Your pathology report for metaplastic carcinoma of the breast

By Jason Wasserman MD PhD FRCPC
September 10, 2025

Metaplastic carcinoma is a rare and aggressive type of breast cancer. It develops when cancer cells from the breast change their appearance and begin to resemble other types of cells. For example, the tumour may contain:

  • Squamous cells (flat cells normally found on the surface of the skin and lining surfaces of the body).

  • Spindle-shaped cells that resemble connective tissue.

  • Cartilage-like (chondroid) or bone-like (osseous) cells.

Because of this variety, pathologists describe metaplastic carcinoma as a heterogeneous group of tumours.

Metaplastic carcinoma accounts for less than 1% of all invasive breast cancers.

Where in the breast does it occur?

Metaplastic carcinoma can develop in any part of the breast. At the time of diagnosis, it is often larger than more common types of breast cancer and may already be at a more advanced stage.

What are the symptoms?

Most patients notice a firm, painless lump in one of their breasts. On imaging studies such as mammography or ultrasound, the tumour usually appears as a well-defined solid mass. Unlike some other types of breast cancer, calcifications are uncommon.

Who gets metaplastic carcinoma?

Metaplastic carcinoma can affect people of any age but is most often found in postmenopausal women. It behaves differently from the more common invasive breast carcinoma of no special type (NST). It is usually a form of triple-negative breast cancer, meaning the tumour does not express estrogen receptors (ER), progesterone receptors (PR), or HER2 (ERBB2).

What causes metaplastic carcinoma?

The exact cause is not fully known. Like other breast cancers, it develops after genetic changes occur in breast cells that allow them to grow uncontrollably. Genes often altered in metaplastic carcinoma include TP53 and PIK3CA, as well as changes in pathways that regulate cell growth and repair.

Research suggests that these tumours may arise when a typical breast carcinoma “dedifferentiates” (changes into a less specialized form) and begins to grow in unusual ways.

How is the diagnosis made?

The diagnosis is usually made after a biopsy, when a small piece of the tumour is removed and examined under the microscope by a pathologist.

Because these tumours often contain a mixture of cell types, careful sampling is essential. The pathologist may see squamous, spindle, or cartilage-like areas, sometimes mixed with more typical carcinoma cells.

Special tests, such as immunohistochemistry, are often performed to confirm that the tumour is a type of breast carcinoma, even when the cells appear very unusual.

Breast biopsy

Histologic subtypes of metaplastic carcinoma

Under the microscope, metaplastic carcinoma can show several different histologic subtypes. These subtypes are defined by the type of cells present and the manner in which the tumour grows. Some tumours show only one subtype, while others contain a mixture. Pathologists often list the different components and estimate their percentages in the pathology report, as this information can be important for prognosis.

  • Squamous cell carcinoma is made up of sheets or nests of cells that look like squamous cells. These cells are flat, with sharp borders, and may produce structures called keratin pearls, which are round deposits of keratin protein.

  • Spindle cell carcinoma is made up of elongated spindle-shaped cells. These cells may grow in interlacing bundles or in patterns that resemble cartwheels (storiform). The nuclei of the cells often vary in size and shape, and in higher-grade tumours, they can appear very abnormal. This pattern can mimic a soft tissue sarcoma, which is why special tests are used to prove the diagnosis.

  • Matrix-producing carcinoma contains areas that resemble cartilage (chondroid tissue) or bone (osseous tissue). These areas are usually mixed with more typical carcinoma or spindle cells. The cartilage-like regions appear smooth and glassy, while the bone-like regions look hard and mineralized.

  • Adenosquamous carcinoma shows a mixture of gland-forming cells (adenocarcinoma) and squamous cells. A special, low-grade version called low-grade adenosquamous carcinoma features small, well-formed glandular structures intermixed with nests of squamous cells. This subtype usually has a better prognosis than other forms of metaplastic carcinoma.

