Microscopic description and IHC:

The Diff Quik or Romanowsky stain showed clusters of large cells with hyperchromatic enlarged nuclei and prominent nucleoli arranged in clusters. There was an apparent dual population of cells with apoptotic bodies that exhibited foci of nuclear molding.

The Papanicolaou stain showed large cells with similar cytologic features with a high nuclear to cytoplasmic ratio and nuclear atypia

The cell block was helpful in this case, as it showed primitive appearing basaloid type cells arranged in nests, with a palisading border. Immunohistochemistry performed on the cell block showed that the malignant appearing cells were positive for AE1/3, MNF116, P63, and P40. They were negative for synaptophysin, chromogranin, S-100, SOX10, CDX2, and TTF-1. A CK5/6 stain was focally positive. This staining pattern is most consistent with squamous cell carcinoma, with basaloid features, also known as cloacogenic carcinoma.

Discussion:

The patient’s original lymph node biopsy specimen was reviewed, along with the FNA and biopsy of the rectal mass, which all showed to be squamous cell carcinoma with basaloid features. The lymph node biopsy was also sent for chromogenic in situ hybridization for High-Risk HPV, and was shown to be HPV positive.

A small cell neuroendocrine carcinoma is very high on the differential in this case, given the focal stippled chromatin and nuclear molding. However, we would expect this to have stained positive for synaptophysin and chromogranin if it were small cell. It would also ideally show the characteristic “salt and pepper” chromatin more diffusely. Poorly differentiated adenocarcinoma of the rectum is also a strong possibility in this case. However, the cells show no glandular differentiation (which does not necessarily rule out poorly differentiated adenocarcinoma), and in the presence of a positive p16, p63, and HPV test, squamous cell carcinoma is the most likely diagnosis. Without the immunohistochemistry in this case, it would be very difficult to differentiate this lesion from poorly differentiated adenocarcinoma, especially given the location (rectal tumor at dentate line). Both a squamous or adeno- carcinoma could arise from this region. Mucin vacuoles or a translucent foamy cytoplasm may help in diagnosing adenocarcinoma over SCC.

References:

Graham RP, Arnold CA, Naini BV, Lam-Himlin DM. Basaloid Squamous Cell Carcinoma of the Anus Revisited. Am J Surg Pathol. 2016 Mar;40(3):354-60