Unusual granular reactivity for carcinoembryonic antigen in malignant mesothelioma.
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Biomedical subjects
Publications and source records attributed to D V Spagnolo.
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We report 18 cases of primary cutaneous neuroendocrine carcinoma (CNEC, Merkel cell tumor) that occurred mainly in the sun-exposed skin of elderly patients as dermal and subcutaneous masses of generally monomorphic cells with foci of pronounced pleomorphism. All 18 cases showed immunoreactivity for neuron-specific enolase (NSE), whereas 16 of them showed immunoreactivity for another neuroendocrine marker, protein gene product 9.5 (PGP 9.5). Positivity for PGP 9.5 was more intense and more sharply localized to tumor cells than the staining for NSE. Immunoreactivity for keratins detected by AE1/AE3 and CAM 5.2 monoclonal antibodies was found in 16 and 15 cases, respectively, with prominent paranuclear globular staining. One case stained positively for S-100 protein; all were negative for leukocyte common antigen (LCA). Typical ultrastructural features of neuroendocrine differentiation were noted in all of 14 tumors examined. Morphological and immunohistochemical similarities between these neoplasms and pulmonary small-cell anaplastic carcinoma, now thought to be of bronchial basal cell origin, suggest that CNEC are also derived from epithelium. In addition, their dermal location suggests that this epithelium is likely to be adnexal rather than epidermal.
Atypical mycobacteria causing extra-pulmonary disease in man are well documented. These infections are manifested by the presence of ulcers, abscesses and lymphadenitis. Mycobacterium marinum is particularly noted for infections involving the synovium, tendon sheaths, bursae and bone. Of lesser note is Mycobacterium terrae (radish bacillus), a nonchromogen also associated with tenosynovitis. We are not aware of any previous report of the association of M. terrae with synovitis in Australia. This case report describes a culture-proven case of tenosynovitis caused by M. terrae.
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The evaluation of antibodies for diagnostic purposes on routinely processed sections of histologically undiagnosable neoplasms presents special problems. The authors have addressed this problem by constructing a panel of putatively mutually exclusive antibodies and testing it on sections of anaplastic neoplasms. Tissue sections of 120 routinely processed histologically undifferentiated large cell human neoplasms with a histologic differential diagnosis of carcinoma versus lymphoma and/or melanoma were stained with a panel of antibodies composed of monoclonal antikeratin AE1, monoclonal antileukocyte common antigens PD7/26 and 2B11, and rabbit anti-S-100 protein. Only cases not diagnosable by routine morphologic examination were included. PD7/26 and/or 2B11 were positive in 61 cases (supporting lymphoma), AE1 was positive in 17 cases (supporting carcinoma), and anti-S-100 was positive in 25 cases (supporting melanoma). Seventeen neoplasms failed to react with any of the panel antibodies. None of the neoplasms reacted with antibodies directed against two or more different antigens. These results indicate excellent specificity (100%) and good sensitivity (86%) of the panel antibodies on histologically undifferentiated neoplasms. These results are significant on two levels: first, as a test of the panel approach to evaluate antibodies on anaplastic neoplasms, and, second, as a demonstration of the diagnostic utility of the specific panel the authors have employed in such cases.
A frontal lobe neoplasm in a 25-year-old Caucasian man showed the typical histological pattern of a "polar spongioblastoma." Immunoperoxidase staining for glial fibrillary acidic protein (GFAP) was negative while silver stains in paraffin-embedded tissue, and electron microscopy displayed neoplastic cells with neuritic processes. Ultrastructurally there were microtubules, synapses and dense-core neurosecretory granules, all features of a neuroblastic neoplasm. It is suggested that this new growth with its polar spongioblastic appearance is, in fact, a moderately malignant primary cerebral neuroblastoma.
Three adult patients had cerebral malignant gliomas composed predominantly of small cells and displaying many areas of palisading necrosis, which are usually characteristic of glioblastoma multiforme. Light and electron microscopy, however, revealed tumour cells with neuritic processes, while astrocytic differentiation was convincingly excluded. It is suggested that palisading necrosis is not pathognomonic of glioblastoma multiforme and that high grade cerebral neuroblastoma should be considered in the differential diagnosis. The need for comprehensive light and electron microscopic studies for the accurate classification of gliomas is stressed.
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Bladder granulomata were found in 17 (3%) of 539 patients who had bladder biopsy or resection. The finding of granulomata in 13.6% of patients who had at least two surgical procedures, but never in the first biopsy specimen of any patient was highly significant statistically (P much less than 0.001). The occurrence of granulomata exclusively in patients with bladder carcinoma was related to the significantly greater number of biopsies performed in these patients and not to carcinoma, per se. There were two types of granulomata: necrotizing, palisading granulomata (NPG) resembling rheumatoid granulomata; and foreign-body-type granulomata (FBG). They often occurred together in the same specimen, and transitions from FBG to NPG were evident histologically. The granulomata apparently healed by fibrous scarring. Energy-dispersive analysis of x-rays (EDAX) did not reveal any inorganic foreign material, but showed sulphur in some granulomata, possibly released from necrotic stroma and urothelium. Clinical and morphologic evidence is presented indicating that the granulomata arose as a local reaction to tissue necrosis caused by surgery and/or cautery.
