Core Needle Biopsy and Fine Needle Aspiration Alone or in Combination: Diagnostic Accuracy and Impact on Management of Renal Masses.

PURPOSE: Fine needle aspiration with and without concurrent core needle biopsy is a minimally invasive method to diagnose and assist in management of renal masses. We assessed the pathological accuracy of fine needle aspiration compared to and associated with core needle biopsy and the impact on management. MATERIALS AND METHODS: We performed a single institution, retrospective study of 342 cases from 2001 to 2015 with small and large renal masses (4 or less and greater than 4 cm, respectively). Diagnostic and concordance rates, and the impact on management were analyzed. RESULTS: Adequacy rates for fine needle aspiration only, core needle biopsy only and fine needle aspiration plus core needle biopsy were 21%, 12% and 8% (aspiration vs aspiration plus biopsy p <0.026). In the aspiration plus biopsy group adding aspiration to biopsy and biopsy to aspiration reduced the inadequacy rate from 23% to 8% and from 27% to 8% for a total reduction rate of 15% and 19%, respectively, corresponding to 32 cases (9.3%). Rapid on-site examination contributed to a 22.5% improvement in fine needle aspiration adequacy rates. In this cohort 30% of aspiration only, 5% of biopsy only and 12% of aspiration plus biopsy could not be subtyped (aspiration vs biopsy p <0.0001, aspiration vs aspiration plus biopsy p <0.0127 and biopsy vs aspiration plus biopsy p = 0.06). The diagnostic concordance rate with surgical resection was 99%. Conversion of an inadequate specimen to an adequate one by a concurrent procedure impacted treatment in at least 29 of 32 patients. Limitations include the retrospective design and accuracy measurement based on surgical intervention. CONCLUSIONS: Fine needle aspiration plus core needle biopsy vs at least fine needle aspiration alone may improve diagnostic yield when sampling renal masses but it has subtyping potential similar to that of core needle biopsy only.

Prolonged fever and splenic lesions caused by Malassezia restricta in an immunocompromised patient.

Malassezia species are commonly found on human skin as commensals but can cause invasive infections in premature infants and immunocompromised hosts. Due to their fastidious growth, diagnosis of Malassezia infections can prove challenging. Molecular techniques can aid in diagnosis and treatment of invasive infections. We describe the case of a pediatric oncology patient with splenic lesions secondary to Malassezia restricta.

Nondiagnostic category of Milan System for Reporting Pediatric Salivary Gland Cytopathology: outcomes and root cause analysis.

BACKGROUND: Fine-needle aspiration (FNA) results classified as the nondiagnostic category of the Milan system for reporting salivary gland cytopathology (MSRSGC) may be infrequently encountered in children. Clinical management may be challenging due to lack of data regarding outcomes and underlying causes. METHODS: We retrospectively analyzed 106 consecutive pediatric salivary gland FNAs (2000-2020; 45% performed under image guidance). The outcomes of patients with nondiagnostic results were analyzed. Clinical parameters, FNA procedural parameters, and histopathologic parameters were compared between diagnostic and nondiagnostic cases. A root cause analysis was performed using the fishbone diagram and the 5 Whys method. RESULTS: A total of 103 initial FNAs were identified. The nondiagnostic rates for initial and repeat biopsy were 16% (16/103) and 67% (2/3), respectively. Initial nondiagnostic FNAs were most frequently managed by clinical/radiologic follow-up only (56%, 9/16), followed by direct surgery (19%, 3/16) and repeat FNA (19%, 3/16). By histologic and clinical/radiologic follow-up, the risk of malignancy for nondiagnostic cases was zero. Palpation guidance (P < .05), inadequate sampling determined by rapid on-site evaluation (P < .01), and lesions with cystic, vascular, or diffuse nature (P < .05) were significantly associated with nondiagnostic results. By root cause analysis, proceduralist sampling error and lack of ultrasound guidance were the most common primary and secondary causes, respectively. CONCLUSIONS: Pediatric salivary gland lesions of the nondiagnostic MSRSGC category have minimal risk of malignancy and may be successfully managed by clinical/radiologic follow-up. The root causes for nondiagnostic results were often multifactorial and primarily related to proceduralist sampling, characteristics of the lesions, and lack of ultrasound guidance.

Fine-Needle Aspiration Biopsy of Pediatric Salivary Gland Tumors: Analysis of Patient Tolerability, Sedation Requirement, and Procedural Complication.

