Poorly Differentiated Carcinoma: Definition

Print this article

Poorly differentiated carcinoma is a carcinoma (a cancer that starts in the epithelial cells lining the surfaces of organs) whose cells look very abnormal and no longer resemble the healthy tissue they came from. The word differentiated describes how closely cancer cells still look like normal cells. When a carcinoma is poorly differentiated, the cells have lost most of the features of the normal tissue, and it can be harder to tell, just by looking at them, where in the body the cancer began.

“Poorly differentiated” describes the tumor’s grade, not a separate type of cancer or a stage. Grade is one piece of information on a pathology report, and it is considered together with the cancer type, its location, its stage, and other findings. This article explains what poorly differentiated means, how pathologists determine it, and why it matters.

What does poorly differentiated mean?

Grade describes how much cancer cells still look and behave like the normal cells they came from. Pathologists usually divide carcinomas into three grades:

Well differentiated — The cancer cells still look much like normal cells and keep many of the original tissue’s structures. These cancers tend to grow more slowly.
Moderately differentiated — The cells fall in between, with some normal features preserved and some lost.
Poorly differentiated — The cells look very abnormal and keep few of the features of the normal tissue. These cancers tend to grow and spread more quickly.

A related term, undifferentiated carcinoma, is sometimes used for tumors whose cells have lost so many features that they show almost no resemblance to any normal tissue. Grade helps predict how a cancer is likely to behave and is one factor doctors use when planning treatment.

Where does poorly differentiated carcinoma start?

Poorly differentiated carcinoma can arise in many parts of the body. It begins in epithelial cells, which line organs and surfaces such as the skin, the digestive tract, and the lungs. Because the cells no longer resemble the tissue they came from, their appearance alone may not make it clear where the tumor started. When the origin is uncertain, pathologists use additional tests, described below, to help identify it.

How is poorly differentiated carcinoma identified?

A pathologist identifies poorly differentiated carcinoma by examining tumor tissue under a microscope. The tissue is usually obtained during a biopsy or surgery. Under the microscope, poorly differentiated carcinoma looks disorganized: the cells are irregular in size and shape, have large, irregular nuclei (the part of the cell that holds its DNA), and no longer form the orderly structures seen in normal tissue. This loss of normal organization leads the pathologist to grade the carcinoma as poorly differentiated.

Because poorly differentiated cells give few clues about their origin, pathologists often use a test called immunohistochemistry (IHC), which uses antibodies to detect specific proteins in the tumor cells. The proteins that are present help confirm that the tumor is a carcinoma and can point to where it began:

Cytokeratins — Proteins made by epithelial cells. Detecting them confirms that the tumor is a carcinoma. Broad-range markers such as AE1/AE3 are positive in many carcinomas.
Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) — The pattern of these two markers helps narrow down the likely origin. For example, tumors from the lung, breast, and upper digestive tract are often CK7 positive, while tumors from the colon and rectum are often CK20 positive.
Other markers — Depending on the results, the pathologist may add further organ-specific stains to pinpoint the source.

After confirming the diagnosis, imaging tests such as CT, MRI, or ultrasound are used to determine the tumor size and whether it has spread.

Why does the grade matter?

Grade is one of several factors doctors use to understand a cancer and plan treatment. In general, poorly differentiated carcinomas tend to grow and spread more quickly than well differentiated ones, so grade contributes to the overall picture of how a cancer is likely to behave. However, it is only part of that picture. The prognosis (expected outcome) also depends on the type of cancer, its stage (its size and how far it has spread), whether it has reached the lymph nodes or other organs, and how it responds to treatment. Two cancers with the same grade can behave differently depending on these other factors, and treatments such as surgery, chemotherapy, radiation, and other therapies can be effective. A poorly differentiated grade alone does not determine the outcome.

Is poorly differentiated carcinoma the same as the stage?

No. Grade and stage are different. Grade describes how abnormal the cancer cells look under the microscope. Stage describes how large the cancer is and how far it has spread. A cancer can be poorly differentiated but still be found at an early stage, and the two are reported separately. Both are used together, along with other findings, to plan treatment.

Questions to ask your doctor

What type of carcinoma do I have, and where did it start?
If the origin was uncertain, what tests were used to help identify it?
What grade is my cancer, and what does that mean in my case?
What is the stage of my cancer?
How do the grade and stage together affect my treatment options?
Were any special stains or other tests used to confirm the diagnosis?
What are the next steps in planning my treatment?