|Year : 2014 | Volume
| Issue : 4 | Page : 557-559
Colorectal carcinoma up to the second decade of life: An 8-year experience in a tertiary care center
RK Gupta1, S Ali1, P Sakhuja1, D Mukherjee1, AK Agarwal2, AS Puri3
1 Department of Pathology, G B Pant Hospital, New Delhi, India
2 Department of Gastro-Intestinal Surgery, G B Pant Hospital, New Delhi, India
3 Department of Gastro-Enterology, G B Pant Hospital, New Delhi, India
|Date of Web Publication||1-Feb-2016|
Department of Pathology, G B Pant Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Aims And Objectives: To evaluate the demographic pattern, incidence, and histological characteristics of colorectal carcinomas (CRCs) in very young adults diagnosed in the center. Materials And Methods: We retrieved and reviewed slides and data pertaining to all the cases of CRCs and "segregated into decade wise age-groups" from the archives of Department of Pathology. Patients with age ≤20 years diagnosed during the last 8 years (2006–2013) were further evaluated. Results: Totally, 590 cases of CRCs diagnosed over last 8-year period, of which 4.2% (25 cases) presented in the study group (age ≤20 years) with a mean age of 17 years. About 50% of the tumors were either signet ring cell, mucin-secreting or poorly differentiated carcinomas. Four cases occurred in a background of familial adenomatous polyposis (FAP), three of which showed high-grade dysplasia, while in one case, carcinoma-in-situ was diagnosed. In all but two cases, rectum was the site of involvement except FAP cases in which colorectal location was noted. CRCs show a sharp rise in earlier age onset (≤40 years) and an increasing trend was followed in patients between age groups third, fourth, and fifth decades of life over the last 8 years. Conclusion: Colorectal carcinomas show an increasing trend in young age (≤40 years). This change may be attributed to dietary, lifestyle changes, and newer genetic alterations in developing countries. In very young age group (≤20 years), a higher grade and stage at the time of diagnosis and predominantly rectal involvements are the distinct features.
Keywords: Colorectal carcinomas, familial adenomatous polyposis, mucin-secreting, signet ring cell, very young adults
|How to cite this article:|
Gupta R K, Ali S, Sakhuja P, Mukherjee D, Agarwal A K, Puri A S. Colorectal carcinoma up to the second decade of life: An 8-year experience in a tertiary care center. Indian J Cancer 2014;51:557-9
|How to cite this URL:|
Gupta R K, Ali S, Sakhuja P, Mukherjee D, Agarwal A K, Puri A S. Colorectal carcinoma up to the second decade of life: An 8-year experience in a tertiary care center. Indian J Cancer [serial online] 2014 [cited 2020 Jan 24];51:557-9. Available from: http://www.indianjcancer.com/text.asp?2014/51/4/557/175313
| » Introduction|| |
Colorectal carcinoma (CRC) is the third most common cancer both in males and females. It usually occurs after fifth decade of life particularly in western countries. However, recent surge in early age CRCs is described in few studies mainly from developing countries which may be attributed to rampantly changing lifestyle and food habits.,, Approximately 5% of all CRC are due to inherited genetic mutations. Of the remaining 95% of cases, approximately 20% have a positive family history but cannot be categorized to any hereditary CRC syndrome.
An aggressive behavior, high pathological grade, higher stage, and poor prognosis are described in early onset CRCs. Patients usually present with the complaints of bleeding per rectum, altered bowel habit, and weight loss. A high index of suspicion and colonoscopic examination at regular follow-up are the key requirements for early diagnosis of CRCs in these patients. In patients with the above-mentioned symptoms with a family history of CRC, Bethesda guidelines should be strictly followed, and a complete genetic workup done to rule out malignancy. Similarly, in a symptomatic patient with any kind of benign/dysplastic polyp at younger age, a close follow-up is necessary to mandate the earliest detection of malignant changes. In a sporadic case, it takes several steps of different sorts of mutations in oncogenes and tumor suppressor genes for a tumor to develop in due course of time. Environmental factors, mainly the dietary habits are the major contributors to these mutations leading to colorectal carcinogenesis., We undertook this study to evaluate the demographic pattern, incidence, and histological characteristics of CRCs in patients up to the second decade of life, diagnosed in the center.
| » Materials and Methods|| |
We retrieved and reviewed slides and data pertaining to all the cases of CRCs and segregated into age-related decade wise groups [Figure 1]. Patients with age ≤20 years diagnosed over a period of 8 years, from 2006 to 2013, were included in the study [Table 1]. Both biopsy and resected specimens were included in the study. All the slides were reviewed by two pathologists PS and RKG. Cases with diagnostic concurrence were included in this study.
