Kyung-Whan Min

The effect of anabolic steroids on the biomechanical and histological properties of rat tendon.

Twenty-four male rats were divided into four groups, with anabolic steroids and exercise as variables. Biomechanical tests and histological evaluations were performed. The results of the biomechanical tests suggested that anabolic steroids produce a stiffer tendon, which fails with less elongation. The energy at the time when the tendon failed, the toe-limit elongation, and the elongation at the time of the first failure were all affected significantly. Changes in the force at failure were not statistically significant. No alterations of structure were noted when the specimens were viewed with light microscopy. Alterations of the sizes of the collagen fibrils were noted on electron microscopy.

Clear cell ependymoma: a mimic of oligodendroglioma: clinicopathologic and ultrastructural considerations.

Although clear cells resembling oligodendrocytes are known to occur in ependymomas, tumors composed primarily of such cells, i.e., clear cell ependymoma (CCE), are rare. Herein we characterize the clinicopathologic features of eight examples of CCE encountered at Mayo Clinic from 1983 to 1996. The tumors occurred in patients 3-31 years of age and presented as well-demarcated, deeply situated, contrast-enhancing masses, all of which were supratentorial. All but one case lacked classic light microscopic features of ependymoma. Although nearly all were immunoreactive for glial fibrillary acidic protein, it was electron microscopy that showed the diagnostic hallmarks of ependymoma, including complex intercellular junctions, surface microvilli and cilia, and microrosette formation, thus underscoring the importance of electron microscopy in the diagnosis of clear cell ependymomas. The differential diagnosis of CCE includes not only oligodendroglioma, but central neurocytoma and glioneurocytoma. Unlike oligodendrogliomas, CCEs are characterized by their sharp circumscription, hypervascularity as reflected in contrast enhancement on computed tomography and magnetic resonance imaging, their noninfiltrative pattern of growth that displaces parenchyma, and the occasional formation of vague perivascular pseudorosettes. Unlike central neurocytomas and glioneurocytomas, CCE lack secretory granules, vesicles, and synapses by electron microscopy and neuroendocrine markers by immunocytochemistry. In summary, the diagnosis of CCE requires neuroimaging, histologic, and ultrastructural correlation. The latter is essential in a limited biopsy. Ultrastructural studies also play a role in identifying glioneurocytomas. CCEs behave like more ordinary ependymomas. The importance of their recognition is the avoidance of alternative diagnoses and inappropriate therapies.

Skeinoid fibers: an ultrastructural marker of neurogenic spindle cell tumors.

The article describes novel stromal fibrillar aggregates found in three cases of neurogenic spindle cell tumor and eight cases of small intestinal stromal tumor. The aggregates were composed of tangles of curvilinear fluffy fibrils with a periodicity of from 41 to 48 nm with a staining pattern similar to that of collagen fibrils. The overall ultrastructural appearance simulated skeins of yarn, hence they are designated skeinoid fibers. No similar stromal fibers were found in more than 5000 other tumors studied. Their exclusive presence in neurogenic spindle cell tumors suggests the possibility that they are an ultrastructural marker for neurogenic spindle cell tumors and that the eight cases of small intestinal stromal tumors with skeinoid fibers may be of neurogenic origin.

Small Intestinal Stromal Tumors with Skeinoid Fibers in Neurofibromatosis: Report of Four Cases with Ultrastructural Study of Skeinoid Fibers from Paraffin Blocks

Small intestinal stromal tumors (SIST) with skeinoid fibers (SF) are reported in four patients with neurofibromatosis. SF appeared as intercellular eosinophilic globules that stained positively on periodic acid-Schiff stain and bluish on Masson trichrome stain, like those reported previously. Electron microscopic confirmation of SF was carried out on tissue retrieved from paraffin blocks, which revealed diagnostic ultrastructural features of SF. The association of SIST with SF and neurofibromatosis enhances the diagnostic value of SF as a marker of neurogenic spindle cell tumors. This study also underscores the importance of electron microscopy for differentiation of SF from pseudoskeinoid structures, which may mimic SF on light microscopic examination.

