Inspection of Deep Tumor Margins in Mohs Micrographic Surgery for Accurate Cutaneous Squamous Cell Carcinoma Staging

Abstract

Histopathologic analysis of debulk specimens in Mohs micrographic surgery (MMS) may augment high-risk factor identification in cutaneous squamous cell carcinoma (cSCC), leading to tumor upstaging. Existing studies have yet to comment on the location of high-risk factors within tumors. Herein we report four cSCCs initially categorized as well-differentiated that were reclassified to moderate to poorly differentiated on debulk analysis and upstaged accordingly. In all cases, the deep tumor margins displayed morphological differences from other areas, exhibiting less differentiation and/or perineural invasion. Thorough inspection of the deep tumor margins may be required for accurate tumor staging and evaluation of metastatic risk. Case Series Patient 1: An 80-year-old male presented with a 2 cm plaque on the frontal scalp. Biopsy revealed well-differentiated cSCC staged at T2a with Brigham and Women’s Hospital Staging System (BWH), subsequently upgraded to T2b during MMS due to galea involvement. Debulk analysis revealed moderate to poorly differentiated cSCC with the least differentiated cells at the deep margin. Patient 2: A 75-year-old male presented with a 2 cm plaque on the left vertex scalp. Biopsy revealed well-differentiated cSCC staged at T2a (BWH), subsequently upgraded to T2b during MMS due to extension beyond subcutaneous fat and PNI. Examination of the second stage revealed moderately differentiated cSCC with the least differentiated cells at the deep margin. Patient 3: An 86-year-old female presented with a 2.4 cm nodule on the right lower leg. Biopsy revealed well-differentiated invasive cSCC. Debulk analysis revealed moderately differentiated cSSC with the least differentiated cells at the deep margin. Patient 4: An 82-year-old male presented with a 2.7 cm nodule on the vertex scalp. Biopsy revealed well-differentiated cSCC staged at T2a (BWH), subsequently upgraded to T2b during MMS due to extension beyond subcutaneous fat. Debulk analysis revealed moderate to poorly differentiated cSSC with the least differentiated cells at the deep margin in the galea. cSCCs may exhibit intratumor heterogeneity in which predominantly well-differentiated tumors contain focal areas of poorer differentiation. Intratumor heterogeneity complicates tumor risk estimation as a well-differentiated tumor on biopsy may exhibit poor differentiation at a deeper margin. Thus, the most clinically relevant cells for prognosticating risk may not be visible on biopsy, underscoring the utility of close examination of the debulk specimen and deep margin of the Mohs layer. Despite this, most Mohs surgeons endorse immediately discarding debulk specimens without evaluation. These cases reinforce that tumor staging is incomplete until the deep margins are assessed to find the most dysplastic cells.