Gain of the 3q26 region in cervicovaginal liquid-based pap preparations is associated with squamous intraepithelial lesions and squamous cell carcinoma.

BACKGROUND: Chromosomal aberrations have been documented in cervical carcinomas, especially chromosome 3q. The human telomerase RNA gene (hTERC) is located in the chromosome 3q26 region, and its product, telomerase, is involved in the maintenance of chromosome length and stability. Upregulation of telomerase is in general associated with tumorigenesis. In this study, cervicovaginal specimens were analyzed by fluorescence in situ hybridization (FISH) for gain of chromosome 3q26 containing hTERC, and FISH findings were compared with the cytologic and histologic diagnoses. METHODS: Slides prepared from 66 liquid-based preparations from cervical specimens with cytologic diagnoses of negative for squamous intraepithelial lesion or malignancy (NILM, n=4), atypical squamous cells of undetermined significance (ASC-US, n=15), low-grade squamous intraepithelial lesion (LSIL, n=20), high-grade squamous intraepithelial lesion (HSIL, n=24), or cervical squamous cell carcinoma (SCCA, n=3) were analyzed for aberrations of 3q26 using a commercially available two-color FISH probe. The results of the cytologic analysis and those of concurrent or subsequent biopsies, when available, were compared with the FISH-detected 3q26 abnormalities. The Wilcoxon rank-sum test was used to assess associations between 3q26 gains and diagnoses. RESULTS: Gain of 3q26 was significantly associated with the cytologic diagnosis (p<0.0001). Patients with HSIL or SCCA cytology diagnoses had significantly higher percentages of cells with 3q26 gain than did patients with NILM or ASC-US cytologic diagnoses. CONCLUSIONS: FISH can be performed on cervicovaginal liquid-based preparations to detect gain of 3q26. Gain of 3q26 is associated with HSIL and SCCA. This test may be an adjunct to cytology screening, especially high-risk patients.

Efficacy of telecytopathology for preliminary assessment of fine-needle aspirations performed at a remote facility.

INTRODUCTION: The need for real time anatomic pathology services has grown as healthcare systems, traditionally found at large medical centers, expand into smaller communities. The placement of a pathologist is not cost-, time-, or resource-efficient. Telecytopathology can provide rapid offsite evaluation of cytology tissues. This study evaluated the accuracy rate of rendered preliminary assessments for telecytopathology of ultrasound (US)-guided fine-needle aspirations (FNAs) for an offsite facility by comparing preliminary assessment results with the final diagnosis. MATERIALS AND METHODS: The pathology database was searched for telecytopathology US-guided FNAs with rapid offsite evaluation performed at a regional care center from August 2014 to June 2016. A total of 674 consecutive US-guided FNAs from 444 patients were obtained. FNA sites included lymph node (345 cases), breast (178 cases), thyroid gland (71 cases), and others (80 cases). RESULTS: Preliminary assessments of the 674 FNAs were adequate/benign in 275 (41%) cases, adequate/malignant in 182 (27%) cases, adequate/further review needed in 162 (24%) cases, indeterminate/borderline cellularity in 37 (5%) cases, and nondiagnostic in 18 (3%) cases. Final FNA diagnoses rendered included 391 (58%) negative for malignancy, 205 (30%) malignant, 34 (5%) atypical/suspicious for malignancy, 26 (4%) indeterminate cellularity-favor benign, and 18 (3%) nondiagnostic specimens. Concurrent core biopsy was performed in 42 cases and 83 cases were triaged for ancillary studies. The majority (99%) of US-guided FNAs demonstrated concordant preliminary assessments with the final diagnoses. A major discrepancy occurred in 1 case; 5 cases had minor discrepancies. CONCLUSIONS: Remote facility telecytopathology can be utilized as an accurate modality in guiding appropriate tissue acquisition and final diagnosis.

Three-year risk of high-grade CIN for women aged 30 years or older who undergo baseline Pap cytology and HPV co-screening.

