Background Primary cutaneous follicular center‐cell lymphoma (PCFCL) is one of the most common types of cutaneous B‐cell lymphoma. Differences in immunohistochemical expression of BCL2 and CD10 antigens along with the presence of t(14:18) translocation in neoplastic cells have been postulated as relevant clues in differentiating PCFCL from cutaneous lesions secondary to a systemic follicular lymphoma (SCFL). The aim of this study is to evaluate the significance and usefulness of these parameters in a large series of patients. Methods Patients with PCFCL and SCFL diagnosed at three university hospitals in Barcelona, from 2000 to 2015 were reviewed. Clinical, histopathological, immunophenotypical, genetic, and outcome parameters were analyzed. Results Eighty‐one cases (59 PCFCL and 22 SCFL) were included. There were no significant differences between PCFCL and SCFL cases regarding clinical presentation, site of involvement, or predominant type of skin lesions. Most patients in both groups showed positivity for BCL2 and CD10, but strong expression of BCL2 and CD10 was associated with SCFL cases. Although more frequent in SCFL, a small proportion of PCFCL cases also showed the t(14:18) on FISH analysis. Conclusion The intensity of BCL2 expression was found to be the single most valuable clue in differentiating PCFCL from SCFL cases on histopathological grounds.

Patients with older age, anaemia or thrombocytopenia, and without arthralgia are more likely to have malignancy-associated SS. We recommend that patients with SS without clear aetiology should be followed up for at least 16 months to exclude a possible underlying haematological malignancy.