Heavily melanotic perivascular epithelioid clear cell tumor of the kidney

A black-colored and well-circumscribed renal tumor in a 71-year-old woman is reported. The tumor was unique in that it was rich in vasculature and exclusively composed of perivascular epithelioid clear cells. Morphological features were reminiscent of conventional renal cell carcinoma (RCC). However, immunohistochemical examinations showed that the tumor cells did not express any epithelial markers, but diffusely and intensely expressed a melanocytic marker, gp-100/HMB-45. Another striking feature of the tumor was a large amount of cytoplasmic pigment that made the tumor wholly black. The pigment was not stained with Berlin-blue, completely bleached with potassium permanganate, and stained with Fontana-Masson staining, which suggests that the pigment was melanin. Morphological features and immunohistochemical findings indicated that the present tumor was an extreme example of a perivascular epithelioid clear cell tumor with a large amount of melanin, which has not been previously reported. One should be aware of the pure form of perivascular epithelioid clear cell tumor of the kidney because it is sometimes very difficult to differentiate this tumor from conventional RCC. Immunohistochemical examinations and the presence of cytoplasmic melanin can help the differentiation.     

Ependymoma: Ultrastructural Studies of Two Cases

Several unusual ultrastructural findings in two ependymomas are reported. In case 1, a grade I ependymoma of the fourth ventricle, there were rosettes, perivascular pseudorosettes, and tumor cells having unusual intracytoplasmic vacuoles by light microscopy. Ultrastructurally, these vacuoles were frequently microrosettes as well as scattered, degenerated cytoplasmic processes of tumor cells. The lumina of some of the microrosettes were bordered by abnormally long and malformed zonulae adherentiae. In case 2, a recurrent grade III ependymoma of the third ventricle, there were rosettes and perivascular pseudorosettes as well as more cellular and anaplastic areas by light microscopy. Ultrastructurally, the cytoplasmic processes of tumor cells in perivascular pseudorosettes contained frequent dense-core vesicles and occasional parallel arrays of microtubules. These structures do not occur in normal mammalian ependymal cells but do occur in the ependymal tanycyte, a related cell that is plentiful in the walls of the third ventricle. Thus some of the tumor cells of this third ventricle ependymoma appear to have differentiated as tany-cytes.     

Pigmented "black" pheochromocytoma of the adrenal gland: a case report and review of the literature

A pigmented "black" mass was discovered incidentally in a 72-year-old woman. The tumor, which was detected near the upper pole of the left kidney, was cystic and intensely black throughout with the presence of abundant, coarse, dark brown to black pigment granules. Histologic examination showed a proliferation of monomorphous neoplastic cells arranged in a typical zellballen growth pattern. These features indicated a diagnosis of pheochromocytoma. Immunostains for chromogranin A, synaptophysin, and neuron-specific enolase were positive. The immunostain for HMB-45 was negative. Electron microscopy showed neurosecretory-type granules and larger pleomorphic granules, which were considered most consistent with neuromelanin, a waste product of catecholamine metabolism. The evidence of melanin or melanin-like pigment in the adrenal gland has been described in only 10 cases in the literature and is always a microscopic finding. The case reported here is unique for the characteristic black macroscopic appearance and the abundance of pigment.     

Ependymoma: Ultrastructural Studies of Two Cases

Several unusual ultrastructural findings in two ependymomas are reported. In case 1, a grade I ependymoma of the fourth ventricle, there were rosettes, perivascular pseudorosettes, and tumor cells having unusual intracytoplasmic vacuoles by light microscopy. Ultrastructurally, these vacuoles were frequently microrosettes as well as scattered, degenerated cytoplasmic processes of tumor cells. The lumina of some of the microrosettes were bordered by abnormally long and malformed zonulae adherentiae. In case 2, a recurrent grade III ependymoma of the third ventricle, there were rosettes and perivascular pseudorosettes as well as more cellular and anaplastic areas by light microscopy. Ultrastructurally, the cytoplasmic processes of tumor cells in perivascular pseudorosettes contained frequent dense-core vesicles and occasional parallel arrays of microtubules. These structures do not occur in normal mammalian ependymal cells but do occur in the ependymal tanycyte, a related cell that is plentiful in the walls of the third ventricle. Thus some of the tumor cells of this third ventricle ependymoma appear to have differentiated as tany-cytes.     

