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1/20. Lichenoid dermatitis in paraneoplastic pemphigus: a pathogenic trigger of epitope spreading?

    BACKGROUND: In select cases, lichen planus has been observed to be a paraneoplastic condition sometimes associated with paraneoplastic pemphigus, a disease featuring autoantibodies directed against plakin proteins, desmogleins 3 and 1, and a still uncharacterized 170-kd antigen. Epitope spreading describes the phenomenon where underlying chronic inflammation leads to the sequential recognition of new epitopes on self-proteins over time. OBSERVATIONS: Five of 6 patients diagnosed as having paraneoplastic pemphigus had concomitant clinical and histological features of lichen planus. In 1 patient, results of the initial indirect immunofluorescence on rat bladder were negative and only 2 of the 5 antigens were identified by immunoprecipitation. After 1 year of worsening disease, repeated testing confirmed the presence of antibodies directed against all 6 of the implicated antigens, supportive of our hypothesis that epitope spreading may occur in paraneoplastic pemphigus. CONCLUSIONS: lichenoid eruptions may predispose to an early evolutionary stage of paraneoplastic pemphigus. Cell-mediated autoimmunity at the dermoepidermal junction may promote the exposure of self-antigens and the development of subsequent and progressive humoral autoimmunity. As such, paraneoplastic pemphigus may demonstrate epitope spreading in a human, humoral-mediated autoimmune disease.
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2/20. Needle aspiration cytology, immunocytochemistry, and electron microscopy in a rare case of secretory carcinoma of the breast in an elderly woman.

    Needle aspiration was performed on a breast mass in a 91-year-old woman. The cytologic features in the aspirate were a diffuse, prominent, intracytoplasmic vacuolization and secretion in malignant cells and occasional signet ring-like forms. This was confirmed in a subsequent cell block which was made from the aspirate. Immunocytochemical studies showed a positivity for mucin by alcian blue stain in the vacuolated cells which was periodic acid-Schiff positive and resistant to diastase digestion. Oil-red-O staining was negative and on Colloidal iron stain the tumour cells were positive. Immunopositivity to carcinoembryonic antigen, cytokeratin, and epithelial membrane antigen was found in the malignant cells, while on electron microscopy the tumour cells contained a significant amount of intracytoplasmic secretory material. Secretory carcinoma of the breast is a rare tumour and can be diagnosed and differentiated from other breast carcinomas in view of its characteristic cytologic features.
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3/20. Intraductal growth of malignant mammary myoepithelioma.

    This report describes the histologic and immunohistologic features of an intraductal myoepithelial tumor that developed in the breast of a 61-year-old woman. Histologically, the tumor proliferated intraductally, with both a comedo or doughnut pattern and a solid pattern containing narrow fibrovascular cores, mimicking what appeared to be a conventional intraductal carcinoma. No fine papillary or arborizing growth or cribriform formation was observed. Tumor cells at the ductal peripheral zone were polygonal and clear with abundant glycogen in the cytoplasm; they were transformed into nonclear cells with slightly eosinophilic cytoplasm toward the center of the involved ducts. Occasionally, nonclear cells were elongated, with a centrally located cigar-shaped nucleus. These elongated or spindle cells tended to show a fascicular and streaming pattern similar to that of a smooth muscle tumor. Immunohistochemically, alpha smooth muscle actin (alpha-SM-actin) and S-100 protein were expressed in most of the nonclear cells. While clear cells also had a positive reaction for S-100 protein, they were mostly negative or barely positive for alpha-SM-actin. Epithelial membrane antigen (EMA) was also positive in a certain number of polygonal cells. These results support the myoepithelial nature of the present tumor, and some cells might also be immunologically differentiated into ductal epithelial cells. In addition to cytological atypia, frequent mitoses, and central necrosis within ducts, there was a minimal but evident stromal invasion, suggesting histological malignancy in this peculiar tumor.
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4/20. breast cancer pseudometastasis in a sentinel lymph node with cytokeratin-positive debris.

    We report extensive pseudometastasis detected by immunohistochemical (IHC) staining within a sentinel lymph node. An 83-year-old woman underwent simple mastectomy and sentinel lymph node biopsy (SLNB) for infiltrating ductal carcinoma. Intraoperative frozen section of the SLNB specimen appeared histologically negative for metastasis. IHC staining for cytokeratin in permanent sections, however, showed what was reported as micrometastasis in the subcapsular sinus. Since these cells did not resemble the primary tumor cells morphologically, and had actually been called histiocytes in the frozen section, further IHC staining was done. The subcapsular cells were negative for epithelial membrane antigen (EMA) staining, but they were positive for CD68, a macrophage marker. Thus the cytokeratin-positive cells were not metastatic breast tumor cells, but rather were histiocytes with phagocytized cytokeratin debris. This case report illustrates that IHC staining for cytokeratin in SLNB specimens for breast cancer must be supported by morphologic assessment and further appropriate staining before it can become the basis for treatment decisions.
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5/20. Non-palpable ductal carcinoma in situ (DCIS) with microinvasion arising in a radial scar presenting with spiculation alone on mammograms: a case report.

