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ORIGINALARTICLE

Gastrointestinal Stromal Tumors of the Stomachin Children and Young Adults

A Clinicopathologic, Immunohistochemical, and MolecularGenetic Study of 44 Cases With Long-Term Follow-Upand Review of the Literature

Markku Miettinen, MD,* Jerzy Lasota, MD,* and Leslie H. Sobin, MD

Abstract:Gastrointestinal stromal tumors (GISTs), specific KIT- orPDFGRA-signaling driven mesenchymal tumors, are rare in children

and young adults, and their clinicopathologic and molecular genetic

profile is incompletely understood. In this study, we analyzed 44 gas-

tric GISTs occurring by the age of 21 years. There were 32 females

and 12 males, youngest of whom were a 5-year-old boy and an

8-year-old girl. All but 1 of 25 patients under the age of 16 were girls.

The patients most commonly received medical attention because of

chronic, insidious gastrointestinal bleeding with anemia, less com-

monly with acute GI bleeding. Only 1 patient had Carney triad with

pulmonary chondroma. None of the patients had family members with

GIST. The tumors measured from 1.5 to 24 cm (median, 5.6 cm). A

total of 21 tumors with specified location were in the antrum and

8 were in the gastric body. Histologically, 26 tumors were composed

of epithelioid cells, 12 of spindle cells, and 6 of combination thereof.

Mitotic activity varied form 0 to 65/50 HPF (median, 5/50). All but

one of the 24 tumors tested were KIT-positive, and 20 were CD34-

positive. Eleven patients developed liver or abdominal metastases, and

6 of them died of tumor surviving 5.5 to 35.5 years (median, 16 years)

after the first surgery; three of these tumors had a low mitotic activity

and size ,10 cm. Twenty-one patients were alive with no evidence for

disease 7 to 41 years (median, 17 years) after the first surgery. None

of the 13 tumors examined (7 of them 8- to 16-year-old females) had

KIT exon 9, 11, 13, or 17 or PDGFRA exon 12 or 18 mutation as

typically seen in adult GISTs. Gastric GISTs in children have mainly

epithelioid morphology, often occur in antrum, and have a somewhat

unpredictable but slow course of disease. Their pathogenesis may differ

from that of adult GISTs because no KIT or PDGFRA mutations were

found; connection with Carney triad seems infrequent despite demo-

graphic and histologic similarities.

Key Words: gastrointestinal stromal tumor, stomach, child, prog-

nosis, KIT, PDGFRA, mutation

(Am J Surg Pathol 2005;29:13731381)

Gastric stromal tumors (GISTs), the specific KIT-positiveand KIT- or PDGFRA-driven mesenchymal tumors ofthe GI tract, typically occur in older adults and compriseapproximately 60% of all GISTs of all sites.37 Thesetumors seem to be very rare in children and young adults andare mostly reported in the English literature as singlecases and small series with scant data on long-termfollow-up.4,6,10,11,1315,2022,25,26,30,33,34,36,4244,4749,5254 Someof those tumors were reported as gastrointestinal autonomicnerve tumors (GANTs) currently understood as variants ofGIST, based on similar KIT expression and KIT mutations,31

and others as gastric leiomyomas, leiomyoblastomas, and

leiomyosarcomas. Some GISTs in children and young adultsoccur in connection with Carney triad or GIST paragangliomasyndrome, of which a large series was published, including ap-proximately 45 patients 20 years old or younger and showing arelatively indolent course of disease with commonly persistingdisease.7,8

A majority of adult GISTs have gain-of-function muta-tions in KIT or PDGFRA, two closely related receptor tyrosinekinases.16,17,24,27,46 However, there is little information on mu-tation status in GISTs at young age with only 1 case reportedand found to be KIT mutation negative.33 In this study, wepresent a clinicopathologic, immunohistochemical, and mo-lecular genetic analysis of 44 gastric GISTs in children andyoung adults, all but one of which occurred outside the setting

of Carney triad/GIST paraganglioma syndrome.

