A “one in a million” case of colorectal carcinoma – A case report from a tertiary care centre in Mumbai, India

Abstract

Introduction

Colorectal Carcinoma (CRC) has recently been on the rise among children, bearing a prevalence of 1–2 children/adolescents per million people. Here, we present a rare case of CRC in a 14-year-old male, emphasizing the need for development of better screening techniques to diagnose CRC earlier and with adequate time for intervention.

Case presentation

A 14-year-old male visited our hospital with constipation, intermittent per rectal bleed and dull-aching pain abdomen for 2 months. On per rectal examination, a hard mass was identified, approximately 3 cm above the anal verge. Contrast-enhanced CT (Chest and Abdomen) and MRI Pelvis identified a circumferential thickening in the rectum predominantly involving the anterior rectal wall with effacement of fat planes with the Urinary Bladder without infiltrating it. Colonoscopic biopsy identified Signet Ring Adenocarcinoma. A multi-disciplinary decision was taken to treat him with neoadjuvant chemotherapy and radiotherapy (NACT-RT). MRI Pelvis, post-NACT-RT, showed that the previously- effaced fat plane was now clear and an Abdominoperineal Resection (APR) with permanent end- descending-colostomy was done. Histopathology report of the specimen identified a poorly undifferentiated mucin-secreting adenocarcinoma.

Discussion

At presentation, the patient could have been either planned for extensive surgery or NACT-RT. The choice of NACT-RT was justified in our patient and was advantageous as extensive surgery was prevented.

Conclusion

We implore vigilance in cases of rectal masses due to the rising incidence of CRC among children. We also advocate that there must be no hesitation in subjecting adolescents to Chemotherapy and/or radiotherapy, as the benefits significantly outweigh the risks of with-holding.

Highlights

• •Colorectal carcinoma (CRC) has lately increased to 1–2 children/adolescents per million people.
• •The lack of specificity of symptoms leads to delayed diagnosis in almost 90 % of children.
• •CEA levels are non-specific and suspicion of malignancy must be confirmed with colonoscopic biopsy.

1. Introduction

Colorectal Carcinoma (CRC) is a disease seen among adults, with increasing incidence from the late 40s to the mid-60s [1]. Recently, there has been an increasing incidence among children with studies suggesting a prevalence of 1–2 children/adolescents per million people [2].

Risk factors for the development of CRC lack specificity and include non-modifiable risk factors like race, gender, history of Inflammatory Bowel Disease and previous history of CRC in the family [3]. Modifiable risk factors that may contribute to this rising trend include unhealthy cooking methods (with use of synthetic food dyes, monosodium glutamate, titanium dioxide, etc.), dietary modifications and sedentary lifestyle [4].

Due to the paucity of symptoms or their lack of specificity, the diagnosis of CRC among children is generally delayed in almost 90 % of cases. Thus, most cases – around 81 % - have advanced-stage disease that is inoperable at the time of presentation [5].

Guidelines on investigating CRC recommend Faecal occult blood or Faecal immunochemical DNA examination among adults for screening. The natural history of disease in children does not differ by much. Thus, communities employ similar screening methods for children as well. Of late, there have been multiple studies evaluating the diagnostic accuracy of Faecal Calprotectin for CRC screening but meta-analysis does not recommend it. Colonoscopy appears to be the first line investigating modality employed with concurrent CT or MRI to identify local spread or distant metastasis [6].

Treatment protocols employed include surgical resection with adjuvant chemoradiotherapy or a neoadjuvant setting, followed by resection, depending on the stage of presentation, applying the usual principles of oncological management. While surgical resection, probably even radical, remains the mainstay of treatment, adjuvant chemotherapy must be considered in patients with Stage II disease or above – comprising of 5-Fluorouracil and Folic Acid – using capecitabine, oxaliplatin and irinotecan on a case-to-case basis. The use of radiotherapy is generally limited to post-resection situations but can be considered prior to surgery to make it feasible for surgery [7].

Here, we present a case of CRC in a mid-teen male – a rare disease, considering that the incidence is “One in a million”, formulated as per the SCARE criteria [8].