Ossifying Fibromyxoid Tumor: Modified Myoepithelial Cell Tumor? Report of Three Cases with Immunohistochemical and Electron Microscopic Studies

Ossifying fibromyxoid tumors (OFMT) are rare soft tissue tumors of uncertain histogenesis and clinical behavior. Since Enzinger, Weiss, and Liang first described 59 examples in 1989 (Am Surg Pathol. 13:817–827), approximately 150 cases have been reported. Their clinicopathologic features are fairly well characterized and their histogenesis remains unknown. Three examples of soft tissue tumors with typical histopathologic characteristics of OFMT were studied: case 1, a 43-year-old female with a 2.5-cm tumor of the back; case 2, a 56-year-old man with an 8-cm thigh mass; and case 3, an 81-year-old female with a 13.5-cm buttock tumor. For immunohistochemistry, formalin-fixed, paraffin-embedded tissue sections were stained with antibodies against cytokeratin, smooth muscle actin, desmin, vimentin, S-100 protein, EMA, and collagen type IV using standard ABC-peroxidase methods. For electron microscopy, tissue samples fixed in EM-grade buffered formalin were processed according to routine methods. Immunohistochemistry showed that the tumor cells were positive for vimentin and S-100 protein in all 3 cases. Stains for collagen type IV revealed diffusely positive staining in the stroma with a tendency for stronger staining around the cell borders in 2 out of 3 cases. Desmin was positive in one and actin was positive in one other case. By electron microscopy, tumor cells were characterized by centrally located round to oval nuclei with varying amounts of cytoplasm containing scanty cytoplasmic organelles. There were rare profiles of rough-surfaced endoplasmic reticulum (RER) and rare mitochondria with areas of condensed intermediate filaments. No tonofilaments or actin filaments were present. There were multiple short web-like processes, some of which were attached to that of neighboring cells by primitive cell junctions. In all 3 cases, lesional cells showed external lamina (EL), which was abundant in case 1, forming redundant scrolls frequently. In case 2, EL was less prominent and incomplete, and interrupted portions of EL were present only along the periphery of cell columns or nests bordering the stroma. In case 3, which behaved as a malignant tumor, the tumor cells were less differentiated spindle cells with primitive cellular features, and EL was rarely found along the short span of tumor cell borders. In this study, tumor cells in OFMT were polygonal to stellate often with multiple short cytoplasmic processes. The tumor cells were found to form cell clusters attached by primitive intercellular junctions between cytoplasmic processes forming intercellular bridges. The cell borders facing the stroma around cell clusters tended to be flat and had incomplete EL, while no EL was present along the cell borders facing the inner aspect of cell clusters. These ultrastructural findings together with immunophenotypic expression of S-100 protein presented closer resemblance to those of modified myoepithelial cells in pleomorphic adenomas of salivary glands and skin appendages rather than peripheral nerve sheath tumors. The authors conclude that these findings render more support to the hypothesis of myoepithelial histogenesis of OFMT. They also conclude that ultrastructural study not only helps accurate diagnosis, but also may aid in predicting malignant behavior by the degree of deviation from the typical examples of OFMT.

Oligodendroglioma: The Ultrastructural Spectrum

Oligodendroglia, so designated by del Rio Hortega1 on the basis of their cytology, particularly their scant processes, were subsequently postulated by Bailey and Cushing2 to be the progenitors of oligodendrogliomas. The latter authors encountered 9 such tumors in their series of gliomas. Accordingly, they formulated the following description, “Oligodendroglioma is a cellular tumor of peculiar type in which fibrillar astrocytes occasionally appear and the neoplastic cells have spherical nuclei with a heavy chromatin network, and are surrounded by a ring of cytoplasm which stains very feebly by ordinary staining methods. Between the cells is an indefinite material which stains neither for neu-rofibrillae, neuroglia, nor for connective tissue. This material may give the growth somewhat the appearance of the cross-section of a plant. No mitotic figures can be seen. These tumors are prone to become calcified.”

Intestitial Cells of Cajal in the Human Small Intestine: Immunochemical and Ultrastructural Study