OBJECTIVE: Fine-needle aspiration (FNA) biopsy is the standard diagnostic tool recommended by consensus management guidelines for preoperative evaluation of salivary gland tumors in adults. However, its utility in the pediatric population remains debated due to a paucity of data and inherited challenges of pediatric management (patient cooperation, the need for sedation, and procedural complications). METHODS: Consecutive series of 92 FNA biopsies of pediatric salivary gland lesions with available procedural data were included for retrospective analysis. Patient demographics, procedural characteristics, and complications were assessed. RESULTS: Sixty-three patients (68%) tolerated FNA without sedation. Sedation need was significantly associated with younger age, concurrent non-FNA procedure requiring sedation, ultrasound guidance, interventional radiologist as the proceduralist, and radiology suite as the facility setting. The sedation rates for children, and early, middle, and late adolescents were 69%, 32%, 12%, and 10%, respectively, with an optimal cutoff point of ≤12 years for age derived from receiver operating characteristic curve analysis. No significant procedural complications were observed. Sedation did not provide significantly better diagnostic yield. CONCLUSION: FNA biopsy of salivary gland tumors is safe, well tolerated by the pediatric population, and can be effectively performed in an outpatient setting without sedation in most cases. FNA biopsy is a useful tool in the preoperative management of pediatric patients with salivary gland tumors.

Improvement of Pediatric Liver Core Biopsy Adequacy by Reducing Laboratory-Related Tissue Fragmentation and Increasing Portal Tract Yield.

OBJECTIVES: We aimed to identify potential laboratory causes of suboptimal liver biopsy quality and sought to implement corresponding measures to improve biopsy adequacy. METHODS: We prospectively measured the number and size of tissue fragments and the amount of portal tracts in 200 consecutive pediatric medical liver biopsies before and after quality improvement processes were initiated. RESULTS: We identified laboratory-related tissue fragmentation as a significant cause of low biopsy adequacy. The principal approaches to reduce fragmentation included establishment of multistep monitoring of tissue integrity, adjustment of specimen-processing conditions, and laboratory staff education and awareness. These adjustments collectively led to lower overall tissue fragmentation (decreasing from 59% to 24%, P < .01) and higher biopsy adequacy rates (increasing from 32% to 56%, P < .01). The number of evaluable portal tracts increased from 4.4 to 5.7 portal tracts per centimeter of core biopsy tissue (P < .01). CONCLUSIONS: We demonstrated a sustainable improvement in the overall quality of pediatric needle core liver biopsies by reducing tissue fragmentation. Effective laboratory adjustments included monitoring of tissue integrity, modifications of processing conditions, and laboratory staff education.

Application of the Milan System for Reporting Pediatric Salivary Gland Cytopathology: Analysis of histologic follow-up, risk of malignancy, and diagnostic accuracy.

BACKGROUND: The diagnosis and management of salivary gland tumors in pediatric patients can be challenging. The utility of fine-needle aspiration (FNA) cytopathology and the performance of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) in this age group have not been systematically assessed. The paucity of data has contributed to the controversial role of FNA cytopathology in the presurgical management of these patients. METHODS: The authors retrospectively analyzed 104 pediatric salivary gland FNAs (2000-2020). A correlation with the available histopathologic follow-up (n = 54) was performed. The distribution percentages, the risk of neoplasm (RON), and the risk of malignancy (ROM) were assessed for each category of the MSRSGC. RESULTS: The overall sensitivity, specificity, negative predictive value, and positive predictive value of pediatric salivary gland FNAs were 80%, 97%, and 92%, respectively. The RON values for the nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories were 60%, 11%, 100%, 100%, 100%, 100%, and 100%, respectively, whereas the ROM values were 0%, 11%, 100%, 6%, 67%, 100%, and 100%, respectively. The percentage of nonneoplastic FNAs was greater in comparison with the adult population (52% vs 8%). All neoplasms in patients aged 0 to 10 years were malignant, whereas benign neoplasms occurred only in patients aged ≥11 years; this supported an inverse correlation between age and malignancy rate in salivary gland neoplasms. CONCLUSIONS: FNA cytopathology demonstrates excellent diagnostic performance in differentiating malignant and benign pediatric salivary gland lesions. The MSRSGC is a valuable tool for standardization of the reporting and preoperative risk stratification of these lesions.

Instrument Gauge and Type in Uveal Melanoma Fine Needle Biopsy: Implications for Diagnostic Yield and Molecular Prognostication.

