|Year : 2021 | Volume
| Issue : 4 | Page : 763-766
|Sporadic pediatric colorectal carcinoma without known genetic predisposition - Defying the dictum: Learning lesson with review of the literature
Ranjan Agrawal1, Cheena Garg1, Sacheeta Babuta1, Nitesh Mohan1, Arjun Agarwal2
1 Department of Pathology, Rohilkhand Medical College and Hospital, Bareilly, Uttar Pradesh, India
2 Department of Surgical Oncology, Rohilkhand Medical College and Hospital, Bareilly, Uttar Pradesh, India
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|Date of Submission||09-Feb-2021|
|Date of Decision||26-Mar-2021|
|Date of Acceptance||30-Apr-2021|
|Date of Web Publication||20-Oct-2021|
| Abstract|| |
Pediatric colorectal carcinomas are extremely rare with an incidence of nearly 1.3 per million. Diagnosis is usually delayed following a lack of suspicion at this age. Increasing incidence as well as awareness provides an insight into the disease entity. Two cases of childhood colorectal carcinoma, one in an 11 and another in a 19-year-old boy are presented. However, they have been reparted to carry a forarable outcome. Both the cases showed mucin and signet ring cells which indicates an aggressive behavior. The presentation highlights the clinical characteristics and genetic implications in most of the patients. However, both our cases did not show any predisposing or genetic predisposition. These cases are presented to make aware the readers as to how the common dictum can be reversed and adolescents can also be affected by cancer, a disease of the elderly. Early diagnosis can provide a better management and prognosis.
Keywords: Carcinoma, colorectal, genetic, pediatric, signet cells
|How to cite this article:|
Agrawal R, Garg C, Babuta S, Mohan N, Agarwal A. Sporadic pediatric colorectal carcinoma without known genetic predisposition - Defying the dictum: Learning lesson with review of the literature. Indian J Pathol Microbiol 2021;64:763-6
|How to cite this URL:|
Agrawal R, Garg C, Babuta S, Mohan N, Agarwal A. Sporadic pediatric colorectal carcinoma without known genetic predisposition - Defying the dictum: Learning lesson with review of the literature. Indian J Pathol Microbiol [serial online] 2021 [cited 2022 Nov 28];64:763-6. Available from: https://www.ijpmonline.org/text.asp?2021/64/4/763/328546
| Introduction|| |
The usual dictum is that colorectal carcinoma (CRC) occurs in the elderly. Recent reports have challenged this verdict and there is an increasing trend of pediatric onset colorectal cancer (PCRC). Early And timely diagnosis of this entity is difficult especially due to neglect, ignorance, Limited access and also due to a general concept that malignancy is a disease of the elderly leading to presentation in late or advanced stage.
Primary gastrointestinal malignancies constitute approximately 2% of pediatric neoplasms and, of which CRC is the second most common malignancy after primary liver tumors. CRC remains unsuspected in children and majority present in advanced stage. The overall prognosis is poor because of the delay and, advanced stage of diagnosis besides a lack of histological differentiation. Younger patients tend to present with more advanced disease, reflecting different tumor biology., Two cases of PCRC are presented in this publication.
| Case Reports|| |
An 11-year-old boy presented with constipation for 5 months and hematochezia for 3 months. No other significant past or family history was noticed. Laxatives by local practitioners did not provide any relief to his ailment. On examination there was mild pallor only. Ultrasound abdomen showed an irregular non-homogenous circumferential wall thickness in the rectum and sigmoid colon measuring up to 20 mm with luminal narrowing. There were few enlarged para-iliac lymph nodes largest measuring 12 mm.
CECT whole abdomen revealed a well-defined mass lesion in the upper rectum measuring 6 × 4.2 cm. The lesion showed marked heterogenicity with non-enhancement and focal areas of calcification. Anteriorly, the mass abutted both the seminal vesicles and posteriorly the urinary bladder. The walls of rectum and sigmoid colon were thickened. CT scan showed multiple necrotic peripherally enhancing right common iliac and mesorectal lymph nodes, largest measuring 1.8 × 1.4 cm along with few small para-aortic lymph nodes. There was enhancing soft tissue lesion in the presacral space contiguous with the primary mass lesion. Mild ascites was present. However, no obstructive features were noted. Colonoscopy showed an ulcero-proliferative growth about 6-7 cm from the anal verge causing narrowing of the lumen leading to non-negotiation of the scope further. Biopsy of the growth showed mucin secreting poorly differentiated adenocarcinoma [Figure 1]a, [Figure 1]b, [Figure 1]c. Immunohistochemistry showed positivity for Pan CK and CEA markers [Figure 1]d, [Figure 1]e. Lung and abdominal CT survey showed no distant metastasis. The patient underwent surgical intervention. After 1 year of follow-up, no tumor recurrence was noted.
