Ovarian Hilus Cells Research Articles

Bilateral adrenal cortical rests: An interesting innocuous intruder in the fallopian tubes.

Ectopic adrenal rests refer to the presence of adrenal tissue outside its normal anatomical location and are usually discovered incidentally on microscopic examination. Literature suggests its occurrence in diverse extrarenal sites, like the genitourinary system and pelvis. Our case describes the rare occurrence of ectopic adrenal rests in the walls of bilateral fallopian tubes of a 43-year-old female patient who presented with a complaint of heavy menstrual bleeding. A total hysterectomy with bilateral salpingo-oophorectomy was performed. Gross examination revealed adenomyosis with multiple fibroids, and the same was confirmed on microscopy. Additionally, the finding of a well-encapsulated lesion on the walls of both tubes made us relook at the fallopian tubes, which showed a small bright yellow area measuring less than 0.3 cm in the walls, which was consistent with ectopic adrenal rests after ruling out the morphological differentials of Walthard cell nests, aggregates of foamy histiocytes, metastatic renal clear cell carcinoma, displaced ovarian luteinized theca cells, heterotopia of ovarian hilus cells. Immunohistochemistry showed positivity for Melan A and CK7 was negative. The present case helps in investigating the lesser-explored aspect of adrenal rest pathology. It also reiterates need for detailed observation of fallopian tubectomy specimens by pathologists during grossing to avoid overlooking of potentially intriguing entities.

Heterotopic ovarian hilus cells of the salpinx: a case report and literature review

Ovarian hilus cells (OHCs), a counterpart of testicular Leydig cells, are usually found in the ovarian poles and produce androstenedione. Their origin remains a matter of debate, although OHCs are assumed to come from the adrenogenital primordium. OHCs are rarely observed around the poles of the ovary, including the mesoovarium, stroma (perisalpinx) of the salpinx, and the wall of paratubal cysts. Their clinical and pathological characteristics are not well-known because of their rarity. Herein, we present a case of ectopic OHCs in a 48-year-old woman. The patient underwent total hysterectomy and bilateral salpingectomy for vaginal bleeding due to multiple leiomyomas. We incidentally found OHCs in the stroma of the infundibulum of the salpinx, just beneath the tubal epithelium. Their size was less than 1 mm, and they were composed of large cells with central round nuclei and abundant clear or granular cytoplasm. OHCs share morphological and immunohistochemical profiles with ectopic adrenal glands, and the differential diagnosis is sometimes difficult. They do not exhibit microscopic encapsulation or the normal adrenal cortex zonation pattern. The patient was discharged and did not show any abnormal findings during 19 months of follow-up. Analyzing the characteristics of testicular Leydig cells will help understand how OHCs develop and why heterotopic OHCs occur in and around the salpinges.

Two Rare Cases of Paratubal Leydig Cell Nodules: Clinical Relevance and Debated Terminology of a Noteworthy Incidentaloma

Cells with cytologic and immunohistochemical features of Leydig cells are normally present in the ovary and the ovarian hilum, are testosterone-producing, and have been referred to as ovarian hilus cells. Rarely these cells form nests or nodules in extraovarian sites such as the mesovarium or mesosalpinx. Because they are so rare, these nodules can present a diagnostic challenge when first encountered. This report describes 2 such incidental nodules in the mesosalpinx associated with a small paratubal cyst and suggests that the term Leydig cell nodule be preferred over the nonspecific and confusing historical term ovarian hilus cell nest.

Short histological kaleidoscope - recent findings in histology. Part I.

This article is a review of new advances in histology, concerning either classification or structure of different tissular elements (basement membrane, hemidesmosomes, urothelium, glandular epithelia, adipose tissue, astrocytes), and various organs' constituents (blood-brain barrier, human dental cementum, tubarial salivary glands, hepatic stellate cells, pineal gland, fibroblasts of renal interstitium, Leydig testicular cells, ovarian hilar cells), as well as novel biotechnological techniques (tissue engineering in angiogenesis), recently introduced.