|Figure 1: Graph showing year-wise distribution of the total number of colorectal carcinomas patients diagnosed over a period of 8 years in the department|
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|Table 1: Clinicopathological characteristics of CRC patients presented up to second decade of life|
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| » Results|| |
Totally, 590 cases of CRCs diagnosed in the department in 8-year period, of which 4.2% (25 cases) were belonging to the study group (defined as ≤20 years) [Table 2]. However, approximately 38% of the cases occurred in age ≤40 years. In the study group, lowest age of tumor occurrence was 13 years with a mean age of 17 years. A male to female ratio of 1.8:1 was noted. In 76% (19/25) of the patients, only biopsy was available, while in 24% (6/25) of the patients, resection specimens were received. Most of the patients in which only biopsies were available presented with either unresectable disease or presented with recurrence/metastasis after being resected elsewhere. In about 62% of non-familial adenomatous polyposis (FAP) patients, the tumors were either signet ring cell, mucin-secreting or poorly differentiated carcinomas [Figure 2]. Four cases occurred in a background of FAP, three of which showed high-grade dysplasia, while in one case carcinoma-in-situ was diagnosed. In all but two cases, rectum was the sole site of involvement with concomitant involvement of the colon in 16% (4/25) of the patients. In two patients, tumor was located in the sigmoid colon. In one case, diagnosis of carcinoma-in-situ was given due to the superficial nature of the biopsy. Two operated cases presented at T4 stage, one case for re-exploration after radiotherapy and another with multiple peritoneal nodules. However, one operated patient received neoadjuvant therapy outside. Among FAP patients, one had a family history while in one patient, almost whole gastro-intestinal tract was involved including jejunum, duodenum, and pylorus.
|Figure 2: Photomicrographs showing representative histomorphological features of tumors in the study group; HGD; (a) H and E, ×40, CIS; (b) H and E, ×100, MDA; (c) H and E, ×100, SRCA (d) H and E, ×100, PDA (e) H and E, ×100, and MuSA (f) H and E, ×200|
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| » Discussion|| |
Colorectal carcinomas have been described to occur between fifth and sixth decades of life in most of the literature from the western world. However, recently in few studies mainly from developing countries including India, an early age of onset was shown.,, CRCs in young adults comprise about 5–15% of all the colorectal cancer cases. In this study, 4.2% of the CRC occurred in patients ≤20 years in comparison to 1.48% of the cases shown in 2006–2007 individual registry write-up data of population-based cancer registry, Delhi. Relative CRC risk is defined by genetic predisposition and environmental factors, with age being the most important risk factor for sporadic CRC. However, none of the studies showed any specific factors responsible for the surge in the incidence of early onset CRCs.
Several genetic pathways including chromosomal instability (CIN), microsatellite instability (MSI), CpG island methylator phenotype, and serrated pathway are known to play an important role in the pathogenesis of CRCs. CIN is the most common genetic instability accounts for 60% of the CRCs, while MSI involved in 15–20% of the cases including Lynch syndrome as well as sporadic tumors. Microsatellites are repetitive DNA sequences that are prone to errors during DNA replication if the mismatch repair (MMR) system is defective. MSI occur due to inactivation of various MMR genes including hMLH1, hMSH2, hMSH3, hMSH6, and hPMS2. Tumors involving MSI are more commonly right-sided, show mucinous phenotype with crohn's like reaction and diagnosed at lower pathological stages than CIN cancers. MSI testing should be performed especially in young patients with any of the above-mentioned features for prognostication and genetic counseling. However, at present, MSI testing is not done at our center due to unavailability of resources. In most of the studies, 40 years of age have been taken as a standard for early onset CRCs.,,
In our study, age-wise difference in the biological behavior was noted in the form of tumor location and histomorphological pattern [Table 2]. In patients ≤20 years age, rectum was the significantly most common site of involvement (P < 0.05), while in elder patients, a significant difference was not found in tumor location. Like our study, poor histomorphological characteristics such as mucin-secreting and signet ring cell type have been reported in CRC occurring in younger patients.,,,, Similarly, predominant rectal involvement is described in most of the literature, in early-onset CRC.,,, In this series, most of the patients presented with either unresectable disease or recurrence/metastasis after initial diagnosis at some other centers. In developing countries like India, lack of awareness and limitations of resources are the major constraints in timely diagnosis of early onset CRCs. An optimal panel of investigations including digital rectal examination, sigmoidoscopy/colonoscopy etc., and high index of suspicion instead of age of the patient are some of the necessary measures for early diagnosis and intervention for CRCs in young patients. However, due to other common non-neoplastic diseases such as hemorrhoids, gastrointestinal infections, and inflammatory bowel diseases with similar presentations like per rectal bleeding, altered bowel habits etc., in young patients, a lower diagnostic importance is offered to rule out CRCs. A mucinous/signet ring cell morphology, advanced stage at presentation and lack of high index of suspicion are a few underlying factors for poor prognosis of CRCs in young patients. Among all the CRCs cases diagnosed in our department in the 8 years duration, 38.1% (226/590) occurred in patient's ≤40 years of age which is comparable to earlier studies from the Indian subcontinent.,, Furthermore, an increasing trend of CRC occurrence was noted in patients belonging to age groups third, fourth and fifth decades of life in the last 8 years [Figure 1]. This study itself explains an alarming rise in the early onset CRCs in Indian population. Thus, a detailed study in a large cohort is urgently required to evaluate various genetic/causative factors responsible for a steep rise in early onset CRCs. Since this is a tertiary care center and referral patients from different states are the main bulk exact population-based conclusive epidemiological remarks are not feasible.
To conclude a significant occurrence of CRCs in very young patients is observed over the last decade in this study. These early onset CRCs have poor histological grade/stage and predominantly involve rectum, so they share certain characteristics, and their genetic/molecular associations need to be further studied. It is of utmost importance to recognize their presence to facilitate early diagnosis and avoid misdiagnosis in this age group.
This is a retrospective observational study, and number of cases are few (25 cases). In addition, molecular/genetic markers have not been studied.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]