Faculty Bibliography

BACKGROUND: The cytomorphology of anaplastic large cell lymphoma (ALCL) is distinctive yet variable. To the authors' knowledge, to date only small case series have described the cytologic findings noted in patients with ALCL. The current series is the largest case series presented to date to retrospectively review the cytomorpholgic findings noted in patients with ALCL, with specific attention paid to those with anaplastic lymphoma kinase (ALK)-negative ALCL. METHODS: Over a 13-year period, the available Diff-Quik cytology smears and surgical excision specimens taken from patients with ALCL were evaluated. Different clinical and morphologic parameters were evaluated, including ALK status. RESULTS: A total of 37 cases were retrieved and evaluated, 19 of which had both cytology and surgical pathology specimens available for review. ALK-negative ALCL cytology smears were found to have a high number of anaplastic cells compared with ALK-positive cases. The hallmark cells in the ALK-negative cases were not classic. CONCLUSIONS: ALCL can be diagnosed accurately by fine-needle aspiration cytology (FNAC) alone when aided by immunocytochemistry in ALK-positive cases. Ancillary studies should be anticipated such that material for cell block preparation and molecular studies is taken at the time of FNAC. The results of the current study demonstrate the varied FNAC morphology of ALCL. The presence of severe pleomorphism and anaplasia was found to correlate with ALK-negative status

Fine-needle aspiration cytology (FNAC) of the head and neck region is well accepted as a diagnostic procedure in the adult population. FNAC in the pediatric population is gaining acceptance as clinicians add this technique to the diagnostic armamentarium. An experience with FNAC of the head and neck region in the pediatric population is described from 2 large inner-city hospitals. Eighty-five cases were retrieved from patients age <18 years. In 52 cases, clinical or surgical follow-up was obtained and among these cases the specificity and sensitivity of FNA was 93% and 100%, respectively. The high specificity of FNAC allows the clinician to be confident of malignancy in a clinically suspicious lesion of the head and neck in a pediatric patient. Cancer (Cancer Cytopathol) 2007. (c) 2007 American Cancer Society.

The control of intracellular microorganisms such as mycobacteria is largely dependent on the adaptive immune response, specifically the interaction of T helper cells and antigen presenting cells such as macrophages. The interferon gamma (IFN-gamma) pathway activation is crucial for containment and killing of mycobacteria, as evidenced by the fact that defects in this pathway often result in profound infections with both tuberculous and non-tuberculous mycobacteria. We herein report a case of a child with autosomal recessive IFN-gamma receptor 2 (IFN-gammaR2) deficiency who developed hepatic venopathy secondary to disseminated Mycobacterium avium complex (MAC) infection.

BACKGROUND.: There is an unmet clinical need for economic, minimally invasive procedures that use a limited number of cells for the molecular profiling of tumors in individual patients. Reverse-phase protein microarray (RPPM) technology has been applied successfully to the quantitative analysis of breast, ovarian, prostate, and colorectal cancers using frozen surgical specimens. METHODS.: For this report, the authors investigated the novel use of RPPM technology for the analysis of both archival cytology aspirate smears and frozen fine-needle aspiration (FNA) samples. RPPMs were printed with 63 breast FNA samples that were obtained before, during, and after treatment from 21 patients who were enrolled in a Phase II trial of neoadjuvant capecitabine and docetaxel therapy for breast cancer. RESULTS.: Based on an MCF7 cell line model of breast adenocarcinoma, the sensitivity of the RPPM detection method was in the femtomolar range with a coefficient of variance <13.5% for the most dilute sample. Assay linearity was noted from 1.0 mug/muL to 7.8 ng/muL total protein/array spot (R(2) = 0.9887) for a membrane receptor protein (epidermal growth factor receptor; R(2) = 0.9935). CONCLUSIONS.: The results from this study indicated that low-abundance analytes and phosphorylated and nonphosphorylated proteins in specimens that consist of a few thousand cells obtained through FNA can be quantified with RPPM technology. The ability to monitor the in vivo state of cell-signaling proteins before and after treatment potentially will augment the ability to design individualized therapy regimens through the mapping of aberrant cell-signaling phenotypes. The mapping of these protein pathways will further the development of rational drug targets. Cancer (Cancer Cytopathol) 2007. Published 2007 by the American Cancer Society.

