Jonathan H. Hughes

Pitfalls in Salivary Gland Fine-Needle Aspiration Cytology Lessons From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology

CONTEXTnWe use data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology to identify common diagnostic errors in salivary gland fine-needle aspiration (FNA).nnnOBJECTIVEnTo identify salivary gland FNA cases with poor performance characteristics in the Nongynecologic Cytology Program surveys, so that the most common diagnostic pitfalls can be avoided.nnnDESIGNnA retrospective review of the College of American Pathologists Nongynecologic Cytology Programs cumulative data from 1999 to 2003 revealed the most common false-positive and false-negative interpretations on FNA for common salivary gland lesions. Slides that performed poorly were then reviewed to identify the cytologic characteristics that may have contributed to their poor performance.nnnRESULTSnA total of 6249 participant responses with general interpretations of benign (n = 4642) or malignant (n= 1607) were reviewed. The sensitivity and specificity of the participant responses for correctly interpreting the cases as benign or malignant were 73% and 91%, respectively. Benign cases with the highest false-positive rates were monomorphic adenoma (53% false-positive), intraparotid lymph node (36%), oncocytoma (18%), and granulomatous sialadenitis (10%). Malignant cases with the highest false-negative rates were lymphoma (57%), acinic cell carcinoma (49%), low-grade mucoepidermoid carcinoma (43%), and adenoid cystic carcinoma (33%). Selected review of the most discordant individual cases revealed possible explanations for some of the interpretative errors.nnnCONCLUSIONSnThese data confirm the difficulty associated with interpretation of salivary gland FNA specimens. Cytologists should be aware of the potential false-positive and false-negative interpretations that can occur in FNAs from this organ site in order to minimize the possibility of diagnostic errors.

Fine-Needle Aspiration of Pulmonary Hamartoma: A Common Source of False-Positive Diagnoses in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology

CONTEXTnWe use data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology to evaluate the accuracy of fine-needle aspiration (FNA) biopsy for diagnosing pulmonary hamartoma (PH).nnnOBJECTIVEnTo use the performance characteristics of the PH cases in the Nongynecologic Cytology Program to determine the accuracy of FNA for identifying these lesions and to determine potential sources of interpretative errors.nnnDESIGNnA retrospective review of the College of American Pathologists Nongynecologic Cytology cumulative data from 1997 to 2003 was performed to identify the overall accuracy of FNA for diagnosing PH and to determine the most common interpretative pitfalls. The slides from each of the cases of PH in the Nongynecologic Cytology Program were then reviewed in an effort to identify the cytologic characteristics that contributed to the poor performance of these cases.nnnRESULTSnA total of 766 participant responses for 19 PH FNA specimens were reviewed. The specificity of FNA for making the correct general reference interpretation of benign was 78%. The false-positive rate was 22%, with the most common false-positive diagnoses being carcinoid tumor, adenocarcinoma, and small cell carcinoma. The overall accuracy for making the correct specific reference diagnosis of PH was 26%. Microscopic review of the individual cases revealed possible explanations for some of the interpretative errors and the most frequent false-positive interpretations.nnnCONCLUSIONSnCytologists should be aware of the potential false-positive interpretations that can occur in FNAs of PH and the potential reasons for these inaccuracies in order to minimize clinically significant diagnostic errors.

