Claire W. Michael

Interpretation of fine-needle aspirates processed by the Thin Prep® technique: Cytologic artifacts and diagnostic pitfalls. †

The improvement in quality of cytologic preparations with the use of the ThinPrep® methodology has been well‐documented, but the cytologic artifacts resulting from this technique have not been adequately described. This study describes and illustrates the cytologic artifacts introduced by the ThinPrep technique when used on fine‐needle aspirates (FNAs), and evaluates these artifacts as potential diagnostic pitfalls.

Post-thyroid FNA testing and treatment options: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference.

The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine Needle Aspiration (FNA) State of the Science Conference on October 22–23, 2007 in Bethesda, MD. The 2‐day meeting was accompanied by a permanent informational Web site and several on‐line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document addresses follow‐up procedures and therapeutic options for suggested diagnostic categories. Follow‐up options for “nondiagnostic” and “benign” thyroid aspirates are given. The value of ultrasound examination in the follow‐up of “nondiagnostic” and “benign” thyroid aspirates is discussed. Ultrasound findings requiring reaspiration or surgical resection are described as are the timing and length of clinical and ultrasonographic surveillance for cytologically “benign” nodules. Options for surgical intervention are given for the diagnostic categories of “atypical/borderline,” “follicular neoplasm,” “suspicious for malignancy” and “malignant” (http://thyroidfna.cancer.gov/pages/info/agenda/). Diagn. Cytopathol. 2008;36:442–448.

Pregnancy-related changes : A retrospective review of 278 cervical smears

Pregnancy‐related physiologic changes are well recognized. However, the normal range of changes as reflected in the cervical smear have not been adequately described. Review of 278 abnormal cervical smears from 153 pregnant/preabortal and 125 postpartum/abortal patients revealed the following: 21 high‐grade squamous intraepithelial lesion (HGSIL) cases, 46 low‐grade squamous intraepithelial lesion (LGSIL) cases, 185 atypical squamous cells of undetermined significance (ASCUS) cases, and 26 atypical glandular cells of undetermined significance (AGUS) cases. Surgical correlation (excluding 18 products of conception and 153 placentas) was available in 98 (35%) of the cases. Dysplasia was confirmed on biopsy of 11 cases cytologically diagnosed as HGSIL (7 CINII/III and 4 CIN I), 19 cases cytologically diagnosed as LGSIL (6 CIN II/III and 13 CIN I), 35 cases of ASCUS (4 CIN II/III and 31 CIN I), and 2 cases of AGUS (1 CIN III and 1 CIN I). Decidualization was present in six cervical and three endometrial biopsies. The remaining 180 cases revealed pregnancy‐related changes in most of the atypical groups and a few in the dysplasia groups.

Can true papillary neoplasms of breast and their mimickers be accurately classified by cytology

The cytologic accuracy in assessing malignancy in papillary breast neoplasms (PBNs) is controversial. This is further complicated by overlapping features observed in other breast lesions that produce papillary‐like tissue fragments.

Group consensus review minimizes the diagnosis of "follicular lesion of undetermined significance" and improves cytohistologic concordance

