised ovary contained an attached gray-brown mass. Light microscopic and ultrastructural examination revealed the mass to be a steroid cell tumor. Because Reinke's crystals were not present, it was designated to be a steroid cell tumor not otherwise specified. This case represents one of 22 reported cases of steroid cell tumor occurring in children described in the literature, most of which have been associated with heterosexual precocity. To our knowledge, steroid cell tumors are benign when they occur in prepubertal children. Although they are rare, steroid cell tumors of the ovary should be considered in cases of childhood virilization.     

Isodicentric Y chromosome in an Ullrich‐Turner patient without virilization

We report on a 17‐year‐old young woman with Ullrich‐Turner syndrome (UTS), who was found to have a karyotype 45,X/46,X,idic(Y)(q11). She had age‐appropriate genitalia without virilization in spite of the presence of the Y‐derived marker chromosome and SRY locus in 70% of her lymphocytes. Having reviewed the literature, we conclude that a possible explanation for the lack of virilization in these mosaic patients is most likely an uneven distribution of tissue mosaicism (gonadal mosaicism). Am. J. Med. Genet. 91:99–101, 2000. © 2000 Wiley‐Liss, Inc.     

Virilizing lipid cell tumor of the ovary: light and electron microscopic studies

Lipid cell tumor of the ovary is among the rarest tumors belonging to the virilizing group of ovarian neoplasms. A lipid cell tumor of the ovary is described in an 18-year-old woman with secondary amenorrhea, hirsutism, and frank virilization. Current diagnostic features, preoperative and postoperative androgen determinations, and histomorphological and ultrastructural studies are presented. Prompt diagnosis and treatment are emphasized in this potentially malignant and disfiguring androgenic tumor that is readily amenable to surgery.     

An ovarian steroid cell tumor causing virilization and massive ascites

Steroid cell tumors, not otherwise specified (NOS), are rare ovarian sex cord-stromal tumors with malignant potential. The majority of these tumors produce several steroids, particularly testosterone. Various virilizing symptoms such as hirsutism, temporal balding, and amenorrhea are common in these patients; however massive ascites is an infrequent symptom. A 52-year-old woman with the sudden onset of virilization and massive ascites presented for treatment at Severance Hospital. After clinical evaluation, the patient underwent an exploratory laparotomy and a complete surgical staging procedure. She recovered from the surgery uneventfully and was discharged from the hospital five days after surgery. We present here an unusual case of an ovarian steroid cell tumor, NOS, and a brief review of the literature regarding these types of tumors.     

Organizational and activational effects of gonadal steroid hormones on the EEG of male and female rats

To analyze organizational and activational effects of sex steroids on adult rat electroencephalographic activity (recorded at postnatal day 100), seven groups were included: males (48)-intact, neonatally or adult castrated; females (64)-intact, ovariectomized and exposed pre- or neonatally to testosterone propionate. In males, neonatal orchidectomy increased beta relative power, whereas both neonatal and adult castration reduced interparietal correlation. In females, prenatal testosterone administration produced higher theta absolute power; theta relative power was higher in all experimental groups, whereas beta1 and beta2 were decreased by prenatal and increased by neonatal virilization; prenatal virilization enhanced, while neonatal virilization and adult ovariectomy decreased interparietal correlation. These data indicate that females are more sensitive to early prenatal than to neonatal organizational effects of sex steroids, and some electroencephalographic features are feminized in castrated males and virilized in perinatally androgenized females.     

Cytokeratins 20 and 7 in the differential diagnosis of metastatic carcinoma in cytologic specimens

A series of 33 tumor cases (13 fine-needle aspirates and 20 effusion specimens) were evaluated for the expression of two cytokeratin (CK) subtypes; CK 20, expressed primarily in tumors of the GI tract, mucinous ovarian tumors and transitional cell carcinomas, and CK 7, found chiefly in non-GI tract adenocarcinomas, including breast and lung. CK 20 expression was demonstrated immunocytochemically in seven of seven metastatic colon and two of three metastatic transitional cell carcinomas tested. CK 20 was absent in all metastatic carcinomas of breast, ovary, lung, and uterus examined (23 cases). Anti-CK 7 stains were negative in four of six metastatic colonic carcinomas, with equivocal results in the remaining two cases. Metastatic lung, breast, and ovarian carcinomas were strongly positive for CK 7. This study demonstrates that the combined use of anti-CK 20 and anti-CK 7 antibodies is highly sensitive and specific for metastatic colonic adenocarcinoma in cytologic material and thus could play an important role in distinguishing this entity from other common primary carcinomas. Diagn. Cytopathol. 16:132–136, 1997. © 1997 Wiley-Liss, Inc.     

Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Congenital adrenal hyperplasias (CAH) are inherited defects of cortisol biosynthesis. More than 90% of CAH are caused by 21-hydroxylase deficiency (21-OHD), found in 1:10 000 to 1:15 000 live births. Females with 'classical' 21-OHD, being exposed to excess androgens prenatally, are born with virilized external genitalia. Potentially lethal adrenal insufficiency is characteristic of two-thirds to three-quarters of patients with the classical salt wasting (SW) form of 21-OHD. Non-SW 21-OHD may be diagnosed on genital ambiguity in affected females, and/or later on the occurrence of androgen excess in both sexes. Non-classical 21-OHD, detected in > or =1:100 of certain populations, may present as precocious pubarche in children or polycystic ovarian syndrome in young women. 21-OHD is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombination between CYP21 and the closely linked CYP21P pseudogene. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disorder. This close association between genotype and phenotype makes it possible to predict clinical outcome in affected subjects. The risk of SW and prenatal virilization can be estimated, and overtreatment can be avoided in mildly affected cases. Glucocorticoid and mineralocorticoid replacement therapies are the mainstays of treatment, but additional therapies are being developed. A first trimester prenatal diagnosis should be proposed in families in whom molecular studies have been performed previously. The state of heterozygotism can be predicted by hormonal testing and confirmed by molecular studies. Prenatal diagnosis by direct mutation detection in previously genotyped families permits prenatal treatment of affected females in order to avoid or minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before SW crises develop, reducing mortality in this disorder.     

Massive ovarian oedema with production of testosterone

Summary Clinical, biochemical, light- and electron microscopic, and immunocytochemical findings of a 13 1/2 year old girl with delayed menarche and signs of virilization due to massive oedema of the left ovary with activation of stromal cells (hyperthecosis) are presented. Testosterone and oestradiol production by large cells in the voluminous ovary was demonstrated by immunocytochemistry and radioimmunoassay. Massive ovarian oedema may result from partial or intermittent torsion of the mesovary interfering with venous and lymphatic drainage, but not with arterial blood flow.     

Virilizing stromal thecosis of the ovary associated with multiple corpora atretica

Virilism can be associated with a variety of ovarian lesions, including stromal hyperplasia. Focal luteinization, a thickened tunica albuginea, and multiple cystic follicles are histologic features that have been associated with stromal hyperplasia in virilized women. This report describes the case of a 57-year-old woman who presented with a four-year history of virilization. The testosterone level was 13.8 nmol/L (3,980 ng/L). At laparotomy, the ovaries were found to be enlarged, each measuring 4 cm in maximum dimension. Salient histologic findings included diffuse stromal hyperplasia interspersed with a marked increase in the number of corpora atretica. Focal luteinization, including in some corpora atretica, was seen. Electron microscopic study demonstrated cells with increased smooth endoplasmic reticulin and mitochondria with tubular cristae as well as other features consistent with theca cells; Reinke crystals were not seen. The testosterone level normalized after removal of the ovaries, and the signs of virilism gradually abated. These results are compatible with an abnormal stimulation of the ovaries as evidenced by an increased though abortive follicular development, stromal hyperplasia, and focal luteinization.     

Taxol effect: Bizarre mitotic figures (abnormal spindle asters) in a malignant peritoneal effusion: Report of a case

Taxol (Paclitaxol) is a diterpenoid taxane derivative found in the bark and needles of the Western yew, Taxus brevifolia, indigenous to the old growth forests of the Pacific Northwest. As compared with other antineoplastic agents (vinca alkaloids and colchicine) that enhance microtubule disassembly, taxol promotes microtubule polymerization. In interphase cells, abnormal microtubular bundles or arrays are seen. In mitotic cells, abnormal spindle asters form. Such morphologic changes have been described frequently in cell culture systems and in in vitro systems using fresh tumor tissue. To our knowledge, these changes have not been described in a peritoneal effusion specimen from a patient with stage III ovarian cancer treated with taxol. In addition, the mitotic stabilization produced interpretative difficulties in evaluating the peritoneal fluid because a vast majority of the presumed malignant cells were in mitosis and, hence, not evaluable by ordinary cytologic criteria. Diagn. Cytopathol. 1997;17:209–212. © 1997 Wiley-Liss, Inc.