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December 2004

Editors:
Michael Cibull, MD, Professor of Pathology and Laboratory Medicine and Director of Surgical Pathology, University of Kentucky Medical Center, Lexington
Subodh Lele, MD, Assistant Professor of Pathology and Laboratory Medicine, University of Kentucky Medical Center
Melissa Kesler, MD, Hematopathology Fellow, University of Texas Southwestern Medical Center at Dallas

Distinguishing well-differentiated hepatocellular carcinoma from benign liver by fine-needle aspirates
Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma
Small-airway obstruction in chronic obstructive pulmonary disease
Uterine epithelioid leiomyosarcomas with clear cells: reactivity with HMB-45 and use of the term PEComa

Distinguishing well-differentiated hepatocellular carcinoma from benign liver by fine-needle aspirates

Distinguishing well-differentiated hepatocellular carcinoma from benign hepatic lesions is challenging for pathologists using limited diagnostic material such as needle core tissue biopsy and fine-needle aspiration biopsy. The authors tested a hypothesis that the fortification of liver by reticulin along single cell plates should protect benign hepatic lesions from breakdown by the force of aspiration and smearing, whereas the decreased reticulin in well-differentiated hepatocellular carcinoma (HCC) would result in finely granular fine-needle aspiration (FNA) smears. The study involved FNA biopsies of 67 cases of well-differentiated HCC and 109 cases of benign hepatic lesions, including cirrhosis (22), liver cell adenoma (eight), steatosis (seven), focal nodular hyperplasia (six), liver with cholestasis (six), and unremarkable liver sampled from nodular hepatic lesions consistent with the regenerative nodules (60). A slide with the most sample from each case by gross inspection was mixed together. Two observers blinded to the diagnoses were asked to separate the slides into two groups based on smear characteristics by gross inspection. Fragments of rigid fine-needle cores were present in all 109 cases of benign hepatic lesions but absent in 61 of 67 cases of well-differentiated HCC, which presented as finely granular smears. The difference is statistically significant (P<0.001; df=1; chi2=149.3). Using the physical characteristic of liver aspirates as the screening test for malignancy, the sensitivity is 91 percent, specificity is 100 percent, positive predictive value is 94.8 percent, and efficiency is 96.6 percent. The authors concluded that the smear characteristics of liver samples in FNA biopsy correlate to their reticulin status on histology. These physical characteristics can be used as the first clue to distinguish malignant and benign liver aspirates prior to microscopic examination.

Yang GC, Yang GY, Tao LC. Distinguishing well-differentiated hepatocellular carcinoma from benign liver by the physical features of fine-needle aspirates. Mod Pathol. 2004;17:798-802.

Reprints: Dr. G.C. Yang, NYU Medical Center, Cytopathology Laboratory, NB-4S-17, 462 First Ave., New York, NY 10016; grace.yang@nyu.edu

Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma

Detection of micrometastases in sentinel lymph nodes is important for accurate staging and prognosis in melanoma patients. However, a significant number of patients with histopathology-negative sentinel lymph nodes (SLNs) subsequently develop recurrent disease. The authors hypothesized that a quantitative real-time reverse transcriptase polymerase chain reaction (qRT) assay using multiple specific mRNA markers could detect occult metastasis in paraffin-embedded SLNs to upstage and predict disease outcome. The authors performed qRT on retrospectively collected paraffin-embedded SLNs from 215 clinically node-negative patients who underwent lymphatic mapping and sentinel lymphadenectomy for melanoma and were followed up for at least eight years. Paraffin-embedded SLNs (n=308) from these patients were sectioned and assessed by qRT for nRNA of four melanoma-associated genes: MART-1 (antigen recognized by T cells-1), MAGE-A3 (melanoma antigen gene-A3 family), GalNAc-T (β1→4-N-acetylgalactosaminyl-transferase), and Pax3 (paired-box homeotic gene transcription factor 3). Fifty-three (25 percent) patients had histopathology-positive SLNs by hematoxylin-and-eosin staining or immunohistochemistry, or both. Of the 162 patients with histopathology-negative SLNs, 48 (30 percent) had nodes that expressed at least one of the four qRT markers, and these 48 patients also had a significantly increased risk of disease recurrence by Cox proportional hazards model analysis (P<.0001; risk ratio, 7.48; 95 percent confidence interval, 3.70-15.15). The presence of at least one marker in histopathology-negative SLNs was also a significant independent prognostic factor by multivariate analysis for overall survival (P=.0002; risk ratio, 11.42; 95 percent confidence interval, 3.17-41.1). The authors concluded that molecular upstaging of paraffin-embedded histopathology-negative SLNs by multiple-marker qRT assay is a significant independent prognostic factor for long-term disease recurrence and overall survival of patients with early stage melanoma.