We conducted a group consensus review of thyroid aspirates that were previously interpreted as “atypia of undetermined significance/follicular lesion of undetermined significance” (AUS/FLUS) and followed by surgical interventions. The study aimed to investigate if consensus review would minimize the diagnosis of AUS/FLUS with an optimal interobserver agreement and also promote a better cytohistologic concordance. A group of reviewers who were blinded to the corresponding histologic findings simultaneously evaluated a total of 50 aspirates at a multiheaded light microscope. Using the Bethesda System for Reporting Thyroid Cytopathology as a guideline, a consensus interpretation was reached upon review of each aspirate. Interobserver agreement was calculated and recorded. The cytohistologic correlation was then performed between the consensus interpretation and the corresponding histologic diagnosis. The consensus review reclassified 26 (52%) aspirates as non‐neoplasia/benign, 10 (20%) as follicular neoplasm/suspicious for a follicular neoplasm, 1 (2%) as papillary thyroid carcinoma, and 2 (4%) as nondiagnostic. Eleven (22%) aspirates remained AUS/FLUS. The interobserver agreement across the five diagnostic categories ranged from 71.6% to 100% with an average level of 88.8%. Cytohistologic concordance was achieved in 24 of 26 (92.3%) and 9 of 11 (81.8%) aspirates that were reclassified as non‐neoplasia/benign and neoplasia/malignancy, respectively. A diagnostic accuracy of 89.2% (33/37) was obtained in reclassified cases. In conclusion, the group consensus review minimized AUS/FLUS, offered an optimal level of interobserver agreement, and most importantly, promoted excellent cytohistologic concordance in reclassified cases and, therefore, could play a substantial role in the future in reducing reaspiration and/or unnecessary surgeries. Diagn. Cytopathol. 2012.

Diagnostic utility of PAX8 and PAX2 immunohistochemistry in the identification of metastatic Müllerian carcinoma in effusions

Morphologic distinction of Müllerian carcinomas from non‐Müllerian carcinomas in effusion specimens by cytomorphology alone can be diagnostically challenging. Therefore, immunohistochemical adjuncts can be useful in differentiating Müllerian from non‐Müllerian metastases. In this study, we evaluated the expression of PAX8 and PAX2 in malignant effusions collected from patients with known Müllerian and non‐Müllerian carcinomas. Sections from cell blocks prepared from 152 effusion specimens (54 and 98 cases representing metastases from Müllerian and non‐Müllerian primaries, respectively) were immunostained with rabbit polyclonal antibodies against PAX8 and PAX2. Immunopositivity was defined as the presence of strong nuclear staining in at least 25% of the tumor cells. Fifty‐two (96%) and 13 (24%) of the 54 Müllerian carcinomas were positive for PAX8 and PAX2, respectively. PAX8 positivity was seen in only four (4%) of 98 non‐Müllerian carcinomas; these represented metastasis from a large cell neuroendocrine lung carcinoma, papillary thyroid carcinoma, renal cell carcinoma, and acinic cell carcinoma of the parotid gland. PAX2 positivity was not seen in any of the non‐Müllerian carcinomas. The results demonstrate that both PAX8 and PAX2 are highly specific markers for metastatic Müllerian carcinomas in cell block preparations from effusion specimens (96% and 100%, respectively). PAX8, however, is more sensitive than PAX2 in identifying Müllerian carcinomas in fluids (96% versus 24%). Overall, immunohistochemistry for PAX8 and PAX2 represent diagnostically useful adjuncts in identifying a Müllerian carcinoma as a source of a malignant effusion. Diagn. Cytopathol. 2010.

Podoplanin Is a Useful Marker for Identifying Mesothelioma in Malignant Effusions

The diagnosis of malignant mesothelioma in serosal effusions continues to be a major challenge because some of its cytomorphological features closely resemble adenocarcinomas. Immunohistochemistry is a valuable tool in the differentiation of epithelioid mesothelioma from metastatic adenocarcinomas. However, no single antibody has demonstrated absolute sensitivity or specificity. In this study, we evaluated the value of immunostaining pattern for podoplanin to differentiate mesothelioma from adenocarcinomas of various origins.

