LAUSR

To the Editor, We encountered a case of adenocarcinoma derived from adrenohepatic fusion‐related cyst (AHF‐RC). An adrenal mass, 60 mm in a major diameter, was identified by ultrasonography in a 72‐year‐old Japanese man with no chief complaint. A medical check‐ up 5 years earlier had indicated a 30‐mm right adrenal mass, but the size of the mass did not change until the following year. The patient had a smoking history (Brinkman Index: 400–600) and routine alcohol intake. His medical history included hypertension and arrhythmia, and he was being treated with warfarin. There was no family history of malignancy, liver disease, or hereditary disease. The results of serological tests of infection, including hepatitis B surface antigen and anti‐hepatitis C antibody, were negative. The level of carcinoembryonic antigen was 2.6 ng/mL and that of CA19‐9 was 18.3 ng/mL, both of which were within the normal range. Radiologically, computed tomography and magnetic resonance imaging (MRI) identified an oligocystic lesion surrounded by the hepatic capsule on the dorsal side of the liver (Supporting Information: Figure S1A,B). Most of the right adrenal gland was not identified, suggestive of adrenal origin. The cyst contained blood contents (it showed hypointensity on T2‐weighted images and hyperintensity on T1‐ weighted images), and there were at least two mural nodules which were hyperintense on diffusion‐ weighted MRI and showed strong radio‐isotope uptake on fluorodeoxyglucose – positron emission tomography images, suggestive of comorbidity of malignancy. A segment‐6 partial hepatectomy and right adrenalectomy were performed for the radical resection and diagnosis. On gross appearance, there was a blood‐containing cyst (48mm in major diameter) between the liver and the right adrenal gland. Mural nodules were present and protruded into the lumen. A white solid mass with an irregular border was observed in the liver parenchyma adjacent to the cyst (Figure 1a). Histologically, the cyst was attached to the liver parenchyma (Figure 1b), and small bile ductules penetrated into the right adrenal parenchyma (Supporting Information: Figure S1C). Intra‐adrenal bile ductules were dilated and formed a large cyst. Fragmented adrenal tissues were observed multifocally within the cyst wall (Figure 1c). The cyst wall was composed of scar‐like fibrous tissue, and the blood clot and necrotic debris were contained in the lumen. The lining epithelium was composed mainly of monolayered cuboidal‐to‐columnar cells with no‐to‐ mild cytological atypia (Supporting Information: Figure S1D). These lining cells transited into the areas composed of atypical stratified cells with an irregular surface and secondary lumen formation (Figure 1d). Interestingly, multifocal aggregations of foamy macrophages were observed under the epithelium in some area, that was similar to cholesterosis of the gallbladder. In addition, the papillary growth of atypical cells was also observed within the lumen, in which fibrovascular cores showed complex branching and inflexions (Figure 1e). The atypical cells had an increased nuclear‐to‐cytoplasmic ratio and contained an irregularly swollen nucleus with marked nucleoli, suggestive of a carcinoma in situ lesion (Supporting Information: Figure S1E). In the intrahepatic mass, invasive tubular growth of adenocarcinoma cells was observed, reminiscent of small duct‐type intrahepatic cholangiocarcinoma (Figure 1f and Supporting Information: Figure S1F). No remarkable change was observed in the background liver. The immunohistochemical analysis revealed diffuse and strong expressions of cytokeratin (CK)‐AE1/ AE3, CK‐Cam5.2, and CK19 on a series of epithelium, including lining cells, the papillary growth area, and the intrahepatic invasive area. Immunostainings for mesothelial markers (calretinin and D2‐40) and an endothelial marker (CD34) were entirely negative. Interestingly, CD10 was discontinuously immunopositive for the apical surface of the lining cells, but the expression was decreased in the large part of the papillary area and was completely lost in the intrahepatic invasive area (Supporting Information: Figure S2A,C,E). The expression of MUC1 (MUC1/ CORE, clone: Ma695) was observed diffusely on lining cells, but focally on atypical cells with papillary growth and invasive adenocarcinoma cells