Pancreas
Exocrine tumors / carcinomas
Adenosquamous carcinoma
Authors: Orhun Çığ Taşkın, M.D., N. Volkan Adsay, M.D.
Editorial Board Member: Raul S. Gonzalez, M.D.
Deputy Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 1 May 2018
Minor changes: 6 March 2020
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: Adenosquamous carcinoma[TI] pancreas
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Etiology | Radiology description | Radiology images | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Stains | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review answer #1Cite this page: Taşkın OÇ, Adsay NV. Adenosquamous carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreasadenosquamous.html. Accessed August 6th, 2020.
Definition / general
- Malignant tumor consisting of both squamous cell carcinoma and ductal adenocarcinoma components (Digestion 2005;72:104, Cancer 2003;99:372, Int J Pancreatol 1999;26:85, Arch Surg 1999;134:599)
- Closely related to and admixed with pancreatic ductal adenocarcinoma; some authors require 30% squamous differentiation for the diagnosis of adenosquamous carcinoma (Bosman: WHO Classification of Tumors of the Digestive System, 4th Edition, 2010)
- Tumors with less than 30% squamous component behave similar to adenosquamous carcinoma and can be signed out as ductal adenocarcinoma with focal (less than 30%) squamous differentiation
- Metastatic tumor can be solely composed of the glandular component (Mod Pathol 2001;14:443)
- Often has necrotic and cystic areas (Arch Surg 1999;134:599)
Essential features
- Malignant tumor consisting of both squamous cell carcinoma and ductal adenocarcinoma components
- 2% of exocrine pancreatic malignancies
- Adenocarcinoma and squamous components can vary greatly in amount and distribution; some authors require 30% squamous differentiation for the diagnosis of adenosquamous carcinoma
- p63, p40 and high molecular weight cytokeratin highlight the squamous component
- Even more aggressive than ductal adenocarcinoma, with a median survival of less than one year
Epidemiology
- 2% of exocrine pancreatic malignancies
- M:F = 2:1
- Mean age of 65 years (Arch Surg 1999;134:599)
Sites
- Body and tail of the pancreas are more often affected than the head (J Surg Res 2012;174:12)
Etiology
- Ionizing radiation of the pancreas may predispose to the occurrence of adenosquamous carcinoma (Mod Pathol 2001;14:443)
Radiology description
- Similar to pancreatic ductal adenocarcinoma but many cases present with rounder, more lobulated lesion with extensive central necrosis
- Portal venous system may contain tumor thrombus (Abdom Radiol (NY) 2016;41:508)
Radiology images
Contributed by Orhun Çığ Taşkın, M.D.
Cystic and necrotic changes
Treatment
- Similar to pancreatic ductal adenocarcinoma
- If the tumor is operable, complete surgical resection, followed by adjuvant chemotherapy; increasingly, neoadjuvant therapy is utilized (Hum Pathol 2010;41:113, J Gastrointest Oncol 2015;6:115)
- Even more aggressive than ductal adenocarcinoma, with a median survival of less than one year (Gastrointest Cancer Res 2013;6:75)
Gross description
- Large, firm mass of the pancreas with ill defined borders, often with necrotic component, with or without cystic areas
- Some tumors are more demarcated
Microscopic (histologic) description
- Adenocarcinoma component can have all the characteristics of classic pancreatic ductal adenocarcinoma
- Squamous component can show keratinization with intercellular bridges or sheets of squamous cells with keratohyalin granules or pearls; some are adenoacanthoma-like with bland, mature squamous elements, whereas others are more basal-like with high N/C ratio and basophilic appearance
- Adenocarcinoma and squamous components can vary greatly in amount and distribution
- Presence of a tertiary component has been rarely documented (World J Gastroenterol 2014;20:16381, JOP 2007;8:330)
Microscopic (histologic) images
Contributed by Orhun Çığ Taşkın, M.D.
Glandular and squamous components
H&E and p63
p63
Contributed by Raul S. Gonzalez, M.D.
Glandular and squamous components
AFIP images
Adenosquamous carcinoma
Squamous components
Mucoepidermoid pattern
Left: CAM5.2; right: CK13
Images hosted on other servers:
Squamous components
Clear cell component
Rhabdoid component
Keratin stains intermediate filaments of rhabdoid cells
Immunostains
45 year old man with acantholytic pattern, osteoclast-like and pleomorphic giant cells
Cytology description
- Squamous component may be undersampled but malignant squamous cells are highly significant for the diagnosis (Acta Cytol 2013;57:139)
- Glandular and squamous components can both be distinguished
- Dense globules, silhouettes of squamous cells, anucleate squames, atypical cytoplasm and enlarged pyknotic nuclei are present in the prominent necrotic background
- Sheets and clusters of atypical cells with nuclei of variable sizes and shapes (Cancer 2003;99:372)
Cytology images
Contributed by Orhun Çığ Taşkın, M.D.
Pap stain
Cell block, H&E
Cell block, p40
Stains
- Immunoreactivity for AE1 / AE3 is identified
- p63, p40, high molecular weight cytokeratin and CK5 / 6 specifically highlight the squamous component (Mod Pathol 2005;18:1193, Mod Pathol 2009;22:651), whereas CK7 is generally positive in the glandular component
- Both components show MUC1 immunoreactivity (Mod Pathol 2009;22:651)
- Loss of p16 and SMAD4 (DPC4) protein expression (Mod Pathol 2009;22:651)
Molecular / cytogenetics description
- TP53 mutations and 3p loss are commonly encountered
- KRAS mutations in the majority of cases (Mod Pathol 2001;14:443, Mod Pathol 2009;22:651)
- Recently discovered "basal-like" molecular subtype of pancreatic ductal adenocarcinoma is believed to also represent adenosquamous carcinoma (Nature 2016;531:47)
- Both adenomatous and squamous components are believed to originate from the same progenitor cell (J Pathol 2017;243:155)
- Recent case report documents pancreatic adenosquamous carcinoma arising in intraductal papillary mucinous neoplasm (IPMN) in a CDKN2A germline mutation carrier (World J Gastrointest Oncol 2017;9:390)
Differential diagnosis
- Metastasis of adenosquamous carcinoma of the lung:
- Needs to be carefully excluded (Virchows Arch 2004;444:527, Cases J 2010;3:41)
- In addition, TTF1 positivity in adenosquamous carcinoma of the lung may help this differential diagnosis, along with clinical correlation
- Pure squamous cell carcinoma: extremely rare, most cases contain a small amount of glandular component, which is enough to call the tumor adenosquamous carcinoma
Board review style question #1
65 year old man presented with back pain and severe weight loss. Radiologic images showed a 4 cm relatively round, lobulated mass with extensive central necrosis in the pancreatic body. He underwent resection. Histologic sections demonstrated conventional ductal adenocarcinoma admixed with sheets of squamous cells with keratohyalin granules and intercellular bridges. Which of the following immunohistochemical stains will be positive in the squamous areas?
- β catenin nuclear expression
- Chromogranin A
- p63
- Synaptophysin
- Trypsin
Board review answer #1
