Small Intestinal Neoplasms in Pediatrics

I. Overview

This review summarizes epidemiology, clinicopathologic features, diagnosis, staging, management, and prognosis of primary small intestinal neoplasms in children. Primary tumors of the small intestine are uncommon in pediatrics; lymphoid malignancies predominate among malignant lesions, while benign neoplasms and congenital lesions may also present in childhood.

II. Classification and Relative Frequency

Malignant: lymphomas (predominant in children, especially non‑Hodgkin B‑cell and Burkitt lymphoma), adenocarcinoma (very rare), intestinal T‑cell lymphoma (rare), neuroendocrine tumors, sarcomas including GIST (rare in children).
Benign: hamartomatous polyps (Peutz‑Jeghers), juvenile polyps, adenomas, lipomas, leiomyomas, vascular malformations, duplication cysts.

III. Adenocarcinoma of the Small Intestine

A. Epidemiology and Risk Factors

Very rare in children.
Predisposing conditions: familial adenomatous polyposis (FAP), Peutz‑Jeghers syndrome (PJS), chronic Crohn disease of small intestine, other polyposis syndromes.

B. Anatomic Distribution and Presentation

Most common site: duodenum in general; ileal predominance in Crohn disease.
Symptoms often vague: abdominal pain, nausea, weight loss; late features: GI bleeding, small‑bowel obstruction.

C. Diagnosis and Staging

Cross‑sectional imaging (CT enterography, MR enterography), endoscopy (push enteroscopy, capsule, deep enteroscopy) for localization and biopsy; surgical sampling if needed.
Tissue diagnosis required; staging adapted from adult TNM paradigms; pediatric oncology input recommended.

D. Management and Prognosis

Surgical resection with negative margins and lymphadenectomy is primary therapy.
Adjuvant therapies individualized; prognosis depends on stage and resectability.

IV. Small Intestinal Lymphomas

A. Epidemiology and Subtypes

Most common malignant small intestinal tumor in childhood; non‑Hodgkin B‑cell lymphomas predominate (~75%).
Primary GI lymphoma is the most frequent extranodal lymphoma presentation.
Male predominance (approx. 2:1).

B. Burkitt Lymphoma

Represents a large fraction of intestinal NHL in children; male:female ratio high (reported up to 7:1).
WHO variants: endemic (EBV‑associated), sporadic, immunodeficiency‑associated.
Genetic hallmark: t(8;14)(q24;q32) (MYC‑IgH) in >95%.
Presentation: distal ileum/ileocecal mass, intussusception, obstruction, bleeding; rapid onset and proliferation.
Diagnosis: imaging (CT/MR), endoscopy/surgical biopsy; immunophenotype and cytogenetics critical.
Treatment: urgent, intensive multiagent chemotherapy; high cure rates with prompt therapy; risk of tumor lysis syndrome.

C. Other Lymphomas

Diffuse large B‑cell lymphoma (DLBCL) — aggressive, may require combined modality therapy.
MALT / immunoproliferative small intestinal disease — regional, endemic in Mediterranean/Middle East; may respond to antibiotics in early stages; advanced disease treated with surgery and chemotherapy.
Enteropathy‑associated T‑cell lymphoma (EATL) — rare in children; associated with celiac disease in adults; poor prognosis.

V. Mesenchymal Tumors

A. Gastrointestinal Stromal Tumors (GISTs)

Approximately 1.4%–2.7% of all GISTs occur in children.
Likely originate from interstitial cells of Cajal (intestinal pacemaker cells).
In adults, >90% of GISTs express KIT (a transmembrane receptor tyrosine kinase); KIT‑negative adult tumors often have activating PDGFRA mutations.
In contrast, only ~15% of pediatric GISTs are KIT‑positive.
~12% of pediatric GISTs associated with germline mutations in succinate dehydrogenase (SDH) subunits.
Familial GIST: germline KIT mutation, multiple gastric and small‑bowel GISTs, skin hyperpigmentation, dysphagia; associated with paragangliomas (GI autonomic nerve tumors).
Carney‑Stratakis syndrome: GISTs and paragangliomas with germline SDH mutations (no KIT/PDGFRA mutation).
Carney triad: GIST + paraganglioma + pulmonary chondroma (nonhereditary association).
Increased incidence with neurofibromatosis type 1 (NF1); in NF1 pediatric patients, small bowel is a common site (>70%).
Sites: stomach (50%–70%), small intestine (20%–30%; common in NF1), colon/rectum (10%), esophagus (5%).
Presentation: often asymptomatic early; later abdominal mass, GI bleeding, obstruction; chronic anemia is a common pediatric symptom.
Treatment: complete en bloc surgical resection including pseudocapsule is primary. Imatinib (tyrosine kinase inhibitor) effective for KIT/PDGFRA mutant tumors; pediatric response variable depending on mutation/SDH status.
Course: recurrent disease common; long‑term surveillance required.

