ALK‐positive primary cutaneous anaplastic large cell lymphoma: a case report and review of the literature

Abstract

Anaplastic large cell lymphoma (ALCL) limited to the skin is a distinct disease that is designated primary cutaneous ALCL (pcALCL). It has an indolent course with a significantly better prognosis compared to systemic ALCL (sALCL). Anaplastic lymphoma kinase (ALK) expression in lesions of cutaneous ALCL is classically considered to be a marker for skin involvement by sALCL. However, recent reports of patients with ALK-positive pcALCL challenge this concept and raise prognostic and therapeutic dilemmas. Herein, we report a case of ALK-positive pcALCL in a 45-year-old woman who was treated with local radiotherapy. We review previously reported cases in the literature to better characterize this rare variant. Overall, the rates of cutaneous recurrence, systemic dissemination, and disease-related mortality in ALK-positive pcALCL do not differ from those previously reported in pcALCL. ALK-positive pcALCL is diagnosed at younger age and has a better disease course in children compared to adults with lower incidences of skin recurrence and progression to systemic disease. We conclude that ALK-positivity in cutaneous ALCL does not necessarily imply systemic disease. ALK-positive pcALCL has an excellent prognosis and should be treated by excision and/or radiotherapy. However, patients must remain under close long-term follow-up as recurrence and progression to systemic disease may occur.

DNA copy number imbalances in primary cutaneous lymphomas

“…Even if ALK gene rearrangements are rarely seen in cALCL, a subset of case reports describes this gene rearrangement. 25 In our case, copy number gains are positive on the ALK locus gene 2p23.2-p23.1 (in four cases out of 73). Deletions in TP53 gene located on 17p13.1 and PRDM1 (6q21) are also seen in our cases, fact reported by other authors as often events in this type of lymphoma.…”

“…While typically ALK is implicated in the pathogenesis of ALCL (see Subsection CNAs in ALCL) or diffuse large B‐cell lymphoma (DLBCL; see Subsection CNAs in DLBCL), this observation provides a rare report of ALK rearrangement in MF (Fig. ).…”

“…Oncogenes like NRAS (1p13.2), RAF1 (3p25), CBFA2 (21q22.3) and JUNB (19p13.2) are amplified more or less in the 73 samples of ALCL. Even if ALK gene rearrangements are rarely seen in cALCL, a subset of case reports describes this gene rearrangement …”

“…Also, while the probe segmentation resulted in a single segment (2:29193223-29920658 DUP; hg38 coordinates), a cluster of five probes covering the ALK locus suggested for an additional copy number gain. While typically ALK is implicated in the pathogenesis of ALCL (see Subsection CNAs in ALCL) 25,26 or diffuse large B-cell lymphoma (DLBCL; see Subsection CNAs in DLBCL), 27 this observation provides a rare report of ALK rearrangement in MF (Fig. 3).…”

Comments concerning “ALK positive primary cutaneous anaplastic large cell lymphoma: a case report and review of the literature”

“…We read with interest the recent review of literature by Geller et al . on anaplastic lymphoma kinase (ALK)‐positive primary cutaneous anaplastic large cell lymphoma (ALCL) . The authors describe the case of a middle‐aged woman with an ulcerated nodule on the abdomen.…”