Pitfalls in Salivary Gland Cytology.

BACKGROUND: Salivary gland lesions possess diagnostic challenges on fine needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of cytomorphology. Herein, we review common salivary gland neoplasms, their cytomorphologic features, their diagnostic pitfalls, and ancillary studies helpful in achieving an accurate diagnosis. SUMMARY: There are many cytomorphologic overlaps between benign and malignant salivary gland entities. Moreover, metaplasia, cystic changes, and degenerative changes are common findings adding to diagnostic dilemmas. These complicating factors contribute to a minute risk of malignancy in salivary gland lesions that are interpreted as benign on FNA. In rare cases, even malignant salivary gland neoplasms are misinterpreted as benign on aspirated material due to the many cytomorphologic overlaps. For example, benign and malignant neoplasms containing stroma such as myoepithelioma and adenoid cystic carcinoma may be misinterpreted as pleomorphic adenoma. Moreover, diagnosis of salivary gland neoplasms with basal cell features can be confusing on FNA materials; for example, basal cell adenoma can be misinterpreted as adenoid cystic carcinoma. Mucoepidermoid carcinomas have many different appearances on aspirated material due to variable amounts of mucin, degree of nuclear atypia, cellular content, and squamous metaplasia. Acinic cell carcinoma exhibits large cells with abundant cytoplasm on FNA, which can be mistaken for oncocytic cells in oncocytoma or Warthin tumor. Salivary duct carcinoma shows distinct features of malignancy and thus can be mistaken for secondary tumors involving the salivary glands or other malignant salivary gland tumors. The presence of tumor-associated lymphocytes is another underlying cause of misdiagnosis, especially when considering the differential diagnosis of an an intraparotid lymph node. Ancillary studies such as immunohistochemistry and molecular studies are gaining more attention to be utilized on FNA cases. PLAG1 immunostaining, CD117 , DOG1, mammaglobin, and androgen receptor (AR) are examples of commonly used immunostains in diagnosis of salivary gland lesions. MYB gene fusion , rearrangements of the MAML2 gene, ,and ERBB2/HER2 are examples of molecular alterations useful in diagnosis of salivary gland neoplasms. In conclusion, the aim of salivary gland cytology is to differentiate benign entities from the malignant ones and to prevent unnecessary aggressive treatments.

Rapid on-site evaluation (ROSE) of image-guided FNA specimens improves subsequent core biopsy adequacy in clinical trial patients: The impact of preanalytical factors and its correlation with survival.

BACKGROUND: Sufficient tumor collection has become of utmost importance in therapeutic experimental protocols. Rapid on-site evaluation (ROSE) ensures adequate sampling for quantification of biomarkers, molecular analyses, and other ancillary studies. The objectives of this study were to evaluate the role of ROSE in trial-associated fine-needle aspiration (FNA) and to analyze predictors of adequacy and cumulative survival from in-house FNA cases used in clinical trials. METHODS: Clinical trial FNA biopsies performed at a large academic institution were analyzed over 10 months using a comprehensive chart review of the electronic medical records. SPSS version 28 was used for statistical analysis. RESULTS: Three hundred twenty-five FNAs were collected for 57 clinical trials. In total, 225 individual patients had an average of 1.4 FNA procedures each as a result of a multidepartmental collaborative effort. ROSE was performed for all patients, and adequacy was evaluated by cytotechnologists. Seventy-eight percent of samples were considered adequate, 14% were considered less than optimal, and 8% were considered inadequate, with the latter two categories designated together as less than adequate. The imaging modalities were mainly ultrasound-guided (n = 267; 82%) and computed tomography-guided (n = 58; 18%). There was a statistically significant association between adequate sampling and ultrasound-guided biopsies (83%) compared with computed tomography-guided biopsies (59%; p < .01). The effect of body mass index (BMI) on mortality was also a significant finding. The authors observed a survival benefit in patients who had elevated BMIs (range, 25.0-34.9 kg/m2 ) compared with those who were underweight (BMI, <18.5 kg/m2 ) or class III obese (BMI, >35.0 kg/m2 ; p < .01). Therefore, the best predictors of adequacy and mortality were imaging modality and BMI, respectively. CONCLUSIONS: Ultrasound-guided modalities are recommended for obtaining adequate FNA sampling for clinical trials. In addition, patients with cancer who had slightly elevated BMIs (25.0-34.0 kg/m2 ) had increased overall survival in this cohort.

Risk Assessment of Human Papillomavirus-Positive Cytology-Negative Cervical Cancer Screening in Black and White Women.

