Diagnostic accuracy and limitations of fine‐needle aspiration cytology of bone and soft tissue lesions

BACKGROUND:

Fine‐needle aspiration (FNA) cytology is increasingly being used as a diagnostic modality for soft tissue and bone lesions. These diagnoses can be challenging because of a variety of factors, including interpretation and sampling issues. This study investigates the diagnostic utility of FNA biopsy, in addition to the diagnostic pitfalls, in soft tissue and bone cytopathology.

METHODS:

We retrospectively reviewed the soft tissue and bone FNAs over a 4‐year period (2004‐2008), along with available ancillary studies, pathological follow‐up, and clinical data. The cases with a cytologic‐histologic discrepancy were then reviewed.

RESULTS:

A total of 1114 soft tissue and bone FNAs were identified. Of the 1114 aspirates, 525 (47%) were positive for malignant cells, 505 (45.5%) were benign aspirates (including 189 benign lesions/neoplasms), 37 (3.5%) were inadequate, 34 (3%) had atypical cells, and 13 (1%) were suspicious for malignancy. Of the 586 cases (53%) with follow‐up, including 445 cases with histological follow‐up and 141 with ancillary studies, the overall sensitivity was 96%, the specificity was 98%, the positive predictive value was 99%, and the negative predictive value was 92%. A total of 15 false negatives and 3 false positives were identified with errors because of sampling (9 cases), interpretation (7 cases), and screening (2 cases).

CONCLUSIONS:

This large series demonstrates that there can be a high sensitivity and specificity in diagnosing bone and soft tissue lesions by FNA. Our data supports prior studies in the literature in showing that FNA cytology can be a valuable method for diagnosing these lesions. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

多囊卵巢综合征患者血浆内脂素水平的变化及意义

目的:探讨多囊卵巢综合征(PCOS)患者血浆内脂素水平的变化及意义。方法:采用酶联免疫吸附法测定50例PCOS患者和45例健康体检者血浆内脂素水平,采用化学发光法测定空腹胰岛素(FINS)和血清性激素水平,采用葡萄糖氧化酶法测定空腹血糖(FPG)水平,并分析血浆内脂素水平与体重指数(BMI)、腰臀比(WHR)、空腹血糖、空腹胰岛素、胰岛素抵抗指数(HOMA-IR)和血清性激素的关系。结果:①PCOS组血浆内脂素水平为(21.18±4.31)ng/ml,对照组为(12.47±3.38)ng/ml,两组相比有统计学差异(P<0.01);肥胖PCOS组血浆内脂素水平为(22.10±5.20)ng/ml,非肥胖P-COS组为(20.39±3.27)ng/ml,分别高于肥胖对照组(14.68±3.02)ng/ml及非肥胖对照组(10.71±2.53)ng/mL(P<0.01)。②相关性分析显示,PCOS组血浆内脂素水平与WHR(r=0.43,P<0.01)、HOMA-IR(r=0.55,P<0.01)呈正相关。结论:PCOS患者血浆内脂素水平升高;血浆内脂素水平与胰岛素抵抗、肥胖呈正相关。     

Mutation rate at the hprt locus in human cancer cell lines with specific mismatch repair-gene defects

Spontaneous mutation rates at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus were measured in human cancer cell lines defective in the mismatch repair (MMR) genes hMLH1, hPMS2, or GTBP, as well as in a cell line carrying mutations in both hMLH1 and hPMS2. The mutation rate was determined by quantitating mutant frequency increases within a single culture as a function of cell division. These MMR- deficient cell lines exhibited a 50- to 750-fold increase in mutation rate relative to a MMR-proficient cancer cell line. From lowest to highest, the spontaneous mutation rates relative to the MMR-gene defects studied here are as follows: hMLH1- < GTBP- < hPMS2- < hMLH1- / hPMS2-. In addition, a cell line in which MMR was restored by chromosome transfer exhibited a mutation rate 12-fold below the MMR- deficient parental cell line. These data support the notion that MMR plays an important role in controlling the rate of spontaneous mutation and suggest that different MMR-gene defects may vary in their ability to repair different types of DNA mismatches, thus leading to measurable quantitative differences in spontaneous mutagenesis. Furthermore, a difference in mutation rates was observed between a hPMS2-defective cell line (3.1 x 10(-5) mutations/cell/generation) and two hMLH1- defective cell lines (4.0 x 10(-6) and 7.3 x 10(-6) mutations/cell/generation). Assuming the hPMS2- and hMLH1-gene products only function in the proposed hMutL alpha heterodimer, then defects in either gene should yield comparable mutation rates. These data suggest that hPMS2 plays a critical role in MMR, while additional hMLH1 homologues or hPMS2 alone may function to partially complement defects in hMLH1.      

