Pancreas tumours

1. THE PANCREAS
Dr.Sajitha.P.N .

2. Chronic pancreatitis
 Inflammation
 Destruction of exocrine parenchyma
 Fibrosis
 Destruction of endocrine parenchyma –
late stages.

3. Chronic vs acute pancreatitis
 Irreversible impairment of pancreatic
function

4. Causes
 Long term alcohol abuse
 Long standing obstruction of pancreatic duct by
calculi
pseudocysts
trauma
neoplasms
pancreas divisum
 Tropical pancreatitis

5. Causes
 Hereditary pancreatitis
 Idiopathic chronic pancreatitis – CFTR
related
 40%-no cause.

6. Pathogenesis
 Ductal obstruction by concretions-alcoholic
pancreatitis
 Toxic-metabolic
toxins,alcohol – direct toxic effect on acinar cells
 Oxidative stress – alcohol
 Necrosis – fibrosis in hereditary pancreatitis
repeated attacks of acute pancreatitis –
perilobular fibrosis,duct distortion &altered
secretions – loss of parenchyma & fibrosis

7. Chemokines
IL-8
MCP-1
TGF-b
PDGF

8. Morphology
 Parenchymal fibrosis
 Reduced no & size of acini ,relative sparing of islets
 Variable dilatation of the ducts
 Chronic inflammatory infiltrate around lobules & ducts
 Interlobular & intralobular ducts – dilated,contain protein
plugs
 Ductal epithelium – atrophied or hyperplastic
 Ductal concretions

9. Morphology
 Acinar cell loss – constant feature
 Islets of Langerhans embedded in
sclerotic tissue & may fuse
 Eventually islets also disappear
 Gross – gland is hard with extremely
dilated ducts &visible calcified concretions

12. Clinical features
 Different presentations
repeated attacks of moderately severe abd.pain
recurrent attacks of mild pain
persistent abd &back pain
 Silent till pancreatic insufficiency & DM develop
 Recurrent attacks of jaundice or indigestion

13. Diagnosis
 Visualisation of calcifications – by CT or
USG

14. Complications
 Pseudocyst
 Malabsorption,steatorrhea
 Secondary DM
 Pancreatic carcinoma – 40% risk in
hereditary pancreatitis

15. Non neoplastic cysts
 Congenital cysts
 pseudocysts

16. Congenital cysts
 Polycystic disease
 Von Hippel Lindau disease

17. Pseudocysts
 75% of cysts in pancreas
 Localized collections of necrotic-
hemorrhagic material rich in pancreatic
enzymes
 Arise after an epidose of AP & following
traumatic injury to abdomen

18. Pseudocysts
 Solitary
 Size – 2 to 30cm
 Formed by the walling off of areas of
peripancreatic hemorrhagic fat necrosis
with fibrous tissue
 No epithelial lining.
 course

19. Neoplasms
 Cystic neoplasms
 Pancreatic carcinoma

20. Cystic neoplasms
 Serous cystadenomas
 Mucinous cystic neoplasms
 Intraductal papillary mucinous neoplasms
– IPMNs
 Solid pseudo papillary tumor

21. Serous cystadenoma
 Always benign
 25% of cystic neoplasms
 M:F – 1:2
 7th decade of life
 Composed of small cysts - clear,
thin,straw coloured fluid – lined by
glycogen rich cuboidal cells

24. Mucinous cystic neoplasms
 Almost always in women
 Benign,borderline or malignant
 Arise in body or tail
 Painless,slow growing masses
 Cystic spaces filled with thick tenacious
mucin & lined by columnar epithelium with
dense ovary like stroma

27. IPMNs
 Common in men
 Benign,borderline or malignant
 Site – headof pancreas
 Mucin containing cysts
 No “ovarian” stroma
 Arise in the main pancreatic ducts

28. Solid pseudopapillary tumor
 Adolescent girls,young women
 Usually benign
 Large well circumscribed tumors
 Solid &cystic areas –cysts filled with
hemorrhagic debris

29. Pancreatic carcinoma
 Infiltrating ductal adenocarcinoma
 4th leading cause of cancer death in USA
 Highest mortality rates
 5 year survival rate -<5%

