Invasive stratified mucin-producing carcinoma of the colorectum: Expanding the morphologic spectrum of large bowel cancer

Abstract

Abstract Background: Invasive stratified mucin-producing carcinoma is a recently recognized adenocarcinoma with distinctive features. Morphologically, it is characterized by solid groups of tumor cells containing variable amounts of intracytoplasmic mucin stratified throughout the thickness of lesional epithelium. It was first described in the cervix but similar tumors have since been reported in the penis, anus and prostate, with or without an association with human papilloma virus. In the gastrointestinal tract, the phenomenon of epithelial stratification has an interesting embryologic morphogenesis. Gastrointestinal mucosa starts off as nascent columnar epithelium that is subsequently patterned to confer regional specific functions along the cephalocaudal axis. However, in disease states, normal architectural patterning can be disrupted by aberrant differentiation. Given this background and the phenotypic plasticity of neoplastic cells, we were interested in ascertaining whether invasive stratified mucin-producing carcinoma occurs in the colorectum. Methods This was a retrospective study of all 584 cases of colorectal carcinoma accessioned at our institution over a 2-year period (January 2021- December 2022). Cases were analyzed to determine which fulfilled the criteria for invasive stratified mucin-producing carcinoma. Results There were 9 cases of colorectal invasive stratified mucin-producing carcinoma - one pure form and 8 mixed. They showed the classic colorectal (CK20+, CDX2+, CK7-) immunostaining profile but, based on various morphologic criteria, they could be distinguished from conventional adenocarcinoma NOS, mucinous, signet ring cell, medullary, goblet cell and undifferentiated carcinomas. About half the cases were MLH1/PMS2 deficient and BRAF &/or PIK3CA mutated, which aligns with the hypermutated phenotype. Conclusions Colorectal invasive stratified mucin-producing carcinoma appears to be a real entity, best recognized in its early stages. It appears to be a high-grade carcinoma. With tumor progression, it evolves into a mucinous adenocarcinoma with a proclivity towards signet ring cells. In summary, the study of this tumor, particularly in its early stages, provides useful clues to further understanding the biology and progression of large bowel cancer. Further studies are required to learn more about this tumor.