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1/18. Initiation of ectopic epithelial calcification in a calcifying odontogenic cyst.

    Ultrastructural observation was performed on a calcifying odontogenic cyst (COC) associated with an odontoma and arising in the right mandibular region of an 8-year-old Japanese boy. Four types of cells were identified in the epithelial layer of the COC. The basal cells were low columnar in shape and contained some intracellular organelles. They were attached to the neighboring cells with a few desmosomes and resembled inner enamel epithelium of the normal enamel organ. The stellate reticulum-like cells, polygonal in shape, possessed desmosomes and many cytoplasmic projections. Some intracellular organelles and a few bundles of tonofilaments were observed in the cytoplasm. The light oval cells that were pale staining with toluidine blue contained dilated membranous organelles and many relatively evenly distributed tonofilaments. These cells were usually scattered in the vicinity of the focal accumulations of ghost cells, and the cell membrane was discontinuous in parts. The ghost cells contained many bundles of tonofilaments that were 60-240 nm in diameter and arranged in various directions. No intact intracellular organelles were noted in the cytoplasm. They were attached to the neighboring ghost cells with some desmosomes and their cell membrane was discontinuous in parts. A variety of vesicles, 90-450 nm in diameter, were scattered among the tonofilament bundles. Some of these contained needle-like crystals that were considered to be initial calcification sites in ghost cells. These vesicles presented morphological similarities to matrix vesicles, and it is therefore suggested that matrix vesicle-like structures are deeply involved with initiation of calcification of ghost cells in COC.
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2/18. Multifocal, nascent, and invasive myoepithelial carcinoma (malignant myoepithelioma) of the breast: an immunohistochemical and ultrastructural study.

    This report describes the light microscopic (LM), immunohistochemical (IHC), and electron microscopic (EM) features of a multifocal, nascent, and invasive myoepithelial carcinoma of the breast. By LM, the spindle cells disclosed fibrillar acidophilic cytoplasm, mild nuclear atypia, and a low mitotic index. Myoepithelial differentiation was established through IHC (single- and double-labeling techniques) and EM: periductal and infiltrating spindle cells coexpressed total muscle actin, alpha-smooth muscle actin, vimentin, cytokeratin 14, and pankeratin, and their EM features were characteristic of myoepithelial cells, i.e., perinuclear tonofilaments, subplasmalemmal bundles of microfilaments with dense bodies, intermediate junctions, poorly developed desmosomes, pinocytic vesicles, and fragmented external lamina. No invasive epithelial cells disclosed luminal differentiation (by LM, IHC, EM), identifying, thus, this neoplasm as a pure spindle cell myoepithelial carcinoma of the breast.
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3/18. adenomatoid tumor of the uterus: report of a case and review of the literature.

    A case of uterine adenomatoid tumor in a 47-year-old female was studied with both light and electron microscopes. The tumor was circumscribed, 2.5 cm in diameter, and located in the posterior wall of the uterus. In light microscopy, tumor cells showing "signet-ring" appearance arranged in cords or tubules. Hyaluronidase-sensitive acid mucopolysaccharide was present in the cells and luminal surfaces. Mucicarmine stain was negative and periodic acid-schiff reaction was faintly positive. In electron microscopy, the tumor showed basal laminae, well-developed desmosomes and numerous microvilli. Intercellular spaces were present between adjacent cells. Small intercellular spaces were separated from the large lumens by desmosomes and tight junctions, while large spaces communicated with the tubular lumens. Forty-four reported cases of adenomatoid tumor in females were briefly reviewed.
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4/18. Neuroendocrine carcinomas associated with squamous cell carcinomas of the uterine cervix: light and electron microscopic observations in two cases.

    Small cell carcinomas are rare in cervical cancers and appear to be a heterogeneous group of tumors. Neuroendocrine carcinoma of the cervix, one subtype of small cell carcinomas of the cervix, can be identified by characteristic light and electron microscopic criteria. Two cases of neuroendocrine carcinomas associated with squamous cell carcinomas of the uterine cervix are reported in which electron microscopic studies were performed. The presence of small dense-core membrane-bound granules (120 to 160 nm) in cytoplasmic process under electron microscopic observation confirmed the diagnosis of neuroendocrine carcinoma of the cervix. The coexistence of electron dense-core membrane-bound granules, abundant tonofibrils, and desmosomes within the cancer cells, suggests that these tumors may have derived from the multipotential precursor cells with neuroendocrine and squamous differentiation. Because neuroendocrine carcinomas appear to have the highest incidence of recurrence and the poorest prognosis, it is necessary to distinguish these neoplasms from squamous cell carcinomas of the cervix. literature about neuroendocrine carcinomas of the cervix is also reviewed.
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5/18. Merkel cell carcinoma of the head and neck associated with bowen's disease.

    The Merkel cell carcinoma occurs primarily in the skin of the head and neck, and develops in the dermis with a trabecular growth pattern. immunohistochemistry reveals positive staining for neuron-specific enolase, neurofilaments, cytokeratin and chromogranin a. Electron microscopically, the tumor cells contain dense-core granules, spinous cytoplasmic processes, desmosomes, zonulae adherentes and paranuclear filament aggregates besides frequent mitoses, focal necroses and lymphocyte and plasma cell infiltrates. The Merkel cell carcinoma is often co-existent with other malignancies such as squamous cell carcinoma or, as in the present study, with bowen's disease. The definite diagnosis of the Merkel cell carcinoma can be effected only by electron microscopic examination of the tumor.
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6/18. Primary multipotential malignant neoplasm of bone: chondrosarcoma associated with squamous cell carcinoma.

