Se ha denunciado esta presentación.
Utilizamos tu perfil de LinkedIn y tus datos de actividad para personalizar los anuncios y mostrarte publicidad más relevante. Puedes cambiar tus preferencias de publicidad en cualquier momento.

Pancreatic tumours

3.082 visualizaciones

Publicado el

includes mainly histopathology of many important pancreatic tumours.

Publicado en: Salud y medicina
  • Inicia sesión para ver los comentarios

Pancreatic tumours

  3. 3. NORMAL HISTOLOGY Islet of lengarhans Acinar cells
  5. 5. PANCREATIC DUCTAL ADENOCARCINOMA  85% of all exocrine pancreatic cancers  Risk factors : 1) occupation 2) cigarette smoking 3) syndromes with genetic susceptibility - familial breast cancer/ BRCA2 -familial atypical multiple mole melanoma syndrome/P16 -peutz-jeghers syndrome/STK11-LKB1 -hereditary nonpolyposis colorectal cancer/DNA mismatch repair genes -hereditary pancreatitis/ cationic trypsinogen gene
  6. 6. 4) variations in pancreaticobiliary anatomy 5)Age : elderly 6)Sex : male:female—1.6:1 CLINICAL FEATURES  Characteristic painless obstructive jaundice  Pruritus, dark urine, pale stools, steatorrhea  If no jaundice, symptoms are vague e.g. discomfort, anorexia, weight loss  Peripheral venous thrombi & diabetes
  7. 7. LABORATORY EVALUATION  CBC , ESR,  Hepatic function evaluation  Coagulation profile  Nutritional assessment.  Tumor markers : CEA, CA19-9  Radiological  CYTOLOGY  GUIDED BIOPSY  HISTOPATHOLOGY, IMMUNOHISTOCHEMISTRY & ELECTRON MICROSCOPY
  8. 8. LOCATION & GROSS FEATURES  2/3 rd – head of the pancreas  1/3 rd – body & tail of pancreas  Multiple tumours in 20 % of cases  GROSSLY, - poorly delineated, firm - yellowish grey cut surface - rarely massive cystic degeneration - pancreatic ducts- dilated and plugged with necrotic tumour - extrapancreatic extension is common
  9. 9. Gross appearance of typical invasive ductal carcinoma of the head of the pancreas. The tumor is protruding into the duodenal lumen.
  10. 10. MICROSCOPIC FEATURES  Grading- well/moderately/ poorly defferentiated  Low power view- well formed glands, with large lumen, lined by one or few layers of cylindrical or cuboidal epithelium. irregularities in shape & distribution of glands, prominent concentric desmoplastic stroma surrounding the glands.
  11. 11. Pancreatic ductal adenocarcinoma.:It is typical of this tumor type to be well differentiated architecturally(low power view)
  12. 12.  High power view : epithelium show malignant features i.e. marked nuclear pleomorphism, loss of polarity, prominent nucleoli & mitotic activity  Disparity between high degree of cytologic atypia And low level of archirectural atypia.  Invasion : Perineural invasion, invasion of veins, fat invasion  Carcinoma in situ( high grade pancreatic intra epithelial neoplasm) & atypical hyperplasia  Lobular tissue destroyed, islet cell preserved – “insular pancreas”
  13. 13. Pancreatic ductal adenocarcinoma.:It is typical of this tumor type to be well differentiated architecturally but to show marked cytologic atypia
  14. 14. High power view show marked cytologic atypia.
  15. 15.  Non-neoplastic pancreas:  Atrophy  Chronic inflammation,  Fibrosis  Ductal dilatation  Atypical hyperplasia  PanINs
  16. 16. Atypical hyperplastic ductal changes (PanIN) in pancreas affected elsewhere by invasive ductal adenocarcinoma
  17. 17. HISTOCHEMICAL & IHC FEATURES  Mucins : gastric & small intestinal type & lack 8-0- acetyl –N-acety lneuraminic acid, MUC 1 positive  Keratins : CK 7,8,18,19, 15/16, 17, 20  EMA,CEA, CA-19-9, B7 & mesothelin  M1 & cathepsin E & pepsinogen 2  Villin & mapsin  Endocrine & neural markers
  18. 18. MOLECULAR GENETIC FEATURES  Structural rearrangements or loss of genes on 1p, 3p, 6p, 8p & 17 p  Mutations of K-RAS  Inactivating mutations of P16/CDKN2A  Mutations of TP 53  Inactivating mutations of DPC 4 (strongly suggestive)  Overexpression of HER2  Loss or overexpression of DNA mismatch repair genes
  19. 19. OTHER MICROSCOPIC TYPES  Adenosquamous carcinoma  Oncocytic carcinoma  Clear cell carcinoma  Hepatoid carcinoma  Signet ring carcinoma  Basaloid carcinoma  Intestinal type carcinoma  Mucinous carcinoma
  20. 20. Mucin-producing adenocarcinoma of the pancreas associated with large pools of extracellular mucin.
