Wat Zijn de Huidziekten Geassocieerd met Muir-Torre Syndroom?

Muir-Torre Syndrome

Muir-Torre syndrome is a rare, autosomal dominant genodermatosis characterized by the presence of at least one sebaceous gland neoplasm, associated with an underlying visceral malignancy. Muir-Torre syndrome is believed to be a subtype of Lynch Syndrome. Affected individuals are found to have germline mutations predominantly in DNA mismatch repair gene MSH2, and much less frequently, MLH1. The authors report the case of a 55-year-old woman presenting with multiple cutaneous neoplasms including sebaceoma, basal cell carcinoma, and squamous cell carcinoma, personal history of colorectal and endometrial cancer, and family history of colorectal cancer, found to have a deletion at mismatch repair gene MLH1. It is important to recognize the role of these less common gene deletions in producing the Muir-Torre syndrome phenotype, and consider the correlation of cutaneous manifestations with internal disease. The authors discuss the clinical presentation of Muir-Torre syndrome, methods of diagnosis, and the importance of regular medical surveillance to detect and prevent disease progression in Muir-Torre syndrome patients and their family members.

Physical examination revealed a well-developed female in no apparent distress. Her face featured a 4mm non-tender, pearly papule on the right nasal tip along with multiple, scattered, 0.2 to 0.4cm, yellow, lobulated papules, most dense throughout the nose and bilateral cheeks. Chest was without evidence of recurrence or suspicious lesions. The back and extremities demonstrated multiple, scattered, brown, waxy papules and plaques, as well as uniform brown macules consistent with seborrheic keratoses and solar lentigos. At the time of examination, a 3mm shave biopsy was obtained of the lesion at the right nasal tip, which was suspicious for malignancy.

Other sebaceous lesions and terminology

Numerous additional terms have been introduced into the literature, which may encompass the various sebaceous neoplasms. These terms, including “sebaceous epithelioma” and “sebomatricoma”, have variably included sebaceous adenomas, sebaceomas, and non-sebaceous tumours such as basal cell carcinoma with sebaceous differentiation. In addition to a lack of well-defined diagnostic features for these lesions, there has also been disagreement and confusion regarding malignant potential, particularly in the case of the sebaceous epithelioma. 33 – 35 Furthermore, these broad terms do not clearly distinguish the sebaceous tumours most likely to be associated with the MTS 35 . These terms do have some limited degree of support within the literature, but the terms sebaceous adenoma and sebaceoma as defined above will encompass the vast majority of benign sebaceous lesions encountered, although the histological spectrum certainly admits to variation. Conceptually, one could certainly view sebaceomas as “cellular” sebaceous adenomas given their similar clinical contexts and significance. However, sebaceoma is a well-defined entity and it recognizes lesions with prominent basaloid features and sometimes more prominent mitoses as benign and markers of the MTS.

Other rare sebaceous neoplasms include superficial epithelioma with sebaceous differentiation and mantleoma. Superficial epithelioma with sebaceous differentiation is rarely described, but a recent report suggests that it may be more common than previously thought. 35 , 36 It is a benign entity composed of a plate-like epidermal growth with thickened, anastamosing rete ridges and interposing lobules of basaloid cells and mature sebocytes. 36 , 37 Mantleoma is described as a benign folliculocentric tumour with sebaceous differentiation that is thought to replicate the follicular mantle. 38 Fibrofolliculomas and trichodiscomas, benign tumours seen in Birt–Hogg–Dube syndrome, are considered by some to show mantle differentiation as well, and may represent overlap with mantleoma. 39 Perhaps due to their rarity, neither superficial epithelioma with sebaceous differentiation nor mantleoma has a well-defined relationship with MTS, although one patient with superficial epithelioma with sebaceous differentiation reported an internal malignancy. 36

Behandeling

Patiënten moeten zich regelmatig laten controleren op huidafwijkingen. Dit gebeurt naast de controle en behandeling van de kanker. Als een van de huidafwijkingen zich openbaart, is het namelijk belangrijk om dit door een dermatoloog (huidarts) te laten verwijderen. De huidafwijking kan zich namelijk ontwikkelen tot huidkanker. Deze regelmatige screening, ook van directe familieleden van patiënten, wordt uitgevoerd vanaf de leeftijd van 20 jaar. Vanaf de 40 moet dit jaarlijks gebeuren.

Als iemand in uw familie aan dit syndroom lijdt, is het belangrijk dat de hele familie zich regelmatig laat controleren, zowel op darm- en blaaskanker, als op de huidaandoeningen. Ontstaan de huidaandoeningen, ga dan naar een dermatoloog gaan. Hij/zij zal adviezen geven over het (eventueel) verwijderen van de bultjes. Een klinisch geneticus kan meer uitleg geven over de erfelijkheid en overerving van de aandoening.

Review Questions

Coquillard C, Boustany A, DeCoster RC, Vasconez HC. Muir-Torre Syndrome Presenting as a Sebaceous Carcinoma of the Nasal Ala. Am Surg. 2019 Mar 01, 85 (3):e115-e117. [PMC free article : PMC6486836 ] [PubMed : 30947781 ]

Task Force/Committee Members. Vidal CI, Sutton A, Armbrect EA, Lee JB, Litzner BR, Hurley MY, Rating Panel. Alam M, Duncan LM, Elston DM, Emanuel PO, Ferringer T, Fung MA, Hosler GA, Lazar AJ, Lowe L, Plaza JA, Robinson JK, Schaffer A. Muir-Torre syndrome appropriate use criteria: Effect of patient age on appropriate use scores. J Cutan Pathol. 2019 Jul, 46 (7):484-489. [PubMed : 30895633 ]

McCarthy RL, Thomas CL, Isaacs F. Multiple benign adnexal tumours: Anything but benign. Australas J Dermatol. 2019 Aug, 60 (3):234-236. [PubMed : 30671930 ]

Schierbeck J, Vestergaard T, Bygum A. Skin Cancer Associated Genodermatoses: A Literature Review. Acta Derm Venereol. 2019 Apr 01, 99 (4):360-369. [PubMed : 30653245 ]

Wield A, Hodeib M, Khan M, Gubernick L, Li AJ, Kandukuri S. Sebaceous carcinoma arising within an ovarian mature cystic teratoma: A case report with discussion of clinical management and genetic evaluation. Gynecol Oncol Rep. 2018 Nov, 26 :37-40. [PMC free article : PMC6138851 ] [PubMed : 30225334 ]

Kudibal MT, Venzo A. [Muir-Torre syndrome]. Ugeskr Laeger. 2018 Jul 02, 180 (27) [PubMed : 29984696 ]

Torre K, Ricketts J, Dadras SS. Muir-Torre Syndrome: A Case Report in a Woman Without Personal Cancer History. Am J Dermatopathol. 2019 Jan, 41 (1):55-59. [PubMed : 29933315 ]

Brown S, Brennan P, Rajan N. Inherited skin tumour syndromes. Clin Med (Lond). 2017 Dec, 17 (6):562-567. [PMC free article : PMC6297702 ] [PubMed : 29196359 ]

Disclosure: John Gay declares no relevant financial relationships with ineligible companies.

Disclosure: Todd Troxell declares no relevant financial relationships with ineligible companies.

Disclosure: Gary Gross declares no relevant financial relationships with ineligible companies.