Lentiginoses in polycythemia vera patient: Is there a role for JAK2 (V617F) mutation?

Abstract

Lentiginoses is a clinical feature in which lentigines are remarkably present in large numbers or when they occur in a distinctive distribution on apparently normal skin. This entity may be congenital or acquired and may cover a wide spectrum of diseases ranging from an isolated benign pigmentary disorder to numerous syndromes associated with molecular abnormalities.We present a 59-year-old female patient with multiple lentigines which first emerged 3 y ago concurrently with policytemia vera. The patient had found to be positive for Janus Kinase-2 (JAK-2) mutation. Over activation of the pathway due to JAK-2 V617F mutation is a well-known condition in myeloproliferative diseases but has not been reported in melanocytic disorders. Moreover, several signaling pathways have previously been defined with lentiginosis except JAK-STAT pathway. We want to draw attention to the potential effect of JAK-2 mutation in lentigogenesis with this case report.

Keywords: Janus-kinase 2; Polycythemia vera; lentiginosis; tyrosine kinase.

Figure 1.

Multiple brown macular lesion on bilateral lower extremity.

Figure 2.

Homogenous, light brown reticular lines.

Figure 3.

Hypothetical association of JAK2/ROS/RAS crosstalk pathway leading to lentiginosis (Red Arrows). JAK with red midpoint and blue star represents the mutated JAK2.

Figure 4.

(A) Phenolyzer image of Lenginosis and Polyceythemia vera association network over JAK2. http://phenolyzer.usc.edu/done/3350/9wmTwOGoCUhSn14p/index.html.) (B) Phenolyzer Barplot of molecule list most related with PV and Lentiginosis association.

Figure 5.

Real-Time Polymerase chain reaction (RT PCR) based JAK2 V617F mutation analysis of the patient. Upper graphic represents whether RT PCR has occurred. Lower graphic represents the presence of normal and mutant (V617F) allele of JAK2 mutation at DNA of biopsy drawn from skin lentigines of the patient. (TR PCR was done according to manucfacturer's instructions [JAK2 V617F mutation analyses kit, SNP Biyoteknoloji, Ankara, Turkey], using a Rotor Gene 2Plex [Qiagen, Hilden, Germany] and allelic discrimination analysis was done using Rotor Gene Q Series Software 2.1.0.