Gastrointestinal stromal tumour

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Gastrointestinal stromal tumour
Diagnosis in short

Gastrointestinal stromal tumour. H&E stain.

LM spindle or epithelioid or mixed morphology, usu. centred on the muscularis propria
LM DDx schwannoma, leiomyoma, leiomyosarcoma, neurofibroma, desmoid-type fibromatosis
IHC CD117 +ve, DOG1 +ve, CD34 +ve, S-100 -ve
Molecular mutation in KIT gene or PDGFRA gene
Staging gastrointestinal stromal tumour staging
Site stomach, small intestine, other sites

Syndromes Neurofibromatosis type 1, Carney triad, Carney-Stratakis syndrome

Prognosis good to poor - dependent on size, site & mitotic rate

The gastrointestinal stromal tumour, abbreviated GIST, is an uncommon tumour of the gastrointestinal tract.

General

Definition

  • Tumour resulting from a mutation in the KIT gene or PDGFRA (Platelet-derived growth factor receptor, alpha polypeptide) gene.[1]

Epidemiology

  • Arise from Interstitial cells of Cajal.[1]

May be familial/syndromic:[2]

Treatment

Factors predictive of malignant behaviour

Features suggesting a bad prognosis:[1]

  • Large size.
    • Often benign if small size.
  • High mitotic rate (for area 5mm2).
  • Site - small intestine GISTs worse than stomach GISTs.

Small intestine bad prognosis:[1]

  • >5 mitoses/5 mm2 or size >10 cm.

Stomach bad prognosis:[1]

  • >5 mitoses/5 mm2 and size >5 cm.

Location

Most common locations in order:[1]

  • 60% in stomach.
  • 35% in small intestine.
  • 5% elsewhere.

Notes:

  • Small intestinal GISTs have a worse prognosis than gastric ones.[1]
  • GISTs almost never metastasize to the lymph nodes.

Microscopic

Features:

  • Classically, spindle cell morphology ~ 50% of tumours.[4]
    • May be epithelioid (round) ~40% of tumours.
    • Mixed epithelioid and spindle cell tumours ~10% tumours.
  • +/-Cytoplasmic inclusions[5] - perinuclear.[6]
  • Classically splits the layers of the muscularis propria - as this is where the interstitial cells of Cajal are located.[7]
  • +/-Skenoid fibres - extracellular collagen bundles[8] ~ 2-5 x 60 micrometers - uncommon finding.

DDx

Images

IHC

Others:

  • CD34 +ve in 70%.[1]
  • Desmin +ve in 5%.[1]
  • WT1 +ve -- cytoplasmic (28/28 cases[12]).

IHC work-up panel

  • S-100 (neural tumours, rarely +ve in GISTs[1]).
  • CD34, CD117 (GIST).
  • Desmin (muscle tumours).

Molecular tests

See Molecular_pathology_tests#Other.
  • Sequence Kit gene, PDGFRA gene.
    • 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.[13]
    • Secondary mutations of c-kit lead to imatinib resistance,[14] and resistance to other similar inhibitors.

Gastrointestinal stromal tumour staging

GIST has its own staging.

Sign out

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.
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%.

Incidental GIST

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%.

Staging

  • 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.[15]

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

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Miettinen M, Lasota J (October 2006). "Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis". Arch. Pathol. Lab. Med. 130 (10): 1466–78. PMID 17090188. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=130&page=1466.
  2. Agaimy A, Hartmann A (October 2010). "[Hereditary and non-hereditary syndromic gastointestinal stromal tumours]" (in German). Pathologe 31 (6): 430–7. doi:10.1007/s00292-010-1354-6. PMID 20848108.
  3. Blay, JY.; Blomqvist, C.; Bonvalot, S.; Boukovinas, I.; Casali, PG.; De Alava, E.; Dei Tos, AP.; Dirksen, U. et al. (Oct 2012). "Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.". Ann Oncol 23 Suppl 7: vii49-55. doi:10.1093/annonc/mds252. PMID 22997454. http://annonc.oxfordjournals.org/content/23/suppl_7/vii49.full.
  4. Miettinen, M.; Sobin, LH.; Lasota, J. (Jan 2005). "Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up.". Am J Surg Pathol 29 (1): 52-68. PMID 15613856.
  5. Pasquinelli G, Severi B, Martinelli GN, Santini D, Gelli MC, Tison V (April 1995). "Gastro-intestinal stromal tumors: an ultrastructural reinterpretation of the clear cell component". J. Submicrosc. Cytol. Pathol. 27 (2): 251–7. PMID 7757951.
  6. Boşoteanu, M.; Boşoteanu, C.; Deacu, M.; Aşchie, M. (2011). "Differential diagnosis of a gastric stromal tumor: case report and literature review.". Rom J Morphol Embryol 52 (4): 1361-8. PMID 22203947.
  7. Agaimy A, Wünsch PH (August 2006). "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". Langenbecks Arch Surg 391 (4): 322–9. doi:10.1007/s00423-005-0005-5. PMID 16402273.
  8. 8.0 8.1 8.2 Levy, AD.; Patel, N.; Dow, N.; Abbott, RM.; Miettinen, M.; Sobin, LH.. "From the archives of the AFIP: abdominal neoplasms in patients with neurofibromatosis type 1: radiologic-pathologic correlation.". Radiographics 25 (2): 455-80. doi:10.1148/rg.252045176. PMID 15798063.
  9. 9.0 9.1 Greenson, JK. (Apr 2003). "Gastrointestinal stromal tumors and other mesenchymal lesions of the gut.". Mod Pathol 16 (4): 366-75. doi:10.1097/01.MP.0000062860.60390.C7. PMID 12692202.
  10. Deyrup, AT.; Lee, VK.; Hill, CE.; Cheuk, W.; Toh, HC.; Kesavan, S.; Chan, EW.; Weiss, SW. (Jan 2006). "Epstein-Barr virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events: a clinicopathologic and molecular analysis of 29 tumors from 19 patients.". Am J Surg Pathol 30 (1): 75-82. PMID 16330945.
  11. Liegl, B.; Hornick, JL.; Corless, CL.; Fletcher, CD. (Mar 2009). "Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes.". Am J Surg Pathol 33 (3): 437-46. doi:10.1097/PAS.0b013e318186b158. PMID 19011564.
  12. Bing, Z.; Pasha, TL.; Acs, G.; Zhang, PJ. (Jul 2008). "Cytoplasmic overexpression of WT-1 in gastrointestinal stromal tumor and other soft tissue tumors.". Appl Immunohistochem Mol Morphol 16 (4): 316-21. doi:10.1097/PAI.0b013e31815c2e02. PMID 18528287.
  13. Lasota, J.; Jasinski, M.; Sarlomo-Rikala, M.; Miettinen, M. (Jan 1999). "Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas.". Am J Pathol 154 (1): 53-60. doi:10.1016/S0002-9440(10)65250-9. PMID 9916918.
  14. Wada, N.; Kurokawa, Y.; Takahashi, T.; Hamakawa, T.; Hirota, S.; Naka, T.; Miyazaki, Y.; Makino, T. et al. (2016). "Detecting Secondary C-KIT Mutations in the Peripheral Blood of Patients with Imatinib-Resistant Gastrointestinal Stromal Tumor.". Oncology 90 (2): 112-7. doi:10.1159/000442948. PMID 26779618.
  15. Coccolini, F.; Catena, F.; Ansaloni, L.; Pinna, AD. (Feb 2012). "Gastrointestinal stromal tumor and mitosis, pay attention.". World J Gastroenterol 18 (6): 587-8. doi:10.3748/wjg.v18.i6.587. PMID 22363128.