Adenosquamous Carcinoma of the Lung: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
April 29, 2026

---

Adenosquamous carcinoma is a type of lung cancer that contains two distinct kinds of cancer cells: glandular cells — which normally produce mucus and other substances that keep the airways moist — and squamous cells — which normally line the inner surfaces of the airways. Because it contains both cell types, adenosquamous carcinoma shares features with two other forms of lung cancer: adenocarcinoma and squamous cell carcinoma. By definition, each component must make up at least 10% of the tumor for this diagnosis to apply. Adenosquamous carcinoma is relatively uncommon, accounting for roughly 1–4% of all primary lung cancers. Still, it tends to behave aggressively and carries a higher risk of spreading than either pure adenocarcinoma or pure squamous cell carcinoma at the same stage. This article will help you understand the findings in your pathology report — what each term means and why it matters for your care.

What causes adenosquamous carcinoma of the lung?

Tobacco smoking is the most common cause of adenosquamous carcinoma of the lung. The harmful chemicals in cigarette smoke damage the DNA inside airway cells over many years, and this accumulated damage can eventually trigger cancer. However, like adenocarcinoma, adenosquamous carcinoma also occurs in people who have never smoked. In never-smokers, it is more likely to harbor specific genetic changes that can be targeted with treatment.

Other risk factors include:

• Radon gas exposure — Radon is a naturally occurring radioactive gas that can accumulate in homes and buildings. Long-term exposure is a recognized cause of lung cancer.
• Asbestos exposure — Prolonged contact with asbestos fibers, particularly in occupations such as construction, shipbuilding, or mining, increases the risk of developing lung cancer.
• Air pollution and industrial chemicals — Long-term exposure to outdoor air pollution or workplace chemicals is associated with a modestly increased risk.
• Genetic factors — A family history of lung cancer or inherited changes in certain genes may increase the risk, though this is uncommon.

What are the symptoms of adenosquamous carcinoma of the lung?

Symptoms depend on the size and location of the tumor. Adenosquamous carcinoma can arise in both central and peripheral locations within the lung.

Common symptoms include:

• A persistent cough that worsens over time.
• Coughing up blood.
• Shortness of breath.
• Chest pain or discomfort.
• Fatigue and unexplained weight loss.

If the cancer has spread to other parts of the body, additional symptoms may appear depending on which organs are involved. For example, spread to the bones can cause bone pain, and spread to the brain can cause headaches or neurological changes.

How is the diagnosis made?

The diagnosis of adenosquamous carcinoma typically begins when imaging — usually a CT scan of the chest — reveals a suspicious mass or nodule. A biopsy is then performed to obtain a small tissue sample for examination. Depending on the location of the tumor, the biopsy may be done by CT-guided needle biopsy through the chest wall, by bronchoscopy (a flexible tube passed into the airways), or by another minimally invasive technique. In some cases, the diagnosis is confirmed only after the tumor has been surgically removed and the entire specimen is examined.

Under the microscope, a pathologist identifies adenosquamous carcinoma by recognizing both a glandular (adenocarcinoma) component and a squamous cell carcinoma component within the same tumor. The glandular component typically shows cells arranged in gland-like structures, or growing along the surfaces of the air sacs (alveoli) in a pattern called lepidic growth. The squamous component is composed of larger cells that grow in dense sheets or nests, often showing signs of squamous differentiation, such as keratin pearl formation — compact whorls of pink material — or fine connections between adjacent cells called intercellular bridges. Both components must each make up at least 10% of the tumor for the diagnosis of adenosquamous carcinoma to apply. If one component is less than 10%, the tumor is classified by its dominant cell type alone.

To confirm the diagnosis and accurately identify the two components, the pathologist performs immunohistochemistry (IHC). This laboratory technique uses antibodies linked to colored dyes to detect specific proteins inside the cells. The glandular cells typically show positive staining for TTF-1 (a protein associated with lung glandular cells), while the squamous cells show positive staining for p40 and CK5 (proteins associated with squamous cells). Both components are typically negative for chromogranin and synaptophysin — markers of neuroendocrine tumors — confirming that the cancer is not a neuroendocrine carcinoma.

Once the diagnosis is confirmed, imaging — typically CT of the chest and abdomen and often a PET scan — is used to assess how far the cancer has spread and to guide treatment planning.

Histologic grade

The histologic grade of adenosquamous carcinoma is determined by its most poorly differentiated component — meaning that even if one part of the tumor appears relatively well-organized, the grade is set by whichever component looks the most aggressive under the microscope.

