MYC status in HIV-associated Plasmablastic lymphoma: Dual-colour CISH, FISH and immunohistochemistry.

AIMS: We utilised dual-colour chromogenic and fluorescent in situ hybridisation (CISH and FISH) to evaluate c-MYC gene copy numbers and rearrangements within HIV-associated plasmablastic lymphomas (PBL). Thereafter, clinicopathological features were explored.

METHODS AND RESULTS: Sixty-seven patients (N=67) were included from October 2013 to June 2017. Dual-colour CISH, FISH and immunohistochemistry were performed on formalin-fixed paraffin-embedded tumour sections. The female to male ratio was 1.1:1, mean age of 40 ± 10.2 years. HIV seropositive status was confirmed in 98% of patients with a median viral load (VL) of 46 473 copies/mL and a median CD4 count of 170 cells/µL. PBL was documented predominantly at extra-oronasal topographic regions (76%, p-value=0.001) and was frequently confirmed at the nasal site of the oronasal regions (p=0.03). Starry-sky appearance was evident in 31% of PBL, mainly in association with monomorphic tumour morphology (p=0.02). c-MYC protein was expressed in 81%, EBV latent infection was detected in 91%, while dual positivity occurred in 74% of PBL. MYC aberrations included MYC rearrangements (70%), low-level MYC gene copy number increases (41%) and low-level chromosome 8 polypoidy (5%). MYC aberrations were significantly associated with mortality (p=0.02), starry-sky appearance (p=0.01), monomorphic morphology (p=0.02) and c-MYC protein expression of ≥40% (p=0.01). Advanced stage at presentation was significant (74%, p<0.001) and the median overall survival (OS) time was 102 days.

CONCLUSION: Majority of the HIV-associated PBL tumours harbour MYC aberrations. Due to the persistently inferior survival outcome of HIV-associated PBL in the era of antiviral treatment, targeted and/or intensified therapy of oncogenic MYC may need to be explored in future.