Difference between revisions of "Gastrointestinal stromal tumour"

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Gastrointestinal stromal tumour (view source)

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{{ Infobox diagnosis
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Name      = {{PAGENAME}}
| Image      = Gastrointestinal_stromal_tumour_-_high_mag.jpg
| Image      = Gastrointestinal_stromal_tumour_-_very_low_mag.jpg
| Width      =
| Width      =
| Caption    = Gastrointestinal stromal tumour. [[H&E stain]].
| Caption    = Gastrointestinal stromal tumour. [[H&E stain]].
| Micro      = spindle cell ''or'' epithelioid ''or'' mixed morphology
| Micro      = spindle ''or'' epithelioid ''or'' mixed morphology, usu. centred on the muscularis propria
| Subtypes  =  
| Subtypes  =  
| LMDDx      = [[schwannoma]], [[leiomyoma]], [[leiomyosarcoma]], [[neurofibroma]], [[desmoid-type fibromatosis]]
| LMDDx      = [[schwannoma]], [[leiomyoma]], [[leiomyosarcoma]], [[neurofibroma]], [[desmoid-type fibromatosis]]
| Stains    =
| Stains    =
| IHC        = CD34 +ve, CD117 +ve, DOG-1 +ve, S-100 -ve
| IHC        = CD117 +ve, [[DOG1]] +ve, CD34 +ve, S-100 -ve
| EM        =
| EM        =
| Molecular  = mutation in KIT gene ''or'' PDGFRA gene
| Molecular  = mutation in KIT gene ''or'' PDGFRA gene
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| Gross      =
| Gross      =
| Grossing  =
| Grossing  =
| Staging    = [[gastrointestinal stromal tumour staging]]
| Site      = [[stomach]], [[small intestine]], other sites
| Site      = [[stomach]], [[small intestine]], other sites
| Assdx      =
| Assdx      =
| Syndromes  =
| Syndromes  = [[Neurofibromatosis type 1]], [[Carney triad]], [[Carney-Stratakis syndrome]]
| Clinicalhx =
| Clinicalhx =
| Signs      =
| Signs      =
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| Rads      =
| Rads      =
| Endoscopy  =
| Endoscopy  =
| Prognosis  = good to poor - dependent is size, site & mitotic rate
| Prognosis  = good to poor - dependent on size, site & mitotic rate
| Other      =
| Other      =
| ClinDDx    =
| ClinDDx    =
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===Definition===
===Definition===
*Tumour resulting from a mutation in the KIT gene ''or'' PDGFRA (Platelet-derived growth factor receptor, alpha polypeptide) gene.<ref name=pmid17090188/>
*Tumour resulting from a mutation in the KIT gene ''or'' PDGFRA (Platelet-derived growth factor receptor, alpha polypeptide) gene.<ref name=pmid17090188/>
*Cases wild-type for KIT or PDFGRA may harbour defects in the [[succinate dehydrogenase]] complex, NF-1, BRAF, or extremely rarely KRAS.


===Epidemiology===
===Epidemiology===
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*[[Neurofibromatosis|Neurofibromatosis 1]] (von Recklinghausen's disease).
*[[Neurofibromatosis|Neurofibromatosis 1]] (von Recklinghausen's disease).
*[[Carney triad]].
*[[Carney triad]].
*Carney-Stratakis syndrome - GISTs and [[paraganglioma]] - due to mutation in the genes for succinate dehydrogenase.<ref>{{Cite journal  | last1 = Blay | first1 = JY. | last2 = Blomqvist | first2 = C. | last3 = Bonvalot | first3 = S. | last4 = Boukovinas | first4 = I. | last5 = Casali | first5 = PG. | last6 = De Alava | first6 = E. | last7 = Dei Tos | first7 = AP. | last8 = Dirksen | first8 = U. | last9 = Duffaud | first9 = F. | title = Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. | journal = Ann Oncol | volume = 23 Suppl 7 | issue =  | pages = vii49-55 | month = Oct | year = 2012 | doi = 10.1093/annonc/mds252 | PMID = 22997454 | url = http://annonc.oxfordjournals.org/content/23/suppl_7/vii49.full }}</ref>
*[[Carney-Stratakis syndrome]] - GISTs and [[paraganglioma]] - due to mutation in the genes for [[succinate dehydrogenase]].<ref name=pmid22997454>{{Cite journal  | last1 = Blay | first1 = JY. | last2 = Blomqvist | first2 = C. | last3 = Bonvalot | first3 = S. | last4 = Boukovinas | first4 = I. | last5 = Casali | first5 = PG. | last6 = De Alava | first6 = E. | last7 = Dei Tos | first7 = AP. | last8 = Dirksen | first8 = U. | last9 = Duffaud | first9 = F. | title = Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. | journal = Ann Oncol | volume = 23 Suppl 7 | issue =  | pages = vii49-55 | month = Oct | year = 2012 | doi = 10.1093/annonc/mds252 | PMID = 22997454 | url = http://annonc.oxfordjournals.org/content/23/suppl_7/vii49.full }}</ref>


===Treatment===
===Treatment===
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*Large size.
*Large size.
**Often benign if small size.
**Often benign if small size.
*High mitotic rate (for area 5mm^2).
*High mitotic rate (for area 5mm<sup>2</sup>).
*Site - small intestine GISTs worse than stomach GISTs.
*Site - small intestine GISTs worse than stomach GISTs.