Interobserver agreement on microfollicles in thyroid fine-needle aspirates

CONTEXTnAlthough microfollicles are a well-known feature of follicular neoplasms in fine-needle aspirates of the thyroid, the level of agreement about classifying groups as microfollicles is not known.nnnOBJECTIVEnTo determine what features are present in groups that are consistently classified as microfollicles.nnnDESIGNnWe showed 45 small groups of follicular cells each composed of fewer than 50 cells from fine-needle aspirates of the thyroid to 12 members of the College of American Pathologists Cytopathology Committee, who then classified the groups into microfollicles, macrofollicles, and indeterminate groups.nnnRESULTSnTwenty groups were consistently classified as microfollicles, 7 groups as macrofollicles, and 18 groups as indeterminate. Cases that were consistently classified as microfollicles were composed of fewer than 15 cells (19/20 cases), were arranged in a circle with a lumen (13/20 cases) that was at least two-thirds complete (12/20 cases), and were flat (18/20 cases). Cases that were classified as macrofollicular had between 8 and 35 cells, were arranged in sheets composed of at least 15 cells (5/7 cases) or rows of 8 cells (2/7 cases), and were flat (7/7 cases). In contrast, cases that were indeterminate were composed of either 3-dimensional groups (5/18 cases), flat groups of fewer than 10 cells (11/18 cases), or single cells (1/18 cases).nnnCONCLUSIONnNot all small groups of follicular cells are consistently classified as microfollicles, and some are more often classified as macrofollicles. The criteria described here for reproducible microfollicles (<15 cells, arranged in a circle that is at least two-thirds complete, and flat) may help improve the agreement in classification of microfollicles and lead to more consistent classification of thyroid fine-needle aspirates.

Fine-needle aspiration of papillary thyroid carcinoma: distinguishing between cases that performed well and those that performed poorly in the College of American Pathologists Nongynecologic Cytology Program

CONTEXTnAlthough the cytologic features of papillary thyroid carcinoma in fine-needle aspiration specimens are well known, the correlation of these features with the ability of cytologists to identify this tumor has not been well studied.nnnOBJECTIVEnTo compare the cytologic features of cases of papillary thyroid carcinoma that performed poorly with those of cases that performed well.nnnDESIGNnThe cytologic features of 13 cases of papillary thyroid carcinoma from the College of American Pathologists Nongynecologic Cytology Program that performed poorly were compared with those of 15 cases that performed well.nnnRESULTSnCompared with cases that performed well, cases that performed poorly were significantly more likely to lack marked nuclear enlargement (38% vs 100%, P < .001), lack pale chromatin (8% vs 47%, P = .04), and lack intranuclear inclusions (8% vs 53%, P = .02). The differences between the 2 groups in staining, type of preparation, nuclear grooves, nuclear crowding, colloid, cellularity, nuclear pleomorphism, and Hurthle cell change were not significant.nnnCONCLUSIONSnCases of papillary thyroid carcinoma that lack marked nuclear enlargement, pale chromatin, and intranuclear inclusions are significantly more difficult to recognize than cases that have these features. Increased awareness of these types of cases might improve the performance of thyroid fine-needle aspiration in clinical practice.

Fluids—Good and Bad Actors: Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology

CONTEXTnBody cavity fluid examination presents a common and sometimes difficult diagnostic challenge in daily cytology practice. Separating benign from malignant cellular changes may require meticulous screening, careful scrutiny of cellular features, and an understanding of the range of reactive changes. We use the data from the College of American Pathologists (CAP) Interlaboratory Comparison Program in Nongynecologic Cytology (NGC) to identify characteristics of fluids that place them at opposite ends of the diagnostic spectrum.nnnOBJECTIVEnTo assess the features of individual body cavity fluid slides that demonstrated good performance characteristics and compare them to slides that were poor performers.nnnDESIGNnA databank of 10 396 laboratory responses, including a variety of malignant and benign cases obtained from 1997 through 2001, was used to select cases. A cumulative slide history was used to identify slides that performed well or poorly in each reference diagnosis. Cases were confirmed by consensus of 4 CAP Cytopathology Resource Committee members. Observations and characterizations of good and bad performers in each category were recorded and summarized.nnnRESULTSnPercentage of concordance of poor performers ranged from 0% to 58%. Conversely, good performers were identified with high concordance of laboratory diagnosis in each reference category (>80%). Several patterns emerged. Poorly performing cases of adenocarcinoma consisted of slides with rare tumor cells, hypercellular malignant cases without 2 cell populations, and cases with single cells. Poor performance in confirmed squamous cell carcinoma cases related to rare cells without keratinization. Small cell carcinoma and melanoma cases performed poorly when there were few malignant cells. Lymphoma cases demonstrated poor performance when there were abundant pleomorphic lymphoid cells or when rare Reed- Sternberg-like cells were present. Reactive or negative slides performed best with a polymorphous population; poor performers were those with a predominant lymphocyte population mistaken for a hematopoietic neoplasm.nnnCONCLUSIONnClose attention to classic cytologic criteria and careful examination of slides may enhance the educational experience of participants and the performance characteristics of body cavity fluid specimens in the CAP NGC program. Lessons from bad actors in the CAP NGC program may increase awareness of potential diagnostic problems in daily practice or help identify areas for laboratory quality improvement.

