Colonic adenocarcinoma in a pediatric patient: A case report and review of literature

Abstract

BACKGROUND

Colorectal cancer (CRC) is rare in children, though incidence appears to be rising. Some cases are associated with hereditary syndromes and microsatellite instability, both of which involve defects in mismatch repair genes. Diagnosis is frequently delayed due to non-specific symptoms and low clinical suspicion, resulting in advanced-stage disease. Pediatric CRC is often aggressive, with poor outcomes and no routine screening. While the gut microbiota is implicated in adult CRC, its role in pediatric cases remains unclear, warranting further investigation.

CASE SUMMARY

This single-patient case with a matched healthy control for microbiota comparison describes a 14-year-old boy who presented with non-specific symptoms. Examination revealed abdominal tenderness, microcytic anemia, leukocytosis, and elevated inflammatory markers. Imaging showed thickening of the ascending colon, and biopsy confirmed poorly differentiated adenocarcinoma (stage pT3N2b) with lymphovascular invasion, and 13 of 61 lymph nodes were positive for metastasis. He underwent right hemicolectomy. A year later, surveillance colonoscopy revealed a rectal tubular adenoma. Then, he developed anastomosis site recurrence and peritoneal metastasis and underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy with mitomycin. Later, a chest computed tomography scan showed pulmonary nodules, and the patient was treated with additional chemotherapy. In February 2025, a further peritoneal recurrence led to right hydroureteronephrosis. Surgery was delayed at the patient’s request. In June 2025, he presented with bowel obstruction and underwent exploratory laparotomy, venting gastrostomy, and end ileostomy. His code status was subsequently changed to comfort care.

CONCLUSION

Pediatric CRC is aggressive and rare. Integrated genomic and microbiota analyses may enhance understanding and guide future diagnostic strategies.

Key Words: Pediatric; Gut microbiota; Genomics; Early onset colorectal cancer; Case report

Core Tip: This case reports a rare diagnosis of colon cancer in a 14-year-old patient, emphasizing the challenges of delayed diagnosis in pediatric patients due to non-specific symptoms and low clinical suspicion. The report uniquely integrates genomic testing and gut microbiota profiling, revealing potential molecular and microbial contributions to pediatric colorectal cancer pathogenesis. These findings underscore the importance of comprehensive evaluation in early-onset cases and suggest a novel direction for research into the role of the gut microbiota in pediatric malignancies, with implications for diagnosis, prognosis, and management strategies.

INTRODUCTION

Colorectal cancer (CRC) is rare in the pediatric population, accounting for less than 1.0% of all childhood malignancies[1]. Despite its low incidence, recent reports indicate an upward trend in pediatric CRC cases[2-5]. Diagnosis is frequently delayed due to non-specific gastrointestinal symptoms that resemble common benign or infectious conditions, leading to advanced-stage presentation[5]. Clinical suspicion remains low among healthcare providers for this age group. While most CRC cases are sporadic, 10.0%-30.0% are linked to hereditary cancer syndromes[2]. Microsatellites are short tandem repeats of DNA sequences that are scattered throughout the human genome and are highly susceptible to replication errors. The mismatch repair system primarily identifies and corrects these errors, using key proteins such as MLH1, MSH2, MSH6, and PMS2. Accumulation of these errors in the DNA, due to defects in genes coding for these proteins, results in microsatellite instability, which is linked to hereditary cancer predisposition in addition to its clinical significance as a diagnostic and prognostic biomarker in CRC[6].

Pediatric CRCs are often biologically aggressive, with poor prognosis and limited therapeutic options[7]. Further, children are not covered by current CRC screening programs, contributing to late detection[5]. The gut microbiota has emerged as a key player in CRC development[8], though its role is well established only in adults. Pediatric data remain scarce. Here, we report a rare case of colon cancer in a 14-year-old boy, including genomic testing and gut microbiota profiling. A literature review was performed using PubMed and Google Scholar with the terms “pediatric colorectal cancer”, “genomics”, and “microbiota”. This case offers novel insight by integrating genomic and microbiota data and underscores the need for improved awareness and investigation of CRC in younger populations.

