Histological and immunohistochemical characterization of 17 gonadal tumours in koi carp (Cyprinus carpio koi).

Reports on abdominal tumours in koi carp are scarce and most are from the gonads. Their histological diagnosis is challenging due to the occurrence of mixed populations of neoplastic cells and the few availability of cross-reactive antibodies in fish tissues. The present study aims to provide a histopathological characterization of seventeen gonadal tumours, enriched by a wide antibody panel (vimentin, CD117, placental alkaline phosphatase-PLAP, AE1/AE3 cytokeratin, E-cadherin, proliferating cell nuclear antigen-PCNA, müllerian-inhibiting substance-MIS, GATA4 and Inhibin-α) applied on whole and tissue microarray (TMA) sections. Abdominal enlargement was associated with tumours filling 30%-80% of the abdominal cavity; frequently, the gonads had been completely replaced by neoplastic tissue. Twelve cases were characterized as sex cord-stromal tumours (SCSTs), three as germ cell tumours (GCTs), one as mixed germ cell sex cord-stromal tumour (MGCSCST) and one as carcinoma. By immunohistochemistry, PLAP enabled confirmation of GCTs, ovarian carcinoma and the objective identification of a further cell component in 8 out of the 12 SCSTs that were reclassified as mixed tumours. The use of an immunohistochemical panel can help in refining the histological diagnosis, but the morphological diagnosis still represents the main tool for the characterization of these tumours in koi carp.

[Transformation of teratoma in rabdomiosarcoma]. / Transformación de teratoma en rabdomiosarcoma.

Teratomas are malign germ cell tumors composed of two or more tissue layers. When there is specific organ differentiation they are called mature teratoma. They rarely grow aggressively. We report the case of a 29 year-old man with a diagnosis of gonadal germ cell tumor whose evolution was unfavorable owing to transformation into a different phenotype corresponding to a rhabdomyosarcoma. This phenomenon occurs through differential growth of a single histological component of the original tumor or transformation of a somatic lineage that becomes dominant. Transformed tumors such as the one herein described differ from most germ cell neoplasms regarding behavior, prognosis, and susceptibility to established treatments.

Swyer syndrome in a woman with pure 46,XY gonadal dysgenesis: a rare presentation.

46,XY pure gonadal dysgenesis (Swyer syndrome) is a rare cause of disorder of sexual development. It is a genetic aberration characterized by a 46,XY karyotype which are phenotypical females, with female genitalia at birth, and normal Müllerian structures. The condition usually becomes apparent first in adolescence with delayed puberty and primary amenorrhea. Herein the authors present the case of a 27-year-old woman with primary amenorrhea and undeveloped breasts. The patient had pure 46,XY gonadal dysgenesis with hypoplastic uterus, estrogen treatment for amenorrhea, and no neoplastic changes on the histopathology report. The authors highlight the high risk of neoplastic transformation of the patient with gonadal dysgenesis, and 46,XY karyotype should be referred for bilateral gonadectomy. Once the diagnosis of Swyer syndrome is established, early treatment is crucial to prevent the development of gonadal malignancy and to enable a normal sex life, and even carry a fetus in an immature uterus.

Malignant extra-cranial germ cell tumors in children and adolescents. Results following the guidelines of SFOP/SFCE 95 Protocol.

Between September 1995 and December 2010, 99 new consecutive assessable patients with extra-cranial MGCT were treated according to SFOP/SFCE TGM95 Protocol. A "watch and wait" strategy for completely resected stage I-II was observed in cases with preoperative high tumor markers levels. Metastatic disease or alpha fetoprotein levels > 15 000 ng/ml cases were treated by VIP chemotherapy (etoposide, ifosfamide and CDDP) 4-6-courses. All other cases were treated by VBP (vinblastine, bleomycin, and CDDP) 3-5 courses. Median age for the whole group was 11.1 (r: 0-17) years. Males: 49, females: 50. Stage I: 19 patients, stage II: 16, stage III: 31 and stage IV: 3. Gonadal disease occurred in 77 cases. Of 21 completely resected stage I-II patients with MGCT who did not receive chemotherapy after surgery, 6 presented disease progression and were successfully treated by chemotherapy and remained disease-free. There were no significant differences in outcome according to age, gender, initial site, staging, and histological variant or high levels of alpha-fetoprotein. Initial non-responsiveness to VIP chemotherapy was the only significant unfavorable prognostic feature. With a median follow-up of 64 (r: 5-204) months, at 10 years EFS and OS estimates for the whole group were 0.82 (SE = 0.05) and 0.90 (SE = 0.03) respectively. Therapy results of MGCT treated with the SFOP/SFCE 95 strategy were excellent. Initial non-response to front line chemotherapy was the only significant adverse prognostic feature. The "watch and wait" strategy for completely resected disease with initial positive markers proved to be safe with optimal outcome.