Minimizing the diagnosis of “follicular lesion of undetermined significance” and identifying predictive features for neoplasia

We used proposed standard morphologic criteria as a guideline to conduct a 10‐year retrospective review of thyroid fine‐needle aspiration specimens that were originally interpreted as “follicular lesion of undetermined significance” and followed by surgical intervention. We sought to investigate whether the indeterminate diagnosis could be minimized by assessing various cytomorphologic features and identifying the features predictive of neoplasia. Using the standard morphologic criteria, we semi‐quantitatively assessed a total of 24 cytomorphologic features in 123 aspirates and recorded an overall interpretation on completion of the review. Cyto‐histologic correlation was evaluated and logistic regression model was performed to identify cytomorphologic features predictive of neoplasia. Although 32 of 123 aspirates remained in the indeterminate category, the retrospective review reclassified 64 aspirates as non‐neoplasia and 27 aspirates as neoplasia. Histologic confirmation was achieved in 47 (73.4%) non‐neoplastic and 15 (55.6%) neoplastic aspirates with a diagnostic accuracy of 68.1%. Furthermore, our analysis demonstrated that neoplasia is positively associated with the presence of syncytial tissue fragments, isolated microfollicles, follicles with scalloped borders, scant cytoplasm, irregular nuclear membranes, nuclear overlapping, coarse chromatin, and increased cellularity. On the contrary, the presence of honeycombing tissue fragments, background colloid, and histiocytes inversely correlated with neoplasia.

Another quality assurance issue : Amended reports : What do we really know about them ?

The Clinical Laboratory Improvement Amendment (CLIA) of 1988 requires that if a cytology/histology discrepancy is discovered which is significant and affects patient care, an amended report should be issued (Clinical Laboratory Improvement Amendments, Fed Reg 1992;57:7169). Since little is known about such amended reports, a survey was developed to assess how individuals handle discrepancies. The Quality Assurance Task Force from the Papanicolaou Society of Cytopathology created a survey to assess these methods and sent it to all of their members. Fifty‐one individuals responded to the survey. Methods vary widely among institutions. On average, 107 cytologic/histologic correlations are performed each month with the discovery of approximately 2 major and 11 minor discrepancies. Thirty‐nine responders utilize written amended reports and telephone clinicians when a major discrepancy is found. Thirty‐eight individuals indicated that their place of employment has a written policy concerning discrepancies. Time spent in quality assurance issues averaged 8 hr per wk for cytotechnologists and 3 hr per wk for pathologists. Although amended reports are required when significant discrepancies are revealed, a standard practice does not exist. Diagn. Cytopathol. 1998;18:67–70.

The use of immunocytochemical study in the cytologic diagnosis of melanoma: evaluation of three antibodies.

There are limited studies on the utility of immunostaining in cytologic specimens suspected of melanoma. In this study, we examined the performance of the most commonly used antibodies including monoclonal antibodies against Melan‐A (A103), S‐100, and HMB‐45 antigens. Immunostains were performed on formalin‐fixed, paraffin‐embedded cell blocks prepared from 100 cytologic specimens. The specimens consisted of 57 melanomas and 43 nonmelanocytic neoplasms. Of 57 melanomas, 53 showed positive reaction to Melan‐A antibody while 51 and 41 revealed positive immunostaining for S‐100 and HMB‐45, respectively. Of 43 nonmelanocytic neoplasms, 10, 4, and 8 specimens stained positive with an antibody against S‐100, HMB‐45, and Melan‐A, respectively. However, the false‐positive immunostaining for Melan‐A was eliminated in seven of the eight specimens after applying the pretreatment with avidin/biotin blocking reagents. Overall, the highest sensitivity and negative predictive value (NPV) were achieved in Melan‐A antibody (93 and 90%) compared with antibodies to S‐100 (89 and 85%), and HMB‐45 (72 and 71%). Initially, an intermediate specificity and positive predictive value (PPV) were obtained for Melan‐A antibody (81 and 87%) that were greater than S‐100 (77 and 84%), and lower than HMB‐45 (91 and 91%). However, the aforementioned treatment with avidin/biotin blocking reagents improved both specificity (98%) and PPV (98%) for Melan‐A antibody. In conclusion, by blocking endogenous biotin, Melan‐A antibody offers the greatest performance. In terms of cost‐effectiveness, we suggested that Melan‐A antibody should be used as the first‐line antibody for detecting melanoma in the cytologic specimens. Diagn. Cytopathol. 2013.