Esophagus
Carcinoma
Adenosquamous carcinoma
Authors: Selim Sürer, M.D., Raul S. Gonzalez, M.D.
Editorial Board Member: David J. Escobar, M.D., Ph.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Last author update: 24 February 2025
Last staff update: 24 February 2025
Copyright: 2003-2025, PathologyOutlines.com, Inc.
PubMed Search: Adenosquamous carcinoma
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Sürer S, Gonzalez RS. Adenosquamous carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/esophagusadenosquamous.html. Accessed April 2nd, 2025.
Definition / general
- Rare malignant esophageal neoplasm that includes separate malignant glandular and squamous components (World Health Organization [WHO])
Essential features
- Histologic evidence of both squamous cell carcinoma and adenocarcinoma components in the same lesion
- Easily misdiagnosed in preoperative biopsy as squamous cell carcinoma
- Prognosis is most favorable when situated in the upper third of the esophagus and poorest when in the middle third
- Prognosis is poorer than for adenocarcinoma and similar to squamous cell carcinoma
- Patients aged 65 and older, as well as males, show a significantly higher incidence rate compared to the general population
ICD coding
- ICD-O: 8560/3 - adenosquamous carcinoma
- ICD-11: 2B70.Y & XH7873 - other specified malignant neoplasms of esophagus & adenosquamous carcinoma
Epidemiology
- Constitutes roughly 3.1% of all adenosquamous carcinomas in the body and < 1% of all esophageal cancers (J Cancer 2024;15:1442)
- Clinical and demographic data vary between Eastern and Western countries (World J Surg Oncol 2022;20:143)
- Incidence rate is significantly higher among patients aged 65 and older and in males (J Cancer 2024;15:1442)
- Data from the Surveillance, Epidemiology and End Results (SEER) Program at the National Cancer Institute between 1998 - 2010 showed a much higher prevalence in the White population (95.2%) compared to Black (2.5%) and other (2.3%) populations within the United States (J Gastrointest Oncol 2017;8:89)
Sites
- Discrepancies exist between carcinomas occurring in Eastern Asian and Western populations
- Primarily (60 - 67%) located in the lower third followed by the middle third of the esophagus in studies conducted in Western populations (J Cancer 2024;15:1442, J Pers Med 2023;13:468)
- Mainly (66%) located in the middle third of the esophagus in East Asian patients (World J Surg Oncol 2022;20:143)
Pathophysiology
- Various theories have been proposed (J Transl Int Med 2018;6:70)
- Collision tumor wherein 2 distinct stem cells undergo simultaneous and independent malignant transformation
- Potential origin from submucosal glands or ducts (Dig Dis Sci 1987;32:428)
- Reflux with Barrett esophagus as a precursor lesion (Gastroenterology 2002;122:784)
- Rat models have suggested chronic duodenal reflux as a cause (Carcinogenesis 2000;21:1587)
Etiology
- Risk factors similar to those in squamous cell carcinoma of the esophagus (WHO)
- Different factors play a role in the pathogenesis in Western and Eastern countries (World J Surg Oncol 2022;20:143)
- Western countries: smoking, body mass index (BMI) above lowest quartile, gastroesophageal reflux, low fruit and vegetable consumption
- Eastern countries: smoking, alcohol consumption, drinking beverages at high temperatures, poor nutritional status
Clinical features
- Often high grade and late stage when diagnosed, leading to poor prognosis (J Gastrointest Oncol 2017;8:89, J Pers Med 2023;13:468)
- Clinical manifestations similar to those of other types of esophageal cancer (J Thorac Dis 2016;8:2689)
- Dysphagia, retrosternal or upper abdominal pain, loss of weight
- Prognosis is poorer than for adenocarcinoma and similar to squamous cell carcinoma (J Pers Med 2023;13:468)
Diagnosis
- Easily misdiagnosed in preoperative endoscopic biopsy as squamous cell carcinoma, with resection often necessary to confirm biphasic morphology (World J Surg Oncol 2022;20:143)
- Squamous component can involve the epithelium, while the glandular component is often located deeper in the tumor, making it difficult to sample both on biopsy
- Small size of biopsy specimens contributes to this challenge
Radiology description
- Mass lesion may be visible on barium meal study or on computed tomography (CT)
Radiology images
Images hosted on other servers:
Tumor in barium study
Tumor mass on CT
Prognostic factors
- Prognosis is most favorable for tumors in the upper third of the esophagus and poorest for those in the middle third; prognosis is also strongly linked to the rate of local lymph node positivity (J Cancer 2024;15:1442)