MATERIALS AND METHODS

Case MaterialAll cases coded as gastric smooth muscle or stromal

tumors (including any alternative designation) submitted fromthe United States or Canada during 1970 to 1996 (n = 1877)were retrieved. Of these 1877 tumors, 55 occurred at or underthe age of 21 years. Forty-four tumors were histologically

From the Departments of *Soft Tissue Pathology and Hepatic and Gastro-intestinal Pathology, Armed Forces Institute of Pathology, Washington, DC.

The opinions and assertions contained herein are the expressed views of theauthors and are not to be construed as official or reflecting the views of theDepartments of the Army or Defense.

Reprints: Markku Miettinen, MD, Department of Soft Tissue Pathology,Armed Forces Institute of Pathology, 6825 16th Street NW, Bldg 54, RmG090, Washington, DC 20306-6000 (e-mail: [email protected]).

Copyright 2005 by Lippincott Williams & Wilkins

Am J Surg Pathol Volume 29, Number 10, October 2005 1373

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classified as GISTs and included in this study. The classi-fication was based on the known histologic spectrum of KIT-positive gastric GISTs with spindle cell or epithelioid features,and with one exception, on KIT positivity. Based on reclas-sification, 11 tumors were excluded: 4 inflammatory myofi-broblastic tumors, 1 desmoid, 1 small round cell desmoplastictumor, 3 benign mesenchymal tumors not further classified,

and 2 unclassified sarcomas. There were no true leiomyomas,leiomyosarcomas, or schwannomas.

Clinical datawere reviewed from the records, and follow-upinformation was obtained from the hospital records, tumor reg-istries, primary care physicians, patients, or in some cases fromfamily members, according to the institutional review boardapproval.

For the purpose of clinicopathologic comparison, thegastric GISTs were divided into eight groups based on tumormaximum diameter and mitotic activity per 50 high powerfields (HPFs), as previously detailed.40 The groups were de-fined as follows: group 1, tumors 2 cm or less in diameter with5 or fewer mitoses per 50 HPF; group 2, tumors larger than 2 cmand not over 5 cm, with 5 or fewer mitoses per 50 HPF; group3a, tumors larger than 5 cm and not over 10 cm, with 5 or fewermitoses per 50 HPF; group 3b, tumors larger than 10 cm, with5 or fewer mitoses per 50 HPF; group 4, tumors 2 cm orsmaller and with more than 5 mitoses per 50 HPF; group 5,tumors larger than 2 cm and not over 5 cm and with more than5 mitoses per 50 HPF; group 6a, tumors larger than 5 cm andnot over 10 cm with more than 5 mitoses per 50 HPF; group6b, tumors larger than 10 cm with more than 5 mitoses per50 HPF.

Analysis of Histologic ParametersA total of 1 to 26 hematoxylin and eosin-stained slides

(median, 7 slides) were reviewed of each case. Mitotic figureswere counted in 50 fields by searching the most mitoticallyactive areas or until 100 mitoses were found. The total area ofthe 50 fields measured 5.3 mm2. The mitosis counting as wellas enumeration of histologic features was performed blindlywithout knowing tumor outcome.

The tumors were subclassified and histologic featuresenumerated as previously reported.40 By cell type, the tumorswere divided into spindle, epithelioid, or combination types.By subtype, the spindle cell tumors were divided into scle-rosing, palisaded- vacuolated, hypercellular, and sarcomatousones, and the epithelioid tumors were divided into sclerosing,discohesive, hypercellular, and sarcomatous subtypes. The fol-lowing additional parameters were recorded in all cases: nuclearatypia, presence of coagulative or liquefactive necrosis, mucosalinvasion, calcification, organoid pattern, nuclear palisading, andcytoplasmic vacuolization.

ImmunohistochemistryAll tumors with available paraffin blocks or unstained

slides were evaluated. The primary antibodies, sources, dilutions,and pretreatments were the following: CD34, clone QBEND/10,Biogenex, San Ramon, CA 1:40, Sigma protease VIII for2 minutes; KIT (CD117), polyclonal antibody A4502, 1:200(Dako, Carpinteria, CA) with heat-induced epitope retrieval byEDTA buffer; smooth muscle actin, clone 1A3 (Sigma, St.

