Clinical outcomes of local and metastatic testicular sex cord-stromal tumors.

PURPOSE: We evaluated pathological variables of testicular sex cord-stromal tumors, management options and clinical outcomes. MATERIALS AND METHODS: We retrospectively reviewed the records of 48 patients with testicular sex cord-stromal tumors treated at Memorial Sloan-Kettering Cancer Center between 1997 and 2012. Clinical outcomes were compared based on treatment and previously described pathological factors associated with metastatic potential. RESULTS: Of the 48 patients 37 underwent surveillance without retroperitoneal lymph node dissection, including 34 with no high risk feature and 3 with 1. Median followup was 14.5 months (IQR 6.9-32.5). No patient experienced recurrence. Retroperitoneal lymph node dissection was performed in 11 patients, including 6 with clinical stage I disease and 2 or more high risk features who underwent early dissection, 2 with clinical stage IIa disease at diagnosis who underwent early dissection and 3 with clinical stage I disease and 2 or more high risk features who were observed elsewhere but referred to our institution due to retroperitoneal disease. Six patients with clinical stage I disease underwent early dissection, 4 had no evidence of disease at a median followup of 6.6 years and 2 experienced recurrence and died of disease. Neither of the 2 patients with IIa disease at diagnosis experienced relapse. All 3 patients with delayed dissection experienced relapse and 1 died of disease. CONCLUSIONS: Patients with testicular sex cord-stromal tumors and 1 or no high risk feature can be safely observed without retroperitoneal lymph node dissection but longer followup is needed. Given the lack of effective alternative treatments, early retroperitoneal lymph node dissection may be beneficial in those with 2 or more high risk features, or clinical stage IIa disease.

Lymph-node metastasis in stage I and II sex cord stromal and malignant germ cell tumours of the ovary: a systematic review.

OBJECTIVES: The aim of this systematic review is to determine the incidence of lymph-node metastasis in clinical stage I and II sex cord stromal tumours and germ cell tumours of the ovary. METHODS: Relevant articles were identified from MEDLINE and EMBASE and supplemented with citations from the reference lists of the primary studies. Eligibility was determined by two authors. Included studies were prospective or retrospective cohort and cross-sectional studies analysing at least ten patients with clinical early-stage non-epithelial ovarian cancer who underwent lymphadenectomy or lymph-node sampling as part of a staging laparotomy. RESULTS: For sex cord stromal tumours, five articles including 578 patients were analysed and lymph-node metastasis was not detected in the 86 patients who underwent lymph-node removal. The median number of removed lymph nodes was 13 (range 9-29). For malignant germ cell tumours, three articles were eligible including 2436 patients of whom 946 patients underwent lymph-node resection. The mean number of removed nodes was 10 (range 2-14) with a mean incidence of lymph-node metastasis of 10.9% (range 10.5-11.8%). CONCLUSIONS: The incidence of lymph-node metastasis in patients with clinical stage I and II sex cord stromal tumours is low, whereas the incidence in patients with clinical stage I-II germ cell tumours is considerable, although limited data are available.

Increased Rab25 expression is not correlated with peritoneal metastasis of ovarian cancers.

Ovarian cancer is the leading cause of death in gynecological cancer. Studies suggested Rab25 is involved in the pathogenesis of ovarian cancers. We here investigated the expression of Rab25 is in all ovarian cancers and whether the expression of Rab25 is associated with peritoneal metastasis. Fifty-nine ovarian cancer patients were included and the levels of Rab25 measured by immunohistochemistry. Our data showed Rab25 was highly expressed in all subtypes of epithelial ovarian cancers, and two subtypes of germ cell tumors, but not in sex cord stromal tumors. Furthermore, the Rab25 expression was not correlated with peritoneal metastasis of ovarian cancer.

Metastatic adult granulosa cell tumor mimicking a benign pancreatic cyst.

