Primary Cutaneous Large B-Cell Lymphoma Shows Activation of Nuclear Factor Kappa B and Low Incidence of Epstein-Barr Virus

Abstract

Primary cutaneous lymphomas are defined as lymphomas, which are present in the skin without evidence of extracutaneous disease at the time of diagnosis. Primary cutaneous large B-cell lymphoma (PCLBCL) is a subtype of primary cutaneous B-cell lymphoma with a female predominance, occurring in elderly patients and known to have unfavorable prognosis. We evaluated 10 cases of PCLBCL in immunocompetent patients between 2005 and 2008. A panel of immunoperoxidase stains; CD3, CD10, CD20, BCL2, BCL6, and MUM1 were performed on all cases. Nuclear factor kappa B (NF-kappaB) pathway activation was evaluated using an immunostain for P65. The presence of Epstein-Barr virus (EBV) was assessed using Epstein-Barr virus encoded RNA (EBER) in situ hybridization probe. All cases were CD20 positive and CD3 negative. CD10, BCL6, BCL2, and MUM1 were positive in 4/10 (40%), 6/10 (60%), 7/10 (70%), and 7/10 (70%) cases, respectively. NF-kappaB activation was detected in 7/10 (70%) cases. One (10%) case was positive for EBV by in situ hybridization. Interestingly, the EBV positive case was also positive for MUM1 and negative for CD10, indicating an activated immunophenotype. In conclusion, majority of PCLBCL shows activation of NF-kappaB pathway with a low incidence of EBV.

Multiple genetic alterations in primary cutaneous large B-cell lymphoma, leg type support a common lymphomagenesis with activated B-cell-like diffuse large B-cell lymphoma

“…16,18 Lenalidomide, a drug showing clinical activity in myeloma and activated B-cell diffuse large B-cell lymphoma, 49 together with inhibitors of the B-cell receptor signaling pathway has been recently shown to induce synthetic lethality of activated B-cell diffuse large B-cell lymphoma cells by downregulating IRF4 and SPIB transcription factors that in turn downregulate NF-kB pathway. 19 Such molecules could represent an attractive therapeutic option in primary cutaneous large B-cell lymphoma, leg type, as NF-kB pathway seems to be activated 50 and as most of our patients poorly responded to conventional therapy. Deciphering the multiple genetic alterations of each tumor may contribute to select patients for the appropriate inhibiting therapy.…”

Primary cutaneous Epstein‐Barr virus‐positive diffuse large B‐cell lymphoma, not otherwise specified, in a nonimmunocompromised young man: A case report

“…Primary cutaneous EBV‐positive DLBCL, NOS is extremely rare and always effects elderly patients . This condition should be distinguished from EBV‐positive mucocutaneous ulcers; secondary cutaneous EBV‐positive DLBCL, NOS; and primary cutaneous EBV‐positive DLBCL with immunocompromise.…”

“…The optimal treatment and prognosis of primary cutaneous EBV‐positive DLBCL, NOS have not been clearly determined. In the literature, patients with primary cutaneous EBV‐positive DLBCL who are >55 years old show poor outcomes . In one report of an 84‐year‐old man with primary cutaneous EBV‐positive DLBCL who received CHOP chemotherapy, the disease relapsed after the sixth cycle of CHOP, and he died from complications of the disease 9 months after the initial presentation .…”

“…In the literature, patients with primary cutaneous EBV-positive DLBCL who are >55 years old show poor outcomes. [3][4][5][6][7] In one report of an 84-year-old man with primary cutaneous EBV-positive DLBCL who received CHOP chemotherapy, the disease relapsed after the sixth cycle of CHOP, and he died from complications of the disease 9 months after the initial presentation. 7 The authors considered that primary cutaneous EBV-positive DLBCL is an aggressive lymphoma.…”

New developments in the pathology of malignant lymphoma: a review of the literature published from April 2010–July 2010

“…Braghavati et al [44] studied ten cases of PCLBL in order to gain insight in the pathogenesis of this lymphoma that most often present in elderly patients. Only 1/10 cases was EBV-positive and 7/10 had an activated NF-kappaB pathway.…”