
Pleural fluid involvement by high-grade endometrial stromal sarcoma (HG-ESS) is exceedingly rare, with only one previously reported case. We report a case of ZC3H7B::BCOR fusion-positive HG-ESS metastatic to the pleural fluid in a 32-year-old female who presented with pelvic pain and a large uterine mass suspicious for leiomyosarcoma on MRI. Additional imaging showed pulmonary and vertebral lesions suspicious for metastases. A total abdominal hysterectomy with bilateral salpingo-oophorectomy revealed HG-ESS, with RNA sequencing confirming a ZC3H7B::BCOR fusion. Despite trials of chemoradiation, she developed worsening metastatic burden and eventually presented with a large pleural effusion. Pleural fluid cytology demonstrated three-dimensional clusters of spindled to epithelioid tumor cells with high nuclear-to-cytoplasmic ratios and coarse chromatin, an architectural pattern not seen on the primary resection. Correlation with the patient's known primary uterine tumor and its immunophenotypic features helped establish the diagnosis of metastatic HG-ESS. Malignant effusions secondary to sarcoma account for fewer than 6% of cytologic fluid samples. This case expands the limited cytologic literature on metastatic HG-ESS involving pleural fluid and emphasizes that metastatic HG-ESS may display cytomorphologic features that differ from the primary tumor, making correlation with the patient's clinical history and prior resection essential for accurate diagnosis.
Endosalpingiosis is a benign Müllerian inclusion that rarely involves supradiaphragmatic lymph nodes. Malignant transformation in the setting of nodal endosalpingiosis is exceptional. We report a case of low-grade serous carcinoma arising in a cervical lymph node in the setting of endosalpingiosis in a 41-year-old woman presenting with Horner syndrome. Imaging revealed a densely calcified, hypermetabolic supraclavicular lymph node. Fine needle aspiration and core biopsy demonstrated tubal-type epithelium consistent with endosalpingiosis adjacent to a neoplastic micropapillary and cribriform proliferation with psammoma bodies. Immunohistochemistry showed positive staining for PAX-8, estrogen receptor, and WT1, supporting Müllerian origin. The patient had a remote history of serous borderline tumor with noninvasive implants and KRAS and MAPK1 mutations. No recurrent pelvic disease was identified on positron emission tomography-computed tomography. Neck dissection confirmed low-grade serous carcinoma arising in association with nodal endosalpingiosis. This rare presentation underscores the importance of recognizing Müllerian proliferations in cervical nodes to avoid misdiagnosis as metastatic carcinoma.
This editorial highlights the 2026 International Cytology Symposium organized by the Taiwan Society of Pathology in Taipei. Inaugurated in 2015 and resumed following the pandemic, the symposium serves as a specialized continuing education platform designed for practicing pathologists. The 1.5-day program featured interactive microscopic slide tutorials alongside plenary lectures led by distinguished international and local faculty. The 2026 key highlights included the practical integration of the ASCCP risk-based cervical management guidelines within an evolving screening framework, as well as diagnostic approaches for challenging pulmonary and head and neck cytopathology. The symposium underscores Taiwan's active engagement in international professional exchange and its dedication to integrating global diagnostic advances into local clinical practice.
A 26-year-old immunocompetent woman with a history of noninvasive, low-grade papillary urothelial carcinoma presented with persistent upper abdominal pain. Urine cytology, performed for bladder tumor surveillance, revealed globose, yeast-like forms (10-30 μm) with thick walls and multiple narrowly attached peripheral buds in a "ship wheel" configuration-morphology classically associated with Paracoccidioides brasiliensis. Three months later, morphologically identical organisms were identified on routine cervical Papanicolaou (Pap) test, confirmed by PAS and GMS stains on cell block material. Neither specimen showed significant inflammation or epithelial abnormality. Clinical and epidemiologic features were inconsistent with paracoccidioidomycosis: the patient was a young woman of reproductive age (male-to-female ratio 13-20:1 in chronic paracoccidioidomycosis), had no travel to an endemic region, and lacked pulmonary, mucocutaneous, or systemic disease. The morphologic findings were attributed to Cokeromyces recurvatus, a rare dimorphic mucormycete whose sporangiola are virtually indistinguishable from the multiple-budding yeast cells of P. brasiliensis on cytologic preparations. This case is novel in two respects: (1) it represents the first reported simultaneous detection of C. recurvatus in both urine and cervical cytology from the same patient, demonstrating multisite genitourinary colonization and (2) identification via urine cytology performed for bladder tumor surveillance extends awareness of this organism beyond the Pap test setting to urinary cytopathology. With fewer than 15 published human cases, this report reinforces that morphology alone is insufficient for definitive fungal identification when an endemic dimorphic fungus is suspected, and that culture or molecular confirmation (broad-range fungal PCR with DNA sequencing) is essential to avoid misdiagnosis and unnecessary prolonged antifungal therapy.