Sertoli cell tumor and intratubular germ cell neoplasia located in separate gonads in an adolescent patient with complete androgen insensitivity: a case report and review of literature.

Complete androgen insensitivity syndrome (AIS) is an X-linked disorder of sex development. Surgical management entails timely gonadectomy given the risk of malignant transformation. Our patient presented at age 15 years with primary amenorrhea. Initial laboratory testing showed elevated testosterone, luteinizing hormone, anti-Müllerian hormone levels, and 46,XY karyotype. Imaging studies showed no uterus, ovaries, and identified two candidate gonads. She underwent bilateral gonadectomy. Pathology reports revealed Sertoli cell and intratubular germ cell tumors located in separate gonads. Our case is the first report of the youngest patient with AIS with bilateral gonadal tumors derived from different histological origins. We also review literature for reports of AIS patients with gonadal tumors. Currently, there is no consensus for the timing of gonadectomy in AIS patients. However, given the varying potential for malignant transformation of gonads in AIS patients with different phenotypes, development of a standardized treatment guideline is indicated.

Local Control of Perineal Rhabdomyosarcoma: Are Current Recommendations Adequate?

Rhabdomyosarcoma (RMS) is a rare malignancy that can develop in nearly any soft-tissue of the body. Location of the primary tumor affects treatment strategy and prognosis, and RMS of the perineal areas can be especially difficult to treat successfully. RMS is treated systemically with chemotherapy. Local control options include surgical excision, radiation treatment, or a combination of the 2. Treating RMS with radiation treatment can be challenging due to the absence of standardized dosage protocols, along with the presence of conflicting recommendations in the literature. Each case of perineal RMS may benefit from a more individualized treatment plan.

Variation of Gonadal Dysgenesis and Tumor Risk in Patients With 45,X/46,XY Mosaicism.

OBJECTIVE: To describe the gonadal features of patients with 45,X/46,XY mosaicism, and to evaluate the prevalence of gonadal tumor in different phenotypes. MATERIALS AND METHODS: The medical records of consecutive patients with 45,X/46,XY karyotype or its variants who had undergone gonadal biopsy or gonadectomy at a single institute between 1996 and 2017 were retrospectively reviewed. RESULTS: Of 34 patients with 45,X/46,XY mosaicism, a unilateral dysgenetic testis and a contralateral streak gonad was detected in 20 patients (59%), bilateral streak gonads in 9 (26%), and bilateral dysgenetic testes in 5 (15%). A gonad composed of both streak and dysgenetic testicular portions was observed in 7 gonads of 6 patients. All streak gonads were removed, and bilateral gonadectomy was performed in 15 patients raised as girls. Pathologic examination revealed gonadal tumors in 6 of the 34 (18%) patients, including a gonadoblastoma in 7 gonads among 5 patients and an association of dysgerminoma with gonadoblastoma in 1 gonad. All 6 patients who developed gonadal tumor had female genitalia. Postoperative course was uneventful except 1 boy. A seminoma was developed in his soritaly scrotal testis at the age of 16 years. CONCLUSION: The prevalence of gonadal tumor in patients with 45,X/46,XY mosaicism may vary according to the phenotype, and high in patients with female phenotype. Considering the increased risk of gonadal tumors in such patients, early investigation and individual management, including prophylactic gonadectomy, are recommended. In male patients, a close follow-up of the preserved testes is mandatory until adulthood.

Paclitaxel plus ifosfamide and cisplatin in second-line treatment of germ cell tumors: a phase II study.

The aim of this study was to determine efficacy and toxicity of TIP combination (paclitaxel, ifosfamid, cisplatin) as first salvage treatment in patients with relapsed germ cell tumours (GCTs). Excellent results were achieved from TIP combination with a dose 250 mg/m(2) of paclitaxel [5]. Our hypothesis was that comparable efficacy with less toxicity could be achieved even with a lower dose of 175 mg/m(2) paclitaxel in TIP. In 17 consecutive patients with failed standard 1st line treatment, we used four to six courses of paclitaxel 175 mg/m(2) on day 1 and ifosfamide 1,200 mg/m(2) plus cisplatin 20 mg/m(2), both on day 1 through 5, every 3 weeks. Eleven patients achieved favorable response (65%; 95% confidence interval, 42 to 87%) with 7 complete responses (41%). Estimated 2-year disease free survival is 47% (95% CI, 23-71%). Treatment combination was well tolerated and myelosupression was major toxicity. Granulocytopenia Gr3-4 was observed in 8% and febrile neutropenia in 7% of the courses. No case of severe neurotoxicity or treatment-related death was observed. In our study, TIP combination had good toxicity profile. The results however, did not show expected treatment efficacy and we raise the idea of paclitaxel dosage relevance in TIP.

