Multiple pilomatricomas in association with myotonic dystrophy and a family history of melanoma
Authors: Brenda J. Berberian, Todd M. Colonna, Mary Battaglia, Virgina I. Sulica
Journal: Journal of the American Academy of Dermatology (1997)

Pilomatricomas were first described in 1880 by Malherbe and Chenantais 1Malherbe A Chenantais J. Note sur l' épitheliome calcifié des glandes sebacées.Progr Med. 1880; 8: 826-828Google Scholar and were so named in 1961 by Forbes and Helwig. 2Forbes R Helwig EB. Pilomatrixoma (calcifying epithelioma).Arch Dermatol. 1961; 83: 606-618Crossref PubMed Scopus (379) Google Scholar In 1965, Cantwell and Reed 3Cantwell AR Reed WB. Myotonia atrophica and multiple calcifying epithelioma of Malherbe.Acta Derm Venereol (Stockh). 1965; 45: 387-390PubMed Google Scholar first reported the association of pilomatricomas with myotonic dystrophy. Harper 4Harper PS. Calcifying epithelioma of Malherbe and myotonic dystrophy in sisters.Birth Defects. 1971; 7: 343-345PubMed Google Scholarfirst noted the familial coexistence of the two diseases in 1971. Since then, approximately 11 cases of pilomatricomas associated with myotonic dystrophy have been reported; of these, only four have been familial for both diseases. 4Harper PS. Calcifying epithelioma of Malherbe and myotonic dystrophy in sisters.Birth Defects. 1971; 7: 343-345PubMed Google Scholar, 5Chiaramonti A Gilgor RS. Pilomatricomas associated with myotonic dystrophy.Arch Dermatol. 1978; 114: 1363-1365Crossref PubMed Scopus (72) Google Scholar, 6Street ML Rogers RS. Multiple pilomatricomas and myotonic dystrophy.J Dermatol Surg Oncol. 1991; 17: 728-730Crossref PubMed Scopus (24) Google Scholar Myotonic dystrophy is an autosomal dominant disease with variable penetrance and a prevalence of 2:100,000 to 5:100,000. 7Harper PS. Myotonic dystrophy.2nd ed. WB Saunders, London1989Google Scholar It is caused by a tri-nucleotide expansion at the 3′ untranslated region of the myotonin protein kinase gene on chromosome 19. 8Mahadevan M Tsilfidis C Sabourin L et al.Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene.Science. 1992; 255: 1253-1255Crossref PubMed Scopus (1500) Google Scholar The clinical manifestations usually appear in early adulthood and are caused by an inability to relax muscles properly after contraction. The muscles commonly affected are in the hands, face, and forearms. Clinical manifestations include muscle wasting, weakness, frontal balding, cataracts, expressionless facies, and testicular atrophy. Other features may include mental retardation, diabetes mellitus, heart block, and hyperostosis frontalis externa. 3Cantwell AR Reed WB. Myotonia atrophica and multiple calcifying epithelioma of Malherbe.Acta Derm Venereol (Stockh). 1965; 45: 387-390PubMed Google Scholar The following patient illustrates an example of a familial association between pilomatricomas and myotonic dystrophy, with an extensive family history of melanoma. A 26-year-old white man had asymptomatic, slowly enlarging subcutaneous nodules on his right arm and scalp. The lesion on his arm had been present for 7 years, and the scalp lesions had been present for 2 years. Myotonic dystrophy had been diagnosed in 1993. The patient's father had myotonic dystrophy and died at 48 years of age of sudden cardiac arrest. His brother also has myotonic dystrophy. Both maternal and paternal grandfathers had had melanoma, and his father had multiple atypical nevi on his back and upper extremities. Several were removed; histopathologic examination revealed compound nevi. The patient was mentally challenged, with frontal balding, expressionless facies, and decreased muscular strength. Examination revealed several subcutaneous nodules on the scalp and right upper extremity. They were hard, flesh-colored, and nonmobile with a "tent" sign. The tumors were removed, and histopathologic examination confirmed the diagnosis of pilomatricomas. When pilomatricomas occur in patients with myotonic dystrophy, the age at onset is usually later, with a mean age of 24 years 14Vollenweider RS Delozier-Blanchet CD Mesouye I Saurat J-H. Melanoma associated with ring chromosome 7.Dermatology. 1993; 186: 138-143Crossref PubMed Scopus (10) Google Scholar versus a mean age of approximately 12 years in other types. In 75% of patients the tumors are multiple, 4Harper PS. Calcifying epithelioma of Malherbe and myotonic dystrophy in sisters.Birth Defects. 1971; 7: 343-345PubMed Google Scholar, 5Chiaramonti A Gilgor RS. Pilomatricomas associated with myotonic dystrophy.Arch Dermatol. 1978; 114: 1363-1365Crossref PubMed Scopus (72) Google Scholar, 6Street ML Rogers RS. Multiple pilomatricomas and myotonic dystrophy.J Dermatol Surg Oncol. 1991; 17: 728-730Crossref PubMed Scopus (24) Google Scholar whereas in only 3.5% of the other variants are there multiple tumors. In patients with myotonic dystrophy, there are almost always tumors on the scalp, whereas in the other clinical variants the distribution of tumors is random. Four percent of patients with myotonic dystrophy have pilomatricomas. 15Zaim MT. Pilomatricoma with melanocytic hyperplasia: an uncommon occurrence and a diagnostic pitfall.Arch Dermatol. 1987; 123 ([letter]): 865-866Crossref PubMed Scopus (14) Google Scholar Approximately 5% of malignant melanomas are hereditary. The most substantial evidence links chromosome 9p to melanoma,16Taaffe A Wyatt EH Bury HPR. Pilomatricoma (Malherbe): a clinical and histopathological survey of 78 cases.Int J Dermatol. 1988; 27: 477-480Crossref PubMed Scopus (39) Google Scholar but various authors have demonstrated that chromosomes 1,17 6,18 and 719 may also be involved in the pathogenesis. There are reports linking pilomatricomas and melanoma. Zaim20 described melanocytic hyperplasia within a pilomatricoma and suggested that malignant melanoma may arise within a pilomatricoma. Taaffe, Wyatt, and Bury10Harper PS. Calcifying epitheliomas of Malherbe: association with myotonic muscular dystrophy.Arch Dermatol. 1972; 106: 41-44Crossref PubMed Scopus (78) Google Scholar described a patient with pilomatricomas and metastatic melanoma, and Street and Rogers6Street ML Rogers RS. Multiple pilomatricomas and myotonic dystrophy.J Dermatol Surg Oncol. 1991; 17: 728-730Crossref PubMed Scopus (24) Google Scholar described a patient with pilomatricomas whose mother had an unknown skin cancer. This patient's family history of melanoma, coupled with these published reports, suggests that there may be a pleiotrophic effect involving chromosome 9 that induces not only myotonic dystrophy and pilomatricomas but may also contribute to the pathogenesis of melanoma.