No TP63 rearrangements in a selected group of primary cutaneous CD30+ lymphoproliferative disorders with aggressive clinical course

Abstract

Primary cutaneous CD301 lymphoproliferative disorders (CD30 1 LPDs) are a disease spectrum including primary cutaneous anaplastic large cell lymphoma (C-ALCL) and lymphomatoid papulosis (LyP).1 C-ALCL presents as solitary, grouped, or, rarely, multifocal nodules and tumors that often ulcerate. Cutaneous relapses are common, but extracutaneous dissemination occurs in only 10% to 15% of patients and mainly involves regional lymph nodes. [2][3][4] LyP is characterized by a chronic course of recurrent, self-healing papulonecrotic or nodular skin lesions. Extracutaneous disease rarely develops.3 The prognosis of both conditions is usually excellent with a 5-year disease-specific survival of approximately 90% for C-ALCL and almost 100% for LyP. or TP63 rearrangement with 5-year survival rates of 17% and 42%, respectively.8-10

The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas

“…24,31,32 TP63 gene rearrangements are associated with a poor survival in ALK 2 systemic ALCL, but are not or are rarely found in C-ALCL. 33,34 A novel recurrent NPM1-TYK2 gene fusion resulting in constitutive STAT signaling has been described in both C-ALCL and LyP. 35…”

CD30-positive primary cutaneous lymphoproliferative disorders: molecular alterations and targeted therapies

“…To date, no ALK fusions have been reported in LyP, in contrast to pcALCL, and no TP63 rearrangements have been found in these patients. 25,27,28…”

“…They found no cases with a TP63 translocation, and confirmed the lack of specificity of the TP63 immunohistochemistry. 28…”

Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas

“…The different ALCLs represent about 16% of peripheral T cell lymphomas [ 1 ]. As summarized in Table 1 , they form a heterogeneous group of CD30-positive T cell non-Hodgkin lymphomas according to their site of onset (systemic, cutaneous or breast implant-associated) and their genetic features, with several groups according to the presence of ALK rearrangement and subsequent ALK expression defining ALK-positive or ALK-negative ALCLs [ 2 , 3 , 4 ]. ALK-negative ALCL may carry DUSP22 rearrangements and/or TP63 rearrangements.…”

“…ALK-negative ALCL may carry DUSP22 rearrangements and/or TP63 rearrangements. ALK-positive and DUSP22-rearranged ALCLs have a better prognosis than triple-negative ALCL and TP63-rearranged ALCL, which have the worst outcome [ 2 , 3 , 5 , 6 , 7 ]. The site of origin is critical as illustrated by cutaneous ALCL (C-ALCL), which is commonly ALK-negative [ 8 , 9 , 10 ].…”