Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation

Abstract

Background: Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM.

Methods: This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated.

Results: The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52-247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%.

Conclusions: This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features.

Keywords: Colonoscopy; Esophagogastroduodenoscopy; Graft-versus-host disease; Hematopoietic stem cell transplantation; Intestinal transplant-associated microangiopathy; iTAM.

Fig. 1

Pathological images. Endoscopic biopsy specimens obtained from the colorectum of a 16-year-old boy exhibit endothelial cell swelling (A, arrows). An intraluminal thrombus is focally present (B, arrow). The colorectal and ileal mucosa of a 65-year-old woman displays glandular epithelial apoptosis (C, arrows), while the presence of inflammatory cell infiltration in the interstitium is sparse. Intestinal GVHD is characterized by extensive, diffuse lymphocyte infiltration within the mucosa (D) and the infiltration of CD8 + T lymphocytes into the epithelium (E). Gastrointestinal infection with cytomegalovirus was diagnosed based on positive immunostaining for cytomegalovirus (F). The pathological images in D and E, and F are presented as representative examples of intestinal GVHD and CMV infection, not the target patients of this study

Fig. 2

Color charts showing correlation between endoscopic features and affected gastrointestinal segments. E: esophagus; S: stomach; D: duodenum; I: ileum; Ce: cecum; Co: colon; R: rectum; CMV: cytomegalovirus enterocolitis; GVHD: graft-versus-host disease

Fig. 3

Representative endoscopic images of Cases 1 and 2. A 56-year-old man with intestinal transplant-associated microangiopathy (Case 1), showing erosions observed in the ileum (A). A 61-year-old woman (Case 2) demonstrates multiple erosions and villous atrophy in the duodenum (B and C; C, after indigo carmine spraying). The cecum, colon (D and E; E, after indigo carmine spraying), and rectum (F) display multiple erosions and erythematous mucosa. Indigo carmine spraying highlighted the presence of shallow erosions

Fig. 4

Representative endoscopic images of Cases 3 and 4. Diffuse redness and granular mucosa with erosions are observed in the stomach (A and B; B, after indigo carmine spraying) of a 16-year-old male patient (Case 3). In the ileum, erythematous and edematous mucosa with erosions is observed (C). A hemorrhagic ulcer is visible in the ileum (D) of a 58-year-old male patient (Case 4). The vascular pattern is partially indiscernible in the cecum and colon, and the mucosa exhibits a granular appearance (E and F; F, narrow-band imaging)

Fig. 5

Representative endoscopic images of Cases 7 and 8. A 61-year-old male patient (Case 7) presents with esophageal ulcers (A), along with granular mucosa (B), erosions, and spontaneous hemorrhages in the stomach (C). A 20-year-old female patient (Case 8) displays multiple round erosions in the ileum, cecum, and colon (D–F; F, narrow-band imaging)