Dermatopathic lymphadenopathy. Electronmicroscopic, enzyme-histochemical and immunohistochemical study

Dermatopathic lymphadenopathy (DPL) is characterized by lymph node enlargement with reactive process and is generally caused by chronic inflammatory skin disease. Interdigitating reticulum cells (IDCs) with broad cytoplasm, innumerable cytoplasmic interdigitation, and bizarre shaped nuclei are the most striking cell type in DPL. According to the shape of the nucleus, arrangement of the tubulovesicular complexes (TVC) and amount of melanin granules, these cells fall into two types: type I has a marked indented nucleus, innumerable TVC and some desmosomal junctions and fewer melanin granules, while type II has a large amount of melanin granules. On the other hand, LCs contain a few loose melanin granules. It appears that IDCs and Langerhans cells (LCs), surrounded by T-lymphocytes, are similar in morphology and function, but both of them can be characterized by the positive of S-100 protein and Leu 6, absence of lysozymes and CEA by PAP method, and positive of ATP-ase and ACP-ase, and they differ only by having or not having Birbeck granules. The mechanism of the proliferation of IDCs in DPL and delineation of the functional relationship between the accessory cells and the T-lymphocytes remains to be investigated.     

DERMATOPATHIC LYMPHADENOPATHY

Dermatopathic lymphadenopathy (DPL) is characterized by lymph node enlargement with reactive process and is generally caused by chronic inflammatory skin disease. Interdigitating reticulum cells (IDCs) with broad cytoplasm, innumerable cytoplasmic interdigitation, and bizarre shaped nuclei are the most striking cell type in DPL. According to the shape of the nucleus, arrangement of the tubulovesicular complexes (TVC) and amount of melanin granules, these cells fall into two types: type I has a marked indented nucleus, innumerable TVC and some desmosomal junctions and fewer melanin granules, while type II has a large amount of melanin granules. On the other hand, LCs contain a few loose melanin granules. It appears that IDCs and Langer-hans cells (LCs), surrounded by T-lymphocytes, are similar in morphology and function, but both of them can be characterized by the positive of S-100 protein and Leu 6, absence of lysozymes and CEA by PAP method, and positive of ATP-ase and ACP-ase, and they differ only by having or not having Birbeck granules. The mechanism of the proliferation of IDCs in DPL and delineation of the functional relationship between the accessory cells and the T-lymphocytes remains to be investigated. ACTA PATHOL. JPN. 37:887–900, 1987.     

Indeterminate cell tumor of the spleen

Indeterminate cell tumor is an extremely rare neoplasm that mainly occurs in the skin. We report a case of indeterminate cell tumor arising from the spleen, a previously unreported site for indeterminate cell tumor. Histologically, the tumor showed nests, nodules, and sheets of large polygonal cells with mostly oval nuclei; open chromatin; variable nucleoli; and abundant, eosinophilic cytoplasm. Some cells possessed irregularly convoluted nuclei with nuclear grooves and granular cytoplasm, suggestive of Langerhans cells. Immunohistochemically, the tumor cells were diffusely positive for S-100 and CD1a and negative for Langerin. No Birbeck granules were found by electron microscopy. Clinical and radiologic examination showed no other organomegaly or lymphadenopathy. A diagnosis of primary indeterminate cell tumor of the spleen was rendered. To the best of our knowledge, this is the first indeterminate cell tumor reported in the spleen. Biologic insights into dendritic cells in the spleen and the pertinent literature on these entities are reviewed.     

Malignant eccrine spiradenoma with florid squamous differentiation.

Malignant eccrine spiradenoma (MES) is an exceedingly rare neoplasm of cutaneous adnexal origin. To date, 31 cases have been documented in the literature. We herein report an additional case of MES that arose in longstanding eccrine spiradenoma (ES). A 54-year-old woman was seen for a bluish nodular mass on the right flank that previously had been stable for 7 to 8 years and had recently increased in size and become tender. The excised mass (2.8 x 2.5 x 2.5 cm) had no attachment to the overlying epidermis. Microscopically, 2 to 3 sharply demarcated lobules were surrounded by a markedly thickened and hyalinized fibrous capsule. Of the lesion removed, approximately 20% of the tumor showed typical histologic features of benign ES. In the remaining malignant areas, the typical configuration of benign counterpart, consisting of peripheral rows of small dark basaloid cells and central layers of large pale cells partially forming lumina, was replaced with a massive solid proliferation of large pale cells showing nuclear pleomorphism, prominent nucleoli, increased mitotic activity (reaching 12/10 HPF) and loss of PAS-positive basement membrane. There were multiple foci of florid squamous differentiation in the malignant portion. Cytokeratin, focally S-100 and EMA were expressed in large pale cells, whereas alpha smooth muscle actin and S-100 were positive in small dark basaloid cells. Focal reactivity of CEA and EMA was found in the central lumina. P53 was not expressed in benign areas, whilst in malignant areas an occasional nuclear reaction was disclosed.     

