A rare case of primary adenosquamous carcinoma of the liver with gallbladder metastasis.

Abstract

A 67-year-old Taiwanese male who complained of intermittent epigastralgia for 3 months came to our clinic for help. Serum biochemistry examination and tumor markers, carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) were within normal limits. Abdominal computed tomography disclosed a poorly enhanced lesion, 9 cm in diameter, with irregular margin in segments 5 and 8 of the liver (Figure 1A, white arrow). The gallbladder wall was thickened with a poorly enhanced mass lesion (Figure 1A,B, white arrowheads). Laparoscopic right hepatectomy with cholecystectomy was performed. On gross examination, there was a firm yellow solid mass in the liver (9.5 × 8.5 × 7.5 cm) with central necrosis (Figure 1C). The gallbladder showed intact and smooth mucosa and there were three nodules in the wall (Figure 1D, yellow arrows). Microscopically, the liver tumor and nodules on the gallbladder wall were composed of both adenocarcinoma and squamous cell carcinoma components (Figure 1E,F). Immunohistochemistry revealed that cytokeratin 7 (Figure 1G) and cytokeratin 19 were expressed by the glandular structures, whereas the squamous cell component showed nuclear p63 staining (Figure 1H). A primary adenosquamous carcinoma (ASC) of the liver with gallbladder metastasis was diagnosed. The patient refused chemotherapy or radiotherapy and lost to follow-up after the surgery. The majority of ASC present in the respiratory system, followed by the digestive system and the female reproductive system.1 Primary ASC of the liver is extremely rare. Barr and Hancock described the first case in 1975.2 Since then, fewer than 100 cases have been published. There are few cases with lymph node or intrahepatic metastases.2, 3 Primary ASC of the liver is considered as a rare subtype of cholangiocarcinoma which contains both adenocarcinoma and squamous cell carcinoma components. Various theories have been proposed to describe the pathogenesis. It was suggested that chronic inflammation of the bile duct or hepatic cyst could lead to squamous metaplastic change of the normal epithelium, thereby inducing malignant transformation.2, 3 Other studies assumed that ASC arises from squamous metaplasia of preexisting adenocarcinoma cells.2, 3 The preoperative diagnosis of hepatic ASC is generally difficult. A previous study showed that the patient may present with a high level of serum squamous cell carcinoma-related antigen. Nakai et al reported that the level of serum CEA, and CA19-9 were elevated in some cases.4 Computed tomography images could reveal a hypodense lesion with irregular rim enhancement. However, it is still difficult to be differentiated from cholangiocarcinoma, metastatic liver tumor, or liver abscess. The histopathological examination of the hepatic ASC revealed the tumor being infiltrated with solid and glandular areas.3 Adenocarcinoma cells could be cubic or columnar which arranged in atypical glandular growths. Meanwhile, the squamous differentiation is in the form of keratinization, pearl formation, intercellular bridges, or dyskeratosis.2 At present, the management strategy is still uncertain due to the disease's low incidence. Tomioka et al reported the effectiveness of combining surgical resection and radiotherapy.4 Transcatheter arterial infusion chemotherapy may reduce tumor volume.4 Some advocated systemic chemotherapy in the therapeutic course.5 Prognosis of patients with hepatic ASC is extremely poor. It has been reported that the majority of patients expire within 1 year despite surgical intervention.5 All authors declare no conflict of interest.