Challenges in Consistent Histologic Diagnosis of Superficially Invasive Anal Squamous Cell Carcinoma

Superficially invasive squamous cell carcinoma of the anus (SISCCA) is defined as a minimally invasive cancer measuring less than 3 mm in depth and less than 7 mm in horizontal spread. Its subtle morphologic alterations pose a significant challenge for histologic diagnosis.

To evaluate the diagnostic agreement among pathologists for SISCCA and to identify potential areas for improvement.

Four gastrointestinal (GI) and 4 gynecologic (GYN) pathologists independently reviewed digitized hematoxylin-eosin images of 20 anal high-grade squamous intraepithelial lesions with suspected early invasion. Participants classified each lesion as either invasive or noninvasive and selected features indicative of invasion from a list compiled from major textbooks. Cohen κ coefficient was calculated to assess interobserver agreement.

Of the 20 lesions, 8 (40%) received unanimous diagnoses, while 12 (60%) had discrepancies. Overall agreement was moderate (κ = 0.46; 95% CI, 0.29-0.48), with similar levels between the GI (κ = 0.53; 95% CI, 0.45-0.74) and GYN (κ = 0.46; 95% CI, 0.25-0.48) groups (P > .01). The GYN group diagnosed a higher number of lesions as invasive than did the GI group (median, 14.5 versus 10.5; P > .01). In consensus SISCCA diagnoses, the most commonly noted feature was the presence of small irregular tumor nests, followed by desmoplastic response and paradoxical maturation.

Variability in recognizing histologic features indicative of early invasion contributed to the poor reproducibility in the diagnosis of SISCCA. Efforts should focus on refining diagnostic criteria and integrating features that have proved effective in identifying early invasive cancer at other anatomic sites.