• Well differentiated (Grade 1) — Both the glandular and squamous components show features of relatively organized, recognizable cell types with a low number of dividing cells.
• Moderately differentiated (Grade 2) — At least one component shows intermediate features between well and poorly differentiated.
• Poorly differentiated (Grade 3) — At least one component shows marked cellular irregularity and a high number of dividing cells. Most adenosquamous carcinomas fall into this category, which reflects the tendency of this cancer type to behave more aggressively than pure adenocarcinoma or squamous cell carcinoma at the same stage.

Spread through air spaces (STAS)

Spread through air spaces (STAS) means that cancer cells have been found floating within the small airways and air spaces of the lung beyond the edge of the main tumor. These cells have separated from the primary mass and traveled through the natural air channels of the lung.

• STAS not identified — No cancer cells are seen in the air spaces beyond the main tumor edge. This is the more favorable finding.
• STAS present — Cancer cells are identified in the surrounding air spaces. This finding is associated with a higher risk of recurrence after surgery, particularly after limited resections such as wedge resection, and may influence the type and extent of surgery recommended.

Multiple tumors

More than one tumor is occasionally found in the lung. Determining the relationship between multiple tumors is important because it affects staging, treatment, and prognosis.

When multiple tumors look identical under the microscope and share the same molecular profile, they are more likely to represent spread from a single primary cancer to another part of the lung. When tumors differ in appearance or molecular profile — for example, one is adenosquamous carcinoma, and another is pure adenocarcinoma with distinct molecular alterations — they may represent two independent primary cancers that arose separately. Molecular testing can help resolve ambiguous cases. Separate tumor nodules in the same lobe as the primary tumor increase the T stage to pT3; nodules in a different lobe of the same lung are classified as pT4.

Pleural invasion

The pleura is a thin membrane with two layers: the visceral pleura, which covers the outer surface of the lungs, and the parietal pleura, which lines the inside of the chest cavity. Pleural invasion means cancer cells have grown into one or both of these layers.

• Pleural invasion not identified — The tumor has not reached the pleural surface. This is the more favorable finding.
• Visceral pleural invasion — Cancer cells have grown through the elastic layer of the visceral pleura. This increases the T stage and is associated with a higher risk of recurrence.
• Parietal pleural invasion — Cancer cells have grown into the outer pleural layer lining the chest cavity, indicating more advanced local disease.

Lymphovascular invasion

Lymphovascular invasion (LVI) means that cancer cells have been found within blood or lymphatic vessels — the small channels that carry lymph — in or near the tumor. These vessels can act as pathways for cancer cells to travel to lymph nodes or distant organs.

• Lymphovascular invasion not identified — No cancer cells are seen within vessels near the tumor. This is the more favorable finding.
• Lymphovascular invasion present — Cancer cells are found within vessels. This is associated with a higher risk of lymph node involvement and distant metastasis and may influence decisions about additional treatment after surgery.

Surgical margins

Surgical margins are the cut edges of the tissue removed during an operation. The pathologist examines all margins to determine whether the tumor was completely removed. In lung cancer surgery, the margins typically assessed include the bronchial margin (where the airway was divided), the vascular margins (where blood vessels were cut), and the parenchymal margin (the edge of the surrounding lung tissue).

• Negative margin — No cancer cells are seen at the cut edge of the tissue. This indicates that the tumor was fully removed, which is the most favorable outcome.
• Close margin — Cancer cells are present very near the cut edge but do not reach it. Further treatment may be recommended depending on the distance and the specific margin involved.
• Positive margin — Cancer cells are present at the cut edge. This raises concern that some tumor remains and typically leads to discussion of further surgery or radiation therapy.

Lymph nodes

Lymph nodes are small immune organs distributed throughout the chest. During surgery, the surgeon removes lymph nodes from specific locations within the lung and central chest — called lymph node stations — and sends them to the pathologist for examination under the microscope.

The pathology report will describe the total number of lymph nodes examined, their station locations, whether any contain cancer cells, and the size of any deposits found. The number and location of involved lymph nodes determine the nodal stage (N stage). They are among the most important factors in deciding whether additional treatment, such as chemotherapy or radiation, is recommended. In some cases, cancer cells may have broken through the outer wall of a lymph node and spread into the surrounding tissue — a finding called extranodal extension — which indicates more aggressive disease.