Louis, MO, 1:50 no pretreatment); desmin, clone D33 (Dako1:50, heat-induced epitope retrieval by EDTA buffer); S-100protein, polyclonal (Dako, 1:1600, no pretreatment).

The primary antibodies were incubated 1 hour at roomtemperature. The detection was performed using the Envisionnon-avidin-biotin based polymer system (Dako) with diami-nobenzidine as the chromogen.

Molecular GeneticsDNAwas extracted from formalin-fixed, paraffin-embedded

tissue in 13 cases. Sequences of KIT exon 9, 11, 13, 17 andPDGFRA exon 12 and 18 were PCR-amplified and analyzedas previously described.2729

RESULTSA total of 44 patients with GISTs of age of 21 or under

were identified among 1782 patients with gastric GISTs (2.6%).There were 32 females and 12 males with age range 5 to21 years (median and mean, 14.5 years). Only 2 patients were

younger than 10 years: a 5-year-old boy and an 8-year-old girl.All but 1 patient under age 16 were female. The age and sexdistribution is shown in Figure 1.

Clinical FeaturesThe clinicopathologic features are summarized in Table 1.

A great majority of patients with known clinical history (35 of37 patients, 95%) presented with gastrointestinal bleeding. Thiswas most commonly insidious leading to anemia and relatedsymptoms such as syncope and weakness. Six patients werespecified to have hematemesis and 5 had melena, and 3 pa-tients had both. One patient had upper abdominal discomfortand another was diagnosed umbilical hernia caused by tumor.One patient had Carney triad. She had a gastric epithelioid

GIST first excised at the age of 12 years and had surgery forpulmonary chondroma 3 years later. The details of this patientwere reported previously.40 None of the patients had evidencefor paraganglioma, neurofibromatosis type I, or familial GIST;the information was based in addition to documents, interviewof 19 patients or family members.

FIGURE 1. Age and sex distribution of 44 gastric GISTs inchildren and young adults. Pale = males; dark = females.

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TABLE 1. Clinicopathologic Features of the 44 Children and Young Adults With a Gastric GIST

PatientNo.

