Faculty Bibliography

OBJECTIVES/OBJECTIVE:The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly "negative." For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months. METHODS:Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results. RESULTS:There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%. CONCLUSIONS:A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months.

Introduction: Thyroid fine-needle aspiration (FNA) cytology combined with molecular testing guides individualized patient management by providing information regarding tumor biology and the risk of recurrence associated with specific mutations in the indeterminate groups (Bethesda group III-V). Thyroid adenomaassociated (THADA)-IGF2BP3 fusions have been identified as an oncogenic event in thyroid neoplasms, but the clinical-pathologic features and subsequent management are not well-established. Here we report the findings associated with thyroid nodules with THADA-IGFBP3 fusions in our institution.
Material(s) and Method(s): FNA cytology samples of thyroid nodules during 01/2015-12/2016 with the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS; Bethesda III), follicular neoplasm/ suspicious for follicular neoplasm (FN/SFN; Bethesda IV) and suspicious for malignancy (Bethesda V) with corresponding ThyroSeqV2 data were assessed. Molecular test results yielding a THADA gene fusion were identified. In addition, follow-up surgical pathology and available radiology results were reviewed.
Result(s): 186 out of 558 (33.3%) thyroid nodules displayed molecular alterations; 7 out of 186 (3.8%) Bethesda category III-V nodules with ThyroSeq molecular alterations displayed isolated THADA-IGFBP2 fusions (Table 1). The median age was 45 years. The female to male ratio was 5:2. The nodule sizes ranged from 1.8 to 5.0 cm. Four (57%) patients had surgery; three cases displayed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on histology; one case was a follicular adenoma. No patients had recurrence or metastasis on follow-up.
Conclusion(s): Our pilot study shows that thyroid nodules with THADA-IGF2BP3 fusions display low-risk/indolent features. These findings may aid in clinical management decisions in patients presenting with thyroid nodules with isolated THADAIGF2BP3 fusions on molecular testing

Introduction: The utility of The Paris System (TPS) in diagnosing low-grade urothelial neoplasm (LGUN) on urine cytology is controversial due to the strict requirement for fibrovascular cores, and low sensitivity/specificity. Many LGUNs are classified as atypical urothelial cells (AUC) on cytology, which compromises the performance and utility of TPS. Here, we studied cytomorphologic features of LGUN in urine samples to determine which features were commonly observed.
Material(s) and Method(s): Twenty-two urine cytology cases with corresponding (within 2 months) LGUN histologic diagnosis were retrieved for this pilot study and were evaluated by one cytopathologist for the presence of clusters, cercariform cells, hyperchromasia, irregular nuclear rim, papillary architecture +/-fibrovascular core, and nucleus:cytoplasm (N:C) ratio (Figure 1). Hierarchical cluster analysis (Ward's Method) was used to classify the features.
Result(s): Of the 22 urines, one was voided (4.5%) and 21 were instrumented (95.5%). Majority (77.3%) were diagnosed as AUC, 1 was suspicious for urothelial carcinoma (4.5%), 4 cases were graded as LGUN (18.2%, Table 1). Clustering analysis demonstrated that the morphologic features abundantly present in the urine specimen of LGUN included: clusters (77.3%), N:C ratio >50% (85.4%), and papillary architecture without a core (72.7%). The features that were mostly absent in LGUN specimens included: irregular nuclear rim (0%), papillary formation with a core (0%), hyperchromasia (9.1%), coarse chromatin (22.7%), and cercariform cells (36.3%). (Table 2).
Conclusion(s): Papillary formation with a fibrovascular core, the most convincing feature of LGUN, was not present in our pilot cohort of LGUN urines. However, our study describes additional cytomorphologic features that may be useful in identifying LGUN in urine cytology. Our research will continue with the evaluation of a larger cohort of LGUN cases with corresponding urine cytology in order to further investigate these findings

OBJECTIVES/OBJECTIVE:Data on Papanicolaou (Pap) tests with atypical glandular cells (AGCs) with concurrent squamous cell abnormalities (AGC + Sq) are limited. We evaluated histologic outcomes and the role of high-risk human papillomavirus (HR-HPV) testing in this setting compared with AGCs without concurrent squamous cell abnormalities (AGC-alone). METHODS:This study used a retrospective cohort of patients with Pap test diagnoses of AGC + Sq and AGC-alone between October 2013 and August 2021. RESULTS:We included 287 Pap tests from 278 patients. The HR-HPV test was positive in 55% of AGC + Sq cases and 14% of AGC-alone cases (P < .0001). Most AGC + Sq cases displayed squamous lesions (41.5%) or were benign (41.5%) on histology, whereas AGC-alone cases were predominantly benign (72%) or extracervical neoplasms (18%). AGC + Sq cases showed higher rates of significant histologic lesions (P = .0001), which were associated with positive HR-HPV status (P = .0012). In AGC-alone cases, HR-HPV status was associated with significant histology only in patients 50 years of age or younger. In both groups, 20% or more of HR-HPV-negative patients harbored significant lesions. CONCLUSIONS:AGC + Sq represents a distinct group of patients. HR-HPV testing and patient age provide useful information in the evaluation of AGC, but triage based on HR-HPV testing is not recommended because of the potential for missing significant lesions.

Clonorchis sinensis, a liver fluke parasite, infects humans through ingestion of raw or undercooked fish, crabs, or crayfish in endemic areas where the parasite is found. Clonorchis sinensis infects the liver, gallbladder, and bile duct in humans, causing Clonorichiasis. Although the majority of patients are asymptomatic, long-lasting infections may cause severe disease. Without treatment, human infection may persist for the parasite's lifespan (25-30 years). Pathologic diagnosis can be challenging as sampling may demonstrate limited cellularity with minuscule eggs that may be overlooked. Here, we report a rare case of liver fluke eggs diagnosed in bile duct brush cytology.