Ovarian Myxoma: Ultrastructural and Immunohistochemical Findings

The ultrastructural and immunohistochemical findings are reported in two ovarian myxomas, one of which was also associated with a sclerosing stromal tumor of the same ovary. Both neoplasms showed a myxoid, moderately cellular proliferation of spindle and stellate cells interspersed with areas of fibrosis and hemorrhage as well as delicate vascular spaces. Ultrastructurally, stellate neoplastic cells with irregular nuclei and occasional nucleoli were embedded in a mucinous and loose collagen matrix. Their cytoplasm showed abundant intracytoplasmic thin filaments that rarely condensed into poorly formed dense bodies. These thin filaments correlated with immunoreactivity for musclespecific actin and vimentin. The neoplastic cells showed no immunoreactivity with antibodies to desmin, S-100 protein, cytokeratin AE1 :AE3, factor Vlll-related protein, or placental alkaline phosphatase. These ultrastructural and immunohistochemical findings are consistent with myofibroblastic differentiation. These ancillary studies exclude important, clinically more aggressive differential considerations such as myxoid rhabdomyosarcoma, myxoid liposarcoma, myxoid neural tumors, mucinous adenocarcinoma showing pseudomyxomatous change, and myxoid-appearing endodermal sinus (yolk sac) tumor.     

Malignant peripheral nerve sheath tumor with prominent intracytoplasmic vacuolation: Report of a case

A case of malignant peripheral nerve sheath tumor with uncommon features is reported. A mass was noted in the left thigh of a 16 year old man. Histologically, most areas of the tumor exhibited the typical appearance of malignant peripheral nerve sheath tumor, but some tumor cells had rounded nuclei and cytoplasm, resembling an epithelioid pattern. It was noted that some rounded tumor cells showed prominent intracytoplasmic vacuolation. Immunohistochemically, almost all of the tumor cells, including the rounded and vacuolated ones, were positive for S-100 protein and vimentin. Electron microscopic study revealed well-developed cytoplasmic processes, intracytoplasmic intermediate-sized filaments, basement lamina formation and extracellular long-spacing collagens. These findings were compatible with those of Schwann cell differentiation. Moreover, ultrastructurally, the vacuolated spaces contained a few granular materials and were derived from the dilatation of the rough endoplasmic reticulum. It is speculated that intracytoplasmic vacuolation in malignant peripheral nerve sheath tumor would be caused by degeneration of the tumor cells.     

Renal Oncocytoma with Intracytoplasmic Lumina: A Case Report with Ultrastructural Findings of "Oncoblasts"

The authors present a case of renal oncocytoma with numerous intracytoplasmic lumina in a 45-year-old woman, with an emphasis on the ultrastructural findings of so-called oncoblasts. The tumor was located in the upper pole of the left kidney, measuring about 3.3 cm in diameter. Histologically, it was composed of solid nests or acinar growths of so-called oncocytic tumor cells with numerous intracytoplasmic lumina and scattered foci of so-called oncoblasts. The luminal surface was positive for Halés colloidal iron stain. A very small number of glycogen-containing cells were found scattered in a few nests. Immunohistochemically, tumor cells were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and carcinoembryonic antigen. The Ki-67 labeling index was 1.2%. All of the Ki-67-positive cells were oncocytes. So-called oncoblasts were negative for Ki-67. Ultrastructural examination revealed that the predominant tumor cells had cytoplasm packed with round mitochondria and the mitochodria had lamellar long cristae. So-called oncoblasts showed scant cytoplasm with a moderate numberof small mitochondria. Someof themshowed pyknosis which can be regarded as mitochondrial involution. The authors believe that so-called oncoblasts are damaged or involuted oncocytes rather than precursors of oncocytes.     

