Endoscopic ultrasound-guided side-fenestrated needle biopsy sampling is sensitive for pancreatic neuroendocrine tumors but inadequate for tumor grading: a prospective study

Abstract

Accurate pretreatment grading of pancreatic neuroendocrine tumors (PanNETs) is important to guide patient management. We aimed to evaluate endoscopic ultrasound-guided fine needle biopsy sampling (EUS-FNB) for the preoperative diagnosis and grading of PanNETs. In a tertiary-center setting, patients with suspected PanNETs were prospectively subjected to 22-gauge, reverse-bevel EUS-FNB. The EUS-FNB samples (Ki-67EUS) and corresponding surgical specimens (Ki-67SURG) were analyzed with Ki-67 indexing and thereafter tumor grading, (GRADEEUS) and (GRADESURG) respectively. In total 52 PanNET-patients [median age: 66 years; females: 25/52; surgical resection 22/52 (42%)] were included. EUS-FNB was diagnostic in 44/52 (85%). In 42 available FNB-slides, the median neoplastic cell count was 1034 (IQR: 504–3667) with 32/42 (76%), 22/42 (52%), and 14/42 (33%) cases exceeding 500, 1000, and 2000 neoplastic cells respectively. Ki-67SURG was significantly higher compared to Ki-67EUS with a moderate correlation comparing Ki-67EUS and Ki-67SURG (Pearson r = 0.60, r2 = 0.36, p = 0.011). The GRADEEUS had a weak level of agreement (κ = 0.08) compared with GRADESURG. Only 2/12 (17%) G2-tumors were correctly graded in EUS-FNB-samples. EUS-guided fine needle biopsy sampling is sensitive for preoperative diagnosis of PanNET but biopsy quality is relatively poor. Therefore, the approach seems suboptimal for pretreatment grading of PanNET.

Grading medullary thyroid carcinoma on fine‐needle aspiration cytology specimens with the International Medullary Thyroid Carcinoma Grading System: A cytologic–histologic correlation

“…Studies of PanNETs with cytologic-histologic correlation, for instance, have generally found that grading on cytology material is significantly more likely to result in undergrading of cases than overgrading compared to surgical core biopsy or resection material. 9,10,[12][13][14][15][16][17] Case 25 was initially classified as low grade on the basis of review of the primary tumor resection, but when Ki67FNA from the lymph node metastasis was found to be high, rereview of the surgical material confirmed high-grade MTC in the lymph node metastases.…”

“…The finding of limited sensitivity but high specificity for Ki67FNA echoes prior studies comparing cytology and surgical Ki67 PRs in neuroendocrine tumors from other organ systems. Studies of PanNETs with cytologic–histologic correlation, for instance, have generally found that grading on cytology material is significantly more likely to result in undergrading of cases than overgrading compared to surgical core biopsy or resection material 9,10,12–17 …”

“…For the most part, they have found that PanNETs are far more likely to be undergraded than overgraded by FNA compared to surgical material. For instance, in a recent study by Appelstrand et al., all seven cases of grade 1 PanNET were correctly graded by FNA, whereas only two of 12 (17%) grade 2 cases were properly graded, with the rest being undergraded 9 . Similarly, Abi‐Raad et al.…”

“…For instance, in a recent study by Appelstrand et al, all seven cases of grade 1 PanNET were correctly graded by FNA, whereas only two of 12 (17%) grade 2 cases were properly graded, with the rest being undergraded. 9 Similarly, Abi-Raad et al found that all 27 of their grade 1 tumors were properly graded by FNA, whereas only nine of 22 (41%) grade 2 cases were properly graded, with the rest again being undergraded. 10 As a general rule, then, we can infer that FNA has limited sensitivity but relatively high specificity for establishing a higher grade in well-differentiated neuroendocrine tumors by Ki67 PR and mitotic rate.…”

Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms

“…Among the studies, higher levels of concordance have been achieved when only samples with high cellularity were included, when the highest Ki-67 index was considered for grading, and for small lesions of less than 2 cm in diameter. Again, most pitfalls have been found for grade 2 tumours, which are often downstaged [ 83 , 96 , 97 , 98 , 99 , 100 , 101 , 102 ]. An adequate sample size using a needle that allow a total length of the sample of at least 15 mm with prevalence of neoplastic tissue (>80%) should help in minimizing the risks of misinterpretation of tumour grade [ 36 ].…”