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Endoscopic Ultrasound-Guided Franseen Fine-Needle Biopsy for Solid Pancreatic Lesions: A Systematic Review and Meta-Analysis.

INTRODUCTION: Accurate tissue acquisition (TA) of solid pancreatic lesions is essential for guiding treatment with endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) being the preferred method. Among FNB designs, the three-pronged Franseen-tip needle demonstrates strong diagnostic performance, though direct head-to-head comparisons with other FNB designs remain limited. METHODOLOGY: This meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251123856). Eligible studies enrolled patients with solid pancreatic lesions who underwent EUS-guided FNB, directly compared the Franseen-tip with other FNB needles. Six databases were systematically searched through July 2025, and study selection, data extraction, and risk of bias assessment (QUADAS-2 tool) were performed independently by two reviewers. Pooled estimates were generated using random-effects and bivariate hierarchical models. RESULTS: Sixteen studies (2,010 Franseen vs. 2,811 comparator) were included. Bivariate analysis showed that sensitivity and specificity of the Franseen needle were comparable to newer-generation comparator needles (sensitivity 91.3% vs. 94.0%; specificity 99.99% vs. 99.15%), whereas older-generation needles demonstrated lower sensitivity (80.8%) and inferior discriminatory performance (Negative Likelihood Ratio [LR⁻] 0.19 vs. 0.09). Diagnostic accuracy was higher with the Franseen needle (RR 1.07, 95% CI 1.01-1.14; I2 = 69%). Sample adequacy was similar overall (RR 1.04, 95% CI 0.95-1.14) but superior to older-generation needles (RR 1.19, 95% CI 1.02-1.41) and in lesions > 30 mm (RR 1.14, 95% CI 1.02-1.28, I2 = 81.2%). The Franseen needle achieved nominally strong diagnostic performance (DOR 116.6), although small-study effects were observed. Primary procedural outcomes were comparable between Franseen and comparator needles, including technical success (RR 1.00, 95% CI 0.98-1.02) and histological core procurement (RR 1.04, 95% CI 0.92-1.17). The Franseen needle had fewer low-cellularity samples (RR 0.56, 95% CI 0.45-0.69) and lower specimen bloodiness (RR 0.48, 95% CI 0.25-0.90) but a slightly higher overall adverse event rate (RR 1.29, 95% CI 1.06-1.57). CONCLUSION: The Franseen needle provides superior diagnostic accuracy and sample adequacy compared to older-generation FNB needles with comparable performance to newer-generation designs. It reduces low-cellularity samples and specimen bloodiness, although adverse events are slightly increased, with other primary procedural outcomes remaining comparable. TRIAL REGISTRATION: PROSPERO (Registration No. CRD420251123856).

Humans

Application of fine-needle aspiration biopsy for the diagnosis of dysplastic and neoplastic liver cell changes induced by N-nitrosomorpholine in rats.

Male rats were treated with the hepatocarcinogen, N-nitrosomorpholine (NNM, 10 mg ad 100 ml drinking water) for 19 weeks. Repeated fine-needle aspiration biopsies of the liver were performed percutaneously. Cytomorphologic and cytochemical criteria were used for the characterization of dysplastic and carcinoma cells. The alterations seen in the smears were correlated with histopathologic findings in the punctured liver lobes. Cells showing type I dysplasia were recognized in smears obtained from day 7 on. They corresponded to the swollen, glycogen-free cells developing in zone 3 of the Rappaport acinus during the early treatment phases. In later stages type I dysplastic cells were observed in smears. This coincided with the development of neoplastic nodules seen in histopathologic preparations. Carcinoma cells were recognized first after 15 weeks. Marked gamma-glutamyl transpeptidase (gamma-GT) activity could be demonstrated cytochemically in biopsy smears and biochemically in biopsy homogenates during the early phases of NNM-treatment. Simultaneously, a rise in gamma-GT activity was also observed in the serum.

Animals

Transrectal cytological aspiration biopsy in prostatic disease.

Of 761 fine-needle biopsy specimens obtained from the prostate by the method of Franzén, 303 originated from patients in whom either a histological diagnosis had been obtained or cancer had been confirmed by increased levels of prostatic phosphatases. Among palpable cancers, 83% were diagnosed by this method, and none of them gave falsely negative results. Among the cancers with benign palpatory findings and normal phosphatase levels, cytological examination did not show cancer in any of the cases. It is concluded that the method is unsuited for screening of proctatic cancer, but its use is indicated for the confirmation of the diagnosis in cases with abnormal palpatory findings, and when the diagnosis seems likely from the results of biochemical analysis and/or radiographic studies. On these indications, repeated aspiration should be done if the first biopsy specimen does not reveal cancer.