CASE PRESENTATION

Chief complaints

A 14-year-old boy presented with progressive abdominal pain for three months, which worsened in the five days before admission, and was associated with nausea, vomiting, and melena[1].

History of present illness

A 14-year-old Saudi male school student from Riyadh (height: 161 cm; weight: 37 kg) presented with a 3-month history of progressive colicky abdominal pain aggravated by eating, with worsening severity in the five days before admission. He experienced persistent nausea, vomiting with any oral intake, and intermittent melena. He had not sought prior medical evaluation, reported no recent weight changes, and had never smoked. Based on a discussion with his mother, the patient’s diet predominantly consisted of junk food and processed meals. Abdominal computed tomography scan showed focal wall thickening in the ascending colon, and colonoscopy with biopsy confirmed adenocarcinoma in June 2022.

History of past illness

The patient reported no significant disorders in his past illness history.

Personal and family history

The patient is the youngest of three siblings, all with unremarkable medical histories. His parents are first cousins. The patient’s father was affected by prostate cancer, and his maternal cousin was affected by breast and ovarian cancer. Figure 1 shows the pedigree for the patient’s family.

Figure 1 Family pedigree of the proband. Black arrow: Our patient (the proband).

Physical examination

At the first visit in June 2022, abdominal examination revealed mild diffuse tenderness without distension. The patient appeared slightly pale and mildly jaundiced.

Laboratory examinations

Initial laboratory tests (performed in June 2022) demonstrated a white blood cell count of 12.5 × 10⁹/L (normal range, 4.0-12.0 × 10⁹/L) with neutrophilia and eosinopenia. Hemoglobin was 8.3 g/dL (normal range, 12.5-15.5 g/dL), with microcytic hypochromic indices and a mean corpuscular volume of 65.5 fL (normal range, 78-98 fL). Platelet count was elevated at 432 × 10⁹/L (normal range, 150-400 × 10⁹/L). Inflammatory markers were significantly elevated: C-reactive protein was 72 mg/L (normal range, about 8 mg/L), erythrocyte sedimentation rate was 114 mm/hour (normal range, 0-15 mm/hour), and procalcitonin was 0.37 ng/mL (normal range, about 0.08 ng/mL). Total bilirubin was elevated at 27 μmol/L (normal range, about 20.5 μmol/L). Renal and liver function tests were within normal ranges.

Molecular examinations

Molecular testing on the primary tumor by immunohistochemistry showed regular expression of MLH1, MSH2, MSH6, and PMS2. Given the early onset of colon cancer and positive family history for tumors, the patient underwent genetic counselling and thorough genetic analysis on genomic DNA extracted from peripheral blood using a comprehensive hereditary cancers next-generation sequencing panel, whole exome sequencing, and whole genome sequencing, respectively. Excluding carriership findings from the whole exome sequencing and whole genome sequencing (Table 1), no clinically relevant variants that explained the early onset of his cancer were identified. Due to disease recurrence, a FoundationOne CDx panel for solid tumors was performed on formalin-fixed paraffin-embedded tissue from the small intestine. Although tumor mutation burden and microsatellite instability status could not be determined from this test, genomic variants in the SMAD4 and SMARCA4 genes were identified (Table 2). However, these alterations have no clinical implications for therapeutic options.

Table 1 Whole exome sequencing and whole genome sequencing carriership findings.

Gene	Variant	Zygosity	Type	Classification1	Implication
DOCKB	NM_203447.3:c.2606-1G>A	Heterozygous	Splicing	Likely pathogenic (class 2)	Hyper IgE syndrome 2 with recurrent infections
HJV	NM_213653.3:c.225dup	Heterozygous	Frameshift	Pathogenic (class 1)	Albinism, oculocutaneous, type IV
SLC45A2	NM_016180.3:c.-492_-489delAATG	Heterozygous	Non-coding	Pathogenic (class 1)	Hemochromatosis, type 2A

¹Based on the American College of Medical Genetics recommendation.