2. Case presentation

Following the general instructions laid out by the SCARE guidelines, we present to you this case of a 14-year-old male who visited our hospital with chief complaints of constipation and intermittent per rectal bleed for 2 months, associated with non-specific dull aching pain abdomen [8]. On clinical examination, he was vitally stable with a soft abdomen and no signs of obstruction. Local examination of the perianal region showed no abnormality. Bearing a normal anal tone, on per rectal examination, a hard mass at approximately 3 cm above the anal verge with irregular distal borders was identified. There was no blood staining on the tip of the finger at the time of removal.

The patient was diagnosed with subacute bowel obstruction, two months prior to presentation, at a peripheral hospital. He was treated conservatively and was referred to our tertiary care hospital for further evaluation. CEA and CA 19–9 levels at the time were normal. No one in the patient's family had previously been diagnosed with CRC and none of them ever had similar complaints.

Contrast-enhanced CT (Chest and Abdomen) and MRI Pelvis were done, the former being suggestive of a circumferential thickening in the rectum and absent locoregional spread and distant metastasis while the latter suggested a circumferential thickening 3.7 cm above the anal verge extending 5.7 cm above. The lesion had a maximum thickness of 1.8 cm, predominantly involving the anterior wall of the rectum with effacement of fat planes with the Urinary Bladder as shown in Fig. 1. Imaging did not show any evidence of infiltration of the Bladder musculature. The other structures were uninvolved.

Fig. 1.

MRI Pelvis (pre-NACTRT) - The red arrow points out the effacement of fat planes between the lesion and the Urinary Bladder.

A well-targeted colonoscopic biopsy, as shown in Fig. 2, was taken and the histopathological report diagnosed Signet Ring Adenocarcinoma, depicted in Fig. 3. A consensual multi-disciplinary decision was taken to treat him with neoadjuvant chemoradiotherapy (NACRT). The patient received 25 cycles of Neoadjuvant External Beam Radiotherapy lasting for a period of 36 days and Capecitabine for a period of 4 weeks, simultaneously.

Fig. 2.

The black arrow shows the exophytic mass partially occluding the bowel lumen in the anal canal.

Fig. 3.

Histopathological study of the specimen clearly showed signet ring cell type of adenocarcinoma.

Post-NACTRT, after a 4-week period, MRI Pelvis was suggestive of a clear fat plane between the previously-effaced Urinary Bladder and the lesion, as shown in Fig. 4. Consequently, he underwent an Abdominoperineal Resection (APR) with permanent end-descending colostomy. The patient tolerated the procedure well. His post-operative period was uneventful and both the perineal and abdominal wound healed without complication. Histopathology report of the resected specimen diagnosed a poorly undifferentiated mucin-secreting adenocarcinoma with all resected margins being free of tumour involvement. Three out of nine lymph nodes were found to be involved without lymphovascular or perineural invasion. On routine follow-up, the patient has remained asymptomatic, his stoma is healthy and functional and repeat CEA and CA 19–9 levels were normal. Repeat MRI pelvis done in the follow- up period showed no evidence of local recurrence or distant metastasis.

Fig. 4.

MRI pelvis (post-NACTRT) - The red arrow points to the reappearance of free fat planes that were previously effaced between the lesion and the Urinary Bladder.

3. Discussion

A diagnosis of CRC in a mid-teen male appears questionable. As put forth by Tiwari et al., literature on paediatric CRC is limited with no evidence-based literature to identify the incidence of paediatric CRC in the Indian setting. For example, one of the few studies undertaken in Rohtak over an 18-year timeframe, among paediatric patients, found nine cases of Gastrointestinal Carcinoma [1].

As of 2017, as described in the study by Malota et al., there were only 2 cases of non-syndrome- associated cases of CRC in children below the age of 15 years in the world – theirs being the third [9]. In general, CRC in children presents itself as a part of a symptom complex in genetically predisposed patients suffering from any one of Familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), Juvenile polyposis syndrome (JPS), Juvenile hyperplastic polyposis syndrome, Lynch syndrome (hereditary nonpolyposis colorectal cancer (HNPCC)) or Constitutional MMR-deficiency (CMMRD) [7]. While it is important for genomic studies to be added to general screening protocols to identify syndromic disease at an early age, the cost of these tests are a major deterrent to implementation, especially in resource-deficient settings like ours. Our patient was not found to suffer from any of the above hereditary syndromes – making this one in a handful of cases.

