HIGH-GRADE WELL- AND POORLY DIFFER-ENTIATED DIGESTIVE NEUROENDOCRINE NEOPLASMS: CLINICAL IMPLICATIONS FOR DISTINCT ENTITIES

Introduction: Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are rare, with a dismal prognosis. The 2017 WHO subclassified the G3 pancreatic group into high grade (poorly differentiated carcinoma NEC) or neuroendocrine tumors (G3-NET). Yet few data exist on how this subclassification applies to other digestive G3-NEN. Aim: We planned to evaluate the clinical and pathological characteristics of GEP G3-NET and NEC. Materials and Methods: We retrospectively and consecutively collected clinicopathological data of all G3-GEP-NEN patients (pts) from a single institution between 2000 and 2019. Data were gathered from electronic clinical charts and cases with available tumor tissues were centrally reviewed and reclassified according to WHO 2017. The primary endpoint was overall survival (OS), calculated from the date of diagnosis of G3 disease. Descriptive statistics was used to report population characteristics, OS was calculated with the Kaplan-Meier method. Results: Seventy-seven G3-GEP-NEN pts were included: mean age at the diagnosis was 58.9 years (± 15) and 62% (48/77) were males. The most common primary site was gastric (27%, 21/77), followed by pancreas (23%, 18/77), unknown primary (23%, 18/77), colorectal (18%, 14/77) and others (midgut plus anal) with 8% (6/77). Metastatic disease was present in 69% (53/77) at diagnosis and 91% (70/77) evolved to metastatic disease. Overall 77% (59/77) received a platinum-based chemotherapy and 42 (54%) pts underwent only one line of treatment. The reviewed pathology was available in 56% (43/77): 29 cases were NEC (67%) and 14 were G3-NET (33%). This reflects a change in diagnosis of 23% (10/43). In a median follow-up of 57.9 months, the median survival of all pts was 22.9 months. The group with Ki-67 lower than 55% had a median OS of 58 months vs 13 months for Ki-67 above 55% (p = 0.003). The median OS of the non-pancreatic digestive G3-NET, the pancreatic NET-G3 and the GEP-NEC were 61.2, 57.4 and 13.0 months, respectively (non-pancreatic G3-NET vs NEC, p = 0.007). In the non-pancreatic NEC subgroup, there was no OS difference between small versus large cell histology (p = 0.7). Conclusion: Non-pancreatic digestive G3-NET is associated with increased survival compared to non-pancreatic NEC, resembling the prognosis of G2 GEP-NET. This indicates that histological differentiation is essential for prognosis and treatment planning, as some NET-G3 pts may be treated as G2 NET.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
23 October 2019