RESUMEN
The mitochondrial translocator protein (TSPO) has been shown to bind cholesterol with high affinity and is involved in mediating its availability for steroidogenesis. We recently reported that targeted Tspo gene deletion in MA-10 mouse tumor Leydig cells resulted in reduced cAMP-stimulated steroid formation and significant reduction in the mitochondrial membrane potential (ΔΨm) compared to control cells. We hypothesized that ΔΨm reduction in the absence of TSPO probably reflects the dysregulation and/or maintenance failure of some basic mitochondrial function(s). To explore the consequences of TSPO depletion via CRISPR-Cas9-mediated deletion (indel) mutation in MA-10 cells, we assessed the transcriptome changes in TSPO-mutant versus wild-type (Wt) cells using RNA-seq. Gene expression profiles were validated using real-time PCR. We report herein that there are significant changes in nuclear gene expression in Tspo mutant versus Wt cells. The identified transcriptome changes were mapped to several signaling pathways including the regulation of membrane potential, calcium signaling, extracellular matrix, and phagocytosis. This is a retrograde signaling pathway from the mitochondria to the nucleus and is probably the result of changes in expression of several transcription factors, including key members of the NF-κB pathway. In conclusion, TSPO regulates nuclear gene expression through intracellular signaling. This is the first evidence of a compensatory response to the loss of TSPO with transcriptome changes at the cellular level.
Asunto(s)
Células Intersticiales del Testículo/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo , Receptores de GABA/deficiencia , Tumor de Células de Sertoli-Leydig/etiología , Tumor de Células de Sertoli-Leydig/metabolismo , Transducción de Señal , Animales , Sistemas CRISPR-Cas , Línea Celular Tumoral , Mapeo Cromosómico , Matriz Extracelular/metabolismo , Edición Génica , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Mutación INDEL , Masculino , Ratones , FN-kappa B/metabolismo , Tumor de Células de Sertoli-Leydig/patología , TranscriptomaRESUMEN
Polycystic ovary syndrome is the most common cause of hyperandrogenism in young females. Other causes are congenital adrenal hyperplasia (CAH), androgen-producing tumours and drugs. The severity and tempo of virilisation help in distinguishing the tumoural from non-tumoural causes. We report a rare case of non-classic CAH and androgen-producing ovarian tumour in the same patient, causing hyperandrogenism. A 15-year-old female patient presented with secondary amenorrhea, excessive facial hair growth and clitoromegaly for 6 months. Due to severe virilisation, tumoural aetiology was considered. Investigations showed marked elevation of testosterone and mild elevation of 17 hydroxy progesterone (17OHP). Imaging confirmed right ovarian tumour. Adrenocorticotropic hormone stimulated 17OHP, was elevated confirming the diagnosis of underlying non-classic CAH. Surgical removal of the tumour was followed by improvement in hyperandrogenism, but persistent elevation of 17OHP confirmed the underlying presence of non-classic CAH.
Asunto(s)
Hiperplasia Suprarrenal Congénita/diagnóstico , Tumor de Células de Sertoli-Leydig/diagnóstico , 17-alfa-Hidroxiprogesterona/metabolismo , Adolescente , Hiperplasia Suprarrenal Congénita/complicaciones , Hiperplasia Suprarrenal Congénita/metabolismo , Femenino , Humanos , Hallazgos Incidentales , Salpingooforectomía , Tumor de Células de Sertoli-Leydig/complicaciones , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/patología , Virilismo/etiologíaRESUMEN
This descriptive study was carried out at Pathology Department, Shifa International Hospital from 2007 to 2016; all sex cord stromal tumours diagnosed during this time period were included. Epithelial, germ cell and metastatic tumours were excluded from the study. A total of 1254 Ovarian tumours were brought to Shifa of which47 (4%) were labeled as sex cord stromal tumours. Of these 36( 76 %)were granulosa cell tumour (adult33, juvenile3), 7 were labeled as sertoli leydig cell tumours (15%), 3 as thecoma/ fibroma group (7%)and only one case was labeled as microcystic stromal tumour of the ovary (2%). Overall age range for sex cord stromal tumours was 42 (12-71). Immunohistochemistry was done in 41 out of 47 cases. Sex cord stromal tumours of the ovary are rare tumours comprising 4% of the total. Adult Granulosa cell tumour is the commonest tumour seen in our study.
