Anal and Cervical High-Risk Human Papillomavirus Genotyping in Women With and Without Genital Neoplasia.

OBJECTIVE: The aim of the study was to compare the prevalence, genotypes, and rates of concomitant anal and cervical high-risk human papillomavirus (HR-HPV) in women with and without a history of HPV-related genital neoplasia. MATERIALS AND METHODS: This was a prospective cohort study conducted from December 2012 to February 2014. Women with a history of neoplasia were considered the high-risk group. Women without a history of neoplasia were considered the low-risk group. Cervical and anal cytology and HPV genotyping were performed. All women with abnormal anal cytology were referred for anoscopy. RESULTS: One hundred eighty-four women met inclusion criteria. High-risk HPV was detected in the anal canal of 17.4% of the high-risk group and 1.5% of the low-risk group (p = .003). High-risk HPV was detected in the cervix of 30.5% of the high-risk group and 7.6% of the low-risk group (p < .001). Concomitant anal and cervical high-risk HPV was detected in 4.4% of the high-risk group and was not detected in the low-risk group (p = .2). Among women with anal intraepithelial neoplasia 2 or greater (n = 5), 60% had HR-HPV detected in the anal canal while none had HR-HPV detected in the cervix. CONCLUSIONS: Women with a history of genital neoplasia are more likely to be positive for anal and cervical HR-HPV compared with women without a history of genital neoplasia. Although there was no significant difference in rates of concomitant HR-HPV between low- and high-risk groups, HR-HPV can be found concomitantly in the anus and the cervix and may be associated with anal intraepithelial neoplasia or carcinoma.

Evaluation of anal cytology and dysplasia in women with a history of lower genital tract dysplasia and malignancy.

OBJECTIVE: To compare the prevalence of abnormal anal cytology, high-risk anal HPV and biopsy proven anal dysplasia among women with a history of lower genital tract malignancy compared to those with dysplasia. METHODS: A prospective cohort study was performed from December 2012 to February 2014 at outpatient clinics at an academic medical center. Women with a history of high-grade cervical, vulvar, or vaginal dysplasia, or malignancy were recruited. Anal cytology and HPV genotyping were performed. All women with abnormal anal cytology were referred for high-resolution anoscopy and biopsy. RESULTS: Sixty-seven women had a lower genital tract malignancy and 123 had a history of genital dysplasia. Average age in the malignancy group was 52.6years (range 27-86) versus 43.5years (range 21-81) in the dysplasia group (p<0.0002). Similar rates of anal dysplasia were seen in both groups, 12.99% (10 cases) in the malignancy group, versus 12.20% (15) in the dysplasia group (p=1.0). Six women in the malignancy group had anal intraepithelial neoplasia (AIN2+) compared to 2 in the dysplasia group (p=0.03). CONCLUSIONS: We found high rates of abnormal anal cytology and HPV in women with lower genital tract dysplasia and malignancy. We also found high rates of anal dysplasia in both groups with a trend towards increased rate in those women with history of genital malignancy. Since precancerous anal lesions are detectable and treatable, anal cancer screening may be potentially useful in both of these higher risk groups.

Utility of Wnt family member 9b (Wnt9b) immunohistochemistry in the cytologic diagnosis of metastatic breast carcinoma.

Wnt family member 9b (Wnt9b) has been demonstrated as a valuable marker for breast cancer diagnosis in surgical pathology. In this study, we examined the utility of Wnt9b in diagnosing metastatic breast carcinoma in cytology samples. Cell blocks from fine needle aspirations (FNA) and fluid specimens of 96 metastatic breast carcinomas and 123 primary and metastatic non-breast neoplasms from various organ systems were evaluated by Wnt9b and GATA3 immunohistochemistry (IHC). Wnt9b and GATA3 were positive in 81.3% and 92.7% of metastatic breast carcinomas, respectively. Conversely, 93.5% and 90.0% of non-breast, non-urothelial carcinomas were negative for Wnt9b and GATA3, respectively. Wnt9b expression was positive in rare gastrointestinal, gynecological, lung, pancreas, and salivary gland tumors. All twenty-eight urothelial carcinomas were negative for Wnt9b, while twenty-six (92.9%) were positive for GATA3. Wnt9b was slightly less sensitive but more specific than GATA3 in diagnosing metastatic breast cancer in cytology samples. Particularly, Wnt9b shows higher specificity in differentiating breast and urothelial primaries. The combined use of Wnt9b and GATA3 may increase diagnostic accuracy.

