Immunophenotyping of intraepithelial lymphocytes in canine chronic enteropathy and intestinal T-cell lymphoma using endoscopic samples

Human enteropathy-associated T-cell lymphoma (EATL) is considered to be derived from intraepithelial lymphocytes (IELs); however, the origin of canine intestinal T-cell lymphoma (ITCL) remains unclear. Histological, immunohistochemical, and clonality examinations were performed using endoscopically collected canine duodenum samples of mucosal lesions of chronic enteropathy (CE; 73 cases) and ITCL without transmural neoplastic mass lesions (64 cases). Histopathological examinations revealed the intraepithelial accumulation of lymphocytes (called “intraepithelial lymphocytosis”) in 54/73 CE cases (74%) and the epitheliotropism of neoplastic lymphocytes in 63/64 ITCL cases (98%). Immunohistochemically, IELs in CE with intraepithelial lymphocytosis (IEL+CE) were diffusely immunopositive for CD3, with scattered immunopositivity for CD5, CD8, CD20, and granzyme B (GRB). The percentage of CD8+ in CD3+ IELs was significantly lower in IEL+CE than in CE without intraepithelial lymphocytosis (IEL−CE). Double-labeling immunohistochemistry revealed a high percentage of GRB expression in CD8− IEL among IEL+CE. Among 64 ITCL cases, CD3 was immunopositive in 64 (100%), CD5 in 22 (34%), CD8 in 8 (13%), CD20 in 12 (19%), CD30 in 13 (20%), and GRB in 49 (77%). In CD3+ cells, Ki67 immunopositivity was highest in ITCL, intermediate in IEL+CE, and lower in IEL−CE. A clonal TCR gene rearrangement was detected in 1/19 IEL−CE cases (5%), 15/54 IEL+CE (28%), and 38/58 ITCL (66%). These results indicate that the immunophenotype of canine ITCL (CD8−GRB+) is similar to that of the increased IELs in CE. The high proliferative activity and clonality of T cells in IEL+CE suggest that canine ITCL originates from these IELs, similar to human EATL.

Giardia Is Often Overlooked on Histopathologic Examination: A High-Volume, Single-Institution Experience

Aims. Giardia is sometimes missed by the pathologist, and we sought to determine how often this occurs at our institution—a large tertiary care center with a subspecialty gastrointestinal pathology service and what certain clinical and histologic clues can be used to flag cases with a higher likelihood of infection, targeting them for greater scrutiny. Methods and Results We identified a set of patients who tested positive for Giardia with a stool-based test, and who also received a small bowel biopsy at a similar time-point. These biopsies were retrospectively reviewed for Giardia, finding 8 positive cases. The organism was prospectively detected in 4 cases (50%) but overlooked in the remaining 4 cases (50%). Three of the 4 cases missed cases showed only rare organisms. The detected cases tended to more frequently have prominent lymphoid aggregates (3 detected cases, 0 overlooked cases) and intraepithelial lymphocytosis (3 detected cases, 0 overlooked cases). Certain clinical and histologic clues can be used to flag cases with a higher likelihood of infection. Specifically, we found abnormalities of the mucosa (active inflammation, intraepithelial lymphocytosis, villous expansion, prominent lymphoid aggregates) in each case, and 4 of 8 cases were from immunocompromised patients. Finally, 2 of 8 cases were terminal ileum biopsies. Conclusions Biopsies with a histologic abnormality or those from immunocompromised patients should receive greater attention. Routinely looking for Giardia at that terminal ileum is necessary.

Common Etiologies and Clinical Significance of Gastric Intraepithelial Lymphocytosis

Background Increased intraepithelial lymphocytes or intraepithelial lymphocytosis (IEL) in the upper gastrointestinal (GI) tract is a response to various mucosal injury. However, the frequency of gastric IEL in GI tract biopsy is not well documented, and the etiologies of gastric IEL are yet to be defined. Methods Cases with a diagnosis of “intraepithelial lymphocytosis” and “intraepithelial lymphocytes” were retrieved from 25,074 GI biopsies and 8,921 partial gastrectomies in our departmental database (Powerpath) for a 1-year period. The diagnosis of IEL was confirmed by the report and/or slide review. Possible etiology or causes of gastric IEL were investigated by correlation with clinical information from LIS (EPIC). Results A total of 694 cases with IEL were identified from 33,995 GI tract specimens (biopsy and resection). Among 694 cases, 34 (4.89%) were gastric biopsy and resection cases with IEL, whereas 561 (80.8%), 37 (5.3%), and 62 (8.9%) were duodenal, esophageal, and colonic specimens, respectively. Thirty-four gastric cases with IEL were closely associated with morbid obesity (8, 23.5%), H pylori infection (8, 23.5%), celiac disease (5, 14.7%), lymphocytic gastritis (5, 14.7%), nonspecific gastritis (4, 11.4%), inflammatory bowel disease (3, 8.8%), and gastroesophageal reflux disease (1, 1.9%). Seventeen of 34 (50%) cases had IEL in both gastric and duodenal mucosa. Those 17 cases with gastroduodenal IEL had morbid obesity (n = 5), celiac disease (n = 5), lymphocytic colitis (n = 2), inflammatory bowel disease (n = 2), H pylori gastritis (n = 2), and nonspecific gastritis (n = 1). Five patients with a diagnosis of lymphocytic gastritis were treated with a protein pump inhibitor after pathologic diagnosis. Among them, 4 had a followed-up endoscopy in 12 months, and 3 of them showed persistent IEL in a follow-up biopsy. Conclusion Gastric IEL is less common than duodenal IEL. It is associated with a broad differential diagnosis. Follow-up biopsy may be necessary for some types of gastric IEL. Persistent IEL in follow-up biopsy may be suggestive of a different etiology or requires different treatment strategy.

