Primary diffuse large B-cell lymphoma of the oral cavity: germinal center classification

Abstract

Primary lymphomas of the oral cavity are rare and the most frequent type is diffuse large B-cell lymphoma (DLBCL). Recently, several reports have highlighted the value of classifying DLBCL into prognostically important subgroups, namely germinal center B-cell like (GCB) and non-germinal center B-cell like (non-GCB) lymphomas based on gene expression profiles and by immunohistochemical expression of CD10, BCL6 and MUM-1. GCB lymphomas tend to exhibit a better prognosis than non-GCB lymphomas. Studies validating this classification have been done for DLBCL of the breast, CNS, testes and GI tract. Therefore we undertook this study to examine if primary oral DLBCLs reflect this trend. We identified 13 cases (age range 38-91 years) from our archives dating from 2003-09. IHC was performed using antibodies against germinal center markers (CD10, BCL6), activated B-cell markers (MUM1, BCL2) and Ki-67 (proliferation marker). Cases were sub-classified as GCB subgroup if CD10 and/or BCL6 were positive and MUM-1, was negative and as non-GCB subgroup if CD10 was negative and MUM-1 was positive. Immunoreactivity was noted in 2/13 cases for CD10, in 12/13 for BCL6, in 8/13 for MUM-1, and in 6/13 for BCL2. Therefore, 8/13 (58%) were sub-classified as non-GCB DLBCLs and 5/13 (42%) as GCB subgroup. All tumors showed frequent labeling with Ki-67 (range 40-95%). Four of the 8 patients with non-GCB subgroup succumbed to their disease, with the mean survival rate of 16 months. Two patients in this group are alive, one with no evidence of disease and another with disease. No information was available for the other 3 patients in this group. Four of the 5 patients in the GCB subgroup were alive with no evidence of disease and one patient succumbed to complications of therapy and recurrent disease after 18 months. In conclusion, our analysis shows that primary oral DLBCL predominantly belongs to the non-GCB subgroup, which tends to exhibit a poorer prognosis. These findings could allow pathologists to provide a more accurate insight into the potential aggressive behavior and poorer prognosis of these lymphomas.

Fig. 1

Flow chart for GCB classification. Adapted from [9]

Fig. 2

a, b. Periapical radiographs demonstrating irregular radiolucencies with indistinct margins seen in a 56-year-old male with swelling in area of right maxillary canine to molars (Case #8 Table 3). c Section from panoramic radiograph demonstrating lesion arising within the mandible in the right body of the mandible (Case #9 Table 3)

Fig. 3

a 72-year-old male with swelling and obliteration of the anterior maxillary vestibule presented with bone and soft tissue destruction (Case #11 Table 3). b 89 year old female with swelling exhibiting a small ulceration on the surface in the right maxillary vestibule presented with discomfort in denture wearing. (Case #12 Table 3)

Fig. 4

Composite photomicrograph (hematoxyllin and eosin stain) of primary Diffuse large B cell lymphomas in the oral cavity (a and b, c and d). a Diffuse infiltrate of abnormal lymphoid cells (original magnification ×200). b Higher magnification showing that the nuclear size of the abnormal lymphocytes (black arrows) is more than two times the size of normal small lymphocytes (white arrows). Neoplastic cells demonstrating an immunoblastic morphology with prominent central nucleoli are noted in lower left corner (original magnification ×500). c Both diffuse and angiocentric abnormal lymphocytic infiltrates of large cells (original magnification ×200). d Higher magnification showing that typical appearance of centroblastic variant (arrow heads highlight mitotic figures). The nuclear size of the abnormal lymphocytes is more than twice the size of a normal lymphocyte (original magnification ×1000)

Fig. 5

Immunohistochemical study for CD20. All case demonstrated positive reactivity with this antibody. (Original magnification ×400)

Fig. 6

Immunohistochemical panel (magnification ×40) demonstrating positive reactions

Fig. 7

Immunohistochemical study for Ki-67 (magnification ×20). All tumors showed frequent labeling with Ki-67 (ranging from low 40% to high 95%). a low percentage of positivity; b high percentage of staining