Asunto(s)
Tumor de Células de la Granulosa/epidemiología , Neoplasias Ováricas/epidemiología , Tumor de Células de Sertoli-Leydig/epidemiología , Neoplasia Tecoma/epidemiología , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Calbindina 2/metabolismo , Niño , Femenino , Tumor de Células de la Granulosa/metabolismo , Humanos , Inhibinas/metabolismo , Queratinas/metabolismo , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Pakistán/epidemiología , Tumor de Células de Sertoli-Leydig/metabolismo , Tumores de los Cordones Sexuales y Estroma de las Gónadas/epidemiología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/metabolismo , Neoplasia Tecoma/metabolismo , Adulto JovenRESUMEN
DICER1, an endoribonuclease required for microRNA (miRNA) biogenesis, is essential for embryogenesis and the development of many organs including ovaries. We have recently identified somatic hotspot mutations in RNase IIIb domain of DICER1 in half of ovarian Sertoli-Leydig cell tumors, a rare class of sex-cord stromal cell tumors in young women. These hotspot mutations lost IIIb cleavage activity of DICER1 in vitro and failed to produce 5p-derived miRNAs in mouse Dicer1-null ES cells. However, the oncogenic potential of these hotspot DICER1 mutations has not been studied. Here, we further revealed that the global expression of 5p-derived miRNAs was dramatically reduced in ovarian Sertoli-Leydig cell tumors carrying DICER1 hotspot mutations compared with those without DICER1 hotspot mutation. The miRNA production defect was associated with the deregulation of genes controlling cell proliferation and the cell fate. Using an immortalized human granulosa cell line, SVOG3e, we determined that the D1709N-DICER1 hotspot mutation failed to produce 5p-derived miRNAs, deregulated the expression of several genes that control gonadal differentiation and cell proliferation, and promoted cell growth. Re-expression of let-7 significantly inhibited the growth of D1709N-DICER1 SVOG3e cells, accompanied by the suppression of key regulators of cell cycle control and ovarian gonad differentiation. Taken together, our data revealed that DICER1 hotspot mutations cause systemic loss of 5p-miRNAs that can both drive pseudodifferentiation of testicular elements and cause oncogenic transformation in the ovary.
Asunto(s)
ARN Helicasas DEAD-box/genética , Mutación Missense , Neoplasias Ováricas/genética , Ribonucleasa III/genética , Tumor de Células de Sertoli-Leydig/genética , Secuencia de Bases , Sitios de Unión/genética , Western Blotting , Línea Celular , Proliferación Celular/genética , ARN Helicasas DEAD-box/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Células de la Granulosa/metabolismo , Células HEK293 , Humanos , MicroARNs/genética , Datos de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ribonucleasa III/metabolismo , Tumor de Células de Sertoli-Leydig/metabolismoRESUMEN
The patient was a 19-year-old female who presented with a chief complaint of progressive pelvic pain. Preoperative ultrasound of the right ovary revealed an ovarian torsion as the cause of the patient's progressive pain. Laparoscopy confirmed the torsion and revealed a right ovary measuring 10 cm in greatest diameter. Intraoperative incision into the ovary revealed a simple ovarian cystic mass measuring 3.0 x 1.5 x 0.8 cm. A solid component within the cyst was identified. Histological sections of the cystic mass demonstrated mononuclear and hyperchromatic Sertoli cells with a trabecular growth pattern. Clusters of medium-sized epithelioid cells with abundant eosinophilic cytoplasm consistent with Leydig cells were also identified between the trabeculae of Sertoli cells. In addition, focal areas of intestinal type mucinous epithelium were identified embedded within the trabeculae of Sertoli cells. Immunohistochemical studies revealed that the Sertoli cells were positive for calretinin (bright) while the Leydig cells were positive for calretinin (dim), inhibin, CAM5.2 and AE1&3. CEA showed positivity mainly of the intraluminal contents of the mucinous type intestinal epithelium. The patient had an uneventful post-operative course and was disease-free for 3 years.
