Identification of Muir–Torre syndrome among patients with sebaceous tumors and keratoacanthomas

Abstract

The three‐dimensional architecture of the right ventricular myocardium is a major determinant of function, but as yet no investigator‐independent methods have been used to characterize either the normal or hypertrophied state. We aimed to assess and compare, using diffusion tensor magnetic resonance imaging, the normal architecture with the arrangement induced by chronic hypertrophy. We randomized 20 female 5 kg piglets into pulmonary trunk banding (N = 16) and sham operation (N = 4). Right ventricular hypertrophy was assessed after 8 weeks. The excised and fixed hearts were subject to diffusion tensor imaging to determine myocyte helical angles, and the presence of any reproducible tracks formed by the aggregated myocytes. All banding animals developed significant right ventricular hypertrophy, albeit that no difference was observed in terms of helical angles or myocardial pathways between the banded animals and sham group animals. Helical angles varied from ∼70 degrees endocardially to −50 degrees epicardially. Very few tracks were circular, with helical angles approximating zero. Reproducible patterns of chains of aggregated myocytes were observed in all hearts, regardless of group. The architecture of the myocytes aggregated in the walls of the right ventricle is comparable to that found in the left ventricle in terms of endocardial and epicardial helical angles, however the right ventricle both in the normal and the hypertrophied state lacks the extensive zone of circular myocytes seen in the mid‐portion of the left ventricular walls. Without such beneficial architectural remodelling, the porcine right ventricle seems unsuited structurally to sustain a permanent increase in afterload. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.

MSH-6: extending the reliability of immunohistochemistry as a screening tool in Muir–Torre syndrome

“…13,21 Briefly, these include studies on patients with Muir-Torre syndrome showing that expression of both MLH-1 and MSH-2 by immunohistochemistry is highly predictive of microsatellite stability (93%) while loss of either is associated with microsatellite instability (100%). 3,4,20 A good correlation between the two methods has been observed in patients with hereditary nonpolyposis colorectal cancer and also in patients with sporadic carcinomas of the colon and the endometrium. 22 In one study of 19 cutaneous tumors from patients with Muir-Torre syndrome and a germline mutation in MLH-1 or MSH-2 by molecular analysis, immunohistochemistry Figure 1.…”

“…16,17 A clinical diagnosis of this subtype can be made in a patient with concurrent or sequential documentation of a sebaceous neoplasm and a minimum of one internal malignancy or, multiple keratoacanthomas and a visceral malignancy and a positive family history. 3,4,18 The significance of a negative history is perhaps mitigated by reports indicating that patients with Muir-Torre syndrome typically develop their first internal malignancy at an older age. 18 The clinical relevance of identifying patients with an inherited cancer predisposition, necessitates the use of alternative laboratory-based screening methods to identify microsatellite instability or germline mutations in the mismatch repair proteins.…”

“…The former involves molecular analysis of tumoral tissue, while the latter, ascertained immunohistochemically, looks for loss vs maintenance of the more commonly implicated mismatch repair proteins. 3,4,19,20 Several reports attest to the reproducibility of these two methods. 13,21 Briefly, these include studies on patients with Muir-Torre syndrome showing that expression of both MLH-1 and MSH-2 by immunohistochemistry is highly predictive of microsatellite stability (93%) while loss of either is associated with microsatellite instability (100%).…”

“…1,2 The molecular alteration characteristic of neoplasms that develop in patients with Muir-Torre syndrome is microsatellite instability that is believed to be secondary to the coexistence of germline mutations in some mismatch repair protein genes. 3,4 Several early reports have shown that the spectrum of internal malignancies seen in patients with Muir-Torre syndrome is identical to those observed in patients with hereditary nonpolyposis colorectal cancer or the Lynch syndrome and exhibits microsatellite instability and germline mutations similar to those encountered in hereditary nonpolyposis colorectal cancer. [5][6][7][8] These mutations typically involve the mismatch repair proteins MLH-1 and MSH-2 with the majority located in the latter.…”

A two-antibody mismatch repair protein immunohistochemistry screening approach for colorectal carcinomas, skin sebaceous tumors, and gynecologic tract carcinomas

“…14,18,[36][37][38] To our knowledge, only one study has analyzed the expression of all four mismatch repair proteins in skin sebaceous neoplasms (Table 5). 19 Orta et al 19 analyzed 27 patients with one or more sebaceous neoplasms and showed abnormal mismatch repair protein expression in 12 (44%) patients (Table 4).…”