Immunohistochemical study of microphthalmia transcription factor and tyrosinase in angiomyolipoma of the kidney, renal cell carcinoma, and renal and retroperitoneal sarcomas: comparative evaluation with traditional diagnostic markers.

Angiomyolipoma has a unique immunophenotype with co-expression of muscle-specific actin and melanocytic markers such as HMB-45 and Melan-A. The most recently developed melanocytic markers, microphthalmia transcription factor and tyrosinase, have not been studied in the diagnosis of angiomyolipoma. We tested 29 renal angiomyolipomas (21 classic histology, 4 epithelioid variants, 2 lipomatous variants, and 2 leiomyomatous variants) with an immunohistochemical panel, including microphthalmia transcription factor, tyrosinase, HMB-45, Melan-A, and muscle-specific actin. Results were compared with 15 renal cell carcinomas (9 conventional types, 6 with sarcomatoid change), 2 leiomyosarcomas, 5 liposarcomas, and 1 unclassified high-grade sarcoma. Microphthalmia transcription factor expression was seen in 22 of 29 angiomyolipomas, one renal cell carcinoma, and one well-differentiated liposarcoma (that is, 2 of 23 non-angiomyolipomas; sensitivity 75%, specificity 91%). Tyrosinase expression was seen in 4 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 14%, specificity 100%). HMB-45 was positive in 24 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 83%, specificity 100%). Melan-A was expressed by 25 of 29 angiomyolipomas and 0 of 23 non-angiomyolipomas (sensitivity 86%, specificity 100%). Muscle-specific actin was expressed by 29 of 29 angiomyolipomas and 2 of 23 non-angiomyolipomas (both leiomyosarcomas; sensitivity 100%, specificity 91% [100% excluding leiomyosarcomas]). Microphthalmia transcription factor showed the most widespread staining in angiomyolipoma (50% of cases staining more than half of the tumor cells) followed by Melan-A (24% of cases staining more than 50%). Only three cases showed positivity for all four melanocytic markers, while in one case each only microphthalmia transcription factor and Melan-A were positive. We conclude that microphthalmia transcription factor, but not tyrosinase immunostaining, has a sensitivity and specificity that rivals those of the established markers, HMB-45 and Melan-A, in the diagnosis of angiomyolipoma. Our data supports the use of a panel in difficult cases that includes antibodies to microphthalmia transcription factor, either Melan-A or HMB-45, and muscle-specific actin to provide the best mix of high sensitivity, high specificity, nuclear and cytoplasmic immunolocalization, and widespread staining of cells within a given tumor.

Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia.

The aim of this study was to assess the relationship of immunoreactivity of cytokeratin 20 (CK20) and CD44 across the spectrum of urothelial neoplasia using the WHO/ISUP consensus classification. A total of 120 papillary urothelial pTa and pT1 tumors (8 papillomas, 8 neoplasms of low malignant potential, and 42 low-grade and 62 high-grade carcinomas) were immunostained by using CK20 and CD44 antibodies. The relationships of tumor grade, pathologic stage, recurrences, and progression in stage with CK20 and CD44 immunoreactivity were assessed. WHO/ISUP grade correlated with tumor stage (P < 0.005), recurrence (P = 0.02), and progression in stage (P = 0.031). Normal urothelium showed CK20 immunoreactivity restricted to a few umbrella cells. Expression of CD44 in normal urothelium was restricted to the basal cell layer. Loss of CD44 immunoreactivity and increasing CK20 positivity were significantly associated with increasing tumor grade and stage (P < 0.005). An inverse relationship was observed in the staining patterns of CK20 and CD44 within individual cases, as well as in the aggregate data, with 79.2% of tumors with CD44 loss showing CK20 positivity (P < 0.001). In conclusion, CK20 and CD44 immunoreactivity are significantly related to the WHO/ISUP grade and to each other, and our data suggest their potential combined utility in predicting biologic behavior in patients with papillary urothelial pTa and pT1 neoplasms.

[A case of Cushing's syndrome caused by primary pigmentary nodular hyperplasia]. / Un caso de síndrome de Cushing por hiperplasia nodular pigmentaria primaria.

Primary pigmented nodular adrenocortical disease is a rare cause of Cushing's syndrome in children and young adults. It is characterized by hypercorticolism resistant to dexamethasone suppression and at microscopic examination by multiple small black cortical nodules containing large cells with eosinophilic cytoplasm and lipofuscin with internodular cortical atrophy. Its pathogenesis is unknown. Bilateral adrenalectomy is the treatment of choice. We report a case of Cushing's syndrome due to primary pigmented nodular adrenocortical disease in a 32 year old female and review the literature.

Tubular seminoma. An immunohistochemical and DNA flow-cytometric study of four cases.

