Is the Presence of 6 or Fewer Crypt Apoptotic Bodies Sufficient for Diagnosis of Graft Versus Host Disease? A Decade of Experience at a Single Institution.
ABSTRACT Histopathology assessment is crucial for the diagnosis of graft versus host disease (GVHD), as the presence of crypt apoptosis is the cardinal criterion required. However, crypt apoptosis is not limited to GVHD; it also occurs in other conditions such as infection, drug reaction, or inflammatory reactions unrelated to GVHD. To better determine whether the presence of 6 or fewer apoptotic bodies is sufficient for the diagnosis of GVHD, we retrospectively reviewed 78 colon biopsies from 66 patients who received either hematopoietic stem cell (HSCT) or cord blood cell transplantation and whose colon biopsies exhibited apoptotic bodies. Among them, 41 cases contained 6 or fewer apoptotic bodies in the colon biopsy. These biopsies were compared with 141 colon biopsy controls that showed no significant pathologic changes as well as 16 colon biopsies with cytomegalovirus colitis from patients without a history of bone marrow transplantation. Among the 41 cases reviewed, 7 patients had coexisting GVHD in other organs (skin or liver). However, gastrointestinal symptoms of at least 4 HSCT patients whose colon biopsies contained 6 or fewer apoptotic bodies completely resolved in the absence of further intervention for GVHD. The discrepancy between pathologic findings and the clinical course may be due to confounding factors, such as infection or medication-induced injury. Our data suggest that identifying 6 or fewer crypt apoptotic bodies in colon biopsies from HSCT patients is worth reporting in order to alert the clinicians of the possibility of GVHD but not sufficient to render a diagnosis on the pathologic grounds alone. The colon biopsies containing 6 or fewer apoptotic bodies represent a heterogenous group. We suggest this group to be classified as indeterminate for GVHD, instead of diagnosing GVHD outright. Synthesis of all clinical, endoscopic, and pathologic information, including the status of infection, coexisting GVHD involvement in the other organs, and medication, is essential for confirmation of the diagnosis of GVHD.
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ABSTRACT: The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in our study was to find out whether determination of the concentrations of these proteins may be used as a screening method for enteric GVHD. We studied prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that elevated fecal calprotectin levels were significantly associated with presence of GI-GVHD. We found a positive association between high F-calprotectin and severe gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1 antitrypsin was independently associated with GI-GVHD. Testing for fecal calprotectin after allogeneic stem cell transplantation may be a useful screening tool.Scientific Reports 01/2015; 5:7920. DOI:10.1038/srep07920 · 5.08 Impact Factor
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ABSTRACT: Hematopoietic stem cell transplantation (HCT), formerly known as bone marrow transplantation, is an integral part of treatment for many hematological malignancies. HCT is associated with several complications and comorbidities with differential effects on a wide spectrum of organs and tissues. We present an update on HCT-associated complications such as graft versus host disease (GVHD) and infection, with focus on the surgical pathology of the gastrointestinal (GI) tract, liver, and lung. Although the grading system for GI tract acute GVHD was proposed 40 years ago, recent studies have shed light on minimal histologic criteria for diagnosis of GVHD, as well as its differential diagnosis, including histologic effects of various medications. GI dysfunction in autologous transplant recipients is increasingly appreciated and patients are often biopsied. Acute liver injury in HCT is often due to sinusoidal obstruction syndrome (previously known as venoocclusive disease), or acute GVHD. Liver dysfunction at later time posttransplantation may be associated with acute or chronic GVHD, iron overload, or other causes of hepatitis. Lung injury in HCT is multifactorial, and it remains crucially important to diagnose and treat pulmonary infections. The pulmonary biopsy yields clinically unsuspected diagnoses in the majority of cases and its utilization is likely to increase. The pathology of the skin and kidney in HCT patients are detailed in accompanying articles.Advances in Anatomic Pathology 09/2014; 21(5):301-320. DOI:10.1097/PAP.0000000000000032 · 3.10 Impact Factor
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ABSTRACT: The assessment of gastrointestinal (GI) specimens from transplant patients is complicated by the wide range of, potentially rare, pathologies that may be found in this clinical setting. Acute GI graft versus host disease (GvHD) is characterised by epithelial cell apoptosis, although there is increasing recognition that acute and/or chronic inflammation may also be present. By contrast, there are thus far no histological features known to be specific to chronic GI GvHD. Mycophenolate mofetil colitis may mimic both GvHD and inflammatory bowel disease, whereas both CMV and adenovirus infections can cause gland apoptosis. Post-transplant lymphoproliferative disorder should be considered if a Crohn's like histological picture is seen, and granulomas in biopsies from umbilical cord blood recipients should raise a suspicion of cord colitis syndrome. Finally, the GI tract may be involved directly or indirectly by the disease that originally required haematopoietic stem cell or liver transplantation. This article is protected by copyright. All rights reserved.Histopathology 09/2014; 66(4). DOI:10.1111/his.12542 · 3.30 Impact Factor