We report an unusual case of metastatic adult granulosa cell tumor in the head of pancreas mimicking a benign pancreatic cyst in a 43-year-old female. Clinically, it was considered a benign cyst of the pancreas based on its appearance by imaging and that repeated fine-needle aspiration and cytologic examination of cystic fluid failed to identify malignant cells. The cyst in her pancreas grew slowly during the 15 months of close follow-up. Subsequent drainage and open biopsy of the cyst wall established the diagnosis of metastatic adult granulosa cell tumor that was confirmed in pancreaticoduodenectomy specimen. Immunohistochemical study and clinical history were critical to make the correct diagnosis and to differentiate this tumor from other more commonly encountered cystic neoplasms of the pancreas.

Supraclavicular metastases from a sex cord stromal tumor of the ovary.

Metastases to the supraclavicular fossa usually originate from head and neck or infraclavicular tumors. Ovarian primaries of supraclavicular metastases are very rare. Sex cord stromal tumors of the ovary account for 5-8% of all ovarian malignancies and there have been only a few case reports on distant metastases from these tumors. A 46-year-old woman presented to us with a left supraclavicular mass. She had had a sex cord stromal tumor in the right ovary four years before. Comprehensive clinical investigation and fine-needle aspiration cytology were performed. The lesion had the characteristics of a sex cord stromal tumor. To our knowledge, this is the first report of such a case in the English literature. We discuss its pathological and clinical features in the light of the current knowledge.

Bilateral liver metastases from testicular sex cord-stromal tumour.

A 28-year-old man previously diagnosed and treated for testicular sex cord-stromal tumour (TSCST) presented with symptoms of fever, night sweats and fatigue. Following initial investigations for an infectious aetiology, imaging studies detected two large liver lesions. Histopathological assessment of the tumours revealed that they were metastases from the TSCST for which the patient had radical inguinal orchiectomy and retroperitoneal lymph node dissection 5 years prior. The curative-intent management of the bilobar liver metastases necessitated staged resection due to the chemoresistant and radioresistant properties of TSCST. The size of the lesions was such that procedures to induce rapid liver hypertrophy were required between surgeries. Both liver metastases were successfully removed following this approach. The patient remains recurrence-free 1 year after surgery and has maintained predisease levels of performance. Nevertheless, he continues to be followed for routine CT scans at regular intervals.

Co-occurrence of a metastatic mammary liposarcoma and an ovarian sex-cord stromal tumor in a dog.

Sarcoma arising in the mammary gland is a rare tumor in dogs, and primary liposarcoma with metastatic behavior has never been previously reported among canine mammary tumors. A 14-year old female poodle had a mammary mass diagnosed as pleomorphic liposarcoma. Two years following surgical removal, the tumor recurred in the mammary gland with lymph node metastases. In addition, a sex-cord stromal tumor was identified in the ovary. Immunohistochemistry was performed on both tumors that were positive for oestrogen and progesterone receptors. Moreover, the ovarian tumor was positive for calretinin. This is the first report to the authors' knowledge, of the co-occurrence of a pleomorphic liposarcoma of the mammary gland and an ovarian sex-cord stromal (gonadostromal) tumor in the dog.

Testicular sex cord-stromal tumours: the Edinburgh experience 1988-2002, and a review of the literature.

AIMS: Sex cord-stromal tumours of the testis are uncommon tumours, accounting for around 5% of testicular neoplasms. Treatment is primarily surgical, with no adjuvant therapy of proven benefit. We present a single-centre experience over a period of 15 years. MATERIALS AND METHODS: From 1988 to 2002, 18 patients with a diagnosis of sex cord-stromal tumour were referred to our centre. A retrospective analysis of their case notes was made and a pathological review undertaken. RESULTS: Sixteen were Leydig-cell tumours and two were Sertoli cell. For the Leydig-cell tumours, the median age at presentation was 42 years, 50% presented with a testicular mass and 31% with gynaecomastia. Two patients followed a malignant course: one revealing disease dissemination at initial staging, and a second 12 months after potentially curative orchidectomy. Salvage retroperitoneal lymphadenectomy in the latter patient proved unsuccessful. Clinical outcome correlated strongly with the presence of adverse pathological features described previously in the literature. After a median follow-up of 46 months, two patients have developed progressive disease, and two patients have died, one of metastatic Leydig-cell tumour. No patient defined as being of low malignant potential on pathological examination has relapsed outside our review period of 2 years. CONCLUSION: We confirm the overall excellent prognosis for most of the patients with sex cord-stromal tumours of the testis. Compared with most previous reports, pathological features seem to predict with reasonable accuracy the risk of malignant behaviour, and can adequately inform the subsequent review policy.

