JerusalemL practical immuno for hepatobiliary neoplasia
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JerusalemL practical immuno for hepatobiliary neoplasia
- 1. Icahn School of Medicine at MMoouunntt SSiinnaaii Practical Immunohistochemistry for Hepatobiliary Neoplasia Neil Theise, MD Departments of Pathology and Medicine (Digestive Diseases) Mount Sinai Beth Israel Medical Center New York City
- 2. Icahn School of Medicine at MMoouunntt SSiinnaaii Practical Immunohistochemistry for Hepatobiliary Neoplasia Download at: NeilTheise on SlideShare.net Neil Theise, MD Departments of Pathology and Medicine (Digestive Diseases) Mount Sinai Beth Israel Medical Center New York City
- 3. SSOOLLIIDD MMAASSSS FFiibbrroottiicc BBaacckkggrroouunndd NNoo FFiibbrroottiicc BBaacckkggrroouunndd ++ ++ ++ BBeenniiggnn HHeeppaattoobbllaassttoommaa,, eexxcceepptt FFeettaall TTyyppee LLaarrggee RReenneerraattiivvee NNoodduullee DDyyssppllaassttiicc NNoodduullee HHCCCC FFNNHH HHCCAA HHCCCC FFiibbrroollaammeellllaarr HHCCCC HHeeppaattoobbllaassttoommaa,, FFeettaall TTyyppee BBiillee DDuucctt AAddeennoommaa PPeerriibbiilliiaarryy GGllaanndd HHaammaarrttoommaa BBiilliiaarryy AAddeennooffiibbrroommaa AAnnyy ooff:: BBiillee,, HHSSAA,, AArrgg11,, CCDD110,, ppCCEEAA AAnnyy ooff:: BBiillee,, HHSSAA,, AArrgg11 CCDD110,, ppCCEEAA HHeeppaattooccyytteess wwiitthh aannyy ooff:: BBiillee,, HHSSAA,, CCDD110,, ppCCEEAA AANNDD DDuuccttss//ggllaannddss//mmuucciinn//KK1199 CChhoollaannggiiooCCaa MMeettaassttaassiiss CCoommbbiinneedd HHCCCC-- CChhoollaannggiiooCCaa MMaalliiggnnaanntt IImmmmaattuurree aappppeeaarriinngg cceellllss HHeeppaattooccyytteess oorr ootthheerr llaarrggee eeoossiinnoopphhiilliicc cceellllss DDuuccttss//ggllaannddss//mmuucciinn HHeeppaattooccyytteess aanndd dduuccttss//ggllaannddss//mmuucciinn MMeettaassttaassiiss MMeettaassttaassiiss MMeettaassttaassiiss vvoonn MMeeyyeennbbuurrgg ccoommpplleexx BBiillee dduucctt aaddeennoommaa HHSSAA,, AAFFPP,, AArrgg11 AArrgg11,, AArrgg11,, HHSSAA,, CCDD110,, ppCCEEAA AANNDD DDuuccttss//ggllaannddss//mmuucciinn//KK1199
- 4. WHO Tumours of the DDiiggeessttiivvee TTrraacctt,, 44tthh EEdd..
- 5. SOLID MASS Fibrotic Background No Fibrotic Background + + + Benign Hepatoblastoma, except Fetal Type Large Renerative Nodule Dysplastic Nodule HCC FNH HCA HCC von Meyenburg complex Bile duct adenoma Biliary Adenofibroma HSA, AFP, Arg1 Any of: Bile, HSA, Arg1, CD10, pCEA Any of: Bile, HSA, Arg1, CD10, pCEA Hepatocytes with any of: Bile, Arg1, HSA, CD10, pCEA AND Ducts/glands/mucin/K19 CholangioCa Metastasis Combined HCC-CholangioCa Malignant Immature appearing cells Hepatocytes or other large eosinophilic cells Ducts/glands/mucin Hepatocytes and ducts/glands/mucin Metastasis Metastasis Metastasis
- 6. Immunostains for HEPATOCYTES vs. METASTATIC MIMICS
- 7. Immunostains for HEPATOCYTES vs. METASTATIC MIMICS (e.g. RCC, Adrenal, Thyroid)
- 8. DIFFERENTIATION PANEL: HepPar1, Arginase 1 Canalicular pCEA, CD10 AFP, ?LFABP
- 9. HepPar1 Arginase-1 Canalicular CD10 Canalicular pCEA
- 10. A CASE
- 11. H & E
- 14. HepPar 1
- 15. H & E
- 16. Arginase 1 and CD10 negative.
- 17. ANOTHER CASE
- 20. HepPar1
- 21. Arginase 1
- 24. pCEA negative.