Asunto(s)
Tumor de Células de Sertoli-Leydig/patología , Biomarcadores de Tumor/análisis , Femenino , Humanos , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/cirugía , Adulto JovenAsunto(s)
Adenoma/patología , Enfermedades de los Anexos/patología , Neoplasias Primarias Múltiples/patología , Adenoma/metabolismo , Adenoma/cirugía , Adenoma/ultraestructura , Anexos Uterinos/patología , Anexos Uterinos/cirugía , Enfermedades de los Anexos/metabolismo , Enfermedades de los Anexos/cirugía , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patología , Diagnóstico Diferencial , Femenino , Tumor de Células de la Granulosa/metabolismo , Tumor de Células de la Granulosa/patología , Humanos , Histerectomía , Queratinas/metabolismo , Leiomiomatosis/patología , Leiomiomatosis/cirugía , Microscopía Electrónica , Persona de Mediana Edad , Neoplasias Primarias Múltiples/metabolismo , Neoplasias Primarias Múltiples/cirugía , Neoplasias Primarias Múltiples/ultraestructura , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/patología , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía , Vimentina/metabolismo , Proteínas WT1/metabolismoRESUMEN
AIM: To examine the impact of surgical normalization of testosterone on body weight and on glucose and lipid metabolism and insulin sensitivity in a group of hyperandrogenic women with ovarian androgen-secreting tumours (OAST). METHODS: Five consecutive postmenopausal hyperandrogenic patients (aged 63 ± 5 years) with a diagnosis of OAST were prospectively evaluated. Clinical signs, symptoms and metabolic and hormonal parameters were collected at the time of the diagnosis and at follow-up, 12 months after surgical oophorectomy. A group of 15 age-matched and body mass index-matched postmenopausal control women served as a reference group. RESULTS: At baseline, patients with OAST had very high testosterone levels and inappropriately low gonadotrophin levels for their menopausal status. All the women were overweight or obese, and one had a history of polycystic ovary syndrome and Type 2 diabetes. Twelve months after surgical oophorectomy, testosterone and gonadotrophin levels returned to appropriate values for menopausal status in all patients; however, no change in body weight was found. Fasting glucose levels slightly increased (P < 0·05) without any significant change in other metabolic parameters. In the woman with diabetes, a moderate decrease in haemoglobin A1c occurred. Red blood cell count and haematocrit values were normalized (P < 0·05, respectively). CONCLUSION: Normalization of androgen levels achieved after surgical oophorectomy did not cause any significant change in body weight and insulin sensitivity. These findings may offer a different perspective on the impact of hyperandrogenaemia on metabolism.
Asunto(s)
Andrógenos/metabolismo , Hiperandrogenismo/metabolismo , Hiperandrogenismo/cirugía , Neoplasias Ováricas/cirugía , Tumor de Células de Sertoli-Leydig/cirugía , Anciano , Peso Corporal/fisiología , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Hiperandrogenismo/sangre , Hiperandrogenismo/etiología , Resistencia a la Insulina , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Obesidad/metabolismo , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/metabolismo , Síndromes Paraneoplásicos Endocrinos/sangre , Síndromes Paraneoplásicos Endocrinos/metabolismo , Síndromes Paraneoplásicos Endocrinos/cirugía , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/metabolismo , Posmenopausia/sangre , Posmenopausia/metabolismo , Tumor de Células de Sertoli-Leydig/complicaciones , Tumor de Células de Sertoli-Leydig/metabolismoRESUMEN
Herein, we described a case of a 29-year-old female with a large ovarian mass. Fine needle aspiration cytology (FNAC) of the mass showed discrete round to oval cells in a fatty vacuolated background. FNAC diagnosis of dysgerminoma was suggested. The histology of the tumors showed features of poorly differentiated Sertoli-Leydig cell tumors. We discussed the diagnostic pitfalls of this case on FNAC.
