PMC9874694_01
Endoscopic features of HAS. (A, B) White light endoscopy shows a 20-mm type 0-IIa+IIc lesion with submucosal tumor-like change in the greater curvature of the junction between the antrum and body. The lesion has a sense of compactness and fullness with a central depression. (C) NBI shows a brownish area with an indistinct boundary. (D-F) ME-NBI with low (D) and high (E) magnification shows that most parts of the lesion present as a regular microvascular pattern, and there is the presence of a demarcation line, some widened intervening parts, and elongated pits, and only small parts present as an irregular microvascular pattern (indicated by the arrow) (F).
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The lesion has a sense of compactness and fullness with a central depression ( Figures 1A, B ). Narrow-band imaging (NBI) showed a brownish area with an indistinct boundary ( Figure 1C ). Magnified endoscopy with NBI (ME-NBI) at low and high magnification revealed that most parts of the lesion presented as a regular microvascular pattern and only small parts presented as an irregular microvascular pattern, and there was the presence of a demarcation line, widened intervening parts, and elongated pits ( Figures 1D-F ).
Macroscopic morphology of the resected specimen. (A) Macroscopic observation shows a protuberant lesion with a central depression. The surrounding mucosa is smooth, with the converging of the mucosal folds toward the lesion and the fusion of folds. (B) Crystal violet staining of the resected specimen more clearly shows the morphology of the lesion. (C) The lesion and its surrounding tissues are taken every 2-3 mm for histopathological examination according to the cutting standard of early gastric cancer specimens. HAC (red line), representing the areas with hepatoid adenocarcinoma of the stomach; Sig (yellow line), representing the areas with signet ring cell carcinoma; Muc (white line), representing the areas with the formation of mucin.
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The surrounding mucosa was smooth, with converging of the mucosal folds toward the lesion and fusion of the folds ( Figure 2A ). The crystal violet staining for the resected specimen more clearly revealed the morphology of the lesion ( Figure 2B ). The lesion and its surrounding tissues were taken every 2-3 mm for histopathological examination according to the cutting standard of early gastric cancer specimens ( Figure 2C ).
Pathological features of HAS by hematoxylin & eosin (HE) staining. (A) The infiltration of cancer tissue was limited to the mucosa and submucosa and reached the deep layer of the submucosa. The mucosal surface was almost covered by non-neoplastic epithelium (HE, x40 magnification). (B) Some cancer cells were arranged in the form of irregular nests, cords, or micro glandular tubes. The cells were large and cubic in size, rich and eosinophilic in the cytoplasm, and with round or oval nucleus, binucleate and small nucleoli, and hepatocyte-like appearance (HE, x400 magnification). (C) Some cancer cells displayed the form of a signet ring and distributed diffusely (HE, x400 magnification). (D) There was mucus formation in the interstitium of some signet ring cells, the signet ring cells floated in mucus (HE, x200 magnification). (E) The different forms of cancer cells were interlaced with each other (HE, x400 magnification). (F) In the submucosa, the stromal fibrous tissue of the cancer obviously proliferated to form a nodular shape with a clear boundary, and the lymphocyte focally infiltrated and formed lymphoid follicles (HE, x40 magnification).
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The mucosal surface was almost covered by non-neoplastic epithelium ( Figure 3A ). The cells were large and cubic in size, rich and eosinophilic in the cytoplasm, and with round or oval nucleus, binucleate and small nucleoli, and hepatocyte-like appearance ( Figure 3B ). Some cancer cells displayed the form of signet ring and distributed diffusely ( Figure 3C ). There was mucus formation in the interstitium of some signet ring cells, and the signet ring cells floated in mucus ( Figure 3D ). The different forms of cancer cells were interlaced with each other ( Figure 3E ). In the submucosa, the stromal fibrous tissue of the cancer obviously proliferated to form a nodular shape with a clear boundary, and the lymphocyte focally infiltrated and formed lymphoid follicles ( Figures 3A, F ).
Molecular pathological features of HAS by immunohistochemical (IHC) staining and special staining. (A) Cytokeratin (CK) expression in the cytoplasm of two kinds of tumor cells (IHC staining, x200 magnification). (B) Caudal-related homeobox transcription factor 2 (CDX2) expression in the nucleus of the two kinds of tumor cells (IHC staining, x200 magnification). (C) Mucin 2 expression in the cytoplasm of the two kinds of tumor cells (IHC staining, x400 magnification). (D) No alpha fetoprotein (AFP) expression in the cytoplasm of the two kinds of tumor cells (IHC staining, x400 magnification). (E) Glypican-3 expression in the cytoplasm of hepatoid carcinoma cells (IHC staining, x400 magnification). (F) Hepatocyte expression in the cytoplasm of hepatoid carcinoma cells (IHC staining, x400 magnification). (G) Spalt-like transcription factor 4 (SALL4) expression in the nucleus of hepatoid carcinoma cells (IHC staining, x400 magnification). (H) Red periodic acid-Schiff (PAS) staining in the cytoplasms of signet ring cells (IHC staining, x400 magnification).
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Immunohistochemical examination showed that the expressions of cytokeratin (CK) ( Figure 4A ), caudal-related homeobox transcription factor 2 (CDX2) ( Figure 4B ), and mucin 2 ( Figure 4C ) were positive; human epidermal growth factor receptor 2 (HER2), mucin 5AC, AFP ( Figure 4D ), and hCG were negative; and in situ hybridization showed that EBV-encoded RNA (EBER) was negative in the two forms of cancer cells. While the expressions of glypican-3 ( Figure 4E ), hepatocyte ( Figure 4F ), and spalt-like transcription factor 4 (SALL4) ( Figure 4G ) were positive in the hepatoid carcinoma cells. Periodic acid-Schiff (PAS) staining showed that the cytoplasms of signet ring cells were red ( Figure 4H ).