Gastric and Oesophageal Neuroendocrine tumours. Dr Tim Bracey, Consultant Pathologist MBChB PhD MRCS FRCPath
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1 Gastric and Oesophageal Neuroendocrine tumours Dr Tim Bracey, Consultant Pathologist MBChB PhD MRCS FRCPath
2 Intestinal (and BO) endocrine cells in crypt bases NE cell (granules towards vessels) Paneth cell (granules towards lumen)
3 Enteroendocrine system
4 Normal gastric endocrine cells in gland neck
5 Endocrine cells of Merkel cell type in normal oesophageal squamous epithelium
6 Carcinoid, NET or NEC?
7 Innocent-looking but potentially aggressive
8 Call it a NE tumour, grade it, then stage (type and site specific)
9 Characteristic Type I Type II Type III Proportion of all GNETs 70%-80% 5%-10% 10%-15% Associated disease Chronic atrophic gastritis MEN type 1/Z-E (Hypertrophic mucosa) None (normal mucosa) Gender Women > men Women = men Women < men Tumor number Tumor size < 10 mm (77%) < 10 mm Often > 20 mm Tumor location Fundus or corpus Fundus or corpus Any region Histology Well differentiated +Neuroendocrine cell hyperplasia Well differentiated From well to poorly differentiated Invasion depth Mucosa or submucosa (7% involve MP) Mucosa or submucosa Any depth (half to serosa) >70% nodal spread Serum gastrin level High High Normal Gastric ph Low High Normal Metastasis risk 2%-5% 10%-20% > 50% Tumor-related death 0 < 10% 25%-30% Prognosis Excellent Good Poor
10 62F multiple small nodules and erosions in erythematous mucosa
11 Chromogranin positive. MIB1<1%
12 Neuroendocrine cell hyperplasia in other non-tumour biopsies
13 Gastric Endocrine hyperplasia Linear daisy chain >5/gland Micronodular solid nests no wider than neighbouring glands ( um) Adenomatoid interglandular nodules >5 cells with intact basement membrane Dysplasia enlarged/fused nodules less than 0.5mm (otherwise = microcarcinoid)
14 Diagnosis = G1 NET (type 1) with CAG Has had two subsequent endoscopic biopsies showing the same in last two years All tumours less than 1cm
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19 52F (ML) lap excision of gastric NET
20 30mm G1 tumour (MIB<1%) No atrophy or IM -presumed type III sporadic R0 (20mm clear margin)
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22 ENETS/RCPath pn and pm staging
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27 Grading NET Google immunoratio 18.9% ie. G2 <20%
28 Oesophageal NETs LG NETs are exceptionally rare Most in my experience are high grade SmCC and metastatic at presentation Mixed differentiation is more common than the literature would suggest True MANECs are still rare, but they should be managed according to the predominant non- NEC component (ie. SCC or adenocarcinoma)
29 IHC neuro endocrine markers CD56 (N-CAM)
30 Elderly female large friable gastric fundal mass in hiatus hernia CT stage= T3N2M1
31 necrosis Smear, moulding High n:c ratio etc
32 The best IHC for neuroendocrine differentiation? NE punctate staining pattern Normal staining pattern Remember 10% of HG neuroendocrine carcinomas show negative neuroendocrine markers!
33 TTF1 is positive in >70% oesophageal SmCC
34 Case study 7 60 year old male GOJ tumour Biopsy originally reported as poorly differentiated adenocarcinoma On review foci resembling carcinoid tumour.but preoperative staging T3 N1
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38 Chromgranin weak/negative in the signet ring cells
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40 MANECs Must be at least 30% of each component Morphological and immunohistochemical evidence of NE differentiation Does not apply to carcinomas with focal chromogranin/synaptophysin immunoreactivity Grade both components (in the above case both adenocarcinoma and NET were high grade). Pt now has liver mets
41 Case study 8 83 year old male GOJ Siewert 1 tumour Biopsy originally reported as moderately differentiated adenocarcinoma On review foci resembling NET in addition to intestinal adenocarcinoma. preoperative staging T3 N0 Both these patients had PET and octreotide scans to exclude distant mets before neoadjuvant and surgical treatment
42
43
44 Glandular areas negative chromogranin
45 Case study 8 MANEC comprising moderately differentiated adenocarcinoma (intestinal) and G2 endocrine carcinoma No response to neoadjuvant but all nodes clear; T3 N0 (0/27) R1 (0.5mm circumferential) TRG5 (no response)
46 Summary Gastric NETs are increasingly common but usually small, indolent G1 tumours Larger sporadic NETs may need radical surgery but some may be amenable to EMR or ESD High grade tumours and MANECs should be currently staged and managed as conventional OG cancers
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