Table 2 FoundationOne CDx panel for solid tumors.

Gene	HGVS variant	Chromosomal position	Variant’s origin	Variant’s type	Variant allele frequency	Clinical actionability
SMAD4	NM_005359.5:c.1512T>A (p.S504R)	chr18:48604690	Somatic	Missense	5.6%	No therapies or clinical trials
SMARCA4	NM_003072.3:c.1943+1G>T (p.?)	chr19:11113836	Somatic	Splice site	6.3%	No therapies or clinical trials

HGVS: Human genome variation society.

MULTIDISCIPLINARY EXPERT CONSULTATION

Fecal microbiota investigation

Fecal sample collection: A fecal sample was collected from the patient prior to bowel preparation, before undergoing index surgery, and before the initiation of chemotherapy. A matched healthy control was recruited for comparative analysis of the gut microbiota profile. Matching was based on key demographic and anthropometric characteristics, including age (healthy control: 16 years; patient with colon cancer: 14 years), sex (both male), and body mass index (healthy control: 15.2 kg/m²; patient with colon cancer: 13.98 kg/m²). Neither the patient with colon cancer nor the healthy control had used antimicrobial agents, probiotics, prebiotics, or laxatives within the three months prior to fecal sample collection.

A fresh fecal sample was self-collected by each participant and transported to the laboratory at King Abdullah International Medical Research Centre in a biohazard transport container with ice (4.0 °C) within two hours of collection. Once received in the laboratory, each fecal sample was gently homogenized, aliquoted into sterile Eppendorf tubes (Catalog No. 3451, Thermo Fisher Scientific Inc., United States), and stored at -80.0 °C until further processing. DNA/RNA shield fecal collection tubes (Catalog No. R1101, Zymo Research, United States) were used to collect fecal samples according to the manufacturer’s instructions. Each collection tube (with a spoon attached to the cap) was pre-filled with DNA/RNA Shield (9.0 mL) to maintain DNA integrity during prolonged storage. Each participant was instructed on how to collect a fecal sample.

Fecal DNA extraction for gut microbiota investigation: Microbial genomic DNA was extracted from the collected fecal samples using the QIAamp^® PowerFecal^® Pro DNA Kit (Cat. No. 51804, Qiagen, Germany) according to the manufacturer’s instructions, then kept at -80 °C until further analysis. The concentration of the purified DNA was measured using Qubit^® 4.0 Fluorometer (Cat. No. Q33238, ThermoFisher Scientific Inc., United States) with Qubit^TM dsDNA HS Assay Kit (Cat. No. Q32851, Thermo Fischer Scientific Inc., United States).

High-throughput 16S ribosomal RNA gene sequencing and library construction: Polymerase chain reaction (PCR) amplification for the 16S rRNA gene was performed using the Rapid Sequencing DNA-16S Barcoding Kit 24 V14 (SQK-16S114.24; Oxford Nanopore Technologies, United Kingdom) and LongAmp Hot Start Taq 2 × Master Mix (Cat. No, M0533, New England Biolabs, United States) according to the manufacturer’s protocol in a reaction volume of 40.0 μL consisting of 10.0 ng of gDNA and 25.0 μL of the LongAmp Hot Start Taq 2 × Master Mix. Nuclease-free water (Cat. No. AM9937, Thermo Fisher Scientific Inc., United States) was used as a negative control, while ZymoBIOMICS^TM microbial community standard (Cat. No. D6300, Zymo Research, United States) was used as a positive control. The PCR profile for the amplification was as follow: Initial denaturation at 95.0 °C for 1 minute, 25.0 cycles of 95.0 °C for 20.0 seconds, 55.0 °C for 30.0 seconds, and 65.0 °C for 2.0 minutes, followed by a final extension at 65.0 °C for 5.0 minutes, using Veriti 96 Well Thermal Cycler (Applied Biosystems, ThermoFisher Scientific Inc., United States) following the manufacturer’s instructions. The PCR amplicons were pooled and quantified using a Qubit^® 4.0 Fluorometer (Cat. No. Q33238, Thermo Fisher Scientific Inc., United States) with the Qubit^TM dsDNA HS Assay Kit (Cat. No. Q32851, Thermo Fisher Scientific Inc., United States). A total of 100.0 ng of DNA was used for library preparation; the resulting library was sequenced on the GridION sequencer (Oxford Nanopore Technologies, United Kingdom) at King Abdullah International Medical Research Centre for approximately 72.0 hours using R10.4.1 flow cells (FLO-MIN114; Oxford Nanopore Technologies, United Kingdom) according to the manufacturer’s instructions. MinKNOW Software Version 24.11.8 (Oxford Nanopore Technologies, United Kingdom) was used for real-time basecalling for sequenced data according to the manufacturer’s specifications.

