Iwasaki Tomohiro, Kubota Aki, Suzuki Makoto, Terada Tadashi
Department of Pathology, Shizuoka General Hospital No. 4-27-1, Kita-Ando, Aoi-ku, Shizuoka, Shizuoka 420-8527, Japan.
Int J Clin Exp Pathol. 2020 Mar 1;13(3):624-633. eCollection 2020.
We herein report a case of well-differentiated small hepatocellular carcinoma (HCC) with severe lymphocytic infiltrate (SLI) in a 55-year-old male patient with HCV-related cirrhosis. The patient had been followed-up because of HCV-related cirrhosis. He was found to have two small nodules in S8 by imaging techniques, and he underwent S8 segmentectomy. The resected liver showed two small nodules. Both were encapsulated, well-defined, solid, reddish and expansive nodules with fibrous septa. They measured 8 × 8 mm and 15 × 10 mm, respectively. Histologically, both tumours were pure HCC; the smaller showed SLI with lymphocytes/HCC cells ratio over 20, while the larger showed mild lymphocytic infiltration with lymphocytes/HCC cells ratio of 0.8. The smaller HCC was well-differentiated (trabecular thickness <3) HCC-SLI with Edmondson II = I cytologic atypia, while the larger was moderately-differentiated (trabeculae >3) HCC (Edmondson II>III>I). Extremely well-differentiated Edmondson I HCC or adenomatous hyperplasia areas were seen in the periphery of both HCCs. The patterns of SLI could be classified into the following three: sinusoids (S) type, portal tract (PT) type, lymph follicle (LF) type. In S-type, lymphocytes were infiltrated between the trabeculae. In PT-type, SLI was found to arise from extension from already inflamed PT within HCC or neighboring PT. The HCC cells frequently exhibited moth-eaten or piece meal necrosis in PT-type. In LF-type, lymphocytes were activated, and nuclear dusts were noted. It appeared that LF-type has arisen from preexisting S-type and/or PT-type. We speculated that the entry of SLI was from S in S-type, from incorporated inflamed PT in PT-type, and from both in LF-type. The approximate overall positive ratios of lymphoid cells among inflammatory cells were as follows: CD20 50%, CD3 70%, CD4 50%, CD8 30%, CD138 3%, CD163 40%, granzyme B 2%, smooth muscle actin (SMA) 30%, CD31 30%, CD21 2%, S100 3%, bcl-2 10%, CK19 1%, CD10 1%, CD30 0%, CD56 0% and Ki67 labeling index = 5%. EBV-ISH and HPV IHC were negative. Interestingly, Kupffer cells had myofibroblastic antigen in addition to macrophage antigens, and stellate cells expressed macrophage antigens aside from myofibroblastic antigens. These data suggest that, in the present case, pan-B-cells, pan-T-cells, helper T-cells, cytotoxic T-cells, plasma cells, macrophages, Kupffer cells, stellate cells, myofibroblasts, fibroblasts, endothelial cells, dendritic cells, Langerhans cells, and toxic molecules may play roles in tumour immunology.
我们在此报告一例55岁男性丙型肝炎病毒（HCV）相关肝硬化患者，患有伴有严重淋巴细胞浸润（SLI）的高分化小肝细胞癌（HCC）。该患者因HCV相关肝硬化接受随访。通过影像学检查发现其肝S8段有两个小结节，遂行S8段切除术。切除的肝脏显示有两个小结节。两者均有包膜，边界清晰，质地坚实，呈红色，为有纤维间隔的膨胀性结节。大小分别为8×8毫米和15×10毫米。组织学上，两个肿瘤均为纯HCC；较小的肿瘤显示SLI，淋巴细胞/HCC细胞比例超过20，而较大的肿瘤显示轻度淋巴细胞浸润，淋巴细胞/HCC细胞比例为0.8。较小的HCC为高分化（小梁厚度<3）HCC-SLI，细胞学异型性为Edmondson II = I级，而较大的为中分化（小梁>3）HCC（Edmondson II>III>I）。在两个HCC的周边均可见到高分化的Edmondson I级HCC或腺瘤样增生区域。SLI的模式可分为以下三种：窦状隙（S）型、门静脉（PT）型、淋巴滤泡（LF）型。在S型中，淋巴细胞浸润于小梁之间。在PT型中，SLI被发现是由HCC内已发炎的PT或邻近PT延伸而来。PT型中的HCC细胞常表现为虫蚀状或碎片状坏死。在LF型中，淋巴细胞被激活，并可见核尘。似乎LF型是由先前存在的S型和/或PT型发展而来。我们推测，SLI在S型中来自窦状隙，在PT型中来自合并的发炎门静脉，在LF型中则来自两者。炎症细胞中淋巴细胞的大致总体阳性率如下：CD20为50%，CD3为70%，CD4为50%，CD8为30%，CD138为3%，CD163为40%，颗粒酶B为2%，平滑肌肌动蛋白（SMA）为30%，CD31为30%，CD21为2%，S100为3%，bcl-2为10%，CK19为1%，CD10为1%，CD30为0%，CD56为0%，Ki67标记指数=5%。EBV原位杂交（ISH）和HPV免疫组化（IHC）均为阴性。有趣的是，库普弗细胞除了有巨噬细胞抗原外，还有肌成纤维细胞抗原，而星状细胞除了有肌成纤维细胞抗原外，还表达巨噬细胞抗原。这些数据表明，在本病例中，全B细胞、全T细胞、辅助性T细胞、细胞毒性T细胞、浆细胞、巨噬细胞、库普弗细胞、星状细胞、肌成纤维细胞、成纤维细胞、内皮细胞、树突状细胞、朗格汉斯细胞和毒性分子可能在肿瘤免疫学中发挥作用。
