CT-guided transthoracic needle aspiration biopsy of subsolid lung lesions.

PURPOSE: To assess the diagnostic performance of computed tomography (CT)-guided transthoracic needle aspiration biopsy (TNAB) in the evaluation of persistent subsolid lung lesions. MATERIALS AND METHODS: A retrospective review of all CT-guided TNABs performed at a single institution from January 2002 to November 2012 was conducted to identify patients with persistent subsolid lung lesions. The diagnostic performance of CT-guided TNAB was assessed through comparison of cytologic diagnoses with core needle biopsy, surgical resection, or imaging and clinical follow-up. The cytologic, histologic, and imaging features of each lesion were characterized, and CT-guided TNAB complications were recorded. RESULTS: In 32 patients, a diagnosis of benign or malignant disease was identified through evaluation of pathologic or follow-up data. There were 18 men and 14 women, with a mean age of 67.1 years ± 9.6 (range, 52-86 y). The mean lesion diameter was 21 mm ± 11 (range, 8-62 mm). A final diagnosis of malignancy was made in 28 cases (87.5%); four benign lesions were also diagnosed. The overall sensitivity of CT-guided TNAB in the evaluation of these lesions was 89.2%, and the specificity and positive predictive value were 100%. Two pneumothoraces (6.3%) were identified. CONCLUSIONS: Among patients with subsolid lung lesions, CT-guided TNAB is safe and shows high sensitivity. The high specificity and positive predictive value of the procedure allow for definitive treatment decisions to be made for most patients.

Testing of integrated human papillomavirus mRNA decreases colposcopy referrals: could a change in human papillomavirus detection methodology lead to more cost-effective patient care?

OBJECTIVES: This study investigates potential colposcopy referral rates, as per the latest American Society for Colposcopy and Cervical Pathology recommendations, following the change in high-risk human papillomavirus (HR-HPV) detection methodology from Hybrid Capture 2 (HC2) to APTIMA at our institution. STUDY DESIGN: Rates of colposcopy referral were compared between two cohorts, each comprising all Pap samples with a diagnosis of atypical squamous cells of undetermined significance (ASCUS) tested for HR-HPV in our laboratory during a 12-month period. Cohorts I and II included Pap samples tested with HC2 (n = 1,856) and APTIMA (n = 1,651), respectively. The rates of quantity not sufficient (QNS) results were determined for all Pap samples during the same time periods. RESULTS: The proportion of HR-HPV-positive Pap samples with an ASCUS diagnosis was significantly lower with APTIMA (42%) than with HC2 (53%; p < 0.0001). APTIMA also resulted in a significantly lower QNS rate among all Pap samples (0.42 vs. 4.3% with HC2; p < 0.0001). CONCLUSION: The change in HR-HPV detection methodology from HC2 to APTIMA has led to a 21% reduction in colposcopy referrals and a 90% decrease in QNS rates at our institution. The new methodology has resulted in more cost-effective patient care and fewer insufficient samples requiring repeat HR-HPV testing.

An interinstitutional review of the value of FNAB in pediatric oncology in resource-limited countries.

Fine-needle aspiration biopsy (FNAB) has been widely accepted as a reliable diagnostic modality in the general pediatric population, but its role in pediatric oncology still remains elusive. With new treatment protocols subscribing to preoperative chemotherapy, the need for a quick, minimally invasive, and accurate diagnostic procedure has arisen. This study assesses the feasibility of FNAB in childhood malignancies to render a specific diagnosis on which treatment can be initiated. An 11-year retrospective study was done on FNABs in patients 19 years and under referred for clinically malignant mass lesions. Cases were confirmed with histology, immunocytochemistry, flow cytometry, or clinical follow-up. Of the 357 patients referred for FNABs, 36 patients were lost to follow-up and 31 FNABS were inadequate. A total of 290 cases were included in the study, of which 68 (23%) cases were benign and 222 (77%) were malignant. The most frequently occurring tumors were nephroblastoma (68), non-Hodgkin's lymphoma (39), rhabdomyosarcoma (22), Hodgkin's lymphoma (22), and neuroblastoma (22). The sensitivity of the procedure for neoplasia was 96.6%, the specificity 97.0%, positive predictive value 99.0%, and negative predictive value 90.1%, with a diagnostic accuracy of 96.7%. The ability of FNAB to enable a specific diagnosis to be made, that is correct and accurate subtyping of the tumor on which chemotherapy or radiotherapy could be commenced was 75.7%. This study shows that FNAB can be used with confidence to confirm malignancy in children. With clinicoradiological correlation and the aid of ancillary techniques, FNAB allows a rapid and accurate preoperative diagnosis for definitive therapy commencement in most cases.