Bioinformatics analysis of fecal microbiota: Raw FAST5 files produced from sequencing were converted to FASTQ format using Dorado v5.8.6. The resulting FASTQ files were quality-controlled with NanoPlot v1.42 to evaluate read quality, including Phred scores and length distributions. Adapter trimming was done with Porechop_ABI v0.5.0 (default settings), followed by length filtering with SeqKit v2.10.0 to exclude reads shorter than 1300 bp or longer than 1600 bp. Microbial abundance tables were produced using the Emu pipeline v3.5.1 with default parameters, and a pre-built reference database combining the Ribosomal RNA Operon Copy Number Database (rrnDB v5.6) and National Center for Biotechnology Information 16S RefSeq, then analyzed in R Studio using the Phyloseq package v1.50.0. Preprocessing included removal of taxa with abundances < 10, exclusion of mitochondrial and chloroplast reads, and contaminant filtering with the decontam package v1.12 (prevalence method; cutoff = 0.1) based on negative controls. Relative abundances were then calculated for the samples. Positive controls (ZymoBIOMICS^TM microbial community standard) and negative controls (nuclease-free water) were utilized in parallel with the study samples throughout DNA extraction, amplification, and sequencing to monitor contamination and to validate the performance and accuracy of the taxonomic classification pipeline.

Fecal microbiota results: In the patient with colon cancer sample, 286157 sequencing reads were retained after quality curation, yielding 114 observed taxa, a Shannon diversity index of 3.36, and an inverse Simpson index of 13.90. In comparison, the healthy control sample had a lower sequencing depth (31723 reads) and 84 observed taxa. The Shannon index was comparable (3.37), while the inverse Simpson index was slightly higher in the control (16.08). Fecal microbiota sequencing revealed a distinct microbial community signature in the patient (Figure 2). At the phylum level, Fusobacteria (0.6%) were detected only in the patient. Both Firmicutes (91.7%) and Bacteroidetes (4.0%) showed higher relative abundances in the patient than in the control. In contrast, the relative abundance of Proteobacteria (3.6%) was lower in the patient. At the species level, the following bacteria were detected only in the patient: Anaerostipes hadrus (5.6%), Fusicatenibacter saccharivorans (4.9%), Lactobacillus rogosae (4.9%), Anaerobutyricum hallii (2.7%), and Ruminococcus gnavus (2.4%). In addition, several species exhibited higher relative abundance in the patient compared to the control, including Faecalibacterium prausnitzii (31.0%), Blautia luti (8.3%), Gemmiger formicilis (7.3%), Lachnospira eligens (6.5%), Eubacterium rectale (6.4%), and Roseburia hominis (4.7%). Conversely, the patient’s fecal microbiota showed lower relative abundance of Blautia sp. SC05B48 (6.8%), Dysosmobacter welbionis (3.4%), and Lachnospiraceae bacterium GAM79 (2.4%) compared to the healthy control.

Figure 2 Relative abundance of fecal bacterial taxa in a pediatric patient with colon cancer and a matched healthy control. The charts depict the composition of the fecal microbiota at the phylum, genus, and species levels, showing the relative abundance of each taxon in both individuals. Basic metadata for the patient and healthy control are included for comparison. A: Healthy control; B: Patient.