p53 expression, DNA content and cell proliferation in primary and synchronous metastatic lesions from ovarian surface epithelial-stromal tumours.

The aim of this study was to investigate biological heterogeneity between primary and metastatic ovarian cancer lesions from individual patients as a means of elucidating steps in clinical progression. Cancer tissue from 61 untreated patients with ovarian surface epithelial-stromal tumours was examined. p53 expression detected immunocytochemically by the PAb1801 antibody, DNA content evaluated by flow cytometry, and cell proliferation evaluated as the [3H]thymidine labelling index were investigated in primary tumours and corresponding synchronous metastases. The frequency of p53 positivity was similar in primary (62%) and metastatic (66%) sites, with an agreement between the two lesions from the same patient in 97% of the cases. Similarly, aneuploidy frequency (80%) and DNA indices were superimposable in primary and metastatic lesions from the same patient, with a 94% agreement. The frequency of aneuploidy was higher in p53-positive than in p53-negative lesions. An overall poor agreement (rs = 0.44) was observed for proliferative activity of primary and metastatic lesions, due to a heterogeneous profile in omental with respect to primary tumours, which was mainly evident in p53-positive cancers. Conversely, cell proliferation of peritoneal, abdominal and pelvic lesions was qualitatively similar to that of the primary tumour in 88% of patients.

Non-Leydig sex-cord tumors of the testis. The place of immunohistochemistry in diagnosis and prognosis. A study of twenty cases.

In 20 sex-cord tumors of the testes, we investigated immunohistochemistry as a possible method for histopathological diagnosis and evaluation of prognosis. We examined the following molecules: inhibin, CD99, cytokeratin, vimentin, MIB-1, estrogen receptors and progesterone receptors. These tumors of the testes comprised 18 Sertoli cell tumors (ScT) and two undifferentiated sex-cord tumors (USCT). Four tumors have been considered as malignant, because of metastatic spread. Inhibin was expressed by the tumor cells in 80% of sex cord tumors, without any correlation to the degree of differentiation and only in 25% of the malignant cases. Inhibin is a specific marker for sex-cord tumors of the testis and is particularly useful for the diagnosis of USCT. CD99, vimentin, keratin, progesterone and estrogen receptors were expressed in, respectively, 60%, 75%, 35%, 65% and 20% of cases; 95% expressed one of the three following markers: inhibin, CD99 or vimentin. Proliferation index MIB-1 was equal to or higher than 30% in the four malignant cases versus less than 20% in other cases. Lack of inhibin expression and a proliferation index (MIB-1) greater than 30% should be considered as a criterion in favor of malignancy.

Malignant gonadal stromal tumor.

A case of malignant gonadal stromal tumor is reported, and the 24 cases reported in the English and Japanese literature are reviewed. A thirty-four-year-old male visited our hospital with a painless tumor in the left scrotum. Left high orchiectomy was performed under a diagnosis of testicular tumor, and histologic examination of the resected specimen demonstrated that it was a malignant gonadal stromal tumor. There has been no evidence of disease for forty-one months following surgery. Of the 15 cases reported in the English literature, retroperitoneal lymph node dissection was performed in 3 cases, and metastasis was present in the resected lymph nodes in 2 of the cases. These 3 patients survived with no evidence of disease for follow-up periods ranging between six months and five years. However, lymph node metastasis was observed in 5 of 6 patients who underwent orchiectomy alone or in combination with radiation to the retroperitoneal lymph nodes. The 3 patients described in the Japanese literature who had received high orchiectomy and retroperitoneal lymph node dissection survived with no evidence of disease for follow-up periods ranging from eighteen months to forty-one months following surgery. These findings indicate that retroperitoneal lymph node dissection is useful as a treatment for malignant gonadal stromal tumor. However, the prognosis for patients with advanced disease is very poor, because neither chemotherapy nor radiotherapy is effective. Corroborative study of many patients is necessary to understand the pathophysiology of malignant gonadal stromal tumor and to develop useful treatments.

