The value of molecular diagnostics in primary cutaneous B-cell lymphomas in the context of clinical findings, histology, and immunohistochemistry

Abstract

Primary cutaneous B-cell lymphoma (PCBCL) is classified into 3 major subtypes: primary cutaneous follicle center lymphoma (PCFCL); primary cutaneous marginal zone B-cell lymphoma (PCMZL); and primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT). Diagnosis of PCBCL is mainly based on clinical and (immuno)-histochemical grounds. We investigated the diagnostic value of the BIOMED-2 Concerted Action BMH4 CT98-3936 protocol in PCBCL. We analyzed with the BIOMED-2 Concerted Action BMH4 CT98-3936 protocol skin specimens from patients with well-defined clinical and (immuno)-histologic PCBCL (n = 18) in comparison with benign lymphocytic infiltrates (n = 9). For molecular staging we also investigated 13 extracutaneous samples from 6 patients with PCLBCL, LT. Each sample was investigated at least twice. Monoclonality was detected in all of 5 PCFCL; 5 of 6 PCMZL; all of 6 PCLBCL, LT; and 2 of 9 benign lymphocytic infiltrates. In 5 of 6 patients with PCLBCL, LT, a clone corresponding to the clone detected in the skin was detected in 3 of 5 bone-marrow, 4 of 5 blood, and 1 of 3 lymph node specimens. DNA amplification using tubes A and B of IgH was not possible in PCFCL/PCMZL, benign lymphocytic infiltrates, and extracutaneous specimens of PCLBCL, LT, even after repeated analysis up to 11 times. Pseudomonoclonality was identified by repeated analyses in one case of PCMZL and in one case of benign lymphocytic infiltrate. A multicentric, randomized, blinded study is necessary to confirm our results. Molecular diagnosis supports the clinical and (immuno)-histologic diagnosis in PCBCL. In PCLBCL, LT, molecular staging may be useful. Tubes C through E of IgH and Igκ analyses seem to be superior to tubes A and B of IgH. Each sample should be analyzed at least twice to assess the possibility of pseudomonoclonality.