Age(y r) Sex

Size(cm) Location

Mitoses/50 HPF

CellType

PrognosticGroup

Recurrences/Metastases(yrs from onset) Follow-Up (yrs) Outcome

1 5 M 14.5 Anterior wall 0 E 3b

2 8 F 8 LC 18 E 6a Abdominal mets, 18 18 AWD

3 10 F 5 LC 10 E 5

4 10 F 5.7 3 E 3a 8.6 ANED5 10 F .10 LC 8 E 6b Gastric recurrence, 13,

gastrectomy29.4 ANED

6 10 F ND Cardia, posterior wall

14 (met) E Liver mets, durationunknown

35.5 DOD

7 11 F 3 Antrum 16 E/S 5

8 11 F 5 0 E 2 7 ANED

9 11 F 5 Antrum, LC 3 E 2

10 11 F 6 Antrum, posterior wall 37 S 6a Liver mets, 4.5 5.6 DOD

11 11 F 7 Antrum, near LC 16 E 6a

12 12 F 2.7 LC 6 S 5

13 12 F 5 Antrum, LC 18 E 5 Gastric recurrences, 9 and 30,total gastrectomy

41.2 ANED

14 12 F 6 Distal 2 E 3b Liver mets, 4.5 8.9 AWD

15 12 F 8.5 LC 7 E 6a Liver mets,at presentation

AWD

16 13 F 4.3 Fundus, LC, post wall 4 S 2 Liver mets, time of diagnosis unknown

6.5 DOD

17 13 F .10 Distal, GC 11 E 6b Liver mets, 14 20.4 DOD

18 14 F 3.5 LC 2 E 2 28 ANED

19 14 F 4.5 Upper body 7 E 5 13 ANED

20 14 F 6 LC 4 E/S 3a 20.7 ANED

21 14 F 6 Antrum, posterior wall 1 E 3a Liver mets, 7 21.5 AWD

22 14 F 7 Antrum, LC 1 E/S 3a 27.5 ANED

23 14 F 9 Antrum 6 S 6a

24 15 F 3.5 Antrum, fundus,multiple

6 E/S 5 8.1 ANED

25 15 F 24 Distal stomach 65 E 6b Abdominal and liver mets, 4 11 DOD

26 16 F 1.5 Antrum 1 E

27 16 M 4 Antrum, LC 9 S 5 10.8 ANED28 16 M 8 2 E 3a Liver mets, 22 23.3 DOD

29 17 M 2.7 6 S 5 Liver mets, 11 11.3 AWD

30 17 M 4 Antrum, LC 2 E 2 17.3 ANED

31 17 M 5 Antrum, LC 30 S 5 31.2 ANED

32 18 F 3.5 3 E/S 2

33 18 F 5.5 Distal, posterior wall 2 S 3a

34 18 M ND Cardia, posterior wall 7 E 12.2 ANED

35 19 F 1.5 Antrum 4 E 2 17.5 ANED

36 19 F 6.5 Antrum, anterior wall 16 S 6a

37 19 F 12 Posterior wall 3 E 3b 16.6 ANED

38 19 M 3.8 Distal body 0 E 2

39 19 M 5 Fundus 15 S 5 29.3 ANED

40 19 M 6 Antrum 12 E 6a 14.7 ANED

41 20 M 7 GC, anterior 3 S 3a 34.2 ANED

42 21 F 3.5 Antrum 0 S 2 7.4 ANED

43 21 F 7 Body 13 E/S 6a 10.1 ANED

44 21 M 7 Mid-body 2 E 3a multiple 17.3 ANED

LC, lesser curvature; GC, great curvature; ANED, alive with no evidence of disease; AWD, alive with disease; DOD, dead of disease; mets, metastases.

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A majority of the tumors with specified location occurredin the antrum (n = 21). Eight tumors were known to occur inthe gastric body (3 in fundus, 2 in cardia, and 3 elsewhere). Atleast 2 patients had multiple tumors: 1 (patient no. 24, Table 1)had two tumors: one in the antrum and another in the fundus,and another (patient no. 44, Table 1) had multiple tumornodules in gastric body. In addition, four tumors were grossly

multinodular, probably representing a single tumor in one regionof the stomach.

The types of primary operation varied from simple localexcision (n = 4) to total gastrectomy (n = 1). Most commonwas partial gastrectomy, usually antrectomy (n = 12), followedby wedge resection (n = 11). Seven patients had subtotalgastrectomy. Two patients underwent total gastrectomy upongastric recurrence 15 and 30 years after the primary tumor.

PathologySelected pathologic features are shown in Table 1. The

tumor size varied form 1.5 cm to 24 cm (median, 6 cm). In4 cases, the size of the primary tumor was not available, buttwo of these tumors were known to be over 10 cm.

Representative images are shown in Figure 2. Histo-logically, the majority of the tumors (26 of 44, 76%) had purelyor predominantly epithelioid morphology; 6 of these caseshad focal spindle cell areas. The epithelioid tumors varied frommoderately to highly cellular and were most commonly sub-classified as hypercellular (n = 18) based on densely packedcells yet lacking sarcomatous features by low-mitotic rate;4 epithelioid tumors were overtly sarcomatous with high mi-totic activity, 3 sclerosing, and 1 of discohesive subtype. Twelvetumors had purely or predominantly spindle cell pattern, and4 of these cases had focal epithelioid cytology. The spindle celltumors were subtyped as sclerosing (n = 2), palisading-vacuolated(n = 4), hypercellular (n = 3), and sarcomatous (n = 3). Sixtumors contained mixed epithelioid and spindle cell compo-nents and did not fit into subclassification.

The mitotic rate varied from 0/50 to 65/50 HPFs (me-dian 6/50 HPFs). Typical feature in these tumors were muscleinvasion between gastric smooth muscle fibers (34 cases); thisoften created a plexiform growth pattern with alternating areasof tumor and normal smooth muscle. Perinuclear vacuolizationwas also typical, seen in 30 cases. Seven epithelioid tumorshad well or partially developed organoid pattern (Fig. 2A)and 7 spindle cell tumors but none of the epithelioid tumorsshowed nuclear palisading resembling that commonly seen inschwannoma (Fig. 2E).

