Intracholecystic tubular non-mucinous neoplasm (ICTN) of the gallbladder: a clinicopathologically distinct, invasion-resistant entity.
Adenoma
Gallbladder
Preinvasive neoplasm
Pyloric
Tubular Papillary
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
26
05
2020
accepted:
17
06
2020
revised:
26
05
2020
pubmed:
22
7
2020
medline:
31
3
2021
entrez:
22
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32691142
doi: 10.1007/s00428-020-02877-7
pii: 10.1007/s00428-020-02877-7
doi:
Substances chimiques
Biomarkers, Tumor
0
MUC5AC protein, human
0
MUC6 protein, human
0
Mucin 5AC
0
Mucin-6
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
435-447Références
Abraham SC, Wu TT, Klimstra DS et al (2001) Distinctive molecular genetic alterations in sporadic and familial adenomatous polyposis-associated pancreatoblastomas: frequent alterations in the APC/beta-catenin pathway and chromosome11p. Am J Pathol 159:1619–1627. https://doi.org/10.1016/s0002-9440(10)63008-8
doi: 10.1016/s0002-9440(10)63008-8
pubmed: 11696422
pmcid: 1867075
Adsay NV (2015) Gallbladder, extrahepatic biliary tree, and ampulla. In: Mills SE, Greenson JK et al (eds) Sternberg’s diagnostic surgical pathology, 6th edn. Wolters Kluwer Health, pp 1770–1846
Adsay NV, Klimstra DS (2014) Benign and malignant tumors of the gallbladder and extrahepatic biliary tract. In: Odze R, Goldblum J (eds) Surgical pathology of the GI tract, liver, biliary tract, and pancreas, 3rd edn. Elsevier, Philadelphia, pp 1021–1054
Adsay NV, Kloppel G, Fukushima N et al (2010) Intraductal neoplasms of the pancreas. In: Bosman FT, Carneiro F, Hruban RH et al (eds) WHO Classification of tumours of the digestive system, 4th edn. IARC, Press, Lyon, pp 304–313
Adsay V, Jang KT, Roa JC et al (2012) Intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are >/=1.0 cm): clinicopathologic and immunohistochemical analysis of 123 cases. Am J Surg Pathol 36:1279–1301. https://doi.org/10.1097/PAS.0b013e318262787c
doi: 10.1097/PAS.0b013e318262787c
pubmed: 22895264
Adsay NV, Jang KT, Ohike N et al (2013) International consensus study on the terminology and diagnosis of tumoral intraepithelial neoplasms (“adenomas” and “intracystic papillary neoplasms” of WHO-2010) of the gallbladder (abstract). Mod Pathol 26:422A. https://doi.org/10.1038/modpathol.2013.20
doi: 10.1038/modpathol.2013.20
Adsay V, Mino-Kenudson M, Furukawa T et al (2016) Pathologic evaluation and reporting of intraductal papillary mucinous neoplasms of the pancreas and other tumoral intraepithelial neoplasms of pancreatobiliary tract: recommendations of Verona Consensus Meeting. Ann Surg 263:162–177. https://doi.org/10.1097/SLA.0000000000001173
doi: 10.1097/SLA.0000000000001173
pubmed: 25775066
pmcid: 4568174
Albores-Saavedra J, Henson DE, Klimstra DS (2000) Benign epithelial tumors of the gallbladder. In: Rosai J, Sobin LH (eds) Tumors of the gallbladder, extrahepatic bile duct, and ampulla of vater. Atlas of tumor pathology. Armed Forces Institute of Pathology, Washington, DC, pp 21–33
Bagci P, Saka B, Erbarut Seven I et al (2013) Growth patterns of high-grade gallbladder dysplasia: clinicopathologic associations and diagnostic implications in an analysis of 318 cases (abstract). Mod Pathol 26:422A. https://doi.org/10.1038/modpathol.2013.20
doi: 10.1038/modpathol.2013.20
Balci S, Bagci P, Dursun N et al (2014) Complex tubular type intracholecystic papillary tubular neoplasms (ICPN): further Clinicopathologic and molecular characterization. Mod Pathol 27:446A. https://doi.org/10.1038/modpathol.2014.24
doi: 10.1038/modpathol.2014.24
Basturk O, Adsay V, Askan G et al (2017) Intraductal Tubulopapillary neoplasm of the pancreas: a Clinicopathologic and Immunohistochemical analysis of 33 cases. Am J Surg Pathol 41:313–325. https://doi.org/10.1097/pas.0000000000000782
doi: 10.1097/pas.0000000000000782
pubmed: 27984235
pmcid: 5309137
Basturk O, Berger MF, Yamaguchi H et al (2017) Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma. Mod Pathol 30:1760–1772. https://doi.org/10.1038/modpathol.2017.60
doi: 10.1038/modpathol.2017.60
pubmed: 28776573
Basturk O, Aishima S, Esposito I (2019) Intracholecystic papillary neoplasm. In: WHO Classification of tumours. Digestive system tumours. WHO Classification of tumours Editorial board, 5th edn. IARC Press, Lyon, France, pp 276–278
Basturk O, Aishima S, Esposito I (2019) Pyloric gland adenoma of the gallbladder. WHO Classification of tumours. Digestive system tumours. WHO Classification of tumours Editorial board, 5th edn. IARC Press, Lyon, France, pp 271–272