BACKGROUND: Papanicolaou (Pap) cytology and high-risk human papillomavirus (HPV) DNA cotesting for women aged ≥30 years are recommended for the prevention of cervical cancer. The objective of the current study was to evaluate the efficacy of this cotesting for predicting the risk of high-grade cervical intraepithelial neoplasia 3 (CIN3) during a 3-year follow-up period. METHODS: A retrospective database search identified women aged ≥30 years who had baseline HPV and Pap cytology cotesting results in 2007 or 2008 and for whom 3-year follow-up results were available. The cumulative 3-year risks of developing CIN-3 were calculated. RESULTS: The 3-year follow-up data after baseline Pap/HPV cotesting were available for 1986 women (mean age, 53 years). Of the 1668 women who had a baseline Pap-negative (Pap-)/HPV- cotesting result, 1561 (93.6%) had a follow-up Pap cytology result that was negative for intraepithelial lesions or malignancy. Of the 1530 women who had follow-up Pap/HPV cotesting, 1504 (98.3%) had a Pap-/HPV- result. The 3-year cumulative risk of developing CIN-3 was found to be highest for women with a baseline Pap-positive (Pap+)/HPV+ cotesting result (12.5%); the risk of CIN-3 was lower in those with a Pap-/HPV+ result (1.5%; P = .0032) or a Pap-/HPV- result (0.06%; P<.0001). The 3-year cumulative risk of CIN-3 was found to be significantly greater for women with an HPV+ result (4.8%) compared with those with an HPV- result (0.06%; P<.0001). CONCLUSIONS: Pap cytology and HPV cotesting are valuable for stratifying CIN-3 risk. Pap cytology and HPV co-screening at a 3-year screening interval appears to carry a low risk of CIN-3 for women who have a baseline Pap-/HPV- cotesting result. Cancer Cytopathol 2017;125:644-51. © 2017 American Cancer Society.

Efficacy of reflex HPV16/18 genotyping in predicting CIN3/VAIN3 in women with HPV+/Pap- results.

INTRODUCTION: Genotyping for human papillomavirus (HPV) types 16/18 has been recommended for women with HPV+/Pap- co-testing results on cervical cancer screening. In this study, we evaluated the efficacy of reflex HPV16/18 genotyping for predicting high-grade cervical and vaginal intraepithelial neoplasia (CIN3/VAIN3) in women who underwent a HPV16/18 genotyping test following HPV+/Pap- co-testing results. MATERIALS AND METHODS: We retrospectively reviewed records of 175 women who underwent reflex HPV16/18 genotyping after HPV+/Pap- co-testing results at our institution from 2011 to 2013. The HPV16/18 genotyping results using the Cervista HPV16/18 assay were correlated with follow-up data (ie, 107 biopsy and 68 Pap test) to assess the risk of CIN3/VAIN3. RESULTS: In 175 women (median age: 51 years), HPV16 and/or 18 were detected in 47 women (26.9%): 36 with HPV16, 9 with HPV18, and 2 with HPV16 and 18. The cumulative incidence of CIN3/VAIN3 was 4.6-fold higher in women with a positive HPV16/18 genotyping result (10.6%) than in women with a negative HPV16/18 result (2.3%) with a statistically significant difference (P = 0.015). The predictive value of reflex HPV16/18 genotyping for CIN3/VAIN3 was 63% (5 out of 8). CONCLUSIONS: A positive reflex HPV16/18 genotyping result predicts a significantly higher risk of CIN3/VAIN3 than a negative reflex 16/18 HPV result, supporting the need for an immediate colposcopy evaluation in these patients. For women with a negative reflex HPV16/18 genotyping result, an annual HPV/Pap cytology co-testing is a reasonable follow-up to predict non-16/18 HPV-associated CIN3/VAIN3.

Clinical performance of hybrid capture 2 human papillomavirus testing for recurrent high-grade cervical/vaginal intraepithelial neoplasm in patients with an ASC-US Papanicolaou test result during long-term posttherapy follow-up monitoring.

