Aberrant TTF-1 Expression in Peripheral T-Cell Lymphomas: A Diagnostic Pitfall

Area of Science:

• Immunohistochemistry
• Diagnostic Pathology
• Oncology

Background:

• Thyroid transcription factor-1 (TTF-1) is a key marker for thyroid and lung cancers.
• Aberrant TTF-1 expression can occur in other cancers, including colorectal cancer, especially with clone SPT24.
• Previous reports noted TTF-1 positivity in some diffuse large B-cell lymphomas (DLBCL), but its expression in peripheral T-cell lymphoma (PTCL) was unexamined.

Purpose of the Study:

• To investigate the expression of TTF-1 in peripheral T-cell lymphoma (PTCL) and diffuse large B-cell lymphoma (DLBCL).
• To evaluate the utility of different TTF-1 antibody clones in lymphoma diagnostics.

Main Methods:

• Immunohistochemistry was employed to assess TTF-1 expression.
• Two commercially available TTF-1 antibody clones (SPT24 and 8G7G3/1) were used.
• A series of PTCL and DLBCL cases were analyzed.

Main Results:

• TTF-1 expression was detected in 16% of PTCL cases using clone SPT24 (7/43) and 5% using clone 8G7G3/1 (2/43).
• Specifically, 33% of adult T-cell leukemia/lymphomas (ATLLs) and 25% of angioimmunoblastic T-cell lymphomas (AITLs) showed positivity with SPT24.
• All investigated DLBCL cases were negative for TTF-1 expression.

Conclusions:

• TTF-1, while generally specific for thyroid and lung cancers, can be expressed in certain lymphomas, notably PTCL.
• The use of TTF-1 clone SPT24 may lead to false positives in PTCL.
• Pathologists must consider this potential diagnostic pitfall when evaluating tumors of unknown origin using TTF-1.