pathology of pancreatic tumors.pptx

these slides covered pathology of pancreatic tumors

1. pathology of Pancreatic Tumors Ahmed GSR-II moderator: Dr Hunde(MD,Surgeon) may 11, 2022

2. Introduction Anatomy of pancreas Epidemiology, Risk Factors Classification Clinical presentation Work up Reference Outline

3. Fourth leading cause of cancer death Median survival time of all pts is 4-6 months Genetic and environmental factors Surgical resection is still the only potentially curative treatment INTRODUCTION

4. ANATOMY

5. Arterial Supply Venous Drainage

6. Lymphatic Drainage Innervation

7. Epidemiology Worldwide, over 265,000 people contract this disease annually, of w/c 74 % die within the first year after diagnosis Comprising 6% of all cancer-related deaths The incidence is continues to increase, b/c of increased incidence of risk factors(obesity & DM) The etiology is likely involves a complex interaction of genetic and environmental factors It is more common in African Americans and slightly more common in men than women

8. Is notoriously difficult to diagnose in its early stages.  At the time of diagnosis, 52% of all patients have distant disease,29% have regional spread,&10% localised. The relative 5-year survival for localised is 31.5%,for regional 11.5%, for distant 2.7% and the overall 5-year survival rate for this disease is 7.2%.  Epidemiology

9. 2007 Estimated US Cancer Deaths* Lung & bronchus 31% Prostate 9% Colon & rectum 9% Pancreas 6% Leukemia 4% Liver & intrahepatic 4% bile duct Esophagus 4% Urinary bladder 3% Non-Hodgkin 3% lymphoma Kidney 3% All other sites 24% 26% Lung & bronchus 15% Breast 10% Colon & rectum 6% Pancreas 6% Ovary 4% Leukemia 3% Non-Hodgkin lymphoma 3% Uterine corpus 2% Brain/ONS 2% Liver & intrahepatic bile duct 23% All other sites Men 289,550 Women 270,100 4 th leading cause of cancer death

10. Overall, estimates indicate that 40% of pancreatic cancer cases are sporadic in nature. 30% are related to smoking 20% may be associated with dietary factors. Only 5-10% are hereditary in nature. Fewer than 5% of all pancreatic cancers are related to underlying chronic pancreatitis. Epidemiology

11. Age . The risk of developing pancreatic cancer increases with age. Most pancreatic cancers occur in people older than 60. Gender . More men are diagnosed with pancreatic cancer than women. Race . Black people are more likely than Asians, Hispanics, or white people to develop pancreatic cancer. Risk Factors

12. Smoking . Smokers are two to three times more likely to develop pancreatic cancer than nonsmokers. Obesity and diet . Eating a high-fat diet is a risk factor for pancreatic cancer. Research has shown that obese and even overweight men and women have a higher risk of dying from pancreatic cancer. Risk Factors

13. Family history. A person’s chance of developing this cancer increases three-fold if a first-degree relative (mother, father, sister, or brother) had pancreatic cancer. Chronic pancreatitis Hereditary pancreatitis Hereditary pancreatitis HNPCC Hereditary breast & ovarian Ca Peutz-Jeghers syndrome Risk Factors

14. Chemicals. Exposure to certain chemicals (such as pesticides, benzene, certain dyes, and petrochemicals) may increase the risk of developing pancreatic cancer. Hepatitis B infection. Hepatitis viruses are viruses that infect the liver. One recent study has shown that evidence of a previous hepatitis B infection was twice as common in people with pancreatic cancer than in people without the cancer Epidemiology and Risk Factors

15. Diabetes has been known to be associated with pancreatic cancer for many years. glucose intolerance is present in 80% of patients with pancreatic cancer, 20% have overt diabetes, Preexisting type 2 diabetes increases the risk for development of pancreatic cancer by about twofold Diabetes Mellitus

