Intracholecystic tubular non-mucinous neoplasm (ICTN) of the gallbladder: a clinicopathologically distinct, invasion-resistant entity

• Published in: Virchows Archiv : an international journal of pathology 2021-03, Vol.478 (3), p.435-447
• Main Authors: Pehlivanoglu, Burcin, Balci, Serdar, Basturk, Olca, Bagci, Pelin, Erbarut Seven, Ipek, Memis, Bahar, Dursun, Nevra, Jang, Kee-Taek, Saka, Burcu, Ohike, Nobuyuki, Tajiri, Takuma, Roa, Juan Carlos, Sarmiento, Juan M., Reid, Michelle D., Adsay, Volkan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Amyloid; Biomarkers, Tumor - analysis; Carcinoma; Cauliflowers; Cholesterol; Chromatin; Classification; Complexity; Cytoplasm; Databases, Factual; Dysplasia; Female; Gallbladder; Gallbladder cancer; Gallbladder Neoplasms - chemistry; Gallbladder Neoplasms - classification; Gallbladder Neoplasms - pathology; Humans; Invasiveness; Male; Medicine; Medicine & Public Health; Middle Aged; Mucin 5AC - analysis; Mucin-6 - analysis; Mucosa; Neoplasm Invasiveness; Neoplasms; Nodules; Nuclei (cytology); Nucleoli; Original Article; Papillary thyroid carcinoma; Pathology; Polyps; Polyps - chemistry; Polyps - classification; Polyps - pathology; Stroma; Thyroid; Tubules; Tumor Burden; Tumors
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-020-02877-7

Preinvasive tumor-forming gallbladder neoplasms that are composed of small, non-mucinous tubules with complex architecture remain a poorly characterized group. Here, we evaluated the clinicopathological characteristics of this entity. Twenty-eight examples were analyzed. Tumors were invariably pedunculated polyps with thin stalks, often presented as loosely attached intraluminal nodules, with cauliflower architecture (akin to cholesterol polyps) comprised of compact, back-to-back acinar-like, small tubular units with minimal/no cytoplasm showing variable complexity, creating a picture distinct from the other tubular type dysplasia in the gallbladder. Their limited stroma showed distinctive amorphous amyloid-like hyalinization (39%). While some had round nuclei with single prominent nucleoli, others exhibited slightly more elongated nuclei with washed out chromatin reminiscent of papillary thyroid carcinoma. Squamoid/meningothelial-like morules (71%) and subtle neuroendocrine cell clusters (39%) were frequent. The level of cytoarchitectural atypia qualified as high-grade dysplasia (HGD) in all cases, but none were invasive. The background mucosa showed no dysplasia, but cholesterolosis. The majority ( n  = 8/12) showed diffuse MUC6 expression and lacked MUC5AC expression. Based on these observations, 635 gallbladder carcinomas were re-analyzed for residual/adjacent lesions with entity-defining characteristics disclosed here, and none could be identified. Preinvasive tubular non-mucinous neoplasm of the gallbladder, which we propose to classify as intracholecystic tubular non-mucinous neoplasm, is a clinicopathologically discrete entity, which tends to occur in uninjured gallbladders and in association with cholesterol polyps. By being tubular, non-mucinous and MUC6-positive, it is akin to intraductal tubulopapillary neoplasms of pancreatobiliary tract, but it is also different in many other aspects. Although their cytoarchitectural complexity warrants an HGD/carcinoma classification, they do not show invasion and their distinct characteristics warrant their separate classification.