Pigmented granules in functional black adenoma of the adrenal gland: A histochemical and ultrastructural study

A black adenoma of the adrenal gland was laparoscopically removed from an 61-yr-old Japanese female who had clinical and laboratory findings characteristic of Cushing’s syndrome. The tumor consisted of polygonal cells that contained numerous brown pigmented granules of various sizes by routine hematoxylin-eosin staining. The histochemical study showed that the pigment had the characteristics of lipofuscin, not of melanin or neuromelanin. Electron microscopic study revealed tumor cells with two types of pigmented granules. These results show that there might be differences in the lipid metabolism of individual tumor cells in black adenomas of adrenal; which suggests an interesting histogenesis for these granules.     

Melanosis coli--histochemical and immunohistochemical comparison of the pigments of melanosis coli and Dubin-Johnson syndrome

We compared the pigment of melanosis coli with the pigment of Dubin-Johnson syndrome, melanin, and lipofuscin. The pigment of melanosis coli appeared similar to lipofuscin in that it stained positively with periodic acid-Schiff, oil red-0 and Victoria blue stains and revealed negative reactions to the immunohistochemical stains for S-100 protein and neuron specific enolase, but had similarity to melanin as shown by the positive reaction to Fontana-Masson stain and negative autofluorescence. The pigment of Dubin-Johnson syndrome showed the same histochemical and immunohistochemical characteristics as that of melanosis coli. The results indicate that the pigments of melanosis coli and Dubin-Johnson syndrome are identical and are variants of lipofuscin.     

Malignant Melanoma Metastatic to the Testis: A Report of Three Cases with Clinically Significant Manifestations

Three cases of malignant melanoma metastatic to the testis, each of which was a challenge in pathologic interpretation, are reported. The patients were 43, 55, and 80 years of age, respectively. A history of malignant melanoma was not known to the initial examining pathologist in two of the cases. The testicular tumors were all unilateral. One took the form of multiple nodules, but the others were discrete solitary masses. On microscopic examination diffuse, nested, follicular, and fascicular patterns, usually in combination, were seen. The tumor cells had moderate to abundant eosinophilic cytoplasm in two cases, but scanty cytoplasm in a third. In one case there was also a component of cells with copious foamy cytoplasm. Rare areas of melanin pigment were identified in two tumors. Immunohistochemistry for S-100 and HMB-45 was positive in the two cases in which it was performed. In the third case electron microscopy revealed aberrant melanosomes within the tumor cells. The differential diagnosis in these and rare other cases of malignant melanoma involving the testis during life is broad and includes seminoma, malignant lymphoma, and Leydig cell tumor. When the diagnosis is entertained, a search for melanin pigment, immunohistochemical stains for S-100 protein and HMB 45, and further inquiry into the clinical history are often crucial. Int J Surg Pathol 8(1):49-57 2000     

Mammary carcinoma with prominent cytoplasmic lipofuscin granules mimicking melanocytic differentiation

We report a case of mammary carcinoma with striking cytoplasmic pigmentation in a 60-year-old Japanese woman who presented with a self-evident nodular lesion in the left breast. METHODS AND RESULTS: After a fine needle aspiration revealing atypical clusters of cells, an excisional biopsy was performed. Histologically, a partially cystic 18 mm lesion containing a 5-mm mural nodule was present. The mural nodule and adjacent thickened epithelium were comprised of atypical cells focally invading into the cyst wall. Striking abundant granular brown pigment resembling melanin was present in some of the neoplastic cells. The differential diagnosis included metastatic melanoma and mammary carcinoma with melanocytic differentiation. After a series of special stains and immunohistochemical studies, the diagnosis of mammary carcinoma with extensive cytoplasmic lipofuscin pigment was rendered. CONCLUSION: Mammary carcinoma with lipofuscin pigment to the degree seen in this case which mimics melanocytic differentiation has not, to our knowledge, previously been documented.     

