Autopsies remain important in determining an accurate cause of death and for improved understanding of diagnostic deficiencies, as well as for medical education and quality assurance. Keywords:Acute Myeloid Leukemia, Hematopoietic Stem Cell Transplantation, Invasive Candidiasis, Immune Reconstitution Inflammatory Syndrome, Invasive Pulmonary Aspergillosis == Introduction == Infectious and noninfectious pulmonary complications occur in 3060% of patients with hematological malignancy and recipients of hematopoietic stem cell transplantation (HSCT) and are associated with significant morbidity and mortality [1]. [1]. In allogeneic HSCT patients who develop respiratory failure requiring mechanical ventilation, the intensive care unit (ICU) and hospital mortality rates often exceed 80% and 85%, respectively [25]. The factors that contribute to the development of pulmonary complications in these patients include immunologic defects due to the underlying disease and its treatment, conditioning regimens, development of graft-versus-host disease (GVHD), and the type of HSCT [2,6,7]. The spectrum of pulmonary complications in patients with hematological malignancy and HSCT recipients is usually changing because of recent improvements in antineoplastic therapies, such as the use of monoclonal antibodies and other targeted brokers, increased application of HSCT for older patients, widespread use of prophylactic antibiotics and novel antimicrobial brokers, and improvements in supportive care [8]. Prompt investigation and diagnosis of pulmonary complications in patients with hematological malignancies are essential to improving individual survival. Unfortunately, despite the technological improvements in diagnostic screening and imaging modalities, obtaining an accurate clinical diagnosis in these patients remains hard and at times is made only at the time of the postmortem autopsy examination. Autopsy rates in cancer patients are much lower (1334%) as compared to general medical and surgical patients (5364%) [79]. This probably displays the unwillingness on the part of physicians and family members SDZ 205-557 HCl to subject the cancer patient to the same level of scrutiny applied to other major illnesses in determining the primary and contributory causes of death [9]. Additional concerns include legal issues regarding exposition of physicians errors and non-reimbursement for postmortem examinations [10]. This chapter will review the infectious and noninfectious pulmonary findings that have been explained at autopsy in patients with hematological malignancies, including blood and bone marrow transplant recipients. In addition, we discuss the frequently noted diagnostic discrepancies between premortem clinical diagnoses and postmortem autopsy findings in these patients. TCL1B Finally, we spotlight the difficulties in diagnosing many of these conditions antemortem and emphasize the important role of the postmortem examination in accurately establishing the cause of death. Table20.1lists the infectious and non-infectious pulmonary disorders reported in autopsy studies of patients with hematologic malignancy, including HSCT recipients. == Table 20.1. == Pulmonary findings on postmortem studies in patients SDZ 205-557 HCl with hematologic malignancy including HSCT recipients Fungal Invasive pulmonary aspergillosis Candida bronchopneumonia Zygomycetes Trichosporonspp. Fusariumspp. Chaetomiumspp. Pneumocystis jirovecipneumonia Diffuse alveolar damage Diffuse alveolar hemorrhage Lymphoma/leukemia Pulmonary thromboembolism Bronchiolitis obliterans organizing pneumonia Bronchiolitis obliterans Pulmonary veno-occlusive disease Pulmonary alveolar proteinosis Bacterial Vancomycin-resistant enterococci Legionellaspp. Stenotrophomonas maltophilia Staphylococcus epidermidis Staphylococcus aureus Streptococcus pneumoniae Pseudomonas aeruginosa Serratiaspp. Other gram-negative bacilli and streptococcus spp. Viral Cytomegalovirus Herpes simplex virus Respiratory syncytial computer virus Measles computer virus Parasitic Toxoplasmosis == Infectious Findings == == Invasive Fungal Infections == The incidence of invasive fungal infections in patients with hematologic malignancies has increased steadily over the past three decades [11]. This has been attributed to improvements in the prevention or preemptive treatment of bacterial infections and other opportunistic SDZ 205-557 HCl pathogens, particularlyCandidaand cytomegalovirus; increased administration of chemotherapies with profound and continuous immunosuppressive effects on T-cell function (e.g., purine nucleoside analogs, anti-T-cell immunoglobulin, and SDZ 205-557 HCl monoclonal antibodies); and the growing quantity of allogeneic and nonmyeloablative SDZ 205-557 HCl transplantation procedures that carry a higher risk for chronic GVHD [12]. Patients with hematologic malignancies, especially in the neutropenic state after aggressive chemotherapy or HSCT and HSCT recipients with GVHD, are particularly susceptible to invasive fungal infections [13]. Approximately 2050% of patients with hematological malignancies and HSCT recipients have evidence of invasive fungal infections at autopsy [8]. These include invasive aspergillosis and fungal infections due toCandidaspp.,Zygomycetesspp., Trichosporonspp.,Fusariumspp., and variousChaetomiumspecies. In neutropenic patients with acute leukemia, the histopathological pattern of invasive pulmonary aspergillosis (IPA) is usually characterized by scant inflammation, hyphal angioinvasion with a high fungal burden, and considerable coagulative necrosis [12,14]. In contrast, among HSCT recipients with GVHD, the histopathological findings consist of severe lung inflammation and less abundantAspergillusburden. Several autopsy studies in HSCT recipients have shown that IPA is frequently not diagnosed antemortem or prolonged despite diagnosis by sputum or bronchoalveolar lavage (BAL) cultures or by serum galactomannan assay and treatment with amphotericin B [8,1521]. In recent years, treatment of IPA with voriconazole has led to better responses, improved survival rates, and fewer side effects than amphotericin B [22]. Autopsy studies have assisted in describing and confirming the immune reconstitution inflammatory syndrome (IRIS) in patients with IPA who are recovering from the neutropenia [23]. When clinical and radiologic worsening coincides with neutrophil.