Basturk O, Esposito I, Fukushima N et al (2019) Pancreatic intraductal papillary mucinous neoplasm. In: WHO Classification of tumours. Digestive system tumours. WHO Classification of tumours Editorial board, 5th edn. IARC Press, Lyon, France, pp 310–314
Basturk O, Esposito L, Fukushima N et al (2019) Pancreatic intraductal tubulopapillary neoplasm. In: WHO Classification of tumours. Digestive system tumours. WHO Classification of tumours Editorial board, 5th edn. IARC Press, Lyon, France, pp 317–318
Gamachi A, Kashima K, Daa T, Nakatani Y, Tsujimoto M, Yokoyama S (2003) Aberrant intranuclear localization of biotin, biotin-binding enzymes, and beta-catenin in pregnancy-related endometrium and morule-associated neoplastic lesions. Mod Pathol 16:1124–1131. https://doi.org/10.1097/01.mp.0000092953.20717.48
doi: 10.1097/01.mp.0000092953.20717.48
pubmed: 14614052
He C, Fukumura Y, Toriyama A, Ogura K, Sasahara N, Mitani K, Yao T (2018) Pyloric gland adenoma (PGA) of the gallbladder: a unique and distinct tumor from PGAs of the stomach, duodenum, and pancreas. Am J Surg Pathol 42:1237–1245. https://doi.org/10.1097/pas.0000000000001117
doi: 10.1097/pas.0000000000001117
pubmed: 29975247
Hruban RH, Takaori K, Klimstra DS et al (2004) An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 28:977–987
doi: 10.1097/01.pas.0000126675.59108.80
Katabi N, Torres J, Klimstra DS (2012) Intraductal tubular neoplasms of the bile ducts. Am J Surg Pathol 36:1647–1655. https://doi.org/10.1097/PAS.0b013e3182684d4f
doi: 10.1097/PAS.0b013e3182684d4f
pubmed: 23073323
Kloppel G, Adsay V, Konukiewitz B, Kleeff J, Schlitter AM, Esposito I (2013) Precancerous lesions of the biliary tree. Best Pract Res Clin Gastroenterol 27:285–297. https://doi.org/10.1016/j.bpg.2013.04.002
doi: 10.1016/j.bpg.2013.04.002
pubmed: 23809246
Nakanuma Y, Basturk O, Esposito I, Klimstra DS, Komuta M, Zen Y (2019) Intraductal papillary neoplasm of the bile ducts. In: WHO Classification of tumours. Digestive system tumours. WHO Classification of tumours Editorial board, 5th edn. IARC, Press, Lyon
Nakatani Y, Masudo K, Miyagi Y et al (2002) Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules. Mod Pathol 15:617–624. https://doi.org/10.1038/modpathol.3880575
doi: 10.1038/modpathol.3880575
pubmed: 12065775
Reid MD, Losada H, Muraki T et al (2019) Field risk (“field-effect”/“field-defect”) in the gallbladder and biliary tree: an under-recognized phenomenon with major implications for management and carcinogenesis (abstract). Abstracts from USCAP 2019: Pancreas, Gallbladder, Ampulla, and Extra-Hepatic Biliary Tree (1667-1734). Mod Pathol 32:41. https://doi.org/10.1038/s41379-019-0231-y
doi: 10.1038/s41379-019-0231-y
Robinson BS, Fisher K, Pehlivanoglu B, Balci S, Reid MD, Krasinskas AM, Adsay V (2018) CTNNB1-mutations define a subset of preinvasive mass-forming lesions in the gallbladder with reduced malignant potential (abstract). USCAP 2018 Abstracts: Pancreas and Biliary Tree (1863–1933). Lab Invest 98:687. https://doi.org/10.1038/labinvest.2018.19
Roy S, Lam-Himlin D, Montgomery E, Seethala R, Singhi A (2019) Targeted next-generation sequencing (NGS) of intracholecystic papillary-tubular neoplasms (ICPNs) identifies two distinct subtypes and their relationship to gallbladder carcinomas (abstract). Abstracts from USCAP 2019: Pancreas, Gallbladder, Ampulla, and Extra-Hepatic Biliary Tree (1667-1734). Mod Pathol 32:44. https://doi.org/10.1038/s41379-019-0231-y
Saegusa M, Okayasu I (2001) Frequent nuclear beta-catenin accumulation and associated mutations in endometrioid-type endometrial and ovarian carcinomas with squamous differentiation. J Pathol 194:59–67. https://doi.org/10.1002/path.856
doi: 10.1002/path.856
pubmed: 11329142
Schlitter AM, Jang KT, Kloppel G et al (2015) Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases. Mod Pathol 28:1249–1264. https://doi.org/10.1038/modpathol.2015.61
doi: 10.1038/modpathol.2015.61
pubmed: 26111977
Taskin OC, Akkas G, Memis B et al (2019) Sarcomatoid carcinomas of the gallbladder: clinicopathologic characteristics. Virchows Arch 475:59–66. https://doi.org/10.1007/s00428-019-02583-z
doi: 10.1007/s00428-019-02583-z
pubmed: 31177317
pmcid: 7341336
Taskin OC, Bellolio E, Dursun N et al (2019) Non-neoplastic polyps of the gallbladder: a clinicopathologic analysis of 447 cases. Am J Surg Pathol 44(4):467–476. https://doi.org/10.1097/PAS.0000000000001405
doi: 10.1097/PAS.0000000000001405
Yamaguchi H, Shimizu M, Ban S et al (2009) Intraductal tubulopapillary neoplasms of the pancreas distinct from pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 33:1164–1172. https://doi.org/10.1097/PAS.0b013e3181a162e5
doi: 10.1097/PAS.0b013e3181a162e5
pubmed: 19440145