Small intestine bad prognosis:<ref name=pmid17090188/>
Small intestine bad prognosis:<ref name=pmid17090188/>
* >5 mitoses/5 mm^2 ''or'' size >10 cm.
* >5 mitoses/5 mm<sup>2</sup> ''or'' size >10 cm.


Stomach bad prognosis:<ref name=pmid17090188/>
Stomach bad prognosis:<ref name=pmid17090188/>
* >5 mitoses/5 mm^2 ''and'' size >5 cm.
* >5 mitoses/5 mm<sup>2</sup> ''and'' size >5 cm.


===Location===
===Location===
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Notes:
Notes:
*Small intestinal GISTs have a worse prognosis than gastric ones.<ref name=pmid17090188/>
*Small intestinal GISTs have a worse prognosis than gastric ones.<ref name=pmid17090188/>
*GISTs almost never metastasize to the [[lymph node]]s.
*GISTs almost never metastasize to the [[lymph node]]s (except for SDH-B deficient epithelioid GISTs)
**Most common [[metastasis]] locations: [[liver]], abdominal soft tissue.
**Most common [[metastasis]] locations: [[liver]], abdominal soft tissue.


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** May be epithelioid (round) ~40% of tumours.
** May be epithelioid (round) ~40% of tumours.
** Mixed epithelioid and spindle cell tumours ~10% tumours.
** Mixed epithelioid and spindle cell tumours ~10% tumours.
*+/-Cytoplasmic inclusions.<ref name=pmid7757951>{{cite journal |author=Pasquinelli G, Severi B, Martinelli GN, Santini D, Gelli MC, Tison V |title=Gastro-intestinal stromal tumors: an ultrastructural reinterpretation of the clear cell component |journal=J. Submicrosc. Cytol. Pathol. |volume=27 |issue=2 |pages=251–7 |year=1995 |month=April |pmid=7757951 |doi= |url=}}</ref>
*+/-Cytoplasmic inclusions<ref name=pmid7757951>{{cite journal |author=Pasquinelli G, Severi B, Martinelli GN, Santini D, Gelli MC, Tison V |title=Gastro-intestinal stromal tumors: an ultrastructural reinterpretation of the clear cell component |journal=J. Submicrosc. Cytol. Pathol. |volume=27 |issue=2 |pages=251–7 |year=1995 |month=April |pmid=7757951 |doi= |url=}}</ref> - perinuclear.<ref>{{Cite journal  | last1 = Boşoteanu | first1 = M. | last2 = Boşoteanu | first2 = C. | last3 = Deacu | first3 = M. | last4 = Aşchie | first4 = M. | title = Differential diagnosis of a gastric stromal tumor: case report and literature review. | journal = Rom J Morphol Embryol | volume = 52 | issue = 4 | pages = 1361-8 | month =  | year = 2011 | doi =  | PMID = 22203947 }}</ref>
*Classically splits the layers of the ''muscularis propria'' - as this is where the ''interstitial cells of Cajal'' are located.<ref name=pmid16402273>{{cite journal |author=Agaimy A, Wünsch PH |title=Gastrointestinal stromal tumours: a regular origin in the muscularis propria, but an extremely diverse gross presentation. A review of 200 cases to critically re-evaluate the concept of so-called extra-gastrointestinal stromal tumours |journal=Langenbecks Arch Surg |volume=391 |issue=4 |pages=322–9 |year=2006 |month=August |pmid=16402273 |doi=10.1007/s00423-005-0005-5 |url=}}</ref>
*Classically splits the layers of the ''muscularis propria'' - as this is where the ''interstitial cells of Cajal'' are located.<ref name=pmid16402273>{{cite journal |author=Agaimy A, Wünsch PH |title=Gastrointestinal stromal tumours: a regular origin in the muscularis propria, but an extremely diverse gross presentation. A review of 200 cases to critically re-evaluate the concept of so-called extra-gastrointestinal stromal tumours |journal=Langenbecks Arch Surg |volume=391 |issue=4 |pages=322–9 |year=2006 |month=August |pmid=16402273 |doi=10.1007/s00423-005-0005-5 |url=}}</ref>  
*+/-Skenoid fibres - extracellular collagen bundles<ref name=pmid15798063/> ~ 2-5 x 60 micrometers - uncommon finding.
*+/-Skenoid fibres - extracellular collagen bundles<ref name=pmid15798063/> ~ 2-5 x 60 micrometers - uncommon finding.
**Not seen in gastric GISTs.<ref name=pmid12692202/>
**Not seen in gastric GISTs.<ref name=pmid12692202/>
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Image:Gastric_GIST_%282%29.jpg | GIST - low mag. (WC/KGH)
Image:Gastric_GIST_%282%29.jpg | GIST - low mag. (WC/KGH)
Image:Gastric_GIST_%281%29.jpg | GIST - high mag. (WC/KGH)  
Image:Gastric_GIST_%281%29.jpg | GIST - high mag. (WC/KGH)  
</gallery>
<gallery>
Image:Gastrointestinal_stromal_tumour_-_very_low_mag.jpg | Intestinal spindle cell GIST - very low mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_low_mag.jpg | Intestinal spindle cell GIST - low mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_low_mag.jpg | Intestinal spindle cell GIST - low mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_intermed_mag.jpg | Intestinal spindle cell GIST - intermed. mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_intermed_mag.jpg | Intestinal spindle cell GIST - intermed. mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_high_mag.jpg | Intestinal spindle cell GIST - high mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_high_mag.jpg | Intestinal spindle cell GIST - high mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_very_high_mag.jpg | Intestinal spindle cell GIST - very high mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_superf_-_intermed_mag.jpg | Epithelioid GIST - intermed. mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_superf_-_intermed_mag.jpg | Epithelioid GIST - intermed. mag. (WC/Nephron)
</gallery>
</gallery>


