Pamela Michelow

Effectiveness of the cell block technique in diagnostic cytopathology

Background: One of the constraints of the conventional FNA smear is the limited material available for adjuvant diagnostic investigations including immunocytochemistry. The cell block technique employs the retrieval of small tissue fragments from a FNA specimen which are processed to form a paraffin block. It is widely accepted that cell block technique increases the cellular yield and improves diagnostic accuracy. The ability to obtain numerous tissue sections allows for multiple immunostains and other studies to be performed akin to paraffin sections produced in histopathology. Aims: To determine the effectiveness of the cell block technique by comparing cytomorphological preservation and immunocytochemistry (ICC) stains on paired cell block and conventional fine needle aspiration (FNA) samples. Materials and Methods: In this prospective study, material for both glass slides and cell blocks were collected simultaneously during fine needle aspirates from 47 samples comprising lung and liver masses. Grading of cellularity, morphological preservation, architectural preservation, immunocytochemical staining intensity and presence of background staining on paired FNA smears and cell block samples were compared. Each arm of the paired analysis was performed blindly without knowledge of the grading outcome of the other. The Kappa statistic (κ) was used to measure inter-rater agreement. Results: The 47 samples evaluated included FNAs from the lung, 24/47 (51%) and liver, 23/47 (49%). The immunocytochemistry stains consisted of 44/47 (94%) CK7; 44/47 (94%) CK20; 18/47 (38%) TTF1; 10/47 (21%) synaptophysin; 10/47 (21%) Hepar-1 and 7/47 (15%) AE1/3. There was no overall agreement in preservation of cytomorphological detail and ICC staining between the two methods. The Papanicolaou-stained conventional FNA smears fared better than the cell block for the evaluation of nuclear and morphologic characteristics. The ICC stains worked better on the cell block samples due to lack of background and aberrant staining. Conclusion: Direct FNA smears and cell blocks complement each other and our results indicate that both are needed in the diagnostic work-up of patients. The cost implications of performing both techniques on all FNA material warrants further evaluation.

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‐Hodgkins lymphoma (39), rhabdomyosarcoma (22), Hodgkins 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. Diagn. Cytopathol. 2012.

Cervix cancer in African women in Durban, South Africa

In South Africa, nationally, the total age-adjusted incidence rate (ASIR) of cancer in Africans is far lower than that in the corresponding white population, i.e. 87 vs. 280 per 100 000 w1x. However, the cervical cancer rate in African women is far higher: 35.0 vs. 11.7 per 100 000 w1x. In Tanzania, of urban patients, 45% had cervical cancer w2x. It was therefore considered worthwhile to determine the rate in the 1.4 million Africans, including approximately 700 000 women, resident in Durban, during 1994–1999. From hospital admission data, the mean number of urban patients, annually was 167, and the ASIR 45.0 per 100 000. Moreover, the lesions of 65.5% of patients were late, at stages III and IV. Interestingly, interethnically, in the US, regarding African–Americans, whose forebears came mainly from West Africa, their rate, in New Orleans, is 14.0, compared with 7.0 per 100 000 in the white population w3x. In Durban, the

Simulation of Primary Cervical Cancer Screening by the PAPNET System in an Unscreened, High-Risk Community

OBJECTIVE To evaluate the performance of the PAPNET system as a primary cervical cancer screening modality in an unscreened population with a high prevalence of cervical cancer and its precursor lesions. STUDY DESIGN Consecutive cervical smears from 3,106 women, screened and reported in the usual manner, were submitted for analysis by the PAPNET system. The original manual screening diagnoses were compared with those obtained by PAPNET analysis. By inclusion of normal and abnormal smears, this evaluation not only provided quality assurance for the laboratory but also simulated primary screening by automation. RESULTS Comparison of the two methods of screening showed statistically significant superiority of the PAPNET over conventional screening (89.6% vs. 63.8%, respectively) in low grade lesions, including atypical squamous and atypical glandular cells of uncertain significance (ASCUS and AGUS, respectively) and low grade squamous intraepithelial lesion. Conversely, there was no significant difference between PAPNET and manual detection (87.5% vs. 94.6%) for more significant abnormalities, including high grade squamous intraepithelial lesions and invasive carcinoma. CONCLUSION The PAPNET system, which would probably not be affordable as a quality assurance modality only in the public health sector of this country, was shown to be more than sufficiently effective as a primary screening method for the large numbers of women likely to undergo cervical cancer screening in anticipated mass population programs.

