Bone marrow aspirate and biopsy: a pathologist's perspective. II. interpretation of the bone marrow aspirate and biopsy.

Bone marrow examination has become increasingly important for the diagnosis and treatment of hematologic and other illnesses. Morphologic evaluation of the bone marrow aspirate and biopsy has recently been supplemented by increasingly sophisticated ancillary assays, including immunocytochemistry, cytogenetic analysis, flow cytometry, and molecular assays. With our rapidly expanding knowledge of the clinical and biologic diversity of leukemia and other hematologic neoplasms, and an increasing variety of therapeutic options, the bone marrow examination has became more critical for therapeutic monitoring and planning optimal therapy. Sensitive molecular techniques, in vitro drug sensitivity testing, and a number of other special assays are available to provide valuable data to assist these endeavors. Fortunately, improvements in bone marrow aspirate and needle technology has made the procurement of adequate specimens more reliable and efficient, while the use of conscious sedation has improved patient comfort. The procurement of bone marrow specimens was reviewed in the first part of this series. This paper specifically addresses the diagnostic interpretation of bone marrow specimens and the use of ancillary techniques.

Malignant melanoma of the prostate: a case report.

Primary genitourinary melanoma accounts for less than 1% of all cases of melanoma. Melanoma of prostatic origin is extremely rare. These patients are difficult to diagnose and carry a very poor prognosis. Aggressive surgical resection is the current treatment standard. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate.

Carcinoembryonic antigen as a target for specific antitumor immunotherapy of head and neck cancer.

Human carcinoembryonic antigen (CEA) is an oncofetal glycoprotein overexpression of which by gastrointestinal carcinomas is well known. Expression of CEA in head and neck cancer (HNC) is not widely recognized. It is important to note that most of these studies used polyclonal antibodies that may have cross-reactivity with CEA-related antigens. Currently, CEA is being evaluated in preclinical and clinical studies as a target for specific immunotherapy against gastrointestinal adenocarcinomas that express the antigen. This study was conducted to evaluate CEA as a potential target for specific immunotherapy against HNC. Immunohistochemical analysis of tumor tissue from 69 cases of squamous cell carcinoma (SCC) of the head and neck using a CEA-specific monoclonal antibody (COL-1) showed the majority to be positive for CEA. Tumor cell lines derived from human HNC were screened for CEA transcripts using nested reverse transcription-PCR. Constitutive expression of CEA mRNA was detected in 7 of 10 HNC lines. CEA protein was detectable in lysates from all 7 of the lines by quantitative fluoroimmunometry. SDS-PAGE/Western blot analysis of cell lysates from these lines showed a COL-1 immunoreactive product with a molecular weight equivalent to that of CEA. Cell surface expression of CEA was low for the SCC lines; however, there was moderate to strong cytoplasmic staining intensity for all of the CEA(+) HNC lines by immunocytochemistry. Additional supportive evidence for CEA as a target was demonstrated by the presence of cytolytic activity of an HLA-A2-restricted/CEA-epitope-specific human CTL against a CEA-overexpressing HNC-derived SCC line. These results suggest that CEA may be considered as a possible target for specific vaccine-mediated immunotherapy against HNCs.

Clinicopathologic features and long-term outcomes of 293 phyllodes tumors of the breast.

BACKGROUND: Phyllodes tumors (PT) are rare fibroepithelial neoplasms of the breast with unpredictable behavior. We reviewed our single institution experience with PT over 51 years to identify factors predictive of local recurrence (LR) and metastasis. METHODS: From 1954 to 2005, a total of 352 cases of PT were identified; 293 had follow-up. All available pathology slides (90%) were rereviewed for margins, borders, fibroproliferation in the surrounding breast tissue, stromal pattern, stromal cellularity, frequency of mitoses, and necrosis. RESULTS: All cases occurred in women, with a median age of 42, with 203 originally categorized as benign and 90 as malignant. Median follow-up was 7.9 years. A total of 35 patients developed LR at a median of 2 years. In univariate analyses, a higher actuarial LR rate was associated with positive margins (P = .04), fibroproliferation (P = .001), and necrosis (P = .006). PT classified as malignant did not have a higher risk of LR (P = .79). Five patients developed distant disease at a median of 1.2 years. These patients constituted 71% of the seven patients who had uniformly aggressive pathologic features, including large tumor size (>or=7.0 cm), infiltrative borders, marked stromal overgrowth, marked stromal cellularity, high mitotic count, and necrosis. CONCLUSIONS: Positive margins, fibroproliferation in the surrounding breast tissue, and necrosis are associated with a marked increase in LR rates. Efforts should be made to achieve negative surgical margins to reduce risk of LR. Death from PT is rare (2%), and only PT that demonstrate uniformly aggressive pathologic features seem to be associated with mortality.