VI. Smooth Muscle Tumors

A. Intestinal Leiomyomas

Rare benign smooth muscle tumors in the GI tract; more common in proximal gut (esophagus, stomach) than small intestine or colon.
Reported increased incidence in children with HIV and posttransplant immunosuppression.
Presentation: may be incidental or cause obstruction, bleeding, or intussusception.

B. Intestinal Leiomyosarcomas

Rare in children (~0.3% of neoplasms in <15 years); nearly 50% occur in infancy in some series.
Arise from muscularis propria; slight female predominance; slight distal small intestine preference.
Presentation: GI bleeding, obstruction, intussusception, perforation.
Metastatic disease is uncommon in children; prognosis relatively favorable with complete resection.

VII. Neural Tumors

Include benign ganglioneuromas, schwannomas, neurofibromas, granular cell tumors, and malignant peripheral nerve sheath tumors (rare).
Intestinal ganglioneuroma:
- Benign proliferation of ganglion cells and glial elements; can be sessile or pedunculated polyps, occur anywhere in GI tract.
- Solitary lesions often incidental; multiple/diffuse ganglioneuromas associated with syndromes: multiple endocrine neoplasia type 2B (MEN2B), juvenile polyposis syndrome (JPS), Cowden syndrome, neurofibromatosis type 1 (NF1), familial ganglioneuromatosis.
Intestinal neurofibromas:
- Proliferation of bland spindle cells with collagenous stroma; plexiform or multiple lesions suggest underlying NF1.
Intestinal schwannomas:
- Very rare in children; present with mass effect, bleeding, or obstruction.

VIII. Vascular Tumors

A. Benign Hemangiomas and Vascular Malformations

Rare within the small intestine; cutaneous hemangiomas may be associated with syndromes (blue rubber bleb nevus syndrome, hereditary hemorrhagic telangiectasia).
Can act as lead points for intussusception.
Symptoms: GI bleeding, pain from intussusception.

B. Benign Lymphangiomas

Often located in mesenteric soft tissue; present with intestinal obstruction or intussusception.

C. Multifocal Lymphangioendotheliomatosis with Thrombocytopenia

Congenital, benign lesions with multifocal cutaneous and visceral vascular lesions; histology shows dilated thin‑walled vessels and hobnail endothelial cells; GLUT‑1 negative.
Frequent GI involvement (stomach and small intestine) causing bleeding that can be difficult to control.

D. Malignant Vascular Tumors

Angiosarcoma and Kaposi sarcoma are very rare in childhood.
Kaposi sarcoma in pediatric intestine associated with immunosuppression and EBV infection in some cases.

IX. Lipomas

Benign submucosal or serosal adipose tumors; common small bowel locations include ileum and duodenum.
Present with intestinal obstruction, intussusception, or GI bleeding when symptomatic.
CT imaging typically shows low‑attenuation lesion consistent with fat.

X. Secretory (Neuroendocrine) Tumors

A. Carcinoid Tumors / Neuroendocrine Tumors (NETs)

Arise from enterochromaffin (amine precursor uptake and decarboxylation) cells throughout the GI tract; in children, GI tract is most common site.
Appendix is the most frequent pediatric site, followed by stomach, small intestine, and rectum.
Classification by location: foregut, midgut (appendix and small intestine; midgut accounts for many pediatric appendiceal cases), hindgut.
Often incidental at appendectomy; appendiceal carcinoids usually not associated with typical appendicitis symptoms due to distal location.
Symptoms: may be silent or present with obstruction, bleeding, or mass effect; systemic carcinoid syndrome rare in children but possible with large or metastatic tumors.
Carcinoid crisis: severe, potentially life‑threatening release of serotonin, histamine, and catecholamines; more common with foregut tumors and large tumors; rare in children with appendiceal carcinoid. Octreotide is effective for control.
Diagnosis: urinary 5‑hydroxyindoleacetic acid (5‑HIAA) for serotonin‑secreting tumors; imaging with CT/MR and somatostatin receptor imaging (68Ga‑DOTATATE PET) when indicated; histologic confirmation required.
Treatment:
- Appendiceal NET: <1 cm — simple appendectomy usually curative; 1–1.9 cm without mesoappendix involvement — appendectomy may suffice; >2 cm or mesoappendix/serosal involvement — right hemicolectomy often recommended.
- Small intestinal NETs: surgical resection with lymphadenectomy; long‑term surveillance for recurrence/metastasis.