A large number of human neoplasms were tested for their keratin expression in routinely processed tissues by a simple, three-stage immunoperoxidase method using a broadly reactive monoclonal anti-keratin antibody AE1, which recognizes a number of keratin polypeptides distributed in a wide variety of epithelia. All carcinomas, with the exception of hepatocellular, adrenocortical, and basal cell carcinomas and occasional renal cell, pulmonary small-cell, and pulmonary large-cell anaplastic carcinomas, reacted with this antibody irrespective of differentiation, in most instances displaying staining of strong or moderate intensity in the majority of tumor cells. Equivocal results were obtained in some seminomas and dysgerminomas. Malignant melanoma, large-cell lymphoma, Hodgkin's disease, malignant histiocytosis, and stromal mesenchymal elements in all tumors did not show any reactivity with AE1. Even after routine processing, the determinant detected by AE1 is conserved and restricted to epithelial neoplasms. This suggests that AE1 would be valuable in the diagnostic distinction of anaplastic carcinoma from lymphoma and melanoma in routinely processed tissues.
A supraglottic laryngeal neuroendocrine tumour in a 71-year-old female is presented. In addition to the typical features of extra-adrenal paragangliomas it showed unusual, numerous intracytoplasmic lumina and occasional true acini with accumulation of alcian blue and PAS positive secretory product in them which led originally to an erroneous diagnosis of metastatic adenocarcinoma. Ultrastructurally, the tumour was composed of light and dark chief cells containing varying numbers of dense-core secretory granules. Intracytoplasmic lumina and true acini contained microvilli with glycocalyceal material and varying amounts of membranous and amorphous material, possibly secreted via small, smooth-surfaced cytoplasmic vesicles but typical mucin granules were not seen. These features have not been previously described in laryngeal paragangliomas but are seen in endocrine tumours of other sites and have been used as an argument in favour of an endodermal rather than ectodermal origin for endocrine cells in those sites. Laryngeal paragangliomas are often malignant and the presence of spasmodic pain appears to be the most reliable indication of possible malignancy, histological criteria being as yet poorly defined.
Pontine infarcts associated with granulomatous (giant cell) arteritis were the terminal events in a 71-year-old man treated for chronic myeloid leukemia with intermittent Busulphan therapy during the previous ten years. The final admission was precipitated by a severe episode of herpes-zoster infection of the scalp. Since 1950 there have been 25 papers in the English language medical literature describing 36 cases of granulomatous angiitis of the central nervous system (CNS). Seven cases, including this report, were associated with lymphoid malignancies, and five had cutaneous herpes-zoster as well. Virus-like particles were detected in the affected vessels in three patients and in the nearby glial cells of a further case.
A fatal nasopharyngeal malignant fibrous histiocytoma developed in a young male after irradiation of juvenile nasopharyngeal angiofibroma diagnosed 5 years earlier. The sarcoma extended from the nasopharynx into the floor of the pituitary fossa and into both parasellar regions. There was no clinical evidence of any distant spread. Many of the malignant cells contained cytoplasmic granular and globular PAS-positive inclusions shown to be alpha-1-antitrypsin immunohistochemically. Ultrastructurally, this probably corresponded to electron-dense material with distinctive patterns and which had accumulated within distended ergastoplasmic cisternae of the neoplastic cells. Three previously reported case of postirradiation sarcomas arising in nasopharyngeal angiofibroma were said to be fibrosarcomas and none produced alpha-1-antitrypsin.
The cases of a mother and son with a slowly progressive generalised myopathy and Marfanoid features are described. Muscle biopsies showed atrophy, type 1 fibre preponderance, excessive variation in fibre size and shape, and multiple foci of myofibrillar disorganisation with loss of oxidative enzyme activity of the type found in multicore disease.
An extremely rare case of primary extragenital granuloma inguinale affecting the axillae is reported. Clinical, histological, and electron microscopical features of the disease are described, and the rarity, absence of genital lesions, and consequent difficulty in diagnosis are emphasised.
A total of 307 breast neoplasms and tumour-like conditions were reviewed to assess the frequency with which bone and/or cartilage occurred. Of 90 fibroadenomas, 1 (1.1%) and 2 of 158 breast carcinomas (1.3%) contained bone, one benign mesenchymoma contained cartilage, and one benign "mixed" tumour (pleomorphic adenoma) displayed cartilage and bone. Twenty-two papillomas and 34 cases of gynaecomastia did not contain any cartilage or bone. This study confirms the impression that the occurrence of bone or cartilage in human breast neoplasms is rare. These lesions are briefly discussed with reference to the pertinent literature.
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