Leticia Quintanilla-Fend LYWS-275 (C646-15) Institute of Pathology University of Tübingen, Germany

Clinical history A 72 year-old asymptomatic woman, presented in October 2015 with enlargement of a left submandibular lymph node (2.8 cm). The peripheral blood showed: Leukocytes: 12.47 G/L, Hb:13.7 g/dl, platelets: 204 G/L The Lymph node was biopsied (submitted) The BM biopsy was negative. The patient was considered to be in Stage 1A disease.

40x HE 20x HE 40x Giemsa

CD20 CD3 CD5 CD23

BCL2 BCL6 MUM1 CD10

MYC CD30 p53

Cyclin D1 Cyclin D1 BAP

Sox 11 MiB1

Proposed diagnosis Diffuse large B-cell lymphoma, nos with CD30 and cyclin D1 expression with CCND1 trisomy, presenting with stage 1A disease. A primary mediastinal B-cell lymphoma in a submandibular lymph node without mediastinal involvement cannot be ruled out

Interesting features (1) This case was referred to us with the diagnosis of blastoid mantle cell lymphoma due to the unusual morphology and the strong homogeneous expression of cyclin D1. However, the tumor cells were SOX11 and CD5 negative and the FISH analysis did not demostrate a CCND1 break, instead a CCND1 trisomy was identified. The morphology and the phenotype of the tumor cells are reminiscent of PMBL but without mediastinal involvement. Such cases have been recently described (Am J Surg Pathol 2015; 39:1322). The expression of cyclin D1 in DLBCL has been reported in several series representing 1.5 to 15% of all DLBCL cases of both GCB and ABC type. The percentage of cells that expresses cyclin D1 varies with most cases showing a heterogeneous, weak expression in up to 50% of tumor cells. In most cases no CCND1 genetic alterations have been documented. However, rarely like in this case, three copies of CCND1 have been identified by FISH analysis, which is likely the explanation for the strong homogeneous expression of cyclin D1 in this case. This scenario seems to be similar to the situation in plasma cell myeloma, where we demonstrated that extra copies of chromosome 11 explain in some myeloma cases the cyclin D1 expression.

Interesting features (2) The third point of interest is the strong homogeneous expression of CD30. DLBCL with CD30 expression represents around 14 to 25% of all DLBCL cases, depending on the cutoff used. Several studies have shown that CD30+ DLBCL tend to have a more favourable outcome. PMBL were excluded from these studies. Nevertheless, recent gene expression profile analysis has shown that a subset of these CD30+ DLBCLs could represent PMBL without mediastinal involvement, which may partially explain the better prognosis of these tumors. In the present case, the localization of the LN, the morphology, the CD30 and variable CD23 positivity and lack of Ig expression raises the possibility of a nodal PMBL. Gene expression profile analysis is necessary to confirm this diagnosis. Despite cyclin D1 expression, the tumor had a low proliferation rate and the patient presented with stage 1A disease and has responded very well to therapy. This finding underlies the importance of investigating CD30 expression in DLBCL and the possibility of PMBL without evidence of mediastinal involvement.