Hepatocellular carcinoma with prominent neutrophilic infiltrate (?GM-CSF-producing HCC subtype)
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Scanning power view of tumor and adjacent liver
Higher power view of tumor
CK19 immunostain shows rare uptake
Variable Arginase 1 uptake
Patchy albumin mRNA uptake
Heavy uptake of neutrophil elastase
This tumor was diagnosed as a hepatocellular carcinoma with a significant neutrophilic component suggesting that it may represent the granulocyte colony-stimulating factor producing subtype of HCC. Our efforts to assess GM-CSF activity were technically unsuccessful and this classification remains provisional. The possibility of cholangiolocellular carcinoma or mixed HCC-CC was considered, but close examination showed that the tumor cells did not actually form the so-called staghorn pattern of growth, CK19 uptake was minimal, and abundant material compatible with Mallory-Denk bodies argued for a hepatocellular phenotype. Immunocytochemical support was considered weak but consistent with HCC. Torbenson has recently reviewed this topic and concluded that there are 12 established and 6 proposed subtypes of HCC. HCC subtypes differ from HCC growth patterns (i.e., trabecular, solid, pseudoglandular, macrotrabecular) and can have prognostic significance. Those characteristics are summarized in the table below.
Molecular analysis of this tumor using the Oncomine platform found only a suspected copy number loss of the region containing the ARID1A gene. This gene is a member of the SWI/SNF complex and is thought to act as a tumor suppressor. It can undergo alteration in a wide variety of tumors, including HCC and cholangiocarcinomas. The topic of SWI/SNF mutations in HCC has recently been reviewed by Hu et al. Although the literature suggests that ARID1A mutations are associated with a worse prognosis relative to typical HCC, in this particular example of a small incidentally discovered HCC, the patient has been doing well with no evidence of tumor recurrence to date.
Additional provisional subtypes include: chromophobe, combined HCC-CC with stem cell features, lipid-rich, myxoid, syncytial giant cell, and transitional cell. The behavior of each of these relative to typical HCC is unclear.