Comparison of conventional cervical cytology versus visual inspection with acetic acid among human immunodeficiency virus-infected women in Western Kenya.

OBJECTIVE: This study aimed to determine the accuracy of visual inspection with acetic acid (VIA) versus conventional Pap smear as a screening tool for cervical intraepithelial neoplasia/cancer among human immunodeficiency virus (HIV)-infected women. MATERIALS AND METHODS: A total of 150 HIV-infected women attending the Moi Teaching and Referral Hospital HIV clinic in Eldoret underwent conventional Pap smear, VIA, colposcopy, and biopsy. Both VIA and Pap smears were done by nurses, whereas colposcopy and biopsy were done by a physician. Receiver operating characteristic analysis was conducted to compare the accuracies between VIA and Pap smear in sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Among the study participants: VIA was abnormal in 55.3% (83/150, 95% confidence interval [CI] = 47.0%-63.5%); Pap smear showed atypical squamous cells of undetermined significance or worse in 43.7% (59/135, 95% CI = 35.2%-52.5%) and 10% (15/150) of the Pap smears were unsatisfactory. Of the abnormal Pap smears, 3% (2/59) had atypical squamous cells of undetermined significance, 7% (4/59) had high-grade atypical squamous cells, 60% (35/59) had low-grade squamous intraepithelial lesions, 29% (17/59) had high-grade squamous intraepithelial lesions, and 2% (1/59) was suspicious for cervical cancer. Using cervical intraepithelial neoplasia 2 or higher disease on biopsy as an end point, VIA has a sensitivity of 69.6% (95% CI = 55.1%-81.0%), specificity of 51.0% (95% CI = 41.5%-60.4%), PPV of 38.6% (95% CI = 28.8%-49.3%), and NPV of 79.1% (95% CI = 67.8%-87.2%). For conventional Pap smear, sensitivity was 52.5% (95% CI = 42.1%-71.5%), specificity was 66.3% (95% CI = 52.0%-71.2%), PPV was 39.7% (95% CI = 27.6%-51.8%), and NPV was 76.8% (95% CI = 67.0%-85.6%). CONCLUSIONS: Visual inspection with acetic acid is comparable to Pap smear and acceptable for screening HIV-infected women in resource-limited settings such as Western Kenya.

Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis.

OBJECTIVE: To determine whether or not significant differences in the risk of malignancy exist between subgroups of atypical follicular cells in The Bethesda System for Reporting Thyroid Cytology (TBSRTC) in patients who underwent surgical resection. STUDY DESIGN: Between 2004 and 2009, consecutive thyroid fine-needle aspirates at our institutions with a cytologic diagnosis of 'atypical follicular cells' were retrieved and subclassified using the diagnosis and diagnostic comment as: (1) atypical follicular cells with equivocal features of papillary carcinoma [cannot exclude papillary thyroid carcinoma (PTC)] and (2) atypical follicular cells, other patterns. The risks of malignancy for excised nodules were calculated and comparisons were made between these subgroups. Categorical analysis was performed using a 2-tailed Fisher's exact test, and p < 0.05 was considered statistically significant. RESULTS: A total of 7,072 thyroid fine-needle aspiration cases were retrieved, with 1,542 (21.8%) having a histologic follow-up. There were 222 (3.1%) cases of 'atypical follicular cells', with 127 (57.2%) having a histologic correlation and 33 having confirmed malignancies. Atypical follicular cells, cannot exclude PTC, have a significantly higher risk of malignancy than atypical follicular cells, other patterns (45.8 vs. 13.9%, p < 0.01). CONCLUSIONS: Atypical follicular cells with equivocal features of papillary carcinoma is not a low-risk cytologic diagnosis.