    A case of ductal carcinoma in situ (DCIS) with microinvasion arising in a radial scar of the breast is presented. A 57-year-old woman visited our hospital with bloody discharge from her left nipple. There were no abnormal findings on cytology, carcinoembryonic antigen (CEA) level of nipple discharge was <500 ng/ml, and mammograms were normal. After 2 years of careful periodic follow-up, spiculation without a central core appeared on mammograms. The CEA level of the nipple discharge increased to 1,000 ng/ml. Ductgraphy showed a connection between the duct with the discharge and the center of the spiculation. Since these findings suggested malignancy, she underwent segmentectomy of the breast, and pathological examination showed a radial scar and DCIS with microinvasion in the ducts within the radiating bands of fibrous tissues. We discuss the characteristics of a radial scar and its relationship to breast cancer based on our experience and a review of the literature.
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6/20. Intraductal carcinoma of mammary-type apocrine epithelium arising within a papillary hydradenoma of the vulva. Report of a case and review of the literature.

    We report and immunohistochemically document the first (to the best of our knowledge) case of malignancy in which an intraductal carcinoma resembling apocrine breast cancer arose within a papillary hidradenoma of the vulva. Papillary hidradenoma is generally thought to originate from apocrine sweat glands, but a derivation from milk line remnants of the vulva should also be considered. Immunoreactivities for low- and high-molecular-weight cytokeratins, alpha-smooth-muscle-specific actin, carcinoembryonic antigen, S100 protein, and gross cytic disease fluid protein 15, an antigen of apocrine differentiation, show features that resemble those of an intraductal apocrine breast cancer. Positivity for gross cystic disease fluid protein 15 as well as the presence of estrogen and progesterone receptors suggest that tumor cells are controlled by ovarian steroid hormones. To our knowledge, no cases of malignancy arising from a papillary hidradenoma have been proved to date. Therefore, we also discuss previously reported cases of putative cancers that have developed in papillary hidradenomas. In the case presented herein, a local excision with a narrow rim of surrounding tissue was performed, and the patient was alive and well, without signs of recurrence, after 2 years of follow-up.
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7/20. Differentiation of metastatic breast carcinoma from Stewart-Treves angiosarcoma. Use of anti-keratin and anti-desmosome monoclonal antibodies and factor viii-related antibodies.

    A chronic brawny edema developed in the shoulder and arm ipsilateral to the site of a previous mastectomy in a 68-year-old woman. Bluish nodules and telangiectasia admixed with more superficial papules and plaques developed subsequently. Histologically, many of these lesions showed angiocentric clusters of large hyperchromatic tumor cells, often with lumina in the center. It was difficult to differentiate two possibilities, ie, postmastectomy angiosarcoma in lymphedema (Stewart-Treves syndrome) and nodulotelangiectatic metastasis of the original breast carcinoma. Monoclonal anti-keratin antibody and anti-desmosome antibody identified keratin and desmosomes in the tumor cells, whereas staining with factor viii-related antigen yielded negative results. Electron microscopy revealed, in addition to keratin filaments and desmosomes, typical secretory cells and lumen formation. A combined use of specific monoclonal and polyclonal antibodies is helpful in the determination of tumor origins.
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8/20. bowen's disease, Paget's disease, and malignant melanoma in situ.

    The histologic differential diagnosis of skin lesions characterized by large, atypical, clear cells in the epidermis includes bowen's disease, Paget's disease (mammary and extramammary), malignant melanoma in situ (pagetoid precancerous melanosis), mycosis fungoides, Spitz nevus, and artifact. Our experience with these lesions indicates that these diseases can be differentiated immunohistologically by the standard peroxidase-antiperoxidase technique, using antibodies directed against keratin (KER), carcinoembryonic antigen (CEA), and S-100 protein (S-100). Based on a study of 11 cases of bowen's disease, eight cases of Paget's disease, and nine cases of malignant melanoma in situ, we conclude that the atypical clear cells of bowen's disease stain only with antibodies to KER; those of Paget's disease, exclusively with antibodies to CEA; and those of malignant melanoma in situ, with antibodies to S-100. Additionally, we report a case in which clinical and histologic findings suggested bowen's disease, but immunohistologic findings supported the diagnosis of Paget's disease.
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9/20. Paget's disease in gynecomastia: immunohistochemical study of a case.

    A case of Paget's disease and gynecomastia in a 70-year-old man is reported. Paget's disease was connected to an intraductal carcinoma, and the immunohistochemical study revealed similar positivity for cytokeratin A, carcinoembryonic antigen and epithelial membrane antigen in Paget cells and intraductal neoplastic cells whereas Paget cells resulted negative for cytokeratin B and C. The study using monoclonal anti-cytokeratin A (35 beta H11), B (34 beta E12) and C (34 beta B4) could represent a good tool, supporting the theory of a ductal origin of Paget cells. A review of the literature has shown the rarity of Paget's disease in the male breast and revealed only two previous reports with an associated gynecomastia, in 2 patients with Klinefelter's syndrome and infiltrating breast carcinoma.
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10/20. Paget's disease of the nipple resembling an acantholytic disease on microscopic examination.

    Two biopsies of an erosive lesion of the nipple had an appearance of an acantholytic disease without showing malignant cells. Only a third biopsy through the nipple with removal of a larger portion revealed some nests of atypical, large cells with clear cytoplasm, typical of Paget's disease. Immunohistochemical findings with carcinoembryonic antigen confirmed the diagnosis of Paget's disease of the nipple. This is the first case of Paget's disease which shows extensive acantholysis on microscopic examination and which resembles pemphigus vulgaris histologically. Acantholytic diseases are easily distinguished from Paget's disease and have never been mentioned in the differential diagnosis of this disease. A large biopsy through the nipple with the removal of a liberal portion of the nipple is suggested in every case of a suspected unilateral lesion of the nipple in order to avoid the overlooking of small nests of Paget's cells, as in our first biopsies, showing a histological picture of an acantholytic disease.
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