Proliferating thymolipoma: ultrastructural, immunohistochemical, and flowcytometric study.

A superior-anterior mediastinal tumor was excised from a 50-year-old man. The 207-g mass was encapsulated and multilobulated. It contained adipose tissue and abnormal thymic tissue. In some areas the thymic tissue was characterized by cords and nests of epithelial cells lying within either the adipose tissue or a myxoid matrix. Other areas were characterized by cortical thymic tissue with increased numbers of epithelial cells. Foci of normal medullary tissue were present. The prominent epithelial cells were immunoreactive for cytokeratin and nonimmunoreactive for vimentin, S-100, chromogranin, and parathyroid hormone. Flow cytometry showed that the lymphocyte populations were consistent with a late cortical thymic phenotype. The tumor was diploid. By electron microscopy, the prominent epithelial cells had desmosomes and a few tonofilaments. The cytoplasm contained additional organelles including mitochondria, polyribosomes, and occasional lysosomes. Nuclei were oval and had relatively smooth contours, prominent nucleoli, and moderate quantities of heterochromatin. Basal lamina was present around many nests and cords of cells. This is the first such study of a tumor with this histology.

Urachal cystadenoma with abundant glycogen: ultrastructural study.

A cystadenoma arose in the urachus of a 32-year-old man. The mass was a multilocular cystic tumor filled with light yellow mucoid material. It was located in the anterior abdominal wall between the umbilicus and the dome of the urinary bladder. Overall, the mass was 14 cm x 8 cm x 5 cm, with the largest internal cyst being 6 cm in diameter. The lesion was characterized histologically by columnar cells with focal cellular and nuclear stratification. Ultrastructural examination revealed columnar cells with abundant glycogen, moderately pleomorphic microvilli without prominent filamentous cores, and apical mucin vacuoles. Nuclei had pleomorphic contours. An intact basal lamina was present. A similar urachal cystadenoma has not been described.

IDDM patients' sera recognize a novel 30-kD pancreatic autoantigen related to chymotrypsinogen.

We have examined, by western immunoblot analysis, the sera of 16 insulin-dependent diabetes mellitus patients (IDDM) for the presence of autoantibodies against proteins extracted from islet-cell enriched preparations of normal human pancreata. A novel putative autoantigen recognized by late stage IDDM patients sera was identified, and its amino acid sequence was partially determined. Islets of Langerhans were partially purified by a modified collagenase digestion procedure, and subsequent protein extracts were fractionated by one-dimensional or two-dimensional polyacrylamide gel electrophoresis (1-D or 2-D SDS-PAGE). Immunoblot analysis revealed a 30-kD species which was recognized by 4 of 16 IDDM patients sera, but none of 16 normal sera. The 30-kD protein, appeared as a single band on 1-D SDS-PAGE, but was resolved on 2-D gel electrophoresis as several distinct protein species with different isoelectric points (pI's), ranging from 7 to 9. The amino terminal sequence of one such species was partially determined by microsequencing, and the second through the fourteenth amino acids were found to be identical to the corresponding sequence in human chymotrypsinogen. The fifteenth through the eighteenth amino acids were different from the known chymotrypsinogen sequence. This region corresponds with the site that is cleaved to activate chymotrypsinogen. Based on the size and sequence homology, this antigen appears to be related to chymotrypsinogen. We conclude that this 30-kD species may be an autoantigen in some late stage IDDM patients.

Hepatoblastomas: an ultrastructural and immunohistochemical study.

Seven hepatoblastomas were studied by electron microscopy, and four of these were studied by immunohistochemistry. Five tumors were purely epithelial, and two were mixed epithelial-mesenchymal. They showed a spectrum of cellular differentiation ranging from primitive epithelial cells to differentiated cells resembling adult hepatocytes. Glycogen, lipid, basal lamina, and canaliculi were present in all cases. Mitochondria with large, membrane-bound, amorphous inclusions were present in one tumor, and large, complex, basal cell processes were present in two tumors. Ultrastructural features most characteristic of hepatocytes were most common in fetal type hepatoblastomas. Immunoreactive chromogranin cells were present in two tumors, one of which also contained immunoreactive somatostatin cells. The somatostatin-positive tumor had cells with granules resembling those seen in somatostatin-containing cells of normal pancreas and somatostatin-containing neuroendocrine carcinomas. Other immunoreactive substances were present, including alpha 1-antitrypsin (four cases), vimentin (embryonal cells in four cases; fetal cells in three cases), low-molecular weight cytokeratin (embryonal cells in three cases; fetal cells in four cases), and high-molecular weight cytokeratin (embryonal cells in one case; fetal cells in two cases). Osteoidlike material was positive for epithelial membrane antigen, vimentin, and S-100 protein.

