Metaplastic Carcinoma of the Breast: Understanding Your Pathology Report

By Jason Wasserman MD PhD FRCPC
July 2, 2026

Metaplastic carcinoma is a rare type of breast cancer that makes up less than 1% of all invasive breast cancers. It develops when breast cancer cells change their appearance and begin to resemble other cell types, such as flat squamous cells, elongated spindle cells resembling connective tissue, or even cartilage- or bone-like cells. Because of this variety, pathologists describe metaplastic carcinoma as a heterogeneous (mixed) group of tumors.

Metaplastic carcinoma can develop in any part of the breast and can affect people of any age, although it is most often found in postmenopausal women. It tends to be larger at the time of diagnosis and behaves differently from the more common invasive breast carcinoma of no special type (NST). Most metaplastic carcinomas are triple-negative, meaning the tumor cells do not express estrogen receptors, progesterone receptors, or HER2 (as explained in the biomarker section below). 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 metaplastic carcinoma?

The exact cause of metaplastic carcinoma is not fully known. Like other breast cancers, it develops after genetic changes occur in breast cells that allow them to grow in an uncontrolled way. The genes most often altered in metaplastic carcinoma include TP53 and PIK3CA, along with changes in the PI3K/AKT pathway and in genes that control cell growth and repair (such as PTEN and RB1). Research suggests that many of these tumors arise when a more typical breast carcinoma dedifferentiates, meaning it changes into a less specialized form and begins to grow in unusual ways. These genetic changes occur within the tumor and are not inherited.

What are the symptoms of metaplastic carcinoma?

Most patients notice a firm, painless lump in one breast. On imaging such as mammography or ultrasound, metaplastic carcinoma usually appears as a well-defined solid mass. Unlike some other types of breast cancer, calcifications (tiny calcium deposits) are uncommon.

How is the diagnosis made?

The diagnosis of metaplastic carcinoma is usually made after a biopsy, when a small piece of the tumor is removed and examined under the microscope by a pathologist. Because these tumors often contain a mixture of cell types, careful sampling is important. The pathologist may see squamous, spindle, or cartilage-like areas, sometimes mixed with more typical carcinoma cells.

Because the spindle and cartilage-like areas can closely resemble a sarcoma (a cancer of connective tissue), the pathologist usually performs immunohistochemistry (IHC) to confirm that the tumor is a carcinoma (a cancer of epithelial cells). Metaplastic carcinomas typically express proteins such as p63, high-molecular-weight cytokeratins (CK5/6 and CK14), and EGFR, which help prove the diagnosis even when the cells look very unusual. After the diagnosis is made, imaging of the breast is used to measure the size and extent of the tumor and to plan treatment.

Histologic subtypes of metaplastic carcinoma

Under the microscope, metaplastic carcinoma can show several histologic subtypes, defined by the cell types present and how the tumor grows. Some tumors show only one subtype, while others contain a mixture. Pathologists often list the subtypes present and estimate their percentages, because this information can affect prognosis.

Squamous cell carcinoma — Sheets or nests of flat, sharp-bordered squamous cells that may form round deposits of keratin protein called keratin pearls.
Spindle cell carcinoma — Elongated spindle-shaped cells growing in interlacing bundles or pinwheel-like (storiform) patterns. This pattern can mimic a soft tissue sarcoma, which is why confirmatory tests are used.
Matrix-producing carcinoma — Areas that resemble cartilage (smooth and glassy) or bone (hard and mineralized), usually mixed with more typical carcinoma or spindle cells.
Adenosquamous carcinoma — A mixture of gland-forming cells and squamous cells. A distinct low-grade version, low-grade adenosquamous carcinoma, has a better outlook than other subtypes.
Fibromatosis-like carcinoma — Almost entirely bland spindle cells that resemble fibromatosis, a benign fibrous tumor. This subtype tends to have a more favorable outlook.
Metaplastic carcinoma with heterologous mesenchymal differentiation — Tumor areas that look like tissues not normally found in the breast, such as cartilage, bone, or muscle. Careful examination usually reveals an underlying carcinoma component as well.
Mixed carcinoma — More than one of the patterns above within the same tumor.

The pathologist may also note features such as very large, irregular nuclei, frequent mitotic figures (dividing cells), and areas of necrosis (dead tumor cells).