Biopsy, Needle

Characteristics of p53 and Smad4 immunohistochemistry in pancreatic ductal adenocarcinoma and validation by next-generation sequencing.

BACKGROUND: Mutations in four major driver genes -KRAS, CDKN2A, TP53, and SMAD4- are central to the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) and critically inform diagnosis, therapeutic decision-making, and prognostic assessment. Although next-generation sequencing (NGS) is widely regarded as the gold standard for detecting these mutations, its clinical application is often limited by suboptimal analytical efficiency and substantial economic cost. Among these genes, immunohistochemical (IHC) staining for the proteins encoded by TP53 and SMAD4 has been extensively adopted in routine pathology practice. However, standardized IHC pattern classification schemes and rigorous validation of their predictive accuracy for underlying genomic alterations remain lacking in PDAC. METHODS: We retrospectively enrolled 63 PDAC patients and systematically characterized the typical IHC expression patterns of p53 and Smad4. Targeted NGS was subsequently performed on all available tumor specimens, and the resulting mutational profiles were correlated with corresponding IHC findings. Diagnostic performance including sensitivity, specificity and accuracy of p53 IHC for predicting TP53 mutations and of Smad4 IHC for predicting SMAD4 mutations was rigorously evaluated. RESULTS: Among the four canonical driver genes, co-occurring double- or triple-gene mutations were prevalent; within TP53 and SMAD4, missense mutations constituted the most frequent variant type. Using NGS as the reference standard, we validated the diagnostic utility of a three-tiered p53 IHC classification system, particularly in fine-needle biopsy (FNB) specimens. Furthermore, we proposed a novel, refined Smad4 IHC pattern classification that incorporates an "intermediate" category, thereby expanding upon conventional binary interpretation. This new scheme achieved markedly improved mutation prediction accuracy (0.76) compared with traditional approaches (0.57). CONCLUSION: Our study highlights the complementary diagnostic value of p53 and Smad4 IHC relative to molecular testing in PDAC, especially when tissue is limited, as commonly encountered in FNB specimens. The newly established Smad4 IHC classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.

Humans

Estradiol receptor analysis in human breast cancer tissue by isoelectric focusing in polyacrylamide gel.

Isoelectric focusing in polyacrylamide gel combined with limited proteolysis is a simple and specific method for quantitation of estradiol receptors in breast cancer tissue. At least eight different samples can be analyzed simultaneously on one gel, and the whole procedure, including sample preparation, takes less than 7 hr. In comparison with sucrose gradient centrifugation, isoelectric focusing is more sensitive, possibly due to the short time (1.5 to 2 hr) needed for the analysis. Furthermore, only one incubation with tritium-labeled estradiol is needed for an analysis, which means that a smaller amount of tumor tissue is needed than for most other methods. This fact allows analysis of the estrogen receptor content in tumor material obtained from fine-needle biopsy.

Breast Neoplasms

[New aspects and methods in gastroenterological diagnosis].

Advances in the diagnosis of gastrointestinal diseases are achieved by development of new methods and by an improved analysis of the obtained data. New aspects of screening examinations for gastrointestinal cancer in high risk groups concern endoscopic-bioptic methods, the endoscopic retrograde cholangio-pancreaticography, the ultrasonically-guided percutaneous fine-needle biopsy and immunological procedures. An increasing number of gastrointestinal peptides can be determined by radioimmunoassay. Breath tests may improve diagnosis in malassimilation.

Biopsy

Atypical hyperplasia of the prostate. A pitfall in the cytologic diagnosis of carcinoma.

The cytomorphologic features of atypical hyperplasia were studied in fine-needle aspiration biopsies of the prostate. Atypical hyperplasia material was found in 31 cases. The most usual and distinctive cytologic features of atypical hyperplasia were clustering of poorly-differentiated epithelial cells with acinic pattern and fairly regular nuclei. Another relevant feature was the lack of cytoplasmic fluorescence after acridine orange staining. These features make possible the diagnosis of atypical hyperplasia and the distinction from poorly-differentiated carcinoma. The recognition of atypical hyperplasia cells in fine-needle aspiration biopsies of the prostate is important in the avoidance of cytodiagnostic errors.

