Advanced colon cancer coexisting with multiple Osteochondromatosis in a child; coincidence or causality? - A case report

Abstract

Introduction and importance

Childhood colorectal cancers are extremely rare and so is Osteochondromatosis. Both diseases do not have epidemiological records in African countries. The aim of this report is to present a rare coexistence of CRC and multiple enchondromas in a child.

Presentation of case

A case of a 12-year-old boy who presented with a large bowel obstruction secondary to an advanced tumor of the descending colon. He was also diagnosed with multiple osteochondromas affecting legs, arms, ribs, scapula, clavicle and pelvis. No positive family history was recorded. An urgent left hemicolectomy and diverting transverse colostomy was done. The colon can as stage IIIB and the patient received adjuvant chemotherapy. After 8 months of follow up, the colostomy was successfully reversed without any endoscopic signs of tumor growth or distant metastasis.

Clinical discussion

Colorectal cancer in childhood is rare. It may present with aggressive histological subtypes in children as compared to adults. There is little to no reports on the coexistence of colorectal cancer and multiple Osteochondromatosis. Microsatellite instability in DNA tumor is common in Colon Cancer and variety of mutations of EXT-1 and EXT-2 genes goes with Enchondromatosis.

Conclusion

The coexistence of two rare conditions is the remarkable issue in this case report. There are no prior reports in literature. Further genomic sequencing maybe required to better understand this coexistence.

Highlights

• •Late-stage colon cancer is very rare in children.
• •Multiple Osteochondromatosis is uncommon in children.
• •Lynch syndrome and Exostoses show an autosomal dominant pattern of inheritance.
• •Colon Cancer and Exostoses in a same child patient is extremely rare.

1. Introduction

Colorectal cancer (CRC) in the western world is prevalent after the 5th decade of life. In African studies, the disease tends to affect the younger population, is aggressive and has poor prognosis [1]. In Ghana, 42 % of children have access to cancer treatment, and there has been a rise in completion of cancer treatment from 50 % in 2010 to 85 % in 2018 [1]. Although childhood CRC is extremely rare, the incidence is not known due to the scarcity of epidemiological studies [2]. However, some population-based studies reported incidence of 1–2 cases per million. It commonly affects the rectum and transverse colon and adenocarcinoma is the predominant histological type [3]. Most studies on CRC reported few cases of childhood CRC. Yang et al. presented the study with the largest sample size (270) in which most of the pediatric CRC were sporadic in nature [4].

Enchondromatosis is a rare skeletal disorder characterized by multiple benign cartilaginous growths known as enchondromas. These growths may occur on the upper and lower limbs, ribs, skull, spine etc. About 2 % of enchondromas may undergo malignant transformation [5,6]. Various studies have established the estimated prevalence of this condition in children as 1 in 50,000 [6]. Both childhood CRC and enchondromatosis are rare and autosomal dominant. Our search did not reveal any reports of the coexistence of these 2 pathologies in literature. The aim of this report is to present a rare coexistence of CRC and multiple enchondromas in a child.

2. Case summary

A 12-year-old boy was referred to the surgical emergency of Tamale Teaching Hospital with complains of colicky abdominal pain, abdominal distension, vomiting and constipation. He had experience multiple episodes of these symptoms in the past, which resolved spontaneously. There was change in bowel activity. He also had several bony projections on the limbs and trunk. On examination, he looked malnourished and severely dehydrated. He was tachycardic. Abdomen was grossly distended, soft and tympanic with increased bowel sounds. Rectum was empty and no masses palpated. He had multiple bony projections of varied sizes, the largest measuring 9 × 6 cm and the smallest 2 × 2 cm [Fig. 1, Fig. 2].

Fig. 1.

Multiples osteochondromas in the lower limbs.

Fig. 2.

Multiples osteochondromas, A) Ribs. B) Clavicle. C) Scapula. D) Upper Limb.

Abdominal radiographs showed dilated loops of bowel and air fluid levels [Fig. 3B & C]. Skeletal radiographs showed the bony masses were sessile and located in the metaphysis There were also varied bony deformities affecting multiple bony groups except the craniofacial region [Fig. 4, Fig. 5]. The radiological impression was that of Hereditary Multiple Exostosis. Other baseline investigations like full blood count, blood urea and electrolytes were essentially normal. The patient was resuscitated and optimized for an urgent exploratory laparotomy. Laparotomy was performed under general anesthesia with cuffed endotracheal tube. The intraoperative findings were a large bowel obstruction secondary to an advanced constricting tumor in descending colon, about 6 cm to the splenic flexure [Fig. 3A]. There were also multiple mesenteric lymph nodes. There were no peritoneal seedlings or gross metastasis to the liver or spleen.

Fig. 3.

A) Left colon tumor. B) Dilated loops of bowel (plain abdominal X-ray, supine view) and C) air-fluids levels (plain abdominal X-ray, erect view).

Fig. 4.

Lower limbs X-ray, lateral views, showing sessile masses located in the metaphyseal regions.

Fig. 5.

Upper limbs X-ray, PA and lateral views, showing sessile masses located in the metaphyseal regions.

A left hemicolectomy (thus resection of the proximal sigmoid colon, the descending colon and the distal transverse colon) and a diversion transverse colostomy was performed.

