Surgical pathology versus molecular biology.
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Biomedical subjects
Publications and source records attributed to M Sobrinho-Simoes.
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We report a case of cribriform-morular variant (C-MV) of papillary thyroid carcinoma (PTC) in a 27-year-old woman. In addition to conventional cytologic features of typical PTC, the fine-needle aspirate showed numerous epithelial cells with abundant, eosinophilic, very elongated cytoplasm. Microscopically, the tumor was encapsulated and highly cellular and exhibited a mixture of cribriform, follicular, papillary, trabecular, solid, and spindle cell patterns of growth, with morular foci showing peculiar nuclear clearing (biotin-rich nuclei). The cells were cuboidal or tall, with frequent nuclear pseudostratification and abundant eosinophilic cytoplasm. The nuclei were usually hyperchromatic, with grooving, pallor, and pseudoinclusions. Angioinvasion and foci of capsular invasion were observed. Immunohistochemically, the neoplastic cells showed reactivity for thyroglobulin, epithelial membrane antigen, low- and high-molecular-weight cytokeratins, vimentin, neuron-specific enolase, CD15, estrogen and progesterone receptors, and bcl-2 protein. Molecular genetic analysis of the APC gene revealed a mutation in exon 15 at codon 1309 in tumoral tissue but not in peripheral lymphocytes. These findings support a relationship between the morphologic pattern of the C-MV of PTC and the APC gene and the existence of this variant as a sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma.
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Microsatellite instability (MI) characterizing tumors with replication errors (RER+ tumors) was first described in colorectal tumors from hereditary non-polyposis colorectal cancer (HNPCC) patients as well as in sporadic cases. It has also been observed in subgroups of extracolonic sporadic tumors, but there is no consensus as to the number of microsatellite loci to examine, and the threshold percentage of unstable loci required to classify a tumor as RER+. We have recently shown that BAT-26, a mononucleotide repeat microsatellite, was quasi-monomorphic in DNA from normal individuals and from colorectal RER- samples, and showed important size variations in RER+ samples. In the present work, we analyzed BAT-26 allelic profiles in tumors of the breast (n = 107), brain (n = 78), stomach (n = 59), prostate (n = 49), esophagus (n = 36), thyroid (n = 31), endometrium (n = 12), and cervix (n = 10) whose RER status was already known, thus extending BAT-26 analysis to a total of 542 human solid tumors. BAT-26 alleles were quasi-monomorphic in RER- samples (475/481) and shortened in RER+ tumors (57/61), including four tumors shown to have been misclassified on the basis of dinucleotide repeat microsatellite analysis. In 3/481 RER- and 4/61 RER+ cases, BAT-26 size variation was important enough to attract attention, but not sufficient to establish the RER status of the corresponding tumors. In these cases, the analysis of BAT-25 and BAT-34C4, two other mononucleotide repeat microsatellites, was necessary to resolve the ambiguity. There were only 3 false positive cases. In conclusion, BAT-26 was able to identify the RER status of 539 out of 542 tumors from various origins (99.5% efficiency) in a single-step experiment without the requirement for matching normal DNA.
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The morphological, histochemical, and immunohistochemical findings of seven cases of solid cell nests (SCNs) of the thyroid are described. Light microscopy showed two cell types forming the SCNs, which we refer to as "main cells" and "C cells." In all cases "mixed thyroid follicles" (a unique structure lined by follicular epithelium and epidermoidlike cells) were observed in which the histochemical study confirmed the presence of intraluminal acid mucins. Adult adipose tissue and cartilage were found in one case and foci of cartilage were observed in another case in association with the SCN. Immunohistochemical studies showed positivity of "main cells" for carcinoembryonic antigen (CEA), high- and low-molecular weight keratins, neurotensin, and somatostatin. "C cells" were positive for calcitonin, calcitonin gene-related peptide (CGRP), and chromogranin. The two cell types in SCNs were consistently negative for thyroglobulin. Neuron-specific enolase (NSE)-positive cells were found in the vicinity of the SCN. The unusual association of adipose tissue and cartilage as well as the results of the extended immunohistochemical study in this series provides further support to the belief that SCNs and "mixed thyroid follicles" represent remnants of the ultimobranchial body and should be considered normal components of the thyroid gland.
A case of solitary fibrous tumor (SFT) of the thyroid in a 43-year-old woman with a multinodular goiter is reported. This is the first case of SFT described in the thyroid. On histologic, immunohistochemical, and ultrastructural examination, the tumor was identical to SFT of the pleura and other organs. Despite its rarity, SFT should be included in the differential diagnosis of spindle-cell tumors of the thyroid, along with anaplastic carcinoma, spindle-cell medullary carcinoma, and several types of mesenchymal tumors.