Ultrastructure of the epidermal-dermal junction and cutaneous basal lamina in Bowen's disease.

Ten tissue sections from 10 examples of Bowen's disease were excised from paraffin blocks, rehydrated, and incubated in 90% formic acid at 45 degrees C for 18 h. The epidermis was gently removed with the aid of a dissecting microscope, and the remaining dermis with attached basal lamina was processed for scanning electron microscopy. This surface showed a well-preserved basal lamina. The dermal papillae in the areas of Bowen's disease were elongated and had frequent secondary protrusions. The normal 0.5 mu interconnecting corrugations were often replaced by either broad, coarse corrugations or by large areas of smooth-to-undulating basal lamina. This study demonstrates marked alterations in spatial interactions between neoplastic epidermis and underlying dermis in Bowen's disease.

Basal lamina fenestrations in the human colon: transmission and scanning electron microscope study.

Basal lamina at the interface between colonic epithelial cells and the lamina propria was exposed by incubating colonic specimens in 1% boric acid solutions. Examination of this epithelial-stromal interface by scanning electron microscopy (SEM) showed a smooth, slightly undulating basal lamina covering crypts and luminal surfaces. The basal lamina on the luminal surfaces had numerous round or ovoid fenestrations, most measuring 2.5-4.0 microns. These were continuous with channels in the collagen fiber network of the lamina propria. Except very near the surface, no fenestrations were found in the basal lamina lining the crypts. Transmission electron microscopy (TEM) of serial thin sections of colonic mucosa without the epithelial cells removed showed only a few actual basal lamina fenestrations. Rarely, epithelial cell processes extended into the lamina propria through the basal lamina. Most of the fenestrations seen by SEM appeared to correspond spatially by TEM to foci of close contact between the basal lamina and underlying fibroblastic cell processes. At these sites the basal lamina and fibroblastic cell process might be removed along with the overlying epithelial cells during processing with boric acid. These data support functional differences in epithelial-stromal interaction between cell populations lining the luminal surface and those making up the crypt lining and pericryptal fibroblast sheath. The TEM findings demonstrate that the human colonic basal lamina is not absolutely continuous and that the development of basal lamina fenestrations and epithelial cell processes extending into the lamina propria is not pathognomonic of neoplastic transformation and stromal invasion.

Pancreatic cystadenoma in an infant: ultrastructural study.

A 10 x 6 x 4 cm multicystic cystadenoma arose in the pancreas of a 4-month-old male. Microscopically, the cysts were lined by short columnar or cuboidal cells that contained neither mucin nor glycogen. The lining cells had occasional nucleoli, contained electron dense vacuoles and apical aggregates of filaments, and were associated with a basal lamina. This is the youngest patient reported as having pancreatic cystadenoma, and the ultrastructure of the neoplasm was different from the 6 previously studied adult cases, suggesting that infantile and adult cystadenomas are different in nature.

Papillomavirus-induced changes in the topography of the epidermal-dermal junction: a scanning electron microscopic study of basal lamina.

Papillomavirus infects human epidermal cells and causes verruca vulgaris, which is characterized by altered epidermal growth rates and differentiation patterns. There is also a prominent induced dermal proliferative response. Ten formalin-fixed skin specimens from 10 patients, each with histologically characteristic verruca vulgaris, were excised from paraffin blocks, deparaffinized in xylene, and rehydrated in graded ethanol solutions. Hydrated specimens were incubated in 90% formic acid at 45 degrees C for 18 h. Using a dissecting microscope the epidermis was gently separated from the dermis, which then was fixed in 3% glutaraldehyde and processed for scanning electron microscopy. Scanning electron microscopy showed a well-preserved epidermal-dermal junction (EDJ) covered by basal lamina. In comparison with normal EDJ, the EDJ of verruca vulgaris showed markedly elongated dermal papillae. Some papillae were broad and thin, and others were broad and thick. Irregularly shaped and branching secondary papillae were common. Also, there were changes in the basal lamina: the normal corrugation pattern was replaced by relatively smooth undulations or coarse, vertically oriented ridges on papillae. Papillary tips were often smooth. This study shows that there were prominent alterations in the topography of the EDJ and basal lamina in verruca vulgaris. This technique should be useful in evaluating epithelial-connective tissue morphologic interactions in formalin fixed archival tissue in other diseases characterized by alterations in epidermal growth rates and differentiation patterns.

