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. 2022 Oct 27;14(21):5274.
doi: 10.3390/cancers14215274.

Panel Sequencing of Primary Cutaneous B-Cell Lymphoma

Marion Wobser  1 , Patrick Schummer  1 , Silke Appenzeller  2 , Hermann Kneitz  1 , Sabine Roth  2   3 , Matthias Goebeler  1 , Eva Geissinger  3   4 , Andreas Rosenwald  2   3 , Katja Maurus  2   3
Affiliations

Panel Sequencing of Primary Cutaneous B-Cell Lymphoma

Marion Wobser et al. Cancers (Basel). .

Abstract

Background: Primary cutaneous follicular B-cell lymphoma (PCFBCL) represents an indolent subtype of Non-Hodgkin's lymphomas, being clinically characterized by slowly growing tumors of the skin and common cutaneous relapses, while only exhibiting a low propensity for systemic dissemination or fatal outcome. Up to now, only few studies have investigated underlying molecular alterations of PCFBCL with respect to somatic mutations.

Objectives: Our aim was to gain deeper insight into the pathogenesis of PCFBCL and to delineate discriminatory molecular features of this lymphoma subtype.

Methods: We performed hybridization-based panel sequencing of 40 lymphoma-associated genes of 10 cases of well-characterized PCFBCL. In addition, we included two further ambiguous cases of atypical B-cell-rich lymphoid infiltrate/B-cell lymphoma of the skin for which definite subtype attribution had not been possible by routine investigations.

Results: In 10 out of 12 analyzed cases, we identified genetic alterations within 15 of the selected 40 target genes. The most frequently detected alterations in PCFBCL affected the TNFRSF14, CREBBP, STAT6 and TP53 genes. Our analysis unrevealed novel mutations of the BCL2 gene in PCFBCL. All patients exhibited an indolent clinical course. Both the included arbitrary cases of atypical B-cell-rich cutaneous infiltrates showed somatic mutations within the FAS gene. As these mutations have previously been designated as subtype-specific recurrent alterations in primary cutaneous marginal zone lymphoma (PCMZL), we finally favored the diagnosis of PCMZL in these two cases based on these molecular findings.

Conclusions: To conclude, our molecular data support that PCFBCL shows distinct somatic mutations which may aid to differentiate PCFBCL from pseudo-lymphoma as well as from other indolent and aggressive cutaneous B-cell lymphomas. While the detected genetic alterations of PCFBCL did not turn out to harbor any prognostic value in our cohort, our molecular data may add adjunctive discriminatory features for diagnostic purposes on a molecular level.

Keywords: B-cell lymphoma; primary cutaneous follicular B-cell lymphoma; targeted sequencing.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Overview of mutations in primary cutaneous FBCL. Graphical illustration of detected variants within 15 of the analyzed 40 lymphoma-associated genes. Left side of graph: ten cases of PCFBCL (from top to bottom, most frequently to less frequently mutated genes). Right side of graph: two cases of arbitrary B-cell-rich cutaneous infiltrates being finally reclassified as PCMZL.
Figure 2
Figure 2
Localization of the detected splice site mutations within the FAS gene and confirmatory Sanger sequencing (patient #2). (A) Schematic illustration of the detected splice site mutation c.676G > A and processed mRNA lacking exon 8 of case #2. (B) Localization of the annotated mutation p.Asp226Asn at the protein level, leading to a truncated protein p.Glu218Metfs*4. (C) Results of Sanger sequencing of cDNA exhibiting a truncated FAS mRNA transcript lacking exon 8.
See this image and copyright information in PMC

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