Clinicopathologic and Molecular Characterization of Epstein-Barr Virus–positive Plasmacytoma

Abstract

Epstein-Barr virus (EBV)-positive plasmacytoma is a rare plasma cell neoplasm. It remains unclear whether EBV-positive plasmacytoma represents a distinct entity or a variant of plasmacytoma. It shares morphologic features with plasmablastic lymphoma (PBL) and may cause diagnostic uncertainty. To better understand EBV-positive plasmacytoma and explore diagnostic criteria, this study describes 19 cases of EBV-positive plasmacytoma, compared with 27 cases of EBV-negative plasmacytoma and 48 cases of EBV-positive PBL. We reviewed the clinicopathologic findings and performed immunohistochemistry, in situ hybridization for EBV, fluorescence in situ hybridization for MYC, and next-generation sequencing. We found that 63.2% of patients with EBV-positive plasmacytoma were immunocompromised. Anaplastic features were observed in 7/19 cases. MYC rearrangement was found in 25.0% of them, and extra copies of MYC in 81.3%. EBV-positive and EBV-negative plasmacytomas possessed similar clinicopathologic features, except more frequent cytologic atypia, bone involvement and MYC aberrations in the former group. The survival rate of patients with EBV-positive plasmacytoma was comparable to that of patients with EBV-negative plasmacytoma. In comparison to PBL, EBV-positive plasmacytoma is less commonly associated with a “starry-sky” appearance, necrosis, absence of light chain expression, and a high Ki67 index (>75%). The most recurrently mutated genes/signaling pathways in EBV-positive plasmacytoma are epigenetic regulators, MAPK pathway, and DNA damage response, while the most frequently reported mutations in PBL are not observed. Collectively, EBV-positive plasmacytoma should be regarded as a biological variant of plasmacytoma. Thorough morphologic examination remains the cornerstone for distinguishing EBV-positive plasmacytoma and PBL, and molecular studies can be a valuable complementary tool.

Epstein-Barr Virus–Positive Plasma Cell Neoplasms in Immunocompetent Patients

“…EBV-positivity was only found in exceptional cases of PCM/MM 6,11,18,19 . Most EBV-positive plasmacytoma cases reported in previous studies occurred in the upper respiratory tract 5,7,8,13,16,17 . Interestingly, our results revealed that SPB (23.8%, 5/21) had a comparable EBER-positive rate with EMP arising in the upper respiratory tract (19.5%, 8/41; P =0.949).…”

“…MYC rearrangement was also found in a subset of EBV-positive plasmacytoma cases (4/16, 25.0%), where only a relatively small fraction of the cells carried this aberration. Altered genes/pathways related to epigenetic regulators, MAPK signaling, and DNA damage response were detected in EBV-positive plasmacytomas, which were predominantly observed in immunocompromised patients 8 …”

“…Moreover, EBV-positive PCN was mainly reported in immunodeficient patients, while only a few cases occurred in immunocompetent individuals. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] This leaves open the question whether the prevalence of EBV in PCN varies according to the histologic subtype and tumor location in immunocompetent patients. There is also limited information on the distinctive clinicopathological features of EBV-positive PCN, as well as the prognosis of patients with this rare entity.…”

Follicle Center Lymphoma (FCL) of the Lower Female Genital Tract (LFGT)

“…In 10 cases, DNA was available for next-generation sequencing (NGS) using the TruSight Oncology 500 panel (see Table, Supplemental digital content 2, http://links.lww.com/PAS/B503, which shows genes included in the TSO500 DNA panel) and analyzed using in house genomic data analysis platform called Oncogenomics (NIH). As described previously, a set of parameters was used to filter variants and call them significant 20. Copy number variation events were reported with detected fold change (FC) <0.5 for deletion or >2.5 for duplication.…”

“…As described previously, a set of parameters was used to filter variants and call them significant. 20 Copy number variation events were reported with detected fold change (FC) <0.5 for deletion or > 2.5 for duplication.…”