FINAL DIAGNOSIS

In June 2022, the patient was diagnosed with poorly differentiated adenocarcinoma of the ascending colon (signet-ring cell type), pathologic stage pT3N2b, with lymphovascular invasion and 13 of 61 lymph nodes positive for metastasis.

TREATMENT

The patient underwent a right hemicolectomy in July 2022 and received adjuvant chemotherapy (four cycles of oral Capecitabine and Oxaliplatin), which was discontinued due to acute kidney injury and Oxaliplatin induced liver injury, and was kept on Capecitabine only.

OUTCOME AND FOLLOW-UP

A year later, a surveillance colonoscopy identified a rectal tubular adenoma without high-grade dysplasia. At the age of 16, the patient developed anastomosis site recurrence and peritoneal metastasis. He underwent exploratory laparotomy and cytoreductive surgery, including a redo right hemicolectomy and right pelvic peritonectomy with hyperthermic intraperitoneal chemotherapy with mitomycin. The patient was then started on adjuvant chemotherapy (five cycles of 5-fluorouracil, folinic acid and irinotecan). In December 2024, a follow-up chest computed tomography scan revealed suspicious pulmonary nodules. The patient received four cycles of chemotherapy. In February 2025, recurrence was detected again with peritoneal deposits involving the right ureter, resulting in right hydroureteronephrosis. Redo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy was planned, but the patient requested to delay the procedure due to social reasons. In June 2025, the patient presented to the emergency department with generalized abdominal pain, nausea, and vomiting. Imaging showed low-grade small bowel obstruction secondary to peritoneal disease and worsening hydroureteronephrosis. He underwent exploratory laparotomy, venting gastrostomy, and end ileostomy creation. Following this, the patient’s code status was changed to comfort care (Figure 3).

Figure 3 Clinical timeline of a pediatric patient with colon cancer from symptoms onset to current status. Dates are shown in month/year format to clarify the chronological sequence of the patient’s clinical history. XELOX: Oral capecitabine and oxaliplatin; HIPEC: Hyperthermic intraperitoneal chemotherapy.

DISCUSSION

This report presents a unique case of pediatric colon cancer diagnosed at the age of 14 years. The patient initially presented with non-specific symptoms, which contributed to delayed diagnosis and identification of the disease at an advanced stage. A poor prognosis, including recurrence of the disease, marked the clinical course. These findings are consistent with the existing literature, which reports that early-onset CRC is often detected at later stages and tends to exhibit more aggressive behavior than late-onset CRC[9,10].

In agreement with recently published data observing a trend towards an unfavorable prognosis in pediatric patients with microsatellite stable CRC, our patient was found to have a microsatellite stable phenotype in the initial tumor biopsy. The NM_005359.5:c.1512T>A (p.S504R) variant identified in our patient in SMAD4 is a missense variant particularly reported in the Catalog of Somatic Mutations in Cancer database for ovarian, pancreatic, and prostate cancer samples (https://cancer.sanger.ac.uk; accessed on October 27, 2025)[11-13]. SMAD4 is a tumor suppressor gene that codes for a transcription factor (SMAD4 protein), which plays an important role in the transforming growth factor-beta (TGF-β) signaling pathway and several cellular processes, including proliferation, differentiation, apoptosis, and migration[14]. As a core gene involved in the TGF-β signaling pathway, inactivation of SMAD4 compromises TGF-β-mediated epithelial homeostasis, leading to aberrant cellular proliferation, impaired differentiation, and activation of epithelial-to-mesenchymal transition, a key driver of tumor metastasis[15,16]. SMAD4 is altered in 15.3% of 594 patients with colorectal adenocarcinoma in cBioPortal (accessed on December 22, 2025). According to a study by Su et al[17], it is among the seven most commonly mutated genes reported in 15 CRC datasets, with a mutation rate of > 14.0%. SMAD4 expression is a key prognostic factor in CRC, with loss or downregulation associated with advanced disease stage, aggressive tumor behavior, increased metastatic potential, and poorer disease-free and overall survival[18,19]. Moreover, decreased SMAD4 protein expression is observed in 30.0%-40.0% of CRC cases, leading to decreased responsiveness to chemotherapy and an increased risk of tumor metastasis[20-22].