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-297 Mutation in SRY Gene Presenting as Syndromic 46XY Disorder of Sexual Differentiation (DSD)

Introduction Mutations in the SRY gene presenting as sex reversal is rare and not associated with problems in other organ systems. We report a case of a 46 XY adolescent with history of cleft lip and palate, phenotypically female, diagnosed with a mutation in the SRY gene causing sex reversal. Clinical Case A 14 year old phenotypically female patient was referred to our Endocrine clinic for evaluation of delayed puberty. She reported body odor for one year, without breast development, axillary or pubic hair. The family reported normal growth pattern growing at about 2 inches per year. She had a history of cleft lip and palate that had been repaired during infancy. They reported a history of recurrent 4-5 urinary tract infections in her lifetime. Her mother reported menarche at 12 years age, while her father had slightly delayed puberty. On physical examination her height was at z-score -0.63, weight z-score 0.42, BMI z-score 0.74. She had healed surgical scars on her right lip, with no other dysmorphic features. She had Tanner stage I breasts and no pubic or axillary hair. Examination of the external genitalia showed a normal vaginal and urethral opening with no clitoromegaly. Laboratory testing was significant for hypergonadotropic hypogonadism. Bone age was 10 years, therefore significantly delayed. Pelvic ultrasound showed a pre-pubertal uterus measuring 1.9 x 0.3 x 1.0 cm. The right gonad measured 1.5 x 1.0 x 1.1 cm. The left gonad was not visualized and there was no adnexal mass. MRI of the pelvis showed a prepubertal uterus measuring approximately 2 x 1 x 0.4 cm, and possible gonadal tissue measuring 1.2 cm on the left and 1.1 cm on the right, located antero-medial to the external iliac vessels. The urinary bladder was normal. Chromosomal analysis was consistent with 46,XY, ish(Y)(SRY+). Laparoscopic bilateral gonadectomy was performed without any complications. There was no indentifiable gonad on the right side but a formed fallopian tube with fimbria and an adjacent mesonephric duct remnant was identified. On the left side a small dysgenetic gonad with ovarian stroma, müllerian ductal epithelial remnant, ovarian hilar cell nests without germ cells, were identified. Genetic testing was done and was significant for a variant c.380A>G (p.Tyr127Cys), identified in her SRY gene. She was subsequently started on Estrogen supplement to which she is responding well. Conclusion - Mutations in the SRY gene presenting as sex reversal is rare and not reported to be associated with problems in other organ systems. Our patient with 46 XY sex reversal due to SRY mutation, had a history of cleft lip and palate, which has not been reported before to our knowledge. - Variants that disrupt the p.Tyr127Cys amino acid residue in SRYgene has been observed in affected individuals.

Ovarian Leydig cells (OLC): A histomorphological and immunohistochemical study.

Testicular Leydig cells (LC) regulate the proper development of male individuals, both during fetal life (fetal LC) and puberty (adult LC). In the ovaries of adult women, there are cells that are very similar to Leydig cells, the ovarian hilus cells (OHC), which also produce testosterone. The origin of these cells, in both sexes, remains unknown and is still a matter of debate. We have studied the location, characteristics and relationships of the OHC in 90 patients. The indications for oophorectomy were: metrorrhagia (n=9), prolapse (n=8), endometrial hyperplasia (n=14), cancer (endometrial, myometrial, or cervical) (n=35), uterine leiomyomata (n=14), and various ovarian tumors (cysts and benign tumors, borderline and malignant) (n=10). In addition to the hilus, occasionally the nodules, nests and clusters of OHC were located in the mesovarium, the mesosalpinx, and in the medullar and cortical regions of the ovaries. The morphological (including crystalloids of Reinke) and immunohistochemical (positivity for calretinin and alpha-inhibin) findings were similar to those described for testicular LC. Therefore, OHC can be considered ovarian Leydig cells (OLC). LC are usually found in small numbers in the ovaries, but if one looks for them intentionally, one always finds them. Close relationships were observed between the OLC with nerves and vessels. Moreover, an intraneural location of the OLC was demonstrated in all cases, and these intraneural cells showed similar characteristics to extraneural OLC, suggesting that they derive from endoneural cells which are present in the vegetative nerves of the ovaries.