Histologic grade

Breast cancers are given a histologic grade using the Nottingham grading system, which scores how closely the cancer cells resemble normal breast tissue and how quickly they are growing. Most metaplastic carcinomas are high grade (grade 3), reflecting their abnormal appearance and higher growth rate. Two subtypes are important exceptions: low-grade adenosquamous carcinoma and fibromatosis-like carcinoma are low grade and tend to grow slowly. Your report will state the grade, and for metaplastic carcinoma the subtype often carries as much information about likely behavior as the grade itself.

Tumor size

The size of a metaplastic carcinoma is used to determine the pathologic tumor stage (pT, described in the staging section below), and larger tumors are more likely to metastasize (spread) to lymph nodes and other parts of the body. The final size can only be measured after the entire tumor has been removed at surgery, so it does not appear in a biopsy report.

Tumor extension

Metaplastic carcinoma starts inside the breast, but the tumor can grow into the overlying skin or the muscles of the chest wall. This is called tumor extension. Its presence is associated with a higher risk of local recurrence and of spread to distant sites, and it raises the pathologic tumor stage to pT4.

Lymphovascular invasion

Lymphovascular invasion (LVI) means cancer cells have entered small blood vessels or lymphatic channels near the tumor. These vessels can serve as pathways for cancer cells to travel to nearby lymph nodes or other parts of the body. The pathologist reports lymphovascular invasion as “present” (or “positive”) or “absent” (or “negative”). When present, it raises the chance that the cancer could spread or return, and the team may discuss additional treatment such as chemotherapy or radiation therapy.

Margins

A margin is the edge of the tissue removed during surgery. The pathologist examines the margins to determine whether the entire tumor was removed. Margins are assessed only after surgery that removes the whole tumor, not after a biopsy.

Negative margin — No cancer cells at the cut edge. The report may also state how close the nearest cancer cells came to the edge; a wider clear margin lowers the risk of local recurrence.
Positive margin — Cancer cells present at the cut edge, meaning some cancer may remain. Additional surgery or radiation may be considered.

Lymph nodes

Lymph nodes are small immune organs that filter fluid and can trap cancer cells. When breast cancer spreads, it often travels first to the lymph nodes under the arm (the axillary lymph nodes). During surgery, some of these nodes may be removed and examined. The report includes the number of nodes examined, the number that contain cancer, and the size of the largest deposit. It may also mention extranodal extension, meaning cancer has broken through the outer capsule of a node into the surrounding tissue.

Isolated tumor cells — Clusters no larger than 0.2 mm. These are not counted as positive for staging and have little effect on treatment.
Micrometastasis — A deposit larger than 0.2 mm but not larger than 2 mm, reported as pN1mi.
Macrometastasis — A deposit larger than 2 mm, associated with a higher risk of spread and often leading to more intensive treatment. Compared with common breast cancers, metaplastic carcinoma spreads to lymph nodes less often, but it can travel directly through the bloodstream to distant organs.

Biomarker and molecular testing

Biomarker testing in metaplastic carcinoma differs from most other breast cancers because these tumors are usually triple-negative. The results still guide treatment, particularly in advanced disease.

Estrogen receptor, progesterone receptor, and HER2

Every breast cancer is tested for the estrogen receptor (ER), the progesterone receptor (PR), and HER2, because these results usually determine which treatments are likely to work. Metaplastic carcinoma is characteristically negative for all three, a pattern called triple-negative. This means hormone-blocking therapy and HER2-targeted therapy are generally not effective, and chemotherapy is the main systemic treatment.

PD-L1

PD-L1 is a protein that some cancers use to hide from the immune system. In triple-negative breast cancer, PD-L1 testing by immunohistochemistry (reported as a Combined Positive Score, generally 10 or higher) helps determine eligibility for the immunotherapy drug pembrolizumab in advanced or metastatic disease. You can read more in our overview of PD-L1 testing in cancer.

PIK3CA, PTEN, and other molecular changes

Metaplastic carcinomas frequently harbor alterations in the PI3K/AKT growth pathway, including PIK3CA mutations and loss of PTEN, as well as TP53 mutations. These are usually identified by next-generation sequencing. At present, drugs targeting the PI3K/AKT pathway are approved mainly for hormone receptor-positive breast cancer, so for triple-negative metaplastic carcinoma these findings are used primarily to identify eligibility for clinical trials of targeted therapies. Your oncologist will discuss whether molecular profiling is appropriate in your situation.

