Dedifferentiation (dedifferentiated)

In pathology, dedifferentiation describes a process where mature, specialized cells change back (revert) to a less specialized, more primitive form. This is commonly seen in cancer, where tumour cells that were initially more mature and less aggressive become less mature and more aggressive. When cells become dedifferentiated, they tend to grow more rapidly and lose the normal structure and functions typical of healthy cells in their tissue of origin.

What types of tumours commonly show dedifferentiation?

Several different kinds of tumours can undergo dedifferentiation, becoming more aggressive.

Common examples include:

• Liposarcomas: A type of soft tissue tumour. A well-differentiated liposarcoma can become a more aggressive, dedifferentiated liposarcoma.

• Chondrosarcomas: These bone tumours may start as low-grade (slow-growing) chondrosarcomas and later evolve into high-grade, dedifferentiated chondrosarcomas.

• Thyroid carcinomas: Certain thyroid cancers, like papillary or follicular thyroid carcinoma, can dedifferentiate into highly aggressive cancers called anaplastic thyroid carcinoma.

• Renal cell carcinomas: Clear cell renal cell carcinomas (kidney cancers) sometimes dedifferentiate, becoming more aggressive and difficult to treat.

• Gastrointestinal stromal tumours (GISTs): These tumours can dedifferentiate, increasing the risk that the cancer will metastasize (spread) and lowering the overall prognosis (outlook).

Why is dedifferentiation important?

Dedifferentiation matters because it influences many aspects of diagnosis, treatment, and prognosis:

• Prognosis (expected outcome): Dedifferentiated tumours tend to be more aggressive and carry a higher risk of spreading to other parts of the body, typically resulting in a poorer prognosis.

• Treatment: Tumours that become dedifferentiated often respond poorly to standard treatments that worked well against their earlier, more mature forms. This can make them harder to manage and may require new or specialized therapies.

• Diagnosis: Dedifferentiation makes tumours more difficult to diagnose accurately because they no longer closely resemble their original tissue type. Pathologists often need special tests, such as immunohistochemistry or genetic tests, to identify these cancers correctly.

What is the difference between dedifferentiated and undifferentiated?

The terms dedifferentiated and undifferentiated both describe tumour cells that lack mature characteristics, but they mean slightly different things:

• Dedifferentiated: Describes tumour cells that were once mature (well-differentiated) but have reverted to a less mature state. This is a change from a previously more specialized condition to a more primitive one. For example, a well-differentiated liposarcoma becomes dedifferentiated.

• Undifferentiated: Describes tumour cells that never developed mature characteristics and don’t resemble normal cells from the tissue where they originated. These cells were always primitive and have minimal or no specialized features. They tend to be aggressive from the start. An example is undifferentiated pleomorphic sarcoma, which shows no clear features of any specific tissue type.

Questions to ask your doctor

If your pathology report or diagnosis includes the term dedifferentiation, you may want to ask your doctor:

• Has my tumour become dedifferentiated, and if so, what does this mean for my treatment and prognosis?

• Are additional tests needed to better understand the nature of my tumour?

• How does dedifferentiation affect my treatment options?

• Will I require specialized or targeted therapies due to this change?

Understanding the meaning of dedifferentiation can help you become actively involved in your healthcare decisions and better prepare for discussions with your medical team.