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
Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN.The American journal of surgical pathology (Impact Factor: 5.15). 12/2012; 37(4). DOI: 10.1097/PAS.0b013e318272c62a
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 efficacy of hematopoietic stem cell transplantation (HSCT) is greatly hampered by graft-versus-host disease (GVHD) and opportunistic infection; the gastrointestinal tract is one of the main target organs involved by GVHD and opportunistic infectious agents. The presence of crypt apoptosis is the major criterion for the histologic diagnosis of GVHD; however, it can also be seen in infection, especially cytomegalovirus (CMV) colitis. Therefore, the definitive histopathologic diagnosis of GVHD in gastrointestinal tract can be challenging or impossible without reliable ancillary markers. We studied the expression of CD123 and C4d in 38 colonic biopsies from patients with HSCT with acute GVHD and 14 colon biopsies from patients with CMV colitis without history of HSCT. CD123 expression was significantly increased in the acute GVHD group compared with the CMV group (65.8% versus 14.3%; P < .05) with increasing sensitivity in higher-grade GVHD (grades 1-2, 60%; grades 3-4, 72.2%). However, there was no significant difference in C4d deposition between the acute GVHD and CMV groups (68.4% versus 42.9%; P > .05). We further applied CD123 immunostaining to upper gastrointestinal (n = 23) and colonic biopsies (n = 24) in patients with HSCT without evidence of acute GVHD or infection and 11 biopsies from patients who had used mycophenolate. The negative staining of CD123 in all these cases further supports the specificity of CD123 in acute GVHD. In summary, CD123 might be a useful ancillary marker to aid in separating infection from GVHD in patients with HSCT.Human pathology 06/2013; 44(10). DOI:10.1016/j.humpath.2013.02.023 · 2.77 Impact Factor
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ABSTRACT: The last 5 years have seen an expansion of knowledge about the gastrointestinal diseases that may present in haematopoietic stem cell transplant (HSCT) patients and also about new gastrointestinal diseases in this patient population. This article summarizes the recent opinions and findings regarding gastrointestinal graft-versus-host disease, and viral and other opportunistic gastrointestinal infections that can develop in HSCT patients. This article also discusses the more newly described entities of mycophenolate-mofetil-related gastrointestinal injury and cord colitis syndrome. This review emphasizes the need for comprehensive clinical information when assessing gastrointestinal endoscopic biopsies from HSCT patients. It is crucial that both clinicians and histopathologists are aware of several specific but rare gastrointestinal diseases that may develop in these patients, because several of these diseases have specific treatments.Current opinion in supportive and palliative care 04/2014; 8(2). DOI:10.1097/SPC.0000000000000051 · 1.66 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 · 3.23 Impact Factor
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