  • Fibromatosis-like carcinoma is made up almost entirely of bland spindle cells that resemble fibromatosis, a benign fibrous tumour. The cells are usually arranged in long, sweeping fascicles and can infiltrate into the surrounding breast tissue. Compared to high-grade spindle cell carcinoma, the cells look less aggressive, and the prognosis is generally more favourable.

  • Metaplastic carcinoma with heterologous mesenchymal differentiation contains tumour areas that look like tissues not typically found in the breast. These can include cartilage, bone, or even muscle-like tissue. In some cases, these areas look very similar to true sarcomas, but careful examination usually reveals an underlying carcinoma component as well.

  • Mixed carcinoma shows more than one of the patterns described above. For example, a tumour may contain both spindle cell and squamous areas, or a combination of matrix-producing and adenosquamous areas.

In addition to these patterns, pathologists may see features that suggest aggressive behaviour. These include cells with very large, irregular nuclei, high numbers of mitotic figures (dividing cells), and areas of necrosis (dead tumour cells). Due to this wide variation in microscopic appearance, pathologists often describe all the different subtypes present in the final report.

What other tests may be performed?

Pathologists often perform additional tests to understand the tumour better:

  • Immunohistochemistry: Metaplastic carcinomas are usually negative for ER, PR, and HER2 (triple-negative). They often express proteins such as p63, EGFR (HER1), and high-molecular-weight cytokeratins (CK5/6, CK14), which help confirm the diagnosis.

  • Molecular tests: Genetic studies reveal frequent mutations in TP53 and PIK3CA, as well as the loss of PTEN or RB1. These results are mainly of research interest but may become necessary for targeted treatments in the future.

Breast cancer biomarkers

Estrogen receptor (ER) and progesterone receptor (PR)

Hormone receptors are proteins found in some breast cancer cells. The two main types tested are estrogen receptor (ER) and progesterone receptor (PR). Cancer cells with these receptors utilize hormones such as estrogen and progesterone to promote growth and division. Testing for ER and PR helps guide treatment and predict prognosis.

Cancer cells are described as hormone receptor-positive if ER or PR is present in at least 1% of cells. These cancers often grow more slowly, are less aggressive, and typically respond well to hormone-blocking therapies, such as tamoxifen or aromatase inhibitors (e.g., anastrozole, letrozole, or exemestane). Hormone therapy helps reduce the chance of cancer recurrence.

Your pathology report will typically include:

  • Percentage of positive cells: For example, “80% ER-positive” means 80% of cancer cells have estrogen receptors.

  • Intensity of staining: Reported as weak, moderate, or strong, this indicates the number of receptors present in the cancer cells.

  • Overall score (Allred or H-score): This combines percentage and intensity, with higher scores indicating a better response to hormone therapy.

Tumours with ER positivity between 1% and 10% are considered ER low positive. These cancers still usually respond better to hormone therapy compared to ER-negative cancers.

Understanding ER and PR status helps your doctors plan effective treatment tailored to your cancer.

HER2

HER2 (human epidermal growth factor receptor 2) is a protein found on specific breast cancer cells that facilitates their growth and division. Breast cancers with extra HER2 proteins due to a change (amplification) in the HER2 gene are called HER2-positive.

HER2-positive cancers tend to be more aggressive and were once associated with a poorer prognosis. However, effective targeted therapies now significantly improve outcomes for patients with HER2-positive cancers. Knowing the HER2 status helps your doctors choose treatments specifically designed for your type of cancer, often including targeted drugs along with chemotherapy.

Two tests are commonly performed to measure HER2 in breast cancer cells: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).

Immunohistochemistry (IHC) for HER2

Immunohistochemistry (IHC) is a test pathologists use to measure the amount of HER2 protein on the surface of breast cancer cells. To perform this test, pathologists use a small tissue sample from the tumour. They apply special antibodies to the tissue, which bind to HER2 proteins if they are present. These antibodies are then made visible under a microscope by adding a colored dye. By examining the intensity (strength) and amount of colour present, the pathologist determines how much HER2 protein is on the cancer cells.