Activin-ßC modulates gonadal, but not adrenal tumorigenesis in the inhibin deficient mice.

Activins and inhibins are involved in the regulation of several biological processes, including reproduction, development and fertility. Deregulation of the inhibin/activin signaling pathway has been implicated in the progression of reproductive and adrenal cancers. Deletion of the inhibin α-subunit results in up-regulation of the circulating levels of activins and this leads to the development of sex-cord stromal tumors followed by a cancer associated-cachexia in mice. When gonadectomy is performed, development of adrenocortical carcinomas is observed. We previously showed that overexpression of activin-ßC modulates the development of sex-cord stromal tumors and reduces cancer-cachexia in the inhibin-deficient mice by antagonizing the activin signaling pathway. The adrenal cortex and gonads share in common a large subset of genes, consistent with their common embryonic lineage. Additionally, it has been shown that adrenocortical carcinomas adopt an altered cellular identity resembling the ovary. Therefore, a study to assess the impact of overexpression of activin-ßC on the onset of adrenocortical carcinoma in gonadectomized inhibin-deficient mice was warranted. Within the current study we evaluated markers of apoptosis, proliferation, tumor burden, survival analysis and serum levels of activin-A in gonadectomized mice versus sham operated controls. Results showed that overexpression of activin-ßC modulated the development of reproductive tumors but had no effect on adrenal tumorigenesis. Our data reinforces the importance of activin-ßC in reproductive biology and suggest that activin-ßC is a tumor modulator with gonadal specificity.

The steroid profile of a virilizing ovarian tumor.

A case report of a 25-year-old female with a sex cord stromal virilizing ovarian tumor is presented. The pathway of ovarian steroid secretion in this tumor is elucidated with the dominant elements being pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, androstenedione, and testosterone. The tumor primarily made testosterone (T) with lesser elevations of androstenedione (A), dehydroepiandrosterone (DHEA), and dihydrotestosterone (DHT). Expert pathologic opinions differed whether this neoplasm was a Sertoli-Leydig tumor or a virilizing granulosa tumor; therefore, it was probably a gynandroblastoma. A unilateral salpingo-oophorectomy was performed and the patient promptly resumed normal ovarian function with ovulation.

Detection of trisomy 12 on ovarian sex cord stromal tumors by fluorescence in situ hybridization.

Trisomy of chromosome 12 has been frequently described in various neoplasms, particularly in tumors of the female genitourinary tract. Fluorescence in situ hybridization with a centromeric repetitive DNA probe, specific for chromosome 12, was done to detect such cytogenic changes on frozen-tissue sections from 10 cases of ovarian sex cord stromal tumors. The case series was composed by granulosa cell tumors (four cases), fibromas (four cases), thecoma (one case), and Sertoli-Leydig cell tumor (one case). In granulosa cell tumors, the range of trisomy was 12 to 32% and in fibromas 8 to 22%, whereas in the single case of thecoma trisomy was present in 8% and in the Sertoli-Leydig cell tumor in 4% of the nuclei examined. These results represent an additional series of cases of trisomy 12 in ovarian neoplasms, namely, in ovarian sex cord stromal tumors.

Hormone studies in a gynandroblastoma.

Plasma gonadotropin, testosterone, androstenedione, and estradiol levels were determined before and after removal of a 37-pound gynandroblastoma from an 18-year-old virilized, mentally retarded female. Testosterone and androstenedione levels preoperatively were in the normal female range and fell dramatically after castration. Histologic examination showed active atypical granulosa and Sertoli elements. The hormonal data obtained do not account for the marked virilization observed.

Gynandroblastoma of the ovary.

Gynandroblastoma is an extremely rare primary tumour of the ovary showing morphological evidence of both male and female differentiation. We describe the light and ultrastructural features of this tumour and review the present knowledge about its nature, function and behaviour.

Gynandroblastoma in pregnancy: case report and review of literature.

Gynandroblastoma is an extremely rare tumor, composed of sex cord and stromal cells of both ovarian (granulosa-theca) and testicular (Sertoli-Leydig) types. We believe that its occurrence during pregnancy has not been previously reported. The patient was a 32-year-old woman who during her pregnancy was noted to have a progressively enlarging, unilocular left ovarian cyst. Beginning at 18 weeks gestation, the fetus required multiple platelet transfusions for severe alloimmune thrombocytopenia. A viable baby girl was delivered by cesarean section at 39 weeks gestation. At that time, an ovarian cystectomy also was performed. When the histology of the tissue subsequently became known, a left salpingo-oophorectomy was performed for gynandroblastoma. One year later, at the time of laparoscopic sterilization, the examination of the pelvis was normal.

Histogenetic consideration of ovarian sex cord-stromal tumors analyzed by expression pattern of cytokeratins, vimentin, and laminin. Correlation studies with human gonads.