The stem cell kinase CD117 has recently been found to play an important role in the development of interstitial cells of Cajal (ICC), which are currently regarded as pacemaker cells of the gastrointestinal tract. CD117 is expressed in both gastrointestinal stromal tumors (GIST) and ICC, with the latter regarded by many as the progenitor cells of GIST. The authors investigated immunoreactivity of 25 normal surgically removed small intestinal tissues and correlated the findings with electron microscopy (EM) on 12 cases. In all cases CD117-positive cells were frequently seen around the myenteric plexi either singly or in groups. CD117-positive cells on immunostained sections corresponded to the cells appearing as fibroblast-like or undifferentiated primitive mesenchymal cells around the myenteric ganglia and interstitial spaces by EM. In contrast, S-100 stain revealed a fine network of positive staining throughout the muscularis. Branches of nonmyelinated axons and nerve endings were found regularly between myocytes with direct contact with muscle cells by EM. The cells that we could depict as ICC because of their distribution andstaining pattern of CD117 were limited to the nonmuscular mesenchymal cells. No muscle cell-like ICC were found. Instead, the muscle cells in direct contact with nerve endings were often disfigured and the cytoarchitectural contents for muscle cells became less distinct because of lighter staining and loss of definite focal densities among actin filaments. However, these latter cells did maintain most muscle cell features, such as continuous external lamina, caveolae, and some of the peripheral densities. These findings raise a possibility that previous investigators could have included these altered muscle cells into the ICC group. It was also found that intestinal muscularis not only was richly endowed with an elaborate neural network of delicate axonal extensions and dense-core granule containing nerve endings traversing through and between myocytes, but also showed frequent synapse-like direct contact between nerve endings and muscle cells. These findings indicate that enteric nerves may play a major role in the control of intestinal motility, while CD117-positive cells play an accessory role as cells of Cajal as originally speculated. Further studies are necessary to better define and characterize interstitial cells of Cajal, which will be useful in the correlation of the vast number of data concerning the possible role of CD117-positive ICC in the pacemaker function of the intestine and oncogenesis of GIST.

Postirradiation epithelioid angiosarcoma of the breast: A case report with immunohistochemical and electron microscopic study

A case of postirradiation epithelioid angiosarcoma of the breast in a 72-year-old woman is reported. She had had right breast conserving surgery, axillary lymph node dissection, and 50 Gy external beam radiation therapy for infiltrating ductal carcinoma. A skin lesion on the irradiated breast appeared 5 years after completion of radiation. Angiosarcoma was diagnosed in a contralateral axillary mass 8 months later. Light microscopically, the tumor was characterized by a sheet-like growth of epithelioid cells with focal vasoformative areas. Tumor cells were reactive for factor VIII-related antigen, cytokeratin and CD34. Electron microscopically, the tumor cells were round with smooth cell borders. They were closely apposed, occasionally forming a small lumen containing single red blood cells or aggregates of platelets. Groups of tumor cells were enclosed by an external lamina. The tumor cells had abundant cytoplasm with sparse organelles. Rare suggestive Weibel-Palade bodies were present. The immunohistochemical and ultrastructural findings in this postirradiation tumor were in agreement with previously reported findings in non-irradiation-induced epithelioid angiosarcomas.

Peculiar cytoplasmic inclusions in oncocytic adrenal cortical tumors: An electron microscopic observation

Two cases of an oncocytic adrenal cortical tumor that contained peculiar cytoplasmic crystalline inclusions in the tumor cells are presented. The patients were 49- and 72-year-old females without clinical and biochemical evidence of adrenal cortical or medullary dysfunction. The adrenal tumors weighed 80 and 200 g each. These crystalline inclusions were present in groups of longitudinal profiles or clusters of crossly cut aggregates. They appeared in clusters of membrane-bound columns. On longitudinal sections, they appeared as rigid rods of homogenous density measuring 36 nm in width, but when they were cut transversely their paracrystalline nature became apparent. They were composed of closely packed microtubules in rectangular blocks. The microtubules measured 12.5 nm with a hollow center measuring 4.2 nm. The inclusions were within the membrane-bound cisterna of rough-surfaced endoplasmic reticulum. The significance of these inclusions is not clearly understood; however, they have been seen only in adrenal cortical tumors and their presence may be helpful in the differential diagnosis of adrenal oncocytic tumors. One patient presented with a tumor in which gross and microscopic appearance was compatible with a pheochromocytoma. This case exhibited an oncocytic appearance and pronounced cellular pleomorphism. Ultrastructural studies were necessary to recognize the tumor cells as cortical cells. The tumor cells contained abundant mitochondria with tubular cristae, paranuclear parallel stacks of granular endoplasmic reticulum, and relatively prominent smooth endoplasmic reticulum. These features are typical of adrenocortical cells. In addition, frequent tumor cells contained the peculiar cytoplasmic inclusions herein described.

Pineal germinomas and testicular seminoma: a comparative ultrastructural study with special references to early carcinomatous transformation.

We have investigated the ultrastructural characteristics of 16 cases of pineal germinomas and compared them with those of 18 cases of testicular seminomas. Glandular differentiation of tumor cells was found in both though it was more consistently noted in pineal germinomas than in testicular seminomas. This feature was interpreted to represent early carcinomatous transformation of germinoma cells. It not only explains the difficulties occasionally encountered in distinguishing germinoma and its anaplastic variant from embryonal carcinoma, but also has implications for our understanding of germ cell neoplasia, particularly the place of germinoma/seminoma in the nosology of such tumors.