Gastrointestinal Stromal Tumor (GIST)
Succinate Dehydrogenase Subunit B (SDHB) Deficient (PediatricType) GIST
- SDHB deficient GIST include both sporadic tumors and two syndromes that are covered in more detail separately
- Sporadic tumors are predominantly pediatric
- SDHB deficient tumors make up virtually all tumors < age 20 and half of those age 20-30
- Infrequent adult cases have been reported (Rege 2011)
- Most are young adults but reported up to 63 years
- Same behavior and characteristics as pediatric cases
- On followup, some later fulfill criteria for syndromic GIST
- Both syndromic and sporadic SDHB deficient GISTs share features distinct from usual SDHD positive tumors
| SDHB Deficient (Pediatric Type) GIST | Usual GIST, (SDHB Positive) |
| Predominantly pediatric and young adult, rare middle age to older adults | Predominantly older adults |
| F:M ratio as high as 9:1 | M = F |
| All are gastric, most in antrum | May occur throughout gastrointestinal tract |
| Frequently multiple, simultaneous or metachronous | Usually solitary |
| Frequently multilobular | Generally one dominant mass |
| Predominantly epithelioid, occasionally mixed | May be epithelioid or spindled |
| Lymph node metastases common | Lymph node metastases rare |
| Poor response to imatinib | Responsive to imatinib |
| No CKIT or PDGFRA mutations | CKIT or PDGFRA mutations present in about 90% |
| Protracted course (e.g. 15 years), even if metastatic | Poor prognosis if metastatic |
- Genetic basis of SDHB deficient GIST is not well understood
- CKIT and DOG1 stains positive >90%
- Lack CKIT or PDGFRA mutations
- Germline SDHB mutations in Carney-Stratakis syndrome
- No germline or somatic mutations have been found in Carney triad or sporadic cases
- NF1 associated cases do not fit well into the above dichotomy
- Although SDHB positive, they lack CKIT or PDGFRA mutations
- They are not imatinib sensitive
- Although frequently multiple, they are exclusively spindled and restricted to the intestines
- References (see left side bar for general GIST bibliography)
- Miettinen M, Lasota J, Sobin LH. Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature. Am J Surg Pathol. 2005 Oct;29(10):1373-81.
- Prakash S, Sarran L, Socci N, DeMatteo RP, Eisenstat J, Greco AM, Maki RG, Wexler LH, LaQuaglia MP, Besmer P, Antonescu CR. Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature. J Pediatr Hematol Oncol. 2005 Apr;27(4):179-87.
- Agaram NP, Laquaglia MP, Ustun B, Guo T, Wong GC, Socci ND, Maki RG, DeMatteo RP, Besmer P, Antonescu CR. Molecular characterization of pediatric gastrointestinal stromal tumors. Clin Cancer Res. 2008 May 15;14(10):3204-15.
- Rege TA, Wagner AJ, Corless CL, Heinrich MC, Hornick JL. "Pediatric-type" gastrointestinal stromal tumors in adults: distinctive histology predicts genotype and clinical behavior. Am J Surg Pathol. 2011 Apr;35(4):495-504.
- Gill AJ, Chou A, Vilain R, Clarkson A, Lui M, Jin R, Tobias V, Samra J, Goldstein D, Smith C, Sioson L, Parker N, Smith RC, Sywak M, Sidhu SB, Wyatt JM, Robinson BG, Eckstein RP, Benn DE, Clifton-Bligh RJ. Immunohistochemistry for SDHB divides gastrointestinal stromal tumors (GISTs) into 2 distinct types. Am J Surg Pathol. 2010 May;34(5):636-44.
- Gaal J, Stratakis CA, Carney JA, Ball ER, Korpershoek E, Lodish MB, Levy I, Xekouki P, van Nederveen FH, den Bakker MA, O'Sullivan M, Dinjens WN, de Krijger RR. SDHB immunohistochemistry: a useful tool in the diagnosis of Carney-Stratakis and Carney triad gastrointestinal stromal tumors. Mod Pathol. 2011 Jan;24(1):147-51.
- Miettinen M, Wang ZF, Sarlomo-Rikala M, Osuch C, Rutkowski P, Lasota J. Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age. Am J Surg Pathol. 2011 Nov;35(11):1712-21.
- Wang JH, Lasota J, Miettinen M. Succinate Dehydrogenase Subunit B (SDHB) Is Expressed in Neurofibromatosis 1-Associated Gastrointestinal Stromal Tumors (Gists): Implications for the SDHB Expression Based Classification of Gists. J Cancer. 2011 Feb 16;2:90-3.
