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Molecular testing in urinary cytology specimens: Current status and future directions

Chen, Fei; Simsir, Aylin; Cheng, Liang
Bladder cancer is a common type of urological cancer with high recurrence and mortality rates. Currently, it is diagnosed and monitored using minimal invasive cystoscopies and biopsies. Urinary cytology, the most widely accepted noninvasive and more economic urinary diagnosis method, aims to detect high grade urothelial carcinoma with a high specificity but low sensitivity, especially for detecting low-grade tumors. With advancements in molecular techniques, urine based liquid biopsy, artificial intelligence, and the growing interest in precision cytopathology, identification of urinary biomarkers for effective cancer screening, diagnosis, risk stratification, and therapeutic response monitoring has been a key focus of bladder cancer research and clinical practice guideline development. Urine allows noninvasive access to morphological, transcriptomic, epigenetic, and genomic materials from exfoliated cells in contact with tumor tissue. This review offers a comprehensive evaluation of the current utility of urinary biomarkers and technological innovations in cancer diagnosis and minimal residual disease detection. We also discuss the challenges and prospects for integrating molecular cytopathology into daily clinical practice.
PMID: 40055071
ISSN: 1873-2496
CID: 5807962

TERT promoter mutations and additional molecular alterations in thyroid fine-needle aspiration specimens: A multi-institutional study with histopathologic follow-up

Abi-Raad, Rita; Shi, Qiuying; Chen, Fei; Antony, Vijay; Hsiao, Wen-Yu; Simsir, Aylin; Liu, Xiaoying; Brandler, Tamar C; Cai, Guoping
OBJECTIVES/OBJECTIVE:TERT promoter mutations are not infrequently encountered in thyroid carcinomas; however, it is unclear if additional molecular alterations may play a role in determining tumor behavior. METHODS:Fine-needle aspiration (FNA) specimens from 32 patients with TERT promoter mutations detected by ThyroSeq v3 from 4 institutions were included in the study. FNA diagnoses, molecular results, and surgical follow-up were retrospectively reviewed and analyzed. RESULTS:There were 5 benign and 27 malignant neoplasms, including 7 high-grade thyroid carcinomas (HGCs) on histopathologic follow-up. Of 4 cases with an isolated TERT mutation, 3 (75%) cases were malignant. Of 17 cases harboring a co-occurring TERT mutation with 1 additional molecular alteration, 13 (76%) displayed malignancy on histopathologic follow-up. All 11 cases with TERT mutations plus 2 or more additional molecular alterations were malignant on follow-up. Furthermore, HGC was not seen in cases with an isolated TERT mutation, while 80% of cases harboring TERT mutations plus 3 additional molecular alterations showed HGC. CONCLUSIONS:TERT promoter mutations are commonly associated with malignancy, particularly HGCs, when multiple co-occurring molecular alterations are present. However, TERT promoter mutations may occasionally be detected in benign thyroid neoplasms when encountered in isolation or with fewer than 2 additional molecular alterations.
PMID: 39250709
ISSN: 1943-7722
CID: 5690042

Cytomorphologic and Molecular Features of Hyalinizing Trabecular Tumor of Thyroid: Smears and ThinPrep [Meeting Abstract]

Xia, Rong; Sun, Wei; Gupta, Mala; Hernandez, Osvaldo; Chen, Fei; Liu, Cheng; Simsir, Aylin; Shi, Yan
ORIGINAL:0017411
ISSN: 2213-2945
CID: 5743672

Neutrophilic dermatosis in a patient with an IKZF1 variant and a review of monogenic autoinflammatory disorders presenting with neutrophilic dermatoses [Case Report]

Guirguis, Justina; Iosim, Sonia; Jones, Derek; Likhite, Maryel; Chen, Fei; Kesserwan, Chimene; Gindin, Tatyana; Kahn, Philip J; Beck, David; Oza, Vikash S; Hillier, Kirsty
Monogenic diseases of immune dysregulation should be considered in the evaluation of children presenting with recurrent neutrophilic dermatoses in association with systemic signs of inflammation, autoimmune disease, hematologic abnormalities, and opportunistic or recurrent infections. We report the case of a 2-year-old boy presenting with a neutrophilic dermatosis, found to have a novel likely pathogenic germline variant of the IKAROS Family Zinc Finger 1 (IKZF1) gene; the mutation likely results in a loss of function dimerization defective protein based on reports and studies of similar variants. IKZF1 variants could potentially lead to aberrant neutrophil chemotaxis and development of neutrophilic dermatoses. Long-term surveillance is required to monitor the development of hematologic malignancy, autoimmunity, immunodeficiency, and infection in patients with pathogenic IKZF1 germline variants.
PMID: 38413050
ISSN: 1525-1470
CID: 5634772

Copy Number Alterations in Thyroid FNA Specimens: An Association with Oncocytic Features? [Meeting Abstract]

Xia, Rong; Sun, Wei; NIkiforov, Yuri; Shafizadeh, Negin; Belovarac, Brendan; Liu, Cheng; Shi, Yan; Hodak, Steven; Chen, Fei; Simsir, Aylin; Brandler, Tamar
ORIGINAL:0017413
ISSN: 2213-2945
CID: 5743692

Gene Expression Alterations, Assist Players of Driver Mutations Toward Malignancy in Thyroid Nodules? [Meeting Abstract]

Belovarac, Brendan; Chablani, Sumedha; Brandler, Tamar; Sun, Wei; Shafizadeh, Negin; Shi, Yan; Hodak, Steven; Chen, Fei; Simsir, Aylin; Xia, Rong
ORIGINAL:0017412
ISSN: 2213-2945
CID: 5743682

HPV Cotesting of Unsatisfactory Papanicolaou Tests: Implications for Follow-up Intervals

Chen, Fei; Hsu Lin, Lawrence; Hindi, Issa; Sun, Wei; Shafizadeh, Negin; Szeto, Oliver; Brandler, Tamar C; Simsir, Aylin
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.
PMID: 37052613
ISSN: 1943-7722
CID: 5479502

Genomic Profiling of Metastatic Tumors in Pleural Effusion Specimens: Comparison of Fresh Supernatant, Fresh Cell Pellet, and Cell Block Material for Testing [Meeting Abstract]

Chen, Fei; Belovarac, Brendan; Shen, Guomiao; Feng, Xiaojun; Brandler, Tamar; Jour, George; Sun, Wei; Snuderl, Matija; Park, Kyung; Simsir, Aylin
ISI:000990969800303
ISSN: 0023-6837
CID: 5525432

Utility of Urine Cytology Specimens for Molecular Profiling in Detection of High-Grade Urothelial Carcinoma [Meeting Abstract]

Chen, Fei; Belovarac, Brendan; Shen, Guomiao; Feng, Xiaojun; Jour, George; Sun, Wei; Snuderl, Matija; Simsir, Aylin; Park, Kyung
ISI:000990969800304
ISSN: 0023-6837
CID: 5525442

Liver fluke eggs in bile duct brush cytology: An unexpected diagnosis during evaluation of a biliary stricture

Chen, Fei; Aguero-Rosenfeld, Maria; Simsir, Aylin; Brandler, Tamar C
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.
PMID: 35984297
ISSN: 1097-0339
CID: 5300282