SDH-proficient spindle-cell pediatric gist with peritoneal and umbilical metastatic deposits: A rare case report

Abstract

Gastrointestinal stromal tumors (GISTs) are rare in children, comprising less than 2% of all GISTs and showing distinct clinical, radiologic, and molecular characteristics compared with adult cases. We present an 11-year-old girl with SDH-proficient spindle-cell pediatric GIST associated with peritoneal and umbilical metastatic deposits. Pediatric GISTs differ significantly from adult GISTs in biology and behavior. This case highlights these differences, emphasizing radiologic–pathologic correlation and the need for multidisciplinary management. Contribution: This case illustrates the rare case of Pediatric GIST, its imaging and pathological findings and its differentiating features from adult GIST.

Graphical abstract

Introduction

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors arising from interstitial cells of Cajal [1]. While they are relatively common in adults, pediatric GISTs are rare, accounting for less than 2% of all cases [1]. In the majority of adult GISTs, activating mutations occur in the KIT or PDGFRA receptor signaling pathways; however, approximately 10%-15% lack these mutations and are termed wild-type GIST which are of 3 types: Pediatric GIST, associated with NF 1 and Sporadic. They tend to metastasize to lymph nodes, peritoneum and liver and are associated with SDH deficiency [2]. Because of overlapping features with infectious or inflammatory diseases like abdominal tuberculosis, diagnosis can be delayed or missed. We report a case of SDH-proficient spindle-cell pediatric GIST in an 11-year-old girl with peritoneal and umbilical metastatic deposits emphasizing radiologic-pathologic correlation.

Case presentation

An 11-year-old female presented with complaints of abdominal pain localized to the umbilicus for 2 months. The pain was intermittent, mild-to-moderate in intensity, and unrelated to food intake. The child also had loss of appetite, constipation, and an evening rise of temperature. She had received antitubercular therapy (ATT) empirically for 6 months elsewhere without symptomatic improvement. There were no significant past surgical history and no known family history of gastrointestinal stromal tumors, neurofibromatosis type 1, Carney triad, Carney-Stratakis syndrome, or other hereditary tumor syndromes.

On examination, a tender infraumbilical swelling measuring approximately 1.5 × 1.5 cm was noted, which was mobile. Mild tenderness and a vague lump were palpable in the right iliac fossa (RIF).

Baseline laboratory investigations were within normal limits, including complete blood count, liver function tests, and renal function tests. Representative reference ranges at our institution were: hemoglobin 11.5-15.5 g/dL, total leukocyte count 4-11 × 10⁹/L, platelet count 150-450 × 10⁹/L, serum creatinine 0.5-1.0 mg/dL, serum bilirubin <1.2 mg/dL, AST 10-40 U/L, and ALT 7-56 U/L.

The child was referred for ultrasound examination (Fig. 1) which revealed an ill-defined heterogeneously hypoechoic lesion measuring approximately 4.7 × 3 cm in the right iliac fossa, showing internal vascularity, and close proximity to the right ovary (Fig. 1A and B).A second heterogeneous hypoechoic nodule measuring ∼1.5 × 1.5 cm was seen in the subcutaneous plane at the umbilical level (Fig. 1C and D). For further characterization of the lesions, Contrast enhanced CT scan of the abdomen was done (Fig. 2) which revealed a relatively well-defined heterogeneously enhancing right iliac fossa lesion in close relation to terminal ileal loop and caecum. The right ovary is visualized separately from the lesion (Fig. 2A and D). Adjacent omentum/mesentery appeared thickened with fat stranding. A soft tissue nodule is noted in the subcutaneous plane at the level of umbilicus showing heterogenous enhancement. (Fig. 2B and C). There was also a small enhancing nodular lesion seen adjacent to the caecum (Fig. 2C). Multiple mesenteric lymph nodes were noted, predominantly along the ileocolic vascular pedicle, with the largest node measuring approximately 10.1 mm in short-axis diameter. Findings were suggestive of a right iliac fossa mass lesion with differential consideration of terminal ileal, cecal or mesenteric origin, associated with mesenteric lymphadenopathy, peritoneal and umbilical metastatic deposits. For further characterization of the mass lesion, contrast enhanced MRI (Fig. 3) was also performed which revealed a heterogeneously enhancing lesion appearing isointense on T2-weighted images and hypointense on T1-weighted images measuring ∼2.63 × 3.94 × 4.5 cm showing diffusion restriction (Fig. 3A and B). The umbilical metastatic deposit also demonstrated postcontrast enhancement (Fig. 3D).