OBJECTIVES: As we move toward human papillomavirus (HPV) only as the preferred cervical cancer screening method, we performed a retrospective analysis of Black and White women with negative cytology (Papanicolaou negative [PAPneg]) and positive high-risk HPV (hrHPV) (HPVpos) results and determined follow-up. METHODS: We searched our pathology data system for patients with PAPneg/HPVpos results (2017-2019). Follow-up data were reviewed (39 months), and a comparison among race was performed. RESULTS: In total, 1,728 patients were identified (Black, 53%; White, 47%). Twenty-nine percent of the patients had no follow-up with no difference among the races. HPV 16 was more common among Whites (P < .01), while non-16/18 hrHPV was more common among Black patients (P = .01). A total of 30 (3.3%) Black and 26 (3.2%) White patients were diagnosed with cervical intraepithelial neoplasia grade 2/3 (CIN 2/3). More White women were diagnosed on biopsy alone (negative endocervical curettage) compared with Black women (20 vs 9, P < .01). Meanwhile, there were 21 Black and 6 White women with CIN 2/3 on endocervical curettage (P = .01). CONCLUSIONS: Follow-up of women with PAPneg/HPVpos remains a challenge. There was no disparity in follow-up when cohorts were compared. However, Black women had higher numbers of high-grade intraepithelial lesions on endocervical curettage.

The Value of Second-Opinion Consultation in Nongynecologic Cytopathology.

OBJECTIVES: The value of consultation in pathology has been well documented in surgical pathology, but there are few comprehensive studies of consultation cases in cytopathology. Here we report our experience with cytopathology consultation cases at a large academic center. METHODS: A review of consultation cases at our institution was performed by searching our laboratory information system. The contributing institution's diagnosis was compared with that rendered by the reviewing cytopathologist to assess major and/or minor diagnostic discrepancies. RESULTS: In total, 928 cases were reviewed with the following distribution: fine-needle aspiration (FNA, 79.4%), exfoliative nongynecologic cytology (18.3%), and cases with both FNA and nongynecologic cytology (2.3%). There were 379 (40.8%) true consults and 549 (59.2%) confirming consults. A total of 586 (63.1%) cases were in agreement with the outside pathologist, 78 (8.4%) cases had major discrepancies, and 264 (28.4%) cases had minor discrepancies. Major discrepancies were most common for pancreas (38.5%), lymph node (11.5%), and soft tissue sites (9.0%). CONCLUSIONS: Of the cases, 8.4% had major diagnostic discrepancies between the original diagnosis and the consultation diagnosis, which is consistent with reported values in surgical pathology consultation studies. The findings support the importance of second-opinion consultation in cytopathology to guide patient care.

Comparison of Cervical Cancer Screen Results on Female-to-Male Transgender Patients With Female Patients.

OBJECTIVES: There are limited data on cervical screen results from female-to-male (FTM) transgender patients. Herein, we compiled demographic information and cervical screen testing on FTM transgender patients and compared with age-appropriate controls. METHODS: A search of our previous and current databases was performed for Papanicolaou (Pap) tests from patients taking testosterone and/or with a diagnosis of gender dysphoria, transsexualism, or transvestism. Patient data were reviewed. Relative risks of abnormal Pap smear and human papillomavirus (HPV) infection were calculated against age-matched controls. RESULTS: Eighty-nine Pap tests from FTM transgender individuals were identified, with a mean age of 31.3 years (range, 21-60 years). The Pap test diagnoses were distributed as follows: negative for intraepithelial lesion (n = 84, 94.4%), atypical squamous cells of undetermined significance (n = 0), low-grade intraepithelial lesion (n = 4, 4.5%), and high-grade squamous intraepithelial lesion (n = 1, 1.1%). Fifty (56.2%) patients had concurrent high-risk HPV testing with four (8%) positive results. Relative risk was 0.625 (95% confidence interval [CI], 0.25-1.59; P = .32) for an abnormal Pap test and 0.55 (95% CI, 0.19-1.52; P = .24) for HPV compared with 267 age-matched controls. Of note, 13.5% of patients older than 21 years had documentation of never having a prior Pap test in our medical record. CONCLUSIONS: In our study, FTM transgender individuals were not at a higher or lower risk of HPV infection or abnormal Pap test result compared with women. However, larger studies are needed to support our findings.

Extruded polymer films pigmented with a heterogeneous ion-pair based lumophore for O2 sensing.

A novel approach to polymeric Ru(II)-diimine luminescent O2 sensors is described. The Ru(II)-diimine, tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) dichloride ([Ru(dpp)3](2+)), is first ion-paired to the surface of heterogeneous TiO2 particles, rendered negatively charged due to the alkali nature of the aqueous solution, to produce an O2 sensitive pigment with a strikingly high oxygen sensitivity (i.e. PO2 (S = 1/2) = 0.002 atm, where PO2 (S = 1/2) is defined as the amount of oxygen required to reduce the initial, oxygen free luminescence by 50%), and a rapid response to oxygen. The pigment is extruded in low density polyethylene (LDPE) to produce a thin (60 µm), flexible, O2 sensing plastic film, with an O2 sensitivity (PO2 (S = 1/2) = 0.84 atm) comparable to the more traditional homogeneous lumophore ion-pair based O2 sensor ink films reported in the literature.