In line with existing literature on males being affected with CRC, as stressed upon by Mahajan et al., our patient was of the male gender as well [10]. At the time of presentation common diagnoses like constipation, haemorrhoids or anal fissures were considered. The possibility of polyps was considered, albeit with no suspicion of malignancy as most are juvenile hamartomatous polyps and the vast majority of them are solitary and sporadic as elucidated by Chandel et al. [11] Extensive review of literature further weakens a provisional diagnosis of CRC in this age group.

Per rectal examination, as has been described by Mahajan et al., was helpful in identifying the cause for the patient's symptoms [10]. The suspicion of malignancy was considered in the differential diagnosis, albeit less likely. Tissue diagnosis was obtained by means of colonoscopy. Consensus suggests that approximately 75 % of diseases can be diagnosed on colonoscopic biopsies, as postulated by Nambu et al [12].

Literature review describes CEA, a tumour marker, to be unreliable. Therefore, radiological investigation is preferred over CEA [10]. The poor nature of CEA being used for diagnosis has been emphasised in our study, as our patient's CEA levels were normal.

The role of imaging modalities like CT and MRI hold true for diagnosis of CRC in children, as they would for adults. As put forth by Lee et al., MRI is the recommended modality for pre-operative assessment while planning for surgical resection [13].

Colonoscopic biopsy of the lesion identified Signet Ring Adenocarcinoma. Histopathological study of the resected specimen reported a Poorly Undifferentiated Mucinous Adenocarcinoma. Literature suggests that this is the most common type of CRC seen in children. Studies also suggest that it is more aggressive than the types seen in adults, and less responsive to chemotherapy, either in the neoadjuvant or adjuvant setting [1,5,9,10]. Post-NACTRT, an MRI Pelvis showed that the fat plane was maintained between the lesion and the Urinary Bladder. General consensus suggests that the addition of radiotherapy is needed to not only shrink tumour size but to also improve prognosis post-surgery [14].

Retrospectively, the patient had presented at Stage IIIb. As per recommendations, described by Mathey et al., the patient could have been either planned for extensive surgery with radical resection and anastomosis or NACTRT [7]. Considering the debilitating nature of radical surgery, our decision to subject the patient to neoadjuvant therapy was validated. Although response was minimal, the lesion turned resectable, preventing extensive dissection and resection, which was beneficial for our patient.

4. Conclusion

• •Better screening techniques need to be identified to diagnose CRC in children expeditiously, to prevent morbid surgeries.
• •When required, there must be no hesitation in subjecting adolescents to Chemotherapy and/or radiotherapy, as the benefits significantly outweigh the risks of with-holding.
• •Efforts must be made to identify case specific concurrent chemotherapy and radiotherapy regimen to tackle adolescent CRC due to the failure of existing medication to elicit a favourable response.

Consent

All authors declare that ‘written informed consent’ was obtained from the patient and their legal guardian (father) for publication of this case report and accompanying images. A copy of the written consent is available for review by Editor-in-Chief of this journal on request.

Ethical approval

Ethics Committee approval was obtained prior to submission of this manuscript for publication from the Ethics Committee for the Academic Research and Projects (ECARP) in the Tertiary Care Centre where this study was carried out.

Funding

The authors declare that there was no financial support provided for the conduct of the research and/or preparation of this manuscript by any sponsor(s).

Guarantor

Jayashri Sanjay Pandya.

CRediT authorship contribution statement

Chirantan Suhrid and Sundaresh Prabhakar designed the study, were instrumental in investigating the patient and managing the patient in the pre-operative and post-operative period. They also wrote the protocol and the first draft of the manuscript after thorough review of existing literature. Sagar Ramesh Ambre was one of the main surgeons involved in the surgery and gave valuable inputs about the management of the patient in the pre-operative and post-operative period. Jayashri Sanjay Pandya was one of the main surgeons involved in the surgery and mentored the other authors in their work towards fruition of this paper. Jayashri Sanjay Pandya was in-charge of the patient's overall management and took key decisions that altered the course of the patient's treatment, eventually resulting in his full recovery. All authors read and approved the final manuscript.

Declaration of competing interest

The authors declare that no competing interests exist.