==IHC==
==IHC==
*CD34 +ve in 70%.<ref name=pmid17090188/>
*CD117 +ve in 95%.<ref name=pmid17090188/>
*CD117 +ve in 95%.<ref name=pmid17090188/>
**[[Mast cell]]s are the internal positive control.
**[[Mast cell]]s are the internal positive control.
*[[DOG1]] +ve.<ref name=pmid19011564>{{Cite journal  | last1 = Liegl | first1 = B. | last2 = Hornick | first2 = JL. | last3 = Corless | first3 = CL. | last4 = Fletcher | first4 = CD. | title = Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. | journal = Am J Surg Pathol | volume = 33 | issue = 3 | pages = 437-46 | month = Mar | year = 2009 | doi = 10.1097/PAS.0b013e318186b158 | PMID = 19011564 }}</ref>


Others:
*CD34 +ve in 70%.<ref name=pmid17090188/>
*Desmin +ve in 5%.<ref name=pmid17090188/>
*Desmin +ve in 5%.<ref name=pmid17090188/>
*DOG1 +ve.<ref name=pmid19011564>{{Cite journal  | last1 = Liegl | first1 = B. | last2 = Hornick | first2 = JL. | last3 = Corless | first3 = CL. | last4 = Fletcher | first4 = CD. | title = Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. | journal = Am J Surg Pathol | volume = 33 | issue = 3 | pages = 437-46 | month = Mar | year = 2009 | doi = 10.1097/PAS.0b013e318186b158 | PMID = 19011564 }}</ref>
*WT1 +ve -- cytoplasmic (28/28 cases<ref name=pmid18528287>{{Cite journal  | last1 = Bing | first1 = Z. | last2 = Pasha | first2 = TL. | last3 = Acs | first3 = G. | last4 = Zhang | first4 = PJ. | title = Cytoplasmic overexpression of WT-1 in gastrointestinal stromal tumor and other soft tissue tumors. | journal = Appl Immunohistochem Mol Morphol | volume = 16 | issue = 4 | pages = 316-21 | month = Jul | year = 2008 | doi = 10.1097/PAI.0b013e31815c2e02 | PMID = 18528287 }}</ref>).
**More sensitive than CD117.
 
