Abstract
To determine the frequency of granulomatous inflammation within hepatocellular carcinoma (HCC) and its clinicopathologic associations. Fifty-eight HCCs (51 explants, 3 lobectomies, and 4 segmentectomies) were reviewed. Five (8.6%) cases (F/M=1/4, mean age: 63.6) were identified with granulomas.1/5 had history of neoadjuvant therapy. 4/5 patients presented with early stage (pT1/2). All were well-differentiated (Grade1-2/4). The mean number of tumor foci was 3.6, with a median size of 2.2 cm. All of them had advanced fibrosis. No difference was identified from cases without granulomas (n=53) in terms of prognosis and aforementioned parameters (p > 0.05). Granulomas were mainly concentrated in peripheral parts of the tumors. One case with nodule-in-nodule formation had granulomas lined along the border of the inner nodule. In 2 cases, granulomas were identified in steatohepatitic areas, while another had clear cell change. Only 1 had necrotizing granulomas, none with acid resistant bacilli. Two cases revealed concomitant granulomas in the adjacent liver parenchyma in addition to the tumor stroma. Except for one with a history of tuberculosis, none of the cases had a granulomatous disease. This is the largest case series of HCCs with granulomas by far. Our data revealed neither clinicopathologic and prognostic difference nor definite etiology related to granulomas. Yet, association with steatotic and clear tumor cells suggests the role of cytoplasmic content, while distribution of granulomas points to host immune response.
Highlights
Granulomatous inflammation is a unique type of chronic inflammatory response [1]
Among the 58 hepatocellular carcinoma (HCC) included in this study, which to our knowledge represents the first cohort to date analyzed for this purpose, 5 cases (8.6 %) had granulomas
There are 2 more cases not included in the table since there is no detailed information about the patient’s characteristics. One of these is a HCC case with intratumoral granulomas written by Neville et al [18], and the other is a rare case diagnosed as hepatocellular neoplasm of uncertain malignant potential [19]
Summary
Granulomatous inflammation is a unique type of chronic inflammatory response [1]. it does not indicate a definite etiology, its detection limits the differential diagnosis list leading to effective treatment. Consecutive 58 hepatic resections (51 explants, 3 lobectomies and 4 segmentectomies) diagnosed as HCC, approximately in a period of five years were included Nonspesific histiocytic reactions such as histiyocytes around tumor necrosis, microsphere-related foreign body reactions, or isolated histiyocytic giant cells dispersed in tumor stroma were excluded. All the relevant parameters required to determine pT (AJCC 8th ed.) were noted in additon to tumor size, histologic grade (based on Edmondson and Steiner grading system), histologic subtype, and tumor necrosis of five largest foci [16,17] Granulomas and their characteristics; distribution throughout the tumor (in the center or at the periphery), presence of necrosis, accompanying inflammatory cells (lymphocytes and eosinophils), and Langhans type giant cells were reviewed. Ziehl-Neelsen staining was performed in each tumor block with stromal granulomas
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