Oncocytic Variant of Pancreatic Neuroendocrine Tumors are Associated with Aggressive Characteristics

Document Type

Conference Proceeding

Publication Date

3-1-2024

Publication Title

Lab Invest

Abstract

Background: Prognostic stratification of well-differentiated PanNETs has been fraught with challenges. Recently in some studies, oncocytic PanNETs have been found to display some aggressive characteristics but data on this issue have been limited. Design: Previously unpublished PanNETs with distinctive oncocytic features (defined as N/C ratio <¼, abundant granular/eosinophilic cytoplasm, smooth nuclear membrane, & single prominent eccentric nucleolus; Fig. 1) constituting ≥25% of the tumor were retrieved. Clinicopathologic analysis was performed and contrasted with non-oncocytic PanNETs. An NGS assay characterizing ≥410 genes was performed in selected cases. Results: Among 434 systematically reviewed PanNETs, 17(4%) were qualified as oncocytic. Along with 3 additional cases identified from consultation files, the characteristics of these 20 cases were as follows: F/M=6/14 (0.43 vs 0.93 in non-oncocytic PanNETs; p=0.131), mean age=63 yrs (vs 57; p=0.068). Patients presented with larger/more advanced tumors with a mean size of 6.5cm (vs 3.5; p<0.001) and 75% were pT3/T4 (vs 40; p=0.033); Microscopically, in 17 cases, >50% of the tumor exhibited an oncocytic phenotype. Characteristic salt&pepper chromatin of PanNETs was often limited/absent. All (100%) tested cases were positive for chromogranin and/or synaptophysin, while negative for trypsin, chymotrypsin & arginase. Mean Ki-67 index was 7% (vs 4; p=0.001); 100% were G2 or G3 (vs 60; p=0.001). 90% revealed LVI, 45% revealed PNI. The metastasis rate was 62% (almost twice as high as non-oncocytic PanNETs; p=0.021) with 11/17 having LN mets and 6/13 liver mets. By NGS, DAXX was found to be mutated in 5/5 tested cases, MEN in 3/5, PTEN in 2/5, SMAD and MTOR in 1/5. F/U was available for 13 patients with a median survival of 92 mos, 4 patients died of disease. The overall 5-yr survival rate was 77% (vs 97; p=0.002; Fig. 2). For oncocytic PanNETs, there was 6.8 times risk of adverse outcome than non-oncocytic PanNETs. Conclusions: Oncocytic PanNETs (4% of all PanNETs) are aggressive tumors that present at advanced T stage (thus not amenable to watchful waiting), and exhibit many signs of aggressiveness (grade, LVI, PNI, & metastasis) as well as a higher mortality. Presence of DAXX mutation in all patients tested is interesting and may be related to aggressive behavior. When the rest of the prognostic features are not apparent, oncocytic morphology on a biopsy could predict the likelihood of aggressive behavior. Therefore, it should be duly recorded in surgical pathology reports and patients should be placed into close follow-up.

Volume

104

Issue

3

First Page

S1859

Last Page

S1861

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