Your pathology report will describe the results of HER2 IHC testing as a score ranging from 0 to 3+:

  • 0 (negative): No visible staining, meaning no significant HER2 protein is detected. This indicates a HER2-negative tumour, and targeted HER2 treatments will not typically be helpful.

  • 1+ (negative): Weak and incomplete staining. These tumours are still considered HER2-negative and usually don’t benefit from HER2-targeted treatments.

  • 2+ (borderline or equivocal): Moderate staining, meaning the result is unclear. Additional testing, typically a FISH test, is required to determine whether the cancer is HER2-positive or HER2-negative.

  • 3+ (positive): Strong and complete staining on the surface of the cancer cells. This indicates a HER2-positive breast cancer. HER2-positive cancers often grow faster but respond very well to HER2-targeted therapies like trastuzumab.

Fluorescence in situ hybridization (FISH) for HER2

Fluorescence in situ hybridization (FISH) is a test used to examine cancer cells for extra copies of specific genes, such as HER2. In breast cancer testing, FISH is usually performed after the initial HER2 IHC test gives unclear or borderline results.

To perform a FISH test, pathologists use a small tissue sample from the tumour. They add special fluorescent probes to the tissue, which attach specifically to the HER2 genes inside the cancer cells. Under a microscope, these probes glow brightly, enabling pathologists to count the number of copies of the HER2 gene present in each cell.

Your pathology report will typically describe the results of the FISH test as either:

  • Positive (Amplified): The cancer cells have extra copies of the HER2 gene. This is known as HER2-positive breast cancer. These cancers often grow more aggressively but typically respond well to targeted HER2 treatments, such as trastuzumab (Herceptin).

  • Negative (Non-amplified): The cancer cells have a normal number of HER2 gene copies. This is called HER2-negative breast cancer, meaning targeted HER2 therapies are usually not helpful.

Sometimes the report may describe the exact number of gene copies per cell (for example, an average HER2 copy number or a HER2-to-chromosome ratio). These detailed numbers help pathologists and oncologists confirm the HER2 status accurately, guiding the choice of the most effective treatment for your specific cancer type.

Tumour size

​The size of a breast tumour is important because it is used to determine the pathologic tumour stage (pT) and because larger tumours are more likely to metastasize (spread) to lymph nodes and other parts of the body. The tumour size can only be determined after the entire tumour has been removed. For this reason, it will not be included in your pathology report after a biopsy.

Tumour extension

Metaplastic carcinoma starts inside the breast, but the tumour may spread into the overlying skin or the muscles of the chest wall. The term tumour extension is used when tumour cells are found in the skin or muscles below the breast. Tumour extension is important because it is associated with a higher risk that the tumour will recur after treatment (local recurrence) or that cancer cells will metastasize to a distant body site, such as the lungs. It is also used to determine the pathologic tumour stage (pT).

Lymphovascular invasion

Lymphovascular invasion (LVI) means cancer cells have entered small blood vessels or lymphatic channels near the tumour. These vessels act like highways that cancer cells can use to spread to other parts of the body, including nearby lymph nodes.

Pathologists look for lymphovascular invasion by examining tissue under the microscope. If they see cancer cells inside a vessel, the report will say “present” or “positive.” If no cancer cells are found in the vessels, the report will say “absent” or “negative.”

The presence of lymphovascular invasion increases the chance that the cancer could spread or come back. For this reason, your doctor may recommend additional treatment such as chemotherapy or radiation therapy.

Lymphovascular invasion

Margins

A margin is the edge of tissue removed during surgery. Pathologists examine the margins under the microscope to see if any cancer cells are present at the cut edge. This helps determine whether the entire tumour was removed.

Margins are usually only assessed after surgery that removes the whole tumour, not after a biopsy. Your report will say the margin is “negative” if no cancer cells are at the edge and “positive” if cancer cells are present at the edge. If all margins are negative, the report may also include how close the tumour came to the edge.