Asunto(s)
Errores Diagnósticos , Disgerminoma/diagnóstico , Neoplasias Ováricas/patología , Ovario/patología , Tumor de Células de Sertoli-Leydig/patología , Adulto , Biopsia con Aguja Fina/métodos , Diagnóstico Diferencial , Femenino , Humanos , Metabolismo de los Lípidos , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/cirugía , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/cirugía , Vacuolas/metabolismo , Vacuolas/patologíaRESUMEN
Sertoli-Leydig cell tumor is a rare and usually unilateral tumor of the ovary occurring in women's reproductive age. Only about 10% of these patients are over 50 years of age. One third of these patients are suffering from signs of virilisation. This work summarizes the morphological and immunohistochemical characteristics of this tumor in a 56-year old woman with clinical signs of virilisation.
Asunto(s)
Neoplasias Ováricas/patología , Ovario/patología , Tumor de Células de Sertoli-Leydig/patología , Virilismo/patología , Andrógenos/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/metabolismo , Tumor de Células de Sertoli-Leydig/complicaciones , Tumor de Células de Sertoli-Leydig/metabolismo , Testosterona/metabolismo , Virilismo/etiología , Virilismo/metabolismoRESUMEN
Bilateral Sertoli-Leydig cell tumors (SLCTs) of the ovary, especially in association with a cystadenoma, are exceedingly rare. Some SLCTs, usually of poor differentiation, show heterologous elements. We present a case of a 61-year-old woman with bilateral well-differentiated SLCTs in which the Sertoli-Leydig cell component showed leiomyogenic (heterologous) differentiation. Furthermore, on the left side it also was associated with a serous cystadenoma.
Asunto(s)
Cistadenoma Seroso/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patología , Tumor de Células de Sertoli-Leydig/patología , Diferenciación Celular , Cistadenoma Seroso/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Primarias Múltiples/metabolismo , Neoplasias Ováricas/metabolismo , Tumor de Células de Sertoli-Leydig/metabolismoAsunto(s)
Neoplasias Ováricas/diagnóstico , Tumores de los Cordones Sexuales y Estroma de las Gónadas/diagnóstico , Antígeno 12E7 , Antígenos CD/metabolismo , Antígeno CD56/metabolismo , Calbindina 2 , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patología , Moléculas de Adhesión Celular/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patología , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Inhibinas/metabolismo , Antígeno MART-1/metabolismo , Neprilisina/metabolismo , Neoplasias Ováricas/metabolismo , Proteína G de Unión al Calcio S100/metabolismo , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/metabolismo , Factor Esteroidogénico 1/metabolismo , Proteínas WT1/metabolismoRESUMEN
Ovarian cancer is associated with high mortality due to its late onset of symptoms and lack of reliable screening methods for early detection. Furthermore, the incidence of ovarian cancer is higher in postmenopausal women. Mice rendered follicle-depleted through treatment with 4-vinylcyclohexene diepoxide (VCD) are a model of ovary-intact menopause. The present study was designed to induce ovarian neoplasia in this model by treating mice with 7,12-dimethylbenz[a]anthracene (DMBA). Female B6C3F1 mice (age, 28 d) received intraperitoneal sesame oil (vehicle; VCD- groups) as a control or VCD (160 mg/kg; VCD+ groups) daily for 20 d to cause ovarian failure. Four months after the onset of dosing, mice from each group received a single injection of DMBA (VCD-DMBA+ and VCD+DMBA+ groups, n = 15 per group) or vehicle control (VCD-DMBA-, n = 15; VCD+ DMBA-, n = 14) under the bursa of the right ovary. Ovaries were collected 3 or 5 mo after injection and processed for histologic evaluation. Immunohistochemistry was used to confirm classification of neoplasms. None of the animals in the VCD-DMBA- and VCD-DMBA+ groups (that is, mice still undergoing estrus) had tumors at either time point. At the 3-mo time point, 12.5% of the VCD+DMBA+ mice had ovarian tumors; at 5 mo, 57.1% of the VCD+DMBA+ and 14.3% of VCD+DMBA- ovaries had neoplasms. Neoplasms stained positively for inhibin alpha (granulosa cells) and negatively for keratin 7 (surface epithelium), thus confirming classification of the lesions as Sertoli-Leydig cell tumors. These findings provide evidence for an increased incidence of DMBA-induced ovarian neoplasms in the ovaries of follicle-depleted mice compared with that in age-matched cycling controls.