Coagulative necrosis (2 cases) and mucosal invasion(1 case) were rare findings, but foci of liquefactive necrosisoften seen in adult GISTs were not present. None of the tumorshad calcification. Lymph nodes were negative in all 8 cases inwhich nodes were sampled.

Immunohistochemically, all but one of the 24 casestested for KIT (CD117) were positive (96%) typically showingstrong pan-cytoplasmic staining highlighting the tumoralelements from fibrovascular background (Fig. 2G, H). CD34was present in 21 of 25 cases (84%), typically extensively(Fig. 2I), but smooth muscle actin (Fig. 2J), desmin, and S-100protein in none of the 24 cases tested.

Molecular GeneticsAll 13 tumors analyzed (7 of them 8- to 16-year-old girls)

showed wild-type sequences of KIT exons 9, 11, 13, and17, and wild-type sequences of PDGFRA exons 12 and 18.

Follow-UpThe data are summarized in Table 1. Follow-up infor-

mation was available of 32 patients. A total of 21 patients werealive with no evidence of disease with median follow-up of17 years (range, 741 years). Five patients were alive with livermetastasis with median follow-up time of 14 years (range, 922 years). Six patients died of disease (liver metastases) withmedian survival of 16 years (range, 5.535.5 years).

DISCUSSIONGastric GISTs are rare in children and encompass a

spectrum of clinically benign and malignant tumors. Mostcommonly gastrointestinal cancer in children represents alymphoma. However, two studies3,36 found that 2 of 3 and 2 of8 gastric malignancies, respectively, were sarcomas, probablyrepresenting GISTs in the current classification.

Patients at or under the age 16 represent 1.4% and thoseunder the age of 21 years represent 2.5% of all gastric GISTpatients in our series; it is possible that this number overstatesthe frequency of childhood tumors because of consultationbias; a similar frequency was found in an older AFIP serieson gastric epithelioid GISTs.1 However, two recent series of76 and 108 gastric GISTs did not include any children.50,51 Inthe AFIP series of GISTs of other sites, only 1 of 132 rectaland 1 of 156 duodenal GISTs (,1%) occurred in patients at orunder the age of 21 year indicating that intestinal GISTs aremuch less common than the gastric ones at young age.38,39

Based on our series and previously published cases(summarized and referenced in Table 2), a majority of gastricGISTs below the age of 16 years occurs in girls; in our seriesall but 1 of the patients were female. This suggests a devel-opmentally related sex difference, with the occurrence in malesbeing essentially restricted to postpubertal age. According toour findings, GISTs at young age are not associated with NF1or familial occurrence, neither of which was encountered amongthe 44 patients in this study. Only 1 patient in our series hasevidence of Carney triad, suggesting that this syndrome is notassociated with the majority of GISTs of early onset; amongthe 38 previously published cases, 7 (18%) had Carney triad(Table 2). Nevertheless, there is close demographic similarityin the pediatric gastric GIST patients with or without signs orCarney triad, suggesting that these groups may be related.

Certain clinicopathologic features were associated withchildhood GISTs in this series: epithelioid cytology with highcellularity, and location in the antrum in a majority of cases;of all gastric GISTs only 29% occurred in the antrum.40 Pre-viously reported childhood gastric GISTs also had epithelioidcytology in a majority of cases, and antrum and pylorus werecommon locations (cited in Table 2).

Although GISTs in general are known to have KIT orPDGFRA activating mutations with an overall high frequency,none of the 11 subjects in this study had such mutations. Thisstrongly suggests that the pathogenesis of GIST in young age



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FIGURE 2. Typical examples of gastricGISTs in children in young adults. A,Epithelioid GIST with an organoidpattern with superficial resemblanceto paraganglioma. B, Hypercellularepithelioid GIST with pseudorosettes.C, Hypercellular epithelioid GIST witha focal trabecular pattern. D, Sarco-matous epithelioid GIST with a signif-icant mitotic activity. E, Spindle cell

GIST of palisading vacuolized subtype.F, Hypercellular spindle cell GIST.G, Strongly KIT-positivegastric GIST. H,Strongly KIT-positive gastric GIST. I,Strongly CD34-positive gastric GIST.J, All tumors were negative for smoothmuscle actin.



