Q. How is it that a cytopathologist can diagnose invasive squamous cell carcinoma on a Pap smear? This concept does not make sense to me. Cells can be severely abnormal, but I thought that all you could say is they are severely dysplastic. I thought you would need confirmation of invasion through the basement membrane histologically to call it invasive SCC.

A. That’s a great question. You are right that invasive carcinoma breaks through the basement membrane – that’s the thing that defines it as invasive (as opposed to in situ). And you certainly can diagnose that on a histologic section – you look for the basement membrane, and see if the tumor has breached it.

While it is true that you can’t usually see much architecture on Pap smears, you can see other signs that accompany tumor cell invasion. The most reliable of these is something called a tumor diathesis. This refers to the necrotic, inflammatory material that can accompany an ulcerating, invasive tumor. That material is visible on histologic section too – but you’d probably pass right by it in your quest for invasive cells. On a Pap smear, a tumor diathesis is obvious (in fact, it’s often so obvious that it may obscure carcinoma cells). Furthermore, you don’t see a tumor diathesis in non-invasive carcinomas.

The material we refer to as a tumor diathesis is composed of necrotic debris (pinkish granular material), fibrin (small pinkish-orange threads), inflammatory cells, and sometimes old blood (smooth, even, orange-pink material). Check out the photo above, from the Bethesda System website. On the left are squamous cell carcinoma cells with scant cytoplasm and weird nuclei with irregular, coarse chromatin. On the right is the accompanying tumor diathesis, in this case composed of lysed blood, granular debris, inflammatory cells and a single stripped nucleus.

One caveat: a tumor diathesis is not always present in invasive tumors, especially those that have a more exophytic (rather than ulcerative) growth pattern or those that are very minimally invasive. So if you see a tumor diathesis, it means the neoplastic cells are invasive. But if you don’t see a tumor diathesis, the tumor still could be invasive!