Eosinophilic granuloma of lymph node. A case report

Eosinophilic granuloma confined to the lymph node of a 25-year-old Japanese woman is reported. She presented with a low-grade fever and pain in the left cervical region. A finger-tip-sized cervical lymph node was excised for histological study. Microscopically, the normal architecture of the lymph node was distorted, and histiocytoid cells had proliferated mainly in the sinus. Numerous eosinophils and an appreciable number of large multinucleated cells were also observed. Ultrastructurally, Birbeck granules were found in the cytoplasm of the histiocytoid cells. Immunohistochemically, the proliferating cells and multinucleated cells were found to be positive for S-100 protein but negative for lysozyme in the cytoplasm. The patient has been well without recurrence for 10 months after the lymph node biopsy.     

Extraskeletal myxoid chondrosarcoma: a clinicopathological study of six cases]

The clinicopathologic, ultrastructural, and immunohistochemical features of six cases of extraskeletal myxoid chondrosarcoma are described. Light microscopic examination disclosed a lobulated neoplasm consisting of cells that tended to be round or polygonal with plenty of eosinophilic cytoplasm. The tumor cells were arranged in strands and small nests surrounded by abundant myxoid extracellular matrix. Ultrastructurally, these tumor cells displayed the signs of chondroblastic differentiation. The cytoplasm contained numerous rough endoplasmic reticulum, mitochondria and scattered glycogen granules. The intercellular matrix showed amorphous material and electronic dense and fine granules. The tumor cells in all these six cases showed diffuse immunostaining for S-100 protein but were negative for keratin. The data obtained tend to support the chondroblastic origin of this tumor.     

Alveolar Variant of Invasive Lobular Carcinoma of the Breast: An Electron Microscopic Study

Four cases of alveolar variant of invasive lobular carcinoma of the breast were examined by electron microscopy, and their appearance compared with those of in situ and classical invasive lobular carcinoma. The individual tumor cells in the alveolar variant were basically similar to those described in the other two lobular tumors. The neoplastic alveoli consisted mostly of light cells, although a few dark cells were sometimes seen at the periphery. The nuclei were large, rounded and rich in euchromatin. The cytoplasm contained a variable amount of mitochondria and endoplasmic reticulum, and a few cells had intracytoplasmic filaments. Numerous tumor cells with membrane-bound electron-dense granules were occasionally seen. A few cells also had intracytoplasmic lumina. Tumor cells were usually seen in close contact with each other. Interdigitating processes and desmosomes were present. In general the tumor cells were not surrounded by basal lamina, but most alveoli were surrounded by elongated fibroblasts or myofibroblasts. These findings confirm both the lobular and the invasive nature of this distinct variant of breast carcinoma.     

结肠嗜酸细胞癌2例临床病理分析

目的 探讨结肠嗜酸细胞癌的病理组织学特点、诊断及鉴别诊断。方法 对2例结肠嗜酸细胞癌手术切除标本进行光镜、免疫组化染色及电镜观察。结果 结肠嗜酸细胞癌组织学特点为细胞圆形、多边形,胞质丰富,胞质内见弥漫分布的强嗜酸性颗粒,细胞核中度异型性,核仁明显;癌细胞呈巢状排列,伴有腺管及乳头形成。免疫表型：癌细胞CK19、EMA阳性表达,不表达SMA、S-100蛋白及CgA。PAS染色阴性。电镜观察细胞质充满大量线粒体,缺乏内分泌及外分泌颗粒。结论 嗜酸细胞癌是不同于低分化腺癌及神经内分泌癌的一种特殊类型细胞癌。     

Renal oncocytoma with intracytoplasmic lumina: a case report with ultrastructural findings of "oncoblasts".

The authors present a case of renal oncocytoma with numerous intracytoplasmic lumina in a 45-year-old woman, with an emphasis on the ultrastructural findings of so-called oncoblasts. The tumor was located in the upper pole of the left kidney, measuring about 3.3 cm in diameter. Histologically, it was composed of solid nests or acinar growths of so-called oncocytic tumor cells with numerous intracytoplasmic lumina and scattered foci of so-called oncoblasts. The luminal surface was positive for Hale's colloidal iron stain. A very small number of glycogen-containing cells were found scattered in a few nests. Immunohistochemically, tumor cells were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and carcinoembryonic antigen. The Ki-67 labeling index was 1.2%. All of the Ki-67-positive cells were oncocytes. So-called oncoblasts were negative for Ki-67. Ultrastructural examination revealed that the predominant tumor cells had cytoplasm packed with round mitochondria and the mitochodria had lamellar long cristae. So-called oncoblasts showed scant cytoplasm with a moderate number of small mitochondria. Some of them showed pyknosis which can be regarded as mitochondrial involution. The authors believe that so-called oncoblasts are damaged or involuted oncocytes rather than precursors of oncocytes.     

