Malignant sertoli cell tumor in a goose (Anser cygnoides domesticus).

This paper describes the pathologic features of a malignant Sertoli cell tumor found in an adult goose (Anser cygnoides domesticus). At necropsy, in addition to one large tumor mass (15 cm in diameter), multiple small tumor masses were observed over the peritoneum and mesenterium in the coelomic cavity. The large tumor mass was composed of sheets, lobules, and small islands of tumor cells, and elongated tumor cells lying perpendicular to fibrous connective tissue were characteristic. Such histopathologic characteristics were common to all the tumors. The tumor cells were immunohistochemically positive for neuron-specific enolase and S-100, and some tumor cells contained fine intracytoplasmic pigments that stained red by oil red O staining. These findings, taken together with the fact that one testis was markedly atrophied and bore no tumor cells and the other testis was not discernible, the present case was diagnosed as unilateral malignant Sertoli cell tumor arising from the unilateral testis. To our knowledge, this is the first report of Sertoli cell tumor in the goose.

Large cell calcifying Sertoli cell tumor: a clinicopathologic study of 1 malignant and 3 benign tumors using histomorphology, immunohistochemistry, ultrastructure, comparative genomic hybridization, and polymerase chain reaction analysis of the PRKAR1A gene.

Four cases of large cell calcifying Sertoli cell tumor, 3 benign and 1 malignant, with no clinical signs of Carney complex or Peutz-Jeghers syndrome are reported with results of histologic, immunohistochemical, ultrastructural, and comparative genomic hybridization studies. Analysis of PRKAR1A gene was performed on 2 cases. The age range of the patients was 19 to 54 years. The patient with a malignant large cell calcifying Sertoli cell tumor died of disease 4 years after surgery. Patients with benign tumors have had an uneventful follow-up for 1 and 3 years. All tumors were well circumscribed, unencapsulated, and composed of solid sheets, irregular cords, tubular structures, and nests in a fibrous and/or myxoid stroma with cellular atypia in the malignant case. All tumors showed diffuse immunoreactivity for inhibin, vimentin, calretinin, and S100 protein. Focal positivity for cytokeratin (AE1/AE3) was noticed in 1 case. Tumors were negative for CAM 5.2, Mic-2, Melan-A laminin, placental alkaline phosphatase, and alpha-fetoprotein. The proliferation index was 5% and 10% for 2 of the benign tumors and 30% for the malignant tumor. Comparative genomic hybridization was performed in 2 cases. There was no evidence of any major chromosomal changes. In one case, no PRKAR1A gene mutation was found. In the other case, a heterozygous shift mutation c.65_84dup was found, despite the absence of other clinical signs of Carney complex or Peutz-Jeghers syndrome. Although the combination of large cell calcifying Sertoli cell tumor and PRKAR1A mutation fulfills the criteria for establishing a diagnosis of Carney complex, the clinical relevance of finding a PRKAR1A gene mutation in a patient without any clinical signs of Carney complex or Peutz-Jeghers syndrome remains to be established.

Malignant large cell calcifying Sertoli cell tumor of the testis.

A 45-year old man presented with a slow-growing, unilateral beige testicular mass, with a diameter of 4 cm. The testosterone, FSH, LH, estradiol and betahCG serum levels were within normal limits, and there were no associated hormonal syndromes. The patient was treated with inguinal orchidectomy. Microscopically, the tumor was composed of nests of cells with large eosinophilic, slightly granular cytoplasm. There was only a mild degree of atypia and no mitotic activity. The tumor extended into the rete testis. There were intratumoral calcifications, and in the vicinity of the tumor, there was intratubular growth. Although this case is histologically similar to the three previously reported cases of clinically benign large cell calcifying Sertoli cell tumor of the testis with rete testis involvement, the current patient developed right sided para-aortic lymph node metastases 18 months after the initial diagnosis.

Large cell calcifying Sertoli cell tumor of the testis: a clinicopathological, immunohistochemical, and ultrastructural study of two cases.

