Malignant Sex Cord-stromal Tumors Research Articles

Prevalence of lymph node metastasis and prognostic significance of lymphadenectomy in apparent early-stage malignant ovarian sex cord-stromal tumors

ObjectiveThe aim of this retrospective population-based study was to investigate the prevalence of lymph node metastasis in patients with apparent early stage malignant sex cord-stromal tumors (SCSTs) and the effect of regional lymph node sampling/lymphadenectomy (LND) on their survival. MethodsA cohort of patients diagnosed with malignant SCSTs between 1988 and 2012 was drawn from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Overall and Cancer Specific Survival, stratified by performance of LND, were calculated following generation of Kaplan-Meier curves. Comparisons were made using the log-rank and Breslow tests. A multivariate Cox proportional analysis was performed to determine the effect of LND on overall mortality. ResultsA total of 1156 patients with SCST met the inclusion criteria; 1000 (86.5%) and 156 (13.5%) patients had apparent stage I and II disease, respectively. LND was performed in 572 (49.5%) patients. Lymph node metastases were pathologically confirmed in 19 patients (3.3%). Five-year cancer specific survival (CSS) was similar, 92.7% and 94.7%, for patients who did or did not undergo LND, respectively. According to multivariate analysis overall mortality did not differ between the two groups after controlling for age, histology and apparent stage. ConclusionsRegional lymphatic mode metastasis in patients with apparent early stage SCSTs is uncommon and lymphadenectomy did not confer a survival benefit in this cohort.

Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Ovarian Cancer focuses on the less common ovarian histopathologies (LCOHs), because new algorithms were added for LCOHs and current algorithms were revised for the 2016 update. The new LCOHs algorithms include clear cell carcinomas, mucinous carcinomas, and grade 1 (low-grade) serous carcinomas/endometrioid epithelial carcinomas. The LCOHs also include carcinosarcomas (malignant mixed Müllerian tumors of the ovary), borderline epithelial tumors (also known as low malignant potential tumors), malignant sex cord-stromal tumors, and malignant germ cell tumors.

Abridged republication of FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum

Over the past quarter of a century, several scientific developments have challenged traditional concepts in ovarian cancer. First, it was recognized that ovarian cancer is not a homogeneous disease, but rather a group of diseases – each with different morphology and biological behavior. Approximately 90% of ovarian cancers are carcinomas (malignant epithelial tumors), and based on histopathology, immunohistochemistry, and molecular genetic analysis, at least five main types are currently distinguished: high-grade serous carcinoma (HGSC [70%]); endometrioid carcinoma (EC [10%]); clearcell carcinoma (CCC [10%]); mucinous carcinoma (MC [3%]); and low-grade serous carcinoma (LGSC [<5%]) [1,2]. These tumor types (which account for 98% of ovarian carcinomas) can be reproducibly diagnosed by light microscopy and are inherently different diseases, as indicated by differences in epidemiologic and genetic risk factors; precursor lesions; patterns of spread; and molecular events during oncogenesis, response to chemotherapy, and prognosis [2,3]. Much less common are malignant germ cell tumors and potentially malignant sex cord-stromal tumors. The biomarker expression profile within a given histotype is consistent across stages. Ovarian cancers differ primarily based on histologic type. In the era of personalized cancer medicine, reproducible histopathologic diagnosis of tumor cell type is a sine qua non for successful treatment. Different tumor histotypes respond differently to chemotherapy. The FIGO Committee on Gynecologic Oncology unanimously agreed that histologic type should be designated at staging. The finding of high-grade serous tubal intraepithelial carcinoma (STIC), in patients with BRCA mutation undergoing riskreducing salpingo-oophorectomy (RRSO) [4] also influenced the new FIGO staging. Although STIC is capable of metastasizing, and therefore, cannot be considered a true carcinoma in situ, compelling evidence for a tubal origin of BRCA-positive HGSC has accumulated over the past decade [5,6]. The relative proportion of HGSCs of ovarian and tubal derivation is unknown, mainly because tumor growth in advanced-stage cancers conceals the primary site. Even in cases involving BRCA mutation, evidence of a tubal origin of HGSCs is incomplete and a multicentric origin of these tumors cannot be excluded. The process of the proposed changes to the staging of ovarian, fallopian tube, and primary peritoneal cancer started three years ago under the leadership of the Chair of the FIGO Committee on Gynecologic Oncology, Professor Lynette Denny. The proposal was sent to all relevant gynecologic oncology organizations and societies worldwide. The new staging was reached by consensus of those participating in the FIGO meeting held in Rome, Italy, on October 7, 2012 and approved two weeks later. The following is the consensus agreement that resulted from these efforts and represents new criteria for staging of these gynecologic cancers.

FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum: abridged republication.

Over the past quarter of a century, several scientific developments have challenged traditional concepts in ovarian cancer. First, it was recognized that ovarian cancer is not a homogeneous disease, but rather a group of diseases-each with different morphology and biological behavior. Approximately 90% of ovarian cancers are carcinomas (malignant epithelial tumors) and, based on histopathology, immunohistochemistry, and molecular genetic analysis, at least five main types are currently distinguished: high-grade serous carcinoma (HGSC, 70%); endometrioid carcinoma (EC,10%); clear-cell carcinoma (CCC,10%); mucinous carcinoma (MC, 3%); and low-grade serous carcinoma (LGSC, <5%) [1,2]. These tumor types (which account for 98% of ovarian carcinomas) can be reproducibly diagnosed by light microscopy and are inherently different diseases, as indicated by differences in epidemiologic and genetic risk factors; precursor lesions; patterns of spread; and molecular events during oncogenesis, response to chemotherapy, and prognosis [2,3]. Much less common are malignant germ cell tumors and potentially malignant sex cord-stromal tumors. The biomarker expression profile within a given histotype is consistent across stages. Ovarian cancers differ primarily based on histologic type. In the era of personalized cancer medicine, reproducible histopathologic diagnosis of tumor cell type is a sine qua non for successful treatment. Different tumor histotypes respond differently to chemotherapy. The International Federation of Gynecology and Obstetrics (FIGO) Committee on Gynecologic Oncology unanimously agreed that histologic type should be designated at staging. The finding of high-grade serous tubal intraepithelial carcinoma (STIC), in patients with BRCA mutation undergoing risk-reducing salpingo-oophorectomy (RRSO)[4] also influenced the new FIGO staging. Although STIC is capable of metastasizing and, therefore, cannot be considered a true carcinoma in situ , compelling evidence for a tubal origin of BRCA-positive HGSC has accumulated over the past decade [5,6]. The relative proportion of HGSCs of ovarian and tubal derivation is unknown, mainly because tumor growth in advanced-stage cancers conceals the primary site. Even in cases involving BRCA mutation, evidence of a tubal origin of HGSCs is incomplete and a multicentric origin of these tumors cannot be excluded. The process of the proposed changes to the staging of ovarian, fallopian tube, and primary peritoneal cancer started three years ago under the leadership of the Chair of the FIGO Committee on Gynecologic Oncology, Professor Lynette Denny. The proposal was sent to all relevant gynecologic oncology organizations and societies worldwide. The new staging was reached by consensus of those participating in the FIGO meeting held in Rome, Italy, on October 7, 2012 and approved two weeks later. The following is the consensus agreement that resulted from these efforts and represents new criteria for staging of these gynecologic cancer (Table 1). Table 1 2014 FIGO ovarian, fallopian tube, and peritoneal cancer staging system and corresponding TNM

Proportion of ovarian cancers in overall ovarian masses in Thailand.

The primary objective of this study was to assess the proportion of malignancies in ovarian masses during 1st January 2002, to 31st December 2011 at the Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital. A secondary objective was to evaluate associations with patients' clinical characteristics and ovarian malignancy proportion and subtypes. Retrospective descriptive study analyzed data of ovarian masses larger than 3 centimeters in maximal diameter, from the division of Gynecologic Cyto-Pathology at KCMH. SPSS software version 17 (SPSS, Inc, Chicago, IL, USA) was used. A total number of 6,115 patients were included. Among the total ovarian masses studied, 13.7% were malignant. After the age of sixty, the proportion reached almost 40%. It was also above 20% in women younger than 20 years old. During premenarche period, proportion of ovarian malignancies was 50%. Only 1% of ovarian masses were found to be malignant during the pregnancy and post-partum periods. Parity decreasedthe probability of ovarian malignancy during postmenopausal years. Period of menopause did not have any impact on this probability. During the first two decades of life, germ cell malignancy dominated. As the age increased, the percentage of surface epithelial-stromal malignancy increased with a peak at the fifth decade. In contrast, malignant sex cord-stromal cell tumors occurred at a constant rate in each age group after the thirties. Proportion of ovarian cancers in each age group, menstrual and pregnancy status are similar. However there are differences in the distribution of ovarian subtypes especially for the surface epithelial- stromal category.