Mucinous breast carcinomas with abundant intracytoplasmic mucin and neuroendocrine features: light microscopic, immunohistochemical, and ultrastructural study.

Eight mucinous carcinomas of the breast were studied by light microscopy and immunohistochemistry; one was studied by electron microscopy. All 8 cases had abundant, relatively clear cytoplasm that contained mucin. Cells were argyrophil positive and argentaffin negative. Eight cases were positive for neuron specific enolase (NSE), 5 cases for serotonin, 1 case for serotonin and somatostatin and 2 cases for serotonin, somatostatin, and gastrin. None had clinical evidence of abnormal neuroendocrine function. Three patients had axillary lymph node metastases. Only 1 of 5 patients in whom there was clinical followup died of her disease. Electron microscopy of one case showed abundant intracytoplasmic and extracellular mucin, round and pleomorphic dense-core granules, numerous cell processes, and aggregates of intermediate filaments. These cases expand the histologic spectrum of breast carcinomas which may show neuroendocrine differentiation.

Glycogen-rich clear cell carcinomas of the breast. A clinicopathologic and ultrastructural study.

Ten cases of glycogen-rich clear cell carcinoma of the breast are described. Only two previous case reports have been published. These neoplasms are composed of clear cells with abundant glycogen. Ultrastructurally, two cases showed large quantities of non-membrane-bound glycogen and numerous empty glycogen lakes. neoplastic cells formed tight junctions, immature desmosomes, and occasionally had short microvilli. In nine cases the glycogen-rich carcinoma grew in a solid pattern only, while one case had both solid and papillary patterns. One case was associated with a signet-ring cell carcinoma. Seven of nine patients who underwent axillary dissections had nodal metastases. Five patients died with residual disease, and one is currently alive with local skin recurrence. These data suggest that glycogen-rich clear cell carcinoma is associated with frequent lymph node metastases and mortality.

Ultrastructure of abnormal collagen in human tumors.

Abnormal collagen fibrils were identified by transmission electron microscopy in 22 human tumors of differing histogenesis. They were found in a review of 1400 electron microscopy cases. Abnormal collagen fibrils, described by others as amianthoid fibers, composite collagen, collagen flowers and intrafibrillar collagen dysplasia, have been found only rarely in human tumors but commonly in certain connective tissue diseases such as pseudoxanthoma elasticum, Ehlers-Danlos syndromes, Marfan's syndrome, osteoarthritic cartilage, and emphysematous lung among others. Abnormalities in the cases described here included thickened fibrils, fibrillar degeneration of fibrils and irregular external contours. Proposed mechanisms for their formation have included degeneration possibly due to hypoxia or collagenase activity, abnormal collagen biosynthesis, and abnormal tissue levels of glycosaminoglycans. The finding of abnormal collagen fibrils in these 22 human tumors shows that their occurrence is more common than is indicated by previous published reports. Most of the tumors containing abnormal collagen fibrils were mesenchymal or soft tissue tumors. Four neuroendocrine neoplasms had abnormal collagen fibrils.

Basal lamina at the epithelial-connective tissue junction in the rat forestomach, esophagus, tongue and palate: scanning electron microscopic study.

The squamous epithelium lining the rat foregut was removed by incubating fresh, unfixed specimens in 2N sodium bromide. The surface morphology of the exposed subepithelial basal lamina was examined by scanning electron microscopy. Areas examined included hard and soft palates, oropharynx, tongue, esophagus, and forestomach. The basal lamina was continuous were not present at all sites. The saucer-like defects of lymphocyte migration that are present in the basal lamina beneath the squamous epithelium of the skin were not observed in rat foregut. The epithelial-connective tissue interface of the rat esophagus does not have the coiled and branched papillae seen in esophagi of adult humans. The three dimensional shapes of the connective tissue cores of the various lingual papillae are well-demonstrated by this technique and are distinct. The basal lamina of the hard and soft palates are also distinct.

Villous papilloma of the gallbladder in association with leukodystrophy.

A 2-year-old girl with metachromatic leukodystrophy had an unusual papilloma of the gallbladder. The association of metachromatic leukodystrophy and gallbladder disease in children is recognized. The striking anemone-like configuration of this tumor is remarkably unlike those of other papillomas described in the literature.

Extrapulmonary oat-cell carcinoma of the tongue: an electron-microscopic study.

