While the overwhelming majority of colorectal carcinomas (CRC) are diagnosed as adenocarcinoma not otherwise specified, there are numerous under-recognised morphologic patterns of CRC. These patterns are recognised by the WHO, appear in reporting manuals for the American Joint Committee of Cancer, and/or are listed on synoptic reports, while many other variants have either fallen out of favour or are emerging as future bona fide patterns. Herein, we discuss 13 variants: serrated adenocarcinoma, micropapillary adenocarcinoma, medullary carcinoma, neuroendocrine carcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, adenosquamous carcinoma, adenoma-like adenocarcinoma, lymphoglandular complex-like CRC, carcinoma with sarcomatoid components, cribriform-comedo-type adenocarcinoma, undifferentiated carcinoma and low-grade tubuloglandular adenocarcinoma. The purpose of this review is to scrutinise these variants by assessing their clinical characteristics, morphologic cues, as well as pitfalls, and address their prognostic significance. Our analysis aims to bring clarity and updated understanding to these variants, offering valuable insights for pathologists. This contributes to more nuanced CRC diagnosis and treatment strategies, highlighting the importance of recognising a broad spectrum of morphologic patterns in CRC.

Distinguishing colon carcinoma that is surrounded by well-circumscribed lymphoid tissue from adenomas involving lymphoglandular complexes can be difficult. We assessed a multi-institutional international cohort of 20 colorectal carcinomas with associated prominent lymphoid infiltrates, which we referred to as lymphoglandular complex-like carcinoma (LGCC). We collected clinical and endoscopic features, including lesion size, endoscopic appearance, location, procedure, follow-up, AJCC stage, and mismatch repair status. We recorded the presence of the following histologic features: haphazard gland distribution, gland angulation, gland fusion, solid nest formation, single-cell formation, stromal desmoplasia, presence of lymphovascular invasion and perineural invasion, presence of lamina propria, cytologic atypia as low- or high-grade, presence of goblet cells in the invasive component, and the presence of a surface lesion. Most cases (9 of 13) were described endoscopically as sessile polyps with an average size of 1.56 cm. Most cases (90%) were associated with a surface lesion, of which the majority were tubular adenomas, though a subset was associated with sessile serrated lesions with dysplasia (3 of 18). All cases of LGCC demonstrated haphazard gland distribution and either gland angulation, fusion, or solid nest formation. A portion of cases demonstrated single-cell infiltration (35%) and desmoplasia (50%), and rarely lymphovascular invasion was present (5%). A subset (10%) of cases invaded beyond the submucosa. Deficient mismatch repair was present in 22% (2 of 9) of cases for which it was performed. In cases of colectomy or completion colectomy, nodal metastasis was present in 38% (3 of 8). No cases demonstrated disease recurrence or disease-specific mortality. Overall, LGCC represents an enigmatic subset of carcinomas that is important to distinguish from adenomas involving lymphoglandular complexes due to its varying prognostic outcomes.

Gut-associated lymphoid tissue (GALT) carcinoma, also termed dome-type carcinoma, is an infrequent distinctive subtype of colorectal adenocarcinoma and only 18 cases have been reported in the English medical literature. These tumors have unique clinicopathological features and are considered to have a low malignant potential with favorable prognosis. Herein, we described a case of a 49-year-old male with intermittent hematochezia for 2 years. Colonoscopy revealed a sessile broad-based polyp of approximately 20 mm × 17 mm in the sigmoid colon 260 mm away from the anus, with a slightly hyperemic surface. Histologically, this lesion showed typical GALT carcinoma. The patient was followed up for one and a half year and he did not experience any discomfort, such as abdominal pain or hematochezia, and no tumor recurrence occurred. Moreover, we reviewed the literature, summarized the clinicopathological features of GALT carcinoma, and highlighted its pathological differential diagnosis to further explore this infrequent type of colorectal adenocarcinoma.

Colorectal epithelial neoplasm extending into the submucosal gut-associated lymphoid tissue (GALT) can cause difficulties in the differential diagnosis. Regarding GALT-associated epithelial neoplasms, a few studies favor the term "GALT carcinoma" while other studies have mentioned the term "GALT-associated pseudoinvasion/epithelial misplacement (PEM)".

The clinicopathologic characteristics of 11 cases of colorectal epithelial neoplasm associated with submucosal GALT diagnosed via endoscopic submucosal dissection were studied.

Eight cases (72.7%) were in males. The median age was 59 years, and age ranged from 53 to 73. All cases had a submucosal tumor component more compatible with GALT-associated PEM. Eight cases (72.7%) were located in the right colon. Ten cases (90.9%) had a non-protruding endoscopic appearance. Nine cases (81.8%) showed continuity between the submucosal and surface adenomatous components. Nine cases showed (81.8%) focal defects or discontinuation of the muscularis mucosae adjacent to the submucosal GALT. No case showed hemosiderin deposits in the submucosa or desmoplastic reaction. No case showed single tumor cells or small clusters of tumor cells in the submucosal GALT. Seven cases (63.6%) showed goblet cells in the submucosa. No cases showed oncocytic columnar cells lining submucosal glands.

Our experience suggests that pathologists should be aware of the differential diagnosis of GALT-associated submucosal extension by colorectal adenomatous neoplasm. Further studies are needed to validate classification of GALT-associated epithelial neoplasms.

Several types of colorectal cancers are associated with a prominent lymphoid component, which is considered a positive prognostic factor. We report a case of a dome-type carcinoma of the cecum in a 57 year old female. The sessile, non-polypoid lesion histologically consisted of a tubulovillous adenoma with low-grade dysplasia. The submucosal invasive component showed low-grade architectural features that included cystically dilated glands containing eosinohilic debris. Immunohistochemical studies displayed retention of the four mistmach repair proteins, consistent with a stable phenotype. After 3 years, the patient remains free of recurrence. A literature review highlighted striking similarities between dome-type carcinoma and the gut-associated lymphoid tissue carcinoma, the two sharing an intimate association with the gut associated lymphoid tissue.The two variants might therefore be grouped into a unified category.

Cancer in ulcerative colitis (UC) originates in dysplastic crypts, adenomatous growths (UCAG), and UC-associated adenomas (UCAD). The aim of the present study was to compare the histological phenotypes between UCAG, UCAD, and sporadic colorectal adenomas in non-colitics (non-UCAD), as well as between UC-associated carcinomas (UCC) and carcinomas in non-colitic patients (non-UCC).

Three thousand and forty nine sections from 96 colectomy specimens in patients with UC-pancolitis and carcinoma were reviewed.

Villous phenotypes were more frequent in UCAG (48%) than in UCAD (26%) and non-UCAD (11%), and serrated phenotypes more frequent in UCAD (29%) than in UCAG (12%) and non-UCAD (8%). Tubular phenotypes were far less frequent in UCAG (14%) than in UCAD (45%) and non-UCAD (80%). Villous and signet ring cell cancer phenotypes were more frequent in UCC (22% and 8%, respectively) than in non-UCC (9% and 0.8%, respectively). Six UCC (5.6%) were de novo carcinomas.

Invasive carcinomas were found in one-half of the UCAG and in one-third of the UCAD, indicating that both lesions are important in cancer development in UC. The different proportions of histological phenotypes found in UCAG, UCAD, and non-UCAD on the one hand, and UCC and non-UCC on the other, suggest that chronic protracted inflammation might have modified the stem cell receptors that receive the molecular signals that program structural configurations in neoplastic glands. This is the first study reporting the occurrence of serrated and microtubular UCAG and of de novo carcinomas in UC.