Documentation of immunocytochemistry controls in the cytopathologic literature: a meta-analysis of 100 journal articles.

Although a detailed description of the procedure and tissue used as controls is considered a necessary component in surgical pathology articles in which immunohistochemistry is utilized, such documentation seems less stringent in the cytopathologic literature. A comprehensive literature search was done for articles published in English within the last 15 years on nine of the most widely used antibodies in cytopathology. Individual case reports were excluded. Of the 100 articles reviewed, 13 articles were review articles or commentaries and hence not included in the analysis. Only 11 (13%) of the remaining 87 articles described positive and negative controls run on identically prepared samples. Forty-seven articles (54%) either did not mention controls or did not run controls as separate specimens. Sixteen articles (18%) included a vague statement about controls. Twelve (14%) commented only on the negative control, included only histology tissue controls, or included cell block controls, but the study also included other types of preparations, such as cytospins. One article (1%) did not include controls because of insufficient material. The College of American Pathologists recognizes the impracticality of maintaining separate positive control samples for every possible combination of fixation, processing, and specimen type. However, more stringent documentation of procedure and use of controls in the cytopathologic literature will ensure that immunocytochemistry results in diagnostic cytopathology as well as in research are valid and reproducible.

HPV is detectable in virtually all abnormal cervical cytology samples after reinvestigation of HPV negatives with multiple alternative PCR tests.

The demonstration of human papillomavirus (HPV) in 99.7% of cervical carcinoma surgical specimens from around the world required investigations by multiple alternative polymerase chain reaction (PCR) assays. A similar approach may therefore be necessary to best characterize HPV prevalence and genotype distribution among cervical cytology samples. In an earlier study, 752 of 799 (94.1%) abnormal and 82 of 300 (27.3%) normal cytology specimens tested HPV positive after PCR using GP5+/6+primers. This study has reinvestigated the "HPV negative" abnormal samples (20 atypical squamous cells of undetermined significance, 5 low-grade squamous intraepithelial lesion, 14 atypical squamous cells, cannot exclude HSIL, 6 high-grade squamous intraepithelial lesion) and an age-matched cohort of "HPV negative" normal (negative for an intraepithelial lesion or malignancy) samples by PCR using PGMY09/11, FAP59/64, and LCR-E7 primers. PGMY09/11-GP5+/6+ nested PCR was performed on samples that were HPV negative by PGMY09/11 PCR. After the first 3 assays, HPV was detected in 41 of 45 (91.1%) abnormal and in 10 of 47 (21.3%) normal samples (P<0.0001). Eighteen HPV genotypes were detected and in some samples the genotype that was identified differed between the tests. The nondetection of common HPV genotypes (eg, HPVs 6, 11, 16, and 18) was notable. High-grade histopathology was found for 2 patients with HPV52-positive cytopathology. Combined with our earlier study, HPV (40 different genotypes) is shown in 99.5% of abnormal samples (99.8% inclusive of the nested PCR data). These findings show that HPV genotype and prevalence estimates are dependent on the method(s) of detection and indicate that suboptimal analytical sensitivity for one or more of the less common high-risk HPV genotypes could lead to impaired clinical sensitivity. HPV may be causal in almost every instance of abnormal cervical cytology; however, passenger HPV that is incidental to an abnormality may also have been detected.

Ductal lavage of cancerous and unaffected breasts: procedure success rate and cancer detection.

OBJECTIVE: To evaluate ductal lavage (DL) performance in women with known breast cancer and to assess cell yield from contralateral high-risk breasts. STUDY DESIGN: Women with newly diagnosed breast cancer were offered study participation. They underwent bilateral nipple aspiration, followed by DL of those ducts demonstrating nipple aspiration fluid (NAF) production. The procedures were conducted in the operating room prior to definitive surgery. Samples were interpreted masked as to which breast was malignant, and the interpretation used a 5-category scheme: insufficient, benign, mildly atypical, markedly atypical or malignant. RESULTS: A total of 23 women with 24 cancers were enrolled, ranging in age from 32 to 76. One had ductal carcinoma in situ; there were 13 T1, 6 T2 and 4 T3 lesions. NAF was identified in 72% of breasts, more commonly in cancerous than unaffected breasts. DL was performed on 33 breasts; of these, 55% were adequate. Only 16.6% of samples from malignant breasts contained abnormality, marked atypia in 1 and malignancy in 3. No samples from unaffected breasts demonstrated cellular abnormalities. CONCLUSION: The low sensitivity of DL performed on malignant breasts to identify abnormal cells adds to the growing body of evidence that this is not an effective tool in identifying existing breast cancer. Numbers are small, but the ability of DL to identify atypia in unaffected high-risk breasts may also be suboptimal. Future efforts should focus on molecular markers of risk and on alternate means of cell or tissue retrieval.

