Mucosal fungi promote gut barrier function and social behavior via Type 17 immunity.

Fungal communities (the mycobiota) are an integral part of the gut microbiota, and the disruption of their integrity contributes to local and gut-distal pathologies. Yet, the mechanisms by which intestinal fungi promote homeostasis remain unclear. We characterized the mycobiota biogeography along the gastrointestinal tract and identified a subset of fungi associated with the intestinal mucosa of mice and humans. Mucosa-associated fungi (MAF) reinforced intestinal epithelial function and protected mice against intestinal injury and bacterial infection. Notably, intestinal colonization with a defined consortium of MAF promoted social behavior in mice. The gut-local effects on barrier function were dependent on IL-22 production by CD4+ T helper cells, whereas the effects on social behavior were mediated through IL-17R-dependent signaling in neurons. Thus, the spatial organization of the gut mycobiota is associated with host-protective immunity and epithelial barrier function and might be a driver of the neuroimmune modulation of mouse behavior through complementary Type 17 immune mechanisms.

Dietary interventions to prevent high-fructose diet-associated worsening of colitis and colitis-associated tumorigenesis in mice.

Diet is believed to be an important factor in the pathogenesis of inflammatory bowel disease. High consumption of dietary fructose has been shown to exacerbate experimental colitis, an effect mediated through the gut microbiota. This study evaluated whether dietary alterations could attenuate the detrimental effects of a high-fructose diet (HFrD) in experimental colitis. First, we determined whether the procolitic effects of a HFrD could be reversed by switching mice from a HFrD to a control diet. This diet change completely prevented HFrD-induced worsening of acute colitis, in association with a rapid normalization of the microbiota. Second, we tested the effects of dietary fiber, which demonstrated that psyllium was the most effective type of fiber for protecting against HFrD-induced worsening of acute colitis, compared with pectin, inulin, or cellulose. In fact, supplemental psyllium nearly completely prevented the detrimental effects of the HFrD, an effect associated with a shift in the gut microbiota. We next determined whether the protective effects of these interventions could be extended to chronic colitis and colitis-associated tumorigenesis. Using the azoxymethane/dextran sodium sulfate model, we first demonstrated that HFrD feeding exacerbated chronic colitis and increased colitis-associated tumorigenesis. Using the same dietary changes tested in the acute colitis setting, we also showed that mice were protected from HFrD-mediated enhanced chronic colitis and tumorigenesis, upon either diet switching or psyllium supplementation. Taken together, these findings suggest that high consumption of fructose may enhance colon tumorigenesis associated with long-standing colitis, an effect that could be reduced by dietary alterations.

GLUT5 is a determinant of dietary fructose-mediated exacerbation of experimental colitis.

The Western diet has been suggested to contribute to the rising incidence of inflammatory bowel diseases. This has led to the hypothesis that fructose, a component of the Western diet, could play a role in the pathogenesis of inflammatory bowel diseases. A high-fructose diet is known to exacerbate experimental colitis. This study tested whether the expression of GLUT5, the fructose transporter, is a determinant of the severity of experimental colitis during elevated fructose consumption and whether ileal inflammation is associated with altered GLUT5 expression in Crohn's disease. Studies in genetically engineered mice showed that in comparison to Glut5+/+ mice, feeding a 15 kcal% fructose diet to Glut5-/- mice led to worse dextran sodium sulfate (DSS)-induced colitis. This effect was associated with elevated levels of colonic fructose and a shift in the fecal microbiota in Glut5-/- mice. Importantly, treatment with broad-spectrum antibiotics protected against the worsening of colitis mediated by dietary fructose in Glut5-/- mice. Gene expression analysis revealed that GLUT5 levels are reduced in the intestines of patients with ileal Crohn's disease. Moreover, levels of GLUT5 negatively correlated with expression of proinflammatory mediators in these samples. Collectively, these results demonstrate that dietary constituent (fructose)-host gene (GLUT5) interactions can shape the colonic microbiota, thereby impacting the severity of colitis.NEW & NOTEWORTHY This study provides the first evidence that reduced levels of GLUT5, the fructose transporter, worsen experimental colitis upon fructose feeding, an effect mediated by changes in the gut microbiota. Moreover, GLUT5 expression is reduced in Crohn's ileitis. Overall, these findings demonstrate the importance of interactions between dietary fructose and host GLUT5 as determinants of both the composition of colonic microbiota and severity of experimental colitis.