Cytomorphology of intraductal papillary neoplasm of the biliary tract.

Intraductal papillary neoplasms of the bile duct (IPNBs) are papillary epithelial proliferations with delicate fibrovascular cores within dilated bile ducts. They are thought to be premalignant lesions with potential to progress invasive tumors. To our knowledge, there are no prior descriptions of IPNB cytomorphology. A 58-year-old male presented with painless jaundice and elevated liver function tests was found to have an intraluminal mass within the left hepatic duct. A bile duct brushing diagnosed as "atypical cells present" showed a cellular specimen composed of papillary groups and linear strips of mostly cuboidal/columnar cells with mild atypia and vacuolated cytoplasm. A left hepatic lobectomy including extrahepatic bile ducts showed the mass consisted of papillary cores lined by pancreatobiliary-type epithelium with mild-to-severe atypia, consistent with IPNB with a focus suspicious for invasion. The cytomorphologic features described in the current case suggest intraductal papillary neoplasm but may not be specific since similar features could be seen in other bile duct tumors and even in nonneoplastic conditions such as stent or cholelithiasis. However, it is worthwhile to report papillary hyperplasia with atypia in common bile duct brushings in order to avoid a false-negative diagnosis, especially in the context of a filling defect by images which does not appear to be a stone.

A 10 year retrospective review of fine needle aspiration cytology of cystic lesions of the breast with emphasis on papillary cystic lesions.

BACKGROUND: Fine needle aspiration cytology (FNA) is a simple, safe, cost effective, and accurate method for diagnosis of cystic lesions of the breast. Our study aims to correlate FNA cytology of cystic lesions of the breast with the histologic diagnosis. METHODS: During a period of 10 years (2007-2017), 314 cases of breast cystic lesions were retrieved from a total 1073 cases of breast FNAs. Of these, 78 cases from 77 patients (mean age = 54.6, female: male = 76:1) with simultaneous FNA and core needle biopsy (CNB) and/or excision specimen were reviewed. The FNA cytology reports were correlated with the histology results of CNB (n = 72) and breast excision (n = 20). RESULTS: Overall, 73 of 78 (93.6%) FNA cases were concordant with CNB and/or excision results. Fifty-five benign FNAs were all concordant with histology and reported as benign (negative predictive value = 100%). The positive predictive value of FNA with a malignant diagnosis was 100%, 71.4% for a suspicious diagnosis, and 33.3% for atypical cytologic diagnosis. Two of six papillary lesions were discordant with the concurrent CNB, but the FNA results were concordant with the final histology on excision. CONCLUSIONS: FNA allows accurate diagnosis of benign cystic lesions. FNA also plays a prominent role in evaluating cystic papillary lesions of the breast and helps to prevent false negative results on the simultaneous CNB. It is essential that FNA and CNB diagnoses be used in combination to make the correct diagnosis and for clinical management.

Use of visual inspection with acetic acid, Pap smear, or high-risk human papillomavirus testing in women living with HIV/AIDS for posttreatment cervical cancer screening: same tests, different priorities.