Biomarker and molecular testing

Biomarker testing is a standard and essential part of the workup for adenosquamous carcinoma of the lung, particularly in patients with advanced or metastatic disease. Because adenosquamous carcinoma is classified as non-small cell lung cancer (NSCLC), it is tested using the same comprehensive molecular panel used for adenocarcinoma and squamous cell carcinoma. Targetable driver mutations — especially EGFR mutations, found in approximately 10–15% of cases — do occur in adenosquamous carcinoma and directly determine which treatments are available. Testing is performed on biopsy tissue or the surgically removed tumor using next-generation sequencing (NGS), immunohistochemistry (IHC), PCR, and FISH.

EGFR

EGFR (epidermal growth factor receptor) mutations cause a growth-regulating protein on the surface of cancer cells to remain permanently activated, driving uncontrolled cell division. These mutations are more common in never-smokers, women, and people of East Asian ancestry, though they can occur in anyone. In adenosquamous carcinoma, EGFR mutations are found in approximately 10–15% of cases. When present, EGFR-mutated tumors often respond well to targeted drugs called tyrosine kinase inhibitors (TKIs). Osimertinib (Tagrisso) is the current first-line standard of care for advanced EGFR-mutated NSCLC and is also approved as adjuvant therapy for resected stage IB–IIIA EGFR-mutated disease. Your report will describe the result as either “EGFR mutation detected” or “EGFR mutation not detected,” specifying the mutation type if found.

ALK

ALK rearrangements occur when the ALK gene fuses with another gene, creating an abnormal protein that drives tumor growth. These rearrangements are found in approximately 3–5% of NSCLC cases, including a small proportion of adenosquamous carcinomas, and are more common in younger patients and never-smokers. ALK-positive tumors respond well to ALK-targeted TKIs, including alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena). Your report will describe the result as ALK rearrangement positive or ALK rearrangement not detected.

ROS1

ROS1 rearrangements occur in approximately 1–2% of NSCLC cases and are more common in never-smokers and younger patients. ROS1-positive tumors respond well to ROS1-targeted TKIs, including entrectinib (Rozlytrek) and crizotinib (Xalkori). Your report will describe the result as ROS1 rearrangement positive or ROS1 rearrangement not detected.

BRAF

BRAF V600E mutations keep a cell growth signaling pathway permanently active. These mutations are found in approximately 1–3% of NSCLC cases, including adenosquamous carcinoma. Tumors with this mutation can be treated with the combination of dabrafenib (Tafinlar) and trametinib (Mekinist). Your report will state the result as “BRAF mutation detected” or “BRAF mutation not detected.”

MET

MET exon 14 skipping mutations keep the MET growth-signaling protein active longer than normal, continuously driving tumor cell division. These mutations occur in approximately 3–4% of NSCLC cases and are more common in older patients. MET-positive tumors respond to MET-targeted TKIs, including capmatinib (Tabrecta) and tepotinib (Tepmetko). Your report will describe the result as MET exon 14 skipping detected or MET exon 14 skipping not detected.

RET

RET rearrangements occur in approximately 1–2% of NSCLC cases and are more common in never-smokers. RET-positive tumors respond well to RET-targeted TKIs, including selpercatinib (Retevmo) and pralsetinib (Gavreto). Your report will describe the result as RET rearrangement positive or RET rearrangement not detected.

NTRK

NTRK gene fusions are rare in NSCLC (less than 1%). Still, they are clinically important because tumors with these fusions often respond dramatically to TRK-targeted therapies — larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) — regardless of where in the body the cancer started. Your report will describe the result as NTRK fusion-positive or NTRK fusion-negative.

KRAS

KRAS mutations lock a molecular on/off switch for cell growth in the “on” position, causing cancer cells to divide continuously. These are among the most common mutations in lung adenocarcinoma and also occur in adenosquamous carcinoma, particularly in smokers. The most actionable mutation is KRAS G12C. Sotorasib (Lumakras) and adagrasib (Krazati) are approved for previously treated KRAS G12C-mutated NSCLC. Your report will state whether the result is KRAS mutation detected or KRAS mutation not detected, specifying the mutation type.

ERBB2 (HER2)

ERBB2 (HER2) exon 20 insertion mutations drive tumor growth and occur in approximately 2–4% of NSCLC cases. Trastuzumab deruxtecan (Enhertu) is approved for HER2-mutated NSCLC after prior platinum-based chemotherapy, with response rates of approximately 55% in clinical trials. Your report will describe the result as ERBB2 (HER2) mutation detected or ERBB2 (HER2) mutation not detected.