Glypican-3 protein expression in primary and metastatic melanoma: a combined immunohistochemistry and immunocytochemistry study.

BACKGROUND: The incidence of melanoma is increasing. Fine-needle aspiration (FNA) is critical in documenting recurrent/metastatic disease in established cases. The potential of metastatic melanoma (MM) to mimic epithelial tumors presents a diagnostic dilemma. In liver FNA, the distinction between hepatocellular carcinoma (HCC) and MM is a frequent challenge. Glypican-3 (GPC3), a heparan sulfate proteoglycan, is a highly sensitive and specific marker for HCC. Serum GPC3 was shown to be expressed in 40% of primary melanomas (PMs), but to the authors' knowledge no tissue studies to date have assessed GPC3 expression in MM. In this study, GPC3 protein expression was investigated in FNAs from MM, and in corresponding histologic sections from the primary tumors. METHODS: Sixty archival, direct FNA smears or CytoLyt-fixed samples from 50 patients with MM were retrieved together with formalin-fixed, paraffin-embedded specimens available from 17 corresponding PMs. All cases were stained with anti-GPC3 antibody. FNA and core biopsy specimens from HCCs and benign liver were used as positive and negative controls. GPC3 expression was divided into 2 categories: negative (negative or weak cytoplasmic staining) and positive (moderate or strong cytoplasmic with membranous accentuation). RESULTS: All FNAs from MM cases were negative (0 of 60) for GPC3. The exact 95% Clopper-Pearson confidence interval was 0.0% to 5.96%. Only 1 case of PM (1 of 17; 5.9%) demonstrated weak focal cytoplasmic staining (regarded as negative). CONCLUSIONS: In the current study, all MM and PM cases in archival FNAs and tissue sections were found to be negative for GPC3. These data suggest that GPC3 is not expressed in melanoma using the 1G12 clone.

Follicular and Hürthle cell lesions of the thyroid: can inconclusive results be minimized?

OBJECTIVE: To assess the cytologic criteria for distinguishing neoplastic from nonneoplastic follicular cell and Hürthle cell thyroid lesions. STUDY DESIGN: Ten previously described and commonly used cytologic criteria were evaluated and graded on a 0-4 scale in a consecutive series of thyroid fine needle aspirations (FNAs) reported as follicular or Hürthle cell neoplasms or lesions. Scoring was compared to subsequent surgical outcome. RESULTS: A total of 93 (57fo llicular cell and 36 Hühle cell) cases was analyzed. No individual cytologic feature was helpful in distinguishing benign neoplarms from malignancy in either category (p > 0.05), but 4 or more coexistent cytologic features in combination were identified in 50.0% of follicular neoplasms, 13.6% of Hürthle cell neoplasms and none of the nonneoplastic lesions. An unexpected number (13 of 93, 14.0%) of unrecognized papillary carcinomas, some of follicular subtype, was encountered. CONCLUSION: In this series, the indeterminate thyroid FNA category could have been reduced by diagnosis of samples with 4 or more of the studied criteria as definite follicular (50% of cases) or Hürthle cell (13.6% of cases) neoplasms and by more astute recognition of papillary carcinomas (14.0% of cases), which blend into this category, often as a result of less-than-optimal sampling or preservation.

Effectiveness of the ThinPrep Imaging System: clinical experience in a low risk screening population.