Cytologic features of high-grade squamous intraepithelial lesion in ThinPrep Papanicolaou test slides: comparison of cases that performed poorly with those that performed well in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology

CONTEXTnConventional Papanicolaou (Pap) test slides of high-grade squamous intraepithelial lesions (HSILs) that are frequently misdiagnosed are known to have relatively few dysplastic cells. Whether this is true of cases of HSIL in ThinPrep Pap Test specimens is not known.nnnOBJECTIVEnTo determine if cases of HSIL in ThinPrep specimens that are frequently missed have relatively few dysplastic cells.nnnDESIGNnThe cytologic features of 16 ThinPrep cases of HSIL that performed poorly in the College of American Pathologists Interlaboratory Comparison Program were compared with 22 ThinPrep Pap Test cases that performed extremely well.nnnRESULTSnSignificantly more cases that performed poorly had fewer than 250 dysplastic cells (13/16) than cases that performed well (3/22) (P <.001).nnnCONCLUSIONnThinPrep Pap Test cases with a diagnosis of HSIL that performed poorly in this program had significantly fewer dysplastic cells than those that performed well.

Leukemia/Lymphoma in Cerebrospinal Fluid: Distinguishing Between Cases That Performed Well and Poorly in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology

CONTEXTnAlthough the cytologic features of leukemia/lymphoma in cerebrospinal fluid specimens are well known, the correlation of these features with the ability of cytologists to identify this tumor have not been well studied.nnnOBJECTIVEnTo identify the morphologic features of leukemia/lymphoma in cerebrospinal fluid that are associated with good performance and poor performance in an educational interlaboratory comparison program; and to identify the morphologic features associated with how well a slide performs with regard to its reference diagnosis.nnnDESIGNnThe performance of 147 cases of leukemia/lymphoma in the College of American Pathologists Interlaboratory Comparison Program in Non-gynecologic Cytology was analyzed. The cytologic features of a subset of 31 cases composed of relatively equal numbers of Romanowsky-stained and Papanicolaou-stained specimens were further evaluated, and those that performed poorly (n = 12) were compared with those that performed extremely well (n = 19).nnnRESULTSnFor all cases of leukemia/lymphoma in the program, the rate of misclassification as benign for cases with Papanicolaou stain was significantly higher than for those with Romanowsky stain (9.5% vs 2.6%, P < .001). Compared with cases that performed well, slides that performed poorly were more likely to have less than 200 abnormal cells (42% vs 5%, P = .02). The size of the tumor cells and preservation were not significant.nnnCONCLUSIONnCases of specimens of leukemia/lymphoma in cerebrospinal fluid are more likely to be misdiagnosed as benign if they are Papanicolaou-stained or have 200 abnormal cells.