PD-L1

PD-L1 is a protein that some cancer cells display on their surfaces to evade the immune system. Drugs called checkpoint inhibitors block this mechanism, allowing the immune system to recognize and attack the cancer. PD-L1 is measured by immunohistochemistry and reported as the Tumor Proportion Score (TPS) — the percentage of tumor cells showing surface PD-L1 staining. Testing is performed on all newly diagnosed advanced adenosquamous carcinomas and directly guides immunotherapy decisions in patients without a targetable driver mutation.

• TPS <1% — PD-L1 negative. Chemotherapy combined with immunotherapy is generally preferred over immunotherapy alone.
• TPS 1–49% — Low to intermediate PD-L1 expression. Pembrolizumab combined with chemotherapy is a standard first-line option.
• TPS ≥50% — High PD-L1 expression. Pembrolizumab (Keytruda) alone is a standard first-line option.

Mismatch repair (MMR) and microsatellite instability (MSI)

Mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) are uncommon in lung cancer but can occur. When present, these tumors are eligible for pembrolizumab under its tumor-agnostic approval, regardless of PD-L1 level. Testing is performed by immunohistochemistry for the four MMR proteins (MLH1, PMS2, MSH2, MSH6). Your report will describe the result as MMR intact (pMMR) or MMR deficient (dMMR).

Tumor mutational burden (TMB)

Tumor mutational burden (TMB) is a measure of the number of mutations in a cancer cell’s DNA. Tumors with a high mutation count (TMB ≥10 mutations per megabase of DNA) tend to produce more abnormal surface proteins, making them more visible to the immune system and more likely to respond to immunotherapy. Pembrolizumab is approved for any solid tumor with TMB ≥10 mut/Mb that has progressed after prior treatment. TMB is measured by NGS and reported as a numerical value in mut/Mb.

For more information about biomarker testing in cancer, visit the Biomarkers and Molecular Testing section of MyPathologyReport.

Pathologic stage (pTNM)

Adenosquamous carcinoma of the lung is staged using the TNM system based on AJCC 8th edition criteria. The T category describes the size of the tumor and whether it has grown into nearby structures. The N category indicates whether cancer has spread to nearby lymph nodes. The M category — which describes spread to distant organs such as the brain, bones, or liver — is determined by imaging rather than the pathology specimen and is typically not reported in the surgical pathology report. Together, T, N, and M are combined to determine an overall stage, ranging from I (earliest) to IV (most advanced).

Tumor stage (pT)

• pT1a — Tumor is 1 cm or smaller, surrounded by lung or visceral pleura, with no involvement of the main bronchus.
• pT1b — Tumor is larger than 1 cm but no larger than 2 cm, otherwise meeting T1a criteria.
• pT1c — Tumor is larger than 2 cm but no larger than 3 cm, otherwise meeting T1a criteria.
• pT2a — Tumor is larger than 3 cm but no larger than 4 cm; or the tumor — regardless of size — has grown into the visceral pleura, involves the main bronchus without reaching the carina, or is associated with partial lung collapse.
• pT2b — Tumor is larger than 4 cm but no larger than 5 cm, otherwise meeting T2a criteria.
• pT3 — Tumor is larger than 5 cm but no larger than 7 cm; or the tumor has grown into the chest wall, phrenic nerve, or parietal pericardium; or a separate tumor nodule is present in the same lobe as the primary tumor.
• pT4 — Tumor is larger than 7 cm; or the tumor has grown into major structures such as the heart, large blood vessels, trachea, esophagus, or spine; or a separate tumor nodule is present in a different lobe of the same lung.

Nodal stage (pN)

• pNX — Lymph nodes were not examined.
• pN0 — No cancer cells found in any lymph nodes examined.
• pN1 — Cancer cells found in lymph nodes within the lung or near the main airway on the same side of the chest (intrapulmonary, hilar, or peribronchial nodes; stations 10–14).
• pN2 — Cancer cells found in lymph nodes in the central chest on the same side (ipsilateral mediastinal or subcarinal nodes; stations 4–9).
• pN3 — Cancer cells found in lymph nodes on the opposite side of the chest or in the lower neck (contralateral mediastinal, contralateral hilar, scalene, or supraclavicular nodes). This indicates advanced nodal disease.