Primary mediastinal melanotic schwannian tumors: A clinicopathological and immunohistochemical study of 5 cases

Mediastinal neurogenic tumors are unusual and more so is the presence of melanotic neurogenic tumors. We present five cases of mediastinal melanotic neurogenic tumors. The patients are five men between the ages of 34 and 43 years (average: 38.5 years). All patients presented with non-specific symptoms that included back pain and cough. Diagnostic imaging revealed the presence of a posterior mediastinal mass without connection to the spinal canal, and surgical resection was accomplished in all of the patients. Histologically, the five tumors showed a spindle epithelioid cellular proliferation, nuclear atypia, mitotic activity, and melanin deposition. Histochemical stain for Fontana Masson clearly demonstrated the presence of melanin pigment in all the cases, while S-100 protein was only focally positive in tumor cells. Other immunohistochemical stains including SOX-10, MITF, HMB-45, and Melan A were negative. Clinical follow-up showed that two patients died 22 and 30 months after initial diagnosis; one remains alive, 6 months after initial diagnosis; two patients were lost to follow up. Melanotic neurogenic tumors represent a diagnostic challenge for pigmented thoracic tumors and careful analysis of the morphology and immunohistochemistry is required to lead to proper diagnosis.     

Primary malignant melanoma of the larynx

Primary malignant melanoma of the larynx is a rare clinical entity. Only 53 cases have been reported in the medical literature to date. This report describes a case of primary malignant melanoma arising in the larynx and diagnosed by histologic examination of an excisional biopsy specimen. The patient was a 53-year-old man with a history of smoking and hoarseness. There was no clinical evidence of other primary malignant melanocytic lesions. Microscopically, the tumor consisted of polygonal-epithelioid cells admixed with more elongated, spindle-shaped cells. The majority of the cells demonstrated dark brown cytoplasmic and nuclear melanin. Marked pleomorphism and abnormal mitoses were also identified. Despite significant ulceration and disruption of the epithelium, in situ malignant melanocytes were recognized within the remaining portion of the epithelium. Immunohistochemical studies were positive for S100, HMB-45, and vimentin, while cytokeratin and iron stains were negative. Based on the clinical and histologic findings, a diagnosis of primary malignant melanoma of the larynx was established.     

Infratentorial giant cell ependymoma: a rare variant of ependymoma

We describe a giant cell ependymoma occurring in a 50-year-old man. The mass was located in the posterior aspect of the foramen magnum, extending from the cerebellar tonsil to the upper cervical spine. The tumor was a highly cellular neoplasm showing biphasic histology. Diffuse sheets of non-cohesive atypical giant cells, having eccentrically located single or multiple nuclei and plump eosinophilic cytoplasm, partly infiltrated the desmoplastic inflammatory stroma. Parts of perivascular pseudorosette-forming or pseudopapillary areas were composed of atypically elongated cells, which looked like conventional anaplastic ependymoma. There was a transitional area between two patterns. Numerous mitoses and focal necrosis were observed. Immunohistochemically, the tumor cells were immunoreactive for glial fibrillary acidic protein, vimentin, S-100 protein, and CD99. None of the tumor cells showed immunoreactivity for epithelial membrane antigen except for the intracytoplasmic lumen of a few vacuolated cells. Ultrastructurally, tumor cells were ependymal in nature; we noted cytoplasmic intermediate filaments and intercellular microrosettes with microvilli, cilia, and long zonula adherens. The features of this tumor, e.g. its superficial location, mixed giant cells, perivascular pseudorosettes or papillaries, complicated its differentiation from rhabdoid/papillary meningioma. However, immunohistochemistry and electron microscopy confirmed the diagnosis of ependymoma. The giant cell variant should be included in the subclassification of the ependymoma.     

Pigmented Pheochromocytoma: an Unusual Variant of a Common Tumor

Pheochromocytoma is a neuroendocrine tumor arising from the adrenal medulla. A number of variants of pheochromocytoma are known; however, pigmented pheochromocytoma is extremely rare, with only few cases reported in literature. We report the cases of two patients with pigmented pheochromocytoma. Case 1 was a 28-year-old female who presented with complaints of breathlessness, palpitations, and anxiety for 5 years, which had worsened over the last 8 months. Computed tomography (CT) abdomen showed a right suprarenal mass. Case 2 was that of an 18-year-old girl who presented with similar complaints and was diagnosed with hypertension. CT abdomen showed bilateral adrenal masses. Urinary vanillyl mandelic acid was raised in both patients. Sections examined from all three tumors showed cells arranged in Zellballen pattern, separated by thin fibrovascular septae. Tumor cells showed moderate to marked nuclear pleomorphism in case 1. Mitoses were, however, not seen. There was no evidence of capsular or vascular invasion. Many of the tumor cells showed intracytoplasmic black pigment, which was positive for Fontana–Masson and was bleach-labile, confirming it as melanin. Hemosiderin deposition was also identified. Large areas of hemorrhagic necrosis were seen in case 1. Tumor cells were immunopositive for chromogranin and synaptophysin, while they were negative for HMB-45. Electron microscopy was performed. A final diagnosis of pigmented pheochromocytoma was rendered in both cases. Pigmented pheochromocytoma is a very rare tumor, which needs to be differentiated from other pigmented tumors like malignant melanoma of adrenal gland and pigmented adrenal adenoma. Histochemistry and immunohistochemistry help in making this distinction.     