The significance of focally enhanced gastritis in haematopoietic stem cell transplant recipients.

AIMS: The histological diagnosis of acute gastric graft-versus-host-disease (aGVHD) in patients with a history of haematopoietic stem cell transplant (HSCT) is based on the presence of epithelial cell apoptosis and karyorrhectic debris. There is, however, limited information on the histological findings in patients who develop symptoms several months after transplant. Focally enhanced gastritis (FEG), defined by the presence of focal periglandular lymphohistiocytic inflammation with neutrophilic or lymphocytic intra-epithelial infiltration of gastric glands, has been described in patients with inflammatory bowel disease and in HSCT patients. The pattern closely resembles the focal periductal inflammation and lymphocytic exocytosis seen in chronic GVHD of the salivary gland. We sought to evaluate the significance of FEG in HSCT patients. METHODS AND RESULTS: Gastric biopsies from 151 HSCT patients who underwent endoscopies for GVHD-like symptoms were identified. Time from transplant to biopsy, presence of extra-gastric GVHD, medications and outcome were noted. Thirty-five biopsies showed FEG and 21 showed aGVHD; the remainder were either normal or showed non-specific changes. Twenty-one (60%) FEG patients had concurrent histologically proven extra-gastric GVHD. The time to biopsy in FEG patients was significantly longer than in aGVHD patients (162 versus 57 days, P < 0.01). Prior or subsequent gastric biopsies of 14 patients in the FEG cohort were also evaluated and, of these, six showed aGVHD while one showed persistent FEG. CONCLUSIONS: These findings suggest that FEG probably represents a form of late-occurring GVHD. This histological pattern should not be overlooked when identified in gastric biopsies from HSCT patients.

Morphological spectrum of immune check-point inhibitor therapy-associated gastritis.

AIMS: Immune check-point inhibitors are frequently used in the treatment of a variety of solid tumours. The mechanism of action of these drugs involves up-regulation of cytotoxic T cells, which can lead to a lack of self-tolerance and immune-related adverse events, including those involving the gastrointestinal tract. This study was performed to characterise the histological features of immune check-point inhibitor therapy-associated gastritis. METHODS AND RESULTS: Gastric biopsies from patients on immune check-point inhibitor therapy with clinical suspicion of drug-associated gastrointestinal injury were identified. The predominant histological pattern of injury, distribution of injury, degree of tissue eosinophilia and prominence of apoptosis were recorded. Presenting symptoms, treatment and follow-up data were obtained by medical chart review. The 12 patients included in the study group were treated with ipilimumab, nivolumab or pembrolizumab for a variety of tumours. Symptoms at presentation included nausea, vomiting and diarrhoea. Chronic active gastritis with intra-epithelial lymphocytosis and prominent apoptosis was seen in eight of 12 patients, and was the most useful combination for the diagnosis of drug-induced gastritis in these patients. Four patients showed focal enhancing gastritis with a lymphohistiocytic cuff around inflamed glands reminiscent of Crohn's disease. One of those four patients was homozygous for the ATG16L1 Crohn's disease-associated gene variant, but had no history of inflammatory bowel disease. Ten patients responded to medication withdrawal and steroid therapy, while two required treatment with infliximab. CONCLUSIONS: Awareness of the morphological spectrum of immune check-point inhibitor therapy-associated gastritis is important for the accurate diagnosis and prompt management of these patients.

Malformations, choristomas, and hamartomas of the gastrointestinal tract and pancreas.

