Recurrent primary cutaneous marginal zone lymphoma: a comparative study of initial tumours, recurrences, and outcomes in 61 patients

Abstract

Aims: Primary cutaneous marginal zone lymphoma (PCMZL) is considered a lymphoproliferative disorder (International Consensus Classification, ICC) or an overt lymphoma (WHO-HAEM5). Seeking evidence for a reactive process or true lymphoma, we retrieved recurrent PCMZLs from the French Study Group of Cutaneous Lymphoma (GFELC) database.

Methods: Histology, phenotype (light-chain restriction, immunoglobulin, and immune-receptor translocation-associated protein-1 [IRTA1] expression) and B-cell clonality at diagnosis and recurrence were compared according to recurrence site (local, locoregional, or distant) and outcomes.

Results: Initial lesions of the 61 patients (mean age 52) were mostly isolated on the trunk (48%) and classified T1 (70%). Times to first recurrence for local, locoregional, and distant recurrences, were 20, 29, and 37 months, respectively. Light-chain restriction type did not differ significantly between local/locoregional recurrences and distal recurrences (P = 0.06; n = 60). The same B-cell clones were identified for 23/42 local/locoregional recurrences, while 5/19 distant recurrences showed different clonal profiles (P = 0.0003). No tumour expressed IRTA1. Fifty-eight tumours were heavy-chain (IgG/IgG4) class-switched PCMZLs and 3 IgM+/IgD- PCMZLs. All IgM+ tumours underwent either transformation (skin or brain) into diffuse large B-cell lymphomas (DLBCLs) and extracutaneous spreading.

Conclusion: As suggested by WHO-HAEM5, immunoglobulin phenotype assessment (IgM alongside IgD) appears to be a possible valuable tool in the initial diagnosis of PCMZL to differentiate between the indolent class-switched PCMZL (IgM-negative) and IgM+ (IgD-) PCMZL, which has an uncertain prognosis. The variation in B-cell rearrangements and light chain restriction observed in distant recurrences of PCMZL may suggest different antigen-driven stimulation processes.

Keywords: heavy‐chain class‐switched; primary cutaneous marginal zone lymphoma; primary cutaneous marginal zone lymphoproliferative disorder; transformed marginal zone lymphoma.

Figure 1

Histological findings. (A, HES×20) Dense dermal multinodular infiltrate of small lymphoplasmocytoid B cells, lymphoid follicles with a germinal centre (clearly observed on the CD21‐lablled section), and rare plasma cells. (B, HES×20) Superficial nodular dermal infiltrate raising the epidermis, often clinically considered basocellular carcinoma. (C, HES×20) Differential diagnosis with follicle centre B‐cell lymphoma often seen on the trunk. (D, HES×20 and HES×100) plasma cell‐rich PCMZL with kappa light chain restriction (ISH ×100). [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

IgM or IgG/IgG4 class‐switched phenotype. (A, x100) IgG class‐switched tumour. (B, x40) IgG4 class‐switched tumour. (C) Naïve or memory IgM+ B‐cell on an IgG‐class switched tumour: colocalized CD21, IgM and IgD expression. (D) IgM+ recurrent PCMZL: B cells are diffusely IgM+ but IgD–. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Transformed‐MZL (t‐MZL) in a 70‐year‐old woman. (A) First photo of PCMZL (2016) and (B, HESx10) its histology. (C) That woman's local‐regional recurrence (2021) with (D, HESx10) two parts: PCMZL (*) and t‐MZL (**). (E*) Nontransformed component (HESx100) with low proliferative index (Ki67:10%) but IgM+ expression on (IgD–) B cells. (F**) t‐MZL component with large‐cell enrichment (HESx100), high proliferative index (Ki67: 70%) and diffuse IgM+ expression on (IgD–) B cells. [Color figure can be viewed at wileyonlinelibrary.com]