Division of Anatomical Pathology, Faculty of Health Sciences, National Health Laboratory Service, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Soweto, Gauteng, South Africa.
Department of Haematology and Molecular Medicine, Somatic Cell Genetics Unit, Faculty of Health Sciences, National Health Laboratory Service, University of the Witwatersrand, Soweto, Gauteng, South Africa.
Histopathology. 2021 Jul;79(1):86-95. doi: 10.1111/his.14336. Epub 2021 Apr 28.
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.
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).
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.
我们利用显色原位杂交（CISH）和荧光原位杂交（FISH）来评估 HIV 相关浆母细胞淋巴瘤（PBL）中 MYC 基因拷贝数和重排。此后，我们回顾性探索了临床病理特征。
共纳入 67 例患者，98%（63/64）患者 HIV 血清学阳性，中位病毒载量为 55587（IQR 273582）拷贝/ml，中位 CD4 计数为 170（IQR 249）细胞/μl。平均年龄为 41 ± 10.1 岁，女性占 54%。PBL 主要发生在口腔外或鼻腔外的解剖区域。33%的病例表现出星空（SS）样外观，与单形性形态学相关（P 值=0.02）。81%的病例表达 c-MYC 蛋白，90%的病例检测到潜伏 EBV 感染。67%的 HIV PBL 中存在 EBER ISH 阳性和 MYC 重排。MYC 异常包括 MYC 重排（70%）、低水平的 MYC 基因拷贝数增加（43%）、同时存在 MYC 重排和 MYC 基因拷贝数增加（49%）以及低水平的 8 号染色体三体（6%）。HIV PBL 中的 MYC 异常与 SS 外观（P=0.01）、单形性形态学（P=0.03）、c-MYC 蛋白表达≥40%（P=0.03）和死亡率（P=0.03）显著相关。大多数患者（77%）存在晚期（Ann Arbor III/IV 期）疾病，HIV PBL 的中位总生存期为 75 天（95%CI 14-136）。
大多数 HIV 相关 PBL 肿瘤存在 MYC 异常。由于在抗病毒治疗时代，HIV 相关 PBL 的生存结果仍较差，因此未来可能需要探索针对致癌性 MYC 的靶向和/或强化治疗。
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