Congenital and hamartomatous lesions of the gastrointestinal tract cause diagnostic challenges for surgical pathologists. Many of these are merely histologic curiosities, whereas others have substantial clinical implications because they herald cancer syndromes or associated anomalies. Although a comprehensive discussion of all developmental abnormalities that can occur in the gastrointestinal tract is beyond the scope of a single manuscript, some entities are more likely to be encountered by surgical pathologists, have important clinical consequences, or pose diagnostic difficulties. The purpose of this review is to discuss the more common malformations and choristomas, as well as hamartomatous lesions that may be clinically important due to their risk for cancer development, frequent associations with heritable cancer syndromes and other anomalies, or potential to simulate other entities.

Mutational landscape of goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix is distinct from typical carcinoids and colorectal adenocarcinomas.

There is limited data on the spectrum of molecular alterations in goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix. We used next generation sequencing to determine mutations of potential pathogenetic and therapeutic significance in this rare group of tumors. Adequate DNA was successfully extracted in 34/46 cases and the final group included 18 goblet cell carcinoids and 16 adenocarcinoma ex goblet cell carcinoids. Illumina TruSeq™ was used for sequencing exons of a custom 282 gene panel using an Illumina HiSeq 2000. All cases had a minimum coverage depth of at least 50 reads. After filtering through the Exome Sequencing Project, the number of mutations per case ranged from 0-9 (mean:3). The mutational burden in adenocarcinoma ex goblet cell carcinoids was significantly higher than goblet cell carcinoids (mean 5 vs. 3; p < 0.05) but the spectrum of alterations overlapped between the two groups. The most frequent mutations included ARID1A (4/34), ARID2 (4/34), CDH1 (4/34), RHPN2 (4/34), and MLL2 (3/34). Some mutations typically seen in conventional colorectal adenocarcinomas were also identified but with much lower frequency (APC :4/34; KRAS :2/34). MLL2 and KRAS mutations were only seen in adenocarcinoma ex goblet cell carcinoids and TP53 mutations were limited to poorly differentiated adenocarcinoma ex goblet cell carcinoids (2/34). Copy number changes could be evaluated in 15/34 cases and showed low copy number gains in CDKN1B (6/15) and NFKBIA (6/15), among others. The overlapping molecular alterations suggest that goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids are best considered two grades of differentiation of the same tumor rather than two distinct histological types. Mutations in TP53, CDH1 and MLL2 mutations were predominantly present in the adenocarcinoma ex goblet cell carcinoid group consistent with transformation to a higher grade lesion. The unique mutational profile also offers an explanation for the poor chemosensitivity in these tumors and highlights the need for developing new targeted therapies.

Gastric pyloric gland adenoma: a multicentre clinicopathological study of 67 cases.

AIMS: There is limited information regarding the clinicopathological and immunohistochemical characteristics of gastric pyloric gland adenomas (PGAs). METHODS AND RESULTS: Sixty-seven cases of gastric PGA from 57 patients were analysed. PGAs occurred with similar frequency in men and women (47.4 and 52.6%, respectively), with a mean age of 66 years. Most presented in the gastric body/fundus (67.2%). Fifteen cases (22.4%) developed against a background of autoimmune gastritis (AIG), whereas normal mucosa was seen in 35.8%. Only 16.4% (11 cases) developed in patients with a genetic predisposition, most commonly familial adenomatous polyposis. Low-grade lesions had a mean size of 1.5 cm, while PGAs with high-grade dysplasia (HGD) or adenocarcinoma had a mean size of 3.5 cm (P < 0.001) and more commonly showed tubulovillous architecture (50.0 versus 25.6% in low-grade dysplasia; P = 0.040). Most PGAs (61.2%) co-expressed mucin (MUC)5AC and MUC6 (mixed type), which was associated significantly with HGD or adenocarcinoma (P = 0.013). AIG was also associated with HGD (P = 0.027), but genetic predisposition did not correlate with the grade of dysplasia (P = 0.793). The recurrence rate of PGA was similar for high- (11.8%) and low-grade lesions (7.4%) (P = 0.624). CONCLUSIONS: The risk of HGD increases with the size of PGA, tubulovillous architecture and the presence of AIG as well as mixed immunophenotype. As the overall local recurrence rate is less than 10%, PGAs may be treated conservatively, but they should be excised completely if possible, particularly if they are large or show high-grade features.