We describe the postmortem findings of a 47-year-old man with Fabry disease, an X-linked glycolipid storage disorder, who was on enzyme replacement therapy with recombinant alpha-galactosidase A for more than 2 years. The patient had widespread atherosclerotic coronary artery disease that culminated in a massive acute myocardial infarction. Atherosclerotic lesions were seen in the right and left coronary systems, aorta, and the basilar artery. Typical Fabry cardiomyopathy and glomerular nephropathy were found. With the exception of vascular endothelial cells, extensive glycolipid storage deposits were seen in all vascular and nonvascular cells and organ systems. We conclude that, at least in this patient, repeated infusions with alpha-galactosidase A over a prolonged period did not appreciably clear storage material in cells other than vascular endothelial cells. These findings also illustrate accelerated atherosclerosis in susceptible patients with Fabry disease

BACKGROUND: Simple, rapid tissue processing that preserves macromolecules will enhance translational research capabilities. Traditional fixative-based approaches for specimen preservation are ideal for histologic evaluation but are not conducive to molecular studies of nucleic acids and protein. Tissue cryosections preserve macromolecule integrity, but the process is labor intensive and technically challenging. To the authors' knowledge to date, an alternative method capable of retrieving cells while providing adequate histologic detail yet preserving macromolecule integrity has been lacking. In the current study, the authors evaluated the utility of using manual exfoliation of clinical tissue samples as a means of obtaining cells for molecular analysis. This technique possesses the advantages of fixed and frozen tissue sections without their drawbacks. This simple, rapid, nonfixative based technique is capable of preparing cells from human clinical material for further isolation without compromising the preservation of macromolecules in the tissue. METHODS: Cells from a variety of clinical resection specimens from solid tumors were directly scraped from the tissue samples using the edge of a glass microscope slide and smeared onto another slide for cytologic evaluation. The manually exfoliated cells were evaluated microscopically for cytologic quality and cellular quantity. Pure cell populations were procured by laser capture microdissection (LCM) with subsequent extraction of nucleic acids and proteins. The integrity and suitability of the recovered nucleic acids and proteins for molecular analysis were evaluated using the polymerase chain reaction (PCR), reverse transcriptase-PCR, and reverse-phase protein microarray, respectively. RESULTS: Manual exfoliation permits the selection of homogeneous cell populations by LCM based on well established cytologic characteristics. DNA and mRNA, of comparable quality to frozen sections, can be amplified from the manual exfoliation cells. Proteins of similar quality can be recovered using this technique and quantitated via reverse-phase protein microarray. CONCLUSIONS: Molecular macromolecules of high quality and sufficient quantity can be retrieved from human clinical samples using manual exfoliation and LCM to procure specific cell populations. The manual exfoliation technique does not destroy the original tissue source, thereby allowing subsequent formalin tissue fixation. The technique of manual exfoliation in conjunction with LCM can enable the molecular profiling of a sampled selected cell population. Because it does not destroy the original tissue, histologic correlation can be combined with molecular profiling

Joseph Janvier Woodward was an assistant surgeon in the US Army during the Civil War, coauthored the definitive works on the mortality and morbidity of that war, attended at the autopsy of President Lincoln, and attended President Garfield after he was shot. He revolutionized the field of photomicroscopy and was one of the first pathologists to use aniline dyes as tissue stains. Yet despite the occasional biographical sketch every few decades, he is largely unknown today. Herein, we review his contributions to surgical pathology and medicine and present modern-day photomicrographs of 140-year-old slides from Woodward's original collection

MagSafe ammunition is a type of unconventional prefragmented ammunition. A fatal tangential gunshot wound involving MagSafe ammunition is presented. The ammunition and wound characteristics are discussed.

Primary glioblastoma multiforme (GBM) commonly overexpresses the epidermal growth factor receptor (EGFR) gene and its ligand-independent mutant, EGFRvIII. Amplification of the EGFR gene has been implicated in the pathogenesis of primary GBM, in particular the small cell phenotype, and this finding may contribute to its aggressive clinical behavior. Anti-EGFR clinical trials for GBM are being conducted, and it would be useful to identify a rapid technique to determine whether EGFR expression and the small cell phenotype are associated with a response to therapy. In the present study we examined 56 cases of GBM using chromogenic in situ hybridization (CISH). CISH analysis and morphology identified 22 small cell (SCGBM) and 22 non-small cell glioblastoma (NSCGBM), and 12 cases of a mixed phenotype. Fourteen cases of SCGBM (14/22) showed EGFR amplification, while only 5 NSCGBM (5/22) cases showed amplification. We have therefore used CISH as an efficient, economic and reliable means for routinely assessing EGFR amplification in GBM, including the small cell variant

Ovarian cancer is one of the most aggressive gynaecological malignancies and most often the high mortality is a direct result of delays in diagnosis. The development of an ovarian cancer-specific biomarker for the early detection of disease has the capacity to improve the dismal survival rate. Currently, there are multiple investigations that are utilising both genomic and proteomic technologies to identify genes, gene products and proteins that may potentially identify diagnostic ovarian cancer biomarkers. Here, we review the studies that are involved in biomarker development for the detection of ovarian cancer