Margins are important because a positive margin means some cancer may still be in the body. If this happens, your doctor may recommend more treatment, such as another surgery or radiation. A negative margin, especially with a wider distance from the tumour, lowers the risk that the cancer will come back.

Margin

Lymph nodes

Lymph nodes are small immune organs that filter fluid in the body and help fight infections. When breast cancer spreads, it often travels first to nearby lymph nodes, especially those under the arm (called axillary lymph nodes).

Lymph node

During surgery, some lymph nodes are removed and examined under a microscope. The pathology report includes the number of lymph nodes tested, how many contain cancer, and the size of the cancer deposits. Sometimes, the report also mentions extranodal extension, which means the cancer has spread beyond the lymph node.

There are different types of lymph node involvement:

  • Isolated tumour cells (ITCs) are tiny clusters no larger than 0.2 millimeters. These are usually not counted as positive for staging and have little impact on treatment decisions.

  • Micrometastasis refers to cancer clusters between 0.2 and 2 millimeters. This may increase the risk of recurrence slightly and could influence treatment decisions. The report may label this as “pN1mi.”

  • Macrometastasis refers to larger clusters over 2 millimeters. This indicates a higher risk of spread and usually leads to more intensive treatment, such as chemotherapy or radiation.

Lymph node results help determine the cancer stage and guide decisions about further treatment.

Lymph node metastasis

Residual cancer burden index

The residual cancer burden (RCB) index measures the amount of cancer remaining in the breast and nearby lymph nodes after neoadjuvant therapy (treatment given before surgery). The index combines several pathologic features into a single score and classifies the cancer’s response to treatment. Doctors at the University of Texas MD Anderson Cancer Center developed the RCB (http://www.mdanderson.org/breastcancer_RCB).

Here’s how the score is calculated:

  1. Size of the tumour bed in the breast: Pathologists measure the largest two dimensions of the area where the tumour was located, called the tumour bed. This area may contain a mix of normal tissue, cancer cells, and scar tissue from the therapy.
  2. Cancer cellularity: Cancer cellularity estimates the percentage of the tumour bed that still contains cancer cells. This includes both invasive cancer (cancer that has spread into surrounding tissue) and in situ cancer (cancer cells that have not spread).
  3. Percentage of in situ disease: Within the tumour bed, pathologists also estimate the percentage of cancer that is in situ, meaning that the cancer cells are confined to the milk ducts or lobules and have not spread into the surrounding tissue.
  4. Lymph node involvement: The number of lymph nodes containing cancer cells (positive lymph nodes) is counted, and the size of the largest cluster of cancer cells in the lymph nodes is also measured.

These features are combined using a standardized formula to calculate the RCB score.

Based on the RCB score, patients are divided into four categories:

  • RCB-0 (pathologic complete response): No residual invasive cancer is detected in the breast or lymph nodes.
  • RCB-I (minimal burden): Very little residual cancer is present.
  • RCB-II (moderate burden): A moderate amount of cancer remains.
  • RCB-III (extensive burden): A large amount of cancer remains in the breast or lymph nodes.

The RCB classification helps predict a patient’s likelihood of staying cancer-free after treatment. Patients with an RCB-0 classification typically have the best outcomes, with the highest chances of long-term survival without recurrence. As the RCB category increases from RCB-I to RCB-III, the risk of cancer recurrence increases, which may prompt additional treatments to reduce this risk.

How is metaplastic carcinoma staged?

The pathologic staging system for metaplastic carcinoma of the breast helps doctors understand how far the cancer has spread and plan the best treatment. The system mainly uses the TNM staging, which stands for Tumor, Nodes, and Metastasis. Early-stage cancers (like T1 or N0) might only require surgery and possibly radiation, while more advanced stages (like T3 or N3) may need a combination of surgery, radiation, chemotherapy, and targeted therapies. Proper staging ensures that patients receive the most effective treatments based on the extent of their disease, which can improve survival rates and quality of life.