PURPOSE: To systematically evaluate and compare the effects of using small-gauge needles and vitrectors on the ability to obtain adequate diagnostic and prognostic uveal melanoma biopsy specimens. DESIGN: Comparative evaluation of biopsy instruments. METHODS: Survival of uveal melanoma cells was evaluated in vitro following needle aspiration. Five therapeutically enucleated eyes were sampled in triplicate for ex vivo diagnostic biopsy experiments with 25 gauge (25 G) needle, 27 gauge (27 G) needle, and 27 G vitrector. During surgery in 8 patients, paired diagnostic transscleral fine needle aspiration biopsies were performed using both 25 G and 27 G needles. A review of cytologic specimens was performed by a panel of 3 expert cytopathologists. A retrospective chart review was performed to evaluate 100 consecutive tumors undergoing prognostic biopsy for gene expression profiling to assess the relationship between needle gauge and prognostic adequacy. RESULTS: No significant cell shearing of uveal melanoma cells occurred in vitro with 25 G, 27 G, or 30 G needles. For ex vivo biopsy samples, diagnostic yield was 100% using 25 G needle (5/5) or 27 G vitrector (5/5) but 60% using a 27 G needle (3/5). For in vivo samples, no difference in diagnostic yield was found between 25 G (75%, 6/8) or 27 G (75%, 6/8) needle sizes. Of 100 molecular prognostic biopsy samples evaluated, 65 were obtained using 27 G needles; for these biopsies, the prognostic yield was 65/65 (100%). CONCLUSIONS: For diagnostic biopsy of uveal melanoma, a larger-gauge needle or a 27 G vitrector may have better overall cellularity and diagnostic yield when compared to a 27 G needle. However, for much more common molecular prognostic testing, a 27 G needle provided adequate sample in 100% (65/65) of cases, and a larger needle provided no additional benefit.

Diagnostic renal mass biopsy is associated with individual categories of PADUA and RENAL nephrometry scores: Analysis of diagnostic and concordance rates with surgical resection.

BACKGROUND: Renal mass biopsy (RMB) is a safe and accurate method for diagnosis and clinical management of renal masses. However, the non-diagnostic rate is a limiting factor. We tested the hypothesis that imaging characteristics and anatomic complexity of the mass may impact RMB diagnostic outcome using the preoperative aspects and dimensions used for an anatomical (PADUA) classification and radius-exophytic/endophytic-nearness-anterior/posterior-location (RENAL) score. MATERIAL AND METHODS: Single institution, retrospective study of 490 renal masses from 443 patients collected from 2001 to 2018. Outcome measurements include (1) diagnostic and concordance rates amongst RMB types and RMB with surgical resection specimens; (2) association between diagnostic RMB and anatomical complexity of renal masses. The analysis was conducted in unselected masses and small renal masses (SRMs). RESULTS: RMB was performed by fine needle aspiration (FNA), core needle biopsy (CNB), or both (FNA+CNB). Non-diagnostic rate was significantly higher for FNA compared to CNB and FNA+CNB in both unselected and SRMs. Subset analysis in the FNA+CNB group showed similar diagnostic rates for FNA and CNB. In unselected masses, specificity for FNA, CNB, and FNA+CNB was 100%. Sensitivity was higher for CNB (90.1%, P = 0.002) and FNA+CNB (96.3%, P = 0.004) compared to FNA (66.7%). For unselected masses, endophytic growth predicted a non-diagnostic CNB. R.E.N.A.L location entirely between the polar lines (central) and entirely above the upper polar line predicted a diagnostic CNB. Sonography-guidance predicted a diagnostic FNA. For SRMs, non-diagnostic CNB was associated with endophytic growth, while diagnostic CNB was associated with renal sinus invasion and operator experience. More cystic masses were sampled by FNA, but diagnostic results were similar for FNA and CNB. CONCLUSIONS: Endophytic growth consistently predicted a non-diagnostic CNB in unselected and SRMs, whereas sonography-guidance predicted a diagnostic FNA. Cystic masses could be adequately sampled by FNA.

Incidence and malignancy rates of indeterminate pediatric thyroid nodules.

BACKGROUND: The American Thyroid Association guidelines task force currently recommends definitive thyroidectomy or lobectomy after an indeterminate thyroid biopsy in children. This recommendation is based on evidence of a greater incidence and a higher risk of malignancy compared with adults in earlier pediatric studies. Such management may lead to overtreatment and unnecessary surgery for many children in the United States. METHODS: The objective of the current study was to re-evaluate pediatric thyroid nodules and assess the overall percentages and malignancy rates for indeterminate thyroid biopsies in children. In total, 302 pediatric thyroid fine-needle aspirations (FNAs) were analyzed retrospectively (2001-2018). Distribution percentages and malignancy rates were calculated for each category of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). RESULTS: Two indeterminate TBSRTC groups (atypia of undetermined significance/follicular lesion of undetermined significance and follicular neoplasm/suspicious for a follicular neoplasm) had much lower distribution percentages and malignancy rates compared with earlier pediatric series and American Thyroid Association guidelines. A meta-analysis further supported these findings and demonstrated distinctly different malignancy rates for the indeterminate groups (atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for a follicular neoplasm, and suspicious for malignancy), suggesting the need for TBSRTC category-specific management recommendations rather than a nondiscriminatory, up-front surgical approach. CONCLUSIONS: Adult patients with indeterminate preoperative thyroid cytopathology are followed by repeat biopsy and possibly molecular testing before undergoing definitive surgery. However, in children, the guidelines are considerably more aggressive and recommend definitive surgery after the first indeterminate thyroid biopsy. Here, the largest pediatric cohort to date with meta-analysis is presented, and the authors propose a re-evaluation of this up-front approach to pediatric thyroid care.