OBJECTIVES:Cytology of soft tissue tumours poses a diagnostic challenge due to their morphological heterogeneity and cytomorphological overlap between benign and malignant lesions. The IAC-IARC-WHO Reporting System for Soft Tissue Cytopathology introduces a standardised six-tier diagnostic framework aligned with the WHO Classification of Tumours. This systematic review and meta-analysis aimed to evaluate the overall diagnostic accuracy of soft tissue cytology and to determine the pooled risk of malignancy (ROM) for each WHO category, thereby assessing the clinical utility of this reporting system as a risk-stratified framework for the management of soft tissue lesions. METHODS:A systematic literature search was conducted in PubMed and other electronic databases till February 2026, with no date restrictions, following the PRISMA-DTA guidelines. The studies reported soft tissue cytology cases with the histopathological confirmation and had sufficient categorical detail to map to the IAC-IARC-WHO reporting system; they were eligible for inclusion. Data extraction, category mapping and quality assessment using the QUADAS-3 were performed. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-) and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Hierarchical summary receiver operating characteristic (HSROC) curves were generated, and I2 statistics were used to assess heterogeneity. Subgroup analyses were performed for cytology method, geographic origin and study design. Meta-regression was conducted using histopathological verification rate, malignancy prevalence and publication year as covariates. The pooled ROM for WHO categories was calculated, and the certainty of evidence was assessed using the GRADE framework. RESULTS:Thirty-seven studies were included; About 32 studies, comprising of 6773 histologically verified cases, were analysed for diagnostic accuracy. The pooled sensitivity was 84.9%, the pooled specificity was 96.8% and the overall diagnostic accuracy was 92.79%. The LR+ was 26.85, the LR- was 0.155 and the DOR was 172.7. The pre-test probability was 41.3%, and the post-test probability of malignancy was raised to 95%, while a negative result reduced it to 10%. The pooled ROM observed was 26.4%, 4.8%, 31.6%, 48.5%, 74.5% and 93.5% for the insufficient/non-diagnostic/inadequate, benign, atypical, STNUMP, suspicious for malignancy and malignant categories, respectively. Significant heterogeneity was observed in sensitivity (I2 = 69%), whereas moderate heterogeneity was observed in specificity (I2 = 49%). No significant publication bias was detected, and the GRADE certainty of evidence was rated very low (⊕◯◯◯) due to serious concerns in the risk of bias, indirectness and inconsistency domains. CONCLUSION:The present study demonstrates high specificity and an increase in ROM from the benign category, followed by the insufficient/non-diagnostic/inadequate category and the malignant categories, confirming validity and supporting the role of cytology as a reliable malignancy-confirmation tool and risk-stratified decision-support system in the preoperative management of soft tissue tumours. The very-low grade certainty was due to incomplete histopathological verification, retrospective study designs and inadequate blinding in most included studies, underscoring the need for well-designed prospective studies that use the WHO soft tissue cytology reporting system and include complete histopathological follow-up to generate high-certainty evidence for clinical guideline development.
Fluid overload-associated B-cell lymphoma (FO-LBCL) is a B-cell neoplasm that presents as serous effusions without detectable tumor masses and Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8) infection. Here, we report a case of an 81-year-old female patient with FO-LBCL (Stage IVA) who presented with pericardial and pleural effusions. The patient had no underlying medical condition that could lead to fluid overload. Cytological examination of both effusions revealed medium- to large-sized lymphoid cells with high nucleocytoplasmic ratios, irregular nuclei, dense chromatin, prominent nucleoli, mitotic figures, basophilic cytoplasm, and lymphoglandular bodies. A cell block of the pleural fluid effusion showed that atypical lymphoid cells were positive for CD20 and CD79a, and negative for CD3, KSHV/HHV-8, and Epstein-Barr virus. The Ki-67 labeling index was 95%. The patient underwent systemic chemotherapy and achieved complete remission without pleural or pericardial recurrence during the 3-year follow-up period. As FO-LBCL is diagnosed based on cytological material, together with clinical and imaging findings, immunohistochemical analysis of the cell block is useful for confirming the diagnosis and selecting tailored therapies.
