- Yale 614 例 HCC 中 32 例（5.2%）见瘤内肉芽肿（ITG），均为非坏死性；患者均无结节病、原发性胆汁性胆管炎或明确感染。
- ITG 与 MASLD 背景、脂肪性肝炎型 HCC（68.8% 对 20.7%）、瘤内淋巴细胞炎症及较明显的瘤周炎症显著相关；肉芽肿相关炎症以 T 细胞、尤其 CD4 阳性 T 细胞为主。
- 诊断陷阱：活检中显著的 ITG 可能掩盖 HCC。单因素分析生存较好，多因素校正后不显著（HR 0.52，P = 0.098）。
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摘要
瘤内肉芽肿（ITG）在肝细胞癌（HCC）中鲜有描述，在有限的活检标本中可能掩盖恶性病变。我们回顾性复查了 2010—2023 年诊断的 614 例 HCC，识别伴 ITG 的肿瘤，并将其临床病理特征和总生存与无 ITG 的 HCC 进行比较。32/614 例（5.2%）发现 ITG。所有肉芽肿均为非坏死性；其中 3/32 例背景肝亦有肉芽肿。患者均无结节病、原发性胆汁性胆管炎或有记录的感染。伴 ITG 的患者以男性为主（23/32，71.9%），平均年龄 67.5 岁。代谢功能障碍相关脂肪性肝病（MASLD）是最常见的基础肝病（13/32，40.6%）。与无 ITG 的 HCC 相比，伴 ITG 的 HCC 与以下因素显著相关：MASLD（13/32，40.6% 对 98/582，16.8%；P = 0.0072）、脂肪性肝炎亚型（22/32，68.8% 对 119/576，20.7%；P < 0.0001）、瘤内淋巴细胞性炎症（26/28，92.9% 对 366/572，64.0%；P = 0.0001），以及至少中度的瘤周炎症（11/18，61.1% 对 60/255，23.5%；P = 0.003）。肉芽肿相关炎症以 T 细胞为主，并富集 CD4 阳性 T 细胞。单因素分析中，伴 ITG 的患者总生存较好（P = 0.004）；但在校正年龄、肿瘤大小、分期和 MASLD 病因后，该关联减弱且未达统计学显著（HR 0.52，95% CI 0.20–1.11；P = 0.098）。在 II 期肿瘤中，伴 ITG 患者的生存呈临界改善（P = 0.05）。显著的 ITG 可能在活检标本中掩盖 HCC。上述结果支持 ITG 是一种少见但可识别的 HCC 相关肿瘤微环境，富集于 MASLD 相关的脂肪性肝炎型 HCC。
- Of 614 HCCs at Yale, 32 (5.2%) had intratumoral granulomas (ITG), all non-necrotizing; no patient had sarcoidosis, PBC or documented infection.
- ITG was associated with MASLD, steatohepatitic subtype (68.8% vs 20.7%), intratumoral lymphocytic and at least moderate peritumoral inflammation; granuloma-associated inflammation was T-cell predominant, enriched for CD4+ cells.
- Pitfall: prominent ITG may mask HCC in biopsies. Better survival on univariable analysis was not significant after adjustment (HR 0.52, P = 0.098).
Scope: PubMed abstract only. The article is subscription-only (Unpaywall: closed) and ScienceDirect returned 403 to this site, so full text, figures and tables were not collected.
Abstract
Intratumoral granulomas (ITGs) are rarely described in hepatocellular carcinoma (HCC) and may obscure malignancy in limited biopsy specimens. We retrospectively reviewed 614 HCCs diagnosed from 2010 to 2023 to identify tumors with ITG and compared clinicopathologic features and overall survival with HCCs lacking ITG. ITG was identified in 32/614 cases (5.2%). All granulomas were non-necrotizing; 3/32 cases also had granulomas in background liver. No patient had sarcoidosis, primary biliary cholangitis, or documented infection. Patients with ITG were predominantly male (23/32, 71.9%), with a mean age of 67.5 years. Metabolic dysfunction-associated steatotic liver disease (MASLD) was the most common underlying liver disease (13/32, 40.6%). Compared with HCCs without ITG, HCCs with ITG were significantly associated with MASLD (13/32, 40.6% vs 98/582, 16.8%; P = 0.0072), steatohepatitic subtype (22/32, 68.8% vs 119/576, 20.7%; P < 0.0001), intratumoral lymphocytic inflammation (26/28, 92.9% vs 366/572, 64.0%; P = 0.0001), and at least moderate peritumoral inflammation (11/18, 61.1% vs 60/255, 23.5%; P = 0.003). Granuloma-associated inflammation was T-cell predominant and enriched for CD4-positive T cells. In univariable analysis, patients with ITG had improved overall survival (P = 0.004); however, the association was attenuated and did not reach statistical significance after adjustment for age, tumor size, stage, and MASLD etiology (HR 0.52, 95% CI 0.20-1.11; P = 0.098). Among stage II tumors, patients with ITG had borderline improved survival (P = 0.05). Prominent ITG may mask HCC in biopsy specimens. These findings support ITG as an uncommon but recognizable HCC-associated tumor microenvironment enriched in MASLD-related steatohepatitic HCC.