XI. Clinical Presentation — Common Themes

Nonspecific symptoms dominate: abdominal pain, nausea/vomiting, weight loss, GI bleeding, anemia, obstructive symptoms, palpable mass.
Acute presentations: intussusception (particularly with polyps or lymphoma), perforation, hemorrhage, or obstruction.
Chronic features: malabsorption, protein‑losing enteropathy, failure to thrive in children.

XII. Diagnostic Workup

A. Initial evaluation

History including family/personal history of polyposis or cancer predisposition; physical exam; baseline labs (CBC, electrolytes, LFTs, albumin, inflammatory markers).
Consider genetic evaluation when syndromic features or family history present (FAP, PJS, NF1, MEN2B, SDH‑related syndromes).

B. Imaging and endoscopy

Contrast‑enhanced CT abdomen/pelvis, MR enterography, ultrasound for intussusception; PET/functional imaging for NETs or staging lymphoma as appropriate.
Endoscopic modalities: upper endoscopy, colonoscopy with ileoscopy, capsule endoscopy, device‑assisted deep enteroscopy for visualization and biopsy; surgical exploration when endoscopy nondiagnostic or lesion submucosal.

C. Pathology and molecular testing

Histopathology with immunophenotyping, cytogenetics, and molecular testing: MYC translocations for Burkitt, KIT/PDGFRA and SDH testing for GIST, MMR testing and other panels when hereditary cancer syndromes suspected.

XIII. Staging and Multidisciplinary Care

Multidisciplinary teams (surgery, pediatric oncology/hematology, gastroenterology, radiology, pathology, genetics, nutrition) essential for optimal outcomes.
Use tumor‑specific staging: pediatric lymphoma staging (Murphy/St. Jude), TNM for adenocarcinoma, disease‑specific systems for NETs/GISTs; tailor staging to histology.

XIV. Treatment Principles

Surgery — primary modality for localized adenocarcinoma, symptomatic benign lesions, complicated lymphomas/obstructing masses, and resection of NETs/GISTs when feasible.
Chemotherapy — cornerstone for lymphomas (Burkitt, DLBCL) per pediatric protocols; anthracycline‑based regimens for advanced MALT variants and other sarcomas as indicated.
Targeted therapy — imatinib for KIT/PDGFRA mutant GISTs, somatostatin analogs for symptomatic NETs; molecular profiling guides targeted options.
Radiation — limited role in young children; consider selectively for local control in older children or palliation.
Supportive care — nutritional support, transfusions, infection prophylaxis, tumor lysis prevention, psychosocial support.

XV. Prognosis and Outcomes

Outcomes vary by histology and stage. Pediatric lymphomas, especially Burkitt, have favorable outcomes with prompt, intensive therapy. Adenocarcinoma prognosis depends on stage and complete resection. GIST outcomes depend on mutation status and resectability; pediatric GIST biology differs from adults.
Long‑term follow‑up for growth, nutrition, late effects of therapy, and secondary malignancy surveillance is critical.

XVI. Genetic Syndromes and Surveillance

Recognize FAP, PJS, juvenile polyposis, NF1, SDH‑related syndromes, MEN2B, Cowden, and Lynch contexts; institute syndrome‑specific surveillance (e.g., Spigelman staging and upper GI surveillance in FAP).
Genetic counseling and family testing indicated when hereditary syndromes suspected.

XVII. Red Flags and When to Refer

Persistent unexplained abdominal pain, weight loss, GI bleeding, anemia, palpable abdominal mass, recurrent intussusception, obstructive symptoms, or family history of polyposis or early GI cancer — early referral to pediatric subspecialists and oncology/genetics is warranted.