  21. 21. SPREAD AND METASTASIS  Peri pancreatic soft tissue  Invasion into the duodenum & common bile duct  Vascular & neural invasion  Lymphnode metastais  Distant metastasis TREATMENT  PRIMARILY SURGICAL
  22. 22. PROGNOSIS Overall 5 year survival rate is 4 % or less Mean survival of 3 months Factors related to prognosis are :  Tumour stage  microscopic grade  Tumor size  Tumour less than 4.5 cm in diameter– longest survival  Blood vessel invasion & retroperitoneal margin of resection—decreased survival  Lymphnode metastasis
  23. 23.  DNA ploidy  TGF- β1 expression– related to better differentiated tumours—better outcome  Cytokeratin 20 expression—decreased survival  Mapsin expression—better prognosis  SMAD4 gene mutation—worse prognosis
  24. 24. ANAPLASTIC CARCINOMA  Also known as PLEOMORPHIC, SARCOMATOID OR UNDIFFERENTIATED CARCINOMA  Highly distinctive morphology and highly aggressive course  > 50 years, male predilection  Three morphologic types:  1)  Large no. of bizzare multinucleated cells  Poor cellular cohesion(loss of E-cadherin expression)  Lymphnode & hematogenous metastasis common
  25. 25.  2) tumour largly composed of spindle shaped cells  3)solid tumour of small monotonous round cells  Immunohistochemically, keratin, EMA & CEA positive  Prognosis : extremely poor
  26. 26. Sarcomatoid carcinoma of the pancreas associated with areas of clear- cut glandular differentiation. The two components are sharply separated, resulting in a carcinosarcoma-type appearance.
  27. 27. GIANT CELL TUMOUR OF PANCREAS  Distinct morphologic appearance and better prognosis  Grossly, large and hemorrhagic  Microscopically, dual polulation :  Uniform spindle cells of mesenchymal origin with cytological atypia  Multinucleated giant cells (=osteoclasts)  Nuclei of osteoclast like cells are uniform small and mitoses and bizarre forms are absent.
  28. 28. Gross appearance of giant cell tumor of pancreas. There is a large hemorrhagic mass in the head of the pancreas that is protruding into the stomach.
  29. 29. Microscopic appearance of giant cell tumor of the pancreas. Osteoclast-like multinucleated giant cells are seen scattered among mononuclear neoplastic elements showing a high degree of atypia
  30. 30. CYSTIC PANCREATIC NEOPLASMS  Tumours in which cystic configuration is universally present and part of their definition(i.e. cystadenoma & cystadenocarcinoma)  Two distinct categories : microcystic and mucinous MICROCYSTIC CYSTADENOMA  Also known as glycogen rich or serous cystadenoma.  Usually in elderly  Some cases aassociated with VHL gene mutations
  31. 31. A and B, Microcystic adenoma of pancreas. A, The tumor, which is sharply outlined, shows numerous small cysts. B, Close-up of another case showing innumerable cystic cavities separated by a thin fibrous wall.
  32. 32.  Grossly, large multiloculated mass with individual cavities small and filled with serous fluid; cut surface is spongy.  Microscopically,  Multiple small cysts lined by small, flat or cuboidal cells with abundant amount of glycogen.  A layer of myoepithelial cells present.  Prominent vascularization is present.  Ultrastructurally, prominent microvilli seen  Immunohistochemically, reactive for EMA, LMW keratin, alpha-inhibin, NSE, MUC6, calponin  Fliud has a low level of CEA level.  Excision is curative
  33. 33. Microcystic cystadenoma showing typical multilocular appearance.
  34. 34. High-power view of microcystic cystadenoma showing lining of cuboidal epithelium with optically clear cytoplasm.