Clear cell ductal adenocarcinoma of pancreas: a case report and review of the literature

We present a unique carcinoma of the pancreas with predominantly clear cell morphology (>95% clear cells). Mucicarmine stain revealed abundant intraluminal and intracytoplasmic mucin. Immunohistochemically, the cells were positive for the epithelial markers cytokeratin 7 and CAM 5.2, and were focally positive for cytokeratin 20. These cells also expressed monoclonal carcinoembryonic antigen. Stains for the neuroendocrine markers synaptophysin and chromogranin were negative, as were stains for vimentin, p53, HMB-45, and CD10. An additional outstanding feature was the presence of dense intraluminal and intracytoplasmic hyaline globules, which were immunohistochemically positive for alpha1-antitrypsin. Sequencing of the K-ras oncogene revealed a point mutation in codon 12, providing molecular evidence of ductal origin. In the proper morphologic context supported by immunohistochemistry, clear cell carcinoma can be regarded as a rare variant of ductal adenocarcinoma.     

Primary intraosseous melanotic schwannoma of the fibula associated with the Carney complex

Described herein is a rare case of intraosseous melanotic schwannoma (MS) occurring in a long bone of a 13-year-old girl with a loss of heterozygosity (LOH) at 17q22-24, which contains the PRKAR1A gene encoding the protein kinase A regulatory subunit 1-a. Plain radiography and magnetic resonance imaging revealed a 10 cm expansile osteolytic lesion involving the proximal fibula. An excisional biopsy revealed a cellular tumor consisting of mildly pleomorphic spindle or oval to polygonal cells with frequent intranuclear pseudoinclusions, intracytoplasmic melanin pigments, nuclear palisades, Verocay body-like structures, and psammomatous calcifications. The tumor cells showed strong immunoreactivity for S-100 protein, HMB-45, and neuron-specific enolase. Ultrastructurally, the tumor cells were invested by continuous, multiplied external lamina and conspicuous melanosomes in various stages of maturation. These observations were compatible with psammomatous melanotic schwannoma (PMS). In addition, the detection of LOH for PRKAR1A strongly suggests that PMS in the present case is a manifestation of the Carney complex (CNC).     

Carcinosarcoma of female urethra with melanocytic differentiation

Carcinosarcoma arising from the female urethra is rare. We report an unusual case of urethral carcinosarcoma from a female patient with melanocytic differentiation. The tumor consists of a high-grade papillary serous carcinoma with psammoma bodies and a mesenchymal component with area of heterologous (cartilaginous) element. More interestingly, there are epithelioid tumor cells containing melanin pigment. On immunohistochemical stains, the epithelioid tumor cells are positive for S100, HMB45 and Mart-1, but negative for cytokeratin. This case represents an unusual carcinosarcoma with areas of melanocytic differentiation. Such rare tumors have been occasionally reported in the breast, uterus, kidney, and lung. These cases demonstrate the capacity of tumor cells to differentiate into divergent elements, supporting the concept of pluripotent tumor stem cells.     

Epithelioid angiosarcoma of the kidney: a diagnostic dilemma in fine-needle aspiration cytology

Epithelioid angiosarcomas (EAS) of kidney are rare and aggressive tumors with noncharacteristic imaging features that overlap with those of inflammatory conditions and renal cell carcinoma (RCC). We report the fine-needle aspiration (FNA) cytology findings of a case of EAS that involved the left kidney of an 83-year-old male. The smears and cell block sections showed pleomorphic epithelioid cells with ample cytoplasm, eccentric nuclei, occasional cytoplasmic hyaline globules, and rare intracytoplasmic lumina. Immunohistochemical stains performed on cellblock sections showed that the tumor cells were positive for vimentin, CD31, CD34, Factor VIII, and CD10, but showed no staining for cytokeratins AE1/AE3 and 8/18, HMB45, CD45, smooth muscle actin, and S100. The morphological and immunohistochemical distinction between EAS, primary tumors of the kidney, and other epithelioid and rhabdoid neoplasms is discussed.     

