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. 2021 Jul;79(1):86-95.
doi: 10.1111/his.14336. Epub 2021 Apr 28.

MYC status in HIV-associated plasmablastic lymphoma: dual-colour CISH, FISH and immunohistochemistry

Sugeshnee Pather  1 , Thembi Mashele  1 , Pascale Willem  2 , Moosa Patel  3 , Yvonne Perner  4 , Mantoa Motaung  1 , Natasha Nagiah  2 , Faadil Waja  3 , Vinitha Philip  3 , Atul Lakha  3 , Martin J Hale  4
Affiliations

MYC status in HIV-associated plasmablastic lymphoma: dual-colour CISH, FISH and immunohistochemistry

Sugeshnee Pather et al. Histopathology. 2021 Jul.

Abstract

Aims: We utilised chromogenic and fluorescence in-situ hybridisation (CISH and FISH) to evaluate MYC gene copy numbers and rearrangements within HIV-associated plasmablastic lymphomas (PBLs). Thereafter, clinicopathological features were explored retrospectively.

Methods and results: Sixty-seven (n = 67) patients were included and the HIV seropositive status was confirmed in 98% (63 of 64) with a median viral load of 55 587 (IQR 273 582) copies/ml and median CD4 count of 170 (IQR 249) cells/µl. The mean age was 41 ± 10.1 years and females comprised 54%. PBL was documented predominantly at extra-oronasal topographic regions. Starry-sky (SS) appearance was evident in 33% in association with monomorphic morphology (P-value 0.02). c-MYC protein was expressed in 81% and latent EBV infection was detected in 90%. EBER ISH-positive status and MYC rearrangement occurred in 67% of HIV PBL. MYC aberrations included MYC rearrangement (70%), low-level increase in MYC gene copy numbers (43%), concurrent MYC rearrangement and increased MYC gene copy numbers (49%) as well as low-level chromosome 8 polysomy (6%). MYC aberrations in HIV PBLs were significantly associated with SS appearance (P -0.01), monomorphic morphology (P - 0.03), c-MYC protein expression ≥40% (P - 0.03) and mortality (P - 0.03). There was advanced stage (Ann Arbor III/IV) at presentation (77%) and the median overall survival for HIV PBL was 75 days (95% CI 14-136).

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.

Keywords: CISH; FISH; HIV; MYC gene; plasmablastic lymphoma.

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References

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