  35. 35. MICROCYSTIC CYSTADENOCARCINOMA  Microcystic appearance similar to that of adenoma.  Nuclear atypia, perineural invasion and aneuploid DNA pattern present.  Rare metastasis.
  36. 36. MUCINOUS CYSTIC NEOPLASMS  Seen in younger age group than microcystic tumours  Predominant in women  Mostly in body and tail  Two categories: mucinous cystadenoma & mucinous cystadenocarcinoma  Large multilocular cyst lined by tall columnar mucin producing cells, often forming papillae  Stroma is very cellular resembling that of ovarian stroma(also phenotypically)
  37. 37. Mucinous cystadenoma of pancreas. The lesion is unilocular and contains abundant inspissated mucin. Mucinous cystadenocarcinoma. This tumor, which was invasive at the microscopic level, shows areas of hemorrhage and solid growth.
  38. 38. Mucinous cystadenoma of pancreas. The lining is monolayered and made up of well-differentiated mucinous epithelium.
  39. 39. Mucinous cystadenoma with underlying ovarian-type stroma: hematoxylin–eosin
  40. 40.  Diagnosis of malignancy regquires presence of invasion of wall by neoplastic gland and frank anaplasia of superficial component.  Aspiration of fluid: tall columnar cells, higher levels of CEA & lower levels of elastase1.  Total excision is recommended.  Metastasis: usually restricted to abd. Cavity.  Histochemically, expression of MUC5AC, MUC2 with lack of MUC1
  41. 41. INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS & PANIN  Distinct type of intraductal pancreatic tumour  Interplay of two factors : epithelial proliferation and mucinous secretion  WHEN EPITHELIAL PROLIFERATION PREDOMINATE  Multicentric involvement of major ducts with papillary lesion, cribriform pattern and cytologic atypia  Two subtypes: gastric & intestinal  WHEN MUCINOUS SECRETION PREDOMINATES  Gross dilatation of ducts filled with mucus  Microscopically, epithelium is columnar, mucous secreting and well differentiated
  42. 42. Gross appearance of intraductal papillary carcinoma. The tumor massively involves several major pancreatic ducts
  43. 43. Microscopic appearance of the same case, showing a complex papillary architecture
  44. 44. Mucus-hypersecreting intraductal carcinoma. There is marked dilation of a major pancreatic duct accompanied by fibrosis and atrophy of the surrounding parenchyma. This duct contained large amounts of mucin in its lumen.
  45. 45. Microscopic appearance of the same case showing a papillary configuration associated with mucin hypersecretion.
  46. 46.  Progression : spread slowly & eventually progress to invasive adenocarcinoma  Histochemically, heterogenous mucin expression  At molecular level, mutations of K-RAS gene, overexpression of HER2 product. Protein product of DPC4 gene is present in all cases.  Main D/D : mucinous cystic neoplasms (female predominance, no communication with ducts, ovarian type stroma)
  47. 47. PANCREATIC INTRAEPITHELIAL NEOPLASIA (PANIN)  This entity is very similar to IPMN  Relate to caliber of duct : large for IPMN & small for PanIN  Thus, IPMN is , as a rule, clinically detectable, grossly visible with grossly identifiable mucin and well formed papillae AND reverse is true for PanIN.
  48. 48. ACINAR CELL TUMOURS AND TUMOUR LIKE CONDITIONS  ACINAR CELL HYPERPLASIA  Incidental finding  May be confused with langerhans islets
  49. 49.  ACINAR CELL ADENOMA  Solid pattern of growth  Entity of very doubtful existence  ACINAR CELL CYSTADENOMA  Uni/multicystic lesion lined by well differentiated acinar cells  Usually not connected with pancreatic ductal system.  ACINAR CELL CARCINOMA  Uually in adults  Intraabdominal mass with or without jaundice  Widespread subcutaneous fat necrosis
  50. 50.  Grossly, relatively well circumscribed fleshy mass, avergaing 11 cm in diameter, with hemorrhage and necrosis.  Microscopically,  Cellular without desmoplastic stroma  Pattern: solid, trabecular, glandular, papillary  Nuclei round to oval, only mild pleomorphism, single prominent nucleoli & variable mitotic activity  Cytoplasm-abundant, eosinophilic granular  PAS positive diastase resistant zymogen granules  Immunoreactivity for trypsin, chymotrypsin, lipase, amylase, anti- BCL10
  51. 51. Acinar cell carcinoma. The cut surface is solid and has a necrotic center. It lacks the fibrous component usually seen in ductal adenocarcinoma.
