bromochloroacetic-acid and Sertoli-Cell-Tumor

The fifteenth case of malignant Sertoli cell tumour is reported and the literature is reviewed. The reported case was unilateral with lung metastases. Immunohistochemical examination showed positive staining reaction within the tumour cells for vimentin and cytokeratin, while AFP, HCG, PLAP, EMA and CEA were not found, which is in accordance with the staining pattern found in normal Sertoli cells.

Topics: Aged; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Immunohistochemical studies of human fetal Sertoli cells (SCs) have shown transient expression of cytokeratin (CK) and desmin (DES) that is replaced after birth by expression of vimentin (VIM) and inhibin-α (INH-α). Human Sertoli cell tumours (SCTs) are characterized by re-expression of CK and DES. The aim of the present study was to evaluate immunohistochemically the expression of VIM, INH-α, CK and DES in normal and neoplastic canine SCs. Normal testicular tissue from three adult dogs, one 6-month-old puppy and two neonatal pups was examined in addition to samples from 21 canine SCTs. VIM was not expressed by neonatal SCs, but was present in SCs from the puppy, the adult dogs and in all SCTs. Conversely, INH-α was expressed by neonatal SCs and most SCTs, but not by normal SCs of adult dogs and the puppy. DES and CK were expressed only by some SCTs. These results show that, contrary to findings in man, canine SCs do not express VIM at the time of birth. SCs from neonatal dogs do express INH-α, but such expression was lost in the puppy and the adult dogs. Canine SCs therefore differ from human SCs, as expression of INH-α characterizes immature SCs, whereas the expression of VIM characterizes mature SCs. Canine SCTs may express CK and DES, suggesting that the neoplastic cells undergo de-differentiation during transformation.

Topics: Animals; Desmin; Dog Diseases; Dogs; Immunohistochemistry; Inhibins; Keratins; Male; Sertoli Cell Tumor; Sertoli Cells; Testicular Neoplasms; Testis; Vimentin

Topics: Aged; Biomarkers; Carcinoid Tumor; Carcinoma, Endometrioid; Diagnosis, Differential; Female; Granular Cell Tumor; Humans; Hysterectomy; Keratin-7; Keratins; Krukenberg Tumor; Middle Aged; Mucin-1; Ovarian Neoplasms; Sertoli Cell Tumor; Sex Cord-Gonadal Stromal Tumors

Sertoli cell tumours (SCT) are rare and poorly explored neoplasias, and the genetic features of these uncommon tumours are largely unknown. Data about chromosomal aberrations in human SCT of the testis are very rare. We present in this paper the first molecular-cytogenetic study of SCT of the testis. DNA was isolated from paraffin-embedded tumour material from 11 patients with unilateral SCT. We used comparative genomic hybridisation to investigate changes in DNA copy number. The detected DNA imbalances showed variation from case to case, indicating a high genetic heterogeneity. Chromosomal aberrations were detected in 9 of the 11 tumours evaluated, with 13 losses versus 14 gains. The most frequent aberrations detected were gain of chromosome X (5 of 11 cases) followed by losses of entire or part of chromosomes 2 and 19 in three cases. This study suggests a high variability in histomorphological and genetic patterns. Only gain of the entire chromosome X seems to be a frequent aberration in these tumours. Further studies of these tumour types are necessary to clarify the significance of chromosomal alterations in carcinogenesis of SCT.

Topics: Adult; Aged; Calbindin 2; Child, Preschool; Chromosome Aberrations; Genome, Human; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Infant; Inhibins; Keratins; Male; Middle Aged; Nucleic Acid Hybridization; S100 Calcium Binding Protein G; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Sertoli cell tumor of the testis (not otherwise specified) in a 43-year-old man is reported. Macroscopically, the testicular mass measured 3.0 x 2.3 x 1.5 cm and was well circumscribed. The cut surface was white to tan-gray in color. Neoplastic cells with eosinophilic cytoplasm proliferated with solid and tubular structures. Neoplastic cells focally contained vacuoles of various sizes in the cytoplasm. Cystic formation and cord formation in the hyalinized stroma was also observed. Immunohistochemically, neoplastic cells were positive for cytokeratin 8, chromogranin A and synaptophysin, but neoplastic cells were negative for placental alkaline phosphatase, inhibin-alpha and pancytokeratin. The stroma in the tumor center and capsule contained a significant number of myofibroblasts that were positive for alpha-smooth muscle actin and negative for h-caldesmon, but no CD34-positive stromal cells were detected in the stroma of the tumor center. Ultrastructurally, neoplastic cells had cytoplasmic processes and abundant rough endoplasmic reticulum and lipid droplets in the cytoplasm. However, dense core granules were absent. It is important to differentiate between Sertoli cell tumor and carcinoid tumor because of the positive reaction for neuroendocrine markers in both tumors. Myofibroblasts are a major stromal component of Sertoli cell tumor of the testis.

