Gastrointestinal tumours

Key points

GI tumours very rare

Most common benign: polyps

Most common malignant: Non-Hodgkin Lymphoma 75%, carcinoid 15%, colonic adenocarcinoma 5%, gastric carcinoma 3%

Polyps

Juvenile polyps

Hamartomas

Single, usually left sided

Can have bleep if autoamputates

Can be mistaken for rectal prolapse

Criteria: <4, nil extra intestinal, no relevant family history

Juvenile polyposis syndrome

Familial in 70% - autosomal dominant

Bleeding, anaemia

Growth factor beta mutations - SMAD4 (risk for gastric cancer), BMPR1A, and ENG

20% malignancy by age 34 - colorectal and gastric cancers

Associated with HHT - look for epistaxis, pulmonary AVM

Cardiac (mitral valve prolapse), renal (duplex), gynae (bifid uterus/vagina)

Investigations:

Echo, renal USS

Genetics for patient and family

Management:

MDT + clinical genetics team

Endoscopy surveillance (upper + lower) - starting age 12-15, every 1-2 years (2023 Matsumoto et al Japanese guideline)

Endoscopic polypectomy +/- bowel/gastric resection if multiple - weak evidence

Cowden syndrome

PTEN mutation - autosomal dominant

Polyposis syndrome - hamartomas

Mucocutaneous lesions, palmoplantar keratoses

Papillary Thyroid, endometrium, kidney, breast, colorectal cancers (colon cancer risk is same as general population)

Bannayan-Riley-Ruvalcaba syndrome

PTEN mutation - autosomal dominant

GI polyps - Hamartomas

Macrocephaly, penile lentigines (lipomaspigmentation), multiple lipomas, developmental delay

Peutz-Jeghers syndrome

Polyps - hamartomas

Likely in jejunum

Mucocutaneous pigmentation - lips

STK11/LKB1 mutation - autosomal dominant

Other cancers:

Colorectal

Small bowel

Gastro-oesophageal

Lung

Breast

Gynaecological

Testicular - Sertoli cell and seminoma

Surveillance ESPGHAN 2019 guidleline:

Testicular examination at every clinical assessment

Upper and lower endoscopy starting age 8 or earlier if polyps, then approximately every 3 years (but should be individualised)

Capsule endoscopy and MRE can also be used

Polyps >15mm should be reseceted due to risk of complications such as intussusception

Prophylactic polypectomy does not reduce cancer risk as tumours will often arise de novo

A male with Peutz-Jeghers presenting with abnormal growth spurt/feminisation/gynaecomastia should be urgently investigated for Sertoli cell tumour

Intussusception in Peutz-Jeghers syndrome should have primary laparoscopic/open reduction

Radiological or endoscopic reduction is not appropriate

Intra-op, a full polypectomy of the small bowel incuding intraoperative enteroscopy is recommended

Familial adenomatous polyposis (FAP)

APC mutation 5q21-q22

Attenuated type presents later, fewer than 100 polyps, same cancer risk

Severe subtypes - sparse: 100s polyps, profuse: 1000s polyps

Almost 100% malignancy before age 50

Histology of adenomatous polyps - Villous (greatest risk of dysplasia), tubular or tubulovillous

Can also have:

• Hepatoblastoma

• Ampullary duodenal cancer

• Papillary thyroid cancer

• Central nervous system tumours

• Desmoid tumours

• Can have congenital hypertrophy of retinal pigment epithelium

Surveillance BSG/ACPGBI/UKCGG 2019 guidelines:

Annual colonoscopy starting age 12, every 1-3 years

Annual OGD starting age 25, frequency depending on disease stage

US/Canadian guidelines recommend aFP screening until age 7 for hepatoblastoma, and annual thyroid exam starting age 15

Some centres use NSAIDS to reduce polyp burden

Gardner syndrome (FAP association)

Polyposis syndrome - variant of FAP

Extra colonic tumours - commonly desmoid, papillary thyroid, skull osteoid

Turcot syndrome (FAP association)

Polyposis syndrome - variant of FAP + intracranial neoplasm

Primary gastric tumours in children

Gastrointestinal stromal tumours

Leiomyosarcoma

Adenocarcinoma

Teratoma/germ cell tumour

Lymphoma - treat for H.Pylori

Rhabdomyosarcoma

Hamartoma

Vascular tumours

Adenoma

Gastrointestinal stromal tumours (GIST)

Arise from interstitial cells of Cajal

KIT mutation (exon 11) or PDGFRA tyrosine kinase

Staining for c-kit + smooth muscle actin

Possibly more aggressive in children

Metastasises to Liver

Resect + adjuvant therapy with imatinib if high risk (Tyrosine Kinase Inhibitor)

