11/04/07 Morning session - Newton Wong - Gastrointestinal Stromal Tumours
These are my own notes from the session and I cannot therefore vouch for their complete accuracy!
I have photographed some of the microscope slides that were distributed before the training day and some of the pictures are linked from the explanations.
Diagnoses are in bold type and marked with an asterisk
Notes after some of
the cases are in smaller type and include differential diagnoses
Notes after some of the cases are in smaller type and include differential diagnoses
Please see information
supplied by Dr
Wong for full clinical details
Please see information supplied by Dr Wong for full clinical details
50yom gastric antrum
CD117 and CD34 +ve
*Spindle cell GIST
43yom gastric antrum
previously known as leiomyoblastoma commonly stomach (if omentum usually epithelioid)
Ep less likely to express CD34 and CD117 but this one is CD 117
PDGFRa also responds to imatinib despite lack of cd117 usually have this mutation instead
D842V mutation predicts poor response to imatinib
Mixed cell type GIST - both cell types have same mutation!
Peripancreatic tumour (recurrence of tumour in patient case A).
stroma with only scattered CD117 negative spindle cells adjacent to an area of
recurrent tumour comprising spindled cells with increased nuclear pleomorphism
compared with the original tumour (scarred hyaline area presumably that responded
to the imatinib )
(downstaging inoperable tumour)
(CD117 negative) GIST
*Recurrent (CD117 negative) GIST
usually 2nd mutation in exons 13-21, or pre-existing clone in original tumour allowed to grow after treatment
New drug Sunitinib, shown to work on imatinib-resistant GISTs
* Pleomorphic GIST
Important differential diagnosis poorly diff carcinoma - ck neg in this case
Mutation analysis needed
to establish diagnosis
needed to establish diagnosis
52 yom ?pancreatic ca
* CD117 negative GIST
SFT, inflammatory myofibroblastic polyp (different morphology), Angiosarcoma (can
express cd117), KS .
.bcl-2 not useful in diagnosis of gists
* Synovial sarcoma
(but can apparently get focal ck positivity in GISTs)
Mucosa confined neural spindle cell tumour with ganglion cells diffusely infiltrating between crypts. ie. diffuse ganglioneuromatosis.
?History of NF1 or MEN2b
DD benign fibroblastic polyp (cd34, sma), perineurioma (EMA)
Duodenal tumour. Abutting pancreas
* GIST in a patient with NF1
in a patient with NF1
Ulcerated tumour adjacent to and undermining the non-dysplastic sq mucosa
S100 but also membranous cd117 (be wary of membrane + cd117 in GIST). was initial hope MM (and SCLC) could be treated by imatinib because of +cd117 but trials not helped.
* Malignant melanoma
Note most melanomas
lose CD117 expression as they become malignant. Uveal melanomas however are more
likely to retain expression.
Note most melanomas lose CD117 expression as they become malignant. Uveal melanomas however are more likely to retain expression.
(look up other cd117+ tumours - see list here)
CD34 and bcl-2 positive,
CD34 and bcl-2 positive, CD117 negative
DD c-kit negative GIST
SI mucosa with predom subserosal
bland monomorphic spindle cell tumour infiltrating submucosa and focally extramural
fat. Abundant collagenous stroma , curvilinear thin walled blood vessels
, curvilinear thin walled blood vessels
focal sma positive
* Mesenteric fibromatosis (desmoid tumour)
48yof pelvic ?rectal tumour.
ER positive, on experimental tamoxifen
DD angiomyofibroblastoma (but this would have more of a 'pushing' edge)
Note ER alpha pos have never been identified in GIST
83yof widespread peritoneal nodules and mets
* Metastatic Endometrial stromal sarcoma
CD10 positive, previous endometrial stromal sarcoma!!
General main DD of GISTs
- neural (S100)
- SM tumours (can be malig in stomach, usually benign in bowel)
- inflammatory fibroid polyps
-inflammatory myofibroblastic tumour (previously known as inflammatory pseudotumour)
- Desmoids (usually morphologically distinct)
- ALWAYS CONSIDER CARCINOMA METS ESP FROM FEMALE GENITAL TRACT!
If difficult case, can always send formalin fixed tissue to BRI for mutation analysis