Michael R. Henry

The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

Abstract The terminology for human papillomavirus (HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.

The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.

The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) project was co-sponsored by the College of American Pathologists (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP) and included 5 working groups; three work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted upon at the consensus meeting. The final approved recommendations standardize biologically-relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.

False positive endoscopic ultrasound fine needle aspiration cytology: incidence and risk factors

Objective It is broadly accepted that the false positive (FP) rate for endoscopic ultrasound fine needle aspiration (EUS FNA) is 0–1%. It was hypothesised that the FP and false suspicious (FS) rates for EUS FNA are greater than reported. A study was undertaken to establish the rate and root cause of discordant interpretation. Design Using a prospectively maintained endoscopic database, cytohistological discordant EUS FNA examinations from 30 July 1996 to 31 December 2008 were identified retrospectively. Setting Tertiary referral centre. Main outcome measures Discordant FNA was defined by positive or suspicious FNA cytology in the absence of malignancy or neoplasm in the subsequent surgical pathology specimen, specifically in the absence of neoadjuvant therapy. Three cytopathologists conducted a blinded review of randomised discordant and matched specimens. Results FNA was performed in 5667/18 066 (31.4%) patients undergoing EUS, of whom 2547 had cytology results interpreted as ‘positive’ or ‘suspicious’ or ‘atypical’ for malignancy or neoplasm. Subsequent surgical resection without prior neoadjuvant therapy was performed in 377 patients with positive or suspicious cytology. The FP rate was 20/377 (5.3%) and increased to 27/377 (7.2%) when FS cases were included. The incidence of discordance was consistent over time (1996–2002: 10/118 (8.6%) vs 2003–2008: 17/259 (6.6%); p=0.5) and was higher in non-pancreatic FNA (15%) than pancreatic FNA (2.2%; p=0.0001). Two-thirds of the non-pancreatic FP cases involved sampling of perioesophageal or perirectal nodes in patients with luminal neoplasms or Barretts oesophagus. Following pathological re-review, discordance was attributed to translocated cell contamination/sampling error (50%) or cytopathologist interpretive error (50%). Conclusions These findings refute the accepted paradigm that FP cytology rarely occurs with EUS FNA. Further investigation revealed that FP FNA developed secondary to endosonographer technique or initial cytological misinterpretation, and is particularly likely when perioesophageal or perirectal nodes are aspirated in the setting of a luminal neoplasm or Barretts oesophagus. Further study is needed to determine the significance of these findings and potential impact on the performance of FNA and patient outcomes.

Practices of participants in the college of american pathologists interlaboratory comparison program in cervicovaginal cytology, 2006.

CONTEXT Liquid-based preparations (LBPs) and human papillomavirus testing have led to changes in cervical cytology practices. The College of American Pathologists attempts to track practice patterns using a supplemental questionnaire, which allows laboratories to report diagnostic practices. OBJECTIVE To analyze the 2006 reporting practices and to compare the results with the 2003 survey data. DESIGN Questionnaire was mailed to 1621 laboratories. Participants included laboratories enrolled in the 2006 College of American Pathologists Gynecologic Proficiency Testing Program or the educational Interlaboratory Comparison Program in Gynecologic Cytology. RESULTS Of the 679 responding laboratories (response rate, 42%), most (97.8%; n = 664) had implemented the Bethesda 2001 terminology. The median rate for all preparations with low-grade squamous intraepithelial lesions was 2.5% (2.9% for LBPs) compared with a 2003 median rate of 2.1%; the increase was confined to LBPs. Rates for high-grade squamous intraepithelial lesions (median, 0.5%) and atypical squamous cells have changed little. High-grade squamous intraepithelial lesions and unsatisfactory rates varied at statistically significant levels between types of LBPs. Most atypical squamous cell cases were subclassified as undetermined significance (median, 4.3%). The median ratio of atypical squamous cells to squamous intraepithelial lesions and carcinomas for all specimen types combined was 1.5, similar to the 2003 median ratio of 1.4. The median rates for findings of squamous cell abnormalities for 2006 were significantly higher for LBPs than for conventional smears. CONCLUSIONS Most responding laboratories have implemented the Bethesda 2001 terminology. There is an increase in LBP low-grade squamous intraepithelial lesion rates when compared with 2003 data. Liquid-based preparations have higher median squamous intraepithelial lesion and atypical squamous cell rates.