Ganglioneuroma

Solitary polypoid - arises from submucosa/mucosa - resembles juvenile polyp

Ganglioneuromatosis polyposis is characterised by loose aggregates of mature ganglion cells in the colonic mucosa - similar to FAP

Associated with cutaneous lipomas

Diffuse ganglioneuromatosis is diffuse enlargement of neuronal elements in the submucosal and myenteric plexus - part of MEN2B syndrome

Should resect due to concerns about malignant transformation. Subtotal colectomy has been used

Neurofibroma

Associated with Neurofibromatosis 1

Bleed, obstruction, intussusception, perforation

Carcinoid tumours

Arise from neuroendocrine cells

80% appendix, 20% respiratory + rest of GI tract

<10% metastasise

Found incidentally on 1:200-1000 appendix specimens

Can be functional (more likely if extra-appendiceal) or non-functional

Secrete serotonin ( 5-hydroxytriptomine 5HT), histamine, noradrenaline, dopamine, bradykinin, prostaglandins

Does not often cause appendicitis in children - small tumours may be normal/physiological in children

Appears as yellow bulbous mass at tip of appendix

Histology - round cells, uniform nuclei, forming rosettes around blood vessels

Investigation and management

If appendiceal:

US National Cancer Institute guidelines for Paediatrics -

Appendicectomy only regardless of size, lymph node status and histology - no investigations required in follow up

If Extra-appendiceal:

Resect lesion + lymphadenectomy - Segmental bowel resection if larger than 1.5cm

Explore for synchronous tumours

Good outcomes

Adult guidelines:

If appendiceal, <2cm with no symptoms - no further investigation

If positive margins or >2cm LN involvement -

Urine 5-hydroxyindoleacetic acid, serum chromogranin A, CT + octreotide NM scan

Then proceed to right hemi + LN excision

For unresectable tumours - give octreotide to slow progression

Leiomyosarcoma

Risks - EBV, HIV, immunocompromised, previous retinoblastoma

Most commonly in jejunum + colon

Grow outward from submucosa, not into lumen

Histology - Expression of α smooth muscle actin

-ve for CD117, differentiating it from GIST

Favourable prognosis

Standard scenario

Patient presents with GI polyp(s)

Concerns:

1. Polyp complications - bleeding, intussusception

2. Is it part of a syndrome, are there more?

3. What is the malignancy risk

Family history, examination - perioral or penile pigmentation

Genetics

Upper + lower endoscopy if diagnosis in doubt

If polyp biopsied - Hamartoma or Adenoma

Hamartoma:

Juvenile

Peutz-Jeghers

Cowden

BRR syndrome

Adenoma:

FAP

Gardners

Turcot

Manage as per above

Consider:

Looking for associated tumours

Surveillance schedule

References

Shelton, Julia S, et al. "Gastrointestinal Tumors." Pediatric Surgery NaT, American Pediatric Surgical Association, 2020. Pediatric Surgery Library, www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829678/all/Gastrointestinal_Tumors.

Matsumoto T et al. Clinical Guidelines for Diagnosis and Management of Juvenile Polyposis Syndrome in Children and Adults-Secondary Publication. J Anus Rectum Colon. 2023 Apr 25;7(2):115-125. doi: 10.23922/jarc.2023-002. PMID: 37113581; PMCID: PMC10129355.

Garofola C, Jamal Z, Gross GP. Cowden Disease. [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525984/

Hearle N et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res. 2006 May 15;12(10):3209-15. doi: 10.1158/1078-0432.CCR-06-0083. PMID: 16707622.

Latchford A, Cohen S, Auth M, Scaillon M, Viala J, Daniels R, Talbotec C, Attard T, Durno C, Hyer W. Management of Peutz-Jeghers Syndrome in Children and Adolescents: A Position Paper From the ESPGHAN Polyposis Working Group. J Pediatr Gastroenterol Nutr. 2019 Mar;68(3):442-452. doi: 10.1097/MPG.0000000000002248. PMID: 30585892.

Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, Ilyas M, Kaur A, Lalloo F, Latchford A, Rutter MD, Tomlinson I, Thomas HJW, Hill J; Hereditary CRC guidelines eDelphi consensus group. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut. 2020 Mar;69(3):411-444. doi: 10.1136/gutjnl-2019-319915. Epub 2019 Nov 28. PMID: 31780574; PMC7034349.

Maria Isabel Achatz et al; Cancer Screening Recommendations and Clinical Management of Inherited Gastrointestinal Cancer Syndromes in Childhood. Clin Cancer Res 1 July 2017; 23 (13): e107–e114. https://doi.org/10.1158/1078-0432.CCR-17-0790

PDQ Pediatric Treatment Editorial Board. Pediatric Gastrointestinal Neuroendocrine Tumors Treatment (PDQ®): Health Professional Version. 2024 Jan 3. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–. PMID: 31661208.