An extrapulmonary oat-cell carcinoma arose in the tongue of a 62-year-old man who had a long history of cigarette smoking and ethanol ingestion. At presentation, he had the primary tongue lesion and cervical lymph-node metastases only, and search for a pulmonary primary was negative. Ten months later he died with metastases to liver, cerebrum, ribs, vertebrae, calvarium, and clavicle. Electron microscopy demonstrated cells with cytoplasmic processes and many dense-core neurosecretory granules that had a tendency to concentrate in the processes. Cells were linked by desmosomes. Electron microscopy is necessary for definitive diagnosis of extrapulmonary oat-cell carcinomas.

Malignant sex cord-stromal tumor of testis.

We report a case of sex cord-stromal tumor in the testis, which metastasized to the retroperitoneal space, resulting in death 13 months after orchiectomy. The primary lesion consisted of granulosa cells, theca cells, Sertoli cells and undifferentiated gonadal stroma. Biopsy of the retroperitoneal metastasis showed predominance of the Sertoli cell component.

Migration of lymphocytes through the cutaneous basal lamina in normal skin: an ultrastructural study.

Incubation of skin in 2 N sodium bromide allows separation of dermal and epidermal layers leaving an intact basal lamina covering the dermal portion. Examination of the surface of the dermis by SEM shows cells migrating through the basal lamina. By scanning and transmission electron microscopy, these cells have the characteristics of lymphocytes. The migrating lymphocytes produce a sequence of basal lamina deformations including dome formation, effacement of corrugations, and central fenestrations with hole formation allowing lymphocyte passage. Following passage there is reestablishment of a relatively smooth basal lamina in the crater base, effacement of the crater rim, and finally reformation of basal lamina corrugations. This deformability of the basal lamina supports the hypothesis that basal lamina is thixotropic. This study is the first demonstration in three dimensions of lymphocyte traffic across the basal lamina, an important component of skin-associated lymphoid tissue (SALT).

Scanning electron microscopic study of the epithelial-mesenchymal junction of the esophagus.

This is a study of the appearance by scanning electron microscopy of the stromal papillae and basal lamina at the epithelial-mesenchymal junction of the human esophagus. After incubation in 2N sodium bromide at 60 degrees C. for 1 hour, the squamous epithelium was removed gently under the dissecting microscope from esophageal specimens from six normal human esophagi. The remaining stromal surface covered by an intact smooth basal lamina was examined "en face" by scanning electron microscopy. Transmission electron microscopy confirmed that the separation following NaBr was between the basal cell plasma membranes and the basal lamina, and that the basal lamina and subbasal connective tissue were well-preserved and attached normally to each other. Complex topographical patterns consisting of various numbers of simple and branched papillae and blade-like stromal folds were observed. Papillae had helical contours because of the spiral capillaries within them. Subepithelial capillaries were also visible as interconnecting linear ridges in the interpapillary zones. There was great variation in papillary length and patterns between individuals, but there was no difference in patterns or papillary length in sections taken from lower, middle, and upper portions of the esophagus in a given patient. These findings suggest that comparisons of absolute length of stromal papillae in different individuals should not be interpreted as a pathologic change. The results reveal an unexpected complexity in this epithelial-stromal interface.

Age-related changes in the cutaneous basal lamina: scanning electron microscopic study.

Scanning electron microscopy of human epidermal-dermal basal lamina demonstrated striking age-related changes. The basal lamina from abdominal skin was exposed in specimens from 26 humans by separation of epidermis and dermis after treatment with sodium bromide solutions. Transmission electron micrographs demonstrated the split to be in the lamina lucida. Scanning electron microscopy of mature epidermal-dermal junction and basal lamina showed distinct dermal valleys; tall, dome-shaped dermal papillae; and basal lamina arranged in prominent corrugations that tended to be oriented vertically on papillae and irregularly on interpapillary zones. Skin from subjects in their 7th through 10th decades demonstrated progressive loss of dermal valleys, flattening and widening of dermal papillae, and loss of basal lamina corrugations.

Peliosis of the spleen. Report of a case and review of the literature.

Peliotic lesions of the liver and spleen are rare and usually occur in patients with wasting diseases, such as tuberculosis and cancer, or in patients who have received treatment with anabolic-androgenic steroids. Peliosis appears grossly as blood-filled, cyst-like or nodular lesions, 1 to 5 mm in diameter, that are distributed throughout the parenchyma of the affected tissue but do not alter the size of the organ. Intraperitoneal rupture of a peliotic bleb can be fatal. Peliosis of the spleen usually occurs in conjunction with peliosis hepatis, but in this subject with myelofibrosis and myeloid metaplasia who underwent autopsy, the lesions were present only in the spleen.