GnRH analogue use in postmenopausal hyperandrogenism: long-term remission

To the Editor, The medical therapy of postmenopausal hyperandrogenism remains poorly described. The effectiveness of short-term GnRH analogues in suppressing androgens is generally indicative of the ovarian origin of the androgen production, and its benign nature [1–3], although very rarely adrenal tumours secreting androgen responsive to GnRH agonist have been reported [4]. Here we report a rare case of longterm GnRH analogue-induced suppression of androgens of ovarian origin. A 78-year-old woman was referred for investigation of severe hyperandrogenism. She had noticed the progressive appearance of hirsuties over her face and body over a period of 3–4 years, her face becoming plethoric, with concomitant deepening of her voice which became more husky, and increasing temporal recession. She had gained around 10 kg in weight, and reported increased libido for 2 years. She was treated for hypertension with agents not considered to be causative of hirsutism. Clinical examination confirmed significant hirsutism: both her serum testosterone and androstenedione levels were markedly elevated at 21.3 nmol/l (NR \ 2.9) and 17.8 nmol/l (normal 3–8), respectively, with a normal serum DHEAS. Serum testosterone failed to suppress on a low-dose dexamethasone suppression test (16.8 nmol/l at 48 h, with normal suppression of cortisol). Her serum gonadotrophins were appropriately elevated for the menopause (FSH 40.2 U/l, NR [ 25; LH 21.9 U/l, NR [ 16), and her estradiol appropriately low (157 pmol/L, NR 18.4–201). Basal 17-hydroxyprogesterone was normal, excluding the common form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Imaging (CT scanning, MRI) did not show any adrenal or ovarian abnormality, while a transvaginal US scan showed a slightly bulky uterus without thickening of the endometrium. The most likely diagnosis at this stage was either bilateral ovarian hilar cell hyperplasia or hyperthecosis, or a small Leydig cell tumour in one or both ovaries. Ovarian venous catheterisation was not considered as we have previously noticed the lack of utility of this procedure in this situation [5]. A single longacting 10.8 mg subcutaneous injection of goserelin (Zoladex LA, AstraZeneca) was given which induced the suppression of the serum testosterone level to 0.7 nmol/l 2 months later. The GnRH dependence of androgen secretion was taken to be indicative of an ovarian origin. Treatment with the GnRH agonist was continued for 17 months (subcutaneous injections every 3 months), and her serum testosterone levels remained within the normal range (0.9 and 1.6 nmol/l) for a further 27 months off treatment. Significant improvement of her symptoms was noticed; 11 months later the patient died from overwhelming sepsis due to methicillin-resistant S. aureus unrelated to her endocrine condition. In this case, in addition to representing a functional diagnostic tool, the use of GnRH analogues offers a valuable therapeutic approach which is a particularly useful mode of therapy in patients for whom surgical intervention is not appropriate for diverse reasons. Indeed, only rare M. Gueorguiev Department of Endocrinology, St Bartholomew’s Hospital, London EC1A 7BE, UK

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 Hilus Cell Heterotopia

The eutopic location of ovarian hilus cells in the hilar stroma of the ovary and in the adjacent mesovarium is widely recognized. Hilus cell heterotopia, that is, the presence of normal hilus cells in an abnormal site, is rare and there are only a few case reports and 1 earlier systematic study of this phenomenon in the literature. Hilus cell heterotopia has been reported in the fimbrial stroma of the fallopian tube, paratubal and parafimbrial cyst walls and usually takes the form of discrete, circumscribed nodules or clusters of hilus cells. We report a series of 6 cases of hilus cell heterotopia, all of which were identified in association with other underlying pelvic pathology and in patients over 40 years of age. We have shown that hilus cell heterotopia is not limited to the fallopian tube but can also involve the subcapsular ovarian cortex and may have an infiltrative (rather than a nested) growth pattern that can resemble metastatic carcinoma, potentially mimicking a metastatic lobular carcinoma of the breast. This is particularly relevant in patients in whom staging procedures are carried out for gynecologic pelvic neoplasms, and for those few patients who also have a history of concurrent carcinoma, particularly of the breast.

Identical twins with ovarian hilar cell hyperplasia: A case report

Identical twins with ovarian hilar cell hyperplasia: A case report

Ovarian Steroidogenesis and Serum Androgen Levels in Patients with Premature Ovarian Failure

Women with premature ovarian failure (POF) have been reported to have lower serum androgen levels compared with normal women. We reviewed the androgen profiles of 143 POF patients and found androgen levels above normal for postmenopausal women in 16% of these subjects. To determine the source of androgens in those women, we studied the available ovarian biopsy samples of 15 POF patients with increased androgen levels using immunohistochemistry, with a panel of antibodies directed against the main steroidogenic enzymes. Five of the ovarian biopsies exhibited abnormal follicles characterized by hypertrophied theca interna expressing steroidogenic enzymes involved in androgen synthesis. In five other biopsies, the steroidogenic activity was scarce and confined to a small number of ovarian stromal cells, sometimes situated in the proximity of follicular remnants. Finally, in five patients, we found no histological evidence of present or past follicular development beyond the quiescent follicular stage, and no steroidogenic cells were detected by immunohistochemistry. Our findings suggest that ovarian theca-derived cells are a source of androgens in some women with POF, whereas in others, as in most postmenopausal patients, the adrenals or the ovarian hilus cells may synthesize a significant quantity of androgens under LH stimulation.