Chondroid syringoma (mixed tumor of the skin). A clinicopathological study of 13 cases

The clinicopathology of 13 cases of chondroid syringoma were examined. The ages of the patients ranged from 26 to 86 years, with an average of 48 years. There were eight males and five females. Ten tumors out of the thirteen appeared on the face. Only one patient out of ten was suspected of recurrence in follow-up information. Histologically, all tumors consisted of epithelial cells, chondroid or myxoid matrix, and other strumal elements. The tumors were histologically classified into two types; twelve tumors had tubular and cystic lumina lined by two layers of epithelial cells, and only one case had small lumina lined by only a single layer. By an immunohistochemical study with a PAP method, positive stainings of keratin were observed in all cases, and S-100 protein in all but one. Ultrastructurally, the tumor cells showed features of an epithelial cell. Some ultrastructural differences were noted between two types of chondroid syringoma. Type I tumor cells had many tonofilaments in cytoplasm, but cytoplasmic filaments in type II were of the intermediate-type.     

Clear cell papulosis of the skin: a case report from Singapore

Clear cell papulosis of the skin is a rare condition; to our knowledge only 12 cases have been reported. Here, we report for the first time a case of clear cell papulosis with cytokeratin 7 expression and provide a comprehensive literature review. A 16-month-old girl presented with 3 hypopigmented lesions in the pubic region that were 3 to 9 mm in diameter; 1 lesion was papular, and the other 2 were macular. A skin biopsy revealed acanthosis with a proliferation of clear cells along the basal and suprabasal layers of the epidermis occurring in small clusters and singly. The cells had round to oval regular nuclei with abundant to moderate lightly eosinophilic to clear cytoplasm and intracytoplasmic mucin. Immunostaining produced positive results for carcinoembryonic antigen, AE1/3, epithelial membrane antigen, cell adhesion molecule 5.2, and cytokeratin 7 and negative results for gross cystic fluid disease protein, S100, and HMB-45. Clear cells of clear cell papulosis are mucin-positive and S100-negative glandular-secretory epithelial cells with histogenetic features of Toker cells of nipple and Paget cells. Immunohistochemical features support an eccrine secretory cell origin because the clear cells are consistently and strongly positive for carcinoembryonic antigen, positive for cell adhesion molecule 5.2, and negative or rarely positive for gross cystic fluid disease protein.     

CHONDROID SYRINGOMA (MIXED TUMOR OF THE SKIN)

The clinicopathology of 13 cases of chondroid syringoma were examined. The ages of the patients ranged from 26 to 86 years, with an average of 48 years. There were eight males and five females. Ten tumors out of the thirteen appeared on the face. Only one patient out of ten was suspected of recurrence in follow-up information. Histologically, all tumors consisted of epithelial cells, chondroid or myxoid matrix, and other strumal elements. The tumors were histologically classified into two types; twelve tumors had tubular and cystic lumina lined by two layers of epithelial cells, and only one case had small lumina lined by only a single layer. By an immunohistochemical study with a PAP method, positive stainings of keratin were observed in all cases, and S-100 protein in all but one. Ultrastructurally, the tumor cells showed features of an epithelial cell. Some ultrastructural differences were noted between two types of chondroid syringoma. Type I tumor cells had many tonofilaments in cytoplasm, but cytoplasmic filaments in type II were of the intermediate-type.     

A case of basaloid-squamous carcinoma of the esophagus: Immunohistochemical and ultrastructural studies

A case of basaloid-squamous carcinoma of the esophagus in an 83 year old man is reported. The esophageal tumor showed a fungating growth at the junction of the middle and lower esophagus and was composed microscopically of submucosal multiple nests with solid and cribriform-like patterns accompanied with a small focus of squamous cell carcinoma adjacent to the overlying esophageal epithelium. The structural features closely resembled those of basaloid-squamous carcinoma. The submucosal tumor cells were immunohistochemicaliy positive for epithelial membrane antigen, wide spectral keratin, alpha actin and S-100 protein. By electron microscopy, the tumor cells had microvilli, des-mosomes and bundles of myofilaments, and replicated basement membranes were frequently observed adjacent to the nests. The positive immunoreaction of S-100 protein and alpha actin and the existence of bundles of myofilaments indicated that the present tumor did not correspond well with basaloid-squamous carcinoma. In addition, there was no evidence of true glandular lumina in the tumor nests, a finding which was inconsistent with that of adenoid cystic carcinoma. From the immunoreactivity of S-100 protein and ultrastructural features, it was considered that the present submucosal tumor had originated from undifferentiated pluripotential primitive cells, which differentiated to myoepithelial cells.     