Asunto(s)
9,10-Dimetil-1,2-benzantraceno/toxicidad , Carcinógenos/toxicidad , Ciclohexenos/administración & dosificación , Folículo Ovárico/efectos de los fármacos , Neoplasias Ováricas/inducido químicamente , Tumor de Células de Sertoli-Leydig/inducido químicamente , Compuestos de Vinilo/administración & dosificación , Animales , Femenino , Inmunohistoquímica , Inhibinas/metabolismo , Queratina-7/metabolismo , Ratones , Neoplasias Ováricas/metabolismo , Tumor de Células de Sertoli-Leydig/metabolismoRESUMEN
Sertoli-Leydig cell tumor (SLCT) is a rare tumor involving the ovary. Approximately 20% of SLCT are associated with heterologous elements that are either of endodermal or mesodermal origin. The gastrointestinal-type epithelium is the most commonly described endodermal heterologous element. SLCT with benign and borderline mucinous neoplasm has been reported in the literature. However, SLCT with mucinous adenocarcinoma as heterologous element has been rarely documented. Herein, we describe a rare case of intermediately differentiated Sertoli-Leydig cell tumor with mucinous adenocarcinoma as the heterologous element in a 21-year-old woman. She presented with throbbing lower abdominal pain and was found to have a large, complex left ovarian mass on imaging studies. She underwent left salpingo-oophorectomy, appendectomy and lymph node staging. Gross examination of the surgical specimen showed a large, encapsulated, solid-cystic mass completely replacing the ovary. Microscopically, the tumor was composed of intermediately differentiated Sertoli-Leydig cell tumor and well-differentiated mucinous adenocarcinoma. Interestingly, the bulk of the tumor (more than 90%) was composed of mucinous adenocarcinoma, whereas the SLCT component comprised less than 10% of the total tumor. The mucinous adenocarcinoma expressed positivity for CK20, CEA, CDX2 and CK7, and the SLCT component was positive for inhibin expression. The histopathological features and results of immunostaining were consistent with the diagnosis of the intermediately differentiated SLCT with mucinous adenocarcinoma as the heterologous element. This case was a diagnostic challenge as more than 90% of the tumor was composed of mucinous adenocarcinoma and SLCT constituted only the minor part of the tumor. This feature was in contrast to the previously described two cases, where mucinous adenocarcinoma as heterologous element was present as microscopic foci. This case highlights the importance of identifying the SLCT component in a case of an apparently pure mucinous adenocarcinoma in a young patient.
Asunto(s)
Adenocarcinoma Mucinoso/patología , Neoplasias Ováricas/patología , Tumor de Células de Sertoli-Leydig/patología , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/cirugía , Diferenciación Celular , Femenino , Humanos , Inmunohistoquímica , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/cirugía , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/cirugía , Adulto JovenRESUMEN
Desmoplastic small round cell tumor (DSRCT) is a rare aggressive tumor primarily involving serosal surfaces in adolescents and young men. Diagnosis is based on specific clinicomorphologic, immunohistochemical, and genetic features. We report here a variant of DSRCT involving the ovaries that mimics the Sertoli-Leydig cell tumor in a 21-year-old woman complaining of abdominal pain. Abdominal ultrasonography and computed tomography showed a right adnexal mass. She had a slightly raised serum CA-125 level. Frozen section examination identified the right ovarian mass as a poorly differentiated Sertoli-Leydig cell tumor. The surgically resected tumor and left ovary and omentum implants found during laparoscopy were diagnosed as DSRCT with Leydig cell hyperplasia. Immunohistochemically, the tumor cells were negative for epithelial markers but were positive for calretinin and inhibin. The patient is still undergoing chemotherapy at 8 months after initial presentation with partial response. This case showed that DSRCT with unusual immunohistochemical profiles and Leydig cells hyperplasia pose a diagnostic challenge. Molecular genetic techniques may help in these cases.
