Clear-Cell Adenocarcinoma of the Gallbladder with Alpha-Fetoprotein Production: A Case Report and Review of the Literature

Abstract

Gallbladder tumors are the fifth most common cancers of the gastrointestinal tract with poor prognosis and low survival. The most common type is adenocarcinoma of which the clear cell type is an unusual histologic variant with alpha-fetoprotein (AFP)-producing gallbladder carcinoma, reported extremely rarely, which makes the index case an uncommon entity. AFP secretion by gallbladder carcinomas may occur given the similar embryological origin of liver and gallbladder. Herein we report a case of an incidental carcinoma of the gallbladder in a 60-year-old woman with an elevated serum AFP concentration at presentation, who underwent cholecystectomy for cholelithiasis and was rendered the diagnosis of AFP-producing clear cell carcinoma of the gallbladder through histopathology and immunohistochemistry. Her postoperative laboratory tests showed a decline in AFP levels to normal respectively. The clinical and pathologic importance of AFP production by clear-cell adenocarcinoma of the gallbladder (CCG) has thus far remained completely obscure. However, we must recognize the entity of this tumor because accurate and early diagnosis of CCG is imperative to avoid misdiagnosis as possible secondary metastasis and consequent delay in appropriate surgical intervention. Relevant medical history of a patient, various imaging studies, foci of classical adenocarcinoma within the tumor, and an efficient immunohistochemical panel can be informative and assist in arriving at an accurate diagnosis.

Gallbladder Clear Cell Carcinoma: Report of a Rare Case and Literature Review

“…Bittinger et al initially determined that if CK7 and CEA reactivity is detectable, then the lesion is either primary of the gallbladder or metastatic of a lung mass, excluding clear cell carcinomas of other tissues [ 20 ]. In later years, Zhang et al and Dixit et al observed that CEA and CK7 were strongly stained in the gallbladder but were negative in nearly all other clear cell carcinomas, including the renal one [ 5 , 17 ]. More recently, Sarangi et al added that CCG is also positive for CK19, which is not seen in renal clear cell carcinoma [ 19 ].…”

“…This phenomenon was observed by Vardaman and Albores-Saavedra and they suggested that such neoplasms should be considered primary until proven otherwise [25]. During the following years, that CEA and CK7 were strongly stained in the gallbladder but were negative in nearly all other clear cell carcinomas, including the renal one [5,17]. More recently, Sarangi et al added that CCG is also positive for CK19, which is not seen in renal clear cell carcinoma [19].…”

“…Case Reports in Surgery Adenocarcinoma is the most common histological type of GBC [15], whereas the clear cell subtype is diagnosed exceedingly rare. Since 1926, which is considered the year that the first case of the clear cell subtype was reported, up to 2021 only 19 cases are published [5,[16][17][18][19][20][21][22][23][24][25]. Thus, CCG accounts for less than 1% of all gallbladder malignancies [16].…”

Poorly differentiated adenocarcinoma with signet ring cells of the gallbladder producing a high level of alpha-fetoprotein: A case report

“…Only a few cases of AFP-producing gallbladder carcinomas have been reported in the literature, and most of these cases have exhibited papillary or hepatoid morphologies and poor prognosis [14] . Primary AFP-producing gallbladder carcinomas reported in the recent English literature consist of four histologic types: undifferentiated carcinoma, poorly differentiated carcinoma, clear cell carcinoma, and hepatoid carcinoma ( Table 1 ) [15] , [16] , [17] , [18] . In our patient, histopathological studies revealed poorly differentiated adenocarcinoma with signet ring cells, and immunohistochemical studies showed AFP production.…”