CONTEXT: Women who have been treated for high-grade cervical or vaginal intraepithelial neoplasia (CIN or VAIN) or invasive carcinoma are at risk for recurrent/persistent disease and require long-term monitoring. The role of human papillomavirus (HPV) testing in this setting is unclear. OBJECTIVE: To evaluate the clinical performance of the Hybrid Capture 2 (HC2) HPV test for recurrent/residual high-grade CIN or VAIN in patients with a posttherapy abnormal squamous cells of undetermined significance (ASC-US) Papanicolaou test result. DESIGN: We reviewed the follow-up data on 100 patients who had an ASC-US Papanicolaou test and HC2 HPV results after treatment for high-grade CIN/VAIN or carcinoma. Human papillomavirus genotyping was performed for women with a negative HC2 result whose follow-up biopsy revealed CIN/VAIN 2+. RESULTS: The patients' mean age was 47 years. The HC2 test result was positive in 33% of the patients. Follow-up biopsy was available for 17 of these patients (52%) and for 25 of the 67 patients (37%) with a negative HC2 result. A total of 5 of the patients (29%) with a positive HC2 result and 2 of the patients (8%) with a negative HC2 result had CIN/VAIN 3 on follow-up biopsy, a statistically insignificant difference (P = .10). Human papillomavirus 16/18 genotypes were detected in the CIN/VAIN 2+ lesions of 5 patients with a negative HC2 result. CONCLUSIONS: HC2 yielded a false-negative rate of 8% for CIN 3. HC2 testing therefore may not be sufficient for triage of patients with an ASC-US Papanicolaou test result. Patients with ASC-US during long-term posttherapy follow-up need close monitoring, with colposcopic evaluation if clinically indicated.

Reliability of immunostaining using pan-melanoma cocktail, SOX10, and microphthalmia transcription factor in confirming a diagnosis of melanoma on fine-needle aspiration smears.

BACKGROUND: Accurate fine-needle aspiration (FNA) diagnosis of metastatic melanoma is of therapeutic and prognostic significance and often requires ancillary studies. To the authors' knowledge, the reliability of immunostaining using a pan-melanoma cocktail, Sry-related HMG-BOX gene 10 (SOX10), and microphthalmia transcription factor (MITF) in confirming a diagnosis of melanoma on FNA smears has not been studied to date. METHODS: This retrospective study included 50 FNA cases with a definitive diagnosis of melanoma. Twenty-nine cases were epithelioid type (group 1), and 21 cases were predominantly spindle cell type with or without an epithelioid component (group 2). Each case was immunostained using pan-melanoma cocktail, SOX10, and MITF. Staining intensity and the percentage of positive cells were recorded. RESULTS: The pan-melanoma cocktail was positive in 43 cases (86%), SOX10 was positive in 50 cases (100%), and MITF in 45 cases (90%). SOX10 and MITF demonstrated nuclear staining with stronger and more diffuse staining with less or no background staining compared with pan-melanoma cocktail, which displayed cytoplasmic staining. For pan-melanoma cocktail and SOX10, the detection rates were identical in groups 1 and 2 (86% with pan-melanoma cocktail and 100% with SOX10). For MITF, the detection rate was higher in group 1 compared with Group 2 (93% vs 86%). CONCLUSIONS: In the current study, SOX10 was found to have the highest overall detection rate, followed by MITF and pan-melanoma cocktail. The pan-melanoma cocktail and SOX10 performed equally well for groups 1 and 2, and MITF had a higher detection rate in group 1. Overall, SOX10 and MITF appeared to be superior to the pan-melanoma cocktail and SOX10 seemed better than MITF in confirming a diagnosis of melanoma on FNA smears.

The role of SOX11 immunostaining in confirming the diagnosis of mantle cell lymphoma on fine-needle aspiration samples.

BACKGROUND: Mantle cell lymphoma (MCL) demonstrates cytologic features that overlap with those of other types of B-cell non-Hodgkin lymphomas (B-cell NHLs) containing small to medium-sized cells. The accurate diagnosis of MCL is important because MCL has relatively more aggressive biologic behavior and thus requires specific treatment regimens. Fine-needle aspiration (FNA) is used for diagnosing or staging lymphoma, often with the help of immunophenotyping by flow cytometry. However, the cellularity of an FNA sample may not be high enough for flow cytometry, leading to diagnostic difficulty. SOX11 immunostaining is helpful in the diagnosis of MCL in histologic sections. However, to the authors' knowledge, its diagnostic value for FNA samples has not been studied to date. METHODS: Immunostains for SOX11 were performed on 69 FNA cases with final diagnoses of MCL (13 cases, including 10 classic type and 3 blastoid variant), marginal zone lymphoma (8 cases), follicular lymphoma (10 cases), small lymphocytic lymphoma (12 cases), Burkitt lymphoma (9 cases), plasma cell myeloma (7 cases), and benign lymph nodes (10 cases). Preparation types included cytospin slides (65 cases), direct smears (2 cases), and cell block sections (2 cases). The percentage of positive cells (defined as nuclear staining) and staining intensity were recorded. RESULTS: All 13 cases of MCL were positive for SOX11 staining, with 12 cases demonstrating diffuse positivity. All other types of B-cell NHL cases, plasma cell myelomas, and benign lymph nodes were found to have negative results. Weak staining was found in 1 MCL case of blastoid variant. CONCLUSIONS: SOX11 immunostaining on FNA samples is highly sensitive and specific for MCL and can be used as a reliable adjunct to confirm MCL, especially in a recurrent setting.

