Dedifferentiation (dedifferentiated)

Dedifferentiation (or dedifferentiated) in pathology refers to the process where mature, specialized cells revert to a more primitive, less specialized state. This phenomenon is typically observed in cancer cells, where the tumor progresses from a differentiated, often less aggressive state to a less differentiated, more aggressive state. Dedifferentiated cells exhibit higher levels of proliferative activity and tend to lose the structural and functional characteristics typical of their tissue of origin.

Types of tumors showing dedifferentiation

Several types of tumors can undergo dedifferentiation. Some common examples include:

1. Liposarcomas: These soft tissue tumours can progress from a well differentiated liposarcoma to a more aggressive dedifferentiated liposarcoma.
2. Chondrosarcomas: Initially presenting as low grade chondrosarcomas, they can evolve into dedifferentiated chondrosarcomas, showing high grade sarcomatous components.
3. Thyroid carcinomas: Papillary or follicular thyroid carcinomas can dedifferentiate into anaplastic thyroid carcinomas, which are highly malignant.
4. Renal cell carcinomas: Clear cell renal cell carcinomas may dedifferentiate, leading to a higher grade and more aggressive tumour phenotype.
5. Gastrointestinal stromal tumours (GISTs): GISTs can dedifferentiate, leading to a higher risk of metastasis and poorer prognosis.

Why is dedifferentiation important?

Dedifferentiation is significant for several reasons:

1. Prognosis: Tumors that have undergone dedifferentiation are typically associated with a worse prognosis due to their increased aggressiveness, higher metastatic potential, and resistance to conventional therapies.
2. Treatment: Dedifferentiated tumors often exhibit resistance to treatments that are effective against their more differentiated counterparts. This necessitates the development of new therapeutic strategies and can complicate patient management.
3. Diagnosis: The process of dedifferentiation can lead to tumors that no longer resemble their tissue of origin, making accurate diagnosis more challenging. Pathologists must rely on a combination of histological, immunohistochemical, and molecular techniques to correctly identify and classify these tumors.

Dedifferentiated versus undifferentiated

Dedifferentiated and undifferentiated are terms used to describe the state of tumour cells, but they refer to distinct concepts:

• Dedifferentiated: This term is used when tumour cells that were once differentiated (having specific structural and functional characteristics) lose these features and revert to a more primitive state. Dedifferentiation implies a regression from a previously more differentiated state. For example, a well differentiated liposarcoma can dedifferentiate into a more aggressive, less differentiated form.
• Undifferentiated: The term undifferentiated describes tumour cells that lack specialized features and do not resemble the normal cells of the tissue from which they originated. These cells have minimal or no differentiation from the outset. Undifferentiated tumours are often high grade and aggressive, as they lack the structural and functional characteristics of normal cells. An example would be undifferentiated pleomorphic sarcoma, which shows no specific differentiation towards any tissue type.

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Atlas of Pathology