Difficult cases of thyroid pathology.
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Diagnosis, Differential↗
Biomedical subjects
Manuel Sobrinho-Simões
Publications and source records attributed to Manuel Sobrinho-Simões.
Mucins as key molecules for the classification of intestinal metaplasia of the stomach.
Mucins and mucin-associated carbohydrates have a distinct expression pattern that can be modified under pathological conditions. Normal gastric mucosa expresses MUC1 and MUC5AC in foveolar epithelium and MUC6 in the glands. Lewis type-1 chain antigens (Le(a) and Le(b)) are expressed in foveolar epithelium, whereas Lewis type-2 chain antigens (Le(x) and Le(y)) are expressed in the glands. In this study we used monoclonal antibodies to evaluate the pattern of mucins and Lewis type-1 carbohydrates in intestinal metaplasia (IM) and compared it with IM types determined using histochemistry. In type-I or complete IM we found expression of MUC2 intestinal mucin and decreased/absent expression of MUC1, MUC5AC and MUC6. In type-II/III or incomplete IM there was co-expression of MUC2 and the mucins expressed in the stomach. No major differences were detected among the three IM types regarding expression of Lewis antigens. Furthermore we observed that sialylated compounds other than sialyl-Le(a) are responsible for histochemical detection of sialomucins and that sulpho-Le(a/c) is expressed in the presence or absence of sulphomucins detected using histochemistry. We conclude that mucin immunohistochemistry may replace classic histochemistry for the classification of IM into complete and incomplete types. The present study challenges the distinction of type-II from type-III IM since we did not observe major differences in the expression profile of mucins and Lewis type-1 carbohydrates. Finally, it seems necessary to evaluate the predictive value of IM according to the presence of specific sulphated carbohydrates (e.g. sulpho-Le(a/c)) rather than histochemically detected sulphomucins.
Carcinoma↗
Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a clinicopathologic and immunohistochemical analysis of ten cases of an aggressive form of differentiated thyroid carcinoma.
In an attempt to advance and improve the characterization of the so-called diffuse follicular variant of papillary thyroid carcinoma (diffuse FVPTC) we studied a series of 59 thyroid carcinomas consecutively treated in a specialized center. The clinicopathologic and some of the immunohistochemical characteristics (uPA-R, Lewis X, Sialyl Lewis X, and MIB-1) of ten cases of FVPTC displaying a multinodular or diffuse pattern of growth, and histologic features similar to those previously described in diffuse FVPTC, were compared with those of common papillary thyroid carcinoma (PTC, 25 cases) and common FVPTC (8 cases). Cases of diffuse FVPTC differed significantly from common PTC and FVPTC in targeting younger patients and in exhibiting a prevalence of multicentricity, extrathyroid extension, nodal metastasis, and vascular invasion. Immunohistochemically, diffuse FVPTC cases were characterized by the overexpression of uPAR and sialyl Lewis X. No differences were observed regarding MIB 1 immunoreactivity. Regardless of the term used to designate the multicentric, invasive form of FVPTC (diffuse or multinodular FVPTC) it is crucial to acknowledge the existence of cases of FVPTC with a guarded prognosis that should be distinguished from the classic, uninodular form of FVPTC.
Adult↗
Clinicopathologic and Prognostic Significance of the Expression of Mucins, Simple Mucin Antigens and Histo-Blood Group Antigens in Papillary Thyroid Carcinoma.
We have previously analyzed the expression of MUC1, underglycosylated MUC1, MUC2, MUC5AC, Tn, sialyl Tn, Lewis(a), sialyl Lewis(a), Lewis(x), and sialyl Lewis(x) in papillary thyroid carcinoma (PTC). The present study of 26 thoroughly scrutinized cases of PTC with "good" or "bad outcome" and a minimum of 10 yr of follow-up (or until death of the patients) was undertaken in an attempt to find if there is any relationship between the expression of the aforementioned antigens and the clinicopathologic and morphologic features of the cases and to evaluate the prognostic significance of the immunohistochemical pattern of PTC. We observed a significant or suggestive association between the expression of MUC1, underglycosylated MUC1, MUC2, Lewis(a), and Lewis(x) and the older age of the patients, and a suggestive association between Lewis(x) expression and lymph node metastasis and venous invasion. There was also a strong correlation between extrathyroid invasion, lymph node metastasis, intrathyroid dissemination, and venous invasion and patients outcome thus demonstrating, once more, the prominence of the classic clinicopathologic and morphologic features in the prognostic evaluation of PTC. The immunohistochemical study of mucins, simple mucin antigens, and histo-blood group antigens did not provide additional prognostic information, but for the significant association of Lewis(x) immunoreactivity to the group of "bad outcome."
Journal Article↗
Papillary Thyroid Carcinoma Overexpresses Fully and Underglycosylated Mucins Together with Native and Sialylated Simple Mucin Antigens and Histo-Blood Group Antigens.
We studied the immunohistochemical expression of mucins (MUC1, underglycosylated MUC1, MUC2, MUC5AC, and MUC6), simple mucin antigens (Tn, sialyl Tn, and T), and histo-blood group antigens (type 1-Lewis(a) and sialyl Lewis(a) type 2-Lewis(x) and sialyl Lewis(x)) in a series of 26 papillary thyroid carcinomas (PTC), 6 follicular carcinomas, and a control group of 32 cases of "normal" thyroid parenchyma adjacent to the tumors. PTC expressed more often, more intensively, and more extensively every antigen but MUC6, which was not observed in any case. The expression of MUC5AC was also extremely rare. MUC1 expression was related to the expression of underglycosylated MUC1, MUC2, Lewis(a), and sialyl Lewis(a). A trend toward an association between the expression of MUC1 and that of type 2 histo-blood group antigens was also observed. Whenever there was a dissociation between the expression of type 1 and type 2 Lewis antigens, MUC1 appeared closely related to type 1 and independent from type 2 histo-blood group antigens. We conclude that MUC1 plays a pivotal, though not exclusive, role in the glycosylation features of well differentiated thyroid carcinomas. Despite the prominent expression of mucins and carbohydrate antigens in PTC, no significant differences were observed between PTC and follicular carcinoma thus ruling out the possibility of using the aforementioned antigens as diagnostic markers per se.
Journal Article↗
Vascular invasion in thyroid and gastric carcinomas.
The molecular, biological, and histopathologic features related to vascular invasiveness of gastric and thyroid carcinomas, with an emphasis on glandular (intestinal) carcinoma of the stomach and follicular thyroid carcinoma, are reviewed from a clinicopathologic standpoint.
Adenocarcinoma, Follicular↗