A total of 30 sex cord-stromal tumors including 9 adult type and 5 juvenile type granulosa cell tumors (GCTs), 4 Sertoli-Leydig cell tumors (SLTs), 1 gynandroblastoma, 5 thecomas, 2 fibromas and 3 sclerosing stromal tumors were immunohistochemically evaluated by means of cytokeratins of different molecular weight, vimentin and laminin with regard to the histogenesis of these tumors and to the embryogenesis of the sex cord and stroma of developing gonads. For comparison, 7 embryonic gonads, 9 fetal and 9 adult ovaries, 14 fetal and 5 postnatal testes, and 1 gonadoblastoma were also examined. The coelomic epithelium of all gonads were positive for both cytokeratins (CAM 5.2 and AE1) and vimentin. In fetal ovaries, the granulosa cells of primordial follicles express low molecular weight cytokeratins only and those cells of more maturing follicles did not express any cytokeratin or vimentin. In adult ovaries, the granulosa cells of primordial follicles coexpressed low molecular weight cytokeratins and vimentin, but those cells of more maturing follicles expressed vimentin only. In fetal testes before 20 weeks gestational age, the Sertoli and Leydig cells did not express any cytokeratins and vimentin. After that time, both cells expressed vimentin only throughout life. The rete ovarii and rete testis from fetal to adult life coexpressed both low molecular weight cytokeratins and vimentin. The rete ovarii in all ages and rete testis in prenatal and childhood ages were surrounded by the laminin-positive basement membrane, however, the rete testis in adult were not. In neoplasia, the GCTs, thecomas, fibromas, and sclerosing stromal tumors expressed vimentin only.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation, with emphasis on the malignant Triton tumor.

Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation can be divided into three groups. Group I consists of tumors with only sarcomatous differentiation. Included in this group are malignant mesenchymoma, dedifferentiated chondrosarcoma, and the dedifferentiated retroperitoneal liposarcoma. Epithelial or Sertoli-Leydig cell elements represent the second component of tumors in group II. The best known tumor in this group is the malignant mullerian mixed tumor, but other well described tumors with rhabdomyosarcomatous differentiation are the carcinosarcoma, mullerian adenosarcoma, Sertoli-Leydig cell tumor, mammary cystosarcoma, and blastomas. Most of the tumors in groups I and II are derived from mesenchymal tissue. A neuroectodermal origin is shared by all tumors in group III. This includes the medulloblastoma, retinoblastoma and, most frequently, the malignant Triton tumor. The tumors in all three groups are clinically malignant to a varying degree.

Ectopic ACTH syndrome due to bilateral ovarian androblastoma with double, gynandroblastic differentiation in one ovary.

A case of fulminant Cushing's syndrome due to an ectopic ACTH secretion in a patient with bilateral ovarian sex-cord stromal tumour is reported. Surgical resection of the ovaries as well as the inhibitors of steroid synthesis and cytostatics caused only transient improvement because the widespread neoplastic dissemination progressed very quickly.

Structural study of a possible neoplasia detected in Mytilus galloprovincialis collected from the Ria of Vigo (NW Spain).

Several specimens of Mytilus galloprovincialis, collected in the Ria of Vigo over a non-consecutive 2 yr period (1993 to 1994 and 1996 to 1997), presented a possible gonadal neoplasm, entailing morphologically abnormal germinal cells distributed throughout the follicle and invading the adjacent storage tissue. In some cases, affected cells were noted in gonoducts and in haemic sinusoids. Prevalence of this anomaly in the samples was 6%, and all affected individuals were found between April and June. During the rest of the year, individuals presented normal gonadal tissue.

Gynandroblastoma of the ovary. A case report.

An ovarian gynandroblastoma was found in a 59-year-old woman. The tumor consisting of mixed Sertoli-Leydig cells and granulosa-theca cells demonstrated no malignant features. Bisexual cells in gynandroblastoma derived from a common gonadal mesenchyme precursor or indifferent cell. The excision of appendages with tumor or hysterectomy was sufficient.

Origin of unreactive hyaline bodies from erythrocytes in genital tumors.

Two genital tumors, one a lipid virilizing cell tumor of the ovary, the other an ovarian Sertoli-Leydig cell tumor with retiform pattern, were studied focusing attention on the numerous eosinophilic hyaline bodies that were present both in the extracellular spaces and within the cytoplasm of the proliferating cells. Histochemistry and immunohistochemistry revealed that they were PAS positive and alpha-1-fetoprotein negative. Under electronmicroscopy these hyaline bodies appeared to correspond to variably altered red blood cells: red blood cell ghosts, erythrocytes with Heinz bodies, phagocytosed erythrocytes. Our findings could explain the origin of at least a part of the hyaline bodies found in similar or in other unrelated pathologies.