Papillon-Lefèvre Syndrome and Malignant Melanoma

Abstract

Papillon-Lefèvre syndrome (PLS) is a rare autosomal-recessive genodermatosis characterized by palmoplantar hyperkeratosis and severe early-onset periodontitis. The development of malignant cutaneous neoplasms within the hyperkeratotic lesions of the syndrome is quite rare. Here, we report on a 51-year-old Japanese woman with PLS associated with recurrent malignant melanoma (MM). Mutation analysis of the cathepsin C gene revealed that the proband was homozygous for a missense mutation, c.415G→A, which is predicted to result in the amino acid substitution p.G139R. Including our case, 4 families have been described as having PLS with MM, 3 of which are Japanese, implying a high incidence of melanoma development in Japanese PLS patients. We suggest that hereditary palmoplantar keratoderma (PPK) in Japanese patients might be predisposed to MM. A literature review revealed that in 18 cases of MM-associated PPK, 13 (76%) were Japanese, suggesting a high incidence of MM in Japanese PPK patients. This tendency might be attributable to the high frequency of acral lentiginous melanoma in Japanese subjects, in contrast to a lower frequency of this subtype in Caucasians.

Evidence for a Founder Mutation in the Cathepsin C Gene in Three Families with Papillon-Lefèvre Syndrome

“…Some patients may also be predisposed to pyodermas, and sometimes severe and even fatal internal abscesses may occur [22]. It has also been found that Japanese PLS patients are predisposed to develop melanoma at sites of hyperkeratosis [1]. …”

“…Cathepsin C (CTSC), also known as dipeptidyl aminopeptidase I, is a lysosomal proteinase of the papain type that functions in removing dipeptides from the amino terminus of its substrates [1,2]. It is chemically composed of 4 identical units.…”

“…For instance, immune cells such as natural killer cells and T lymphocytes require the presence of activated granzyme A and granzyme B in order for them to be able to exert their cytolytic activity, and these granzymes are activated by the cleavage of their N-terminal peptide that is performed by CTSC. Therefore, mutations in the CTSC gene are expected to lead to an increased frequency of infections [1,7,9,10]. Similarly in the skin, mutations in CTSC might affect the epithelial differentiation process and lead to hyperkeratosis [11].…”

Cathepsin C Gene 5′-Untranslated Region Mutation in Papillon-Lefèvre Syndrome

“…Occasionally, severe infections such as liver abscesses or pneumonia occur [2,7]. Recently, a high incidence of malignant melanoma development has been reported in Japanese PLS patients [8]. …”

Papillon-Lefèvre syndrome and squamous cell carcinoma: a case report

“…Variation in the clinical presentation of PLS has been observed [11-13]. Malignant cutaneous neoplasms arising in the hyperkeratotic skin of PLS patients are very rare [14,15]. To date, an association between Papillon-Lefevre syndrome and two cases of malignant melanoma has been reported [14,15].…”