Endosalpingiosis in peritoneal washings in women with benign gynecologic conditions: thirty-eight cases confirmed with paired box-8 immunohistochemical staining and correlation with surgical biopsy findings.

BACKGROUND: To better define the cytomorphologic spectrum of endosalpingiosis in peritoneal washings (PWs) and thereby facilitate their distinction from well differentiated serous carcinoma, the authors examined PWs from women who underwent surgery and pathologic staging of lesions other than Mullerian malignancies and correlated the findings with surgical specimens. METHODS: This was a retrospective review of medical records and PW specimens from 100 consecutive patients who had PWs coded as both "endosalpingiosis" and "negative for carcinoma" between 2002 and 2012. Thirty-eight of these patients had no gynecologic malignancies. Specimens had been prepared using cytocentrifugation and were stained using the Papanicolaou method. The cytologic findings evaluated were cell arrangement, number of cell groups per case, cellular atypia, and psammoma bodies. Smears also were assessed for paired box-8 (PAX8) immunostaining. The authors compared patients' staging biopsy findings with the findings from a review of the PWs. RESULTS: PW specimens from 35 of 38 patients (92%) exhibited classic endosalpingiosis features: tubular or small branching papillary structures, some with psammoma bodies. Specimens from the 3 remaining patients displayed nonclassic features consistent with dislodged fallopian tube epithelium or endometriosis. From 2 to 20 clusters per slide and from 4 to 50 groups per case were identified. In a few cases, some cell clusters exhibited up to moderate cytologic atypia. Surgical findings included endometriosis, endosalpingiosis, both endometriosis and endosalpingiosis (12 patients; 31.6%), and a variety of unrelated pelvic lesions. All cases were PAX8-positive, confirming their Mullerian origin. CONCLUSIONS: Endosalpingiosis in PWs can be diagnostically challenging. Awareness of intraoperative techniques and correlation with surgical biopsy findings are necessary to avoid a misdiagnosis of malignancy.

Ultrasound-guided fine-needle aspiration biopsy of thyroid bed lesions from patients with thyroidectomy for thyroid carcinomas.

BACKGROUND: To evaluate the efficacy and the limitation of fine-needle aspiration (FNA) biopsy in thyroid bed lesions, a retrospective review was performed of the medical records of thyroid cancer patients who underwent ultrasound-guided FNA biopsy of the thyroid bed at The University of Texas MD Anderson Cancer Center over a 5-year period. METHODS: Data were reviewed on 220 FNA biopsies taken from thyroid bed lesions in 195 patients who had undergone thyroidectomy for thyroid carcinoma. Thyroid bed FNA results were compared with clinical follow-up, including neck dissection results. RESULTS: Recurrent carcinoma was diagnosed by FNA biopsy in 139 of 220 (63%) cases. Neck dissections were performed for 112 sites identified by FNA biopsies, and recurrent carcinoma was confirmed in 110 sites. The concordance between positive and/or suspicious FNA diagnosis and positive neck dissection results was 98% (118 of 120 cases). A false-positive FNA occurred in one patient with follicular thyroid carcinoma. The other discrepancy was attributed to failure to remove the lesion by neck dissection. The diagnostic accuracy of thyroid bed FNA was 100% in papillary and medullary thyroid carcinoma and 93% in follicular thyroid carcinoma. Suspicious and rare false-negative FNA results were attributed to low cellularity and lack of characteristic cytomorphologic features of thyroid carcinoma. CONCLUSIONS: Ultrasound-guided thyroid bed FNA biopsy is accurate and efficient in triaging patients who require post-thyroidectomy follow-up for recurrent thyroid carcinoma. Caution should be taken in the interpretation of FNA specimens that have low cellularity and lack characteristic cytologic features of thyroid carcinoma.

