Composite hepatocellular carcinoma and small cell carcinoma with early nodal metastasis

Abstract

Rationale:Hepatocellular carcinoma (HCC) is known to grow in a mosaic pattern, and it can sometimes be combined with non-hepatocellular cells. Despites the variety of combination, HCC with a significant neuroendocrine carcinoma (NEC) component remains very rare. Most of the reported cases were treated as conventional HCC with a relatively poor prognosis. Early diagnosis may lead to a better treatment modality. Here, we report a case of composite HCC and small cell carcinoma (SCC) with nodal metastasis of the SCC component alone.Patient concerns:A 65-year-old man with chronic viral hepatitis C presented with abdominal discomfort for 2 months. Computed tomography and angiography of the liver showed a 4.3 cm hypervascular tumor in segment 4 and enlargement of the perihilar and paracaval lymph nodes.Interventions:Extended left lobectomy and regional lymph node dissection were performed.Diagnosis:The hepatic tumor was heterogeneous with two distinct gross components. The green part showed a grade III hepatocellular carcinoma with an immunoreaction to Hep Par 1, glypican 3 and α-fetoprotein, whereas the white part exhibited a small cell carcinoma, as evidenced by expressions of chromogranin A and synaptophysin. The lymph node was metastasized by the SCC component. The SCC part was also positive for vimentin with perivascular accentuation. ß-catenin immunostain showed reduced membranous expression in the SCC component, as compared to HCC.Outcomes:The patient expired 39 days after the surgical intervention.Lessons:Clinicians should be highly alert to a composite hepatic tumor, especially in dealing with a small heterogeneous tumor (< 5 cm) with early lymph node metastasis.

Incidental Collision Tumor of Hepatocellular Carcinoma and Neuroendocrine Carcinoma

“…They observed β-catenin staining in both components of the tumor and stated that these findings did not support exon 3 mutations in the CTNNB1 gene. In our case, similar to the case presented by Liu et al , 10 a strong β-catenin staining was observed in the HCC component. However, we did not observe β-catenin expression in the NEC component, leading us to speculate that in these tumors, divergent underlying molecular pathways might take place that involve the β-catenin pathway.…”

“…However, 3 of the 7 reported collision tumors of HCC-NEC were also detected in cirrhotic background. 6 , 10 , 20 These data support that HCC-NEC should be considered either clinically and pathologically in all patients with chronic liver diseases, regardless of the presence of cirrhosis.…”

“…Recently, in an elegant study, Baker et al 21 detected a CTNNB1 gene mutation (S33F located in exon 3) in both components of a collision tumor of HCC-NEC and suggested a common cell origin. On the other hand, in a recent report, Liu et al 10 did not find similar results by immunohistochemistry. They observed β-catenin staining in both components of the tumor and stated that these findings did not support exon 3 mutations in the CTNNB1 gene.…”

“…Although two tumors were observed concurrently, a transition between them was not observed. 6 – 10 These findings are in contrast with combined tumors that consist of two distinct tumors that are contiguous and intermingle with each other. 11 – 19 , 21 Another important problem to be solved in making a diagnosis of primary hepatic NEC is the discrimination of primary NEC and from metastatic NEC, as the liver is the most frequent site of metastasis for NEC.…”

“…Rarely, metastases to lymph nodes and omentum have been described ( Table 2 ). 6 , 10 , 11 , 15 , 18 An important problem in these cases is the difficulty to detect which component of the tumor determines the behavior of the tumor. In a great majority of recent cases, only the NEC component has been detected in the metastatic focus.…”