The Cytyc ThinPrep Imaging System was FDA approved based on a multi-institutional clinical trial, in which the HSIL+ prevalence rate was 0.7%. This study determines the effectiveness of the Imager in clinical practice at an academic medical center with a historical HSIL+ rate of 0.25%. Cytological interpretations were compared for two 12-month periods pre- and post-Imager implementation. Data was compiled by cytologic diagnoses, and variations in prevalence rates were analyzed for statistical significance. Interpretations of ASC-US, ASC-H, and LSIL were correlated with Digene Hybrid Capture2 High Risk HPV DNA testing; interpretations of ASC-H, LSIL, and HSIL+ were correlated with subsequent surgical follow-up. ASC-US, ASC-H, and LSIL detection rates increased 34, 48, and 29%, respectively, with the Imager (P<0.001); whereas the detection of HSIL increased 24% (P<0.051). Surgical correlation revealed no statistical differences in the positive predictive value (PPV) for ASC-H and LSIL. However, an increase in the PPV of HSIL was found (P<0.05). High risk HPV results were lower for ASC-US (P<0.001), but statistically equivalent for ASC-H and LSIL. Results of surgical correlation and HPV testing validated an increase in detection rates of ASC-H, LSIL, and HSIL, as well as increased PPV of HSIL with the ThinPrep Imaging System.

Glypican-3 immunocytochemistry in liver fine-needle aspirates : a novel stain to assist in the differentiation of benign and malignant liver lesions.

BACKGROUND: Glypican-3 (GPC3) is a heparan sulfate proteoglycan which is elevated in the serum of patients with hepatocellular carcinoma (HCC), but not in healthy blood donors, or patients with benign liver disease. GPC3 immunohistochemistry (IHC) is a promising marker of HCC in surgical pathology. This study explores the value of GPC3 expression in liver fine-needle aspirates (FNAs) by immunocytochemistry (ICC), and compares its sensitivity and staining intensity with that of IHC. METHODS: Archival cytologic material in hepatic FNAs from 20 patients with HCC, 20 patients with metastatic tumors, and 20 patients with benign lesions, were studied. Correlating surgical specimens and/or cell blocks were available for GPC-3 IHC in 16 patients with HCC. All slides were stained with GPC3-1G12 antibody with appropriate positive and negative controls. Staining intensity was graded as 0, no staining; 1, weak cytoplasmic staining; 2, moderate cytoplasmic staining; 3, strong cytoplasmic staining with membranous accentuation. Grades 0 and 1 were regarded as negative; grades 2 and 3 were considered positive for GPC3. RESULTS: In the HCC group, positive staining was found in 18/20 (90%) samples. In contrast, GPC3 ICC of 20/20 (100%) metastatic tumors and 20/20 (100%) benign cases displayed negative staining, no cases showing moderate or strong expression. The sensitivity and specificity of GPC3 in HCC ICC were 90% and 100% respectively. The surgical sections and cell blocks of HCC demonstrated positive staining less frequently, in 11/16 (68.8%) cases, with 12/16 (75%) correlation with ICC. CONCLUSIONS: Results indicated positive staining for GPC3 as defined in 90% of liver FNAs from HCC patients. All metastatic tumors and benign aspirates studied were negative for GPC3. ICC was superior to IHC in 25% of cases. This pilot study supports the diagnostic utility of GPC3 in hepatic FNAs to aid in distinction of HCC from metastatic tumors and benign liver lesions.

Prevalence and risk factors for anal cytologic abnormalities and human papillomavirus infection in a rural population of HIV-infected males.

PURPOSE: This study was designed to determine the prevalence and risk factors for anal squamous intraepithelial lesions and human papillomavirus infection in a rural population of HIV-infected males. METHODS: A cross-sectional study was performed. Risk factors were collected. Anal Papanicolaou smear and human papillomavirus screening for oncogenic types were performed. RESULTS: Of 211 eligible male patients, 149 (70.6 percent) participated. HIV transmission risk was predominantly males who have sex with males (82 percent). The mean duration of HIV infection was 9.9 years. Ninety (60 percent) males had abnormal anal cytology, including atypical cells of unknown significance 40 (26 percent), low-grade squamous intraepithelial lesions 28 (19 percent), and high-grade squamous intraepithelial lesions 22 (15 percent). Human papillomavirus was detected in 61 percent. Binary logistic regression adjusted risks for abnormal anal cytology included: males who have sex with males (P<0.001), human papillomavirus infection (P<0.001), history of anogenital warts (P=0.014), and the mean lowest CD4 count (abnormal cytology, 158 (standard deviation, 135), negative cytology, 208 (standard deviation, 180; P=0.017)). Twenty-two patients with high-grade squamous intraepithelial lesions underwent colorectal surgical examination and anoscopy. Two (10 percent) were found to have invasive squamous-cell carcinoma and three (15 percent) others had mass lesions with high-grade squamous intraepithelial lesions. CONCLUSIONS: Anal squamous intraepithelial lesions and oncogenic human papillomavirus are highly prevalent in males infected with HIV and living in a rural setting.

