Lung

• Malignant neoplasm showing components of both squamous cell carcinoma and adenocarcinoma (each comprising at least 10% of the tumor)

• Resectable adenosquamous carcinoma patients had higher pleural invasion incidence, poorer differentiation and worse survival compared with squamous cell carcinoma and adenocarcinoma patients (Jpn J Clin Oncol 2022;52:1456)
• EGFR mutated adenosquamous carcinomas appear to have better prognosis (Pathol Int 2013;63:77)
• Adenosquamous carcinomas without EGFR mutations show a moderate response to immune checkpoint inhibitor (ICI) based immunotherapy (Front Immunol 2022;13:944812)
• High CXCR4 expression predicts a poor prognosis in resected lung adenosquamous carcinoma (J Cancer 2020;11:810)
• Adenocarcinomatous predominant subtype of adenosquamous carcinoma of the lung (ASC) is associated with a better prognosis than the squamous cell carcinoma predominant subtype (J Cancer 2020;11:810)

Contributed by Roseann Wu, M.D., M.P.H.

Images hosted on other servers:

Contributed by Roseann Wu, M.D., M.P.H.


Images hosted on other servers:

• TTF1 in adenocarcinoma component and p40 and CK5/6 in squamous component
• CK7
• Reference: StatPearls: Non-Small Cell Lung Cancer [Accessed 17 February 2025]

• EGFR and KRAS mutations, both characteristic of adenocarcinoma, have been reported in adenosquamous carcinoma
• EGFR amplification is frequent in adenosquamous carcinoma
• References: J Clin Med 2024;13:5711, Am J Transl Res 2024;16:126

• Lung, right lower lobe, biopsy:
  • Compatible with adenosquamous carcinoma (see comment)
  • Comment: The tumor displays both glandular and squamous differentiation, characteristic of adenosquamous carcinoma. This is a rare and aggressive subtype of non-small cell lung carcinoma. The patient's clinical presentation and radiological findings support the pathological diagnosis. Further molecular testing and staging studies may be necessary for appropriate treatment planning. Immunohistochemical staining shows positivity for thyroid transcription factor 1 (TTF1) in the adenocarcinoma component, confirming its pulmonary origin. Positivity for p40 and p63 is observed in the squamous component, confirming its squamous differentiation.

• Semin Diagn Pathol 2014;31:271, Oncotarget 2015;6:23905, Eur J Cardiothorac Surg 2012;41:357, J Cardiothorac Surg 2010;5:92

Which of the following is true about pulmonary adenosquamous carcinoma?

1. Always shows both components in metastases
2. Has a better prognosis than pure adenocarcinoma or squamous cell carcinoma
3. May harbor EGFR or KRAS mutations
4. Requires immunohistochemistry for diagnosis
5. Shows a benign squamous component

C. May harbor EGFR or KRAS mutations. It is important to recognize pulmonary adenosquamous carcinoma, as these tumors may harbor targetable mutations seen in adenocarcinomas, such as EGFR or KRAS. Answer B is incorrect because pulmonary adenosquamous carcinoma has a worse prognosis than either adenocarcinoma or squamous carcinoma. Answer A is incorrect because only 1 of the 2 components may be seen in metastatic sites. Answer D is incorrect because the diagnosis is made with at least 10% of each component by histology, not immunohistochemistry. Answer E is incorrect because both the adenocarcinoma and squamous cell carcinoma components are malignant.

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Reference: Adenosquamous carcinoma

Which of the following statements regarding lung adenosquamous carcinoma is accurate?

1. Always benign and does not exhibit metastatic potential
2. Characterized by a glandular and squamous differentiation
3. Commonly presents as a purely neuroendocrine tumor
4. Exclusively composed of squamous cell carcinoma elements
5. Primarily affects the bronchial cartilage and not the epithelial cells

B. Characterized by a glandular and squamous differentiation. Lung adenosquamous carcinoma is a subtype of non-small cell lung cancer (NSCLC) that contains both glandular (adenocarcinoma) and squamous (squamous cell carcinoma) differentiation. This histological pattern differentiates it from other types of lung cancer. Answer A is incorrect because adenosquamous carcinoma is, by definition, a malignant neoplasm. Answer C is incorrect because adenosquamous carcinoma cells are not neuroendocrine in origin. Neuroendocrine neoplasms are a separate entity from lung neoplasms with different morphology, clinical presentations and immunohistochemical profile. Answer D is incorrect because by definition, adenosquamous carcinomas must contain at least 10% components of both adenocarcinoma and squamous cell carcinoma by histomorphology. Answer E is incorrect because this entity arises from the epithelium of the lung.

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Reference: Adenosquamous carcinoma

Which of the following clinical features is commonly associated with lung adenosquamous carcinoma?

1. Limited association with smoking history
2. Overexpression of the ALK gene fusion
3. Paraneoplastic production of PTH related peptide
4. Peripheral, cavitary lesions on chest imaging
5. Strong female predominance among affected patients

D. Peripheral, cavitary lesions on chest imaging. Lung adenosquamous carcinoma often presents with peripheral cavitary lesions on chest Xray, which can be a distinguishing feature. This radiological appearance may be indicative of necrotic or cavitated areas within the tumor. Answers A, B, C and E are incorrect because they are not commonly associated with lung adenosquamous carcinoma.

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Reference: Adenosquamous carcinoma