Predictors of Malignancy in Patients with Cytologically Suspicious Thyroid Nodules

BACKGROUND Fine needle aspiration (FNA), although very reliable for cytologically benign and malignant thyroid nodules, has much lower predictive value in the case of suspicious or indeterminate nodules. We aimed to identify clinical predictors of malignancy in the subset of patients with suspicious FNA cytology. METHODS We reviewed the electronic medical records of 462 patients who had FNA of thyroid nodules at our institution with a suspicious cytological diagnosis, and underwent surgery at Mayo Clinic between January 2004 and September 2008. Demographic data including age, gender, history of exposure to radiation and use of thyroid hormone was collected. The presence of single versus multiple nodules by ultrasonography, nodule size, and serum thyroid-stimulating harmone (TSH) level before thyroid surgery were recorded. Analysis of the latter was limited to patients not taking thyroid hormone or antithyroid drugs at the time of FNA. RESULTS Of the 462 patients, 327 had lesions suspicious for follicular neoplasm (S-FN) or Hürthle cell neoplasm (S-HCN), 125 had cytology suspicious for papillary carcinoma (S-PC) and 10 had a variety of other suspicious lesions (medullary cancer, lymphoma and atypical). Malignancy rate for suspicious neoplastic lesions (FN+HCN) was ∼15%, whereas malignancy rate for lesions S-PC was 77%. Neither age, serum TSH level, or history of radiation exposure were associated with increased malignancy risk. The presence of multiple nodules (41.1% vs. 26.4%, p=0.0014) or smaller nodule size (2.6±1.8 cm vs. 2.9±1.6 cm, p=0.008) was associated with higher malignancy risk. In patients with cytology suspicious for neoplasm (FN, HCN) malignancy risk was higher in those receiving thyroid hormone therapy than in nonthyroid hormone users (37.7% vs. 16.5%, p=0.0004; odds ratio: 3.1), although serum TSH values did not differ significantly between thyroid hormone users and nonusers. CONCLUSION In patients with cytologically suspicious thyroid nodules, the presence of multiple nodules or smaller nodule size was associated with increased risk of malignancy. In addition, our study demonstrates for the first time, an increased risk of malignancy in patients with nodules suspicious for neoplasm who are taking thyroid hormone therapy. The reason for this association is unknown.

Metastasis to the thyroid gland: report of a large series from the Mayo Clinic.

Objectives:Metastases to the thyroid gland are not as unusual as previously believed. This study reports the largest number of patients with metastatic disease of the thyroid to date, confirms the accuracy of fine-needle aspiration (FNA) in diagnosing metastasis, and reviews the incidence and management through our institutional experience. Methods:This study entailed review of all thyroid FNAs performed at Mayo Clinic, Rochester during the period 1980 to 2010 and identified 97 patients with a metastatic solid neoplasm of the thyroid gland. Results:Frequent primary tumor sites included kidney (22%), lung (22%), and head and neck (12%). The median age at discovery of thyroid metastasis was 63 years. The time from diagnosis of primary tumor to metastasis to the thyroid gland was most considerable for renal cell carcinoma (mean 113 mo). Forty-one patients underwent thyroid resection with an average tumor size of 3 cm. Median survival in all patients with metastases was 20 months (range, 1 to 228 mo). Patients who underwent thyroid resection had a median survival of 30 months (range, 3 to 171 mo), whereas survival in patients without thyroid surgery was 12 months (range, 1 to 228 mo, log-rank test P=0.09). Conclusions:Our experience over the last 30 years confirms that FNA remains a sensitive and specific method to detect metastases to the thyroid. In any patient with a history of a malignancy, a new thyroid mass should be promptly evaluated for recurrent malignancy as early diagnosis and surgical resection resulted in a nonstatistically significant increased median survival.