Asunto(s)
Carcinoma de Células Pequeñas/patología , Células Intersticiales del Testículo/patología , Neoplasias Ováricas/patología , Tumor de Células de Sertoli-Leydig/patología , Adulto , Antineoplásicos , Calbindina 2 , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia , Inmunohistoquímica , Inmunofenotipificación , Inhibinas/biosíntesis , Masculino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/secundario , Proteína G de Unión al Calcio S100/biosíntesis , Tumor de Células de Sertoli-Leydig/metabolismoRESUMEN
AIMS: To analyse both the clinicopathological and immunohistochemical findings in six cases of uterine tumours resembling ovarian sex cord tumours with a predominant epithelial retiform component resembling the rete ovarii (RUTROSCT) and to compare their immunophenotype with tissues containing retiform structures such as the normal rete ovarii, retiform Wolffian adnexal tumour (RWAT) and ovarian retiform areas of Sertoli-Leydig cell tumours (ORSLCT). METHODS AND RESULTS: Six RUTROSCTs were analysed. The average age of patients was 65 years, and all tumours behaved in a benign fashion. Four were intracavitary and two intramural. Two cases were misdiagnosed as malignant in endometrial biopsy specimens and one in the hysterectomy specimen. Histologically they had a tubulopapillary or glomeruloid formation; a sex-cord-like or endometrial stromal component was absent or comprised at most 30% of the tumour. RUTROCST showed consistent positivity for CAM5.2, cytokeratin (CK) 7, vimentin, calretinin, progesterone receptor and apical CD10. CD56 and alpha-inhibin were positive in half of the cases. Epithelial membrane antigen, desmin, smooth muscle actin and calponin were negative. Comparatively, rete ovarii and RWAT had a similar positivity for CK7, CD56, CD10 and calretinin. ORSLCT differed in its conspicuous positivity to CD56, CD10, alpha-inhibin and calretinin, but absent CK7 expression. CONCLUSIONS: RUTROSCTs have benign behaviour but may be confused with various uterine adenocarcinomas or metastases. Correct diagnosis should avoid overtreatment. The immunophenotype of retiform areas is similar to that of adult rete ovarii and RWAT with minor divergence from ORSLCT.
Asunto(s)
Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/metabolismo , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patología , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Antígeno CD56/metabolismo , Calbindina 2 , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Inhibinas/metabolismo , Queratina-7/metabolismo , Persona de Mediana Edad , Mucina-1/metabolismo , Neprilisina/metabolismo , Proteína G de Unión al Calcio S100/metabolismo , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/patologíaRESUMEN
SOX-9, an essential factor for male sexual development, can be induced by prostaglandin D2 in a Sry-independent mechanism. Recent data suggest that the hedgehog pathway is involved in the differentiation of normal Sertoli and Leydig cells. The purpose of our study was to investigate the mechanisms involved in the differentiation of ovarian sex cord-stromal tumour (SCST) cells. Two Sertoli-Leydig cell tumours and two granulosa cell tumours with a minor Sertoli element were studied using immunohistochemistry on paraffin-embedded tissue sections. Sertoli cells expressed anti-Mullerian hormone (AMH), SOX-9, prostaglandin D synthase (Pgds) and bcl-2 (in four of four cases); sonic hedgehog (Shh) and p53 (in three of four cases) and androgen receptors (AR; in one of four cases). Ki-67 index ranged from 10% to 50%. Leydig cells expressed Shh and AR (two of two cases), while they showed no expression of p53, bcl-2 and 0% Ki-67 index. Granulosa cells expressed AMH, Pgds, Shh, estrogen receptors, progesterone receptors, AR and bcl-2 (in two of two cases) and p53 (in one of two cases). Ki-67 index was 10% and 40%, respectively. Further investigation is required to clarify the role of the molecules outlined above in the histogenesis of ovarian SCST, as Pgds-mediated SOX-9 upregulation could provide a reasonable explanation for the presence of testicular differentiation in ovarian SCST.