Active chemotherapy for metastatic stromal cell tumor of the testis.

Metastatic stromal cell tumors of the testis are largely refractory to chemotherapy. We report a case of a young man with widely metastatic testicular stromal cell tumor who achieved complete clinical remission following chemotherapy with etoposide, ifosfamide, cisplatin, and bleomycin.

Steroid cell tumors of the ovary: clinical, ultrasonic, and MRI diagnosis--a case report.

Steroid cell tumors of the ovary are rare sex-cord neoplasms which account for less than 0.1% of all ovarian tumors. They have been divided into two subtypes according to their cell of origin as follows: stromal luteoma, and Leydig cell tumors, and a third subtype with lineage unknown is a steroid cell tumor, not otherwise specified (NOS). The clinical presentation may take many forms, including pain, abdominal distention and bloating, but perhaps the most interesting and noticeable presentations are those related to the hormonal activity and virilizing properties of the tumor. No radiological features of the steroid cell tumor, NOS have been presented in the literature. This report presents the MRI and ultrasonographic findings of a patient having steroid cell tumor, NOS, of the right ovary with metastasis to the uterus.

Rarely occurring spontaneous metastasizing testicular tumors in rats. Histopathologic and ultrastructural features.

Testicular tumors are not uncommon in aging rats. However, metastasis from these neoplasms to several distant visceral organs has not been reported. Testicular tumors were observed in a total of 18 (1.34%) Sprague-Dawley rats out of 1340 males examined. Out of these 18 neoplasms, interstitial tumors were observed in 12 rats, of which 11 were benign and one malignant. Spermatic seminomas were observed in two (0.15%) cases (one benign and one malignant). Both rats with malignant testicular neoplasms were sacrified in extremis. Remaining four tumors were classified as mesotheliomas. Detailed gross, histopathologic and electron microscopic features of primary testicular neoplasms with metastases to several distant visceral organs are described and discussed.

Metastatic ovarian sex-cord stromal tumor with annular tubules in a patient without Peutz-Jeghers syndrome.

Sex-cord stromal tumors (SCSTs) with annular tubules (SCTATs) are a small class of ovarian lesions that possess histologic features of both Sertoli and granulosa cells. Approximately one-third of patients with SCTAT also have Peutz-Jaghers syndreome, which makes these cases especially rare. Patients with non-PJS-associated SCTAT make up the remaining two-thirds; 20% of these cases have a metastatic presentation. Metastasis of these tumors to the head and neck region has only been reported in a few instances. In this article we report a case of a 25-year-old woman who presented with "a lump in her throat" and was ultimately diagnosed with SCTAT. We also discuss the current protocols in the diagnosis and treatment of this entity.

Clinical characteristics and outcomes of uterine tumors resembling ovarian sex-cord tumors (UTROSCT): a systematic review of literature.

