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

• Published in: Journal of the American Academy of Dermatology 2011-01, Vol.64 (1), p.135-143.e4
• Main Authors: Felcht, Moritz, MD, Booken, Nina, MD, Stroebel, Philipp, MD, Goerdt, Sergij, MD, Klemke, Claus-Detlev, MD
• Format: Article
• Language: English
• Subjects: Adult; Aged; benign lymphocytic infiltrate; Biological and medical sciences; BIOMED-2; Biopsy, Needle; Cohort Studies; Dermatology; Diagnosis, Differential; Female; Germany; Hematologic and hematopoietic diseases; Humans; IgH rearrangement; Igκ; Immunohistochemistry; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - pathology; Lymphoma, B-Cell, Marginal Zone - genetics; Lymphoma, B-Cell, Marginal Zone - pathology; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Medical sciences; Middle Aged; molecular biology; Neoplasm Staging; Pathology, Molecular - methods; primary cutaneous B-cell lymphoma; rearrangement; Sensitivity and Specificity; Skin Neoplasms - pathology
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2009.12.062

Background 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. Objective We investigated the diagnostic value of the BIOMED-2 Concerted Action BMH4 CT98-3936 protocol in PCBCL. Methods 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. Results 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. Limitations A multicentric, randomized, blinded study is necessary to confirm our results. Conclusion 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.