===IHC work-up panel===
===IHC work-up panel===
*S-100 (neural tumours, rarely +ve in GISTs<ref name=pmid17090188/>).
*S-100 (neural tumours, rarely +ve in GISTs<ref name=pmid17090188/>).
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**Kit gene sequencing is being done more frequently as of late-- if a mutation is found it suggest the drug ''[[imatinib]]'' will be effective.
**Kit gene sequencing is being done more frequently as of late-- if a mutation is found it suggest the drug ''[[imatinib]]'' will be effective.
**Exon 11 mutation associated with malignant behaviour.<ref name=pmid9916918>{{Cite journal  | last1 = Lasota | first1 = J. | last2 = Jasinski | first2 = M. | last3 = Sarlomo-Rikala | first3 = M. | last4 = Miettinen | first4 = M. | title = Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. | journal = Am J Pathol | volume = 154 | issue = 1 | pages = 53-60 | month = Jan | year = 1999 | doi = 10.1016/S0002-9440(10)65250-9 | PMID = 9916918 }}</ref>
**Exon 11 mutation associated with malignant behaviour.<ref name=pmid9916918>{{Cite journal  | last1 = Lasota | first1 = J. | last2 = Jasinski | first2 = M. | last3 = Sarlomo-Rikala | first3 = M. | last4 = Miettinen | first4 = M. | title = Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. | journal = Am J Pathol | volume = 154 | issue = 1 | pages = 53-60 | month = Jan | year = 1999 | doi = 10.1016/S0002-9440(10)65250-9 | PMID = 9916918 }}</ref>
**Secondary mutations of c-kit lead to imatinib resistance,<ref name=pmid26779618>{{Cite journal  | last1 = Wada | first1 = N. | last2 = Kurokawa | first2 = Y. | last3 = Takahashi | first3 = T. | last4 = Hamakawa | first4 = T. | last5 = Hirota | first5 = S. | last6 = Naka | first6 = T. | last7 = Miyazaki | first7 = Y. | last8 = Makino | first8 = T. | last9 = Yamasaki | first9 = M. | title = Detecting Secondary C-KIT Mutations in the Peripheral Blood of Patients with Imatinib-Resistant Gastrointestinal Stromal Tumor. | journal = Oncology | volume = 90 | issue = 2 | pages = 112-7 | month =  | year = 2016 | doi = 10.1159/000442948 | PMID = 26779618 }}</ref> and resistance to other similar inhibitors.
==Gastrointestinal stromal tumour staging==
{{Main|Gastrointestinal stromal tumour staging}}
GIST has its own staging.


==Sign out==
==Sign out==
<pre>
STOMACH (MASS), LESSER CURVE, WEDGE RESECTION:
- GASTROINTESTINAL STROMAL TUMOUR (GIST).
-- MARGINS NEGATIVE FOR GIST.
COMMENT:
The tumour stains as follows:
POSITIVE: CD117, CD34.
NEGATIVE: Desmin, S-100.
</pre>
<pre>
SMALL BOWEL (ILEUM), RESECTION:
- GASTROINTESTINAL STROMAL TUMOUR (GIST), LOW-GRADE, NO RISK OF
  PROGRESSIVE DISEASE.
-- MARGINS NEGATIVE FOR GIST.
-- PLEASE SEE TUMOUR SUMMARY.
- THREE BENIGN LYMPH NODES.
COMMENT:
The tumour stains as follows:
POSITIVE: CD117, CD34.
NEGATIVE: Desmin, S-100.
PROLIFERATION (Ki-67): <1%.
</pre>
====Incidental GIST====
<pre>
Partial Stomach, Sleeve Gastrectomy:
- Stomach wall with incidental GASTROINTESTINAL STROMAL TUMOUR (GIST), 2 mm in maximal dimension.
-- Margin clear.
- Gastric mucosa within normal limits.
Comment:
The tumour stains as follows:
POSITIVE: DOG1, CD117, CD34.
NEGATIVE: desmin, S-100.
PROLIFERATION (Ki-67): <2%.
</pre>


===Staging===
===Staging===
*The stage is primarily determined by the tumour size and mitotic grade.
*The stage is primarily determined by the tumour size and mitotic grade.
**In the stomach, the mitotic grade determines whether a given tumour is Stage I or Stage III.<ref>{{Cite journal  | last1 = Coccolini | first1 = F. | last2 = Catena | first2 = F. | last3 = Ansaloni | first3 = L. | last4 = Pinna | first4 = AD. | title = Gastrointestinal stromal tumor and mitosis, pay attention. | journal = World J Gastroenterol | volume = 18 | issue = 6 | pages = 587-8 | month = Feb | year = 2012 | doi = 10.3748/wjg.v18.i6.587 | PMID = 22363128 }}</ref>
**In the stomach, the mitotic grade determines whether a given tumour is Stage I or Stage III.<ref>{{Cite journal  | last1 = Coccolini | first1 = F. | last2 = Catena | first2 = F. | last3 = Ansaloni | first3 = L. | last4 = Pinna | first4 = AD. | title = Gastrointestinal stromal tumor and mitosis, pay attention. | journal = World J Gastroenterol | volume = 18 | issue = 6 | pages = 587-8 | month = Feb | year = 2012 | doi = 10.3748/wjg.v18.i6.587 | PMID = 22363128 }}</ref>
===Micro===
The sections show a spindle cell lesion that is well-circumscribed and without significant
nuclear pleomorphism. No lymphocytic cuff is surrounding the lesion.  The lesion is focally
seen at the inked soft tissue margin. Three mitoses are seen in 5 mm*mm.


==See also==
==See also==
Mark
109

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