  52. 52. Acinar cell carcinoma of the pancreas showing a well- differentiated acinar arrangement of the tumor cells.
  53. 53. Acinar cell carcinoma showing a trabecular pattern of growth that may be confused with that of an endocrine tumor.
  54. 54. Strong immunoreactivity for lipase in acinar cell carcinoma.
  55. 55. SOLID-PSEUDOPAPILLARY TUMOUR  Also known as papillary and solid epithelial neoplasm.  Common in young women  Grossly, large tumour with well developed capsule with areas of hemorrhage and necrosis on cut surface.  Microscopically, very cellular.  Pseudopapillae covered by several layers of epithelial cells with thick fibrovascular core having prominent mucinous changes  Nuclei are ovoid & folded with indistinct nucleoli and few mitosis.
  56. 56. Solid and pseudopapillary tumor of pancreas. (low power view)
  57. 57. Solid and pseudopapillary tumor of pancreas. Note the accumulation of myxoid material around the vessels.(high power view)
  58. 58.  Immunohistochemically, reactive for keratin, vimentin, desmoplakin, trypsin, insulin & glucagon(capacity for dual differentiation)  Progesterone receptors positive.  Genetically, β-catenin gene mutation.  Treatment is surgical  Overall prognosis is excellent.
  59. 59. PANCREATOBLASTOMA  Most common pancreatic neoplasm in childhood.  In some cases, asso. with beckwith-wiedmann syn and familial adenomatous polyposis of colon  Bimodal age: mean- 2.4 & 33 years.  Grossly, avg tumour size is 10 cm & partial encapsulation is the rule.  Microscopically, very cellular tumour  Solid sheets and nests of uniform epithelial cell with well formed acinar structure and dilated ductular formations.  ‘SQUAMOID CORPUSCLES CONSTANT AND CHARACTERISTIC  Stroma abundant.
  60. 60. Pancreatoblastoma showing a predominantly solid pattern of growth but also small rosette-like glandular formations.
  61. 61. Pancreatoblastoma showing a large squamoid corpuscle surrounded by small glands.
  62. 62.  Immnunohistochemically,  Evidence of acinar, endocrine and ductal differentiation.  AFP  Squamoid corpuscles : CK8/18/19, EMA positive  Genetically,  Nuclear translocation of β catenin  Loss of heterozogosity of chromosome 11p  Prognosis in infants is favourable.
  64. 64. GENERAL CLINICAL FEATEURES  Tradinitionally designated as islet cell tumours  Many arise from primitive multipotent cells located within ducts.  Most occur in adults.  Many associated with MEN syndromes, VHL disease, neurofibromatosis type 1 or tuberous sclerosis
  65. 65. GENERAL MORPHOLOGIC FEATURES  Common location : body & tail of pancreas.  Grossly, pinkish cast resembling spleen or congested lymphnode.  No well defined capsule.  May contain large amount of fibrous tissue, calcification and bone.  Microscopically,  Small relatively uniform, cuboidal cells with centrally located nuclei and acidophilic finly granular cytoplasm.  Nuclear enlargement and other abberations.
  66. 66.  4 patterns : solid, gyriform, glandular and nondescript  reffered to as A/B/C/ &D or 1/2/3/4  Relation with further types : predominantly gyriform – beta/alpha cell type. glandular – G or VIP cells. solid tumours – any cell type.  Stroma– highly vascular  Abundant hyaline material may be seen.  Amyloid in insulin secreting neoplasm(IAPP)
  67. 67.  CLINICALLY,  May be nonfunctional or functional  Immunohistochemically,  Reactive for epithelial markers(CK7 CEA,)  Panendocrine markers  NESP-55  Markers specific for various peptide hormones.  Genetically  6q loss, mutation in MEN1 gene, allelic loss of 11q,  NO inactivation of DPC4
  68. 68. SPECIFIC TYPES BETA CELL TUMOURS  Most common & better  < 10 % affected by MEN 1.  Presents with whipples traid when functional.  90% solitary, 70% measures 1.5 cm or less  Microscopically, gyriform or solid pattern.  Ultrastructurally, dense core secretory granules.  Immunohistochemically, reactive for insulin, proinsulin,  As a rule malignant variety has shorter history & more pronounced hypoglycemia.