The utility of fine needle aspiration in HIV positive children.

Objective:  To determine the spectrum of disease, diagnostic accuracy and adequacy of fine needle aspirates (FNA) in human immunodeficiency virus (HIV) positive children who present with mass lesions.

Comparison of Analytical and Clinical Performances of the Digene HC2 HPV DNA Assay and the INNO-LiPA HPV Genotyping Assay for Detecting High-Risk HPV Infection and Cervical Neoplasia Among HIV-Positive African Women.

Objectives:To compare the Hybrid Capture 2 human papillomaviruses (HPV) DNA assay (HC2) and the INNO-LiPA HPV Genotyping Extra assay (INNO-LiPA) for cervical cancer screening in HIV-1–infected African women. Design:The tests were compared for agreement in detecting high-risk HPV (hr-HPV) and performance to detect squamous intraepithelial lesions (SIL), by cytology, and cervical intraepithelial neoplasia, by histology, in cervical samples from 1224 women in Burkina Faso (N = 604) and South Africa (N = 620). Results:When considering the 13 hr-HPV types detected by HC2, 634 (51.8%) and 849 (69.4%) samples were positive by HC2 and INNO-LiPA, respectively. Agreement between assays was 73.9% [adjusted kappa coefficient value, 0.44 (95% confidence interval: 0.43 to 0.53)]. Agreement improved with analysis restricted to women with high-grade cervical lesions [adjusted kappa coefficient value, 0.83 (95% confidence interval: 0.74 to 0.91)]. The prevalence of hr-HPV, as determined by HC2 and INNO-LiPA, was 34.5% and 54.5%, respectively, in samples with normal cytology, 48.0% and 68.0%, respectively, in samples with atypical squamous cells of undetermined significance, 51.8% and 75.2%, respectively, in samples with low-grade SIL, and 86.3% and 89.8%, respectively, in samples with high-grade SIL/atypical squamous cells that cannot exclude HSIL. Sensitivity, specificity, positive, and negative predictive values for the diagnosis of histological high-grade lesions (CIN2+) were 88.8%, 55.2%, 24.7% and 96.7%, and 92.5%, 35.1%, 19.1% and 96.6% for HC2 and INNO-LiPA, respectively. Conclusions:HC2 has lower analytical sensitivity but higher specificity than INNO-LiPA for diagnosing high-grade lesions; the 2 tests presented a comparable clinical sensitivity. HC2 might be suitable for cervical cancer screening in HIV-1–infected African women, but its use in resource-limited settings merits to be further evaluated in comparison with other prevention strategies.

Rapid rescreening of cervical smears as a quality control method in a high‐risk population

Objective:  Cancer of the cervix is one of the commonest cancers in South Africa. Accurate cytological diagnosis is one of the prerequisites for an effective cervical screening programme and requires the implementation of appropriate quality assurance modalities. This study was undertaken to determine if rapid review of reportedly negative cervical smears is a useful internal quality assurance modality in an unscreened population with very high rates of cervical carcinoma.

Performance of careHPV for detecting high-grade cervical intraepithelial neoplasia among women living with HIV-1 in Burkina Faso and South Africa: HARP study.

Background:The careHPV assay is a test for high-risk (HR) human papillomaviruses (HPV) detection designed to be affordable in resource-poor settings. We evaluated the performance of careHPV screening among 1052 women living with HIV/AIDS included in the HARP (HPV in Africa Research Partnership) study in Burkina Faso (BF) and South Africa (SA).Methods:Cervical samples were tested for HR-HPV by the careHPV and the INNO-LiPA HPV genotyping Extra assays. All women had Pap smear testing, visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) and colposcopy. Cervical biopsies were obtained for participants who were HR-HPV DNA positive by careHPV or who had abnormalities detected on cytology, VIA/VILI or colposcopy.Results:Overall, 45.1% of women had a positive careHPV test (46.5% in BF, 43.8% in SA). The careHPV positivity rate increased with the grade of cytological lesions. Sensitivity and specificity of careHPV for the diagnosis of CIN2+ (n=60, both countries combined) were 93.3% (95% confidence interval (CI): 83.8–98.2) and 57.9% (95% CI: 54.5–61.2), respectively. Specificity increased with CD4 count. careHPV had a similar clinical sensitivity but higher specificity than the INNO-LiPA assay for detection of CIN2+.Conclusions:Our results suggest that careHPV testing is a reliable tool for cervical cancer screening in HIV-1-infected women in sub-Saharan Africa.