OBJECTIVES: Few studies have addressed optimal follow-up for HIV-infected women after cervical treatment. This study aimed to compare performance of three available tests to detect posttreatment cervical disease in HIV-infected women in Kenya. DESIGN: This is a prospective cohort study. METHODS: At least 6 months following cryotherapy, 517 HIV-infected women were evaluated concurrently with visual inspection with acetic acid (VIA), papanicolaou (Pap) smear, and high-risk human papillomavirus (HR-HPV) testing. Women positive by any test (≥low-grade squamous intraepithelial lesion for Pap) were scheduled for colposcopy and biopsy. Among 248 with histological confirmation [and 174 assumed to be truly negative for cervical intraepithelial neoplasia (CIN)2+ after testing negative by all three tests], the ability of each test alone, or in combination, to detect CIN2+ was calculated to determine their utility in posttreatment follow-up. RESULTS: The median age of women was 35 years, 68% were WHO stage 1-2, with a median CD4 cell count of 410 cells/µl, and 87% were on combination antiretroviral therapy. At a median of 6.3 months posttreatment, 64% had an abnormal screen by VIA, Pap, and/or HR-HPV. Among women with histological confirmation, 72 (30%) had persistent/recurrent CIN2+. As single tests, Pap correctly classified the most cases (83%) and had the highest specificity [91% (88 and 95%); sensitivity 44% (35 and 53%)], whereas HR-HPV had the highest sensitivity [85% (75 and 96%); specificity 54% (49 and 58%)]. VIA was not sensitive [27% (18 and 36%)] for the detection of posttreatment CIN2+ [specificity 82% (79 and 86%)]. CONCLUSION: With the goal to minimize the number of false negatives (e.g. not miss CIN2+ posttreatment) in this population that is high-risk due to both prior cervical disease and HIV infection, HR-HPV-based algorithms are recommended.

Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women.

OBJECTIVE: To compare the prevalence of abnormal anal cytology and high-risk human papillomavirus (HPV) among women with a history of HPV-related genital neoplasia with women without a history of HPV-related genital neoplasia. METHODS: A cross-sectional cohort study was performed from December 2012 to February 2014. Women were recruited from outpatient clinics at an academic medical center. Women with a history of high-grade cervical, vulvar, or vaginal cytology, dysplasia, or cancer were considered the high-risk group. Women with no history of high-grade anogenital dysplasia or cancer were considered the low-risk group. Human immunodeficiency virus-positive women were excluded. Anal cytology and HPV genotyping were performed. Women with abnormal anal cytology were referred for high-resolution anoscopy. RESULTS: There were 190 women in the high-risk group and 83 in the low-risk group. The high-risk group was slightly older: 57 years compared with 47 years (P=.045); 21.7% of low-risk women had abnormal anal cytology compared with 41.2% of high-risk women (P=.006). High-risk HPV was detected in the anal canal of 1.2% of the low-risk group compared with 20.8% of the high-risk group (P<.001). Among women who underwent anoscopy, no anal dysplasia was detected in the low-risk group, whereas 13.4% in the high-risk group had anal dysplasia with 4.2% having anal intraepithelial neoplasia 2 or greater (P<.001). CONCLUSION: Human immunodeficiency virus-negative women with a history of lower genital tract neoplasia are more likely to have positive anal cytology, anal high-risk HPV, and anal intraepithelial neoplasia. Anal cancer screening should be considered for these high-risk women. LEVEL OF EVIDENCE: II.

Preoperative High-Resolution Ultrasound for the Assessment of Malignant Central Compartment Lymph Nodes in Papillary Thyroid Cancer.

BACKGROUND: The identification and removal of malignant central compartment lymph nodes (MCLN) is important to minimize the risk of persistent or recurrent local disease in patients with papillary thyroid cancer (PTC). While the diagnostic accuracy of preoperative ultrasound for the assessment of lateral compartment node metastases is well recognized, its role in the identification of central compartment node metastases in patients with PTC is less established. This study delineates the utility of high-resolution ultrasound (HUS) for the assessment of MCLN in patients with PTC. METHODS: A retrospective chart review was performed of 227 consecutive patients who underwent total thyroidectomy for biopsy-proven PTC by a single endocrine surgeon in an academic tertiary care center between 2004 and 2014. Preoperative sonographic results were compared to postoperative pathology reports to determine the accuracy of HUS for the assessment of MCLN. Statistical analysis also included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: HUS identified abnormal central compartment nodes in 51 (22.5%) patients. All 227 patients underwent a careful central compartment node exploration. One hundred and four (45.8%) patients had MCLN identified by surgery, of whom 65 (62.5%) had a negative preoperative central compartment HUS. The sensitivity and specificity of preoperative HUS for the assessment of MCLN were 0.38 and 0.90, respectively. The PPV and NPV were 0.76 and 0.63, with an accuracy of 0.66. CONCLUSION: Preoperative HUS is quite specific for the identification of MCLN in patients with PTC. The present findings emphasize, however, that a negative HUS does not obviate the need for careful exploration of the central compartment to minimize the risk of persistent or recurrent local disease.

