Effects of Tumor Localization, Age, and Stage on the Outcomes of Gastric and Colorectal Signet Ring Cell Adenocarcinomas.

Signet ring cell adenocarcinomas (SRCCs) are a rare histological adenocarcinoma subtype, classically thought to have a worse prognosis than conventional adenocarcinomas. The majority of these cancers occur in the stomach, colon, and rectum. Their rarity means that most epidemiological studies into their pathology are often underpowered, and interpretations from these reports are mixed. In this study, we use the Surveillance, Epidemiology, and End Results Program (SEER) database to examine the effects of tumor localization, age, and stage on gastric and colorectal cancer outcomes. For early onset localized and regional gastric cancers, SRCCs have the same overall risk of mortality compared to conventional adenocarcinomas. Over the age of 50 years, SRCCs have worse outcomes across all stages. Gastric SRCCs are 2-3-fold more likely in younger patients, and more heavily favor the distal stomach. Like conventional adenocarcinomas, proximal gastric SRCCs have decreased survival. Across all ages, stages, and locations, colorectal SRCCs have worse outcomes. SRCCs favor the right colon, but outcomes are significantly worse for the left colon and rectal cancers. Relative to adenocarcinomas, colorectal SRCCs have the worst outcomes in younger patients. Overall, these results provide insights into SRCC disease patterns that cannot be surmised outside of population-level data.

Malignant Transformation of Long-Standing Ileal Crohn's Disease Likely Favors Signet Ring Cell Adenocarcinoma Histology.

Signet ring cell adenocarcinomas (SRCCs) are a rare and aggressive histological subtype of adenocarcinomas typically with poor prognosis usually secondary to late stage at detection. In the small bowel, they constitute only 1% of all malignancies. In the last decade, there have been multiple case reports and small case series that have identified SRCCs, typically in the ileum, in patients with Crohn's disease. Crohn's disease is a transmural inflammatory condition that normally manifests in the distal ileum and colon, and is known to temporally increase the risk of malignancy. Given the profound rarity of SRCCs, establishing an association between Crohn's disease and SRCC is challenging. In this study, we performed a systematic review of case reports and small case series describing small bowel SRCCs in Crohn's disease patients. Most cases were found in the distal/terminal ileum, at a mean age of 59 years old. Virtually all tumors were locally advanced (pathological T stage 3 and 4), typically with at least N1 nodal disease. Two case studies (one is a case-control study and the other a cohort design) demonstrated that small bowel SRCC, as opposed to conventional adenocarcinoma, was significantly correlated to a history of Crohn's disease (35% vs. 0%, 73.5% vs. 28.5%), with a propensity to arise in the ileum (95% vs. 30%, 66.7% vs. 42.1%), and at earlier mean age (43 vs. 68 years, 53.7 vs. 61.7 years). We additionally used the Surveillance, Epidemiology, and End Results (SEER) database for insights into the clinicoepidemiological characteristics of ileum SRCCs. SRCCs composed 28.1% of all ileal SRCCs, compared to 11.0% for the adenocarcinomas, with a younger age at diagnosis (60.7 vs. 64.6 years), more distant disease at presentation (41.3% vs. 26.4%), and shorter overall median survival time (20 vs. 39 months). In summary, while there is limited direct evidence to support an association between small bowel SRCC and Crohn's disease, the phenomenon has been increasingly documented in the literature in the last decade. Clinicians treating Crohn's disease patients should consider this in their differential diagnosis, particularly when managing disease complications, as early detection and surgical intervention offer the best prognosis.

Location Has Prognostic Impact on the Outcome of Colorectal Mucinous Adenocarcinomas.

Mucinous (colloid) adenocarcinomas (MAs) are a rare histological subtype of tumors defined by extracellular mucin comprising more than 50% of the tumor. These tumors are on a continuum of mucin-producing malignancies with signet ring cell adenocarcinomas (SRCCs), which instead produce intracellular mucin. Mucin-containing cancers occur primarily in the stomach and colon, where for SRCCs, outcomes are relatively worse in the proximal stomach and the rectum. It is not known if MAs have similar outcomes. In this study, we use the Surveillance, Epidemiology, and End Results (SEER) database to examine the effects of tumor localization, age, sex, and stage on colorectal and gastric cancer outcomes for MAs. For right colon cancers, MAs are more common, particularly in females, and have slightly better or equivalent outcomes across all stages and ages compared to conventional adenocarcinomas, but outcomes are progressively worse compared to conventional adenocarcinomas for left colon and rectal cancers. Unlike SRCCs, MAs have similar outcomes to conventional adenocarcinomas in all stomach locations. Overall, these results suggest that MAs have an intrinsically different tumor biology in the left colon and rectum that promotes pathogenesis. Decoding this phenomenon could lead to more effectively tailored patient treatment regimens.

Epidemiology of Undifferentiated Carcinomas.

Undifferentiated carcinomas are rare cancers that lack differentiation, such that they cannot be classified into any conventional histological subtype. These cancers are uniquely codified and are contrasted to carcinomas with an ascertained histology that are grade classified as poorly differentiated, undifferentiated, or anaplastic. Given their rarity, there are no standardized overviews of undifferentiated carcinomas in the literature, and it is unknown if their classification indicates a unique prognosis profile. In this study, we summarize the clinicodemographic and mortality outcomes of undifferentiated carcinomas in twelve primary sites and for unknown primaries, comprising 92.8% of all undifferentiated carcinomas diagnosed from 1975-2017 in the Surveillance, Epidemiology, and End Results Program (SEER). Incidence has decreased to 4 per 1 million cancer diagnoses since 1980. Relative to the most common undifferentiated cancers with a defined histology, undifferentiated carcinomas have overall worse prognosis, except in nasopharyngeal and salivary gland cancers (hazard ratio (HR) 0.7-1.3). After correction for age, sex, race, detection stage, and treatment (surgery, chemotherapy, and radiotherapy), the mortality HR averages 1.3-1.4 for these cancers relative to histologically ascertainable undifferentiated cancers. However, there is a wide variance depending on site, signifying that survival outcomes for undifferentiated carcinomas depend on factors related to site tumor biology.