Differential Diagnosis (DDx)

General: Arguably the most important step in the path towards a definitive diagnosis is the development of a differential diagnosis, particularly in anatomic pathology / surgical pathology. Although we are not that far removed from the days when molecular-genetic testing and immunohistochemistry were not widespread or readily available, they have made it far easier to narrow a differential diagnosis to a definitive one. Equally, however, a lot of money can be spent, time lost, and confusion generated if the initial differential diagnosis is either too broad or simply based on the wrong set of available information.

Information sets:

• Demographics: Age, race, sex, ... may all play an important role in prioritizing a potential DDx list.
• Social history: Occupation, smoking/EtOH, place of origin, place of residence, ....
• Medical history: Although obvious in many ways, it is not uncommon that rudimentary, absent, or misinterpreted/incorrect medical history is initially provided to a pathologist. Previous surgeries? Treatment (radiation, chemotherapy, other)? Known genetic abnormalities? Familial disorders?
• Imaging: Particularly critical in bone pathology, but also important in neuropathology and potentially so with other sources. This ties in with location, and may be a helpful check — did you see as many nodules as the radiologist? can you explain the apparent invasion described by the radiologist? etc.
• Location: Again obvious in many ways, but should be particularly stressed in neuropathology. Cell of origin, likelihood of malignancy, etc. in some circumstances may all be suggested by location alone.
• Pathologic history: Abundantly obvious, although unless someone else notifies the pathologist it can be difficult to know the answer; thus, many practices have a system to at least alert that there are previous cases signed out by their practice. Are there previous specimens? How were they signed out? Do the previous cases need to be (re)viewed? Although the new diagnosis does not have to match the old, there needs to be a good explanation if they don't.