30. Precursor lesions
 Pancreatic intra epithelial neoplasia –
PanINs
 The epithelial cells in PanINs show
dramatic telomere shortening
 A critical shortening may predispose these
lesions to accumulate progressive
chromosomal abnormalities & develop
invasive carcinoma

31. Molecular carcinogenesis
 K-RAS-80 to 90%
 P16 -95%
 SMAD4 -55%
 P53 -50 to 70%
 Methylation abnormalities -
hypermethylation

32. Etiology
 Smoking
 Diet rich in fats
 Hereditary pancreatitis

33. Familial syndromes
 HNPCC Lynch II variant
 Hereditary breast &ovarian cancer
 Familial atypical multiple mole melanoma
syndrome –FAMMM
 Hereditary pancreatitis – PRSS1
 Peutz-Jeghers syndromes

34. Epidemiology
 Age -60 to 80yrs
 blacks

35. Site
 Head -60%
 Body -15%
 Tail -5%
 Entire gland -20%

36. Morphology
 2 characteristic features
highly invasive
intense desmoplastic reaction
 Ca –head-obstruct CBD –jaundice
 Ca –body&tail –remain silent

37. Gross
 Hard,stellate ,gray-white
 Poorly defined masses

39. Microscopy
 Moderately to poorly differentiated
adenocarcinoma
 Malignant glands are
atypical,irregular,small,bizzare &lined by
anaplastic cuboidal to columnar cells
 Highly aggressive ,infiltrative growth pattern
 Dense stromal fibrosis
 Perineural & lymphatic invasion +

41. Other variants
 Acinar cell ca
 Adenosquamous ca
 Undifferentiated with osteoclast like giant
cells

42. Spread
 Local – retroperitoneal space –
spleen,adrenals,vertebral column,tr.colon
& stomach
 Lymphatic –
peripancreatic,mesenteric,gastric,omental
&portahepatic LNs
 Distant – lung,bone

44. Clinical features
 Silent
 Pain
 Obstructive jaundice
 Weight loss,anorexia,gen.weakness
 Trousseau sign
 Diagnosis – USG,CT

45. Course
 Brief & progressive
 <20%-resectable
 No specific markers

46. Pancreatoblastoma
 Children -1 to 15yrs
 Rare
 Malignant
 Microscopy – squamous islands admixed
with undifferentiated cells

47. Tumors –Endocrine Pancreas
 PEN
 B cells – insulin -68%
 A cells – glucagon -20%
 D cells – somatostatin-10%
 PP cells – pancreatic polypeptide-2%
 D1 cells – VIP
 Enterochromaffin cells - serotonin

49. PEN
 2% of all pancreatic neoplasms
 Adults
 Anywhere along the pancreas
 Single or multiple
 Benign or malignant
 Functional or nonfunctional

50. Unequivocal criteria for malignancy
 Mets to regional LNs or distant organs
 Vascular invasion
 Gross invasion of adjacent viscera

51. Insulinoma -hyperinsulinism
 Cell of origin –B cells
 Most common PEN
 Clinical triad – attacks of hypoglycemia
confusion,stupor &loss of consciousness
ppted by fasting or exercise &relieved by
administration of glucose

52. Morphology
 Benign
 Solitary
 Arise in ectopic pancreas
 Often <2cm, encapsulated, pale to
redbrown nodules
 Microscopy- giant islets

53. Clinical features
 Hypoglycemia –mild
 Lab findings – high circulating levels of
insulin,high insulin glucose ratio
 Treatment surgical removal

54. Gastrinoma-Zollinger-Ellison
syndrome
 Gastrinoma triangle – duodenum,pancreas &
peripancreatic soft tissue
 Zollinger-Ellison syndrome –
hypergastrinemia,hypersecretion of gastric acid
&peptic ulceration
multiple ulcers in duodenum & stomach
ulcers in unusual locations - jejunum
unresponsive to usual modalities of therapy

55. Morphology
 Gastrinoma triangle
 >50% - locally invasive or metastasised
 Treatment - excision

57. MEN-1 associated gastrinomas
 Multifocal
 25% of gastrinomas

58. Rare PEN
 Glucagonoma –A cells
 Somatostatinomas –D cells
 VIPomas –D1 cells-
 Carcinoid tumors

59. Diffuse hyperplasia of islets
 Nesidioblastosis
 Neonates & infants
 Maternal diabetes,Beckwith- Wiedemann
syndrome