Mesenchymal neoplasms of the gastrointestinal tract what s new? Newton ACS Wong Department of Histopathology Bristol Royal Infirmary
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1 Mesenchymal neoplasms of the gastrointestinal tract what s new? Newton ACS Wong Department of Histopathology Bristol Royal Infirmary
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4 Talk plan Summary from 2010 talk. What s happened since GISTs then other neoplasm types. Diagnostic and clinical relevance.
5 Gastrointestinal stromal tumour (GIST)
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7 a) Jee IST b) Ger IST
8 Summary of 2010 GIST talk DOG1 Prognostication Chemotherapy Wild type GISTs
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10 + CD117 + = it is a GIST! DOG1 CD117
11 Since 2010 DOG1 Co-expression of CD117 and DOG1: Adenocarcinoma and squamous cell carcinoma (sarcomatoid) Neuroendocrine neoplasms Melanoma and synovial sarcoma
12 DOG1 CD117 MNF116
13 Since 2010 DOG1 Co-expression of CD117 and DOG1: Adenocarcinoma and squamous cell carcinoma (sarcomatoid) Neuroendocrine neoplasms Melanoma and synovial sarcoma
14 Since 2010 DOG1 Co-expression of CD117 and DOG1: Adenocarcinoma and squamous cell carcinoma (sarcomatoid) Neuroendocrine neoplasms Melanoma and synovial sarcoma
15 DOG1 CD117
16 + CD117 + = it is a GIST! DOG1 CD117
17 Summary of 2010 GIST talk DOG1 Prognostication Chemotherapy Wild type GISTs
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19 Prognostication for GIST Miettinen/AFIP classification applies well to most adult GISTs Paediatric/wild type GISTs do better than predicted by AFIP system.
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21 Since 2010 Prognostication Use 5 mm 2 rather than 50 HPFs TNM7 Poor take-up (ESMO) Serosal tumour rupture (Joensuu)
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23 Since 2010 Prognostication Use 5 mm 2 rather than 50 HPFs TNM7 Poor take-up (ESMO) Serosal tumour rupture (Joensuu)
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28 Tumour rupture Candidate for adjuvant Rx? Mention in report!
29 Summary of 2010 GIST talk DOG1 Prognostication Chemotherapy Wild type GISTs
30 Since 2010 Chemotherapy Adjuvant imatinib: High risk (+/- moderate)?tumour rupture Three years Mutation analysis
31 Mutations of tyrosine kinases (TKs) CD117 / c- (Platelet derived growth factor receptor alpha) Hornick et al. Hum Pathol 2007; 38: 679.
32 PRIMARY RESISTANCE / SENSITIVITY IMATINIB: Sensitive primary mutations Resistant primary mutations KIT exon 11 KIT exon 9 (but dose escalation) Upstream small mutations > KIT exon 17 downstream large deletions SUNITINIB: Sensitive primary mutations PDGFRA exon 18 (e.g. D842V) Wild type Resistant primary mutations KIT exon 9 KIT exon 11 Wild type PDGFRA exon 18 (D842V)
33 Summary of 2010 GIST talk DOG1 Prognostication Chemotherapy Wild type GISTs
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35 Paediatric GISTs (all wild type)
36 Wild type GISTs in adults Syndromic (Neurofibromatosis 1, Carney triad and Carney Stratakis) Sporadic / non-syndromic
37 Wild type GISTs in adults Syndromic (Neurofibromatosis 1 and Carney syndromes) Sporadic / non-syndromic
38 Since 2010 Wild type GISTs
39 Wild type GISTs in adults Syndromic (Neurofibromatosis 1 and Carney syndromes) Sporadic / non-syndromic
40 Gastric Epithelioid/MCT Multinodular Multifocal Nodal spread Wild type Imatinib resistant Poorly predicted by AFIP system
41 Gastric Epithelioid/MCT Multinodular Multifocal Nodal spread Wild type Imatinib resistant Poorly predicted by AFIP system
42 Nodes and GISTs If gastric, epithelioid/mixed cell type and younger female, should surgeon harvest nodes? Block any lymph nodes available.
