Primary cutaneous follicular helper T‐cell lymphoma: diagnostic pitfalls of this new lymphoma subtype

Abstract

The recently proposed entity of cutaneous follicular helper T (T(FH)) cell lymphoma (CT(FH)CL) harbors distinct clinical and histopathologic features. Here, diagnostic pitfalls are exemplified in a case report and by review of the literature. A 45-year-old patient developed rapidly growing nodules and plaques on upper arms and buttocks, which were initially misdiagnosed as primary cutaneous follicle center B-cell lymphoma (CFCL). Consequently, systemic therapy with rituximab failed and consecutive skin biopsies revealed CT(FH)CL (CD3+CD4+CD10+PD-1+bcl6+ICOS+CXCL13+). Interestingly, the prima vista PD-1-positive and CD10-positive tumor cells lost PD-1 expression in follow-up biopsies while retaining CD10, ICOS and CXCL13 expression. All biopsy specimens displayed an identical clonal T-cell population. Initially, nodules were controlled by local radiotherapy and oral psoralen combined with ultraviolet A (PUVA) therapy. However, disease recurred and progressed rapidly with disseminated nodules. Treatment with bexarotene, methotrexate and polychemotherapy failed to stop disease progression. Finally, modified total skin electron beam radiation resulted in complete remission. Disease stabilized on maintenance therapy with bexarotene in combination with ultraviolet A (UVA) therapy. The case highlights that because of concomitant B-cell stimulation, CT(FH)CL clinicopathologically is prone to be mistaken for CFCL. Importantly, CT(FH)CL might lose PD-1 while retaining CD10 expression in later stages, which may lead to confusion in distinguishing CT(FH)CL from CFCL.

Primary Cutaneous Follicle Center Lymphoma

“…2 It can easily be misdiagnosed as PCFCL because it often displays a nodular architecture, includes numerous B cells, and expresses follicular markers, including CD10 and BCL6. 38,40 Similar to PCFCL, patients tend to be older (60 years) and present with multiple plaques, papules, and/or nodules, although they are more likely to be numerous, widely dispersed and involve the extremities. 38,41 However, close attention to the lymphoid infiltrate reveals that the neoplastic cells are atypical T cells that show a follicular helper T cell immunophenotype.…”

“…38,41 However, close attention to the lymphoid infiltrate reveals that the neoplastic cells are atypical T cells that show a follicular helper T cell immunophenotype. 38,40 Primary cutaneous follicular helper T-cell lymphoma may also show syringotropism, a finding that is not seen in PCFCL. 38 These patients do not respond to rituximab.…”

Cutaneous localization of angioimmunoblastic T‐cell lymphoma may masquerade as B‐cell lymphoma or classical Hodgkin lymphoma: A histologic diagnostic pitfall

“…TFH‐derived PTCL mimicking B‐cell lymphoma or cHL are well reported in lymph node . Primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder, a cutaneous lymphoproliferative disorder that derives from a skin‐homing CD4+ T‐cell with TFH‐cell characteristics may be misdiagnosed as cutaneous B‐cell lymphoma, usually as extranodal marginal zone lymphoma (MZL), because of a major B‐cell infiltrate . Of interest, AITL cutaneous presentation may also be suggestive of extranodal MZL as showed by Kaffenberger et al Careful assessment of the T‐cells is thus required to assess the correct diagnosis.…”

“…[30][31][32] Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, a cutaneous lymphoproliferative disorder that derives from a skin-homing CD4+ T-cell with TFH-cell characteristics may be misdiagnosed as cutaneous B-cell lymphoma, usually as extranodal marginal zone lymphoma (MZL), because of a major B-cell infiltrate. 33,34 Of interest, AITL cutaneous presentation may also be suggestive of extranodal MZL as showed by Kaffenberger et al 35 Careful assessment of the T-cells is thus required to assess the correct diagnosis. Moreover, the pathologist should look for unusual Interestingly, their expression is maintained in extranodal dissemination of AITL.…”

Cutaneous CD4 + small–medium T‐cell Lymphoma

“…8.5). PD-1 expression can get lost in follow-up biopsies [21]. For a detailed discussion of such cases see the section on primary cutaneous T follicular helper (T FH )-cell lymphoma in this chapter.…”