BACKGROUND:Thyroid nodules are common in clinical practice, with most being benign despite the increasing incidence of thyroid cancer. The American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) is widely used to stratify malignancy risk and guide fine-needle aspiration (FNA) decisions based on ultrasound features and size thresholds. However, concerns exist that nodules below these thresholds may still harbor clinically significant disease. The present study aimed to evaluate the prevalence of clinically significant cytopathologic findings in thyroid nodules that did not meet ACR TI-RADS biopsy criteria but underwent FNA, and to investigate the clinical rationale for performing biopsy in these cases. This study was designed to evaluate a selected subgroup of guideline-discordant biopsies rather than the overall diagnostic performance of the ACR TI-RADS system. METHODS:This retrospective observational research included 163 thyroid nodules from 163 patients who underwent ultrasound-guided FNA between 2018 and 2025. All nodules were below ACR TI-RADS size thresholds for biopsy. Cytology was classified using the Bethesda System. Primary outcome was the prevalence of clinically significant cytology (Bethesda V-VI), and secondary outcomes included expanded clinically relevant cytology (Bethesda III-VI), histopathologic findings, tumor staging, and indications for biopsy. Statistical analysis included descriptive statistics and Fisher's exact test. RESULTS:Bethesda V-VI and III-VI cytology was identified in 9.8% and 20.2% of nodules, respectively. Malignancy was observed across TI-RADS categories, including 3.1% of TI-RADS 3, 17.7% of TI-RADS 4, and 66.7% of TI-RADS 5 nodules. Among 23 surgically resected nodules, 20 were confirmed malignant. Most of them were early-stage tumors, although some exhibited nodal involvement or local advancement. No specific biopsy rationale was significantly associated with malignancy. CONCLUSIONS:Thyroid nodules below ACR TI-RADS biopsy thresholds may still harbor clinically significant cytopathology. While TI-RADS remains a useful risk stratification tool, reliance solely on size-based thresholds may lead to missed malignancies. Selective use of FNA based on clinical judgment and additional risk factors may improve early detection. These findings should be interpreted within the context of a selected cohort of nodules that underwent biopsy despite not meeting ACR TI-RADS size criteria and should not be construed as an assessment of the overall performance of the ACR TI-RADS system.
INTRODUCTION:Core needle biopsy (CNB) and fine needle aspiration cytology (FNAC) are routinely used in the diagnosis of hepatic nodules. Despite their advantages, both procedures have certain limitations. Recently, the combined use of FNAC and CNB in the same setting has been explored. We report a series of 29 combined hepatic FNAC-CNB procedures performed by an interventional cytopathologist. This series was compared with 50 cases of hepatic FNAC and 27 cases of hepatic CNB performed separately by clinicians and radiologists. MATERIALS AND METHODS:Twenty-nine combined FNAC-CNB procedures performed over a 5-year period were analyzed. FNAC diagnoses were compared and integrated with subsequent CNB diagnoses, and the impact of CNB on the diagnostic process was evaluated. In addition, 50 cases of hepatic FNAC and 27 cases of hepatic CNB performed outside our outpatient setting were analyzed to assess diagnostic performance in different workflows. RESULTS:When combined with FNAC, CNB had a positive impact on the diagnostic process in 82.8% of cases (n = 24/29), resulting in a complete diagnostic process in 89.7% of cases (n = 26/29). Without the combination of ROSE and CNB, FNAC alone achieved a complete diagnostic process in 60.0% of cases (n = 30/50), while CNB performed without FNAC and ROSE yielded a complete diagnostic process in 55.7% of cases (n = 15/27). CONCLUSIONS:The combined use of FNAC and CNB in a single setting improves diagnostic performance, optimizes specimen management, and identifies patients truly in need of CNB.