Topics: Adult; Biomarkers, Tumor; Chromogranin A; Chromogranins; Cytoplasm; Humans; Immunohistochemistry; Inhibins; Keratins; Male; Neurosecretory Systems; Sertoli Cell Tumor; Synaptophysin; Testicular Neoplasms

The distinction of Sertoli cell tumors from seminoma is critical to ensure proper treatment. Although usually straightforward, we highlight herein 13 malignant Sertoli cell tumors of the testis with light microscopic features that mimicked seminoma. All of the cases were received in consultation, 10 with submitting diagnoses of seminoma, usually of classic type, but three cases of spermatocytic type. Patients ranged from 15 to 80 years of age (median 37 years); all presented with testicular masses. The tumors were typically firm, white to yellow-tan, and often had foci of hemorrhage. The dominant microscopic pattern was nested or sheet-like, with some tumors having secondary patterns of trabeculae-solid tubules, hollow tubules, and pseudofollicles. Tumor cells were polygonal with conspicuous clear cytoplasm in 12 cases; the cytoplasm was focally eosinophilic in 10 cases, but this was never conspicuous. Nine tumors had cytoplasmic vacuoles, and three of four that were investigated stained for intracytoplasmic glycogen. Nuclei were small (5) to medium-sized (8), round-to-oval (13), and vesicular with irregular contours (11). Nucleoli were present in 11 tumors (six small; five large). Stromal fibrosis (12) and lymphoid infiltrates (10) were conspicuous, and tumor necrosis (11) and vascular invasion (8) also were seen. Mitotic figures ranged from <1 to 21/10 high power fields (HPF) (median 1/10 HPF). Staining for inhibin-alpha, epithelial membrane antigen, and cytokeratin (AE1/AE3) was positive in four of four, six of six, and three of six cases, respectively; placental alkaline phosphatase was negative in all five tumors investigated. The nested growth pattern, prominence of clear cells, lymphoid infiltrate, inconspicuous tubular differentiation, cytoplasmic glycogen, and prominent nucleoli caused these tumors to be mistaken for seminomas. The smaller, less pleomorphic nuclei of Sertoli cell tumors, their lower mitotic rate, and the absence of intratubular germ cell neoplasia are helpful differential features. Immunohistochemistry is a useful adjunct in confirming the diagnosis of Sertoli cell tumor, but only if the overlapping features are appreciated by conventional microscopy and the diagnosis of Sertoli cell tumor included in the differential.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Inhibins; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Proteins; Seminoma; Sertoli Cell Tumor; Testicular Neoplasms

A Sertoli cell carcinoma of the ovary with lung metastases mimicking neuroendocrine carcinoma is presented. Lung metastases frequently occur. Primary and secondary tumors may exhibit similar growth patterns and differentiating primary from secondary tumors may be troublesome. This process may be more difficult when metastases occur from a tumor in which metastases are uncommon and morphologically resemble only a small portion of the primary tumor. We report the case of a 52-year-old woman who underwent resection of a 4,550-g Sertoli cell tumor of the ovary. Histologically, in addition to the characteristic tubular pattern of growth, 5% of the tumor consisted of poorly differentiated areas with tumor cells in sheets, a high mitotic rate, and areas of necrosis. Eleven months after this surgery she presented at a different institution with multiple pulmonary nodules. Microscopic examination of a subsequently resected lung nodule showed histologic findings similar to those of the poorly differentiated areas of the ovarian tumor and initial immunohistochemical studies showed positive staining for cytokeratin, neuron-specific enolase, and focal positivity for synaptophysin. Without knowledge of the ovarian tumor the lung lesion was interpreted as large-cell neuroendocrine carcinoma. On review of the clinical history and comparison with the previous surgical material, however, both tumors showed similar light microscopy and immunohistochemical reactivity, and a final diagnosis of metastatic Sertoli cell tumor was made. Immunohistochemical staining for inhibin revealed weak positivity in the poorly differentiated areas of the ovarian tumor but not in the lung metastasis. This is one of the rare reports of ovarian Sertoli cell tumor metastasizing to the lungs and it emphasizes the importance of complete clinical histories, ancillary studies, appropriate sampling, and review of archival material in such unusual cases.