Total testosterone and DHEAS levels as predictors of androgen-secreting neoplasms: A populational study

Androgen excess affects between 2% and 10% of women. While the majority of these patients suffer from polycystic ovary syndrome, a few present with an androgen-secreting neoplasm. An elevated circulating total testosterone level and dehydroepiandiosterone sulfate (DHEAS) level have been proposed as screening methods for detecting ovarian and adrenal androgen-secreting neoplasms, respectively. To determine the predictive value of these tests for androgen-secreting tumors in a population of consecutive hyperandrogenic patients, we studied 478 consecutive untreated hyperandrogenic patients presenting over a ten-year period (1987-97). All had at least two of the following features: (1) oligomenorrhea (i.e. cycles > 35 days or < 8 cycles/year), (2) hyperandrogenemia (i.e. a total or free testosterone, or DHEAS > 95th percentile of controls), or (3) hirsutism (i.e. a modified Ferriman—Gallwey score ≥ 6). None of these patients had a prior diagnosis of an androgen-secreting neoplasm. Basal levels of testosterone and DHEAS were determined in all patients, with transvaginal sonography and an adrenal computed tomography scan in select individuals. Of the 478 patients included, 65% had hirsutism and oligomenorrhea; 20% had hyperandrogenic oligomenorrhea; and 15%) had hirsutism and hyperandrogenemia, without overt oligomenorrhea. Overall, 11 (2.3%>) patients had a total testosterone > 8.7 nmol/l (250 ng/dl), of which one actually had an androgen-secreting neoplasm (i.e. true-positive). This postmenopausal patient presented with rapidly progressive virilization, and demonstrated an ovarian hilar cell tumor at surgery. The calculated sensitivity of an elevated testosterone level (> 8.67 nmol/l) for a neoplasm was 100% (1/1), the specificity was 98% (467/477), and the negative predictive value was 100% (467/467), but the positive predictive value was only 9% (1/11). Ten subjects had DHEAS levels > 16.3 μmol/l (6000 ng/ml), and none was diagnosed with an adrenocortical tumor. Although the sensitivity and positive predictive value of a high DHEAS for a neoplasm could not be calculated due to the absence of a test case, the specificity was 98% (468/478) and the negative predictive value was 100% (468/468).These data suggest that the measurement of testosterone and DHEAS is not a cost-effective method of screening for these tumors, due to the low frequency of the disorder and the fact that clinical evaluation alone is often sufficient screening.

The fine structure of the human ovarian hilus cells.

The fine structure of the human ovarian hilus cells.

Ovarian hilar cells and testicular Leydig cells in anencephaly.

The presence of ovarian hilar cells in anencephaly has been investigated and compared with the presence of testicular Leydig cells in the same condition. The examination of 29 anencephalic ovaries and 49 controls showed that up to 36 weeks of gestation there was a preponderance of ovarian hilar cells in anencephalic monsters as compared with controls. Similar observations were made with regard to ovarian follicles which showed more pronounced maturational changes than controls. However, during the last month of gestation both these processes were more marked in the controls. These findings are in marked contrast to our previous observations on the testes in anencephalic monsters which showed significantly less Leydig cells than controls throughout the third trimester of pregnancy. It is assumed that these appearances are due to the fact that testes and ovaries are not strictly comparable structures and may, therefore, react in a different way to hormonal stimulation. This is of particular interest as the placental chorionic gonadotrophin levels which stimulate the development of testicular Leydig cells and, supposedly, the development of ovarian hilar cells are normal in anencephaly.

Morphology and morphogenesis of the Stein-Leventhal ovary and of so-called "hyperthecosis".