Fig. 1.

Transverse grey-scale ultrasound of the right iliac fossa obtained using a low-frequency convex transducer (A) demonstrates an ill-defined, heterogeneously hypoechoic lesion (black arrow) in close relation to the right ovary (white arrowhead) and lying lateral to the urinary bladder (white arrow). Color Doppler ultrasound using a high-frequency linear transducer (B) shows the lesion to be well defined, hypoechoic, and solid with mild internal vascularity. Transverse grey-scale ultrasound at the level of the umbilicus using a high-frequency linear transducer (C) reveals a heterogeneous hypoechoic nodule (white arrow) in the subcutaneous plane, which on color Doppler (D) demonstrates mild internal vascularity.

Fig. 2.

Contrast enhanced axial CT scan of lower abdomen shows (A) The right iliac fossa mass (white arrow) appears heterodense with heterogeneous postcontrast enhancement. (B) The subcutaneous umbilical lesion (white arrow) also demonstrates heterodensity with heterogeneous enhancement. (C) A tiny enhancing subserosal metastatic deposit is seen along the caecum (white arrow), and the enhancing umbilical metastatic deposit is also visualized (white arrowhead) and (D) The right iliac fossa lesion (white arrowhead) is seen separately from the right ovary (white arrow) with maintained fat planes.

Fig. 3.

Axial MRI images of the lower abdomen. (A) Diffusion-weighted image (b = 1000 s/mm²) demonstrates hyperintense signal within the right iliac fossa lesion (yellow arrow). (B) Corresponding ADC map shows hypointensity within the lesion (yellow arrow), confirming true diffusion restriction. (C) Postcontrast T1-weighted image demonstrates heterogeneous enhancement of the lesion (white arrow) and (D) The metastatic umbilical deposit also shows heterogeneous postcontrast enhancement (white arrow).

Although the precise site of origin could not be established with certainty on imaging, an ileal or cecal or mesenteric origin was considered most likely.

For staging, contrast-enhanced CT of the thorax demonstrated no evidence of pulmonary metastasis or other significant thoracic abnormality. No hepatic metastases were identified.

Histopathological findings

Ultrasound-guided biopsies were taken from the primary lesion and the umbilical lesions. Microscopy showed diffuse sheets and focal fascicles of spindle-shaped tumor cells with oval to elongated nuclei, vesicular chromatin, and scant cytoplasm in a myofibrillary background (Fig. 4). Numerous ecstatic vessels with perivascular hyalinization were present. Mitoses were low (0-1/10 HPF), and no necrosis was seen [2]. These findings favored a spindle-cell neoplasm of benign to intermediate morphology.

Fig. 4.

(A) Linear cores of spindle cell neoplasm with varying cellularity (H&E, 40X). (B) Tumor cells are arranged in fascicles and diffuse sheets (H&E, 100X) and (C)Tumor cells are spindle-shaped with an elongated nucleus (H&E, 200X). The cells are mildly pleomorphic with vesicular chromatin and abundant eosinophilic cytoplasm (H&E, 400X).

Immunohistochemistry showed strong positivity for DOG1 and CD34 with positivity for CD117. S-100 and SOX-10 were negative. SDHB expression was retained, indicating an SDH-proficient gastrointestinal stromal tumor. Ki-67 proliferation index was low (6%-8%) (Fig 5).

Fig. 5.

Immunohistochemical evaluation demonstrating positivity for CD117 (A), DOG1 (B), and CD34 (C), supporting the diagnosis of gastrointestinal stromal tumor. The Ki-67 proliferation index was approximately 6%-8% (D).

Final Diagnosis was SDH-proficient spindle-cell gastrointestinal stromal tumor (GIST) with peritoneal and umbilical metastatic deposits.

Following diagnosis, the patient underwent open transperitoneal excision of the mesenteric mass along with excision of the umbilical deposit at a tertiary referral center. Molecular testing for KIT, PDGFRA, BRAF, NF1, NTRK, and SDH-complex gene mutations was not performed due to financial constraints. Following surgery, the patient was commenced on adjuvant imatinib therapy (400 mg once daily) and remains under regular clinical follow-up.