Large cell calcifying Sertoli cell tumor of the testis (LCCSCT) is a rare tumor that is usually benign and multifocal. It may be associated with hereditary endocrine anomalies such as Carney's and Peutz-Jeghers syndromes. Malignant forms are exceptional. Two cases of LCCSCT, one malignant and one benign are described. Both were composed of cords and trabeculae of large polygonal cells embedded in a myxoid and fibrous stroma with areas of calcification. The malignant tumor showed nuclear atypia, necrosis, and abundant mitoses. The cells were positive for vimentin and S-100 protein, and the intercellular space for laminin and collagen type IV. By electron microscopy, nucleolonemas and multilayered basal lamina were seen. The benign tumor was positive for vimentin and S-100 protein, and ultrastructurally showed less basal lamina.

Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature.

We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature. All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophilic cells, with focal calcifications, as well as a substantial neutrophilic infiltrate in 11 of them. Analysis of our cases and those in the literature showed that the malignant tumors were unilateral and solitary and occurred at a mean age of 39 years (range 28-51 years), whereas the benign neoplasms were bilateral and multifocal in 28% of cases and occurred at a mean age of 17 years (range 2-38 years). Only one malignant tumor occurred in a patient with evidence of a genetic syndrome (Carney syndrome), whereas 36% of benign tumors had various genetic syndromes or endocrine abnormalities. Most of the tumors in the latter cases were bilateral and multifocal. There were strong associations of malignant behavior with size >4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and mitotic rate greater than three mitoses per 10 high-power fields. All malignant cases exhibited at least two of these features, whereas all benign cases lacked any of them. The presence of any one of these features in a solitary large cell calcifying Sertoli cell tumor, especially in a patient >25 years of age, should be viewed as suspicious for malignant behavior, whereas the presence of two or more of these features indicates a strong probability of a malignant course. "Low" percentages (< or =35%) of tumor cells staining for proliferating cell nuclear antigen (PCNA) also may correlate with benign behavior, but some benign tumors have high PCNA values. Ki-67 values (MIB-1 antibody) did not correlate with biologic behavior, nor did immunostains for p53 protein.

Cytological, histological and ultrastructural findings of a pure benign Sertoli cell tumor.

A pure Sertoli cell tumor of the testis in a 26-year-old man is reported, with cytologic, histologic and ultrastructural findings. The preoperative cytological diagnosis allowed a conservative surgical approach.

Nuclear bodies appearance rate in canine testicular Sertoli cell tumor.

A number of nuclear bodies (NB) were observed in the canine testicular Sertoli cell tumors (SCT). We statistically examined nineteen cases of canine SCT concerning the NB appearance rate (NBAR), and also examined the NBAR in four cases of the normal testicular Sertoli cells. The mean value of the total number of the NBAR of SCT was significantly higher than that of normal Sertoli cells. The SCT were classified into three groups according to the Nielsen and Lein's histological classification (1974): intratubular SCT without invasion, intratubular SCT with invasion, and diffuse type SCT. The mean value of NBAR of the diffuse type SCT was significantly higher than that of the intratubular SCT with and without invasion, and there was no significant difference between the mean values of NBAR of the latter two groups. The distribution of NBAR of the diffuse type SCT was significantly different from that of the intratubular SCT with and without invasion. On the other hand, the individual differences of NBAR of the diffuse type SCT and the intratubular SCT with invasion was significantly higher than that of the intratubular SCT without invasion. The present study suggests that the increase of NBAR in canine SCT might be correlated with the tumor invasive progression.

Oxyphilic Sertoli cell tumor of the ovary: a report of three cases, two in patients with the Peutz-Jeghers syndrome.