Topics: Carcinoma, Neuroendocrine; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Inhibins; Keratins; Lung Neoplasms; Middle Aged; Ovarian Neoplasms; Phosphopyruvate Hydratase; Sertoli Cell Tumor; Synaptophysin

Ovarian endometrioid carcinomas with sertoliform features (SECs) are infrequent and often misinterpreted as sex cord-stromal tumors. The clinicopathologic features and immunohistochemical expression of keratin, epithelial membrane antigen (EMA), inhibin, and estrogen and progesterone receptors were evaluated in 13 cases of SEC. The women were 41 to 89 years of age (mean, 60 yr) with abdominal enlargement secondary to a unilateral ovarian mass as the most frequent clinical presentation. One patient displayed virilization. At presentation, 10 patients were Stage I, one was Stage II and two were Stage III. The tumors were composed of compact anastomosing cords and small tubules embedded within a fibrous stroma. Nuclear features were Grade 1 or 2 in all but one tumor. Areas of conventional endometrioid carcinoma were observed in 12 cases. An adenofibromatous component comprising 5 to 60% of the lesion was present in seven cases. All 12 cases examined immunohistochemically were positive for keratin and EMA and negative for inhibin with focal, luteinized stromal cells positive for inhibin in 10 cases. Estrogen and progesterone receptors were positive in 10 and 11 cases, respectively. Follow-up on 6 of 10 patients with Stage I and the one patient with Stage II disease displayed no evidence of disease 10 to 120 months (mean, 57 mo). Progressive disease and death occurred at 12 and 72 months only in the two women with Stage III disease, one of which had an associated serous carcinoma in the contralateral ovary. Adequate sampling, a careful search for areas of conventional endometrioid carcinoma, and immunohistochemical studies (including EMA, keratin, and inhibin) are helpful in the evaluation of ovarian tumors with sex cord-stromal features. SEC should be considered a well-differentiated endometrioid carcinoma despite the presence of a solid, sex cord-like proliferation, with a good prognosis when confined to the ovary.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Endometrioid; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Inhibins; Keratins; Middle Aged; Mucin-1; Neoplasm Staging; Ovarian Neoplasms; Ovary; Receptors, Estrogen; Receptors, Progesterone; Sertoli Cell Tumor; Sertoli-Leydig Cell Tumor; Sex Cord-Gonadal Stromal Tumors

Five cases of large cell calcifying Sertoli cell tumour of the testis not associated with complex dysplastic syndromes are reported. The age of the patients ranged from 13 to 34 years and all the tumours were histologically similar, having large, isomorphic, non-mitotic, eosinophilic Sertoli cells with foci of calcification. Flow cytometry demonstrated the cells to be diploid or hypodiploid. All cases were positive for vimentin and focally positive for low molecular weight keratin. The present cases, together with a review of the 22 previously reported tumours, demonstrate that there are two clear cut types of large cell calcifying Sertoli cell tumour; those which are associated with complex dysplastic syndromes and which are bilateral and multifocal, and those which are not associated and are unilateral and focal. Prognosis in all of our cases was uniformly good despite invasion of the rete testis in two cases. It is considered that conservative resection of the tumour is the treatment of choice in cases not associated with complex dysplastic syndromes, since the malignancy rate is low.

Topics: Adolescent; Adult; Calcinosis; Diagnosis, Differential; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Male; Sertoli Cell Tumor; Testicular Neoplasms; Ultrasonography; Vimentin

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.

Topics: Adult; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasms, Multiple Primary; Ovarian Neoplasms; Peutz-Jeghers Syndrome; Sertoli Cell Tumor; Sex Cord-Gonadal Stromal Tumors; Vimentin

We have studied immunolocalization of all steroidogenic enzyme involved in sex steroids biosynthesis, P-450 side chain cleavage (P-450scc), 3 beta hydroxy steroid dehydrogenase (3 beta-HSD), P-450 17 alpha hydroxylase (P-450(17 alpha)) and P-450 aromatase (P-450arom) and that of vimentin and cytokeratin in 14 cases of testicular sex cord-stromal tumours (6 Leydig cell tumours, 5 Sertoli cell tumours, 2 fibromas and 1 granulosa cell tumour) as well as 4 cases of hyperplasia (2 Leydig and 2 Sertoli). Leydig cell tumour expressed all four steroidogenic enzymes examined, indicating that this tumour can synthesize oestrogen from cholesterol. In 2 cases of Sertoli cell tumour, the tumour cells with clear cytoplasm and without Reinke's crystals expressed P-450ssc, 3 beta-HSD and P-450(17 alpha), suggesting the capability of androgen production in these tumour cells. Fibromas and granulosa cell tumour were negative for the enzymes examined. In immunohistochemistry of intermediate filaments, Leydig cell tumours demonstrated only vimentin. Sertoli cells in hyperplasia and non-neoplastic testis expressed only vimentin but Sertoli cell tumours expressed both cytokeratin and vimentin. Cytokeratin immunoreactivity was correlated with morphological epithelial differentiation in Sertoli cell tumour. These findings in testicular Sertoli cell tumour are considered to represent the multiple differentiation capacity of this neoplasm. Immunohistochemical study of steroidogenic enzymes and intermediate filaments provided new insight into neoplastic steroidogenesis and the differentiation capacity of testicular sex cord-stromal neoplasms.

