Overlapping Features of Primary Cutaneous Marginal Zone Lymphoproliferative Disorder and Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorder

Abstract

Primary cutaneous marginal zone lymphoproliferative disorder (PCMZL) and primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+ TLPD) are indolent lymphoproliferative disorders. However, cases with overlapping features can be challenging. We identified 56 CD4+ TLPD and 38 PCMZL cases from our pathology archives. Clinical, morphologic, and immunophenotypic features were reviewed. Polymerase chain reaction for immunoglobulin (IG) and T-cell receptor gamma (TRG) gene rearrangements were analyzed. Next-generation sequencing studies were performed on 26 cases with adequate material, 19 with CD4+ TLPD, and 7 with PCMZL. CD4+ TLPD presented mostly (91%) as solitary lesions, located in the head and neck area (64%), while PCMZL occurred mostly in the upper extremity (47%) and trunk (34%). Lesions were sometimes multiple (40%) and recurrences (67%) were more common. Cases of PCMZL had an increase in reactive CD3+ T cells, with frequent programmed cell death protein 1 expression, whereas cases of CD4+ TLPD often contained abundant reactive B cells. Twenty-five cases were identified as having overlapping features: 6 cases of PCMZL were clonal for both IG and TRG; 11 cases of CD4+ TLPD were clonal for IG and TRG and 6 cases of CD4+ TLPD had light chain–restricted plasma cells. By next-generation sequencing, 23 variants were detected in 15 genes, with PCMZL more likely to show alterations, most commonly affecting TNFAIP3 and FAS, altered in 5 cases. Both entities have an indolent clinical course with response to conservative therapy and management, and warrant interpretation as a lymphoproliferative disorder rather than overt lymphoma.

CD27/CD70 pathway activation in primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder

“…For the other TP53 variant we were not able to retrieve a PCR product sufficient for sequencing. Our data suggest that TP53 mutations are rare in PCSM‐LPDs, a finding recently reported by another group [21].…”

Tissue Eosinophilia in B-cell Lymphoma

“…The tumor microenvironment with abundant T cells and histiocytes, and often increased PD-1-positive cells is common to many marginal zone lymphomas. 4,18 These features are reminiscent of those commonly observed in PTCL, especially AITL, and thus may prompt diagnostic considerations for T-cell lymphoma.…”

Deciphering the spectrum of cutaneous lymphomas expressing TFH markers

“…In these patients, a monoclonal B-cell population was found, without monoclonal T-cell population, and the diagnosis of MZL could be made. The study of clonality may therefore be helpful in these cases of MZL with TFH hyperplasia of the microenvironnement 10 . Moreover, this study also highlights the value of comparing molecular techniques in cases of suspected cutaneous localization of systemic lymphoma.…”

“…Mutations do not seem correlated to prognosis in MZL: 44% of indolent cases among the mutated cases and 60% of relapses among the non-mutated cases. However, the panel targeted the most relevant genes for lymphoma diagnosis but did not cover all exons for some genes (e.g., KMT2D) and lacked a few select genes (e.g., FAS, SLAMF1, SPEN, and NCOR2), which are described in cutaneous MZL 10,32 . This could explain the negativity of some cases and the lack of correlation with the clinical course.…”