    A primary neoplasm of the proximal humerus in a 68-year-old woman was unique histologically in that it contained both malignant cartilaginous and squamous cell components. The epithelial differentiation was confirmed by the demonstration of keratin by immunohistochemical techniques and of basement membrane, tonofilaments, and well-formed desmosomes by electron microscopy. The patient died 3 1/2 years after the onset of symptoms, without clinical evidence of either a primary tumor elsewhere or metastasis. The differential diagnosis from other bone tumors with epithelial differentiation, such as adamantinoma and "primitive multipotential primary sarcoma," is discussed. This is a rare primary neoplasm of bone of unknown histogenesis. Intermutability or metaplasia between mesenchymal and epithelial tissues is a possibility. The tumor probably originated from multipotential stem cells with the ability to undergo biphasic or dual differentiation toward mesenchymal and epithelial elements.
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7/18. Multifocal malignant melanoma of the esophagus.

    We have described a case of primary melanoma of the esophagus in an asymptomatic patient. The tumor presented as a multinodular filling defect on a routine barium swallow. The distal esophagus and a proximal portion of the stomach were resected. The patient died ten days postoperatively of klebsiella sepsis. Grossly, the surgical specimen showed multiple polypoid tumors which arose from separate pigmented areas shown microscopically to be melanoma in situ. By electron microscopy, the tumor cells contained numerous melanosomes in various stages of melanization. Primitive hemidesmosomes were found where a basal lamina was present. Better developed desmosomes interconnected the melanocytes.
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8/18. Establishment and characterization of a human colon carcinoma cell line (KMS-4) from a patient with hereditary adenomatosis of the colon and rectum.

    A human colon carcinoma cell line was established from a metastatic lymph node of a patient with hereditary adenomatosis of the colon and rectum (ACR). Cells of this line, designated KMS-4, have been continuously propagated in culture during the past 24 months. The cells growing on the surface of culture dishes showed epithelial features, and, when inoculated into athymic nude mice, produced adenocarcinomas with a morphology similar to that of the original tumor. Electron micrographs showed that the cultured cells have desmosomes and numerous surface microvilli typical of colon epithelium. Chromosomal analysis revealed the cell line to be of human origin with a diploid mode of chromosome number, but the karyotypes examined were all abnormal. Most of the metaphases commonly had such abnormalities as 7p , 12p , 13, 16 and 17p , accompanied by loss of chromosome No. 19 and/or 20, and, interestingly, all the metaphases contained 7p and 13. The cells had a log phase doubling time of 48 to 72 h. The cloning efficiency of the cells was 0.06% in the soft agar medium. Neither 12-O-tetradecanoylphorbol-13-acetate nor bile acids enhanced cell proliferation. The cells abundantly secreted CEA protein into the culture medium (700 ng/ml/106 cells during a 48 h period). The present colon carcinoma cell line derived from a genetically defined individual with ACR should prove useful for research in human oncology or genetics.
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9/18. Benign peripheral nerve sheath tumors (neurofibromas) of the lacrimal gland.

    Two patients, a 43-year-old woman and a 62-year-old man, developed benign peripheral nerve sheath tumors (neurofibromas) of the lacrimal gland, in the former case of the deep orbital lobe, and in the latter of the palpebral lobe. A neurogenic tumor was not seriously considered clinically in either case, because of the paucity of previous reports on the occurrence of neural tumors in the lacrimal fossa region. Instead, in the first case a benign mixed tumor was considered the most likely clinical diagnosis, whereas in the second the coexistence of a swelling in the parotid gland raised the possibilities of a lymphoid tumor or a leukemia. Due to unusual light microscopic features, transmission electron microscopy was required to secure unequivocal diagnoses. In the orbital lobe tumor, an encapsulated spindle cell proliferation without nuclear palisading but with focal areas of myxoid change suggested either a cellular benign mixed tumor or a schwannoma. The palpebral lobe lesion displayed a myxoid spindle cell proliferation that had splayed apart the ducts and acinae of the lacrimal gland, to impart the overall appearance of a benign mixed tumor. The ducts, however, were multilaminar rather than possessing the usual double cellular layer seen in classical benign mixed tumors, and the glandular units contained zymogen granules, which are typically not seen in benign mixed tumors. Electron microscopy disclosed in both lesions the presence of interrupted basement membrane material partially surrounding the tumor cells, long spacing collagen (banded basement membrane material), and poorly developed desmosomes, features compatible with a neural tumor. Neither myofilaments, tonofilaments, nor ductal-type granules sometimes observed in benign mixed tumors were discovered. The tumor cells in these cases therefore failed to demonstrate clear-cut Schwann cell characteristics (eg, continuous basement membranes, pseudo-mesaxons, tangles of cell processes), and more closely resembled perineural cells that have been described in ultrastructural studies of peripheral nerve tumors including neurofibromas of other sites.
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10/18. The brenner tumor: a report of multiple tumors.

    A case of multiple Brenner tumors was studied with light and electron microscopy. Among the epithelial elements, argyrophil cells were found in addition to the typical "transitional" and mucus-secreting cells. In some areas, it was not possible to distinguish epithelial from tumor stromal cells. By electron microscopy, dense-core secretory granules were identified, as well as previously undescribed cytoplasmic tubular bodies. Some epithelial cells were intimately associated with reticulin and collagen. Some stromal cells had desmosomes, dense bodies, incomplete basal lamina, and, occasionally, multivesicular bodies, which suggests epithelial differentiation. Previous authors have documented morphologic similarities and continuity between Brenner-tumor epithelium and ovarian cells of almost every type. The inference is that there are multiple possible sources for the brenner tumor. classification must therefore be based on realize differentiation rather than presumed cell of origin.
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