Updates in the Pathologic Diagnosis and Classification of Epithelial Neoplasms of Urachal Origin

Since the publication of the World Health Organization "blue book" in 2004, several recent studies have provided new insights on the pathologic aspects of urachal neoplasms. The proposed updates include modified criteria for the diagnosis of urachal carcinoma. A uniform nomenclature for cystic tumors was lacking, and it is recommended that urachal mucinous cystic tumors should be separated and classified in a manner similar to ovarian mucinous neoplasms. The spectrum includes mucinous cystadenoma, mucinous cystic tumor of low malignant potential, mucinous cystic tumor of low malignant potential with intraepithelial carcinoma, and microscopically or frankly invasive mucinous cystadenocarcinoma, with 65% of cystic tumors classified as mucinous cystic tumor of low malignant potential. Most importantly, it has been shown that progression-free survival of noninvasive mucinous cystic tumors is significantly better than noncystic invasive adenocarcinoma. This development, along with prior descriptions of urachal villous adenoma, has also reaffirmed the occurrence of benign tumors of urachal epithelial origin. For noncystic (usual) invasive adenocarcinomas, the traditionally described histologic subtypes of enteric, mucinous, signet ring cell, not otherwise specified, and mixed remain appropriate, with 50% of tumors classified as mucinous subtype. Although this subtyping is helpful in diagnosis and differential diagnosis, the clinical significance of subtyping adenocarcinoma is still uncertain. Rare nonglandular morphologies such as urothelial, squamous, and neuroendocrine carcinoma in urachal carcinomas have been described in detail with proposals for their own set of diagnostic criteria. These criteria are based on unique features of urachal nonglandular carcinomas. Among the immunomarkers studied, only β-catenin and CK7 may be of help in the distinction of urachal from colorectal adenocarcinoma. Awareness of the expression profile of immunomarkers such as CDX2, P504S (racemase), PSMA, claudin-18, and REG IV in urachal tumors and in tumors in the differential diagnosis is important to avoid overreliance of these markers in the diagnosis. Limited studies have identified KRAS mutations interestingly only in mucinous adenocarcinoma and exclusive of MSI loss, and mutations in BRAF are not present. Several alternative tumor staging approaches (eg, Mayo, Ontario, TNM systems) different from the traditional staging proposed by Sheldon are used that provide better tumor distribution across stages; however, the prognostic utility of the stage substratification has yet to be validated in large prospective studies. Evidence though suggests that staging urachal cancer is most pertinent when dichotomized to tumors that have spread outside versus within the perivesical tissue. Only high tumor stage and residual tumor after surgery have been shown to be independent predictors of outcome. This review updates the contemporary classification of urachal epithelial tumors, which has informed the upcoming 2016 classification of World Health Organization tumors. We provide modified criteria for diagnosing urachal adenocarcinomas, which remains a clinico-pathologic exercise. The role of ancillary diagnostic methodology and issues pertaining to staging and prognostication are presented.