A Case of Disseminated Histoplasmosis in a Patient with Rheumatoid Arthritis on Abatacept.

Biologic agents are effective treatments for rheumatoid arthritis but are associated with important risks, including severe infections. Tumor Necrosis Factor (TNF) α inhibitors are known to increase the risk of systemic fungal infections such as disseminated histoplasmosis. Abatacept is a biologic agent with a mechanism different from that of TNFα inhibitors: It suppresses cellular immunity by competing for the costimulatory signal on antigen-presenting cells. The risk of disseminated histoplasmosis for patients on abatacept is not known. We report a case of abatacept-associated disseminated histoplasmosis and review the known infectious complications of abatacept. While the safety of resuming biologic agents following treatment for disseminated histoplasmosis is also not known, abatacept is recommended over TNFα inhibitors for rheumatoid arthritis patients with a prior serious infection. We discuss the evidence supporting this recommendation and discuss alternative treatments for rheumatoid arthritis patients with a history of a serious infection.

Soft tissue tumors of the sinonasal tract.

Primary soft tissue tumors arising in the sinonasal tract are rare. While many mesenchymal neoplasms have been reported in the nasal cavity, sinuses, and nasopharynx, few are distinctive to this anatomic region. Some tumor types are relatively more common in this area, such as schwannoma and rhabdomyosarcoma. Nasopharyngeal angiofibroma and sinonasal hemangiopericytoma are unique entities of the sinonasal tract, as well as the recently characterized biphenotypic sinonasal sarcoma. This review discusses the clinical, morphologic, and immunohistochemical features and currently known molecular data of the more frequently encountered soft tissue tumors of the sinonasal tract.

Null-Cell Ectopic Pituitary Adenoma of the Nasal Cavity.

An ectopic pituitary adenoma (EPA) is an uncommon type of pituitary adenoma, accounting for only 2% of all pituitary adenomas. EPAs are benign tumors that can occur anywhere along the migratory embryonic path of the pituitary gland and have no relationship to intrasellar elements. They are usually hormonally active and have a minor female predominance. The clinical features of EPAs are highly dependent on its hormonal activity, anatomical location, and its local mass effect. Appropriate radiological imaging is essential for the evaluation of EPAs. Imaging investigations show a normal pituitary gland and sellar turcica, provide details on the size of the tumor, its margins, and extent, and help with surgical planning. The criteria for diagnosing an ectopic pituitary adenoma depend on detailed histopathological examination. EPA management should be individualized. We present a case of a 71-year-old male who presented with a 9-month history of left nasal obstruction, purulent nasal discharge, and intermittent anterior epistaxis. The patient was being managed by his general practitioner for chronic rhinosinusitis but failure of his symptoms to resolve prompted a visit to the otorhinolaryngologist. The patient was diagnosed with a null-cell ectopic pituitary adenoma through histological analysis of a biopsy specimen that showed adenohypophyseal cells without cell-type-specific differentiation. The patient subsequently underwent an endoscopic endonasal excision and had an uneventful hospital stay.

Laparoscopic adrenalectomy for a giant adrenal teratoma: A case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Teratomas typically are benign gonadal neoplasms, arising from more than one embryonic germ layer. Extragonadal teratomas are rare and primary adrenal teratomas more so, with few documented cases. We present one such case, diagnosed via CT, resected via laparoscopic adrenalectomy, and confirmed on histology. To the best of our knowledge, this is the first case documented in the Caribbean. CASE PRESENTATION: A 38-year-old obese female with restrictive lung disease presented with right back/flank pain due to a non-functional 10.5 cm right adrenal mass on CT, likely a giant myelolipoma. Further radiologic review suggested this was instead a mature adrenal teratoma. She underwent a laparoscopic adrenalectomy and histology confirmed a mature adrenal teratoma. CLINICAL DISCUSSION: Most adrenal tumours are incidentalomas and are usually benign adenomas. Primary adrenal teratomas account for 1 % of teratomas and 0.13 % of adrenal tumours. They may be mature or immature; the latter carries a greater risk of malignancy. Benign adrenal teratomas are typically non-functional and commonly mistaken for myelolipomas on imaging. Adrenalectomy is required due to the risk of malignant transformation. The laparoscopic approach depends on size, localized tissue invasion and technical considerations, but offers advantages for the patient if possible. CONCLUSIONS: Though uncommon, preoperative radiologic diagnosis of an adrenal teratoma is possible and should be completely resected after a functional workup. A laparoscopic adrenalectomy is preferred once this can be done safely, even when very large, with surgical and oncologic outcomes equivalent to an open approach combined with the known advantages of laparoscopic surgery.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Pathology of the liver in copper overload.