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.     

Melanotic medullary thyroid carcinoma: A case report with review of the literature

Melanotic medullary thyroid carcinoma is morphologically defined by the presence of melanin deposits in the cytoplasm of tumor cells. It is an extremely rare variant with only 15 cases described in the literature to date and only one report of diagnosis by fine needle aspiration (FNA) biopsy. A 51-year-old woman presented with neck swelling. An ultrasound examination revealed a single solid nodule in the right thyroid lobe that measured 5.4 × 4.7 × 4.3 cm. Laboratory examination revealed elevated levels of serum calcitonin (8643.0 pg/ml), carcinoembryonic antigen (CEA) (86.2 ng/ml), and chromogranin A (123.2 ng/ml). An FNA biopsy of the thyroid nodule revealed predominantly single plasmacytoid cells with round to oval eccentric nuclei and dark brown intracytoplasmic granules. Immunohistochemical studies with Melan-A performed on a cell block slide confirmed that the granules contained melanin. The tumor cells were also positive for calcitonin, CEA, synaptophysin, AE1/AE3, CAM5.2, and HMB-45(focal); the tumor cells were negative for chromogranin, thyroglobulin, PAX8 and TTF-1. The diagnosis was reported as melanotic variant of medullary thyroid carcinoma. The patient underwent a total thyroidectomy which revealed tumor cell expression of insulinoma-associated protein 1 and confirmed neuroendocrine differentiation. Shortly after she presented with tumor recurrence in the thyroidectomy bed. The tumor cells were positive for only S100, SOX10, and Melan-A. Molecular analysis with the SEMA4 Solid Tumor Panel revealed mutations in the HRAS, PIK3CA, PIK3R1, MYC, and CCND3 genes. The final diagnosis was reported as melanocytic medullary thyroid carcinoma with high grade transformation and loss of epithelial and neuroendocrine expression.     

Subset of Vascular Dendritic Cells Transforming into Foam Cells in Human Atherosclerotic Lesions

It has been previously demonstrated that S-100 positive vascular dendritic cells are involved in human atherosclerosis and they usually show a low level of accumulation of lipids in their cytoplasm, even though they located among foam cells and cellular debris in atherosclerotic lesions. During ongoing immunohistochemical investigations, however, we have found that a few S-100 positive cells exhibited a foam cell appearance. Therefore, we undertook an electronmicroscopic examination to see if any foam cells exhibit the distinctive features of vascular dendritic cells such as the presence of dense granules and a tubulovesicular system uniquely found in well differentiated dendritic cells. Foam cells exhibiting the typical characteristics of vascular dendritic cells were indeed found. Their cytoplasm contained a large number of lipid vacuoles and cisterns of the tubulovesicular system as well as dense granules which, in contrast to lysosomes present in macrophages, did not transform into phagolysosomes. The formation of a central lamina inside cisterns of the tubulovesicular system was also detected. These pentalaminal structures, comprised of two parallel limiting membranes and a central lamina, are similar to the Birbeck granules present in human epidermal Langerhans cells. From our present observations we speculate that the defense mechanisms against extensive lipid accumulation may be broken in some vascular dendritic cells, causing them to transform into foam cells.     

Glassy-Cell Carcinoma of the Cervix: Case Report with a Light and Electron Microscopy Study

A case of glassy-cell carcinoma of the cervix is reported. In the literature the tumor is regarded as an undifferentiated form of mixed carcinomas of the cervix. At the light microscopic level the tumor cells are characterized by a moderate amount of cytoplasm of ground-glass appearance that stains faintly blue with hematoxylin, a distinct cell wall that stains with eosin or with periodic acid-Schiff (PAS), and large vesiculated nuclei with prominent nucleoli. In the cytoplasm of very few tumor cells, a minute amount of Alcian blue-positive material is demonstrated. At the electron microscopic level the tumor cells show distinct cell borders with interdigitating cytoplasmic projections that contain many desmosomes. Cytoplasmic tonofilaments were demonstrated in few tumor cells. The nuclei show a euchromatic appearance with prominent mesh-basket nucleoli. The cytoplasm contains abundant ribosomes, polyribosomes, and round to oval mitochondria with transverse cristae. Some cells contain a prominent Golgi apparatus with many lysosomelike structures. A very few cells have small intracytoplasmic lumina with microvilli and annulate lamellae. The assumption that the glassy-cell carcinoma of the cervix represents a poorly differentiated adenosquamous carcinoma finds support from our ultrastructural study.