The Bethesda System 2001: an update of new terminology for gynecologic cytology

From the inception of TBS in 1988, it has been well received by the pathology and clinical communities. The need for a unifying system of nomenclature was so great that most of the laboratories in the United States, as well as in numerous countries worldwide, quickly adopted TBS. By 1991, only 2 years after the initial publication of the initial TBS, 57% of United States laboratories were using the system. By 1994, almost 90% of laboratories were using TBS [28]. Although explanations for such a quick acceptance of TBS are many, one of the leading reasons is, most certainly, the sound and thoughtful basis for all of the elements of TBS. These include: (1) nomenclature that provides uniform diagnostic terminology to facilitate unambiguous communication between the laboratory and the clinician; (2) diagnostic categories that incorporate the latest scientific information on the pathogenesis and prognosis of cervical lesions; and (3) incorporation of the evaluation of specimen adequacy as an integral part of the report. From the beginning, TBS was more than just a diagnostic lexicon. When Drs. Kurman and Solomon decided that something had to be done about the diagnostic mess in GYN cytology, they did not develop another system. Instead, they convened an international consensus conference to look at the problem and come up with a comprehensive, relevant solution. The input from the entire community, which lent strength to the initial TBS, has continued to the present. This is highlighted by the enormous amount of input that was received by the 2001 TBS forum groups that enabled them to fine tune the existing terminology to meet the needs of todays clinicians. The result, continues to be an evolving, comprehensive, and clinically relevant entity, that should meet the needs of pathologists and clinicians for the foreseeable future.

Clinical decision support with automated text processing for cervical cancer screening.

Objective To develop a computerized clinical decision support system (CDSS) for cervical cancer screening that can interpret free-text Papanicolaou (Pap) reports. Materials and Methods The CDSS was constituted by two rulebases: the free-text rulebase for interpreting Pap reports and a guideline rulebase. The free-text rulebase was developed by analyzing a corpus of 49 293 Pap reports. The guideline rulebase was constructed using national cervical cancer screening guidelines. The CDSS accesses the electronic medical record (EMR) system to generate patient-specific recommendations. For evaluation, the screening recommendations made by the CDSS for 74 patients were reviewed by a physician. Results and Discussion Evaluation revealed that the CDSS outputs the optimal screening recommendations for 73 out of 74 test patients and it identified two cases for gynecology referral that were missed by the physician. The CDSS aided the physician to amend recommendations in six cases. The failure case was because human papillomavirus (HPV) testing was sometimes performed separately from the Pap test and these results were reported by a laboratory system that was not queried by the CDSS. Subsequently, the CDSS was upgraded to look up the HPV results missed earlier and it generated the optimal recommendations for all 74 test cases. Limitations Single institution and single expert study. Conclusion An accurate CDSS system could be constructed for cervical cancer screening given the standardized reporting of Pap tests and the availability of explicit guidelines. Overall, the study demonstrates that free text in the EMR can be effectively utilized through natural language processing to develop clinical decision support tools.

ASCCP Patient Management Guidelines Pap Test Specimen Adequacy and Quality Indicators

Our objective was to provide management guidelines according to Papanicolaou (Pap) test specimen adequacy based on literature review and expert opinion. A task force named by the American Society for Colposcopy and Cervical Pathology (ASCCP) conducted a literature review and discussed appropriate management. The Steering Committee of the ASCCP and other experts reviewed the guidelines. The guidelines recommend a repeated Pap test in 12 months for most women undergoing routine annual/biennial screening if the current Pap test is negative but either lacks an endocervical/ transformation zone component or is partially obscured. Indications for considering an earlier repeat are also provided. The preferred managementfor unsatisfactory Pap tests is a repeated Pap test within a short interval of 2 to 4 months. The management guidelines will help promote optimal and uniform follow-up of women according to Pap test specimen adequacy.

Identification of malignant cytologic criteria in pancreatobiliary brushings with corresponding positive fluorescence in situ hybridization results.

Cytologic evaluation of pancreatobiliary brushings is specific but poorly sensitive for malignancy. Detection of polysomic cells by fluorescence in situ hybridization (FISH) is significantly more sensitive than routine cytology with similar specificity. The purpose of this study was to identify cytologic criteria most associated with malignancy in specimens unaffected by sample failure. Endoscopic brushings were split equally for routine cytologic and FISH analyses per clinical practice. We retrospectively evaluated 16 cytologic criteria on Papanicolaou-stained slides. We assumed that the presence of polysomic cells by FISH indicated successful tumor sampling in specimens from patients with pathologic evidence of malignancy on follow-up. We compared cytologic criteria of malignant brushings with corresponding positive FISH results (positive control, n = 39) with those without evidence of malignancy and corresponding negative FISH results (negative control, n = 30). The presence of single abnormal cells, irregular nuclear membranes, and enlarged nuclei were independent predictors of malignancy by logistic regression (P < .05).