- 25. Immunostains for BENIGN VS. MALIGNANT HEPATOCYTES
- 26. Immunostains for BENIGN VS. MALIGNANT HEPATOCYTES CD34 and reticulin! Oldies, but goodies!
- 27. CD34 in HCC – always complete and diffuse
- 28. CD34 in HCC – always complete and diffuse
- 29. CD34 in HCA – usually incomplete or “patchy”
- 30. A CASE: 44 y.o. obese man with 5 cm liver tumor (“incidental” on imaging for other reason); MRI showed typical diagnostic HCC features in a central part of the tumor. Underwent chemoembolization with NO response. Decision to resect.
- 35. CD34
- 36. CD34 HCC HCA Non-tumor
- 38. Tumor diagnosis: HCC arising in Inflammatory HCA (we will return to this shortly…)
- 39. TRIPLE MALIGNANCY PANEL: Glypican-3 Heat Shock Protein-70 Glutamine Synthetase
- 40. CCaassee AA CCaassee BB
- 42. Glypican-3: In hepatocellular lesions, positive stain strongly supportive of HCC PLEASE NOTE!!!!
- 43. Glypican-3: In hepatocellular lesions, positive stain strongly supportive of HCC. IF AND ONLY IF THE TUMOR CELLS ARE HEPATOCYTIC do we order this stain! If NOT hepatocytic, this is NOT an hepatocytic marker! PLEASE NOTE!!!!
- 44. SOLID MASS Fibrotic Background No Fibrotic Background + + + Benign Hepatoblastoma, except Fetal Type Large Renerative Nodule Dysplastic Nodule HCC FNH HCA HCC von Meyenburg complex Bile duct adenoma Biliary Adenofibroma HSA, AFP, Arg1 Any of: Bile, HSA, Arg1, CD10, pCEA Any of: Bile, HSA, Arg1, CD10, pCEA Hepatocytes with any of: Bile, Arg1, HSA, CD10, pCEA AND Ducts/glands/mucin/K19 CholangioCa Metastasis Combined HCC-CholangioCa Malignant Immature appearing cells Hepatocytes or other large eosinophilic cells Ducts/glands/mucin Hepatocytes and ducts/glands/mucin Metastasis Metastasis
- 45. DDxx:: BBeenniiggnn hheeppaattoocceelllluullaarr nnoodduullee,, ?? FFNNHH vvss LLCCAA FNH HCA OORR?? DIAGNOSIS
- 46. Dx: Benign hepatocellular nnoodduullee,, ?? FFNNHH vvss LLCCAA 2211sstt cceennttuurryy:: CChheecckk iimmmmuunnoossttaaiinniinngg ffoorr:: GGlluuttaammiinnee SSyynntthhaassee,, LLFFAABBPP,, bbeettaa--CCaatteenniinn SSeerruumm AAmmyyllooiidd AA aanndd//oorr CC--rreeaaccttiivvee PPrrootteeiinn >>>> LLCCAA sseeee:: ppaappeerrss ooff BBiioouullaacc--SSaaggee//ZZuuccmmaann--RRoossssii
- 47. FFNNHH WWHHOO TTuummoouurrss ooff tthhee DDiiggeessttiivvee TTrraacctt,, 44tthh EEdd.. GGlluuttaammiinnee SSyynntthheettaassee ((GGSS))::
- 48. Adenoma Variants: search “Bioulac-Sage P” FFrroomm ““WWHHOO TTuummoouurrss ooff tthhee DDiiggeessttiivvee TTrraacctt””,, 44tthh EEdd..
- 50. LFABP
- 51. Adenoma Variants: search “Bioulac-Sage P” FFrroomm ““WWHHOO TTuummoouurrss ooff tthhee DDiiggeessttiivvee TTrraacctt””,, 44tthh EEdd..
- 59. Beta-catenin in normal liver
- 60. Beta-catenin
- 61. Beta Catenin Activation Glutamine synthetase expression
- 63. Beta Catenin Activation Glutamine synthetase expression CAVEAT!!! Beta-catenin 10% Glutamine Synthetase 90%
- 64. Adenoma Variants: search “Bioulac-Sage P” FFrroomm ““WWHHOO TTuummoouurrss ooff tthhee DDiiggeessttiivvee TTrraacctt””,, 44tthh EEdd..
- 65. Inflammatory HCA Keratin 7 Case 3
- 67. A CASE
- 74. Features: Fibrous stroma Ductular reactions Inflammation Could be FNH or Inflammatory HCA
- 75. Features: Sinusoidal dilatation and congestion. Suggests Inflammatory HCA?
- 76. Glutamine Synthetase Appears relatively normal distribution in original biopsy
- 77. C-reactive protein C-reactive protein Appears widespread in the lesional pieces of tissue
- 79. Inflammatory HCA vs. Focal Nodular Hyperplasia ? Relatively normal GS + Diffuse, strong CRP = ?