XVIII. Research Directions and Knowledge Gaps

Need pediatric‑specific outcome data, staging guidelines, prospective studies of multimodality therapy, and studies of genomic profiling to guide targeted therapy in pediatric small bowel neoplasms.
Long‑term survivorship research on late effects, growth, nutrition, secondary malignancies, and psychosocial outcomes required.

XIX. Practical Summary and Key Points

Small intestinal tumors are uncommon in children; lymphomas (notably Burkitt) predominate among malignant lesions.
Mesenchymal tumors (GIST) are rare but biologically distinct in children with lower KIT positivity and associations with SDH mutations, Carney syndromes, and NF1.
Diagnosis requires imaging and tissue diagnosis; treatment is tumor‑specific and multidisciplinary.
Pediatric lymphoma outcomes are generally favorable with modern chemotherapy; other tumor prognoses depend on histology, stage, and molecular features.

Pediatric Small Bowel Tumors — Comparison Table

Tumor	Frequency in children	Typical site	Key features / presentation	Management & prognosis
Lymphoma (Non‑Hodgkin, incl. Burkitt)	Most common malignant small intestinal tumor in children	Distal ileum, ileocecal region, cecum, appendix	Rapid abdominal pain, intussusception, mass, obstruction, GI bleeding	Systemic multiagent chemotherapy; surgery for complications; high cure rates for Burkitt with prompt therapy
Adenocarcinoma	Very rare in children	Duodenum generally; ileum in Crohn disease	Vague pain, weight loss, late GI bleeding or obstruction	Surgical resection with lymphadenectomy; adjuvant therapy individualized; prognosis stage‑dependent
Gastrointestinal stromal tumor (GIST)	Rare; ~1.4%–2.7% of GISTs occur in children	Stomach > small intestine; small bowel common in NF1	Often asymptomatic early; later mass, chronic anemia, GI bleeding, obstruction	Complete en bloc resection; imatinib for KIT/PDGFRA mutant disease; recurrent disease common; long‑term surveillance required
MALT / Immunoproliferative SI disease (α‑chain)	Uncommon; regionally endemic in Mediterranean/Middle East	Small intestine (variable)	Malabsorption, protein‑losing enteropathy, weight loss, anemia, clubbing	Early disease may respond to antibiotics; advanced disease requires surgery and chemotherapy
Enteropathy‑associated T‑cell lymphoma (EATL)	Very rare in children	Small intestine	Associated with enteropathy in adults; pain, obstruction; poor prognosis	Chemotherapy ± surgery; prognosis guarded
Diffuse large B‑cell lymphoma (DLBCL)	Uncommon	Any small intestinal segment	Aggressive mass, obstruction, bleeding	Systemic chemotherapy; prognosis variable based on stage and response
Neuroendocrine tumor / Carcinoid	Rare in children	Appendix > stomach > small intestine > rectum	Often incidental; possible obstruction or bleeding; carcinoid syndrome rare	Surgical resection; appendectomy often curative if <1 cm; larger lesions may need hemicolectomy; good prognosis if localized
GIST (familial / SDH‑deficient)	Rare; notable familial or SDH mutations in pediatrics	Stomach and small intestine	Multiple tumors in familial cases; associations with paragangliomas and Carney syndromes	Surgical resection; variable TKI response if KIT/PDGFRA negative; lifelong surveillance recommended
Leiomyoma / Leiomyosarcoma	Very rare	Proximal gut more common; distal small intestine preference for leiomyosarcoma	Bleeding, obstruction, intussusception, perforation	Local surgical resection; leiomyosarcoma prognosis favorable if completely resected
Ganglioneuroma / Neural tumors	Rare	Any GI segment	Polypoid lesions or diffuse involvement; may be incidental or cause obstruction	Local excision for symptomatic lesions; evaluate for syndromic associations
Vascular lesions (hemangioma, lymphangioma)	Rare	Small intestine, mesentery	GI bleeding, intussusception, obstruction; multifocal lesions in syndromes	Surgical resection or interventional therapy for bleeding; supportive care for diffuse disease
Lipoma	Uncommon	Ileum, duodenum	Submucosal fatty lesion causing obstruction, intussusception, or bleeding	Local resection or polypectomy; excellent prognosis

Notes: Table cells present concise single‑line summaries for quick comparison; management and prognosis must be individualized by histology, stage, molecular testing, and multidisciplinary input.