A study of 34 full-thickness Stein-Leventhal ovarian wedges and 30 age-matched control ovaries allowed comparison of the entire ovarian cross-sections and quantification of their features. As compared with controls, Stein-Leventhal ovaries showed on average (i) double the cross-sectional area, (II) the same number of primordial follicles, (iii) double the number of ripening and subsequent atretic follicles from the earliest stages, (iv) a tunica increased by 50 per cent and more collagenized, (v) cortical stromal thickness increased by a third, (vi) subcortical stroma, whether deep cortical or medullary in site, increased five times, (vii) ovarian hilus cell nests four times as frequently. The increased subcortical stroma was derived partly from the regressive conversion into stroma of the over-numerous older follicles, so augmenting steadily with duration, and partly from a concurrent stromal hyperplasia. Stromal smooth muscle and lutein cell nests were each found in four-fifths of cases. So-called "hyperthecosis," in which such nests are combined with marked stromal increase, is arguably just a late stage of Stein-Leventhal morphology. The whole picture may result directly or indirectly from the raised LH output, although androgens possibly promote early follicle ripening.

Steroid secretion and testosterone binding in a woman with an ovarian hilus cell tumor and thyrotoxicosis

Presented is the case of a 21-year-old woman with an ovarian hilus cell tumor and thyrotoxicosis. Despite massivley elevated of serum testosterone, virilization was lacking and cyctic ovulatory menses were maintained. Hypersecretion of thyroxine and an increased circutating testosterone-estradiol binding globulin (TeBG) resulted In a level of free testosterone lower than expected, thereby perhaps accounting for the negligible androgen effect. Determinations of peripheral and ovarian venous steroids provided the first In vivo evidence for the preferred synthesis of testosterone via the AΔ5 pathway in a hilus cell tumor. (Am. J. Osstet. Gynecol. 141:535,1981.)

Ovarian hilar cell tumor with coexistent polycystic ovary syndrome and myometrial hypertrophy

Ovarian hilar cell tumor with coexistent polycystic ovaries and diffuse myometrial hypertrophy have been found in a 34-year-old virilized woman with a markedly elevated plasma level of testosterone. Following total abdominal hysterectomy and bilateral salpingo-oophorectomy, the plasma level of testosterone returned to normal. Light microscopic examination of the tumor showed polygonal cells with abundant eosinophilic cytoplasm. A few cells contained intracytoplasmic crystals of Reinke. Electron microscopy revealed abundant endoplasmic reticulum forming vesicles and whorls and numerous pleomorphic mitochondria with peripherally located tubular cristae: ultrastructural features of cells engaged in synthesis of hormones. Immunoperoxidase studies of formalin-fixed, paraffin-embedded tissue demonstrated the presence of testosterone within ovarian tumor, ovarian stroma, and granulosa cells lining the follicular cysts.

Histopathology and ultrastructure of ovarian hilus cell tumor: Report of two cases

Two ovarian hilus cell tumors were studied. One was obtained from a virilized woman, while the other was an asymptomatic incidental finding at surgery performed because of an associated ovarian cyst. The ultrastructural findings were compared with those of the few reported cases in the literature. Comparisons were also made with normal and neoplastic testicular Leydig cells, the homologues of ovarian hilus cells. Intranuclear paracrystalline inclusions were observed in the neoplastic hilus cells of both cases. Complexly structured cytoplasmic crystals were found only in Case 1. A clue to the existence of these particular inclusions was the presence of small eosinophilic masses in corresponding locations in the histologic sections. Neither type of inclusions has been previously described. It is postulated that these and related types of structures are precursors of Reinke crystals. Actual Reinke crystals were not encountered. Prominent cytoplasmic features included vesicular smooth endoplasmic reticulum, frequent large mitochondria with tubular cristae, numerous lipid deposits, membranous whorls, lysosomes, and peroxisomes. Pigment or lipofuscin granules were not observed. Although certain ultrastructural differences existed between the two tumors, they were insufficient to explain why only the patient of Case 1 showed masculinizing effects. The overall histopathology and ultrastructure of ovarian hilus cell tumors are strikingly similar to those of testicular Leydig cell neoplasms.

Ultrastructural and enzyme histochemical study of ovarian hilar cells in women and their relationships with sympathetic nerves

The ultrastructure of normal ovarian hilar cells, both during the reproductive era and after the menopause, shows evidence of steroid hormone synthesis. In this respect these cells are very similar to Leydig cells in that they contain mitochondria with a dense matrix, a highly developed smooth endoplasmic reticulum, Reinke crystals, and microcystalline inclusions. The latter are much more numerous than in the normal testis. Their enzymatic activities are quite similar to those of Leydig cells. Ovarian hilar cells seem to originate from progressive metamorphosis of fibroblastic cells under the induction of sympathetic nervous structures. Their relations with hilar nerves are of three types: simple direct membrane contact without a Schwann cell sheath, intimate intracytoplasmic relationships, and specialized contacts, which are comparable to a synapse.