Changes in Participant Performance in the Test-Taking Environment : Observations From the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program

CONTEXTnBecause the consequences of making an interpretive error on a proficiency test are more severe than those made on an educational challenge, the same slide may exhibit different performance characteristics in the 2 different settings.nnnOBJECTIVEnThe results of the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program (PAP PT) provide the opportunity to compare the performance characteristics of the field-validated slides in the PAP PT environment with those of the same graded slides in the College of American Pathologists Educational Program (formerly known as the PAP Program).nnnDESIGNnAll participant responses for negative (category B) and positive (categories C and D) validated slides in the 2006 PAP PT were used to determine the error rates of participants. These data were compared with the historical error rates observed on the same validated slides in the graded PAP Program.nnnRESULTSnThe performance characteristics of the slides in the PAP PT environment were statistically different from those in the Educational PAP Program. In proficiency testing both cytotechnologists (P < .001) and pathologists (P = .002) were more likely to interpret validated category B slides as category C or D and less likely to interpret category C slides as category B (P < .001). These differences were more pronounced among cytotechnologists than among pathologists.nnnCONCLUSIONSnIn the test-taking environment, both cytotechnologists and pathologists appear to use a defensive strategy that results in upgrading of category B slides. This trend is more pronounced among cytotechnologists.

Summary of the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program.

CONTEXTnCreating a tool that assesses professional proficiency in gynecologic cytology is challenging. A valid proficiency test (PT) must reflect practice conditions, evaluate locator and interpretive skills, and discriminate between those practitioners who are competent and those who need more education. The College of American Pathologists Gynecologic Cytology Proficiency Testing Program (PAPPT) was approved to enroll participants in a nationwide PT program in 2006.nnnOBJECTIVEnReport results from the 2006 PAPPT program.nnnDESIGNnSummarize PT results by pass/fail rate, participant type, and slide-set modules.nnnRESULTSnNine thousand sixty-nine participants showed initial PT failure rates of 5%, 16%, and 6% for cytotechnologists, primary screening pathologists, and secondary screening pathologist, respectively. The overall initial test failure rate was 6%. After 3 retests, 9029 (99.6%) of the participants were able to achieve compliance with the PT requirement. No participant tested out; however, 40 individuals dropped out of the testing sequence (8 cytotechnologists, 9 primary screening pathologists, 23 secondary screening pathologists). Initial failure rates by slide-set modules were 6% conventional, 6% ThinPrep, 6% SurePath, and 5% mixture of all 3 slide types.nnnCONCLUSIONSnA total of 99.6% of individuals enrolled in the 2006 PAPPT program achieved satisfactory results. The data confirm that cytotechnologists have higher initial pass rates than pathologists and pathologists who are secondary screeners perform better than those who are primary screeners. There was no difference identified in overall pass rates between the slide-set modules. Further analysis of data should help define the results and ongoing challenges of providing a nationwide federally mandated proficiency testing program in gynecologic cytology.

Cytologic Features of Squamous Cell Carcinoma in Conventional Smears Comparison of Cases That Performed Poorly With Those That Performed Well in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology

CONTEXTnCharacteristic cytologic features have been identified that distinguish cases that are always identified from those that are sometimes missed in the College of American Pathologists Gynecologic Cytology Program for a variety of different lesions and preparations.nnnOBJECTIVEnTo compare the cytologic features of cases of squamous cell carcinoma in conventional smears that perform poorly and well.nnnDESIGNnThe cytologic features of 8 conventional smear cases of squamous cell carcinoma that performed poorly in the College of American Pathologists Interlaboratory Comparison Program were compared with 17 cases that performed extremely well.nnnRESULTSnA total of 2387 individual interpretations were recorded. Of the 86 incorrect responses, 6.2% were for repair, and 0.8% were for Trichomonas. Cases that performed well were significantly more likely to have greater than 1000 dysplastic cells (16/17 vs 4/8, P = .02) and be keratinized (13/17 vs 1/8, P = .007). Obscuring inflammation and cell size were not significant.nnnCONCLUSIONnConventional smears with a diagnosis of squamous cell carcinoma that were always identified were significantly more likely to have greater than 1000 cells and be keratinized than cases that performed poorly.