Acridines

Primary pulmonary salivary gland-type tumors in cytopathology practice: A systematic review and meta-analysis.

BACKGROUND: Primary pulmonary salivary gland-type tumors (PSGTs) are rare but clinically significant tumors that originate from the submucosal glands of the tracheobronchial tree. Cytologic samples taken during bronchoscopy are a key component of preoperative evaluation. However, cytologic diagnosis remains challenging because of the submucosal growth and morphologic overlap of PSGTs. In addition, current knowledge of the cytohistologic correlation of PSGTs is fragmented. The objective of this study was to assess the effectiveness of cytologic diagnoses of PSGTs. METHODS: A comprehensive, systematic literature search of the PubMed database was conducted to identify studies with cytologic and histologic diagnoses of PSGTs. Comprehensive data on diagnostic and clinical factors, when available, were collected for all individual patients. The data were tabulated in Microsoft Excel and analyzed using OpenMeta (Analyst) software. RESULTS: In total, 49 studies comprising 106 patients were identified. Final cytohistologic concordance was demonstrated in 48.1% of cases. Fine-needle aspiration showed the highest sensitivity (75.0%), followed by bronchial/tracheal washing (38.1%), and bronchial brushing (34.2%). Adenoid cystic carcinoma was the most common histologic subtype, accounting for 67 cases, followed by mucoepidermoid carcinoma, which accounted for 27 cases. CONCLUSIONS: The cytologic diagnosis of rare PSGTs remains challenging. Overall, cytohistologic concordance was 48.1%. However, fine-needle aspiration demonstrated greater diagnostic accuracy than exfoliative cytology and may facilitate a more accurate preoperative assessment.

Humans

Approaches to thyroid nodules in paediatric cancer predisposition syndromes.

OBJECTIVE: The objective of this work was to summarize current evidence and practical management considerations for thyroid nodules in children and adolescents with cancer predisposition syndromes (CPSs), focusing on follicular cell-derived nodules and non-medullary thyroid carcinoma (NMTC). METHODS: We synthesized current paediatric guideline recommendations and recent cohort, pathology, and molecular studies addressing CPS-associated nodular thyroid disease, including PTEN hamartoma tumour syndrome (PHTS), DICER1 syndrome, familial adenomatous polyposis, and related endocrine neoplasia syndromes. RESULTS: Evidence quantifying syndrome-stratified malignancy risk among paediatric CPS patients presenting with nodules remains limited and is largely derived from mixed-age or retrospectively ascertained cohorts with surveillance and verification bias. High-resolution ultrasound (US) is central to risk stratification. US-guided fine-needle aspiration (FNA) is a cornerstone of evaluation yet frequently yields indeterminate results, particularly in follicular-patterned and encapsulated lesions (e.g. PHTS and DICER1 syndrome), and sampling error is accentuated in polyclonal multinodular disease. Molecular testing may aid aetiologic clarification and, in selected settings, risk refinement. However, panels optimized for sporadic adult disease may have reduced 'rule-out' utility in CPSs. Biochemical assessment (TSH ± free thyroxine) complements imaging, while routine thyroglobulin is not recommended, and thyroid autoantibodies should be viewed as adjunctive rather than directive markers in CPSs. CONCLUSION: Management of thyroid nodules in paediatric CPSs is best approached through integrated, multidisciplinary risk assessment that combines expert ultrasound, context-aware cytology and molecular interpretation, and shared decision-making. This review proposes a CPS-adapted, multidisciplinary risk assessment framework and highlights the need for prospective multicentre registries and harmonized protocols to define syndrome-specific outcomes and evidence-based thresholds for surveillance and intervention.

Humans

Diagnostic utility of high-risk HPV polymerase chain reaction-based testing in head and neck FNA specimens with indeterminate cytomorphology.

