Challenging tumors, including metastatic, poorly differentiated, and undifferentiated cancer

The American Cancer Society estimates that there are 1.4 million new cancer diagnoses annually in the United States. Of these new cases, up to 10% are of tumor types not readily classifiable in the course of the initial diagnostic workup.¹

There are several reasons why a tumor's primary site of origin can be difficult to identify:

• The cancer is found in an unexpected location.
• The cancer is found in multiple locations, indicating metastatic disease.
• The tumor cells are poorly differentiated or undifferentiated, making them difficult to interpret.

Limitations of current technologies: Many diagnostic tools are available to clinicians today. These include immunohistochemistry (IHC), cytogenetic studies, electron microscopy, and imaging procedures such as computed tomography (CT), mammography, magnetic resonance imaging (MRI), and positron emission tomography (PET). However, in the case of difficult-to-classify tumors, even these advanced technologies identify the tumor origins in only about 20% to 25% of instances.²

• IHC is a type of assay in which antigens are visualized using antibodies followed by fluorescent dye or enzyme markers; pathologists use various combinations of dyes to identify the tissue of origin of a tumor. However, IHC may lack the specificity and sensitivity to address the full range of potential tumor types. ³


• Cytogenetic studies, which assess chromosomal abnormalities, can provide insights in a number of specific tumor types. However, this technique is limited because diagnostic chromosomal abnormalities have been identified in only a select number of tumor types to date. ⁴


• Imaging techniques have been valuable tools in the assessment of patients with ambiguous or hard-to-classify tumors. CT, MRI, and PET scans can all be helpful; however, while they may pinpoint the anatomic location and stage of a tumor, they cannot confirm its tissue of origin ⁵

Learn why challenging tumors present complex challenges to care providers.

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