Asunto(s)
Diferenciación Celular , Tumor de Células de la Granulosa/patología , Neoplasias Ováricas/patología , Tumor de Células de Sertoli-Leydig/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Adulto , Femenino , Tumor de Células de la Granulosa/metabolismo , Proteínas Hedgehog/metabolismo , Humanos , Oxidorreductasas Intramoleculares/metabolismo , Lipocalinas/metabolismo , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptores Androgénicos/metabolismo , Estudios Retrospectivos , Factor de Transcripción SOX9/metabolismo , Tumor de Células de Sertoli-Leydig/metabolismo , Tumores de los Cordones Sexuales y Estroma de las Gónadas/metabolismo , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Sertoli-Leydig cell tumours with a retiform pattern similar to the pattern of the rete testis are a subtype of sex cord-stromal tumours recognized in the human WHO histological classification of ovarian tumours but not in the equivalent classification for domestic animals. The morphology of the tumour may be confused with that of the more common ovarian epithelial tumours. The gross, microscopical and immunohistochemical features of a canine retiform Sertoli-Leydig cell tumour and its comparison with the human counterpart are presented in this report. Both ovaries were enlarged and cystic. Microscopically, the tumour was cystic with tubulopapillary growth characterized by narrow, elongated branching tubules. Immunohistochemically, the tumour cells expressed alpha-inhibin, while epithelial membrane antigen was not detected, indicating a sex cord-stromal origin of the tumour. Additionally, the tumour cells expressed cytokeratin and vimentin in addition to oestrogen receptor alpha and progesterone receptor.
Asunto(s)
Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/patología , Inhibinas/biosíntesis , Mucina-1/biosíntesis , Neoplasias Ováricas/veterinaria , Tumor de Células de Sertoli-Leydig/veterinaria , Animales , Diagnóstico Diferencial , Perros , Femenino , Inmunohistoquímica , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/patologíaRESUMEN
OBJECTIVE: To describe the clinical history and ultrasound findings in women with ovarian Sertoli cell, Sertoli-Leydig cell and Leydig cell tumors. METHODS: Women with a histological diagnosis of Sertoli cell tumor, Sertoli-Leydig cell tumor or Leydig cell tumor who had undergone preoperative ultrasound examination were identified from the databases of each of three participating ultrasound centers. The tumors were characterized on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions published by the International Ovarian Tumor Analysis (IOTA) group. In addition, all images were reviewed and described using pattern recognition. RESULTS: Of 22 patients identified, 15 had Sertoli-Leydig cell tumors, two had Sertoli cell tumors and five had Leydig cell tumors. Four patients were postmenopausal, one 48-year-old woman had undergone hysterectomy, 16 were of fertile age and one was a 4-year-old girl. Most patients (82%, 18/22) had endocrine symptoms, the most common being bleeding disturbance (64%, 14/22) and hirsutism (32%, 7/22). Twenty-two (96%) of 23 tumors (one woman had bilateral tumors) contained a solid component; 16 (70%) were purely solid. Pattern recognition showed that the Leydig cell tumors were small solid tumors (four of five had a largest diameter of 1-3 cm) and the two Sertoli cell tumors were somewhat larger solid tumors (4 cm and 7 cm); the Sertoli-Leydig cell tumors were either small (3-4 cm) or medium-sized (6-7 cm) solid tumors, or multilocular solid tumors of any size (3-18 cm) with purely solid areas mixed with areas of innumerable closely packed small cyst locules. CONCLUSIONS: On the basis of endocrine symptoms, the woman's age and ultrasound findings, it should be possible to suggest a correct preoperative diagnosis of Sertoli cell, Sertoli-Leydig cell or Leydig cell tumors in many cases.