Diagnosing seminoma: practicalities and problems

Classical seminoma is the most commonly encountered testicular neoplasm. Most clinically localised seminomas are now managed by surveillance, though adjuvant chemo or radiotherapy can be given. The diagnosis of seminoma can be relatively straightforward, but may present unforseen challenges leading to inappropriate treatment or serious misdiagnosis in a number of ways. 1) Thorough macroscopy. Seminomas require rigorous blocking. This is because tiny amounts of non-seminoma may be missed, leading to potential under-treatment. Inflammatory lesions and granulomatous lesions may also harbour small foci of seminoma and should be treated with suspicion. 2) Unusual histological patterns. Some seminomas show unusual features. They may show frequent syncytiotrophoblastic cells leading to misdiagnosis as choriocarcinoma. A minority show tubular elements or even signet ring change. 3) Mimicks. Solid type yolk sac tumour may mimic seminoma as well as a number of other entities, especially some malignant sex cord stromal tumours. The former should be considered for adjuvant treatment, while the latter may require a prophylactic retroperitoneal lymph node dissection. Spermatocytic seminoma, especially when monomorphic may be mistaken for seminoma. Close morphological inspection allied to to judicious use of immunochemistry and knowledge of clinical details including serology is essential for the accurate diagnosis of seminoma.

English

Sertoli-Leydig cell tumor (SLCT) is a rare (less than 0.5%), primary malignant sex cord stromal tumor of ovary, which may present with or without hormonal manifestations. Literature regarding biological behavior during pregnancy and/or puerperium is sparse. We aim to report an androgen producing SLCT, in a 22 year old post partum (8 months) female, who presented with torsion and no clinical features of virilization. The detailed clinicopathological characteristics are presented with a review of relevant literature. SertoliLeydig cell tumor, though rare, should be kept as a differential diagnosis in the evaluation of unilateral adnexal mass with features of hyperandrogenemia. To the best of our knowledge, this is possibly the first case of SLCT presenting with torsion in the absence of virilization; inspite of biochemical evidence of androgen excess.

Non Peutz-Jegher syndrome associated malignant sex cord stromal tumor with annular tubules

Sex cord stromal tumor with annular tubules (SCTAT) is a distinctive, rare subtype of sex cord stromal tumor of the ovary, predominant component of which has morphological features intermediate between that of granulosa cell and sertoli cell. The majority of ovarian SCTAT are benign. So far, malignant behavior in SCTAT has been reported only in sporadic cases. We have presented a case of malignant SCTAT in a 35-year-old lady with no associated Peutz-Jegher (P-J) syndrome.

Granulosa cell tumours of the ovary

Granulosa cell tumours are rare, potentially malignant sex cord stromal tumours of the ovary. They are unique in their presentation and histological features. Many of them are hormone-producing and this property helps them to present early unlike other epithelial ovarian cancers. As a result, most of them will be in an early stage at the time of initial diagnosis. The tumour can manifest in young girls as a juvenile form and conservative management with unilateral salpingo-opherectomy may be an option in them as 95% are unilateral. Surgery is the treatment of choice and initial staging laparatomy a determinant recurrence. Advance stage of the tumour, its size (>5 cm), mitotic figures (>10/hpf), nuclear atypia and absence of call-exner bodies are poor prognostic factors. Such tumours are characterised by late recurrences and this necessitates a prolonged follow-up. Tumour markers such as inhibin and estradiol are useful in follow-up. Chemotherapy, radiotherapy and hormone replacement therapy have very little role in the initial treatment and may be suggested in case of recurrences. With appropriate treatment, a better survival rate can be achieved as against other ovarian malignancies. Methods used for locating, selecting and synthesising data: A search of Medline and Cochrane data base for the period from 1999 to 2010 was carried out to include relevant systematic reviews, meta-analysis, randomised controlled and other clinical and rare case reports. The date of the last search was January 2010.