Discussion

Pediatric GISTs differ substantially from adult GISTs in clinical behavior, molecular profile, and biological characteristics. A strong female predominance (≈70%) has been observed [3]. Clinical symptoms vary but commonly include abdominal pain, anorexia, constipation, vomiting, or gastrointestinal bleeding. Because of nonspecific symptoms, children are often misdiagnosed with acute or chronic abdominal conditions, whereas up to 30% of adults remain asymptomatic.

Ultrasound is typically the first-line modality, followed by contrast-enhanced CT for characterization, assessment of origin, involvement of adjacent structures, and detection of metastases. GISTs usually appear as well-circumscribed enhancing soft-tissue masses, sometimes with necrosis, hemorrhage, fat components, or calcification. CT is recommended by the European Society for Medical Oncology (ESMO), although MRI is preferable when available due to superior soft-tissue resolution and the absence of ionizing radiation.

Histopathology provides the definitive diagnosis. In pediatric GISTs, epithelioid or mixed patterns are more common; spindle-cell morphology, as seen in our case, is rare [4]. Unlike adults—where 80% express KIT or PDGFRA mutations—pediatric GISTs frequently lack these mutations and may exhibit SDH deficiency [5]. However, SDHB retention in our case indicates an SDH-proficient tumor, which is even less common.

Based on the available clinicopathological findings, the tumor was categorized as high-risk/metastatic GIST. Risk stratification parameters are summarized in Table 1.

Table 1.

Risk stratification of the present case.

Parameter	Finding
Primary site	Ileal/mesenteric
Tumor size	4.5 cm
Mitotic rate	0-1/10 HPF
Tumor rupture	Not identified
Peritoneal deposits	Present
Umbilical deposit	Present
Metastatic status	Present (peritoneal and umbilical metastases)
Risk category	Metastatic GIST

The presence of peritoneal and umbilical metastatic deposits at diagnosis classified the lesion as metastatic disease despite the relatively low mitotic activity.

The presence of an umbilical metastatic deposit in the present case is particularly unusual. Umbilical involvement may occur secondary to peritoneal dissemination with extension along embryological remnants, lymphatic spread, or direct implantation of tumor cells. Although umbilical metastases (Sister Mary Joseph-type nodules) are well recognized in gastrointestinal malignancies, they have rarely been described in pediatric GIST, making this an uncommon manifestation of disease spread.

The present case is noteworthy for several reasons. Compared with typical pediatric GISTs, which are usually gastric in location, epithelioid or mixed in morphology, and frequently associated with SDH deficiency, the present case demonstrated a spindle-cell phenotype with retained SDHB expression and an unusual pattern of peritoneal and umbilical metastatic dissemination. Furthermore, the lesion arose in the right iliac fossa with imaging findings favoring an ileal or mesenteric origin. The clinical and radiological presentation closely mimicked alternative diagnoses including abdominal tuberculosis, ovarian neoplasm, lymphoma, inflammatory myofibroblastic tumor, desmoid tumor, and soft-tissue sarcoma, resulting in a broad differential diagnosis. This case highlights the value of multimodality imaging in narrowing the site of origin and extent of disease, while emphasizing the indispensable role of histopathological and immunohistochemical evaluation in establishing the diagnosis. Early recognition of such atypical presentations facilitates timely surgical management, appropriate adjuvant therapy, and multidisciplinary follow-up.

Surgical resection remains the primary treatment modality for pediatric GIST. The efficacy of tyrosine kinase inhibitors, particularly imatinib, is influenced by the tumor's molecular characteristics. While KIT- and PDGFRA-mutant tumors generally demonstrate favorable responses, SDH-deficient and other wild-type GISTs often show variable therapeutic benefit. Consequently, molecular characterization is increasingly important for guiding treatment decisions and prognostication.

A limitation of the case report is the absence of comprehensive molecular profiling, including KIT, PDGFRA, BRAF, NF1, NTRK, and SDH-complex gene testing, which could not be performed because of financial constraints.

Author contributions

VY: Drafting of the manuscript; SS: Drafting of the images; PS: Concept and final editing of the manuscript; TP: Final editing of MRI findings; MS: Final editing of biopsy and IHC images.

Patient consent

The authors confirm that written, informed consent for publication of the clinical details and images was obtained from the patient’s parents.