Fine-Needle Aspiration-Based Grading of Pancreatic Neuroendocrine Neoplasms Using Ki-67: Is Accurate WHO Grading Possible on Cytologic Material?

INTRODUCTION: The World Health Organization (WHO) has provided grading guidelines for pancreatic neuroendocrine neoplasms (PanNENs) based on mitotic count and Ki-67 proliferation index. Due to the desire to provide earlier tumor grading for clinical management decisions, some groups have proposed grading PanNENs at the time of fine needle aspiration (FNA) using Ki-67 proliferation rates. While a Ki-67 can be performed on FNA cell blocks, there are potential sampling limitations with this technique that may affect the reliability of the Ki-67 result. MATERIALS AND METHODS: Forty-nine PanNENs with FNA cell blocks and corresponding resection material were evaluated by immunohistochemistry for expression of Ki-67. Ki-67 proliferation rate was calculated based on cell counts of >500 cells in the highest staining areas. Ki-67 scores from FNA cell blocks were correlated with Ki-67 scores from resection specimens. RESULTS: The FNA Ki-67 proliferation rates overall did not correlate well with the resection specimen. A linear regression analysis of the correlation between FNA %Ki-67 and resection %Ki-67 showed a slope of 3.2 and an R2=0.58. The average difference in Ki-67 proliferation rate between FNA and resection was 5.9%. Thirty-nine percent (19/49 cases) of PanNENs showed discordant grading between the FNA cell block and resection specimen. Almost all (18/19) discordant cases demonstrated a lower FNA-based grade as compared to the resection grade. CONCLUSIONS: FNA cell block grading using Ki-67 frequently led to under-grading of the tumor. This finding is consistent with concerns that FNA may not provide accurate grading due to the limited sampling of the tumor.

Molecular testing of NSCLC using a platform for rapid detection of multiple oncogenetic mutations.

INTRODUCTION: Molecular testing has become the standard of care for treatment of non-small cell lung cancer. Cytologic samples are frequently the only diagnostic material obtained due to the reduced procedure-related morbidity of fine-needle aspiration. This is a report of our laboratory's experience using cytology specimens for molecular testing of lung tumors. MATERIALS AND METHODS: All tumors were tested in the Molecular Diagnostics Laboratory at Vanderbilt University Medical Center using the ABI PRISM SNaPshot Multiplex Kit and a separate laboratory-developed test. The assay included testing for KRAS, BRAF, NRAS, PIK3CA, MEK1, AKT1, PTEN, and EGFR mutations. Specimens were tested using a paraffin-embedded cell block, and a percentage of tumor cells was determined to establish adequacy of the sample. Ten percent or more tumor cells was considered adequate. Eighty-five cytology specimens were referred for testing, and 12% were considered inadequate. Specimens tested included 55 adenocarcinomas, 6 squamous cell carcinomas, 5 large cell neuroendocrine carcinomas, 2 small cell carcinomas, and 7 categorized as non-small cell carcinoma, unable to further differentiate. Primary lung tumors as well as lung tumors metastatic to other tissues were tested. The samples ranged from 3 mm to 15 mm, and all but 1 sample had >10% tumor cells on initial and final hematoxylin and eosin slides. RESULTS: Forty-eight mutations were identified in 42 tumors: 21 KRAS, 22 EGFR, 1 BRAF, 1 NRAS, 1 PIK3CA, 1 ERBB2, and 1 MEK1. Thirty-three tumors were negative for the mutations tested. CONCLUSIONS: The DNA yield from cytology specimens is routinely adequate for molecular mutation analysis of lung cancer.

Diagnostic and therapeutic challenges in hepatic epithelioid hemangioendothelioma.

BACKGROUND: Epithelioid hemangioendothelioma is a very rare, low-grade vascular tumor known to arise in soft tissues and visceral organs. Clinical diagnosis of hepatic epithelioid hemangioendothelioma remains a challenge, and although it is frequently managed with a liver transplant due to its multifocal nature, recurrence is a common complication. METHODS: We review recent advances in the diagnosis of hepatic epithelioid hemangioendothelioma, including major genetic breakthroughs, and discuss efforts to reduce post-liver transplant recurrence of hepatic epithelioid hemangioendothelioma.