Reproductive disturbances in multiple neuroendocrine tumor syndromes

In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

Malignant undifferentiated sex cord-stromal testis tumor with brain metastasis: Case report

Metastatic undifferentiated sex cord-stromal testis tumors are uncommon. We would like to present a rare case of undifferentiated sex cord-stromal testis tumor with brain metastasis. After presenting with a painless right testicular mass, the patient underwent right radical orchiectomy and retroperitoneal lymph node dissection. One month later, the patient had no visible evidence of tumor recurrence on the follow-up computed tomography of the chest, abdomen, and pelvis. Three months after the first follow-up, the patient was readmitted for new onset of shortness of breath, and 7th and 12th cranial nerve palsy. Computed tomography of the chest and magnetic resonance imaging of the brain showed evidence of distant metastasis. To our knowledge, undifferentiated sex cord-stromal tumor with brain metastasis has not been reported. As with any new onset neurologic deficits in patients with solid tumors, the presence of brain metastases should be considered.

Does retroperitoneal lymph node dissection have a curative role for patients with sex cord-stromal testicular tumors?: Mosharafa AA, Foster RS, Bihrle R, Koch MO, Ulbright TM, Einhorn LH, Donohue JP, Department of Urology, Indiana University School of Medicine, Indianapolis, IN

Cancer 2003;98:753–7 Background Sex cord-stromal tumors account for < 5% of all adult testicular tumors, and 10% are malignant. Due to the limited reported experience, there is no agreement on the best management, especially in patients who have tumors with malignant pathologic features or who present with metastatic disease. The authors attempt to evaluate the role of retroperitoneal lymph node dissection (RPLND) in the management of patients with these malignant sex cord-stromal tumors. Methods Reviewing the Indiana University testis cancer registry revealed 17 patients who underwent RPLND for sex cord-stromal tumors. Pathology was reviewed for features suggestive of malignancy. The data examined included clinical and pathologic stage, surgical procedure, additional therapy received, and outcome. Results Pathology included Leydig tumors in six patients, Sertoli tumors in four patients, sex cord-stromal tumors in five patients, a granulosa cell tumor in one patient, and a poorly differentiated non-germ cell tumor in one patient. Nine patients had histologic features suggestive of malignancy. Clinical stage at surgery was Stage I in nine patients and Stage IIA-IIIA in eight patients. Patients underwent modified or bilateral RPLND. Nine patients had pathologic Stage I tumors, and the remaining eight patients and had pathologic Stage IIB-IIIA tumors. Follow-up ranged from 8 months to 11 years. Of the eight patients with Stage II-III disease, six patients eventually died of metastatic disease despite additional radiotherapy and/or chemotherapy. Conclusions Sex cord-stromal tumors have a potentially aggressive malignant behavior that is difficult to predict based on clinical and pathologic features. Although the therapeutic role of RPLND in patients with small-volume metastatic retroperitoneal tumors is unclear, RPLND remains an option to be performed immediately after orchiectomy, especially in patients who have tumors with malignant features and/or small-volume metastatic disease.

Does retroperitoneal lymph node dissection have a curative role for patients with sex cord-stromal testicular tumors?