My approach to pancreatic fine needle aspiration.

Pancreatic fine needle aspiration cytopathology has earned a reputation as a rapid, safe, accurate and cost-beneficial modality of investigation of pancreatic mass lesion. Optimal results can be expected only if these procedures are undertaken regularly in gastroenterology departments processing large numbers of patients; occasional aspirators cannot exploit the technique to full potential. Professional teams following a dedicated approach to patient selection and management develop requisite expertise over time. Cytodiagnosis rests as much on morphological examination as on the milieu in which is it practised, and as much on sample quality as on cellular criteria. This article focuses attention on specimen handling, with particular reference to rapid on-site evaluation. The significance of particular cytodiagnoses in patient care is evaluated, and tumour types that may be encountered are enumerated and illustrated.

Distribution of human papillomavirus types in ThinPrep Papanicolaou tests classified according to the Bethesda 2001 terminology and correlations with patient age and biopsy outcomes.

BACKGROUND: A survey of the distribution of human papillomavirus (HPV) types across the spectrum of cervical cytologic categories defined by the Bethesda 2001 guidelines was conducted with the objective of examining how HPV detection by polymerase chain reaction (PCR) analysis may benefit the management of patients who have abnormal Papanicolaou (Pap) test results. METHODS: DNA samples from women with no intraepithelial lesion or malignancy (NLM) (n = 300 samples); atypical squamous cells of undetermined significance (ASC-US) (n = 200 samples); low-grade squamous intraepithelial lesion (LSIL) (n = 200 samples); atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H) (n = 200 samples); and high-grade squamous intraepithelial lesion (HSIL) (n = 200 samples) were tested for HPV using a modified general primer (GP)5+/GP6+ PCR assay and dot-blot hybridization with type-specific oligonucleotide probes (PCR assay analytical sensitivity: 1-100 copies of HPV, depending on the HPV type, in a background of 100 ng human DNA). RESULTS: HPV was detected in 27% of NLM samples, in 89.5% of ASC-US samples, in 97.5% of LSIL samples, in 93% of ASC-H samples, and in 96.5% of HSIL samples. Thirty-seven different HPV types were identified in total. One or more of 13 high-risk (HR) HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) were detected in 53% of samples that were diagnosed as ASC-US (59.0% of patients younger than age 30 yrs; 45.5% of patients age 30 yrs and older), in 55.5% of samples that were diagnosed as LSIL (60.0% of patients younger than age 30 yrs; 44.0% of patients age 30 yrs and older), in 80% of samples that were diagnosed as ASC-H, and in 87.5% of samples that were diagnosed as HSIL (P < 0.001). HPV-16 was detected in 17.5% of ASC-US samples, in 15.5% of LSIL samples, in 48.5% of ASC-H samples, and in 49.0% of HSIL samples (P < 0.001). Among abnormal smears, HR HPV was significantly more common in women younger than age 30 years compared with women age 30 years and older (P < 0.002). Follow-up biopsy data were obtained for 359 patients. A "benign" biopsy result was recorded for 47 of 64 women (73.5%) with ASC-US, 30 of 66 women (45.5%) with LSIL, 39 of 87 women (45.0%) with ASC-H, and 26 of 142 women (18.0%) with HSIL and was most common in women age 30 years and older (P < 0.0001). Cervical intraepithelial neoplasia (CIN) Grade I (CIN-I) was found in 14.0% of women with ASC-US, in 39.5% of women with LSIL, in 8.0% of women with ASC-H, and in 7.0% of women with HSIL. CIN-II was diagnosed in 9.5% of women with ASC-US, in 13.5% of women with LSIL, in 19.5% of women with ASC-H, and in 24.0% of women with HSIL. CIN-III was identified in 2 women (3.0%) with ASC-US, in 1 woman (1.5%) with LSIL, in 24 women (27.5%) with ASC-H, and in 71 women (50.0%) with HSIL. CONCLUSIONS: HR HPV testing by PCR of samples diagnosed according to the Bethesda 2001 guidelines may benefit the management of patients with ASC-US or patients with LSIL, especially among women age 30 years and older, by allowing exclusion from referral for biopsy of women who are negative for HR HPV types. However, the small numbers of women who had CIN-III detected after a diagnosis of ASC-US or LSIL limited the assessment of test sensitivity.