Tanycytic Ependymoma

Tanycytic ependymoma is an uncommon fibrillar variant of ependymoma characterized by streams of piloid, or hair-like, cells having “ependymal” nuclei. True ependymal rosettes are absent, and perivascular rosettes are inconspicuous. Misinterpretation as schwannoma or astrocytoma is a diagnostic problem and well-documented cases are scarce. The purpose of this report is to document the ependymal features of the neoplasm and to increase awareness of the entity's existence. Biopsy tissues from three patients with tanycytic ependymoma were examined. All tumors consisted of sheets of spindle cells that were positive for glial fibrillary acidic and S-100 proteins. Ultrastructural examination showed characteristic ependymal features, including intracytoplasmic intermediate filaments, prominent intercellular junctions, numerous slender surface microvilli, and microvilli-lined lumina. Accurate recognition of the ependymal nature of this spindle neoplasm requires a high index of suspicion. Because the spindle cells are immu-noreactive with antibodies to both glial fibrillary acidic and S-100 proteins, ultrastructural confirmation of ependymal features is necessary.     

Pigmented composite paraganglioma-ganglioneuroma of the urinary bladder

We report a case of a pigmented composite paraganglioma-ganglioneuroma of the urinary bladder in a 70-year-old female. Grossly, the tumor measured 6.5 cm in diameter and had arisen from the base of the urinary bladder. Histologically, the tumor was composed of approximately equal components of paraganglioma and ganglioneuroma, which were partly separated and partly mixed, and intermingled with each other. There were foci of ample dark brown pigmentation in the cytoplasm of chromaffin paraganglioma cells. The pigment was Masson-Fontana-positive and had been bleached by hydrogen peroxide (H2O2). Electron microscopy showed large, abundant, pleomorphic electron-dense granules consistent with neuromelanin. In addition, there were numerous electron-dense neurosecretory-type granules. Neuromelanin, melanin or lipofuscin are occasionally observed in paragangliomas, although the occurrence of these pigments has never been described in a composite tumor originating from either adrenal medulla or extraadrenal paraganglia. To the best of our knowledge, our report represents the first case of pigmented composite paraganglioma-ganglioneuroma and expands the morphological spectrum of these unusual tumors.     

C-Kit-positive metastatic malignant pigmented clear-cell epithelioid tumor arising from the kidney in a child without tuberous sclerosis

We report the first pediatric case of malignant pigmented epithelioid clear-cell tumor arising from kidney; the lesion occurred in a 12-year-old girl without tuberous sclerosis. The tumor was widely metastatic to the retroperitoneum and chest, and the patient died of the disease 9 months after diagnosis, despite active chemotherapy. Pigmented epithelioid clear-cell tumor of the kidney is a rare variant of epithelioid angiomyolipoma and a member of the family of perivascular epithelioid cell tumors (PEComas). The tumor demonstrated overlapping features between clear-cell sugar tumor and epithelioid variant of angiomyolipoma. Tumor cells were positive for HMB-45 expression, negative for any evidence of muscular differentiation, and contained melanin pigment and premelanosomes in the cytoplasm. Diffuse C-Kit (CD117) positivity was identified throughout the tumor. This is the first report of C-Kit–positive malignant PEComas.     

Pigmented neuroendocrine tumor of the lung,showing neuromelanin

A pigmented neuroendocrine tumor was discovered incidentally in a 62-year-old woman through examination by chest computed tomography. The tumor was located in the left lower lobe, S6, of the lung and was 8 mm in diameter. The preoperative percutaneous needle biopsy was interpreted as a tumor suggestive of small cell carcinoma. Histological examination of the operated lobectomy material revealed that the nodule was a neuroendocrine tumor consisting of mainly spindle-shaped cells and several pigmented cells. Electron microscopy showed several dense-core neurosecretory-type granules in tumor cells, as well as abundant, pleomorphic electron-dense granules in pigmented cells much larger in size and most consistent with lipofuscin or neuromelanin. No melanosomes or premelanosomes were identified. Considering the result of ultrastructural and histochemical studies, the pigment was considered most likely neuromelanin. Neuromelanin is found in neurons of substantia nigra and locus ceruleus, and sympathetic ganglion cells. It is rarely found in neuroendocrine tumors and we review the available reports regarding pigmented carcinoid tumor.