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TABLE 2. Summary of 38 Previously Published Cases of Gastric GISTs/GANTs in Children and Young Adults

Case No. Age (yr) Sex Tumor Size (cm) Location Mitoses/HPF

1 3.5 F 3 0/50

2 4 M 5.7 3 4.8 3 4.3 Fundus ,2/HPF

3 7 F 4 3 4 Antrum, posterior wall Easily found

5 9 F Large Distal stomach 5/10

6 10 F 8 3 5 (rec) Posterior wall, LC ND

7 10 F Multiple, ad 2 cm 0/50

8 10 F 8 LC 2/10

9 10 F 5.5 3 3.4 3 1.5 Fundus, posterior

10 10 M 6.5 3 5.5 3 3 Antrum, anterior wall 30/50

11 11 F 8.5 LC 15/10

12 11 F 18.5 3 16 3 11 GC 7/50

13 11 F 11.0 Body and antrum 8/50

14 11.5 F 5.5 3 2.5 25/50

18 11.7 F 4.5 LC

15 11 M 12 3 10 LC

16 11 M 12 3 9 3 6 Near pylorus, GC 1/10

17 12 F 13 3 4.5 LC 5-6/50

19 13 F Large rare

20 13 F 3.8 Antrum, posterior wall 28/10

21 13 F Huge, .15 Antrum, LC ,5/50

22 13 F 8 cm+, multiple nodules Near cardia, antrum 0/50

23 13 M Pylorus

24 14 F 8.0 Body, posterior wall 14/50

25 14 F Large, multinodular 2/50

26 15 F 10 Antrum, LC ,1/50

27 15 F 0.52.7, multiple nodules Pylorus 1/25

28 15 F 16 cm, multiple

29 15 M 9.0 Body and antrum 4/50

30 15 M 32 3 24 3 15 250/50

31 16 F 0.25 multiple nodules Fundus, body, duodenum ,1/20

32 16 F 15 3 8, multiple nodules Midbody to pylorus, LC

33 16 F 5.0 Distal stomach 3/10

34 16 M 8 3 8 3 7 LC 4/50

35 17 F 7 cm (estimated)

36 17 F

37 17 F 1/50

38 19 F Multiple

Case No. Cell Type KIT Comment Follow-Up (yr) Outcome Reference

1 S 1 yr DOD, liver mets 54

2 E + 13

3 E 47

5 E + 0.5 AWD, liver mets* 13

6 E/S 8.5 ANED, rec at 8 yr 13

7 Diagnosed as GANT 1.3 ANED 30


9 S 18.0 ANED 36, 5310 E/S + 15


12 S + 1.5 ANED 15

13 E 18.0 AWD, liver mets 21

14 E + 12.7 ANED 10

18 S/E 4.3 ANED, with treated liver mets 20



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groups may differ from that in adults. Previously another sub-group of GISTs, those occurring in neurofibromatosis 1 pa-tients, has been reported to be negative for KIT and PDFGRAmutations.23 Recently, one gastric GIST in an adult with Carneytriad12 and another, pediatric one without it33 were also foundnegative for KIT and PDGFRA mutations. If the KIT/PDGFRAmutation negativity applies to Carney triad-associated GISTsin general, pediatric gastric GISTs with or without Carney triadmay have a similar pathogenesis, possibly involving alterna-tive mode of KIT activation than the type of mutationstypically seen in GISTs. More studies are needed to under-stand the pathogenesis of pediatric gastric GISTs.

