Primary gastrointestinal lymphomas account for approximately 1-4% of all gastrointestinal malignancies, with the colon being the least commonly affected site. Diffuse large B-cell lymphoma represents the most frequent histological subtype, but primary colonic involvement remains exceptionally rare. Double-expressor lymphomas, characterized by MYC and BCL2 protein co-expression without underlying genetic translocations, constitute 20-30% of DLBCL cases and are associated with inferior outcomes compared to standard DLBCL. The rarity of primary colonic DLBCL combined with double-expressor phenotype presents unique diagnostic and therapeutic challenges.

A 59-year-old male with no significant medical history presented with a 2-month history of progressive right lower quadrant abdominal pain, anorexia, and 5 kg weight loss. The patient denied fever, night sweats, or B-symptoms. Physical examination revealed mild right lower quadrant tenderness without palpable lymphadenopathy, hepatosplenomegaly, or other abnormalities.

Laboratory evaluation demonstrated mild normocytic anemia (hemoglobin 11.2 g/dL) with normal leukocyte and platelet counts. Biochemical studies showed elevated lactate dehydrogenase (560 U/L) with normal renal and hepatic function. Infectious disease screening including HIV, hepatitis B, and hepatitis C serologies were negative.

Computed tomography of the abdomen revealed a heterogeneous 6-cm mass involving the ascending colon wall without regional lymphadenopathy or hepatosplenic involvement. Colonoscopy identified an ulcero-vegetative mass in the ascending colon causing luminal narrowing, initially suspected to represent adenocarcinoma.

Histopathological examination of colonoscopic biopsies revealed diffuse proliferation of medium-to-large sized atypical lymphoid cells with prominent nuclear atypia and high mitotic activity. Comprehensive immunohistochemical analysis demonstrated strong CD20 positivity with focal CD10 expression and positive MUM1, consistent with germinal center B-cell origin. Critical findings included diffuse BCL2 positivity and MYC expression in 70% of cells, establishing double-expressor status. The proliferation index (Ki-67) was extremely high at approximately 90%. CD3 and CD5 were negative, excluding T-cell lymphoma.

Fluorescence in situ hybridization (FISH) analysis for MYC, BCL2, and BCL6 gene translocations was negative, ruling out double-hit lymphoma and confirming the diagnosis as double-expressor DLBCL rather than high-grade B-cell lymphoma with MYC and BCL2 rearrangements.

The final diagnosis was primary colonic diffuse large B-cell lymphoma, germinal center subtype, with double-expressor phenotype (MYC+/BCL2+) and extremely high proliferative activity.

This case illustrates several important clinical and pathological considerations. Primary colonic DLBCL is extraordinarily rare, often mimicking adenocarcinoma both clinically and endoscopically, potentially leading to diagnostic delays or mismanagement. The double-expressor phenotype, present in this case, represents an aggressive biological subset associated with poor prognosis and potential resistance to standard R-CHOP therapy.

The absence of genetic translocations distinguished this case from double-hit lymphoma, which would have warranted even more intensive treatment approaches. However, the double-expressor status combined with extremely high Ki-67 suggests consideration of dose-adjusted EPOCH-R or other intensified regimens over standard R-CHOP.

The isolated colonic presentation without nodal or bone marrow involvement represents stage I disease, potentially offering better outcomes despite the adverse biological features.

Primary colonic DLBCL with double-expressor phenotype represents a rare but aggressive entity requiring prompt recognition and specialized treatment. Comprehensive immunohistochemical and molecular evaluation is essential for accurate classification and optimal therapeutic decision-making in this challenging clinical scenario.