BACKGROUND: Fine-needle aspiration (FNA) is critical in the initial diagnosis of many high-risk human papillomavirus (HR-HPV)-associated, metastatic oropharyngeal squamous cell carcinomas. Updated guidelines recommend HR-HPV-specific polymerase chain reaction (PCR) analysis over p16 immunohistochemistry on FNA specimens because p16 performs poorly on cytology material. PCR-based assays on liquid cytology material have demonstrated excellent analytic performance; however, the diagnostic utility of a positive HR-HPV PCR result in specimens with indeterminate cytomorphology remains uncharacterized. METHODS: The authors retrospectively identified 279 head and neck FNA specimens that had paired HR-HPV PCR testing on residual liquid cytology material over a 5-year period. The positive predictive value for histopathologically confirmed squamous cell carcinoma on surgical follow-up was calculated within each cytologic interpretive category. RESULTS: The HR-HPV PCR results were positive in 50.2% of specimens, negative in 40.9%, and indeterminate in 9.0%. The HR-HPV positivity rate ranged from 0% in specimens categorized as negative for malignancy to 57.3% in cytologically positive specimens, with 19.0%, 41.2%, and 50.0% positivity in the atypical, suspicious, and nondiagnostic categories, respectively. Among cytologically indeterminate specimens with positive HR-HPV PCR results (n = 14), the positive predictive value was 100% (95% confidence interval, 78.5%-100.0%). Blinded slide review additionally identified 15 cytologically positive specimens in which the definitive malignant interpretation depended substantially on HR-HPV positivity; all 15 were confirmed as squamous cell carcinoma. CONCLUSIONS: A positive HR-HPV PCR result on liquid cytology material carries a positive predictive value of 100% for malignancy in cytologically indeterminate head and neck FNA specimens. These findings support integrating HR-HPV PCR analysis into routine cytologic interpretation with the potential to upgrade some indeterminate specimens to malignant when HR-HPV is detected, expediting definitive treatment and sparing patients additional, invasive sampling.

Humans

Aspiration cytology and outpatient excision of breast lumps.

Fine-needle aspiration biopsy was performed in 30 consecutive women with clinically non-malignant breast lumps. All aspirates were shown to be benign on cytology and the lumps were excised under local anaesthetic at the outpatient department. Frozen section and paraffin section histology of the excised lump confirmed the diagnosis. Follow-up at the outpatient department and a postal questionnaire revealed the following wound complications: redness (70%), bruising (55%), and discharge (35%). Outpatient excision of solid breast lumps is a safe, rapid, and economical method of treating non-malignant breast lumps, if it is preceded by an accurate cytological interpretation of a technically satisfactory aspirate.

Adolescent

Innovation in medical diagnosis--the Scandinavian curiosity.

Fine-needle aspiration biopsy is a major diagnostic tool in Scandinavia, where 8000 such biopsies may be done in a large metropolitan hospital each year. The procedure is rapid, inexpensive, and technologically simple, yet it has found only limited, albeit increasing, acceptance in medical practice outside Scandinavia. Although the differences between Scandinavian and other medical systems may explain why the technique is not used more widely, there seems to be an underlying reluctance among medical communities to accept subjective types of innovation compared with objective innovation.

Biopsy, Needle

Cytologic and Surgical Correlation of TERT-Mutated Indeterminate Thyroid Nodules: A Case Series.

IntroductionTelomerase reverse transcriptase (TERT) promoter mutations is a relatively novel mutation that has been linked with thyroid cancers. This study examines the frequency, cytology and histo-morphologic features, and clinical outcomes of TERT-mutated indeterminate thyroid nodules.MethodsA retrospective review of Bethesda III and IV thyroid cytology specimen sent for ThyroSeq® testing (2019-2022) was performed, selecting those with TERT mutations. Demographics, cytologic features, surgical diagnoses, and follow-up data were analyzed.ResultsAmong 567 specimens tested, 12 (2%) harbored TERT mutations; 4 had TERT alone, and 8 had additional mutations. Average age of patients was 69 years (92% > 50 years). Eight had surgical follow-up: 50% were malignant, 25% were benign and 25% were of uncertain malignant potential. Additionally, 62% were oncocytic nodules. Clinical follow-up showed all evaluated patients were alive without recurrences or metastases at last contact.ConclusionIn our cohort, TERT promoter mutations were rare in indeterminate thyroid nodules (2%) and frequently accompanied by additional molecular changes. It is more frequently detected in older patients. Unlike prior reports describing TERT mutations exclusively in malignant thyroid tumors, our findings encompassed a broader histological spectrum, including benign, uncertain malignant potential and malignant lesions.

Humans

Afirma genomic sequencing classifier performance in young patients with cytologically indeterminate thyroid nodules.