Copper accumulation in the liver is associated with cellular and apoptotic injury. Wilson disease is the most well-characterized disorder of disordered copper metabolism. Other less-common disorders include Indian childhood cirrhosis, endemic Tyrolean infantile cirrhosis, and idiopathic copper toxicosis. The histopathologic spectrum of the liver in Wilson disease is extremely variable and overlaps among the different entities, though this review will focus on the pathology of Wilson disease. The findings lack specificity, although characteristic findings are observed. Unlike other disorders of copper overload, the pathologic changes are typically sequential, ranging from little or no significant findings to cirrhosis with or without widespread hepatocellular damage. Steatosis and glycogenated nuclei are frequent. Staining of copper is an unreliable method of diagnosis of Wilson disease, whether there are minimal histologic abnormalities or chronic liver disease. Copper and copper-associated protein accumulation may also be seen in chronic biliary obstructive processes.

Highlights and Perspectives From a Collaborative Global Health Pathology Experience in Trinidad and Tobago.

OBJECTIVES: Global health education is important during residency training in exposing doctors to conditions that are not common in the United States and developing their awareness of global health care disparities. Most medical decisions are based on results from anatomic or clinical pathology laboratories, which are essential services for appropriate medical care in international settings. Nevertheless, US pathology residency trainees have limited global health exposure and thus are rarely exposed to diagnostic services in these settings. Moreover, literature documenting what is needed to create a global health elective in pathology is limited. METHODS: We designed an international pathology elective in Trinidad and Tobago involving one main public hospital site and several off-site laboratories. Objectives and goals were established before the rotation. Apart from daily mentor-led education sessions, the trainee participated in teaching, quality improvement projects, and cultural experiences. Engagement with medical officers, personnel staff, and people in the community was encouraged.Results: Challenges encountered included funding, transportation, limited laboratory resources, medical registration, and malpractice insurance. These were mitigated through carefully planned steps, including communicating with registration bodies and liaising with pathology organizations for funding. CONCLUSIONS: Overall, the global health rotation was successful. We provide a detailed roadmap for other pathology training programs interested in establishing similar global health electives.

Global Pathology Training in Residency and Fellowship: A Mutually Beneficial Intervention.

CONTEXT.­: Most cancers occur in lower and middle income countries, where pathologists are scarce. Despite this, few pathology training programs offer global health electives, and trainees are not exposed to challenges associated with practicing in resource-restricted settings. OBJECTIVE.­: To implement a global health elective model aimed at exposing trainees to global health while alleviating overburdened pathologists in resource-restricted settings. DESIGN.­: For 1 year, trainees at 2 US institutions reviewed cases shipped weekly from a pathology lab serving Trinidad and Tobago and Guyana. Turnaround time, specimen type, and trainee and clinician satisfaction were assessed. RESULTS.­: Trainees reviewed an average of 16 cases per week. Average turnaround time was 6 days. There was no significant difference between the turnaround time for the US trainees and the pathologist based in the lab in Trinidad. Trainees and clinicians reported a high level of satisfaction, and the collaboration was fruitful, resulting in the publication of a case report. CONCLUSIONS.­: We demonstrate that collaboration between US trainees and laboratories in resource-restricted settings, in the form of a global health elective, is mutually beneficial.

Interobserver agreement and the impact of mentorship on the diagnosis of inflammatory bowel disease-associated dysplasia among subspecialist gastrointestinal pathologists.