16. Broadly speaking, there are three basic types: Ductal adenocarcinoma >90% of pancreatic cancers with a 4% 5-year survival (worst of any cancer) Neuroendocrine tumors aka islet-cell tumors, rare Cystic neoplasms account for <1% of pancreatic cancers Types of Pancreatic Neoplasms

17. Much less commonly, tumors begin in the islets of Langerhans , the endocrine component. These are known as islet cell tumors or pancreatic neuroendocrine tumors . These can be functionally inactive islet cell carcinomas or benign or malignant functioning tumors such as insulinomas , glucagonomas , and gastrinomas . Types of Pancreatic Neoplasms (Endocrine)

18. Tumor grows without producing hormones is called non-functioning. If the tumor produces a hormone(s), the hormone(s) may cause metabolic imbalances, such as a very low blood sugar level (such as the case with insulinomas ) or a very high blood sugar level (such as with glucagonomas ), or other problems like severe diarrhea (a symptom of VIPomas , which produce a substance called vasoactive intestinal peptide). Most pNETs are sporadic but they can be associated with hereditary endocrinopathies including MEN1,VHL,NF1,sydromes Types of Pancreatic Neoplasms (Endocrine)

19. most common functional pNETs. Whipple’s triad. Sx. fasting hypoglycemia, serum glucose level <50 mg/dL, relief of Sx. with given glucose. Types of Pancreatic Neoplasms Insulinoma

20. 90% are benign and solitary, and only 10% are malignant. evenly distributed throughout head, body, and tail of the pancreas. Dx. Routine laboratory studies low blood sugar, elevated Serum insulin levels & C-peptide levels usually localized CT scanning and EUS. cont..

21. ZES is caused by Gastrinoma, an endocrine tumor that secretes gastrin, leading to acid hypersecretion and peptic ulceration. Time of Dx, 21% of pts have diarrhea. 70-90%,found in Passaro’s triangle Approximately 50% of gastrinomas metastasize to LN or liver and therefore considered malignant Dx. hormonal test, >1000 pg/mL SSTR (octreotide) scintigraphy in combination with CT Types of Pancreatic Neoplasms Gastrinoma

22. very rare tumor of the pancreatic alpha cells that results in the overproduction of the glucagon. typically associated with rash (NME), wt loss and mild DM Dx. confirmed by serum glucagon levels, >500 pg/mL Types of Pancreatic Neoplasms Glucagonoma

23. r are pNET arise delt cells of endocrine pancreas. originate proximal pancreas or pancreatoduodenal groove. 60% ampulla & periampullary The most common presentations are abdominal pain 25%, jaundice 25%, cholelithiasis 19%. Dx. confirming elevated serum somatostatin levels, >10 ng/mL. Types of Pancreatic Neoplasms Somatostatinoma

24. Cystic neoplasms of the pancreas account for fewer than 5% of all pancreatic tumors. Consist of benign serous cystadenomas , premalignant mucinous cystadenomas , and cystadenocarcinomas . Intraductal mucinous pancreatic neoplasms can be benign or malignant and usually manifest as a cystic dilation of the pancreatic ductal system. Types of Pancreatic Neoplasms (cysts)

25. It is important to determine if the cancer started in the exocrine or endocrine component of the pancreas, as the diagnosis and treatment of each type is much different. The most common type of pancreatic cancer is called ductal adenocarcinoma , or simply, adenocarcinoma . Types of pancreatic cancer Exocrine

26. Ductal - Adenosquamous (4% of all) -Signet ring cell -Undifferentiated (anaplastic) -Mucinous colloid (2%) 85 % IPMN invasive ca 2-3% MCN with invasive ca 1% Solid pseudopapillary <1 % Acinar cell ca <1 % Pancreatoblastoma <1% Serous cystadenoca <1 % WHO CLASSIFICATION OF EXOCRINE Ca