Clinical and Histopathologic Predictors of Disaccharidase Deficiency in Duodenal Biopsy Specimens

Objectives Disaccharidase (DS) activity in duodenal biopsy specimens is the gold standard for diagnosing DS deficiency. We investigated strategies to reduce the need for DS testing and whether clinical or histopathologic factors predict DS deficiency. Methods A retrospective chart review analyzed 1,678 DS results in children, biopsy indication(s), and duodenal histopathology. Results One or more DSs were abnormal in 42.8%. Sufficient lactase predicted sucrase, palatinase, and maltase sufficiency (negative predictive value 97.7%). Three patients had sucrase-isomaltase deficiency (0.2%). DS deficiency was more common in biopsy specimens for positive celiac serology (78.0%). Villous blunting, intraepithelial lymphocytosis, and active inflammation predicted DS deficiency; a combination of any two had an 81.4% positive predictive value. Conclusions Utilization could be reduced by only testing cases with normal duodenal histopathology and ongoing clinical suspicion for DS deficiency after reviewing pathology. In cases with suspected celiac disease and/or mucosal injury, DS deficiency is common and likely secondary, limiting test utility.

Duodenal Bulb Histology in Paediatric Celiac Disease: A Case–Control Study

Background Controversy exists about optimal methods for duodenal biopsy in diagnosis of celiac disease (CD), in terms of both number of samples and anatomic location. The reliability of duodenal bulb biopsy has been questioned given that normal bulb architecture may mimic disease. However, multiple studies have reported patients with CD have histopathological lesions limited to proximal changes in the duodenal bulb alone. Methods We retrospectively compared duodenal and duodenal bulb histology in a population of paediatric patients with CD and compared with a population of nonceliac controls at Stollery Children’s Hospital, 2010 to 2012. Results Fifty-seven paediatric patients diagnosed with CD and 16 nonceliac controls were included in the study. Fifty-three celiac patients (93.0%) had histopathology consistent with CD (modified Marsh score of 3A, 3B or 3C) in the duodenal bulb. The modified Marsh classification differed significantly between duodenum and duodenal bulb in nine celiac patients (15.8%). Of these, five (8.8%) had Marsh 3 in the bulb and Marsh 0 in the distal duodenum. Among controls, no patients had villous atrophy in either the distal duodenum or duodenal bulb, and all patients had a modified Marsh score of 0 at both sites. Conclusions The results of this study reinforce that duodenal bulb samples are critically important for diagnosing CD in paediatric patients. We suggest that duodenal bulb samples be submitted in separate containers from distal duodenal samples to facilitate accurate interpretation. In contrast to prior reports, we found villous blunting and intraepithelial lymphocytosis are actually uncommon findings in paediatric patients with nonceliac gastrointestinal disorders.

Intraepithelial Lymphocytosis of the Resection Margin in the Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma

Background: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a disease involving the intestine and is often diagnosed in surgically resected specimens. The disease prognosis of MEITL is fatal because of rapid recurrence and leakage after excision. Recently, in microscopic finding of MEITL, intraepithelial lymphocytosis in mucosa that were grossly intact has been reported. In this study, we evaluated the intraepithelial lymphocytosis of the resection margin to determine the reason for the early recurrence or leakage in MEITL. Materials and Methods: We reviewed the medical records of all patients who were diagnosed with small intestine lymphoma from January 1995 to June 2018 at our medical center. We analyzed a tissue array from 8 patients diagnosed with MEITL. The expression of CD3, CD5, and CD8 were analyzed by immunohistochemistry. Results: A total of 8 cases of small intestine lymphoma were collected in this period. There were three men (37.5%) and five women (mean age 55 years). Two patients died without initiation of chemotherapy. Six patients received chemotherapy after resection of MEITL (4 patients received CHOP regimens, 2 patients received ProMACE-CyBOM regimens), but five patients died within 6 months (mean survival time 4.1 months, range 0.3-12.1 months). Only one patient survived for 5 years. On gross examination, the distance to the resection margin was 7.58 cm (3.8-14.0 cm) on average. Microscopic examination revealed intraepithelial lymphocytosis at least of one of the resected margins in all case. Immunohistochemical staining for CD3, CD5, and CD8 was performed on the resection margins. As a result, severe intraepithelial lymphocytosis accompanied by aberrant loss of CD5 was observed in 6 cases (75%). Conclusion: In the MEITL, an intraepithelial lymphocytosis accompanied by aberrant CD5 loss is frequently observed in the resection margin, even if the resection margin is grossly intact, and there is no clear microscopic involvement of the lymphoma especially on low power. This fact is thought to be related to the early recurrence or leakage of MEITL at the surgical site. Disclosures No relevant conflicts of interest to declare.