Thyroid Cytopathology with an Emphasis on the ‘Atypical Cells of Uncertain Significance' Category: A 3-Year Audit with Cytohistologic Correlation

Background: The National Cancer Institute meeting of 2007 resulted in the reporting terminology for thyroid cytopathology. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) aims to standardise thyroid cytopathology reporting for cytology centres and clinicians alike. Study Objective: To compare our laboratorys performance against TBSRTC. The second aim was to determine our laboratorys atypia of undetermined significance/follicular cells of undetermined significance (AUS/FLUS) reporting rate and malignant outcomes. Our laboratory subclassifies the AUS/FLUS category into AUS/FLUS not otherwise specified (NOS) and AUS/FLUS cannot exclude malignancy. Materials: All thyroid reports were retrieved from our computerised database for the period of January 1, 2008 to March 31, 2011. Histologic correlation was obtained where available, and cases were classified according to their original diagnosis into 1 of the 6 categories of TBSRTC. Results: A total of 1,767 cases were retrieved. The categories were as follows: inadequate (n = 415; 23%), benign (n = 1,063; 60%), AUS/FLUS (n = 141; 8%) [NOS (n = 93; 5%) and cannot exclude malignancy (n = 48; 3%)] suspicious for follicular/Hürthle cell neoplasm (n = 68; 4%), suspicious for malignancy (n = 37; 2%) and malignant (n = 43; 2%). The malignant rates for the categories were as follows: -6 (26%), 0 (0%), 8 (40%), 9 (38%), 11 (42%), 15 (62.5%), and 15 (94%), respectively. Conclusion: We have shown that the AUS category carries a higher malignant rate than that of the AUS category in TBSRTC of 5-15%. We conclude that subclassifying the AUS/FLUS category into NOS and cannot exclude malignancy helps to better identify patients with an increased risk of malignancy in the AUS/FLUS cannot exclude malignancy category.

Cytopathology of Extracranial Ectopic and Metastatic Meningiomas

Introduction: Extracranial meningiomas may infrequently be encountered as ectopic or metastatic tumors. Their rarity and unique cytomorphology often pose significant diagnostic dilemmas. The aim of this study was to report our experience with a series of ectopic and metastatic meningiomas, characterizing their cytomorphology with histological correlation. Materials and Methods: A retrospective analysis involving 13 patients with cytological preparations from extracranial meningiomas was performed. Cytology cases were correlated with available surgical resection specimens. Data regarding clinical findings, tumor information, cytomorphology, follow-up histological features and immunohistochemistry were recorded and analyzed. Results: There were 5 cases with metastases and 8 ectopic meningiomas. Metastases occurred in the scalp/skull, lung, paraspinal soft tissue and liver. Primary ectopic meningiomas were located in the paranasal sinuses and ear, orbit and neck. Cytomorphological features characteristic of meningiomas were identified in the majority of samples including tightly cohesive clusters of spindled cells, whorls, intranuclear inclusions, nuclear grooves and psammomatous calcification. Unusual cytomorphological features identified in only a few cases included epithelioid cell predominance, abundant inflammatory cells, small-cell change, papillary structures and pseudoacinar growth. Metastatic tumors exhibited more nuclear atypia and occasionally mitoses or necrosis. Meningiomas were shown to be immunoreactive for epithelial membrane antigen, pancytokeratin and vimentin. Conclusion: Although rare, extracranial meningiomas can be encountered in cytologic specimens and should be included in the differential diagnosis when characteristic morphological features of meningiomas are seen. Cytopathologists should be aware that these lesions could be mistaken for other tumors, especially when confounded by atypia and unusual cytomorphological features.