Terminal ileum is the most sensitive site for the histologic diagnosis of grade 4 graft-versus-host disease (GvHD) in the lower GI tract and is a harbinger of poor outcome.

The site of the gastrointestinal (GI) tract where biopsies are most likely to be diagnostic of graft-versus-host disease (GvHD) remains controversial. Recent reports have indicated that biopsies from the rectosigmoid have sufficient sensitivity and specificity for diagnosing GI GvHD and can be obtained via a less invasive flexible sigmoidoscopy procedure. While GvHD histologic grades 1-3 have little correlation with patients' symptoms and overall clinical grade, histologic grade 4 GvHD does correlate with severe clinical presentation and a poor prognosis. We examined cases of lower GI biopsies obtained via a complete colonoscopy with ileal intubation for the evaluation of GvHD within a 2-year period from patients who underwent stem cell transplantation. In our study cohort, grade 4 GvHD was significantly more likely to be identified in a terminal ileum biopsy than in a biopsy from another site in the lower GI tract. Significantly, 5 of 6 patients with histologic grade 4 GvHD diagnosed on ileal biopsies died from complication of severe GI GvHD. Given the poor prognosis of histologic grade 4 GvHD in the terminal ileum, the detection of this finding may serve to inform clinicians that escalation or modification of treatment may need to be considered. Furthermore, our findings suggest that terminal ileal biopsies may help to increase sensitivity for identifying patients at high risk for poor outcome of GvHD.

Topography, morphology, and etiology of lymphocytic gastritis: a single institution experience.

Lymphocytic gastritis (LG) is an uncommon reaction pattern of gastric injury characterized by intraepithelial lymphocytosis of the surface foveolar epithelium and chronic inflammation in the lamina propria. It most commonly occurs in association with gluten-sensitive enteropathy, Helicobacter pylori gastritis, non-steroidal anti-inflammatory drugs, and microscopic colitis. While the topography of LG has been described in gluten-sensitive enteropathy and H. pylori infection, no definite morphologic features have been used to further subcategorize LG based on possible etiologies. Furthermore, new immunotherapy agents have been associated with lymphocytic infiltrate in the gastrointestinal tract, but their association with LG has not been reported. Cases of LG were collected from our institution in the period between August 2011 and September 2017. The topography of LG and morphologic features such as glandular microabscesses, intestinal metaplasia, lymphoid aggregates, surface vs pit distribution of lymphocytes, and number of intraepithelial lymphocytes per 100 epithelial cells were assessed for each case using the updated Sydney System where applicable. Twenty-seven cases of LG were identified in the recent 6-year period at our institution. Gluten-sensitive enteropathy is the main reported cause of LG followed by NSAID injury. Cases of LG associated with gluten-sensitive enteropathy are antral predominant, those associated with H. pylori are body predominant, and those occurring in the setting of NSAID injury show pangastritis. Glandular microabscesses are observed in all cases of LG associated with H. pylori, and not in the setting of GSE or NSAID injury. In addition, a case of LG associated with melanoma immunotherapy has been identified. Topography and morphology of lymphocytic gastritis may point to the cause of injury, allowing for proper treatment of the underlying disease.

Lymphocytic gastritis induced by pembrolizumab in a patient with metastatic melanoma.

Immune checkpoint inhibitors such as programmed cell death-1 inhibitor pembrolizumab have been shown to be effective in metastatic malignancies such as advanced melanoma. Immune-related adverse effects on multiple organs have been described, such as colitis, skin rash, and hypothyroidism. We present the case of a 44-year-old man with advanced melanoma and recurrent lung metastases who developed symptoms of dyspepsia and gastroesophageal reflux disease after 1 month of therapy with pembrolizumab. Gastric biopsy showed histologic features consistent with lymphocytic gastritis, which was absent on a biopsy 2 months before initiation of therapy. Lymphocytic infiltrates likely secondary to increased autoimmunity after use of immunotherapy have been observed in the colon; however, such histologic findings in the upper gastrointestinal tract have yet to be described. Here, we present a case of lymphocytic gastritis in a patient treated with pembrolizumab, suggesting a new manifestation of toxicity.