- 80. Inflammatory HCA vs. Focal Nodular Hyperplasia ? Relatively normal GS + Diffuse, strong CRP = iHCA
- 81. Inflammatory HCA vs. Focal Nodular Hyperplasia ? Relatively normal GS + Diffuse, strong CRP = iHCA SO THE TUMOR IS RESECTED, BECAUSE I TOLD THEM TO!
- 82. Case 5
- 83. Case 5
- 84. Case 5
- 85. Case 5
- 86. Case 5
- 87. Case 5: Glutamine synthetase
- 88. Case 5: Glutamine synthetase
- 89. Inflammatory HCA vs. Focal Nodular Hyperplasia ? BUT!!!! Resected lesion the GS appears to be “Map-like” as seen in FNH and the C-reactive protein not evenly distributed, so not I-HCA
- 90. Dx: Benign hepatocellular nnoodduullee,, ?? FFNNHH vvss LLCCAA
- 91. Dx: Benign hepatocellular nnoodduullee,, ?? FFNNHH vvss LLCCAA WWhhaatt aabboouutt HHCCCC……?? AAss ddiissccuusssseedd,, cchheecckk ffoorr:: tthhiicckknneessss ooff ppllaatteess,, lloossss ooff rreettiiccuulliinn,, CCDD3344 PPlleeoommoorrpphhiissmm,, aanndd GGPPCC--33//HHSSPP7700//GGSS ppaanneell
- 92. SOLID MASS Fibrotic Background No Fibrotic Background + + + Benign Hepatoblastoma, except Fetal Type Large Renerative Nodule Dysplastic Nodule HCC FNH HCA HCC Fibrolamellar HCC Hepatoblastoma, Fetal Type Bile Duct Adenoma Peribiliary Gland Hamartoma Biliary Adenofibroma Any of: Bile, HSA, Arg1, CD10, pCEA Any of: Bile, HSA, Arg1 CD10, pCEA Hepatocytes with any of: Bile, HSA, CD10, pCEA AND Ducts/glands/mucin/K19 CholangioCa Metastasis Combined HCC-CholangioCa Malignant Immature appearing cells Hepatocytes or other large eosinophilic cells Ducts/glands/mucin Hepatocytes and ducts/glands/mucin Metastasis Metastasis Metastasis von Meyenburg complex Bile duct adenoma HSA, AFP, Arg1 Arg1, Arg1, HSA, CD10, pCEA AND Ducts/glands/mucin/K19
- 93. SOLID MASS Fibrotic Background No Fibrotic Background + + + Benign Hepatoblastoma, except Fetal Type Large Renerative Nodule Dysplastic Nodule HCC FNH HCA HCC Fibrolamellar HCC Hepatoblastoma, Fetal Type Bile Duct Adenoma Peribiliary Gland Hamartoma Biliary Adenofibroma Any of: Bile, HSA, Arg1, CD10, pCEA Any of: Bile, HSA, Arg1 CD10, pCEA Hepatocytes with any of: Bile, HSA, CD10, pCEA AND Ducts/glands/mucin/K19 CholangioCa Metastasis Combined HCC-CholangioCa Malignant Immature appearing cells Hepatocytes or other large eosinophilic cells Ducts/glands/mucin Hepatocytes and ducts/glands/mucin Metastasis Metastasis Metastasis von Meyenburg complex Bile duct adenoma HSA, AFP, Arg1 Arg1, Arg1, HSA, CD10, pCEA AND Ducts/glands/mucin/K19 Keratins 7 and 20 and other differentiation markers
- 94. SOLID MASS Fibrotic Background No Fibrotic Background + + + Benign Hepatoblastoma, except Fetal Type Large Renerative Nodule Dysplastic Nodule HCC FNH HCA HCC Fibrolamellar HCC Hepatoblastoma, Fetal Type Bile Duct Adenoma Peribiliary Gland Hamartoma Biliary Adenofibroma Any of: Bile, HSA, Arg1, CD10, pCEA Any of: Bile, HSA, Arg1 CD10, pCEA Hepatocytes with any of: Bile, HSA, CD10, pCEA AND Ducts/glands/mucin/K19 CholangioCa Metastasis Combined HCC-CholangioCa Malignant Immature appearing cells Hepatocytes or other large eosinophilic cells Ducts/glands/mucin Hepatocytes and ducts/glands/mucin Metastasis Metastasis Metastasis von Meyenburg complex Bile duct adenoma HSA, AFP, Arg1 Arg1, Arg1, HSA, CD10, pCEA AND Ducts/glands/mucin/K19 Keratins 7 and 20 and other differentiation markers AND Keratin 19