27. WHO classification : Based upon morphologic and histologic features . Benign — such as serous cystadenoma are reliably cured by surgical removal alone . Premalignant lesions —  MCN and IPMN CLASSIFICATIONOF EXOCRINE PANCREATIC NEOPLASM   Malignant: Ductal adenocarcinoma – ~ 85 % - Signet ring cell carcinoma - Adenosquamous carcinoma (~ 4% of all pancreatic malignancies ) - Undifferentiated ( anaplastic) ca. - Mucinous non-cystic (colloid) ca.(~ 2%) IPMN with an associated invasive ca 2- 3% MCN with an associated invasive ca – 1% Solid- pseudopapillary neoplasm – <1 % Acinar cell carcinoma – <1 % Pancreatoblastoma – <1% Serous cystadenocarcinoma – <1 %

28. Ducts represent only 4% of the tissue but are source of 90% of pancreatic malignancies 2/3 rd in the head or uncinate process 15 % in the body 10 % in the tail Most cases are sporadic Ampullary and periampullary tumors present in a similar fashion but have a slightly better prognosis DUCTAL ADENOCARCINOMA

29. Gross pathology  Majority are gritty, hard, scirrhous , gray-white and poorly circumscribed Histology and grading  Most are moderately to poorly differentiated, with varying degrees of duct-like structures and mucin production Histopathogy

30. typically involves adjacent structures  duodenum, the PV, or SM vessels. striking tendency for perineural invasion both within and beyond the pancreas.  represents the most common site of disease recurrence after resection. Occasionally local extension to the spleen, adrenal glands, vertebral column, transverse colon, and/or stomach. Regional peripancreatic LNs frequently harbor metastatic deposits. Patterns of local spread

31. pancreatic tumors, 95% develop from the exocrine portion of the pancreas, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue. Approximately 75% of all pancreatic carcinomas occur within the head or neck of the pancreas, 15-20% occur in the body of the pancreas, and 5-10% occur in the tail. Pathophysiology

32. The molecular genetics of pancreatic adenocarcinoma have been well studied. Of these tumors, 80-95% have mutations in the KRAS2 gene, and 85-98% have mutations, deletions, or hypermethylation in the CDKN2 gene. 50% have mutations in p53 and about 55% have homozygous deletions or mutations of Smad4. Pathophysiology

33. Families with BRCA-2 mutations, which are associated with a high risk of breast cancer, also have an excess of pancreatic cancer. Assaying pancreatic juice for the genetic mutations associated with pancreatic adenocarcinoma  is invasive but may be useful for the early diagnosis of the disease Pathophysiology

34. Certain precursor lesions have been associated with pancreatic tumors arising from the ductal epithelium of the pancreas.  The main morphologic form associated with ductal adenocarcinoma of the pancreas has been pancreatic intraepithelial neoplasia or PIN.  These lesions arise from specific genetic mutations and cellular alterations that all contribute to the development of invasive ductal adenocarcinoma .  Pathophysiology

35. The initial alterations appear to be related to KRAS2 gene mutations and telomere shortening.  Thereafter p16/CDKN2A is inactivated.  Finally, the inactivation of TP53 and MAD4/DPC4 occur.  These mutations have been correlated with increasing development of dysplasia, and thus the development of ductal carcinoma of the exocrine pancreas. Pathophysiology

36. It is postulated that telomere-shortening, and mutations of the oncogene K-RAS occur at early stages inactivation of the p16 tumor suppressor gene occurs at intermediate stages inactivation of the p53, SMAD4 (DPC4), and BRCA2 tumor suppressor genes occur at late stages. Pathophysiology

37. It is important to note that while there is a general temporal sequence of changes, the accumulation of multiple mutations is more important than their occurrence in a specific order. Pathophysiology

38. Genes PanIN-1 PanIN-2 PanIN-3 Invasive PDAC KRAS2 36% 44% 87% >95% CDKN2A/p16 30% 55% 71% ~90% P53 Rare Rare Rare ~79% DPC4 (SMAD4). Rare Rare 20% to 30% 20% to 30% (localized) 78% (widely metastatic) pathophysiology