The occurrence of GISTs at young age raises thequestion whether this could be linked with familial disease.However, none of our patients, including 19 patients who wereinterviewed, had evidence of GISTs in other family members.Also, there are many differences between pediatric and reported

familial GISTs. The latter manifest in adult age (age range in23 patients with reported details, 1871 years; median, 45 years),and are always associated with constitutional KIT or PDGFRAmutation.2,5,9,18,19,32,35,41,45 In two studies, occurrence in chil-dren of the affected families was specifically excluded, in 1 caseby CT scan.2,32 No KIT or PDGFRA mutations were detectedin pediatric GISTs, indicating a different pathogenesis.

Prognostically, gastric GISTs in children are heteroge-neous. A majority of these tumors are clinically indolent withan excellent long-term prognosis, based on our cases with variablylong follow-up and previously published cases with mostlylimited follow-up (Table 2). Treatable recurrences are not un-common and may reflect initial insufficient excision or multi-focal disease escaping surgical detection at the outset.

In our series 11 of 32 patients with follow-up developedliver metastases, and 6 patients died during the follow-up. Mostof the patients who developed metastases were in unfavorable

TABLE 2. (continued) Summary of 38 Previously Published Cases of Gastric GISTs/GANTs in Children and Young Adults

Case No. Cell Type KIT Comment Follow-Up (yr) Outcome Reference

15 S 0.5 DOD, abdominal and liver mets

36, 53

16 S 2.0 ANED 34

17 E + AWD, liver mets 33

19 7.0 AWD, peritoneal implantsat 5 yr

54


21 E 1.0 ANED 42

22 1.2 AWD, liver mets 54

23 S/E + Monozygotic twin had retroperitoneal paraganglioma

AWD, liver mets 4

24 E 6.0 AWD, liver mets 26

25 54

26 E Also pulmonary chondroma 27.0 ANED, abdominal rec/mets at 9, 16, 20, 25 yr

44

27 S 0.8 AWD, liver mets 25

28 E Also mediastinalparaganglioma

1.5 ANED 14

29 5.0 ANED 26

30 S + 1.3 ANED* 10

31 E Also mediastinalparaganglioma

2.5 ANED 43

32 E/S Also pulmonary chondromaand mediastinal

paraganglioma

9 ANED 11

33 Diagnosed as GANT 9.0 ANED, recurrence, with LNinvolvement at 3 and 5 yr

22

34 S Features of GANT, Alsoretroperitoneal

paraganglioma

0.7 ANED 49, 52

35 + Survivor of a neuroblastomaat the age of 5 mo

1.1 ANED 21

36 E Also retroperitonealparaganglioma

6

37 E 4838 Also 3 para-aortic

paragangliomas6

LC, lesser curvature; GC, greater curvature; mets, metastases; rec, recurrence; ANED, alive with no evidence of disease; AWD, alive with disease; DOD, dead of disease.

*Patient has received imatinib mesylate for treatment. In some cases, age has been rounded to the closest year.



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categories with high mitotic rate, large tumor size, or both.However, 3 of 13 patients with gastric GISTs with favorableparameters associated with only 2% to 3% mortality in gastricGIST patients in general40 developed metastasis (Table 3).

This may suggest that GISTs in young age are somewhat un-predictable and may behave more aggressively than those inadults, as the comparison with our collective data on gastricGISTs shows.

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TABLE 3. Prognosis of 30 GISTs in Children and YoungAdults by Prognostic Groups in Comparison With 1055Gastric GIST Patients

Patients WithMetastases of All in the Group (%)

Prognostic Group

and Definition

Children and

Young Adults

All Gastric

GIST Patients2 (#5 cm, #5/50 HPF) 1/6 (17%) 6/320 (2%)

3A (5 # 10 cm, #5/50 HPF) 2/7 (28%) 8/229 (3%)

3B (.10 cm, #5/50 HPF) 1/2 (50%) 17/140 (12%)

5 (.2 # 5 cm, .5/50 HPF) 1/7 (14%) 16/99 (16%)

6A (.5 # 10 cm, .5/50 HPF) 3/5 (60%) 52/96 (54%)

6B (.10 cm, .5/50 HPF) 2/3 (67%) 89/108 (82%)

Note: Only cases with follow-up and defined tumor size are included.



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