The diagnosis of inflammatory bowel disease (IBD)-associated dysplasia is challenging, and past studies have demonstrated considerable interobserver variability in such diagnoses. This study aimed to assess interobserver agreement in IBD dysplasia diagnoses among subspecialty GI pathologists and to explore the impact of mentorship on diagnostic variability. Twelve GI pathologist mentees and 7 GI pathologist mentors reviewed 163 digitized slides. Participants rendered a diagnosis of negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, or high-grade dysplasia and provided a confidence level for each case. Interobserver agreement and reliability were assessed using Cohen's and Fleiss' kappa (κ) statistics and intraclass correlation coefficient (ICC) analysis. The overall κ coefficient was 0.42 (95% CI: 0.38-0.46). The overall ICC was 0.67 (95% CI: 0.62-0.72). Κ coefficients ranged from 0.31 to 0.49 for mentor/mentee pairs and from 0.34 to 0.55 for pairs of mentees of the same mentor. The combined κ coefficient was 0.44 (95% CI: 0.39-0.48) for all mentees and 0.39 (95% CI: 0.34-0.43) for all mentors. Common features in low agreement cases included mucosal atrophy, areas of stark contrast, serrations, decreased goblet cells, absent surface epithelium, and poor orientation. Participants were confident in most diagnoses, and increased confidence levels generally correlated with higher interobserver agreement. Interobserver agreement among subspecialist GI pathologists in this curated cohort of IBD dysplasia cases was fair to moderate. Mentorship during GI pathology fellowship does not appear to be a significant factor contributing to interobserver variability, but increased experience also does not seem to improve interobserver agreement.

Dietary Fructose Alters the Composition, Localization, and Metabolism of Gut Microbiota in Association With Worsening Colitis.

BACKGROUND & AIMS: The incidence of inflammatory bowel diseases has increased over the last half century, suggesting a role for dietary factors. Fructose consumption has increased in recent years. Recently, a high fructose diet (HFrD) was shown to enhance dextran sodium sulfate (DSS)-induced colitis in mice. The primary objectives of the current study were to elucidate the mechanism(s) underlying the pro-colitic effects of dietary fructose and to determine whether this effect occurs in both microbially driven and genetic models of colitis. METHODS: Antibiotics and germ-free mice were used to determine the relevance of microbes for HFrD-induced worsening of colitis. Mucus thickness and quality were determined by histologic analyses. 16S rRNA profiling, in situ hybridization, metatranscriptomic analyses, and fecal metabolomics were used to determine microbial composition, spatial distribution, and metabolism. The significance of HFrD on pathogen and genetic-driven models of colitis was determined by using Citrobacter rodentium infection and Il10-/- mice, respectively. RESULTS: Reducing or eliminating bacteria attenuated HFrD-mediated worsening of DSS-induced colitis. HFrD feeding enhanced access of gut luminal microbes to the colonic mucosa by reducing thickness and altering the quality of colonic mucus. Feeding a HFrD also altered gut microbial populations and metabolism including reduced protective commensal and bile salt hydrolase-expressing microbes and increased luminal conjugated bile acids. Administration of conjugated bile acids to mice worsened DSS-induced colitis. The HFrD also worsened colitis in Il10-/- mice and mice infected with C rodentium. CONCLUSIONS: Excess dietary fructose consumption has a pro-colitic effect that can be explained by changes in the composition, distribution, and metabolic function of resident enteric microbiota.

Histology of Colorectal Carcinoma: Proven and Purported Prognostic Factors.

Although tumor stage has a profound influence on prognosis, several histologic features are also important. These parameters predict biological behavior and can be used by clinicians to determine whether patients are at high risk for disease progression and, thus, are candidates for adjuvant therapy, particularly when they have localized (ie, stage II) disease. This article summarizes the evidence supporting the prognostic values of various histologic parameters evaluated by pathologists who assign pathologic stage to colorectal cancers. Criteria to be discussed include histologic subtype, tumor grade, lymphatic and perineural invasion, tumor budding, and host immune responses.