Treatment effect

If you received chemotherapy or radiation therapy before surgery — a strategy called neoadjuvant treatment — your pathology report will describe the treatment effect: an assessment of how much of the original tumor was destroyed by that pre-surgical treatment. The pathologist estimates the proportion of the tumor that still contains living (viable) cancer cells and expresses this as a percentage. A lower percentage of viable tumor indicates a better response to treatment. This information helps your oncology team assess how well the pre-surgical treatment worked and guides decisions about any additional therapy after surgery.

What is the prognosis?

The prognosis for adenosquamous carcinoma of the lung is generally worse than for either pure adenocarcinoma or pure squamous cell carcinoma at the same stage, reflecting its more aggressive behavior and tendency to spread early. However, outcomes vary considerably depending on the stage at diagnosis, whether a targetable driver mutation is present, and the response to treatment.

• Stage I — Five-year survival with complete surgical resection is approximately 50–70%, somewhat lower than for pure adenocarcinoma at the same stage.
• Stage II — Five-year survival is approximately 35–50%. Adjuvant chemotherapy and, in EGFR-mutated tumors, adjuvant osimertinib are considered after surgery.
• Stage III — Five-year survival ranges from approximately 15–30%. Combined chemotherapy and radiation, followed by durvalumab immunotherapy consolidation, is standard for unresectable stage III disease.
• Stage IV — As with other NSCLC types, treatment is guided by biomarker results. When a targetable driver mutation is present — particularly EGFR — targeted therapy can meaningfully improve survival compared to chemotherapy alone.

Pathologic features associated with a higher risk of recurrence include poorly differentiated histologic grade, lymphovascular invasion, pleural invasion, positive or close surgical margins, STAS, and lymph node involvement.

What happens after the diagnosis?

After the pathology report is finalized, your doctor will review the findings along with your imaging results, molecular profile, and overall health to develop a treatment plan. Adenosquamous carcinoma is treated as a form of NSCLC by a multidisciplinary team including a thoracic surgeon, medical oncologist, radiation oncologist, respirologist, and pathologist.

For early-stage disease (stages I and II), surgery to remove the tumor is the primary treatment. Options include wedge resection (removal of a small wedge of lung tissue), segmentectomy (removal of a defined anatomical segment), lobectomy (removal of an entire lobe), or — rarely — pneumonectomy (removal of the entire lung). Lobectomy is the standard for most tumors when the patient’s lung function permits. After surgery, adjuvant chemotherapy is recommended for most patients with stage II disease. For patients with EGFR-mutated tumors at stage IB–IIIA, adjuvant osimertinib taken for three years has been shown to reduce the risk of recurrence significantly.

For locally advanced disease (stage III), treatment typically combines chemotherapy and radiation for unresectable stage III NSCLC; durvalumab (Imfinzi), given after definitive chemoradiation, has been shown to improve survival and is now a standard approach.

For advanced or metastatic disease (stage IV), treatment is guided by biomarker results. If a targetable driver mutation is identified — EGFR, ALK, ROS1, RET, MET, BRAF, KRAS G12C, HER2, or NTRK — the appropriate targeted therapy is typically the first-line treatment. If no targetable mutation is present, treatment decisions are guided by PD-L1 expression and may include pembrolizumab alone (TPS ≥50%), pembrolizumab combined with chemotherapy, or other checkpoint inhibitor-based regimens.

Follow-up after treatment includes regular chest CT imaging and physical examinations. Your care team will determine the frequency and duration of follow-up based on your stage and treatment received.

Questions to ask your doctor

• What is the histologic grade of my adenosquamous carcinoma, and what does it mean for my prognosis?
• What proportion of my tumor is adenocarcinoma, and what proportion is squamous cell carcinoma?
• What stage is my cancer, and what does that mean for my treatment options?
• Was STAS (spread through air spaces) found, and does it affect the type of surgery recommended?
• Was pleural invasion or lymphovascular invasion identified in my pathology report?
• Were the surgical margins clear? If not, what are the next steps?
• Did the cancer spread to any lymph nodes, and if so, how many and in which locations?
• What were the results of molecular biomarker testing — particularly for EGFR, ALK, ROS1, and KRAS?
• What was my PD-L1 score, and does it affect my eligibility for immunotherapy?
• Is adjuvant therapy recommended after surgery, and if so, which type?
• If I received treatment before surgery, what did the treatment effect assessment show?
• Are there clinical trials I might be eligible for?
• What is my follow-up schedule, and what symptoms should prompt me to contact you sooner?