The expression of incompatible A carbohydrate antigens in some adenocarcinomas may provide an explanation for the generally observed lower incidence of adenocarcinoma among types O and B versus type A individuals. The chemistry and genetic basis of incompatible A expression is largely unknown. Here, we have screened 31 cases of gastric tumors of phenotype O for the expression of blood group A gene-defined glycosyltransferase by immunohistology on frozen sections using newly developed monoclonal antibodies to the transferases. Three cases were positive, and transferase expression was confirmed by enzyme analysis of extracts from the specimens. Blood group A carbohydrate antigens were also identified immunohistologically in these three cases as well as in five other cases. Thin-layer chromatography immunostaining analysis of glycolipid extracts from the three cases did not confirm the chemical presence of A antigen. The ABO genotype of all patients was found to be OO, showing that all carried O alleles with a structural defect at nucleotide position 261 leading to a shift in the reading frame. The data suggest that incompatible A antigen expression is a result of transferase expression derived from the ABO genes.
Lectin histochemistry and electron microscopy were used to study a series of 13 solid or microacinar medullary carcinomas of the thyroid (MCTs) and compare them with four follicular MCTs and other forms of thyroid cancer. Lectin histochemistry was not found to be of diagnostic value, since the MCT did not display any distinct lectin-binding pattern. This approach demonstrated that all MCTs, irrespective of their histologic appearance, consist of polarized cells, arranged into microfollicles that can be demonstrated readily by electron microscopy. We conclude that all MCTs form follicles, some visible by light microscopy, while others are submicroscopic and apparent only on histochemical staining. Because of the histochemical and ultrastructural similarities between solid MCTs and tumors with a follicular pattern, the latter should not be considered a distinct variant of C-cell neoplasia.
The characteristic scanning electron microscopic features of the normal thyroid gland, benign thyroid lesions such as nodular (adenomatous) and colloid goitre, adenomas and thyroiditis, and malignant tumors such as papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma are described. One or more cilia are present in the center of the follicular surface of almost every epithelial cell in the normal thyroid gland as well as in most goitres. Their number is reduced in adenomas and differentiated carcinomas. Medullary carcinomas and anaplastic carcinomas usually lack cilia. Variation in distribution and appearance of microvilli seems to be related to functional differences in the normal thyroid and goitres. In neoplastic conditions the abundance of microvilli steadily decreases from ordinary papillary carcinomas to follicular variants of papillary carcinoma and to follicular carcinoma. Most of the cells in medullary carcinoma and anaplastic carcinoma have few or no microvilli. Benign and neoplastic Hürthle cells have a very characteristic appearance. Distinct, smooth-surfaced cells are interspersed among cells rich in microvilli. The literature is reviewed. Our own experience from examinations of 264 thyroid specimens is included.
In addition to a description of the basic criteria for the diagnosis of papillary carcinoma, a review of discussions by all workshop participants on the illustrative cases is presented. Areas of consensus included the following: classification of mixed papillary and follicular carcinomas as papillary, regardless of follicular dominance; recognition of three morphological variants--follicular, encapsulated, and diffuse sclerosing; nonspecificity of individual histological criteria, with the necessity to utilize a combination of characteristic features as guidelines for establishing a diagnosis; citing of nuclear features as probably the most important diagnostic criteria, ie, increased N/C ratio, irregularity in outline, and paleness of staining (ground glass appearance); grading of tumors on the basis of either cytological or architectural characteristics remains of unproven prognostic value. (Gross extent of tumor at the first operation remains the most valuable single prognostic criterion.); defining small carcinomas by size rather than using the imprecise term "occult" with its variable definitions including some clinically evident tumors; classifying as undifferentiated those carcinomas presenting a mixed papillary and anaplastic appearance at the time of the first operation, and retaining the papillary designation for papillary cancers which later undergo dedifferentiation; and recognition that thyroglobulin is a constant and keratin an inconstant tumor cell marker, with the latter not specific for distinguishing papillary carcinomas from follicular carcinomas or from hyperplastic adenomas.
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Synovial sarcomas (SS) are malignant soft tissue tumors of unknown origin. Their classification as carcinomas (monophasic synovial sarcomas, MSS) or carcinosarcomas (biphasic synovial sarcomas, BSS) still raises controversy. In an attempt to settle this controversy, an ultrastructural study was undertaken of 25 primary SS (12 BSS and 13 MSS), 5 recurrences (3 BSS and 2 MSS), and 2 metastases (2 BSS) based upon precise selection of different aspects of BSS and MSS on numerous semithin sections from each case. Ultrastructural markers of epithelial type differentiation of neoplastic cells were found in every type of cellular component of SS regardless of the tumoral pattern (biphasic or not). No major differences were found between MSS and the nonglandular areas of BSS (not even regarding the presence of abortive glandular lumina). Cytoarchitectural transitions were frequently observed; these included spindle to epithelioid cell types and fascicular to solid (MSS and BSS) or fascicular to glandular (BSS) patterns. These findings support the assumption that spindle cells of SS are neoplastic and may evolve to glandular cells in SS. Based on the cytogenetic data pointing to a common pathogenesis of both phenotypes (BSS and MSS), SS may represent true carcinomas of soft tissues with a biphasic and/or monophasic pattern depending on the degree of differentiation.