Sex cord-stromal tumors account for < 5% of all adult testicular tumors, and 10% are malignant. Due to the limited reported experience, there is no agreement on the best management, especially in patients who have tumors with malignant pathologic features or who present with metastatic disease. The authors attempt to evaluate the role of retroperitoneal lymph node dissection (RPLND) in the management of patients with these malignant sex cord-stromal tumors. Reviewing the Indiana University testis cancer registry revealed 17 patients who underwent RPLND for sex cord-stromal tumors. Pathology was reviewed for features suggestive of malignancy. The data examined included clinical and pathologic stage, surgical procedure, additional therapy received, and outcome. Pathology included Leydig tumors in six patients, Sertoli tumors in four patients, sex cord-stromal tumors in five patients, a granulosa cell tumor in one patient, and a poorly differentiated non-germ cell tumor in one patient. Nine patients had histologic features suggestive of malignancy. Clinical stage at surgery was Stage I in nine patients and Stage IIA-IIIA in eight patients. Patients underwent modified or bilateral RPLND. Nine patients had pathologic Stage I tumors, and the remaining eight patients and had pathologic Stage IIB-IIIA tumors. Follow-up ranged from 8 months to 11 years. Of the eight patients with Stage II-III disease, six patients eventually died of metastatic disease despite additional radiotherapy and/or chemotherapy. Sex cord-stromal tumors have a potentially aggressive malignant behavior that is difficult to predict based on clinical and pathologic features. Although the therapeutic role of RPLND in patients with small-volume metastatic retroperitoneal tumors is unclear, RPLND remains an option to be performed immediately after orchiectomy, especially in patients who have tumors with malignant features and/or small-volume metastatic disease.

Relaxin-like factor expression in a human ovarian Sertoli-Leydig cell tumor

Relaxin-like factor (RLF), a new member of the insulin-like growth factor family, is a reliable marker for normal Leydig cells in the human postpubertal testis (1). Expression of the RLF gene appears to be developmentally regulated, given that only during puberty is RLF expression up-regulated. We recently demonstrated down-regulation of the human RLF gene in testicular Leydig cell tumors indicating dedifferentiation of the Leydig cells within the tumor (2). Ovarian Sertoli-Leydig cell tumors (SLCTs), histologically typed as androblastomas, are rare, potentially malignant sex-cord stromal tumors exhibiting testicular-like structure and differentiation of various degrees. In the present study, we investigated the expression of RLF, 17alpha-hydroxylase, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), Ki-67, and cytokeratin 18 in a human ovarian SLCT of low differentiation.

Estrogen secretion from a malignant sex cord stromal tumor in a patient with complete androgen insensitivity

We report on a 68-year-old patient with complete androgen insensitivity syndrome (testicular feminization syndrome) in whom an estrogen-secreting malignant sex cord stromal tumor developed in an intraabdominal testis. We believe this to be the first such case to document estrogen secretion by the tumor.(Am J Obstet Gynecol 1997;177:1541-2.)

Malignant Large Cell Calcifying Sertoli Cell Tumor of the Testis

An otherwise normal 48-year-old man had malignant large cell calcifying Sertoli cell tumor of the testis. There were lymph node involvement and albugineal invasion at orchiectomy, and pulmonary metastases developed despite radiotherapy and chemotherapy. Our case and, to our knowledge, the only other reported case of malignant large cell calcifying Sertoli cell tumor had clinical and histopathological features related to aggressiveness, such as unusual patient age, large tumor size, cellular pleomorphism, high mitotic rate, necrosis and aneuploid deoxyribonucleic acid. Such characteristics are not found in benign large cell calcifying Sertoli cell tumors. Associated findings included granular change of the epididymal lining, probably due to compression by the large tumor.

Malignant Sex-cord Stromal Tumor of the Testis: Report of a Case with Special Reference to its Unusual Intracytoplasmic Substructures

A case of malignant sex-cord stromal tumor (gonadal stromal tumor) in the left testis of a 42-year-old man with no sign of hormonal abnormality is reported. Histologically, a large portion of the tumor was composed of solid nests of round cells with a moderate amount of eosinophilic cytoplasm, but some areas contained small spaces somewhat resembling Call-Exner bodies and/or the follicular structures of granulosa cell tumors. In general, however, the tumor cells did not show a clear-cut differentiation into either Sertoli cells or granulosa cells. The tumor, because of its high mitotic rate, lymphatic, venous and capsular invasion, and metastasis to the para-aortic lymph nodes, was considered to be malignant. We simply designated this tumor, therefore, as a malignant sex-cord stromal tumor. An ultrastructural study revealed unique intracytoplasmic bodies composed of multiple stacks of tubular structures which superficially mimicked annulate lamellae. No lipid droplets, Reinke's crystalloids or Charcot-Böttcher filaments were seen. The rarity of the tumor and the presence of unusual substructures prompted us to report the case.