Tumor-agnostic markers

Rarely, a metaplastic carcinoma carries a marker that qualifies for a treatment approved across cancer types regardless of where the cancer started, such as mismatch repair deficiency or high microsatellite instability (pembrolizumab), a high tumor mutational burden, or an NTRK gene fusion. These are checked during comprehensive molecular profiling.

For more information, visit our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

Metaplastic carcinoma is staged using the TNM system of the American Joint Committee on Cancer (AJCC), 8th edition, based on the tumor (T), lymph nodes (N), and distant metastasis (M). The pathologist determines the pT and pN stages from the removed tissue; the M stage is determined by imaging.

Tumor stage (pT)

pT1 — Tumor 2 cm (20 mm) or smaller. Subdivided into pT1mi (1 mm or smaller), pT1a (more than 1 mm up to 5 mm), pT1b (more than 5 mm up to 10 mm), and pT1c (more than 10 mm up to 20 mm).
pT2 — Tumor larger than 2 cm but not larger than 5 cm.
pT3 — Tumor larger than 5 cm.
pT4 — Tumor of any size that has grown into the chest wall or skin. pT4a is growth into the chest wall; pT4b is growth into the skin causing ulcers or swelling; pT4c is both; pT4d is inflammatory breast cancer.

Nodal stage (pN)

pN0 — No cancer in the lymph nodes. Isolated tumor cells only are recorded as pN0(i+).
pN1 — Cancer in 1 to 3 axillary lymph nodes, or micrometastases only (pN1mi), or spread to internal mammary sentinel nodes.
pN2 — Cancer in 4 to 9 axillary lymph nodes, or in internal mammary nodes without axillary involvement.
pN3 — Cancer in 10 or more axillary lymph nodes, in nodes below or above the collarbone, or in a combination of internal mammary and axillary nodes.

What is the prognosis for metaplastic carcinoma?

Compared with more common triple-negative breast cancers, metaplastic carcinomas generally have a less favorable prognosis and tend to respond less well to standard chemotherapy. The overall five-year survival rate is approximately 60%, although this varies considerably by subtype and stage. Spread to lymph nodes is less common than in other breast cancers, but the cancer can travel directly through the bloodstream to distant organs, especially the lungs and brain. Radiation therapy after surgery has been shown to improve survival. The histologic subtype gives additional information about likely behavior:

More favorable subtypes — Low-grade adenosquamous carcinoma and fibromatosis-like carcinoma tend to grow slowly and have a better outlook.
Intermediate subtype — Matrix-producing carcinoma generally has an intermediate outcome.
Less favorable subtypes — Spindle cell carcinoma, squamous carcinoma, and high-grade adenosquamous carcinoma tend to grow and spread more quickly.
Mixed carcinoma — Tumors with several different patterns have been linked to a higher chance of spread.

What happens after this diagnosis?

After a diagnosis of metaplastic carcinoma, care is usually coordinated by a team that may include a breast surgeon, a medical oncologist, a radiation oncologist, and a pathologist. The pathology findings guide which options the team considers, rather than dictating a single path. Surgery removes the tumor, and because these tumors are often large, a mastectomy may be needed, although breast-conserving surgery is an option for smaller tumors. Radiation therapy after surgery is frequently considered because it improves survival. Chemotherapy is commonly used, sometimes before surgery, although metaplastic carcinoma tends to respond less well to chemotherapy than other breast cancers. Immunotherapy may be considered for advanced triple-negative disease based on PD-L1 testing, and molecular profiling may identify eligibility for targeted therapy clinical trials. If treatment is given before surgery, the pathologist reports the extent of residual cancer using the residual cancer burden (RCB) index. Because metaplastic carcinoma can spread to the lungs and brain, follow-up imaging pays particular attention to these sites.

Questions to ask your doctor

What subtype (or subtypes) of metaplastic carcinoma do I have, and what percentage of each is present?
What is the grade of my tumor?
What is the size and pathologic stage (pT and pN) of my cancer?
Is my cancer triple-negative?
Was the tumor completely removed, with negative margins?
Was lymphovascular invasion present?
Did the cancer spread to any lymph nodes?
Was PD-L1 testing performed, and am I a candidate for immunotherapy?
Was molecular (NGS) testing done, and did it identify changes such as PIK3CA, PTEN, or TP53 that could make me eligible for a clinical trial?
Which treatments do my pathology findings make appropriate: surgery, radiation, chemotherapy, or immunotherapy?
Are there clinical trials that might be appropriate for me?
What follow-up and imaging schedule will I need to watch for recurrence, including in the lungs and brain?