Further, the NM_003072.3:c.1943+1G>T (p.?) variant identified in our patient in SMARCA4 is a splice-site variant specifically reported in the Catalog of Somatic Mutations in Cancer database for lung cancer (https://cancer.sanger.ac.uk; accessed on October 27, 2025)[13,23]. SMARCA4 is considered a tumor suppressor gene that encodes the brahma-related gene 1 protein, a subunit of the SWItch/sucrose non-fermentable chromatin remodeling complex implicated in the regulation of gene expression, DNA repair, and cellular growth. SMARCA4 is altered in 5.5% of 594 patients with colorectal adenocarcinoma in cBioPortal (accessed on December 22, 2025). Mutations in SMARCA4 have been associated with oncogenic roles in various cancers, including CRC[24]. These neoplasms are frequently identified at an advanced stage and demonstrate limited sensitivity to standard cytotoxic chemotherapy and immune checkpoint inhibitor-based therapies, contributing to significantly reduced overall survival. Although recognition of SMARCA4-altered tumors has increased in recent years, the complete landscape of cancers driven by SMARCA4 alterations remains poorly delineated[25]. SMAD4 and SMARCA4 affect different pathways and, therefore, are considered independent from each other in their function. To our knowledge, their general co-occurrence has not been described in the literature as being clinically significant or mutually exclusive.

The global incidence of early-onset CRC is rising at a concerning rate[26]. While established risk factors such as red and processed meat consumption, obesity, inflammatory bowel disease, family history of CRC, and CRC-predisposing genetic variants have been well documented, they do not fully explain the increasing number of cases among younger individuals[27]. Recent research has demonstrated the gut microbiota as a potential contributor to CRC development[27]. Gut microbiota dysbiosis, characterized by a reduction in beneficial microbes and overgrowth of pathobionts, has been implicated in colorectal carcinogenesis. Dysbiosis can subsequently disrupt mucosal immunity, compromise epithelial barrier integrity, and promote chronic inflammation, all of which contribute to tumor initiation and progression[27].

In the present case, analysis of the patient’s fecal microbiota revealed a distinct microbial profile compared with that of a matched healthy control. For instance, Ruminococcus gnavus and Anaerostipes hadrus (A. hadrus) were detected only in the patient (Figure 2). R. gnavus has been reported to produce an inflammatory polysaccharide that may promote mucosal inflammation[28], while A. hadrus may play a detrimental role by metabolizing the anticancer drug 5-fluorouracil, potentially diminishing its efficacy in CRC in adults[29]. In contrast, Blautia spp. SC05B48 and Dysosmobacter welbionis (both observed at lower abundance in our patient) have been associated with protective roles in adults[30,31]. However, it is essential to acknowledge that these are exploratory, preliminary findings based on a single case and a single control and are limited by the lack of statistical testing and insufficient control sampling. Due to the scarcity of gut microbiota data in pediatric CRC, the relevance of these microbial differences in children remains unclear and warrants further investigation.

The association between gut microbiota and pediatric CRC remains insufficiently understood. Early-life exposures, such as maternal metabolic conditions, tobacco exposure, cesarean delivery, formula feeding, and early antibiotic use, are known to shape the gut microbiota and influence immune system development[27,32]. These exposures may contribute to dysbiosis and increase susceptibility to CRC later in life. Additionally, lifestyle factors associated with more recent birth cohorts, including dietary patterns, are known to influence gut microbial composition and function, supporting the hypothesis that microbial disruption may mediate environmental risk in early colorectal tumorigenesis[27,32]. In line with this, during an interview with the patient’s mother, it was reported that the patient’s diet consisted predominantly of processed meat and fast food. This dietary pattern may have contributed to the development of early-onset CRC by negatively influencing the gut microbiota and promoting microbial imbalance early in life. However, it is important to acknowledge that this dietary information was based on retrospective maternal recall, which may be subject to recall bias and lacks the objectivity of validated assessment tools. Furthermore, dietary data were not available for the healthy control, limiting the ability to draw comparative conclusions. As such, the role of diet in this case remains speculative and should be interpreted with caution. Future studies should incorporate standardized dietary assessment methods, such as a food frequency questionnaire, to objectively evaluate diet as a modifiable risk factor in pediatric CRC and its influence on the gut microbiota.