The role of human papillomavirus type 16/18 genotyping in predicting high-grade cervical/vaginal intraepithelial neoplasm in women with mildly abnormal Papanicolaou results.

BACKGROUND: The authors compared the predictive value of type 16 and/or 18 human papillomavirus (HPV) versus non-16/18 HPV types for high-grade (grade ≥2) cervical neoplasm/vaginal intraepithelial neoplasm and carcinoma (CIN/VAIN2+) in women with mildly abnormal Papanicolaou (Pap) results (ie, atypical squamous cells of undetermined significance [ASCUS] or low-grade squamous epithelial lesion [LSIL]). METHODS: The authors retrospectively selected Pap specimens with HPV testing results obtained from 243 women (155 with ASCUS and 88 with LSIL Pap results) in their Department of Pathology. HPV genotyping was performed using the EasyChip HPV blot assay. The Pap specimens with HPV16/18 and non-16/18 HPV types were compared with follow-up biopsy results. Follow-up duration ranged from 1 month to 58 months (mean, 26 months). RESULTS: In total, 58 of 155 specimens (37%) that had ASCUS and 29 of 88 specimens (33%) that had LSIL were positive for HPV16/18. CIN/VAIN2+ biopsies were identified in 43 of 155 women (28%) with ASCUS and in 28 of 88 women (32%) with LSIL. Women with ASCUS and HPV16/18 had a significantly higher rate (43%) of CIN/VAIN2+ than women with ASCUS and non-16/18 HPV types (19%; P = .003; odds ratio, 3.10; 95% confidence interval, 1.48-6.53). There was no statistically significant difference in the rate of CIN/VAIN2+ between women who had LSIL and HPV16/18 (45%) and those who had LSIL and non-16/18 HPV types (29%; P = .16; odds ratio, 1.96; 95% confidence interval, 0.77-4.97). CONCLUSIONS: HPV genotyping for HPV16/18 improved risk assessment for women with ASCUS Pap results and may be used to predict the risk of CIN/VAIN2+ to better guide follow-up management.

The triage efficacy of fine needle aspiration biopsy for follicular variant of papillary thyroid carcinoma using the Bethesda reporting guidelines.

Diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) by ultrasound-guided fine-needle aspiration (FNA) is challenging. In this retrospective review, we evaluated triage efficacy (i.e., potential for triggering surgical intervention) in 44 archived FNA biopsies of surgically confirmed FVPTC obtained between December 2006 and December 2008. We compared the original FNA diagnoses with reclassified diagnoses based on 2007 National Cancer Institute (NCI)/Bethesda recommendations, and reviewed FNA cytologic features. Original FNA diagnoses included colloid nodule (7%, 3/44), atypical follicular cells (5%, 2/44), follicular lesion (11%, 5/44), follicular neoplasm (16%, 7/44), suspicious for malignancy/PTC (27%, 12/44), and papillary thyroid carcinoma (34%, 15/44). Reclassified diagnoses included indeterminate (5%, 2/44), colloid nodule (7%, 3/44), atypical cells of undetermined significance [ACUS] (7%, 3/44), Hurthle cell neoplasm (2%, 1/44), follicular neoplasm (7%, 3/44), suspicious for malignancy/PTC (25%, 11/44), and PTC (48%, 21/44). Triage efficacy was 77% (34/44) for original diagnoses versus 82% (36/44) for reclassified FNA diagnoses. We frequently observed cytologic features of PTC, such as nuclear grooves and fine chromatin; conversely, intranuclear inclusions, though present in 77% cases, were scant. Our review findings suggest that lack of characteristic cytologic features of PTC,coexistence with other thyroid lesions, and small tumor size arethe major obstacles to FNA diagnosis of FVPTC. Reclassification of thyroid FNA diagnoses does not significantly improve triage efficacy. Furthermore, FNA diagnoses of follicular neoplasm and suspicious for malignancy are valuable in patients with FVPTC because they trigger triage toward surgical intervention.