43 Gastric Epithelioid/MCT Multinodular Multifocal Nodal spread Wild type Imatinib resistant Poorly predicted by AFIP system
44 SDHB loss Expression of IGFR1 BRAF V600E mutation
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46 SDHB loss Expression of IGFR1 BRAF V600E mutation
47 Wild type GISTs Immunohistochemical marker(s) for wild type GISTs BRAF and IGFR1 targeted treatment
48 No mutation Heterozygous mutation Artefact?
49 Wild type GISTs Immunohistochemical marker(s) for wild type GISTs BRAF and IGFR1 targeted treatment
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51 Gastrointestinal smooth muscle neoplasms Post GIST era Diagnosis (new IHC markers) Classification Grading
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53 Gastrointestinal smooth muscle neoplasms Colorectal mucosal leiomyomas Retroperitoneal uterine-like leiomyomas [can be DOG1+] (Intra)mural smooth muscle neoplasms
54 Smooth muscle IHC markers SMA, Desmin, Caldesmon Smoothelin and PLAP?
55 Smooth muscle IHC markers Caldesmon vs. smoothelin vs. PLAP 31 GI smooth muscle neoplasms (3 leiomyosarcomas) 111 other mesenchymal neoplasms (16 neoplasm types)
56 CALDESMON Leiomyoma: 27/27 Leiomyosarcomas: 4/4 (focally reduced) GIST: 11/20 Angiomyolipoma: 5/5 Glomus tumour: 6/7
57 PLAP Leiomyoma: 27/27 Leiomyosarcomas: 4/4 (focally reduced) Angiomyolipoma: 1/5 DSCRT: 1/1
58 SMOOTHELIN Leiomyoma: 27/27 Leiomyosarcomas: 4/4 (focally reduced) Angiomyolipoma: 1/5 Glomus tumour : 4/7
59 SMOOTHELIN
60 Smooth muscle IHC markers Sensitivity: 100% for all three markers Specificity: Caldesmon 80% PLAP 96% Smoothelin 91%
61 Smooth muscle IHC markers PLAP antibodies: 8A9 monoclonal (Dako) A0268 polyclonal (Dako) PL8-Fm6 monoclonal (Biogenex)
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63 AFIP series Leiomyomas Leiomyosarcomas Oesophagus 48 [ mitoses were 3 [all >50/50hpf] rare ] ( Stomach 3 [all 0/50hpf] 1 [25/50hpf] ) Duodenum 4 [max 1/50hpf] 5 [five > 50/50hpf one 6/50hpf] Jejunum/Ileum 9 [max 3/50hpf] 16 [all > 35/50hpf except one] Colon 0 7 [all > 100/50hpf except one] Rectum 3 [all 0/50hpf] 8 [all >28/50hpf]
64 Intramural GI smooth muscle neoplasms Clearer distinction between leiomyomas and leiomyosarcomas. Borderline/Low grade LMS/STUMP neoplasms are rare and should be treated with complete surgical excision.
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66 New entities RNFP GNET
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69 RNFP Hx of intra-abdominal injury. Well circumscribed. Serosal/subserosal. (Myo)fibroblastic. Keloidal / collagen bundles. Chronic inflammation.
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72 RNFP Hx of intra-abdominal injury. Well circumscribed. Serosal/subserosal. (Myo)fibroblastic. Keloidal / collagen bundles. Chronic inflammation. Non-neoplastic (IgG4 related?)
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74 GNET Clear cell sarcoma-like tumours of the GIT (CCSLTGT). NOT to be confused with clear cell sarcoma of soft parts. Small bowel >> Stomach and large bowel
75 GNET Compared with clear cell sarcoma of soft parts (melanoma marker +ve). Autonomic NS primitive neural stem cell? Poor prognosis.
76 Summary GIST: DOG1 and CD117 Tumour rupture Adjuvant therapy Wild type GISTs
77 Summary PLAP and smoothelin. FNCLCC grading of LMS. If myofibroblastic and inflamed, remember IgG4. If?melanoma, consider GNET.
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