CONTEXT: The Afirma Genomic Sequencing Classifier (GSC) is validated in patients &#x2265; 21 years with a 96% negative predictive value for malignancy when GSC-(B)enign. Afirma GSC has not been formally studied in patients <21 years of age with indeterminate thyroid nodules (ITNs). OBJECTIVE: To evaluate Afirma GSC in young patients with ITNs. DESIGN: Retrospective analysis of Afirma GSC testing. SETTING: ITNs referred for molecular testing in a real-world setting. PARTICIPANTS: Forty-nine ITNs from 49 patients < 21 years of age who had histopathology or 2 years' clinical follow-up data ascertained. INTERVENTION: None. MAIN OUTCOME MEASURE: Afirma GSC test performance. RESULTS: In 49 ITNs from patients aged 9 to 20 years (median 18.5 [interquartile range, 17.3-19.8]), 30 were GSC-B and 19 GSC-(S)uspicious, among which 14 (73.7%) were malignant (ie, true positive) and 5 (26.3%) were benign (ie, false positive). All 30 Afirma GSC-B cases were either histologically (n = 9) or clinically benign (n = 21) (ie, true negative). All 14 malignancies were GSC-S (sensitivity 100% [95% CI, 77-100]); 30/35 clinically or histologically benign cases were GSC-B (specificity 86% [95% CI, 70-95]). Negative predictive value for an Afirma GSC-B result was 100% [95% CI, 88-100]. Genomic alterations were not detected in the 30 GSC-B samples. Among the 14 malignant samples, there were 9 papillary thyroid carcinomas, 1 oncocytic carcinoma, 1 noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and 3 follicular thyroid carcinomas. CONCLUSION: In young patients with ITNs, the Afirma GSC demonstrated an excellent negative predictive value when defining a thyroid nodule result by histology or clinical follow-up.

Thyroid Nodule

Fine-needle aspiration of the breast: diagnoses and pitfalls. A review of 3545 cases.

Fine-needle aspiration is now a recognized diagnostic tool. In the past eight years we have studied 3545 aspirates from the breast, including both cystic and solid masses. All were prepared according to the method of Papanicalaou. The cellular findings are described and discussed. Abnormal cells were found in the aspirates from 90% of the 368 malignancies. Reliable criteria for diagnosis are emphasized and diagnostic pitfalls discussed. Aspiration biopsy was helpful in the management of all patients with breast lesions. The method is rapid, accurate, and essentially complication-free. It should be used with the idea of complementing, not competing with, routine histologic biopsy.

Adenofibroma

Scrape Cytology of DEK::AFF2 Fusion-Associated Papillary Squamous Cell Carcinoma of the Sinonasal Tract Masquerading as Schneiderian Papilloma: A Case Report.

INTRODUCTION: DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a recently characterized sinonasal neoplasm that closely mimics Schneiderian papilloma. Although one report has described fine-needle aspiration cytology of a metastatic lymph node, scrape cytological features from the primary site remain undocumented. CASE PRESENTATION: We report the scrape cytology of this tumor in a 26-year-old woman. While certain features (perivascular arrangement and intracytoplasmic nuclear debris-like structures) overlapped with Schneiderian papilloma, several findings diverged: a predominantly discohesive pattern, nuclear enlargement with anisonucleosis, prominent nucleoli, stippled chromatin distinct from the neuroendocrine pattern, and a crackled cytoplasmic appearance. Immunohistochemistry for synaptophysin and chromogranin A was negative, excluding neuroendocrine differentiation. CD163 immunohistochemistry confirmed that the debris-containing cells were not histiocytes. E-cadherin showed heterogeneous downregulation in the initial biopsy, suggesting a candidate molecular basis for the discohesive pattern. The diagnosis was confirmed by AFF2 immunohistochemistry, DEK break-apart fluorescence in situ hybridization, and reverse transcription polymerase chain reaction with Sanger sequencing. Retrospective AFF2 immunohistochemistry of the initial biopsy, originally diagnosed as Schneiderian papilloma, was positive. The patient remained free of disease progression 34 months after completion of chemoradiotherapy for the antecedent lacrimal sac carcinoma. CONCLUSION: These findings provide the first comprehensive cytological documentation of this entity from a primary sinonasal site and delineate features diverging from Schneiderian papilloma that may prompt ancillary investigations.

Case report

Aspiration cytology in breast cancer. Its relevance to diagnosis.

Fine-needle aspiration cytology as a routine method in the management of breast disease was assessed in 237 patients presenting with a breast lump. The diagnostic accuracy of the method was 95.5% in both benign and malignant lesions. Fine needle aspiration is a safe procedure with an accuracy exceeding that of other diagnostic methods; it does not replace frozen-section histology but improves the management of breast disease by giving accurate preoperative diagnosis.

Adolescent