Topics: 3-Hydroxysteroid Dehydrogenases; Adolescent; Adult; Aged; Aromatase; Child; Child, Preschool; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Leydig Cell Tumor; Male; Middle Aged; Sertoli Cell Tumor; Steroid 17-alpha-Hydroxylase; Testicular Neoplasms; Vimentin

Small cell carcinoma of the ovary is a rare, poorly understood aggressive tumor of young women, associated with paraendocrine hypercalcemia in two-thirds of the cases. Immunohistochemical staining of 15 small cell carcinomas, one-third of which were associated with hypercalcemia, 15 adult granulosa cell tumors, 15 juvenile granulosa cell tumors, and 5 Sertoli cell tumors, was performed with the use of antibodies against cytokeratins (AE-1/AE-3, CAM 5.2, 902), epithelial tumor-associated antigens (B72.3, epithelial membrane antigen [EMA]), vimentin, S-100, neuron-specific enolase (NSE), lysozyme, parathyroid hormone, and chromogranin-A in an attempt to define histogenetically this tumor type. One-third of the small cell carcinomas were positive for EMA, whereas all of them were negative for B72.3 and S-100. In contrast, one-third of the granulosa cell tumors were positive for S-100 and all of them were negative for EMA and B72.3. One of five Sertoli cell tumors were positive for EMA and two were positive for B72.3, but all were negative for S-100. Differences existed in the frequency, intensity, and/or pattern of staining for cytokeratin, vimentin, lysozyme, and NSE among the various tumor types. A single small cell carcinoma from a patient with hypercalcemia stained focally for parathyroid hormone, whereas all 30 granulosa cell tumors and 4 of 5 Sertoli cell tumors were nonreactive. Chromogranin-A staining was noted in four of five small cell carcinomas, none of ten granulosa cell tumors, and two of five Sertoli cell tumors. These immunohistochemical findings, as well as previous light and electron microscopic data, do not clearly indicate any specific cell as the cell of origin of the ovarian small cell carcinoma.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Small Cell; Chromogranin A; Chromogranins; Female; Granulosa Cell Tumor; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Mucin-1; Ovarian Neoplasms; S100 Proteins; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Ovarian endometrioid carcinomas resembling sex cord-stromal tumors (ECSCSs) may simulate Sertoli cell tumors, Sertoli-Leydig cell tumors (SLCTs), and adult granulosa cell tumors (AGCTs), both clinically and pathologically. Differing clinical features and histologic findings are almost always successful in distinguishing these tumor types, although in some cases the differential diagnosis is difficult. Immunohistochemical staining of 17 ECSCSs, 14 Sertoli cell tumors or SLCTs, and 15 AGCTs was performed with the use of antibodies against cytokeratins (AE1/AE3, 902, and CAM 5.2), epithelial tumor-associated antigens (EMA, OM-1, B72.3, and carcinoembryonic antigen B1.1), vimentin, S-100, neuron-specific enolase, and lysozyme to determine the immunohistochemical profile of each tumor type and to define further the nature of the sex cord-like components in ECSCSs. All 17 ECSCSs, none of the 15 AGCTs, and one of 14 Sertoli cell tumors or SLCTs stained with EMA. Staining for OM-1 was almost as helpful diagnostically, with positive results for 15 of 17 ECSCSs, 0/15 AGCTs, and 1/14 Sertoli cell or SLCTs. Antikeratins were immunoreactive with all the ECSCSs as well as some of the AGCTs and Sertoli cell tumors or SLCTs. The B72.3 and B1.1 were immunoreactive with some ECSCSs and Sertoli cell tumors, but were nonreactive with AGCTs. Neuron-specific enolase was demonstrated in 11 of 17 ECSCSs, two of 14 Sertoli cell tumors or SLCTs, and 0 of 15 AGCTs. Vimentin, S-100, and lysozyme were least helpful in the differential diagnosis. These studies suggest that an immunohistochemical approach may be useful in the differentiation of ECSCSs and sex cord-stromal tumors. Furthermore, it supports the conclusion that the sex cord-like cells in ECSCSs are not Sertoli or granulosa cells, but cells of surface epithelial type growing in architectural patterns similar to those of sex cord-stromal tumors.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Diagnosis, Differential; Endometriosis; Female; Granulosa Cell Tumor; Humans; Immunohistochemistry; Keratins; Leydig Cell Tumor; Lysosomes; Male; Ovarian Neoplasms; Phosphopyruvate Hydratase; S100 Proteins; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Topics: Female; Humans; Immunoenzyme Techniques; Keratins; Leydig Cell Tumor; Ovarian Neoplasms; Sertoli Cell Tumor