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TRAINING DAYS

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

Please see information supplied by Dr Wong for full clinical details


Case A

50yom gastric antrum

Well circumscribed fascicles of relatively monomorphic spindle cells

CD117 and CD34 +ve

*Spindle cell GIST

see presentation slides


Case B

43yom gastric antrum

Tumour composed of small monomorphic epithelioid cells and focal clear cell change

*Epithelioid GIST

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!

see presentation slide


Case C

Peripancreatic tumour (recurrence of tumour in patient case A).

Hyaline 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)

*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

see presentation slide


Case D

Sheets of pleomorphic tumour cells with coarse chromatin, angulated nuclei, mitoses and tumour giant cells

* Pleomorphic GIST

Important differential diagnosis poorly diff carcinoma - ck neg in this case

Mutation analysis needed to establish diagnosis

see presentation slide


Case E

52 yom ?pancreatic ca

Cords and angulated lobules of mildly pleomorphic spindle cells.

* CD117 negative GIST

DD Malignant SFT, inflammatory myofibroblastic polyp (different morphology), Angiosarcoma (can express cd117), KS. bcl-2 not useful in diagnosis of gists

see presentation slide


Case F

High grade cellular tumour comprising sheets and fascicles of plump spindle cells. Focally EMA pos

tX-18 translocation

* Synovial sarcoma

(but can apparently get focal ck positivity in GISTs)

see presentation slide


Case G

Mucosa confined neural spindle cell tumour with ganglion cells diffusely infiltrating between crypts. ie. diffuse ganglioneuromatosis.

* Ganglioneuroma

?History of NF1 or MEN2b

DD benign fibroblastic polyp (cd34, sma), perineurioma (EMA)

see presentation slide


Case H

Duodenal tumour. Abutting pancreas

Short interlacing fascicles of monomorphic spindle cells.

* GIST in a patient with NF1

see presentation slides


Case I

Ulcerated tumour adjacent to and undermining the non-dysplastic sq mucosa

Sheets of pleomorphic epithelioid cells with prom nucleoli and cytoplasmic pigment

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.

(look up other cd117+ tumours - see list here)

see presentation slide


Case J

Abdo wall spindle cell tumour with varying cellularity and focal haemangiopericytomatous vascular pattern.

CD34 and bcl-2 positive, CD117 negative

* SFT

DD  c-kit negative GIST

see presentation slide


Case K

SI mucosa with predom subserosal  hypocellular bland monomorphic spindle cell tumour infiltrating submucosa and focally extramural fat. Abundant collagenous stroma, curvilinear thin walled blood vessels

focal sma positive

* Mesenteric fibromatosis (desmoid tumour)

see presentation slide


Case L

48yof pelvic ?rectal tumour.

Hypocellular tumour comprising relatively monomorphic spindle cells in a myxoid stroma. Tumour has an infiltrative border, with entrapped fat and bvs

ER positive, on experimental tamoxifen

*aggressive angiomyxoma

DD angiomyofibroblastoma (but this would have more of a 'pushing' edge)

Note ER alpha pos have never been identified in GIST

see presentation slide


Case M

83yof widespread peritoneal nodules and mets. High grade tumour comprising ovoid cells with minimal cytoplasm and open chromatin; focal spiral artery formation.

* Metastatic Endometrial stromal sarcoma

CD10 positive, previous endometrial stromal sarcoma!!

see presentation slide


 

Notes

Good review on GISTs here

GISTs

95% c-kit

30% sma

5% s100

 

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)

- SFTs

- 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

 

Additional notes

  • (Carneys triad - Epithelioid GIST, extra-adrenal paraganglioma, and pulmonary chondroma)
  • (Gardner syndrome, a variant of familial adenomatous polyposis, an autosomal dominant disease characterized by GI polyps, multiple osteomas, and skin and soft tissue tumors. )
  • control block for CD117 in diagnosis of GIST = intestinal wall (gastric best) with mucosal mast cells, interstitial pacemaker cells [both positive], and muscularis which should be negative
  • beta catenin stains desmoids but not superficial fibromatoses

 

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