Deniz L. Aslan

Pulmonary Complications After Bone Marrow Transplantation An Autopsy Study From a Large Transplantation Center

CONTEXT Bone marrow transplantation (BMT) is used to treat various malignant and nonmalignant disorders. Pulmonary complications are some of the most common causes of mortality in BMT recipients. Poor general health and bleeding tendency frequently preclude the use of definitive diagnostic tests, such as open lung biopsy, in these patients. OBJECTIVE To identify pulmonary complications after BMT and their role as the cause of death (COD). DESIGN The autopsy and bronchoalveolar lavage (BAL) slides and microbiology studies of BMT recipients from a 7-year period were reviewed. RESULTS Pulmonary complications were identified in 40 (80%) of the 50 cases. The most common complications were diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH). Pulmonary complications were the sole or 1 of multiple CODs in 37 cases (74%). All complications were more common in allogeneic BMT recipients. In 19 (51%) of the 37 cases in which pulmonary complications contributed to the death, cultures were negative. Both DAD and DAH, complications commonly reported in the early post-BMT period, were seen more than 100 days after BMT in 33% and 12% of cases, respectively. Five (83%) of 6 cases of invasive pulmonary aspergillosis diagnosed at autopsy were negative for fungi ante mortem (by BAL and cultures). CONCLUSIONS Pulmonary complications are a significant COD in BMT recipients, many of which, especially the fungal infections, are difficult to diagnose ante mortem. The etiology of DAD and DAH is likely to be multifactorial, and these complications are not limited to the early posttransplantation period. Autopsy examination is important in determining the COD in BMT recipients.

Ki-67 Immunoreactivity in the Differential Diagnosis of Pulmonary Neuroendocrine Neoplasms in Specimens With Extensive Crush Artifact

The aim of the present study was to evaluate the usefulness of immunohistochemical markers in the differential diagnosis of pulmonary neuroendocrine tumors with particular emphasis on the preservation of immunoreactivity in areas showing crush artifacts. Specimens from 9 carcinoid tumors (CTs) and 13 small cell carcinomas (SCCs) with crush artifact were stained with antibodies to Ki-67, chromogranin A, synaptophysin, and cytokeratin. The immunoreactivity was well preserved in the crushed areas. Ki-67 was expressed in the crushed areas of all SCCs. Reactivity was diffuse or at least present in 25% of the crushed areas. In contrast, the immunoreactive areas in CTs never exceeded 10%. Immunoreactivity for Ki-67, synaptophysin, chromogranin A, and cytokeratin is well preserved in tissue with crush artifacts and can be interpreted reliably. The diagnosis of SCC should be questioned if fewer than 25% of cells show reactivity for Ki-67.

Use of brain natriuretic peptide to evaluate transfusion-related acute lung injury.

Graft-versus-hose disease (GVHD) and infections are the major complications of allogeneic peripheral blood progenitor cell (PBPC) transplantation. Isolated acute hepatic GVHD is an uncommon complication that is difficult to distinguish from hepatic failure owing to therapy-related toxicity, infections, or veno-occlusive disease. 1 Liver biopsy is diagnostic, characterized by a lymphocytic infiltrate localized mainly in the portal tract. 2 The clinical severity of it is monitored by measuring serum bilirubin, aminotransferases, and alkaline phosphatase. If standard immunosuppressive medications (corticosteroids, cyclosporine, antithymocyte globulin, micofenolate, and tacrolimus) fail to control acute hepatic GVHD, the disease may progress to fatal hepatic failure. Extracorporeal photochemotherapy (ECP) is a therapeutic alternative for patients who do not respond to immunosuppressive medications. 3,4 We report our experience using ECP for acute hepatic GVHD in a 2-year-old girl after two consecutive PBPC transplants for hemophagocytic lymphohistiocytosis (HLH or Griscelli syndrome), a rare autosomal recessive disorder characterized by lymphocytic and macrophage activation, skin and hair pigment dilution, and dysregulation of the immune system. The only curative treatment for HLH is progenitor cell transplantation. 5

Early-onset autoimmune hemolytic anemia after cladribine therapy for Waldenström's macroglobulinemia

BACKGROUND: Purine nucleoside analogs are a class of antineoplastic drugs with potent lymphotoxicity against T and B lymphocytes, causing prolonged lymphopenia and linked to delayed immune complications such as opportunistic infections and more recently autoimmune hemolytic anemia (AIHA), seen mostly in patients with chronic lymphocytic leukemia (CLL). A characteristic temporal relation between fludarabine therapy and the appearance of a warm‐reactive immunoglobulin G (IgG)‐mediated AIHA in patients with CLL has been observed and, in some, the AIHA has been fatal. Whether both fludarabine and cladribine cause AIHA is uncertain because AIHA is commonly seen in patients with CLL without the use of these drugs. In contrast, AIHA is encountered in Waldenströms macroglobulinemia (WM) much less frequently, and the autoantibody is usually cold‐reactive and IgM‐mediated. In a few reported cases of AIHA arising in patients with WM after cladribine therapy, there was a latency of 24 to 60 months between therapy and the onset of AIHA, three of which were warm‐reactive and IgG‐mediated.

Prostatic glands and urothelial epithelium in a seminal vesicle cyst: report of a case and review of pathologic features and prostatic ectopy.