Takeuchi H, Morton DL, Kuo C, et al. Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients. J Clin Oncol. 2004;22:2671-2680.

Reprints: Dr. Dave S.B. Hoon, John Wayne Cancer Institute, Dept. of Molecular Oncology, 2200 Santa Monica Blvd., Santa Monica, CA 90404; hoon@jwci.org

Small-airway obstruction in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease is a major public health concern associated with long-term exposure to toxic gases and particles. The authors examined the evolution of the pathological effects of airway obstruction in patients with this disease. The small airways were assessed in surgically resected lung tissue from 159 patients—39 with stage zero (at risk), 39 with stage one, 22 with stage two, 16 with stage three, and 43 with stage four (very severe) chronic obstructive pulmonary disease (COPD) according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Progression of COPD was strongly associated with an increase in the volume of tissue in the lung wall (P<0.001) and the accumulation of inflammatory mucous exudates in the lumen (P<0.001) of the small airways. The percentage of airways that contained polymorphonuclear neutrophils (P<0.001), macrophages (P<0.001), CD4 cells (P=0.02), CD8 cells (P=0.038), B cells (P<0.001), and lymphoid aggregates containing follicles (P=0.003), as well as the absolute volume of B cells (P=0.03) and CD8 cells (P=0.02), also increased as COPD progressed. The authors concluded that the progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles. These changes are coupled to a repair or remodeling process that thickens the walls of these airways.

Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350:2645-2653.

Reprints: Dr. J. Hogg, St. Paul's Hospital, McDonald Research Wing, Room 166, 1081 Burrard St., Vancouver, BC V6Z 1Y6, Canada; jhogg@mrl.ubc.ca

Uterine epithelioid leiomyosarcomas with clear cells: reactivity with HMB-45 and use of the term PEComa

Some authors have proposed the term perivascular epithelioid cell tumor (PEComa) for uterine epithelioid tumors with clear cells positive for HMB-45. The authors of this study refute the proposal that PEComa be used as a diagnostic term for such tumors of the uterus. They examined five uterine epithelioid leiomyosarcomas with spindle and clear cells in patients without a history of tuberous sclerosis or lymphangioleiomyomatosis and in which the spindle cell areas were at least focally positive for desmin and caldesmon (smooth muscle markers). All tumors were clinically malignant. The amount of clear cells ranged from fewer than one percent to about 80 percent. All tumors expressed smooth muscle actin (SMA), desmin, and caldesmon in varying proportion. All of the tumors, except for the one with fewer than one percent clear cells, were positive for HMB-45 in the clear cell areas. In one case, the clear cells expressed both SMA and HMB-45. The authors, therefore, suggest that the term epithelioid leiomyosarcoma be retained for such tumors to avoid confusion among pathologists and clinicians. They also recommend that such tumors be stained with HMB-45 since some of the tumors may be associated with the tuberous sclerosis complex.

Silva EG, Deavers MT, Bodurka DC, et al. Uterine epithelioid leiomyosarcomas with clear cells: reactivity with HMB-45 and the concept of PEComa. Am J Surg Pathol. 2004;28:244-249.

Reprints: Dr. Elvio G. Silva, University of Texas M.D. Anderson Cancer Center, Dept. of Pathology, Box 85, 1515 Holcombe Blvd., Houston, TX 77030; esilva@mdanderson.org