The histomorphologic features, immunohistochemical reactivity, and DNA content of four cases of a rare tubular variant of seminoma are presented. These neoplasms were characterized by a predominantly tubular architectural pattern that resembled yolk sac tumor, embryonal carcinoma, and sex cord-stromal tumors. The patients' ages were 15, 24, 27, and 44 years. On initial examination, three patients had painless testicular enlargement, and one had a large retroperitoneal mass and a clinically occult primary testicular tumor. The size of the tumors ranged from 1.7 to 6.0 (mean, 4.0) cm. Microscopically, the tumor cells had a tubular or tubulopapillary pattern that consisted of a single layer of cells, often in a back-to-back arrangement with intervening fibrovascular septa. Areas of classic seminoma were present in all cases. Scattered syncytiotrophoblastic giant cells were seen in two tumors. The tumor cells of both the classic and the tubular components of the seminomas were diffusely positive for placental alkaline phosphatase but were negative for cytokeratin and alpha-fetoprotein. DNA flow-cytometric analysis demonstrated abnormal stemlines with hypotetraploid DNA and a mean DNA index of 1.7 in both the classic and the tubular components. The presence of concurrent areas of classic seminoma, similar cytologic features in the tubular and classic seminoma areas, and the identical immunohistochemical and DNA flow-cytometric findings indicate that tubular seminoma is a histologic variant of seminoma. Although the behavior of the tubular variant appeared not to differ from that of classic seminoma in our small series, its recognition is important in the differential diagnosis and management of testicular masses.

Granulosa cell tumor of the adult testis: a clinicopathologic study of seven cases and a review of the literature.

We report a study of seven men, aged 16 to 76 years (average age, 47.4 years) with granulosa cell tumor (GCT) of the testis. Three patients presented with testicular enlargement of several years' duration and a fourth presented with a testicular enlargement of unknown duration. The tumors in three patients were detected during routine physical examination. None of the patients had endocrine-related symptoms. All tumors were well circumscribed and showed the solid, cystic, microfollicular, gyriform, insular, and trabecular patterns typical of GCT of the ovary. Call-Exner bodies were present in three tumors and two tumors had a focal spindle-cell component. In one case the surrounding testicular parenchyma showed Leydig's cell hyperplasia and a Sertoli cell nodule. The tumor cells revealed strong immunoreactivity for vimentin but showed no expression for keratin or epithelial membrane antigen. One patient developed liver and retroperitoneal lymph node metastases 121 months after initial diagnosis and died 13 months later. Another patient initially presented with retroperitoneal lymph node metastasis and developed metastasis to the inguinal lymph nodes 12 months later. Three patients are alive at 1, 4, and 37 months with no evidence of disease. Another patient died of an unrelated condition. Follow-up information was not available for the seventh patient. Twelve cases of GCT of the adult testis have been reported in the literature, with metastases occurring in two: one of these two patients had a tumor for 8 years and died of disease 5 months after diagnosis with multiple metastases and the other had metastasis at the time of diagnosis, but was free of disease for 14 years. Our findings and a review of the literature indicate that GCT of the adult testis is a rare and slow-growing neoplasm with the potential to form distant metastases. Because recurrence or distant metastasis may occur late in the clinical course, long-term follow-up of these patients is recommended.

Primary carcinoid tumor of testis. Immunohistochemical, ultrastructural, and DNA flow cytometric study of three cases with a review of the literature.

The cases of three patients with primary carcinoid tumor of the testis were reported. The patients were 41, 44, and 83 years of age. At initial examination, all three had testicular masses with or without associated pain, and none had the carcinoid syndrome. The tumors measured 4.3 cm, 3.0 cm, and 6.5 cm in dimension. All three tumors manifested classic histologic features of carcinoid tumors. The neoplastic cells exhibited argyrophilia, and all were immunoreactive to chromogranin, serotonin, neuron-specific enolase, and cytokeratin. Two tumors had positive test results for gastrin and one had positive test results for substance P and vasoactive intestinal polypeptide. No tumors reacted with somatostatin, insulin, pancreatic polypeptide, or placental alkaline phosphatase. Intracytoplasmic, membrane-bound, round-to-elliptical pleomorphic granules were identified by ultrastructural analysis in all cases. DNA flow cytometric analysis revealed a low degree (near-diploid) DNA aneuploidy in all cases, with a DNA index of 1.15 in two tumors and 1.3 in the third tumor. The three patients are alive and well 11 years, 7 years, and 6 months, respectively, after diagnosis. A total of 57 cases of this entity, including the 3 reported here, have been reported. Of these, 43 were pure carcinoid, and 14 were associated with teratoma; 6 (11.6%) patients developed metastases. Tumor size and the presence of carcinoid syndrome have been found to correlate with metastatic potential. Neither tumor necrosis nor local tumor invasion (into vessels, tunica albuginea, etc.) correlated with adverse prognosis. Carcinoid tumor of the testis is a rare indolent neoplasm with potential for distant metastases.