Three women, aged 19, 21, and 30 years, two with the Peutz-Jeghers syndrome (PJS), had unilateral ovarian tumors composed of Sertoli cells with abundant eosinophilic cytoplasm. Electron microscopical and immunohistochemical examinations in one case supported the diagnosis of a sex cord tumor. Two patients are well 3 and 20 months postoperatively; the third was well for 15 years when recurrent tumor involving multiple intraabdominal sites was discovered. The occurrence of two of these tumors in patients with PJS and the known increased frequency of sex cord tumors in patients with this syndrome indicate an association. Sertoli cell tumor should be included in the differential diagnosis of oxyphilic ovarian tumors, particularly if there is a tubular pattern.

Experimental Sertoli cell tumors in the mouse and their progression into a mixed germ cell-sex cord proliferation.

Males of transgenic families where the large T protein of polyoma virus is expressed in the seminiferous epithelium of the testis (Sertoli and germ cells) develop bilateral testicular tumors when they become old (15 to 18 months). The histological features of these tumors revealed a neoplastic proliferation of Sertoli cell origin. Occasional isolated germ cells arrested at premeiotic stages were seen in the tumor. They did not participate in tumoral proliferation and their malignant character could not at first be established. Tumor cells injected in athymic (nu/nu) mice generated secondary tumors. In this case, a proliferative component of non-Sertoli origin was clearly evident. Its ultrastructural characteristics and the expression of genes that are transcribed in vivo in male germ cells (c-kit, LDH-X, and Hox a-4) suggest the progression of an initial, apparently pure Sertoli cell tumor into a mixed proliferation.

Large cell calcifying Sertoli cell tumor of the testis. A clinicopathologic, immunohistochemical, and ultrastructural study of two cases.

The clinicopathologic, immunohistochemical, and electron microscopic study of two patients with large cell calcifying Sertoli cell tumors (LCCSCT) of the testis is reported to elucidate the histogenesis of this rare tumor. Both tumors occurred in young individuals (16 and 32 years); case 1 was found incidentally, and the patient in case 2 presented with a 3-4-week history of testicular pain. Evidence of testosterone production was demonstrated in one case. In the same case, at the ultrastructural level Charcot-Böttcher crystalloids were observed. These data support previous reports that LCCSCT shows Sertoli cell differentiation.

[A case of infantile Sertoli cell tumor].

A case of infantile Sertoli cell tumor of the testis is presented. A 2-year-old child visited our hospital with the complaint of painless swelling of the left scrotal content. A solid tumor was demonstrated in the left testis by scrotal echography. Physical and laboratory examinations were within normal limits and alpha-fetoprotein and beta-HCG were not elevated. The left testis was removed. The tumor sized 3.0 x 3.0 x 2.2 cm and weighted 14.5 g. Pathohistological diagnosis was benign Sertoli cell tumor. Tumor cells were vimentin positive and TM-1 reactive antigen positive and revealed electronmicroscopically some features of Sertoli cells such as intermediated microfilament, rich lysosomes and interdigitation between adjacent cells. The patient was well with no evidence of diseases one and a half years after the operation.

Malignant Sertoli and Leydig cell tumour in a boar.

A rare case of Sertoli and Leydig cell tumour was investigated in a 6-month-old boar. The neoplasm was found in the right testis and had metastasized to the liver, spleen, kidneys and diaphragmatic peritoneum. Metastatic nodules were also present in the tissues near the right testis and some neoplastic cells were present in the superficial inguinal lymph node. The neoplastic cells exhibiting severe pleomorphism were divided into Sertoli and Leydig cell types, although in some sites, it was not possible to classify tumour cells clearly as Sertoli or Leydig in type. In the metastatic lesions there were anaplastic Sertoli cells with abundant collagen fibres. Some neoplastic Sertoli cells and a few neoplastic Leydig cells revealed cytoplasmic reactivity for testosterone. Ultrastructurally, the neoplastic cells were characterized by mitochondria with tubulovesicular cristae, smooth endoplasmic reticulum, membranous structures, lysosomes, lipofuscin granules or lipid droplets.

Steroid biosynthesis in the Sertoli-Leydig cell tumor: effects of insulin and luteinizing hormone.

