Undifferentiated carcinoma of the liver: a case report with immunohistochemical analysis
© The Author(s). 2017
Received: 13 November 2016
Accepted: 5 January 2017
Published: 10 January 2017
Undifferentiated carcinoma (UC) of the liver is extremely rare, and its clinicopathological characteristics have not been fully elucidated.
The present study reports the case of a 56-year-old male with UC of the liver. At 16 days post-admission, the patient suddenly succumbed due to intra-abdominal bleeding resulting from a ruptured liver. Macroscopic examination revealed that the hepatic parenchyma was almost completely replaced by innumerable minute nodules. Microscopically, the tumor demonstrated a diffuse proliferation of anaplastic cells that were positive for epithelial membrane antigen and neuron-specific enolase, suggesting neuroendocrine differentiation. Grimelius and Fontana-Masson staining were negative. Neuroendocrine markers were also negative, including chromogranin A, synaptophysin, and S-100 protein. Cytokeratin markers and mesenchymal markers were all negative. Tumor markers, such as α-fetoprotein and carcinoembryonic antigen, were also negative.
Although larger studies involving more patients are required to establish a therapeutic strategy, appropriate chemotherapy following an early diagnosis may be important to UC of the liver because the tumor behaves in an aggressive way.
KeywordsUndifferentiated carcinoma Neuroendocrine carcinoma Liver cancer
Undifferentiated carcinoma (UC) of the liver is an extremely rare malignant neoplasm [1, 2]. The clinicopathological characteristics and clinical course of UC have not been fully clarified, and a therapeutic strategy for unresectable cases has not been established. The present study reports the case of a 56-year-old male with UC of the liver, together with the results of immunohistochemical analysis.
Summary of reported cases of undifferentiated hepatocellular carcinoma of the liver
Extrapulmonary small cell carcinomas are extremely rare and can originate in a variety of sites, including the liver, colon, stomach, esophagus, cervix, gallbladder, and skin [9–14]. Zanconati et al.  reported three cases of unusual small cell primary carcinoma of the liver. All three tumors developed in non-cirrhotic livers and demonstrated rapid clinical evolution, with mortality ensuing between 1 and 5 months post-diagnosis. These tumors were comprised of broad nests of small epithelial cells positive for low-molecular weight keratins and AFP.
In the present case, the tumors were growing in a solid nest comprising small cells with hyperchromatic nuclei and scant cytoplasm, which indicated small cell carcinoma. By contrast, immunohistochemical analysis revealed positive staining for NSE, although it was negative for chromogranin A and synaptophysin, therefore suggesting neuroendocrine differentiation. It is difficult to determine which classification is appropriate for this type of tumor. The tumor is referred to as UC with neuroendocrine features, neuroendocrine carcinoma, or small cell carcinoma of the liver. Thus, a novel entity of the tumor should be established for the accumulation of such cases in the future.
UC grows invasively, features a high incidence of metastasis, and follows a rapid clinical course . However, no therapeutic strategies for unresectable tumors have been established. Moertel et al.  reported the chemotherapeutic results for metastatic UC with endocrine features and concluded that this type of tumor responded strongly to etoposide and cisplatin regimen chemotherapy. Similarly, Nakasuka et al.  reported a case of UC of the liver with neuroendocrine features treated with the same regimen that resulted in a positive clinical course. Other studies reported poorly differentiated/rapidly progressing neuroendocrine tumors  and poorly differentiated neuroendocrine carcinoma of the hepatobiliary tract and pancreas , which were treated with a combination of cisplatin and etoposide.
We herein reported the case of a 56-year-old male with UC of the liver. This tumor demonstrated a diffuse proliferation of anaplastic cells, which were positive for NSE suggesting neuroendocrine differentiation, and showed an aggressive behavior. Therefore, appropriate chemotherapy following an early diagnosis may be important to UC of the liver. In the future, larger studies on UC of the liver should be conducted to analyze an appropriate chemotherapeutic strategy for this rare disease.
The authors would like to thank Enago for the English language review.
All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for the publication of this case report and all accompanying images.
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