The importance of the family tree

Genodermatosis

Dr. Emmanuelle Bourrat

Saint-Louis Hospital

The clinical case
Now it's your turn!
Co-prescription and advice

Clinical case presentation

This 60-year-old man, with no personal medical history, had been experiencing an increase in the number of papules on his face and upper trunk for several years. These lesions were quite monomorphic, with little or no progression. They were papules several millimeters in size, skin-colored, normal, white or yellow, often umbilicated.

A larger lesion on the shoulder and, above all, a significant family history on the mother's side (early colon cancer in the mother and uncle, endometrial cancer in the mother, disseminated cancer before age 50 in the grandfather) prompted a request for a biopsy for histopathological examination.

The histology of this tumor showed a well-circumscribed lesion, largely connected to the surface epidermis, with organoid architecture and a predominance of mature sebocytes. Immunohistochemical study showed loss of hMSH2 and hMSH6 protein expression.

Your turn

What is your diagnosis?

Select 1 answer(s) from the following choices:

Age-related sebaceous hyperplasia

Muir-Torre syndrome

Birt-Hogg-Dubé syndrome

Gorlin-Goltz syndrome, or basal cell nevus syndrome

Wrong answer!

Good answer!

Selected diagnosis

The biopsied lesion is a sebaceous adenoma. In this context of loss of expression of two of the four proteins of the DNA mismatch repair (MMR) system and of familial cancers, Muir-Torre syndrome (MTS) must be considered.

Muir-Torre syndrome (MTS) is a Lynch syndrome characterized by skin lesions consisting of sebaceous tumors (adenomas, sebaceomas, carcinomas) and/or multiple keratoacanthomas.

These two autosomal dominant genetic syndromes share:

A germline mutation in one of the genes encoding one of the four MMR proteins (MLH1, PMS2, MSH2 and MSH6)
Autosomal dominant inheritance
Predisposition to non-polyposis colorectal cancer
Predisposition to other cancers of the “Lynch spectrum”: carcinomas of the endometrium, urinary tract, biliary tract, ovary, small intestine and glioblastomas
Loss of expression by immunohistochemistry of one or more MMR protein markers on all these tumors and a tumor phenotype characterized by microsatellite instability.

The dermatologist may therefore be led to suspect MTS based on multiple sebaceous skin lesions with compatible immunohistochemistry. The diagnosis should be confirmed by genetic testing and the patient referred for multidisciplinary oncological follow-up.

Explanation of wrong answers

Sebaceous hyperplasia is very common after the age of 50, presenting as yellowish, umbilicated papules a few millimeters in size, located in seborrheic areas of the face (forehead, temples and cheeks). Diagnosis is clinical and treatment is for cosmetic purposes (electrocoagulation).
The lesions of Birt-Hogg-Dubé syndrome also predominate on the face and upper trunk, but are flat, milky-white, non-umbilicated papules corresponding to fibrofolliculomas, angiofibromas or trichodiscomas. This autosomal dominant genodermatosis is associated with an increased risk of pneumothorax and renal cancer.
The lesions of Gorlin-Goltz syndrome are basaloid hamartomas of non-specific appearance, or basal cell carcinomas, which are more suggestive and appear mainly in photoexposed areas in young adults. Associated neoplastic complications are mainly medulloblastomas in very young children.

Message from the expert

In the presence of multiple skin tumors, even benign ones, taking a comprehensive family history using a pedigree is an essential step, as is biopsy of a skin lesion. The pattern of inheritance, personal or family history of malignancies and the organs involved, as well as the histological nature of the skin lesions, are all essential for guiding the genetic analysis of a possible cancer-predisposing genodermatosis.

References

_{Frouin E, Dansette D. Case 3^: Cutaneous epithelial tumors [Tumeurs épithéliales cutanées]. Ann Pathol. 2020 Sep;40(5):356-365. French.}
_{https://pubmed.ncbi.nlm.nih.gov/32718768/}