HLA class I and II antigen phenotypes of North American Indians from Minnesota: implications for marrow transplants using unrelated donors

As a result of an appeal for a bone marrow donor for a North American Indian (Native American) patient, 261 Native Americans from our community were typed for HLA-A,B,DR antigens, and 51 were typed for HLA-A,B antigens only. The HLA antigen frequencies of the Native Americans were compared with those of 12,881 white bone marrow donors and were found to differ markedly. To investigate the implications these differences in HLA antigen frequencies would have for the location of unrelated bone marrow donors, the HLA types of 12 Native American bone marrow transplant patients from our institution were used to search among 5389 HLA-A,B,DR-typed white donors in the National Marrow Donor Program file and the file of 261 HLA-A,B,DR-typed Native American donors. In the white donor file, at least two donors were found that matched at all HLA-A,B,DR antigen loci of one Native American patient (8%). Using the Native American donor file, which was less than one-twentieth the size of the white donor file, and HLA-A,B,DR-matched donor was also found for one (8%) of the patients. These results suggest that although donors for nonwhites can be identified in a file of HLA-typed white volunteers, the probability of finding a suitably matched donor for such individuals is enhanced if donors representing racial or ethnic minorities are included in unrelated donor registries.     

湖南省临床艾滋病检测筛查实验室基本情况调查

目的了解各级临床实验室开展HIV血清学筛查试验的情况。方法采用问卷调查方式对141家临床艾滋病检测筛查实验室进行调查,利用Excel表建立数据库并进行分析。结果141家实验室2006年度共检测样本303045份,筛查阳性样本2404份,确认阳性样本276份,筛查阳性检出率和确认符合率分别为0.09%和11.48%。送检样本最多的科室是外、内、急诊和妇儿科。多数实验室采用国产酶联免疫吸附试剂。多数实验室缺少生物安全防护设备。结论进一步加强对实验室的管理,提高检测质量。     

Compound heterozygosity for the shared epitope and the risk and severity of rheumatoid arthritis in extended pedigrees

The objective was to explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis (RA). The population comprised extended pedigrees of 17 multicase RA families. Family members were genotyped for both HLA-DRB1 alleles using restriction fragment length polymorphism (RFLP). Identification of HLA-DRB1*04 variants was performed using the Multiplex ARMS-RFLP technique. Compound heterozygote individuals carrying two different alleles containing the shared epitope (SE) were at greatest risk of developing RA (odds ratio = 36, 95% CI 9.1-143). A synergistic or additive effect of these alleles is suggested. Individuals carrying no SE alleles expressed milder disease, as measured by the Spread Severity (SS) index, compared to compound heterozygotes (P = 0.045). Compound heterozygosity was not invariably associated with severe disease with six (50%) having clinically mild disease at a median age of 57.5 yr and median disease duration of 16 yr. Inheriting two different SE-bearing alleles results in an increased risk of RA and, on average, greater disease severity. This is not, however, invariably associated with severe disease, making it of limited use as a predictor of prognosis.      