BACKGROUND:The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a classification system first released in 2018. It provides a standardized categorization for salivary gland lesions. Cell blocks can be prepared from fine-needle aspirations (FNAs) and can be utilized for the diagnostics of salivary gland lesions. This study aims to evaluate the distribution of the MSRSGC categories and the associated risks of malignancy (ROM) in salivary gland FNAs incorporating cell block preparations. METHODS:A PubMed literature search was conducted between March 3 and May 20, 2025, to identify studies with both cell block and MSRSGC applications in salivary gland FNAs. Data on sample size and the ROM for individual MSRSGC categories were extracted into Microsoft Excel and subsequently analyzed using OpenMetaAnalyst. RESULTS:Five studies were identified with a total of 1132 FNA samples processed to cell blocks. The pooled distributions of samples in the present meta-analysis were 21.9% in non-diagnostic (ND), 6.4% in non-neoplastic (NN), 8.2% in atypia of undetermined significance (AUS), 30.0% in benign neoplasm (BN), 8.0% in salivary gland neoplasm of uncertain malignant potential (SUMP), 1.9% in suspicious for malignancy (SM), and 19.4% in malignant (MN). The pooled ROMs from this meta-analysis was 25.3% in ND, 16.5% in NN, 26.3% in AUS, 2.0% in BN, 28.7% in SUMP, 84.8% in SM, and 97.7% in MN. CONCLUSION:The ROMs of the AUS and SUMP categories were lower than the compared meta-analyses. The cell block application utilizes architecture and ancillary studies, leading to better performance in indeterminate categories.
Intraductal tubulopapillary neoplasm (ITPN) is a rare pancreatic intraductal tumor and recognized precursor of pancreatic ductal adenocarcinoma, accounting for less than 1% of pancreatic exocrine neoplasms and about 3% of intraductal pancreatic neoplasms. Herein, we report an 82-year-old woman with a pancreatic head mass and miliary pulmonary nodules radiologically concerning for pancreatic adenocarcinoma, evaluated by endoscopic ultrasound-guided fine-needle aspiration. Cytology revealed a hypercellular specimen with papillary fronds and clusters of cells arranged in tubular formations with no extracellular as well as intracellular mucin identified; cell block sections showed tubular, cribriform, and papillary architecture with focal high-grade dysplasia. Immunohistochemistry demonstrated diffuse MUC1 positivity with patchy CK7 and CK19 expression and negativity for MUC2, GATA3, and TTF-1, supporting a diagnosis of ITPN. This case highlights the cytomorphologic and immunophenotypic features of pancreatic ITPN on FNA and emphasizes the importance of distinguishing it from intraductal papillary mucinous neoplasm and other pancreatic neoplasms in limited cytology samples.
Cytopathology in Nepal has expanded considerably over recent decades, playing a key role in the diagnosis of both malignancies and infectious diseases. This article reviews the historical evolution, current practices, specimen types, processing techniques, and reporting systems in Nepal. It also outlines cytopathology training, workforce development, and cervical cancer screening initiatives. Despite this progress, access to advanced ancillary techniques such as immunocytochemistry and molecular testing remains limited, with reliance on referral laboratories. Ongoing challenges include resource constraints, uneven infrastructure, and limited subspecialty training opportunities. Strengthening diagnostic capacity through expanded infrastructure, quality assurance, and targeted training will be essential for future growth. Due to limited published data, some observations are based on the authors' experience.
The coexistence of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and Merkel cell carcinoma (MCC) is a well-established but rare association. Collision tumors involving both entities within a single lymph node are exceptionally uncommon and pose considerable diagnostic challenges, particularly on cytological specimens. Here, we report the case of a 68-year-old male presenting with right axillary lymphadenomegaly. Fine-needle cytology (FNC) demonstrated a monomorphic population of intermediate-sized lymphoid cells, along with occasional larger cells exhibiting plasmacytoid features. Flow cytometric immunophenotyping showed a CD19+/CD5+/CD23dim B-cell population with lambda light chain restriction consistent with CLL/SLL, and a second CD45-/CD138+/CD200+/CD81+ population suspicious for aberrant plasma cells, raising the differential diagnosis of plasmacytoma or plasmacytic differentiation of CLL/SLL. Subsequent lymph node excision and histological examination revealed a collision tumor comprising MCC and CLL/SLL. This case highlights a rare but significant pitfall in lymph node FNC specimens, in which small neuroendocrine carcinoma was misinterpreted as an aberrant hematopoietic population.
