MYC Negative Rectal B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Burkitt's Lymphoma in an Immunocompetent Patient

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (BLUI) is a recently added entity to the World Health Organization (WHO) classification to address a grey zone between large B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL). These are rare aggressive lymphomas, which were previously also known as Burkitt's-like lymphoma (BLL). BL and BLUI/BLL of the colon mostly involve the ileocecal region. In the rectum, BL and BLUI/BLL almost always affect patients with the acquired immune deficiency syndrome (AIDS). We report the first case of rectal BLUI/BLL in an immunocompetent patient who is also negative for MYC abnormalities and the EBV early RNA (EBER) in situ hybridization.


Introduction
e border between classical Burkitt's lymphoma (BL) and classical diffuse large B-cell lymphoma (DLBCL) has been a �eld of diagnostic uncertainty [1]. e updated WHO clas-si�cation of tumors of the hematopoietic and lymphoid tissues described these borderline lymphomas as "lymphoma, unclassi�able, with features intermediate between DLBCL and BL" (BLUI) [1]. Rectal BL and BLUI almost always affect patients with the human immunode�ciency virus (HIV) infection [2][3][4]. To the best of our knowledge, this is the �rst case of rectal BLUI in an immunocompetent patient who does not reveal MYC abnormalities and is also negative for EBV early RNA (EBER) in situ hybridization.

Case Report
A sixty-three-year-old heterosexual male with a past history of aortic aneurysm and prostate cancer presented with hematochezia. On examination, a submucosal nodule measuring 6 mm in greatest dimension was noted in the distal rectum about 2 cm from the anal verge. Histopathological examination revealed a monomorphic mucosal lymphoid proliferation with numerous mitotic �gures (Figure 1(a)). Nuclear polymorphism was slightly augmented compared to classic BL. e lymphoid cells expressed CD20, CD10, Bcl6 (Figure 1(d), inset), and Ki-67 (∼100%, Figure 1(b)) and were negative for CD3, CD5, CD23, and Bcl2 ( Figure  1(d)). EBER by in situ hybridization was also negative (Figure 1(c)). ere was no morphologic, �ow cytometric, or cytogenetic evidence of bone marrow involvement. Serologic tests for human immunode�ciency and hepatitis viruses were also negative. MYC translocations and rearrangement could not be detected by FISH. Based on nuclear pleomorphism and lack of MYC abnormalities, a diagnosis of rectal BLUI was made. Hematopathologists from a referral institute also concurred with this diagnosis.

Discussion
Among the gastrointestinal tract non-Hodgkins lymphomas (NHLs), primary gastric lymphomas are most common, whereas large intestinal lymphomas are rare [5]. With respect to the frequency, 62-80% involve the stomach, 13-31% involve the small intestine, and only 4-15% involve the large intestine [5]. e majority of large intestinal lymphomas occur in cecum, where a greater amount of lymphatic tissues are found [3]. Anorectal lymphomas represent only 3% of all gastrointestinal tract lymphomas. In contrast to their rare occurrence in the general population, the incidences of anorectal NHLs in patients with AIDS, particularly in homosexual patients, are very high [6]. BL is a rare aggressive form of NHL composed of monomorphic medium-sized B cells with basophilic cytoplasm and numerous mitotic �gures. It is also characterized by c-MYC translocation and CD10+/bcl-2-/bcl-6+ with a very high Ki-67 proliferation index [7]. BL has been linked to AIDS, homosexuality, and EBV infection in the anorectum and in other organs [6,7]. EBV in a latent form can be demonstrated by EBER in situ hybridization in the majority of BL patients [6,7].
Morphology, immunophenotypic features, and gene expression studies suggest that BL and DLBCL are extreme ends of a spectrum of diseases [1,8]. A group of lymphomas was characterized predominately by the fact that they are hard to assign to the one or the other group. ese lesions in between both classical extremes have been described in the past as Burkitt's-like lymphoma (BLL), atypical BL, gray-zone lymphomas, B-cell lymphoma, unclassi�able, or borderline lymphoma [1]. ese gray zone lymphomas have been recently termed �lymphoma, unclassi�able, with features intermediate between DLBCL and BL" (BLUI) by the updated WHO classi�cation of tumors of the hematopoietic and lymphoid tissues [8].
We present a case of MYC negative rectal BLUI/BLL in an immunocompetent patient. A literature search through PubMed did not reveal any case of rectal BLUI/BLL in an immunocompetent patient. However, it revealed one case of rectal BL in an immunocompetent patient that was positive for EBER in situ hybridization (unlike the present case) [9]. Adult MYC negative BLUI are infrequent, and their clinical course is currently unknown [1]. At present, there is no established standard therapy for this entity [10]. A recent study suggests that MYC positive BLUI patients require more aggressive therapy than R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone-related therapy) such as R-hyper-CVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) [10]. In contrast, MYC negative BLUI patients Case Reports in Pathology 3 can be subdivided into two groups. One patient group is refractory to therapy, including intensive chemotherapy, and has a very poor survival. e second group responds to treatment (either R-CHOP or R-hyper-CVAD) with better survival [10]. Our patient was started on R-hyper-CVAD chemotherapy and is currently without any evidence of recurrence.
Clinicians and pathologists must be aware of this rare aggressive entity while dealing with B-cell lymphomas of the rectum in immunocompetent patients.

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ere is no con�ict of interests for any author.