Asunto(s)
Neoplasias Ováricas/diagnóstico por imagen , Tumor de Células de Sertoli-Leydig/diagnóstico por imagen , Adolescente , Adulto , Biomarcadores de Tumor/metabolismo , Diferenciación Celular/fisiología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Reconocimiento de Normas Patrones Automatizadas/métodos , Pronóstico , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/patología , UltrasonografíaRESUMEN
The biologic role that estrogen receptor (ER) and progesterone receptor (PR) play in ovarian sex cord-stromal tumors is poorly understood. Furthermore, immunohistochemical data on these hormone receptors in this group of neoplasms are limited and conflicting, with many reports suggesting that expression of ERalpha and/or PR is either infrequent or present at low levels in granulosa and Sertoli cell tumors. Immunohistochemical staining for ERalpha and PR was performed in 69 ovarian sex cord-stromal tumors: 41 adult granulosa cell tumors and 28 Sertoli-Leydig cell tumors. Extent of expression was scored based on the percentage of positive cells: 0, 5% or less; 1+, 6% to 25%; 2+, 26% to 50%; 3+, 51% to 75%; and 4+, 76% to 100%. Estrogen receptor alpha and PR were frequently expressed in adult granulosa cell tumors (66% and 98%, respectively) and Sertoli-Leydig cell tumors (79% and 86%, respectively). Diffuse (3+ or 4+) expression of PR was more common in adult granulosa cell tumors (68% vs. 36%; P = 0.013), whereas diffuse (3+ or 4+) expression of ERalpha was more frequent in Sertoli-Leydig cell tumors (50% vs. 20%; P = 0.010). In cases positive for both markers, adult granulosa cell tumors exhibited a focal (1+ or 2+) ERalpha/diffuse (3+ or 4+) PR coordinate profile more commonly than Sertoli-Leydig cell tumors (52% vs. 18%; P = 0.02), whereas Sertoli-Leydig cell tumors displayed a diffuse (3+ or 4+) ERalpha/focal (1+ or 2+) PR profile more frequently than adult granulosa cell tumors (36% vs. 0%; P = 0.0007). We conclude that expression of hormone receptors (based only on frequency of immunostaining) does not allow for distinction from other tumors in the differential diagnosis that are known to be frequently positive for ERalpha and PR such as endometrioid neoplasms. Most adult granulosa cell tumors and Sertoli-Leydig cell tumors share overlapping patterns of expression of ERalpha and PR with each other, but a subset of cases in each tumor category exhibits unique ERalpha/PR immunoprofiles (eg, focal ERalpha/diffuse PR in adult granulosa cell tumors and diffuse ERalpha/focal PR in Sertoli-Leydig cell tumors). These patterns of expression of ERalpha and PR may aid our understanding of the biologic differences between granulosa and Sertoli cell tumors.
Asunto(s)
Receptor alfa de Estrógeno/biosíntesis , Tumor de Células de la Granulosa/metabolismo , Neoplasias Ováricas/metabolismo , Receptores de Progesterona/biosíntesis , Tumor de Células de Sertoli-Leydig/metabolismo , Carcinoma Endometrioide/patología , Diagnóstico Diferencial , Femenino , Tumor de Células de la Granulosa/patología , Humanos , Inmunohistoquímica , Neoplasias Ováricas/patologíaRESUMEN
The propensity for ovarian endometrioid adenocarcinomas to morphologically mimic Sertoli, Sertoli-Leydig, and granulosa cell tumors, is well known. The converse situation, mimicry of an endometrioid neoplasm by a sex cord-stromal tumor, has not been emphasized. In this report, we describe 9 ovarian Sertoli-Leydig cell tumors (5 well differentiated, 4 of intermediate differentiation) with areas containing hollow, sometimes dilated, tubules which resemble endometrioid glands; we refer to these as pseudoendometrioid tubules. The age of the patients ranged from 14 to 57. The tumors, all of which were unilateral except for one, ranged from 3.5 to 19 cm and were variously described as tan, pale, yellow, or gold. The proportion of the tumor made up of pseudoendometrioid tubules ranged from 10% to >90%. When widespread, their presence sometimes resulted in consideration of a borderline endometrioid adenofibroma or a well-differentiated endometrioid adenocarcinoma. However, all the neoplasms contained typical Sertoli tubules and one or more of the characteristic patterns of Sertoli-Leydig cell tumors as well as Leydig cells, although the latter cells were inconspicuous in some cases. Immunohistochemistry, performed in 4 cases, showed that the pseudoendometrioid tubules, as well as the more typical Sertoli cell elements, were either positive for alpha inhibin (3 of 4 cases) or calretinin (3 of 4 cases) or both, although sometimes focally so. These elements were negative with epithelial membrane antigen and cytokeratin 7. In all 4 cases, the pseudoendometrioid tubules were positive with the broad spectrum cytokeratin AE1/3. This report illustrates the potential for ovarian Sertoli-Leydig cell tumors to contain tubules with a pseudoendometrioid appearance which mimic a borderline or malignant endometrioid neoplasm. The presence of more typical Sertoli cell elements and Leydig cells, an absence of squamous elements, endometriosis or associated adenofibroma, and the characteristic immunophenotype assist in diagnosis.