Serial pancreatic juice aspiration cytological examination (SPACE) has recently been recognized as a useful method for detecting high-grade pancreatic intraepithelial neoplasia (high-grade PanIN). However, the cytological features of high-grade PanIN are heterogeneous, and some cases remain difficult to diagnose. We examined the cytological findings of two surgically resected cases of high-grade PanIN detected by SPACE. Quantitative image analysis was performed to evaluate nuclear atypia and chromatin heterogeneity. In addition, hyperspectral imaging analysis was conducted in one case to assess intranuclear spectral heterogeneity. Case 1 demonstrated focal high-grade PanIN with relatively mild cytological atypia, whereas Case 2 showed multifocal high-grade PanIN with numerous markedly atypical cells. Despite these differences, both cases shared heterogeneous nuclear chromatin staining within the same epithelial clusters. Image analysis demonstrated significantly increased nuclear area, decreased circularity, decreased mean nuclear brightness, and increased intranuclear brightness standard deviation in Case 2 compared with Case 1, indicating differences in the severity of nuclear atypia. In contrast, overlapping distributions of intranuclear brightness standard deviation were observed in both cases, suggesting shared intranuclear chromatin heterogeneity. Furthermore, hyperspectral imaging analysis demonstrated increased intercellular spectral heterogeneity in high-grade PanIN compared with normal pancreatic ductal epithelium, supporting the presence of chromatin heterogeneity from an optical perspective. Although the cytological appearance of high-grade PanIN varies among cases, nuclear chromatin heterogeneity may represent a common and diagnostically important feature. Image analysis and hyperspectral imaging may provide useful objective approaches for evaluating such heterogeneity.
Anaplastic thyroid carcinomas (ATCs) harboring oncogenic kinase fusion drivers are rare and highly aggressive malignancies that may benefit from targeted therapy. While fine needle aspiration (FNA) provides an opportunity for early diagnosis, the cytomorphologic features of these kinase fusion ATCs have not been specifically detailed in the literature. We present a focused analysis of three kinase fusion-positive ATCs with detailed cytologic, histologic, and molecular correlations. Our cases demonstrate cytologic features typical of conventional ATC, including marked nuclear atypia, sarcomatoid morphology, increased/atypical mitotic activity, and tumor necrosis. Although no microscopic features were identified cytologically or histologically that specifically distinguish kinase fusion-positive ATC from conventional ATC, negative immunohistochemistry for BRAF V600E and RAS Q61R may serve as an indication for early molecular testing that includes fusion analysis. Rapid genetic analysis would facilitate triage to optimal primary or neoadjuvant systemic therapy. This potentially allows for early patient triage for initiation of systemic and/or targeted therapies. The modest success observed with fusion-targeted therapy as part of a multimodal treatment strategy in our cohort is encouraging, although outcomes may be constrained by co-occurring oncogenic drivers, limited case numbers, and acquired resistance mechanisms.
BACKGROUND:The emergence of personalized therapy and molecular sequencing has significantly transformed the management of advanced non-small cell lung carcinoma (NSCLC). Supernatants obtained from fine needle aspiration (FNA) have been shown to be a reliable source of high-quality nucleic acid for molecular testing. One pre-analytic factor that may influence the success of molecular analysis is the collection medium used for the FNA rinse. METHODS:This prospective study evaluated 31 FNA specimens collected in three different media-CytoRich Red, 10% neutral buffered formalin, or 10% bovine serum albumin (BSA)-to assess their impact on DNA yield and real-time polymerase chain reaction (RT-PCR) outcomes for KRAS (Kirsten rat sarcoma viral oncogene homolog) and/or EGFR (epidermal growth factor receptor) mutations. DNA extraction was performed using the QIAamp DNA FFPE (formalin-fixed paraffin-embedded) Tissue Kit (Qiagen), and RT-PCR was conducted using the QIAGEN therascreen EGFR or KRAS RGQ PCR kits. Concurrent direct smears or formalin-fixed, paraffin-embedded tissue from a cell block or core biopsy served as standard controls. RESULTS:In the CytoRich Red group, 11 specimens (9 adenocarcinomas and 2 NSCLC) were analyzed. All 11 specimens generated results concordant with standard controls. One specimen required repeat DNA extraction due to initial pre-test quality control failure. The formalin group included 12 specimens (7 squamous cell carcinomas [SCC], 3 adenocarcinomas, 1 NSCLC, and 1 large cell neuroendocrine carcinoma). Nine specimens produced concordant results with controls. Two specimens were negative for EGFR mutations, although the corresponding control tissues were not tested. Six required repeat DNA extraction because of initial pre-test failure, and one specimen remained invalid after re-extraction. Eight specimens were collected in BSA (5 adenocarcinomas, 2 NSCLC, and 1 SCC). Five produced concordant results with standard controls, while three specimens failed PCR pre-tests despite repeat DNA extraction. CONCLUSION:In this small cohort, CytoRich Red demonstrated reliable performance for RT-PCR-based mutation testing. FNA supernatant represents a practical alternative specimen for lung cancer molecular analysis and may optimize specimen utilization while preserving cell block material.