  69. 69. Low power view High power view
  70. 70. ALPHA CELL TUMOURS  Two types  1) associated with glucagonoma syndrome  Solitary and large  Non discript microscopic pattern  Atypical granules ultrastructurally  Few cases positive for glucagon.  2)tumours not associated with glucagonoma syndrome  Often multiple & small  Gyriform pattern of growth  Strongly reactive for glucagon  Typical alpha granules
  71. 71. Gross appearance of alpha cell tumor (glucagonoma). The tumor shown exhibits foci of hemorrhage and necrosis
  72. 72. Alpha cell tumor showing a prominent gyriform arrangement of the tumor cells. Tumors with this pattern are usually composed of either alpha or beta cells.
  73. 73. G – CELL TUMOUR  Can produce Zollinger-Ellison syndrome as a result of excessive production of gastrin & reffered to as gastrinoma.  Common site- pancreas followed by duodenal wall and gastric antrum.  Solitary and often clinically malignant.  Microscopically, solid and or glandular.  IHC- gastrin production
  74. 74. Rosette-like gland formation in G-cell tumor (gastrinoma).
  75. 75. OTHER TUMOURS OF ENDOCRINE PANCREAS  VIP producing tumours  DELTA CELL TUMOURS –somatostatin secretion  PP CELL TUMOURS -- secondary or minor component in other tumours  CARCINOID TUMOURS– analogous to other carcinoid tumours seen in G.I . Tract.  SMALL CELL CARCINOMA—similar to its more common pulmonary counterpart.
  76. 76. BEHAVIOUR & PROGNOSIS WHO has proposed three categories : 1. Well differentiated endocrine tumours A. Benign behaviour without extrapancreatic spread or vascular invasion <2 cm in size, <2 mitosis/10hpf, <2% ki-67 positive cells B. Uncertain behaviour without extrapancreatic invasion >2 cm in size, angioinvasive and perineural invasion 2-10 mitosis /10hpf, >2% ki-67 positive cells.
  77. 77. 2. Well differntiated low grade carcinoma any tumour with gross local invasion &/or metastasis. further subdivided into functioning and non- functioning . 3. Poorly differentiated endocrine carcinoma also includes small cell neuroendocrine carcinoma
  78. 78. Tumours Age/sex Gross microscoic IHC Ductal adenocarcino ma Elderly/ M>F Solid, Poorly delineated, fibrosis in surr ound. Area Malignant glands with invasion Mucins : MUC1, CA- 19-9, CEA, CKs Anaplastic carcinoma >50yrs/M>F Large h’gic tumour 3 patterns CK, CEA, EMA Microcystic neoplasms 6th/7th decade, F>M Large multilocular cystic tumour, serous fluid Small cysts lined by cuboidal epi. With or without atypia CK, EMA, MUC6, fliud CEA level Mucinous cystic neoplasm 5th/-6th decade, F>M Large cysts, mucin filled Cysts lined by columnar epi + ovarian type stroma MUC5AC, MUC 2, fluid CEA level SUMMARY
  79. 79. Tumours Age / sex Gross Microscopic IHC IPMN Elderly Involvemenat of ducts, papillary lesion or dilatation Epithelial proliferation or mucus secretion Heterogenous mucin expression Acinar cell carcinoma Adults Well circumscribed, fleshy, large Solid, cellular variable patterns trypsin, chymotrypsin, lipase, amylase, anti- BCL10 Solid pseudopapillar y tumour Young women, F>M Large encapsulated with h’ge & necrosis Pseudopapilla e thick fibrovascular core having mucinous changes keratin, vimentin, desmoplakin, trypsin, insulin & glucagon Pancreatoblas toma Bimodal age(2.4 & 33 yrs) Large(~10 cm), partially encapsulated Solid sheets of epi. Cells + squamoid AFP, CK8/18/19, EMA
  80. 80. REFERENCES  ROSAI AND ACKERMAN’S SURGICAL PATHOLOGY/tenth edition/chapter 15  ROBBINS & COTRAN/ PATHOLOGIC BASIS OF DISEASE/south asia edition/9th edition/chapter 19  Internet
  81. 81. THANK YOU