EP697 - Squamous Cell Colon Carcinoma: A Perplexing Histology

Purpose/Background: Primary squamous cell carcinoma (SCC) of the colon is an exceedingly rare malignancy, representing approximately 0.1-0.25 per 1,000 colorectal cancers, with a predilection for the rectum and right colon. Multiple mechanisms have been proposed, including pluripotent stem cell differentiation, chronic mucosal injury or metaplasia, and squamous transformation of pre-existing adenocarcinoma. Due to its rarity, diagnostic and management guidelines remain undefined. We report a case of synchronous primary cecal SCC and ascending colon adenocarcinoma occurring in a 90-year-old male, aiming to highlight diagnostic considerations, molecular distinctions, and management approach.

Methods/Interventions: A 90-year-old male with a history of prostate cancer (treated with pelvic radiation 11 years prior) presented with generalized weakness, melena, and anemia. Colonoscopy revealed two distinct right-sided masses: a friable cecal lesion and an ulcerated circumferential ascending colon lesion (Fig.1 A and B). Pathology demonstrated poorly differentiated SCC in the cecum (CK5/p40 positive, CK7/CK20 negative, weak SATB2 expression) and conventional adenocarcinoma in the ascending colon. Staging CT and PET imaging confirmed no distant disease or alternate primary source. The patient underwent a robot Xi-assisted laparoscopic right hemicolectomy with ileocolic anastomosis. Biopsies revealed poorly differentiated SCC in the cecum, positive for CK5 and p40, negative for CK7 and CK20, with weak SATB2 expression; and moderately differentiated adenocarcinoma in the ascending colon. Staging with CT and PET-CT demonstrated no distant disease or alternative primary SCC sites (lung, cervix, bladder, esophagus) and no squamous-lined fistulas, fulfilling diagnostic criteria for primary colonic SCC.

Initially scheduled for elective resection, the patient developed worsening anemia, abdominal pain, and constitutional symptoms requiring transfusions and prompting urgent robotic right hemicolectomy with creation of ileocolic anastomosis. The procedure was uneventful.

Results/Outcomes: Surgery was uncomplicated, and postoperative recovery was favorable with stable hemoglobin and no further transfusion requirements. Final pathology confirmed a pT3N0M0 invasive SCC of the cecum and a separate pT1N0M0 adenocarcinoma of the ascending colon, both with negative margins and 29 negative lymph nodes. The adenocarcinoma demonstrated MLH1/PMS2 loss with BRAF mutation, whereas the SCC was mismatch-repair proficient, supporting separate lineages. Given age and stage II disease, no adjuvant therapy was administered. The patient remains clinically stable.

Conclusion/Discussion: Primary colonic SCC is a distinct and aggressive entity requiring exclusion of extracolonic primary sources and squamous-lined fistulas before diagnosis. Surgical resection remains the mainstay of therapy, while adjuvant chemotherapy may improve survival in node-positive or high-risk disease. Molecular profiling in this case confirmed independent tumor origins, underscoring the potential for synchronous malignancies of divergent histology. Expanding case reporting and registry data are essential to establish optimal treatment algorithms and to evaluate the role of adjuvant chemotherapy and immunotherapy in this rare tumor type.

Figure 1: Colonoscopy and Histology
Colonoscopy. (A) Cecal mass. (B) Ascending colon mass. Histology from primary colon squamous cell carcinoma. (C) Hematoxylin and eosin staining. (D) p40 staining revealing squamous cell origin.
Fig. 2: Computed axial tomography
(A) Cecal squamous cell carcinoma and (B) Ascending colon adenocarcinoma.