|Figure 1: (a) Microscopic picture showing signet ring cells (H & E × 40). (b) Histopathology showing adenocarcinoma with mucin (H & E × 100). (c) Section showing mucin pools with floating neoplastic cells (H & E × 40). (d) Neoplastic cells stained positive with Pan– Cytokeratin (IHC × 100). (e) CEA positivity (IHC × 100)|
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A 19-year-old boy presented with constipation and bleeding per rectum since 1 year followed by passage of loose stools off and on since 5 months. There was history of tobacco chewing since 5 years. He also complains of pain in the perianal region. There has been a history of rectal nodule 6 months back, details of which were not available.
CECT revealed concentric wall thickening with areas of calcification involving the anal canal and rectum extending from the anal verge to the rectosigmoid junction. There was extensive soft tissue lesion in the presacral space and enlarged mesorectal and left common iliac lymph nodes. MRI showed a mass lesion in mid and lower rectum with extension into anal region along with extramural vascular invasion. Abdomino-perineal resection was performed. The anal sphincter and left colon were also excised. Permanent colostomy was made.
Histopathology showed ulcerated and dysplastic mucosa lined by tall columnar epithelium with focal replacement by sheets of invading neoplastic cells. The cells were signet ring type with presence of extracellular mucin. Stroma showed marked desmoplasia. There was invasion of all the layers with extension into the pericolorectal tissue. Lymphovascular and perineural invasions were present. Twelve of the thirteen lymphnodes isolated showed evidence of metastasis, largest being 1.5 cm. Extranodal extension was present. Mesenteric fat was free of tumor. The pTNM was labelled according to AJCC 8th edition as pT3 N2b stage. Pan CK and CEA immunohistochemical markers were positive. Ten months post-surgery was recurrence free.
| Discussion|| |
CRC is more prevalent in Europe, North America, and Japan. The incidence of rectal cancer in India is lower than that in the western countries ranking at number ten. PCRC is rare, with an incidence of only one in one million. Incidence of PCRC is increasing worldwide. Majority of the patients present in their teens, with the reported peak at 15 years. The youngest reported patient is a 9-month-old female infant. Despite its rarity, CRC is the most common primary solid malignancy of the gastrointestinal tract among children. Liver and lymph node metastasis and in some cases, peritoneal carcinomatosis has also been reported in the literature.,
Young patients with Peutz-Jeghers syndrome, familial juvenile polyposis, hereditary mixed polyposis syndrome, hereditary non-polyposis colon cancer or Lynch syndrome, familial adenomatous polyposis, ulcerative colitis, and Crohn disease are more predisposed to CRC. Both of our patients did not have any past history of colonic or rectal polyps, any other malignancy or a family history of cancer. Predisposing factors may be noted in only 10% of PCRC which is much higher than in adults. Sporadic cases are also known as in both of our patients.
Presentation of CRC is related to its primary site within the large bowel. Tumors involving the cecum and descending colon may become bulky before being symptomatic. Tumors of the rectum and sigmoid colon may be associated with altered consistency of stool, dyschezia, hematochezia, and anemia. Intestinal obstruction is a feature more common in adolescents than in adults. The differential diagnosis with almost similar clinical presentation includes malignant carcinoid tumor, leiomyosarcoma, malignant fibrous histiocytoma, and metastatic tumors from other sites.