39. Clinical Presentation History

40. Abdominal pain : common presenting symptom it is mid epigastric in location, w/c radiate to the back(sign retroperitoneal invasion) The pain worse when the patient is lying flat About  1/3  of pts may not have pain at time of presentation, 1/3  of pts  have moderate pain & the rest have severe pain Jaundice : due to obstruction of the distal BD associated with nausea, pruritus, dark urine and pale stools Weight loss, anorexia, malaise, fatigue Clinical presentation

41. On physical examination Evidence of jaundice: icteric sclera & skin Skin excoriations from unrelenting pruritus. Mild-to-moderate midepigastric tenderness Palpable GB (Courvoisier sign) in ¼ of pts In advanced case there may be ascites, a palpable abdominal mass, hepatosplenomegaly , supraclavicular nodes and tumour deposits in the pelvis

42. relatively uncommon 5/100000 population <5% of all pancreatic tumors 4th & 6th decades of life. most pNETs are nonfunctional Most pNETs are sporadic but they can be associated with hereditary endocrinopathies including MEN1,VHL,NF1,sydromes Neoplasms of the Endocrine Pancreas EPIDEMIOLOGY

43. History and P/E Laboratory Evaluation CBC RBS LFT Coagulation profile Nutritional assessment Diagnosis

44. Multidetector CT Imaging study of choice For an accurate determination of: Level of biliary obstruction Tumor and critical vascular anatomy Presence of regional or metastatic ds Defines any arterial or venous aberrations Excellent sensitivity (85%) Not as accurate in predicting the need for venous resection Imaging Studies

45. Non-Contrast phase Evaluation of calcifications Early Arterial Phase Evaluates vasculature without interference from venous opacification Late Arterial Phase Distinguish ca from normal tissue by contrast enhancement Hypervascular liver mets in neuroendocrine ca Routine Portal Venous Phase Hypovascular liver mets in Adenocarcinoma Pancreas Protocol Phases

46. Adenocarcinoma : Relatively Hypovascular , hypoattenuating tumors Neuroendocrine tumors: Hypervascular , hyperattenuating tumors

47. Conventional Ultrasound Initial study in OJ Sensitivity ( 75-89%), specificity ( 90-99%) Affected by: Experience Presence or absence of duct obstruction Extent of tumor EUS/FNA: For PV/SMV invasion Less effective for SMA invasion Provide tissue dx Sensitivity and specificity of 92%-95 % For small Tumors (<2 cm)

48. ERCP: Once used for diagnosis Can be Therapeutic A slight increase in complications Early surgery is preferable to stenting MRCP: Non-invasive Detailed 3-D anatomy For cystic lesions The “double-duct” sign No risk of inciting pancreatitis

49. All the current staging modalities  ~80% accuracy in predicting resectability Improves accuracy of predicting resectability to ~98% Avoid Nontherapeutic Laparotomy: 10% to 30% (head) & 50% (body and tail) Possibly best applied on a selective basis: >4 cm Tumors located in the body or tail Equivocal findings of metastasis or ascites on CT Marked weight loss or markedly elevated CA19-9 (>1000 U/mL ) Diagnostic Laparoscopy/ US

50. Limited role Insensitive for early cas Less specific May be as initial Ix: CA19-9 CEA α-fetoprotein CA19-9: 79% Sensitive & 82% specific For Surveillance Normal level < 37U/ml Small ca (<1 cm)  37-100 Mets> 1,000 U/ml Limitation: Elevation in benign d s 10% to 15% do not develop elevation Serum Tumor Markers

51. Tells us whether the lesion is amenable to surgical resection. Only 20% of all patients presenting with pancreatic cancer are ultimately found to have easily resectable tumors with no evidence of local advancement. No survival benefit is achieved for patients undergoing noncurative resections for pancreatic carcinoma. staging

52. Staging

53. Stage grouping is according to Resectability : Stages I and II Localized Resectable Stage III Locally Advanced Unresectable Stage IV Distant Metastatic Disease

54. . T A Resectable pancreatic adenocarcinoma in the head and uncinate process, showing well-preserved fat plane ( arrow ) between tumor ( T ) and SMA( A ).