In vitro steroid production by a virilizing Sertoli-Leydig cell tumor of the ovary was studied. For comparison, stromal tissue from the opposite normal ovary was also incubated under similar conditions. The tumor fragments secreted significantly more testosterone (527 +/- 168 versus 48 +/- 29 pg/mg tissue, p less than 0.001), androstenedione (1188 +/- 400 versus 40 +/- 10 pg/mg tissue, p less than 0.001), and dehydroepiandrosterone (419 +/- 132 versus 73 +/- 25 pg/mg tissue, p less than 0.004) than that of normal ovarian stroma. Measurement of steroids in the ovarian venous serum draining the tumor indicated a peripheral ovarian gradient for both delta 4 and delta 5 steroids. Incubation of tumor fragments with luteinizing hormone alone resulted in a significant increase in the secretion of androstenedione and dehydroepiandrosterone (p less than 0.05). Addition of insulin to luteinizing hormone resulted in significantly greater release of androstenedione than that of treatment with luteinizing hormone alone (p less than 0.04). Addition of insulin had no effect on the release of dehydroepiandrosterone. Luteinizing hormone and insulin, either alone or in combination, failed to produce any change in the secretion of testosterone. We conclude that (1) increased testosterone secretion by Sertoli-Leydig cell tumor resulted from increased availability of precursors from both delta 4 and delta 5 pathways; (2) the tumor was responsive to luteinizing hormone with an increase in the secretion of androstenedione and dehydroepiandrosterone; (3) insulin acts synergistically with luteinizing hormone to increase secretion of androstenedione; (4) the tumor has specific binding sites for insulin; and (5) the increased levels of insulin and luteinizing hormone in polycystic ovarian disease may play a role in the pathogenesis of Sertoli-Leydig cell tumor.

Light microscopic, immunocytochemical and ultrastructural study of a case of Sertoli cell tumor of the testis.

A case of testicular specialized gonadal stroma tumor was evaluated by histologic, ultrastructural and immunohistochemical techniques in a young adult male patient. The neoplastic cells were organized in cords or tubular structures delimited by a basement membrane. The ultrastructural findings suggested a diagnosis of a partially differentiated Sertoli cell tumor. This was also supported by the presence of a vimentin rich cytoskeleton, which is normally present in Sertoli and Leydig cells. The tumor cells did not secrete steroid hormones, as suggested by clinical findings, as well as by hormonal, immunohistochemical, and ultrastructural observations.

Ovarian sex cord tumor with annular tubules.

A pathologic study was done on four cases of ovarian sex cord tumor with annular tubules. All four tumors occurred in young women (11-24 years of age) and were not associated with the Peutz-Jeghers syndrome. Two patients had evidence of hyperestrinism. One patient who had metastasis to the retroperitoneum, left supraclavicular lymph node, and liver confirmed the malignant potential of this tumor. Gross examination revealed tumors that were solid, yellowish, and unilateral, with varying degrees of cystic degeneration. Microscopic examination showed simple or complex annular tubules with prominent basement membranes. Many tumor cells contained lipid in the cytoplasm. Ultrastructural study showed Charcot-Bottcher filaments in all four cases, indicating Sertoli cell differentiation. True lumens and microvilli were identified in one case. The classification of the sex cord tumor with annular tubules as a Sertoli cell tumor, annular tubular type was proposed on the basis of ultrastructural findings.

Sertoli-Leydig cell tumor of the ovary with alpha-fetoprotein production.

A case of poorly differentiated Sertoli-Leydig cell tumor with elevated serum alpha-fetoprotein (AFP) levels occurred in a 17-year-old girl. No germ cell component and no heterologous elements were identified, but a retiform pattern was present. Immunohistochemical studies demonstrated immunoreactivity for AFP and testosterone in Leydig's cells only. Secretion of AFP by Sertoli-Leydig cell tumors has rarely been mentioned previously, and its mechanism is difficult to explain. Non-germ cell tumors must be considered in the differential diagnosis of ovarian tumors with elevated serum AFP levels.