The association between CRC driver mutations and the gut microbiota has been increasingly explored. A recent longitudinal in vivo study investigated this association using an organoid-based orthotopic CRC model, comparing triple-mutant (APC, KRAS, P53; AKP) and quadruple-mutant (APC, KRAS, P53, SMAD4) AKPS mouse models[33]. The authors observed that mice bearing AKPS tumors developed distant metastases, including the lymph nodes, liver, and lungs, within two months, whereas AKP tumor-bearing mice did not develop metastases in the same timeframe[33]. The addition of SMAD4 inactivation appears to promote tumor aggressiveness, potentially due to its role as a key regulator of epithelial-to-mesenchymal transition, an important process in cancer invasion and metastasis. Furthermore, the study reported significant differences in gut microbiota composition between AKP and AKPS mice[33]. While both models showed an increase in the relative abundance of Faecalibacterium and a decrease in Dubosiella, Akkermansia was significantly more enriched in the AKPS group. These findings suggest a potential role for Akkermansia in CRC progression and metastasis, particularly in the context of SMAD4 inactivation[33]. Our patient, who harbored a SMAD4 missense variant, also exhibited aggressive disease and metastasis but did not show higher levels of Akkermansia in the fecal microbiota. This discrepancy may reflect differences between species, host environments, or the influence of other genetic and environmental modifiers[34]. Further, there is a scarcity of published data on gut microbiota composition in pediatric CRC, limiting the ability to make direct comparisons with experimental findings. The lack of age-matched human datasets underscores the need for further investigations to clarify how specific host genetic alterations, such as SMAD4 mutations, shape gut microbial communities in pediatric patients with CRC. More comprehensive, longitudinal studies are warranted to better understand the complex interplay between host genomics and microbiota in this understudied population.

There is growing global concern about the rising incidence of early-onset CRC[35-37]. While hereditary cancer syndromes account for some cases, many remain sporadic and are often diagnosed at advanced stages due to non-specific symptoms. In response to this trend, CRC screening guidelines have recently lowered the recommended starting age from 50 years to 45 years. However, there is increasing recognition that screening programs may need to further adapt to include at-risk children and adolescents[38-40]. Emerging non-invasive diagnostic tools, particularly those leveraging gut microbiota signatures, hold promise for earlier detection in younger populations. Management strategies in young patients generally mirror those for adults, but aggressive, multidisciplinary treatment approaches may be warranted given the often advanced disease stage at diagnosis. Special attention must be given to long-term toxicities, including potential impacts on fertility and development. Further, most clinical trials currently exclude individuals under 18, underscoring a critical gap in evidence-based treatment protocols for pediatric CRC. The present case emphasizes the urgent need to raise awareness among healthcare providers, especially family physicians, to prevent misdiagnosis and delayed recognition. Increased research, enhanced early detection strategies, and tailored treatment approaches are essential to improving outcomes in this vulnerable population.

CONCLUSION

Pediatric CRC remains a rare but increasingly recognized disease with aggressive clinical behavior and delayed diagnosis due to non-specific symptoms and low clinical suspicion. The current case demonstrates the importance of early recognition, comprehensive genomic evaluation, and consideration of the gut microbiota’s role in pediatric CRC pathogenesis. Integration of molecular, microbial, and clinical data may improve understanding and management of early-onset CRC, underscoring the need to promote awareness and expand research in this understudied population.

ACKNOWLEDGEMENTS

The 16S rRNA sequence information was submitted to National Center for Biotechnology Information under the Sequence Read Archive database with BioProject ID PRJNA1327098. All data generated or analyzed during this study are included in this report. Any additional information will be made available from the corresponding author on reasonable request.