Uterine tumor resembling ovarian sex-cord tumors (UTROSCT) is an extremely rare type of uterine tumor, and its clinical characteristics are not fully understood. A systematic literature search was conducted in PubMed and MEDLINE using the keywords, "uterine tumors resembling ovarian sex cord tumors", limited to case reports. Clinico-pathological characteristics and survival data were abstracted and evaluated for the analysis. Among 43 cases reporting UTROSCT, Type I (endometrial stromal tumors with sex cord-like elements, ESTSCLE) and Type II (classic UTROSCT) were reported in 5 (11.6%) and 17 (39.5%), respectively, and nearly half of reported UTROSCT did not subcategorize the histology pattern into Type I or II (unspecified, n=21, 48.8%). Mean age was 52.2. The two most common symptoms were postmenopausal vaginal bleeding (44.2%) and abnormal menstruation (39.5%). The majority underwent total hysterectomy with adnexectomy (65.1%) followed by hysterectomy alone (18.6%) and tumor resection alone (14.0%). Mean tumor size was 6.2cm, and extra-uterine spread was seen in 7.0%. By immunohistochemistry, calretinin expression was significantly correlated with CAM5.2, inhibin, and progesterone receptor expression (all, p<0.05). In survival analysis, disease-free survival (DFS) rates for all 43 cases at 1, 2, and 5 years for all cases were 97.0%, 92.7%, and 69.7%, respectively. Among recurrent cases, median time to recur was 24 months (range 9-48). Decreased DFS was significantly associated with pelvic pain (2-year rate, 81.8% versus 94.7%, p=0.006), histology subcategory (Type I versus II, 23.8% versus 100%, p=0.006), tumor size ≥10cm (75.0% versus 100%, p=0.046), cervical/extra-uterine metastasis (46.7% versus 100%, p=0.024), and lymphovascular space involvement (50% versus 100%, p=0.002). Treatment patterns were not statistically associated with DFS (hysterectomy, p=0.28; and adnexectomy, p=0.38). When histology patterns were examined, Type II disease was associated with less aggressive tumor behavior when compared to Type I disease: extra-uterine spread (Type I versus II, 40% versus 5.9%, p=0.007) and lymphovascular space invasion (50% versus 6.7%, p=0.012). Among 17 cases of Type II disease, disease recurrence was reported in 1 (5.9%) case at 3 years after the initial treatment. In conclusion, our study showed that UTROSCT was often not subcategorized. Because classic UTROSCT has a distinct clinical outcome and characteristic histological patterns when compared to ESTSCLE, distinguishing UTROSCT from ESTSCLE is an integral component of the diagnosis. While classic UTROSCT typically has a favorable prognosis, it has been known to develop a late recurrence. If risk factors for recurrence are absent, both hysterectomy and mass resection alone are possible options for management.

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

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.

Failure of gonadotropin releasing hormone therapy in patients with metastatic ovarian sex cord stromal tumors.

Ovarian sex cord stromal tumors are usually indolent neoplasms that are generally confined to one or both ovaries at the time of diagnosis. The overall prognosis for these women is good though advanced or recurrent tumors occasionally occur. In such instances, if the tumor is localized, surgical or radiation therapy often provides good results; however, diffuse intra-abdominal disease is uncommon and difficult to treat effectively. Recently, synthetic gonadotropin releasing hormone (GnRH) analogue therapy has been advocated as an effective therapy with low toxicity. We report on 2 women whose advanced recurrent ovarian cord stromal tumors failed to respond to repetitive surgical, chemotherapeutic, and GnRH therapies. In these 2 cases, GnRH therapy was not successful in controlling diffuse spread of two separate gonadal stromal tumors. Systemic toxicity was minimal.

Response of metastasized sex cord gonadal stromal tumor of the testis to cisplatin-based chemotherapy.

A 34-year-old man underwent left hemicastration for malignant unclassified sex cord gonadal stromal tumor. At 6 months pulmonary metastases developed and the patient received 3 courses of chemotherapy consisting of cisplatin, bleomycin and etoposide. A residual focus in the right lung was excised and proved to be viable tumor. He then received 2 adjuvant courses of cisplatin, etoposide and ifosfamide. Six months later he was without evidence of disease. A review of the literature revealed 21 previous cases of malignant unclassified sex cord gonadal stromal tumor. Although chemotherapy usually fails in treating Leydig cell tumors our case corroborates 6 previous reports of favorable response to cisplatin-based chemotherapy. This finding suggests that different subtypes of sex cord gonadal stromal tumor respond differently to chemotherapy.