Clinical presentation A 77-year-old man presented to our skin cancer centre with various cutaneous tumours occurring in 2006–2017. Histopathology showed a ‘hidradenocarcinoma’ on the left upper back (2006) and a sebaceous adenoma (figure 1) on the left shoulder (2011). In 2017, he developed a sebaceous carcinoma on the middle upper back, which manifested as a slowly enlarging, asymptomatic nodule. Medical history was significant for curative resection of colorectal cancer in 1988.
The most recent lesion was subjected to extensive immunohistochemical assessment. The neoplastic cells were positive for cytokeratin 5/6, cytokeratin 7, cluster of differentiation antigen 10, adipophilin, androgen receptor, epithelial membrane antigen, KI67 antigen, MLH1 and PMS2, but stained negative for gross cystic disease fluid protein 15, prostate-specific antigen, carbohydrate antigen 19/9, CDX2 protein, hepatocyte-specific antigen, carcinoembryonic antigen, cluster of differentiation antigen 117 and cytokeratin 19. Given the variety of histological manifestations of the patient’s skin neoplasms, further studies were performed. They revealed positive nuclear expression signals for MLH1, MSH6 and PMS2, whereas MSH2 expression was absent in almost all tumour cells (figure 2). Positron emission tomography (PET)/CT and colonoscopy did not detect any pathological findings. However, molecular genetic analysis of peripheral blood showed a heterozygous deletion of exon 7 of the MSH2 gene. Subsequently, several family members tested positive for MSH2 mutations and underwent genetic counselling.
What is your diagnosis?Diagnosis: Muir-Torre syndrome (MTS).
- colorectal cancer screening
- HNPCC syndrome
- muir-torre- syndrome
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The absence of MSH2 expression by immunohistochemistry along with the clinical findings is diagnostic of MTS. MTS is recognised as a phenotypic variant of hereditary non-polyposis colorectal carcinoma syndrome. This rare autosomal dominant genodermatosis is caused by mutations in mismatch repair genes such as MSH2, MLH1 and MSH6, with the majority of variations located in MSH2.1 2 Clinically, it is characterised by the association of sebaceous tumours and/or keratoacanthomas with visceral malignancies, particularly colorectal and urogenital tumours. Colonoscopy, non-contrast CT and cystourethroscopy are gold standard imaging modalities for the detection of such neoplasms and represent excellent tools for the diagnosis and follow-up of MTS in combination with a full-body skin exam.3 4 PET imaging could be used in selected cases. The occurrence of >2 sebaceous neoplasms in areas other than the face and neck in patients under 50 years of age should raise the clinical suspicion of MTS and should therefore prompt a screening for internal malignancies. First-degree relatives of affected individuals should be screened as well. Furthermore, families of patients with MTS should receive genetic counselling.5
Contributors FJ: writing of the manuscript. TTS, JS and JM: histopathology. EL and LZ: senior physicians leader of the tumour ambulance. DS: clinical director. AR: idea of the study, first diagnosis.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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