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.

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.

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.

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.