Case presentation Non diabetic patient with hypoglycemic attacks - - PowerPoint PPT Presentation

Case presentation

Non diabetic patient with hypoglycemic attacks

• 30 years old
• Non diabetic female patient
• History of several unexplained hypoglycaemic

attacks

• CECT- Pancreatic head lesion
• Serum insulin level- elevated

• Underwent central pacreatectomy
• Macroscopy-

The cut surface shows two well demarcated, greyish- white nodules, ranging from 2cm to 0.7cm in maximum diameters.

• Microscopy-

• Multifocal neoplasm
• Organoid architecture
• Nested, acinar patterns and pseudorosette

formation

• Monotonous epithelial cells with regular round

nuclei with salt and pepper chromatin pattern and finely granular cytoplasm

• Mitoses <2/10 HPF
• No necrosis or tumour vascular emboli.

Diagnosis

• Well differentiated multifocal pancreatic

neuroendocrine tumour

Pa Pancr ncreati eatic c Ne Neuroe

• endocr

ndocrin ine e ne neoplasms lasms

• Accounting for 2-5% of all panceratic tumours.
• Commonest age group- 30-60 yrs
• No significant sex difference
• Potentially malignant neoplasms

* Well differentiated types- Pancreatic neuroendocrine tumours (PanNETs) * Poorly differentiated types- Pancreatic neuroendocrine carcinomas (PanNECs)

Etiology

Genetic syndromes Sporadic PanNETs

• 10-20% of cases -due to Germline
• Multiple endocrine mutations in DNA

neoplasia type 1 repair genes.

• von Hipple- Lindau

(MUTYH,CHEK2,BRCA2) Syndrome

• Neurofibromatosis type1
• Tuberous sclerosis
• Glucagon cell hyperplasia and neoplasia

PanNEC usually donot show such associations

2017 WHO classification of neoplasms

• f the neuroendocrine pancreas
• Non functioning(non-syndromic) neuroendocrine

tumours

• not associated with clinical features of hormone

hypersecretion

• Secrete peptide hormones,biogenic sustances like

pancreatic polypeptides and chromogranins *Pancreatic neuroendocrine microadenoma

• Diameter of tumour <5mm

*Non functioning pancreatic neuroendocrine tumour

• Insulinoma
• Glucagonoma
• Somatostatinoma
• Gastrinoma
• VIPoma
• Serotonin producing tumours with and without

carcinoid tumour

• ACTH producing tumour with Cushing syndrome
• Pancreatic neuroendocrine carcinoma
• Mixed neuroendocrine- non neuroendocrine

neoplasms

• Non neuroendocrine component is usually ductal

adenocarcinoma or acinar cell carcinoma.

• Each component should be >30% of the tumour

cell population.

Histological grading and classification

• WHO classification 2010
• PanNETs were graded according to proliferation

index. Mitoses Ki67 G1 <2/10HPF <2% G2 2-20/10HPF 3-20% PanNEC were classified as G3 >20/10HPF >20% PanNEC were further subclassified into small cell CA

• r large cell CA

• WHO CLASSIFICATION 2017

The grading of PanNEN depends on

• proliferation index
• Tumour morphology

Ki67 index Mitotic index Well differentiated PanNENs( PanNETs) PanNET G1 <3% <2/10HPF PanNET G2 3-20% 2-20/10HPF PanNET G3 >20(<55% ) >20/10HPF Poorly differentiated PanNENs(PanNECs) PanNEC(G3) >20% >20/10HPF small cell type Large cell type Mixed neuruendocrine- nonneuroendocrine neoplasm

• Both components are usually high grade(G3)
• Each components should be individually graded , using respective grading systems for each.

Comparison of the WHO classifications of PanNENs

WHO 2010

• NETs G1/G2
• NECs G3

Large cell type and small cell type

• Mixed adenoneuroendocrine CA
• Hyperplastic and preneoplastic

lesions

WHO 2017

• NETs G1/G2/G3(Well

differentiated NEN)

• NECs G3(Poorly

differentiated NEN) Large cell type and small cell type

• Mixed neuroendocrine-

non neuroendocrine neoplasm

The difference between NENs in digestive system and NENs in other

• rgans
• 2015 WHO classification of lungs and thymus

NENs take into account the grade of necrosis in addition to Ki67 proliferation index. Define 3 distinct subgroups

• Typical carcinoid(correspond to NET G1)
• Atypical carcinoid(NET G2)
• Large and small cell NECs

Macroscopy

• NETs -Solitary, well demarcated, tan to yellow

nodules

• NECs – Tan-red or yellowish, solid masses

Necrotic and haemorrhagic areas

Microscopy

• Well differentiated NET
• Organoid architecture including solid

nests,trabeculae,acinar and pseudo rosette formation

• No necrosis
• Monotonous tumour cells with regular nuclei, salt and

pepper chromatin pattern

• Stromal amyloid deposition, psammomatous

calcification, dense stromal fibrosis

• Histo- morphological variants

Clear cell/ lipid rich, oncocytic, pleomorphic, rhabdoid and glandular

 The tumor has a so-called “organoid structure” including ribbonlike and pseudo- rosette patterns.

B

(A). Glandular formation with psammomatous calcification. (B). Clear cell pancreatic NET. (C). Oncocytic pancreatic NET.

A B C

Poorly differentiated NECs

• No differentiated morphology
• Sheets and nests of tumour cells with

pleomorphic, hyperchromatic nuclei and abundant mitoses

• Salt and pepper chromatin pattern is lost
• Necrosis

Histologic features of pancreatic neuroendocrine carcinoma (NEC)(WHO PanNEC G3

Immunohistochemistry

• Diagnostic markers

Synaptophysin, chromogranin A

• Prognostic markers

Ki67, CK19, KIT, CD99, CD44, p27

• Markers to subclassified the functioning PanNETs

 Insulinoma- ISL1,Insulin  Glucagonoma-ISL1, Glucagon  Somatostatinoma- Somatostatin  Gastrinoma- Gastrin  VIPoma-VIP, Peptide histidine methionin  Serotonin producing tumour- serotonin  ACTH producing tumour- ACTH  PanNEC- p53

Insulinoma

• Most common functioning PanNET.
• 20% of all PanNENs
• Composed of insulin producing cells and proinsulin producing cells
• Secrete uncontrolled insulin causing hypoglycaemic syndrome.
• Female > men
• Commonest age- 60 yrs rare in young adults and children
• 10% of cases of insulinomas are multiple
• Associated with MEN type 1

Insulimatosis

• Almost insulinomas are found in the head and tail of the pancreas
• Diagnosis

Whipple triad-1. Hypoglycaemic symptoms

• 2. Plasma glucose <40mg/dl
• 3. symptoms relief following glucose administration
• ther Ix- CT/MRI

PET Prognostic markers- Size of the tumour <2cm- 10 yr survival rate 100% >2cm-10 yrs survival rate30% proliferation index

MCQ

• 1. Genetic syndromes associated with PanNETs
• a. MEN Type 1
• b. Von Hipple Lindau syndrome
• c. neurofibromatosis -1
• d. Tuberous sclerosis
• e. Glucagon cell hyperplsia

• 2. Features of pancreatic neuroendocrine

carcinoma

• a. poorly differentiated
• b. Necrosis
• c. Strongly positive of neuroendocrine markers

d.Usually not associated with genetic syndromes

• e. Good prognosis

Thank you