We report a case of a seminal vesicle cyst containing prostatic glands and urothelial epithelium in a patient with no other urogenital anomalies. The detection of prostatic tissue, which is of endodermal origin, in a seminal vesicle cyst, a mesonephric duct derivative, is unusual. We review the pathologic features of seminal vesicle cysts and discuss the histogenesis of prostatic and urothelial tissue.

c-kit EXPRESSION IN ADENOID CYSTIC CARCINOMA DOES NOT HAVE AN IMPACT ON LOCAL OR DISTANT TUMOR RECURRENCE

Adenoid cystic carcinoma (ACC) is a neoplasm with unpredictable behavior with frequent late relapses that lacks good prognostic indicators. c‐kit tyrosine kinase oncogene has recently been found to be expressed in ACC. The aim of this study is to correlate the expression of c‐kit in ACC with clinical follow‐up.

Ewing Sarcoma and Primitive Neuroectodermal Tumor of the Esophagus: Report of a Case and Review of Literature:

This study presents a case of Ewing sarcoma and primitive neuroectodermal tumor arising in the esophagus of a 44-year-old woman who presented with progressive dysphagia. Imaging studies demonstrated a polypoid lesion in the esophagus. The tumor was characterized by corded and pseudopapillary architecture, cytologic monotony, and low proliferative activity. Immunohistochemical stains were positive for CD99, neuron-specific enolase, vimentin, cyclin D1, p53, and FLI1 gene product. Fluorescence in situ hybridization demonstrated a 22q12 translocation, associated with primitive neuroectodermal tumor in the tumor cells, whereas reverse transcription polymerase chain reaction conformed expression of Ewing sarcoma/FLI1 fusion transcript in the patient’s bone marrow aspirate. Although this is a rare site for this type of tumor to occur, primitive neuroectodermal tumor should be considered in the differential diagnosis of mesenchymal tumors of the esophagus. Genetic analysis is crucial to establish the diagnosis and can be successfully performed on formalin-fixed, paraffin-embedded material and hematopoietic tissue.

Ischemia Modified Albumin Measured by the Albumin Cobalt Binding Test: A Clinical and Analytical Review

Eight million patients with chest pain present annually to emergency departments (ED).1 Five million of this group are judged to have suspected acute coronary syndromes (ACS) and are admitted to the hospital. Less than half ultimately are found to have a cardiac diagnosis, causing costly, unnecessary admissions. Three million of this group are discharged from the ED each year, and 40,000 of these are inadvertently discharged as myocardial infarctions (MI). Mortality rates of missed diagnoses in patients sent home are 2-fold greater than those patients admitted. Thus, there is a considerable amount of clinical interest and research to identify markers of myocardial ischemia that could be monitored during the early, reversible stage of ACS to assist in the appropriate triage of patients presenting with symptoms suggestive of ACS. CE update [chemistry | molecular diagnostics] Ischemia Modified Albumin Measured by the Albumin Cobalt Binding Test: A Clinical and Analytical Review

Accuracy of herpes simplex virus detection in liquid-based (SurePath) Papanicolaou tests: a comparison with polymerase chain reaction.

A review of our institutions Papanicolaou test records over an 11‐yr period showed that liquid‐based Papanicolaou tests (LBPTs) had a significantly higher frequency of diagnoses of Herpes simplex virus (HSV)‐related cellular changes compared to conventional Papanicolaou smears (77/302,841, 0.026% vs. 56/376,173, 0.015%, P = 0.002). To investigate the accuracy of the diagnosis of HSV by LBPT, we performed conventional polymerase chain reaction (PCR) on the residual samples from 258 prospectively collected LBPT and real‐time PCR using a different primer set on a subset of 40 LBPT. Conventional PCR was positive in 22 of 22 cases diagnosed of HSV, 1 of 2 cases diagnosed as suspicious for HSV, and none of 234 LBPT without a cytologic HSV diagnosis. Real‐time PCR was positive in 8 of 8 cases diagnosed as HSV and none of the 32 controls. We conclude that LBPT allows an increased detection of HSV that is highly accurate. Diagn. Cytopathol. 2008;36:94–103.

Parapharyngeal chordoma: A diagnostic challenge and potential mimic of pleomorphic adenoma on fine-needle aspiration cytology

Chordomas are rare tumors that are usually located in the sacrococcygeal and sphenooccipital region. Their cytologic diagnosis is rather straightforward when sampled by fine‐needle aspiration (FNA) from these characteristic locations, especially when physalipherous cells are present. However, chordomas may pose difficult diagnostic challenges when encountered in unusual locations, such as the parapharyngeal region. We report the cytologic findings of a recurrent chordoma sampled through transoral FNA from the parapharyngeal space of a 66‐year‐old woman. As the prior history of chordoma was not available during the rapid onsite evaluation, the presence of bland epithelioid nonvacuolated cells and spindle cells intimately admixed with a fibrillary, intensely metachromatic material led to an initial diagnosis of pleomorphic adenoma. Review of the patients prior pathology specimen and of the Papanicolaou‐stained smears and cellblock sections showing rare multivacuolated (physalipherous) cells led to the correct diagnosis, which was supported by immunoperoxidase stains (cytokeratin AE1/AE3+, S100+, GFAP−). A review of the literature found no previous instances in which chordomas mimicked pleomorphic adenoma on FNA. However, since the two tumors show significant cytomorphologic overlap, including the presence of abundant fibrillary matrix with embedded neoplastic cells and single bland spindle and epithelioid tumor cells with occasional intranuclear pseudoinclusions, we compared their cytologic features. A review of the FNA cytologic features of this case of chordoma and of 17 consecutive cases of pleomorphic adenoma found that the presence of a more abundant, focally vacuolated cytoplasm favors chordoma over pleomorphic adenoma. Diagn. Cytopathol. 2013.