Fine needle aspiration of parathyroid lesions.

OBJECTIVE: To assess the cytologic features of parathyroid lesions and to determine if it is possible to differentiate between parathyroid hyperplasia (PH) and parathyroid adenoma (PA) based on fine needle aspiration (FNA). STUDY DESIGN: FNAs of 14 parathyroid lesions were performed during intraoperative consultation. Alcohol-fixed, Papanicolaou-stained smears and air-dried Diff-Quik-stained smears were prepared in each case. Cytologic features were evaluated. RESULTS: All cases, PA and PH, showed numerous bare nuclei in the background. Ninety percent of PA contained microfollicular groups in addition to sheets and syncytia, while PH was arranged primarily in sheets and syncytia without microfollicles. Nuclear pleomorphism was seen in 33% of PA and absent from PH. CONCLUSION: Careful evaluation of cytologic features might help to differentiate between PA and PH on FNA.

Mammary analog secretory carcinoma of salivary gland: cytologic diagnosis and differential diagnosis of an unreported entity.

Mammary analog secretory carcinoma of salivary gland (MASC) is a recently described salivary gland tumor. Cytologic features of this neoplasm have hitherto not been described in the literature. This report discusses the fine-needle aspiration findings of MASC and its differential diagnosis. Aspirates were richly cellular and consisted of clusters and singly dispersed cells with mild cytologic atypia. Cytoplasm was abundant and finely vacuolated. Signet ring cells were observed. Surgical resection confirmed the diagnosis of MASC.

Improved preoperative definitive diagnosis of papillary thyroid carcinoma in FNAs prepared with both ThinPrep and conventional smears compared with FNAs prepared with ThinPrep alone.

BACKGROUND: ThinPrep (TP) liquid-based preparations are increasingly being used in nongynecologic specimens. Few studies have evaluated TP as a sole diagnostic modality in the setting of thyroid fine-needle aspiration (T-FNA). Herein, the authors evaluate the usefulness of TP as a sole diagnostic modality in a nonsplit sample. METHODS: Consecutive T-FNAs were identified at 2 tertiary care institutions; 1 institution processed thyroid FNA entirely with TP, and the other used a combination of TP and conventional preparations (CP). Cytodiagnoses, surgical pathology, and/or clinical follow-up were recorded. Performance parameters for the 2 settings were compared. RESULTS: A cytologic diagnosis of positive for malignancy was correct in 98.8% of TP + CP cases and in 100% of TP cases. Papillary thyroid carcinoma cases were definitively diagnosed in 53.1% of T-FNAs prepared by TP + CP compared with 34.4% of T-FNAs prepared with TP alone (P = .0015 by Fisher 2-tailed exact test). Of patients ultimately diagnosed with papillary thyroid carcinoma, 89% were initially treated by total thyroidectomy in the TP + CP group compared with 79.5% in the TP-only group (P = .027 by Fisher exact test). CONCLUSIONS: TP as a sole preparatory technique does not improve the usefulness of T-FNA as a screening test. However, combining CP and TP increases the rate of definitive cytologic diagnosis of malignancy in papillary thyroid carcinoma. Thus, combining TP and CP enhances the diagnostic component of T-FNA.