CD5 is a glycoprotein that is typically present on the membranes of mature T cells and is rarely expressed on B cells. CD5 positive (CD5+) DLBCL was recognized as an immunophenotypic subset of DLBCL in the 2008 WHO classification but was eventually removed from the revised 2016 classification. However, the clinical significance of CD5+ DLBCL continues to be a topic of discussion .
De novo CD5+ DLBCL is rare and accounts for 5 to 22% of all DLBCL. It has an inferior survival rate with 5-year overall survival of only 35% compared to CD5 negative (CD5-) DLBCL. Despite being rare it has distinct clinical features of predilection for elderly, female population, elevated LDH, extra-nodal involvement, bone marrow involvement of 28% and CNS involvement at 13% with 40% belonging to high IPI risk group. Majority of CD5+ DLBCL belongs to ABC/non-GCB subtype. Co-expression of BCL-2 and MYC is found in 27% of CD5+ DLBCL whereas its only found in 3% of CD5- DLBCL.
DLBCL is further categorized into molecular subtypes; germinal center-B-cell-like (GCB) and activated B-cell-like (also known as non-GCB). EBV is a less common cause of non-GCB type DLBCL and has been associated with EBV-positive DLBCL of the elderly along with 5 to 10% of DLBCL not otherwise specified . These infections can set off immune cascades in the body triggering sporadic cases of secondary HLH . HLH is a life-threatening disorder of immune activation known to be caused by hematologic malignancies, most commonly NK/T-cell lymphomas  however it can be uncommonly associated with non-Hodgkin’s B-cell lymphomas . Hence, adults with suspected or diagnosed HLH should undergo a work-up for occult lymphomas .
Our patient described above scored 170 on the HScore, a diagnostic score for reactive hemophagocytic syndrome, indicative of 40-54% probability of hemophagocytic syndrome. A score of 169 is considered the best cutoff value with a sensitivity of 93% and a specificity of 86% .
Morphologically CD5+ DLBCL often shows intravascular or intra-sinusoidal filtration pattern. However, our patient’s clinical presentation is somewhat unusual with lack of lymphadenopathy or mass lesions in the liver, predominantly portal pattern of infiltration and absence of bone marrow involvement. Persistent abnormalities in liver function tests prompted further work-up with biopsy that led to earlier diagnosis of DLBCL with the initiation of timely chemotherapy. The patient had resolution of pancytopenia, regression of splenomegaly and normalization of liver function within 2 weeks of discharge, prior to initiation of chemotherapy. This is suggestive of a possibility of DLBCL associated HLH or a viral insult such as EBV triggering the initial presentation, although serology was not conclusive.