Detection of monosomy 7 and trisomy 8 in myeloid neoplasia: a comparison of banding and fluorescence in situ hybridization

Fluorescence in situ hybridization (FISH) is a powerful tool for detection of numerical and structural chromosomal aberrations. We have compared conventional banding techniques and FISH for the detection of monosomy 7 (-7) and trisomy 8 (+8) in 89 patients with myeloid malignancies. Of these patients, 21 had -7, 30 had +8, four had both, and 34 had no aberrations or aberrations other than -7 or +8 as assessed by banding techniques. Sequential samples were available in 23 patients. Alphoid DNA probes specific for chromosomes no. 7 and 8 were used for FISH. As controls, 10 normal bone marrow (BM) samples were hybridized with the chromosomes no. 7 and 8 probes, and in addition all tumor samples were hybridized with a chromosome no. 1 specific probe. The cut-off value for -7 was 18% one-spot cells, and for +8 was 3% three-spot cells. FISH analysis of 44 samples with -7 or +8, and at least 10 metaphases evaluated, showed that the proportions of aberrant metaphase cells mirrored the interphase clone sizes. Most samples with nonclonal metaphase aberrations, including those with only a few metaphases, had increased numbers of aberrant interphase cells: 20% to 80% for -7, and 3% to 43% for +8. Interphase cytogenetics of the 34 samples without -7 or +8 did not show significant cell populations with -7 or +8. In four patients, -7 or +8 could not be confirmed by FISH due to additional structural aberrations, marker chromosomes, or wrongly interpreted banding results. As FISH will be used more and more in cytogenetic diagnosis, clinical follow-up, and therapy monitoring, it will be necessary to standardize FISH procedures and supplement the Standing Committee on Human Cytogenetic Nomenclature (ISCN) definitions of a clone with criteria specifically for in situ hybridization.     

Antithrombin III deficiency: decreased synthesis of a biochemically normal molecule

A 29-yr-old white female has suffered from recurrent venous thromboses over the last 12 yr. Plasma antithrombin III (AT-III) levels were 48% of normal by immunoelectrophoresis and 56% by chromogenic assay. Three of four siblings and the father had similar AT-III levels without associated venous thromboses. Heparin-Sepharose chromatography demonstrated normal behavior of the patient's AT-III. Her purified AT- III could not be distinguished from AT-III purified from a normal control either by SDS polyacrylamide gel electrophoresis or by crossed immunoelectrophoresis, and the heparin cofactor activity and the progressive antithrombin activity of both AT-III samples were identical. Turnover studies were made in the patient using her own purified AT-III labeled with 131I, (*I). The results did not differ significantly from studies made with autologous *I-AT-III in two normal control women. Her fractional breakdown rate of 0.54 total plasma AT- III per day compared with 0.45 and 0.52 in the controls. These studies indicate that the patient synthesizes a normal AT-III molecule at half normal rates.     

Differences in constitutive and post-methotrexate folylpolyglutamate synthetase activity in B-lineage and T-lineage leukemia

Folylpolyglutamate synthetase (FPGS) is responsible for the metabolism of natural folates and a broad range of folate antagonists to polyglutamate derivatives. Recent studies indicated increased accumulation of methotrexate (MTX) polyglutamates (MTX-PG) in blast cells as a predictor of favorable treatment outcome in childhood acute lymphoblastic leukemia (ALL). We determined the expression of FPGS activity in blasts from children with ALL at diagnosis and after treatment with MTX as a single agent, before conventional remission induction therapy. The levels of enzyme activity in ALL blasts at diagnosis (median of 689 pmol/h/mg protein) were significantly higher (P = .003) than those found in acute nonlymphoblastic leukemia (ANLL) blasts (median of 181 pmol/h/mg protein). Comparable lineage differences in normal lymphoid versus nonlymphoid cells suggest a lineage-specific control of FPGS expression, FPGS activity increased in ALL blasts after in vivo exposure to MTX. The median increase in FPGS activity was significantly higher (P = .003) in B-lineage ALL (188%) than in T-lineage ALL (37%). Likewise, the percentage of intracellular long chain MTX-PG (Glu3-6) was significantly higher (P = .02) in B- lineage ALL (92%) than in T-lineage ALL (65%), consistent with higher FPGS activity in B-lineage blasts. This finding could explain, at least in part, the superior outcome in children with B-lineage ALL treated with antimetabolite therapy.