Tumour stage (pT)

This feature examines the size and extent of the breast tumour. The tumour is measured in centimetres, and its growth beyond the breast tissue is assessed.

T0: No evidence of primary tumour. This means no tumour can be found in the breast.

T1: The tumour is 2 centimetres or smaller in greatest dimension. This stage is further subdivided into:

  • T1mi: Tumour is 1 millimeter or smaller.
  • T1a: Tumour is larger than 1 millimeter but not larger than 5 millimeters.
  • T1b: Tumour is larger than 5 millimeters but not larger than 10 millimeters.
  • T1c: Tumour is larger than 10 millimeters but not over 20 millimeters.

T2: The tumour is larger than 2 centimetres but not larger than 5 centimetres.

T3: The tumour is larger than 5 centimetres.

T4: The tumour has spread to the chest wall or skin, regardless of its size. This stage is further subdivided into:

  • T4a: Tumour has invaded the chest wall.
  • T4b: Tumour has spread to the skin, causing ulcers or swelling.
  • T4c: Both T4a and T4b are present.
  • T4d: Inflammatory breast cancer, characterized by redness and swelling of the breast skin.

Nodal stage (pN)

This feature examines if the cancer has spread to the nearby lymph nodes, which are small, bean-shaped structures found throughout the body.

N0: No cancer is found in the nearby lymph nodes.

N0(i+): Isolated tumour cells only.

N1: Cancer has spread to 1 to 3 axillary lymph nodes (under the arm).

  • N1mi: Micrometastases only.
  • N1a: Metastases in 1-3 axillary lymph nodes, at least one metastasis larger than 2.0 mm.
  • N1b: Metastases in ipsilateral internal mammary sentinel nodes, excluding ITCs

N2: Cancer has spread to:

  • N2a: 4 to 9 axillary lymph nodes.
  • N2b: Internal mammary lymph nodes without involvement of axillary lymph nodes.

N3: Cancer has spread to:

  • N3a: 10 or more axillary lymph nodes or two infraclavicular lymph nodes (below the collarbone).
  • N3b: Internal mammary lymph nodes and axillary lymph nodes.
  • N3c: Supraclavicular lymph nodes (above the collarbone).

What is the prognosis for metaplastic carcinoma?

Compared with more common triple-negative breast cancers, metaplastic carcinomas generally have a worse prognosis and tend to respond less well to standard chemotherapy.

  • Lymph node involvement is less common than in other breast cancers, but the cancer can still spread directly to distant organs, especially the lungs and brain.

  • Survival rates are lower than for typical breast cancers of the same size and stage. The overall 5-year survival rate is approximately 60%, although it varies by subtype and stage.

  • Radiation therapy after surgery improves survival, and research is ongoing into better chemotherapy and targeted therapy options.

Prognosis by histologic subtype

Not all metaplastic carcinomas behave the same way. The histologic subtype described in your pathology report can provide important clues about the likely behaviour of the tumour.

  • Low-grade adenosquamous carcinoma and fibromatosis-like carcinoma are associated with a more indolent (slower-growing) course and a better prognosis compared to other subtypes of carcinoma.

  • Matrix-producing carcinoma generally has an intermediate outcome and may do better than spindle cell or squamous types.

  • Spindle cell carcinoma, squamous carcinoma, and high-grade adenosquamous carcinoma tend to behave more aggressively, with a higher chance of spreading and a less favourable prognosis.

  • Mixed carcinoma with several different subtypes often behaves more aggressively, and the presence of multiple patterns has been linked to a worse outcome.

Questions to ask your doctor

  • What subtype of metaplastic carcinoma do I have?

  • Is my cancer triple-negative?

  • What stage is my cancer, and has it spread to lymph nodes or other organs?

  • What treatment options do you recommend (surgery, chemotherapy, radiation)?

  • Are there clinical trials or targeted therapies available for this type of breast cancer?

  • How will we monitor for recurrence after treatment?

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