The resected colon on histopathology revealed a moderately differentiated adenocarcinoma with free margins. About 27 mesenteric lymph nodes were counted. Hence the tumor was classified as a T4bN1bM0 or stage IIIB neoplastic disease. The immediate postoperative was smooth and uneventful. The orthopedic team performed an excision biopsy of the largest bony mass which showed bony trabecular capped by hyaline cartilage that was covered by a fibrous membrane suggestive of an osteochondroma.

The patient was discharged 10 days after the surgery and followed up at the clinic for adjuvant chemotherapy. The colostomy was reversed after the adjuvant chemotherapy and a follow-up colonoscopy was normal (8 months). The caregivers were counseled on the importance of screening all family members for colorectal cancer but they have not done that due to financial constrictions.

3. Discussion

Given the patient's age (12 years) and absence of a family history, we thought the probability of a left colon tumor was exceedingly improbable. We initially suspected Gardner's syndrome because it is similarly defined by the development of osteomas, particularly craniofacial, as well as desmoids cysts on the skin; however, neither of these were present in the patient. On the contrary, bony lesions (enchondromas/exostosis) were found in almost all bone groups except the craniofacial region. There are a number of syndromes that increase the risk of getting CRC, including familial adenomatous polyposis, Peutz-Jehgers syndrome, and Turcot syndrome, however the absence of colonic polyps in the patient ruled them out. Hereditary nonpolyposis colorectal cancer (HNPCC), often known as Lynch syndrome, is the most commonly associated with pediatric CRC. It is responsible for 2–7 % of all colon cancers and has high penetrance [7]. Lynch syndrome is autosomal dominant and is due to mutation in the DNA mismatch genes [7,8]. The colonic tumors in patients with Lynch syndrome vary in the length of their nucleotide sequences. Lynch syndrome may present with CRC in conjunction with other tumors of the endometrium, ovarian, pancreas, prostate, brain, small bowel etc. Our search however, did not reveal a report describing any variant of Lynch Syndrome associated with enchondromatosis [[6], [7], [8], [9]].

Hereditary Multiple Enchondromatosis (HME) is also inherited in an autosomal dominant fashion. HME is associated with mutations in the EXT-1 and EXT-2 genes. EXT-1 is found on chromosome 8q24.11-q24.13, while EXT-2 is found on chromosome 11p11–12 [[10], [11], [12]]. HME may be associated with varied mutation patterns such as frameshift mutations, missense mutations, nonsense mutations and splice-site mutations [13]. An affected person may inherit the disorder from a parent in some situations. It is frequently linked with both skeletal and extra skeletal problems. Bony deformities and limb shortening was noted in our patient. The malignant transformation of the exostosis is frequently the most dangerous consequence. According to recent research, the risk of malignant transformation of enchondromas is approximately 2 % [5,6]. There was not malignant change in the case under discussion. Several unusual factors should be noted about the patient in this case report; the young age, the existence of non-polypoid colon cancer, the advanced stage of the cancer (stage IIIB), osteochondromas not confined to long bones, and the absence of family history. Studies have shown that the role of periodic screening of first degree relatives cannot be overemphasized. In this study the caregivers were counseled on the importance of screening, even without family history, but are yet to do so due to financial constrictions.

Colorectal cancer in children is rare and histologically more aggressive as compared to adults. Approximately 10 % of children with cancer have a hereditary susceptibility according to literature [4]. To the best of our knowledge, our search did not reveal literature reporting the coexistence of CRC and multiple Osteochondromatosis. Further genomic sequencing may be required to establish whether the coexistence of these two pathologies is a variant of a known syndrome or an entirely unreported mutation in literature.

4. Conclusion

The coexistence of two rare conditions is the remarkable issue in this case report. There are no prior reports in literature. Further genomic sequencing maybe required to better understand this coexistence.

This work has been reported in line with the SCARE 2020 criteria [14].

Abbreviations

CRC

colorectal cancer

LS

Lynch syndrome

HMO

Hereditary Multiple Osteochondromatosis

HNPCC

hereditary nonpolyposis colorectal cancer

EXT gen

exostosis gen

Patient perspective

Throughout the course of his treatment, the parents expressed satisfaction with the care their child received.

Informed consent

Written informed consent was obtained from the patient's parents/legal guardian for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

This specific kind of single case report is exempt from ethical approval in our institution. (School of Medicine, University for Development Studies, Tamale, Ghana) as long as the due consent from the patient's parents/legal guardian has been obtained.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contribution

Ramon Andres Ramírez Calas: Conceptualization, study design, writing of paper, images design, critical revision for intellectual content.

Tania González Millán: Data collection, writing of paper, images design, critical revision for intellectual content.

Sheriff Mohammed: Data collection, study design, writing of paper, critical revision for intellectual content.

German Azahares Leal: Study design, images design, critical revision for intellectual content.

Munira Amadu: Study design, writing a paper, critical revision for intellectual content.

Anwar Sadat Seidu: Study design, writing a paper, critical revision for intellectual content.

Guarantor

Ramon Andres Ramirez Calas is the guarantor of the work and accepts full responsibility.

Research registration number

Orcid ID: 0000-0002-8564-5283

Declaration of competing interest

Ramon Andres Ramírez Calas has no conflict of interest.

Tania González Millán has no conflict of interest.

Sheriff Mohammed has no conflict of interest.

German Azahares Leal has no conflict of interest.

Munira Amadu has no conflict of interest.

Anwar Sadat Seidu has no conflict of interest.