There is a clear difference in the disease characteristics between younger and older patients in relation to the stage, grade, tumor location, and survival. PCRC shows a male preponderance (M: F = 2:1). Because of the limited number of cases being reported in the literature, there is controversy about the tumor distribution. In children the CEA levels usually remains normal. Rectal cancers were more common in children than proximal colon cancers with majority presenting in stage III or IV. Delay in diagnosis may be due to lack of access or ignoring symptoms. Segev et al in their study reported that majority of CRC were left sided (83%). Based on this finding they suggested that use of flexible sigmoidoscopy at an early age even in asymptomatics would help in better screening of CRC and help in the early diagnosis. Tumors of rectum and left-sided colon carry a better survival rate probably due to the different embryologic origin of these parts of gut. This difference has implications for both screening modalities including sigmoidoscopy as well as the treatment strategies being practiced.
In adults, CRC usually shows a tubular differentiation. However, in children, mucinous, or signet ring appearance predominate., CRCs are categorized as mucinous adenocarcinomas if more than 50% of the lesion is composed of pools of extracellular mucin that contain malignant cells as acinar structures, layers of tumor cells, or individual tumor cells including signet-ring cells. In mucinous carcinoma, lakes of extracellular mucin are present with floating tumor cells. This mucin absorbs water, swells, and invades the surrounding tissues, helping further spread of the neoplastic cells. Furthermore, mucin interferes with the immunological fight against these malignant cells due to coating by mucopolysaccharides. Signet ring cells lead to early metastasis to the lymph nodes, peritoneal surfaces, and ovaries, further leading to a poor prognosis.
Defective DNA MMR is the genetic or epigenetic defect that leads to hereditary CRC associated with Lynch syndrome and germline mutations in the MMR genes. 17% to 31% of young-onset CRC exhibit defective DNA MMR. These tumors are right sided in origin and carry a better prognosis than CRC with intact DNA MMR. Immunohistochemistry can identify protein products of the MMR genes and help establish mutations in the genes. MSI high/MMR deficient tumors have a better outcome as compared to MSS/MMR proficient tumors. These tumors also do not benefit from adjuvant fluoropyrimidine-based therapy. Consecutively assessment of MSI/MMR status, helps in the prognostication as well as management of patients. A tumor suppressor gene located on chromosome 14 has been proposed to carry an important role in microsatellite stable colonic carcinogenesis. High microsatellite instability (MSI) is one of the most important genetic mutations in PCRC and is due to DNA mismatch repair system. It is the hallmark of early-onset CRC, and Lynch syndrome. Some well-known mutations in DNA mismatch repair genes are MLH1, MSH2, MSH6, and PMS2. On the other hand, mutational inactivation of the adenomatous polyposis coli gene responsible for the FAP is also reported to be higher in adolescents with CRC.
The exact reason for this increased incidence of CRC in young individuals is not clear. Most of these cases are sporadic rather than hereditary. Other risk factors, such as alcohol, smoking red meat, and obesity may also be implicated., Overexpression of epidermal growth factor receptor (EGFR) is likely to play an important role in the oncogenesis and cancer therapy.
Among all the prognostic parameters, tumor stage, intestinal wall invasion, lymph node metastasis, and vascular and perineural invasions are most important. Histological features like well-differentiation presence of peritumoral lymphocytes, tumor budding, TILs, medullary differentiation, and Crohn's-like reaction is predictive of MSI tumors. MSI-H tumors have a better prognosis and survival rate independent of all prognostic factors including tumor stage as compared to MSS tumors. MSI-H CRCs do not respond well to 5-Fluorouracil as a chemotherapeutic agent.
Treatment of choice is complete surgical resection. Adjuvant multi-agent chemotherapy is typically used in advanced stage or high-risk localized diseases. There is Limited role of radiation. Because of a delay in diagnosis many cases may present with luminal obstruction. Complete resection is possible in less than 40% of cases as against 90% in adults. PCRC has a better overall survival despite the fact that majority of them present in later stage maybe since they tolerate treatment better., Morbidity and mortality of these young patients may be improved. The uncommon occurrence of CRC in young adults with no predisposing genetic risk factors demands maintaining a higher search rate especially considering that younger patients present with symptoms of abdominal pain and hematochezia.
| Conclusion|| |
A high index of suspicion, careful clinical and rectal examinations, colonoscopic evaluation and, awareness of an increasing trend of PCRC may lead to early diagnosis with a better survival rate. Early identification may lead to better management and a favorable outcome.
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Conflicts of interest
There are no conflicts of interest.
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MD; FIC Path; MIAC, DHA, Professor & Head, Department of Pathology, Rajshree Medical Research Institute, Bareilly, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
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