The inaugural Asian Federation of Cytology Societies Congress, held at Prince of Wales Hospital in Hong Kong from May 8-10, 2026, represents a major milestone in the development of regional and international collaboration in cytopathology. The meeting brought together cytopathologists, trainees, cytotechnologists, molecular biologists, and researchers from multiple international regions, providing a platform for scientific exchange, educational advancement, and professional networking. Beyond its diverse and outstanding scientific program, the congress highlighted that dedication, mentorship, and consistency make progress possible, achievements that are, above all, driven by human connection and sustained collaboration.
INTRODUCTION:Recently, a standardized reporting system for soft tissue cytopathology was introduced. The aim is to evaluate the diagnostic utility of FNA in the diagnosis of bone and soft tissue lesions by comparing the cytological and histopathological diagnoses in a large group of cases and to determine the risk of malignancy (ROM) rates according to the World Health Organization (WHO) Reporting System for Soft Tissue Cytopathology. MATERIALS AND METHODS:The pathology databases were searched for cases that underwent FNA for bone and soft tissue lesions between 2020 and 2023. Only cases that had available histological follow-up were included. The FNAs are categorized as nondiagnostic (ND), benign, atypical, soft tissue neoplasm of uncertain malignant potential (STNUMP), suspicious for malignancy (SM), malignant (primary/metastatic) according to WHO Reporting System for Soft Tissue Cytopathology. The risk of malignancy (ROM) was calculated for each group. RESULTS:The study consisted of 427 cases, including 30 ND (7%), 322 benign (75.4%), 19 atypical (4.5%), 7 STNUMP (1.6%), 5 SM (1.2%), and 44 malignant (10.3%). The ROM rates were 16.6%, 1.8%, 57.9%, 28.5%, 80%, and 100% for the groups: ND, benign, atypical, STNUMP, SM, and malignant, respectively. The diagnostic accuracy, sensitivity, and specificity of FNA in all bone and soft tissue lesions were 98.6%, 92.3%, and 100%, respectively. CONCLUSION:We conclude that FNA is a simple and accurate technique for assessment of bone and soft tissue lesions. The WHO Soft Tissue Cytopathology Reporting System could improve communication among pathologists and clinicians, simplify clinical management of patients, and support further research in soft tissue cytology.
Sclerosing epithelioid fibrosarcoma (SEF) is a rarely encountered malignant fibroblastic sarcoma with an often aggressive clinical course despite its usually bland histology. We describe a case of a metastatic SEF involving a pleural effusion and describe the cytologic features as well as the use of IHC, particularly MUC4, to support the diagnosis. SEF has only been described in one prior case report in pleural effusion cytology.
BACKGROUND:Timely cervical cytology results are crucial for effective screening and early management of precancerous lesions. However, many low- and middle-income countries face delays in turnaround time (TAT). This study assessed TAT for cytology screening results in South Africa from 2005 to 2023 and identified factors associated with TAT delays. METHODS:We conducted a cross-sectional analysis of public health routine program data from the National Health Laboratory Service for women aged ≥ 15 years. We defined TAT as the time from sample collection to the release of results. The recommended TAT benchmark is 14 days; we defined delays as TAT exceeding 14 days. We used descriptive statistics and multivariable logistic regression to assess TAT trends and factors associated with delays. RESULTS:From 2005 to 2023, 12,246,041 cervical cytology smears were processed. The median age at screening was 38.8 years (IQR: 31.0-41.1), ranging from 15 to 95 years. Median TAT consistently exceeded 14 days, peaking at 25 days between 2014 and 2019. Delays were significantly associated with location, with higher odds in self-sufficient (aOR 2.33; 95% CI: 2.32-2.34) and laboratory-dependent regions (aOR 1.61; 95% CI: 1.61-1.62). Samples processed in referral laboratories had higher odds of delay (aOR 4.08; 95% CI: 4.07-4.10). Seasonal variation also affected TAT delays, with higher odds observed in the third quarter (aOR 1.40; 95% CI: 1.39-1.40) as compared to the first quarter. CONCLUSION:Throughout South Africa, cervical cytology TAT remains above the recommended benchmarks. Delays are driven by structural and operational factors. Strengthening laboratory capacity, optimizing workflows, and transitioning to organized screening programs are critical for timely results and improved cervical cancer prevention outcomes.