Undifferentiated: Definition

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Undifferentiated describes tumor cells that no longer resemble any normal cell type. A pathologist cannot tell from their appearance which tissue they came from. Undifferentiated tumors are malignant, which means they are cancers. Pathologists consider them high grade.

Undifferentiated describes the tumor cells, not a diagnosis on its own. It is part of a cancer’s grade. This article explains what undifferentiated means, how pathologists find where the tumor started, and what the term means for you.

What does undifferentiated mean?

Differentiation is the process that turns young cells into mature cells with a specific job. Pathologists use the word to describe how much a tumor still resembles normal tissue. A well-differentiated tumor looks much like normal tissue. A poorly differentiated tumor looks very different. An undifferentiated tumor shows no clear sign of the normal cell type it came from.

You may also see the word anaplastic on a report. It describes cells that look highly abnormal and have lost their normal tissue organization.

What does an undifferentiated tumor look like under the microscope?

The cells of an undifferentiated tumor lack the features of any normal tissue. They do not form recognizable structures, such as glands. In undifferentiated endometrial carcinoma, for example, the cells grow in sheets. They divide often. Areas of dead tissue are common.

Each tumor type looks a little different. The pathologist cannot name the tissue of origin from the cells alone, so they need additional tests.

Is an undifferentiated tumor cancer?

An undifferentiated tumor is a cancer. Pathologists consider all undifferentiated tumors high grade. Some grading systems specially handle this:

Carcinomas of the endometrium. Undifferentiated carcinoma is high grade by definition. It does not receive a grade of 1, 2, or 3.
Sarcomas. The FNCLCC system scores differentiation from 1 to 3. An undifferentiated pleomorphic sarcoma always scores 3 for differentiation.

How do pathologists find where an undifferentiated tumor started?

Pathologists find the origin of an undifferentiated tumor with immunohistochemistry. This test uses antibodies to mark proteins in the tumor cells. The pathologist interprets the results alongside the tumor site and its appearance. A small first set of stains usually divides the tumor into a broad class:

Carcinoma. A broad epithelial marker, such as a cytokeratin, points to a carcinoma. A carcinoma is a cancer of epithelial cells.
Melanoma or nerve-sheath tumor. Markers such as S100 and SOX10 point to a melanoma or a nerve-sheath tumor.
Lymphoma. Markers such as CD45 point to lymphoma, a cancer of immune cells.

The pathologist adds more stains if the first set doesn’t provide an answer. Some markers appear in more than one tumor class, so the pathologist interprets them carefully. Some tumors are negative for all of these markers. Others need molecular or additional tests to rule out look-alike tumors.

Which diagnoses include the word undifferentiated?

Several tumors carry the word in their names. A few examples are:

Undifferentiated carcinoma of the endometrium. This fast-growing cancer starts in the lining of the uterus. See undifferentiated carcinoma of the endometrium.
Undifferentiated carcinoma of the ovary. See undifferentiated carcinoma of the ovary.
Sinonasal undifferentiated carcinoma. This rare, fast-growing cancer starts in the nasal cavity and sinuses. Pathologists diagnose it only after ruling out look-alike tumors. See sinonasal undifferentiated carcinoma.
Undifferentiated pleomorphic sarcoma. This rare cancer starts in connective tissue. Its cells do not resemble any normal tissue. See undifferentiated pleomorphic sarcoma.
SMARCA4-deficient undifferentiated tumor of the lung. See SMARCA4-deficient undifferentiated tumor of the lung.

Some tumors contain both differentiated and undifferentiated parts. Pathologists call this dedifferentiation.

What might my report say about an undifferentiated tumor?

Reports use a few standard phrases. Each laboratory phrases them a little differently:

Undifferentiated carcinoma, sarcoma, or malignant neoplasm. The tumor cells show no evidence of a normal cell type. The report may name the broad class that the stains support.
Poorly differentiated to undifferentiated. The tumor cells look very abnormal, and the pathologist sees few or no normal features.
High grade. The report states the grade or notes that it is high by definition.
Stain results. The report lists stains that were positive or negative. These results explain how the pathologist reached the diagnosis.

What does undifferentiated mean for prognosis?

Undifferentiated tumors tend to grow faster than low-grade tumors. They are more likely to spread to lymph nodes and other sites. Doctors link them to a worse prognosis. However, grade is only one part of the picture. The type of tumor and its stage matter too. Stage describes the size of the tumor and how far it has spread. Your care team considers all of these findings together.

What happens after a tumor is called undifferentiated?

Next steps depend on the tumor type and its stage. Your care team may order more tests to identify the tumor or to measure its spread. Your doctor can explain the plan for your tumor type.

Questions to ask your doctor

Is my tumor undifferentiated or poorly differentiated?
Where did my tumor start?
Which stains or tests did the pathologist use to identify it?
Do I need more tests to confirm the diagnosis?
What grade is my tumor?
What stage is my cancer?
How does this finding affect my prognosis and treatment options?
Should another pathologist review my slides?