DISCUSSION
The WHO classification scheme includes at least 26 different subtypes of B-cell neoplasms , based on the histologic features , immunohistochemical staining profiles , and genetic translocations . 12 , 13 Leukemias are defined as hematopoietic malignancies involving the bone marrow and peripheral blood , whereas lymphomas commonly involve the lymph nodes or , occasionally , other lymphoid rich sites . Neoplastic B cells are categorized based on their size , unique architectural organization , surface antigen expression , and genetic
12 , 13 , 17 , 19 , 20 translocations .
Diffuse large B-cell lymphoma ( DLBCL ) and chronic lymphocytic leukemia / small lymphocytic lymphoma ( CLL / SLL ) are two of the most common lymphoproliferative disorders in the western world . Non-Hodgkin lymphomas , including DLBCL and CLL / SLL , are the second most common malignancies to arise in the oral cavity , after squamous cell carcinoma . 8 Among lymphomas in the oral cavity , DLBCL is the most common subtype . CLL / SLL more commonly presents in the peripheral blood and bone marrow , however rare cases can arise as solitary , tumor-like proliferations in the
8 , 12 , 17 , 20 mouth .
The treatment and prognosis of lymphomas is highly dependent on the specific variant , and tumor grade and stage . The ability to treat with immunotherapy , in addition to traditional chemotherapy , also affects the prognosis of lymphomas . A full work-up includes advanced imaging , bone marrow biopsy , blood work , lymph node biopsy , and flow cytometry . 12
DLBCL is characterized by the presence of larger than normal B-cells which express CD20 antigen . The Hans Algorithm is used to determine one of two unique phenotypes , based on the expression of CD10 , BCL-6 , and MUM-1 surface antigens . In addition , high grade DLBCL exhibits MYC , BCL-2 , and / or BCL-6 gene rearrangements , referred to as “ double hit ” or
12 , 13
“ triple hit ” lymphomas , respectively .
The treatment of DLBCL varies on the grade of the neoplasm . Low-grade lesions are slow-growing , relatively indolent , and tend to recur after chemotherapy treatment . Many physicians apply a “ watch-and-wait ” protocol to treat these entities , to spare the patient the negative effects of chemotherapy . 14 High-grade , aggressive DLBCLs are treated with radiation and chemotherapy . Chemotherapeutics employed in treating DLBCL include cyclophosphamide , doxorubicin , vincristine and prednisone (“ CHOP ”). Rituximab , a monoclonal antibody targeting the cell surface antigen CD-20 , can be administered , in addition to traditional chemotherapy , to patients whose tumor cells express CD-20 ( R-CHOP ). 2 This powerful drug regimen attacks the neoplasm from two pathways ; the traditional , anti-neoplastic mechanisms present in all cancers , and the immune pathway . About 60-70 % of patients will respond to this drug regimen , whereas the remainder of patients will either not respond to treatment , or relapse after drug therapy concludes . 14
CLL / SLL is characterized by the presence of smaller than normal B-cells organized in loose aggregates known as proliferation centers . The B-cells express both CD20 and CD5 surface antigens . CLL / SLL does not express cyclin D1 , which separates it from mantle cell lymphoma . Cutaneous involvement occurs in 4-20 % of CLL / SLL patients , and can present as a nodular or diffuse skin invasion by lymphocytes , 37 Small lymphocytic lymphoma is the soft tissue equivalent of CLL . These entities are a single disease , with different patterns
16 , 17 of tissue expression .
The clinical course of CLL / SLL is extremely variable . The disease can be indolent , with disease progression seen only 10-15 years after initial diagnosis ; or the disease can progress rapidly with death occurring within two years . 17 Evaluation for chromosomal deletions , TP53 mutation , and IgHV mutations are critical to determine the course of disease , and whether treatment should be initiated . When treatment is indicated , patients begin a drug regimen consisting of fludarabine , cyclophosphamide and rituximab ( FCR ). Just as in R-CHOP therapy , FCR therapy targets malignant cells via anti-neoplastic and immune pathways . 8 , 20 , 21 The patient in our case began a drug regimen consisting of venetoclax and obinutuzumab . These are novel agents that are highly targeted towards BCL-2 and CD-20 proteins , and thus produce less side effects than older medications . Novel agents are currently indicated in refractory or recurrent disease . Clinical trials are ongoing to determine their use in primary tumors . 38
16 JANUARY / FEBRUARY 2022 | PENNSYLVANIA DENTAL JOURNAL