Case reports
- 53 year old man with a 10 cm esophageal tumor diagnosed at autopsy (Oncol Lett 2017;14:4918)
- 71 year old man with a slightly elevated tumor in the lower esophagus (Case Rep Gastroenterol 2019;13:144)
- 77 year old man with adenosquamous carcinoma of the distal esophagus (World J Clin Cases 2021;9:1336)
- 81 year old man presented with a gastroesophageal junction mass (Surg Case Rep 2022;8:82)
Treatment
- Combined treatment incorporating surgery, radiotherapy and chemotherapy is more effective than any single modality alone (J Pers Med 2023;13:468)
Clinical images
Images hosted on other servers:
Lesion in gastroesophageal junction
Lesion in distal esophagus
Gross description
- Diverse macroscopic appearance, including ulcerative, intraluminal, polypoid and sclerotic
- Macroscopically indistinguishable from squamous cell carcinoma (J Transl Int Med 2018;6:70)
Gross images
Images hosted on other servers:
Elevated tumor, gastroesophageal junction
Microscopic (histologic) description
- Biphasic neoplasm characterized by an adenocarcinoma component and a squamous cell carcinoma component, which may have distinct boundaries or show gradual transition
- Any degree of differentiation can be exhibited by either component (J Transl Int Med 2018;6:70)
- Squamous component: keratin pearl formation, zonal differentiation toward the center of the tumor nests, intercellular bridges
- Adenocarcinoma component: tubular or glandular structures, occasional mucin production
- No broad consensus regarding percentage cutoff criteria
- WHO states that component proportions are not relevant
- Japanese Classification of Esophageal Cancer requires that both components comprise at least 20% of the tumor
- Background squamous or glandular dysplasia may be present
Microscopic (histologic) images
Contributed by Raul S. Gonzalez, M.D., Adam L. Booth, M.D., Jerome Cheng, M.D., Maria Westerhoff, M.D. and AFIP
Biopsy
Resection
Smaller resected tumor
Mucosa and submucosa
Mucosa and submucosa
Biopsy, p40 / CK5 IHC
Biopsy, mucicarmine
Positive stains
- Squamous component is positive for squamous markers (p40, CK5)
- Glandular component should produce mucin (mucicarmine)
Sample pathology report
- Distal esophagus, resection:
- Adenosquamous carcinoma (5.5 cm), invading muscularis propria
- Margins of resection unremarkable
- See synoptic report
Differential diagnosis
- Mucoepidermoid carcinoma:
- Tumor nests composed of a tight admixture of intermediate cells, mucin producing cells and malignant squamous cells
- Extremely rare in the esophagus
- Squamous cell carcinoma:
- Pure squamous features, without any glandular component
- Much more common in the esophagus than adenosquamous carcinoma
- Adenocarcinoma:
- Pure glandular features, without any squamous component
- Much more common in the esophagus than adenosquamous carcinoma
Additional references
Board review style question #1
A 70 year old man presents with dysphagia and is found to have an esophageal mass. A biopsy of the mass shows the features pictured. No intermediate cells are present. What is the diagnosis?
- Adenocarcinoma
- Adenosquamous carcinoma
- Mucoepidermoid carcinoma
- Squamous cell carcinoma
Board review style answer #1
B. Adenosquamous carcinoma. This tumor shows a glandular component and a squamous component, both comprising at least 20% of the tumor. Answers A and D are incorrect because both would be purely monophasic or > 80% monophasic. This percentage cutoff is not proposed by all authorities but regardless, this tumor is clearly biphasic. Answer C is incorrect because intermediate cells are not present.
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Board review style question #2
Which of the following is true regarding adenosquamous carcinoma of the esophagus?
- It is easily diagnosed on biopsy
- It is more common in female patients
- It is the most common malignancy of the esophagus
- It may show background squamous or glandular dysplasia
Board review style answer #2
D. It may show background squamous or glandular dysplasia. Esophageal adenosquamous carcinoma has similar clinical features to esophageal squamous cell carcinoma and may show background squamous dysplasia but background glandular dysplasia has also been reported. Answer A is incorrect because only 1 of the 2 components (squamous and glandular) may be sampled on biopsy, leading to misdiagnosis via sampling. Answer B is incorrect because it is more common in male patients. Answer C is incorrect because esophageal adenosquamous carcinoma is very rare.
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