Seeking confidence in the diagnosis of systemic AL (Ig light-chain) amyloidosis: patients can have both monoclonal gammopathies and hereditary amyloid proteins.

Investigators in the United Kingdom have shown that hereditary amyloidosis can be misdiagnosed as Ig light-chain (AL) amyloidosis because family history is an ineffective screen, and tissue staining used to type amyloid is unreliable. Misdiagnosis of AL can lead to inappropriate use of chemotherapy and failure to diagnose a hereditary disease. Over a 3-year period we sought to determine how often both possible sources of amyloidosis occurred in the same patient. We employed an algorithm based on established data and patterns of amyloidosis in order to focus the screening effort. Of 178 consecutive patients referred for amyloidosis, 54 were screened by polymerase chain reaction techniques with primers designed to detect transthyretin, apolipoprotein AI, apolipoprotein AII, fibrinogen Aalpha, and lysozyme variants. Three patients (6% of those screened and 2% of symptomatic patients) had both a monoclonal gammopathy and a hereditary variant. These results justify further study of screening for hereditary variants in patients with apparent AL, and highlight the need for practical techniques for identifying fibrils extracted from tissue.

Possible role of Stat5a in rat mammary gland carcinogenesis.

Signal transducer and activator of transcription (Stat) 5a is a transcription factor mediating the action of specific cytokines, growth factors and hormones on gene expression. In the mammary gland, Stat5a is well recognized for its function in prolactin signaling, lobuloalveolar development, and milk protein expression during pregnancy and lactation. Latent cytoplasmic Stat5a is activated by tyrosine phosphorylation and following dimerization undergoes nuclear import. In the current study, Stat5a expression was examined immunohistochemically in carcinomas induced by the chemical carcinogens 7,12-dimethylbenz[a]anthracene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A high percentage of carcinomas showed nuclear labeling of Stat5a [44 of 68 (65%)] with Stat5a nuclear labeling index ranging from 18 to 77%. In contrast, control normal mammary gland tissue displayed cytosolic expression. Carcinomas with different Stat5a staining patterns (cytoplasmic or nuclear) showed a statistical difference for the proliferating cell nuclear antigen (PCNA) labeling, tumor differentiation, nuclear grade, mitotic activity, and tumor size. High Stat5a nuclear expression was closely correlated with the higher-grade carcinomas. Stat5a nuclear expression was also detected in intraductal proliferations (10 of 21 lesions) and in ductal carcinomas in situ (13 of 15 lesions). Immunohistochemical analysis was further carried out in human breast cancers. Stat5a nuclear expression was detected in ductal and lobular carcinomas and DCIS at a frequency of 48% (15/31), 33% (2/6), and 40% (2/5), respectively. Nuclear expression of Stat5a in human breast cancers also correlated with the PCNA nuclear labeling index. The findings implicate activated Stat5a in mammary gland cancer development in the rat and human.

Diagnostic sensitivity of bronchoalveolar lavage versus lung fine needle aspirate.

Bronchoalveolar lavage (BAL) and lung fine-needle aspirate (LFNA) are commonly performed as the first line of investigation for a myriad of pulmonary problems associated with abnormal imaging findings (mass, cavitary lesion, infiltrates, etc.). The relative sensitivities of these two procedures are not well established for cytologic diagnosis of lesions for any single disease event. Records were searched for single pulmonary disease events with closely timed BAL and LFNA, as defined by both procedures occurring within

Hepatocellular carcinoma in HCV-infected patients awaiting liver transplantation: genes involved in tumor progression.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death in the world. The present study aimed to investigate the genes involved in viral carcinogenesis and tumor progression in liver transplant recipients with hepatitis C virus (HCV) and HCC. To accomplish this, we performed the analysis of hepatic gene expression in HCV-infected liver recipient patients with stages of disease ranging from early cirrhosis with preserved volume and function to late cirrhosis with diminished volume and function with and without HCC. We found consistent differences between the gene expression patterns in HCV-HCC and those of early HCV-cirrhosis, late HCV cirrhosis, and normal control livers. The expression patterns in HCC were also readily distinguished between early and advanced HCC tumor stages. Moreover, we found different gene expression patterns between early cirrhosis and late cirrhosis. In conclusion, these findings confirm the presence of multiple molecular alterations during HCV-HCC hepatocarcinogenesis and, clinically, indicate the possibility for identifying prognostic factors associated with HCC progression in liver transplant patients waiting for a donor and/or posttransplantation recurrence.