|Year : 2021 | Volume
| Issue : 3 | Page : 472-478
Retrospective analysis of histopathological spectrum of premalignant and malignant colorectal lesions
Henisha T Tahiliani, Asha P Purohit, Shashank C Desai, Puja Bhavesh Jarwani
Gujarat Cancer Society Medical College, Hospital & Research Center, Ahmedabad, Gujarat, India
|Date of Submission||29-Apr-2021|
|Date of Decision||19-Jul-2021|
|Date of Acceptance||22-Sep-2021|
|Date of Web Publication||08-Oct-2021|
Puja Bhavesh Jarwani
Assistant Professor, Dept. of Pathology, Gujarat Cancer Society Medical College and Research Center, Opp. D.R.M. Office, Naroda Rd, near Chamunda Bridge, Ahmedabad, Gujarat 380025
Source of Support: None, Conflict of Interest: None
Background: Colorectal cancers (CRCs) arise due to the progression of acquired or hereditary premalignant lesions. Therefore, an early diagnosis is essential to devise suitable preventive strategies against CRC.
Objectives: We aimed at determining the prevalence and pattern of distribution of premalignant and malignant colorectal lesions and to assess their histopathological features.
Materials and Methods: This retrospective study was conducted in the Department of Pathology at the Gujarat Cancer Society Medical College, Hospital and Research Center, a tertiary care hospital in Ahmedabad, Gujarat, India, between August 2018 and July 2020. Patients with malignant or premalignant lesions in the colorectal region who underwent biopsy and surgical resection were included, regardless of their age and sex. They were categorized as premalignant or malignant after the histopathological examination. The clinical history and details related to the age, gender, and anatomical site were obtained from the hospital records. The findings were analyzed using descriptive statistics.
Results: A total of 150 colorectal biopsies and resected specimens with premalignant and malignant lesions were included in the analysis. Of these, 36 (24%) were benign and 114 (76%) were malignant. There were 98 (65.3%) male and 52 (34.7%) female patients in the cohort. There were 34.7% of the patients who were in the sixth decade of life and only 0.7% were in the first decade. The most commonly involved site was the rectum (32.7%). Ulcerative colitis (UC) (63.8%) was the most common premalignant lesion, and adenocarcinoma not otherwise specified (79.8%) was the most common malignant colorectal lesion.
Conclusions: Premalignant and malignant colorectal lesions usually develop in older persons and have a male predilection, with the rectum being the most commonly involved site. UC is the most common premalignant colorectal lesion, and adenocarcinoma is the most common malignant colorectal lesion.
Keywords: Colorectal, malignant, premalignant, colon cancer, rectal cancer
|How to cite this article:|
Tahiliani HT, Purohit AP, Desai SC, Jarwani PB. Retrospective analysis of histopathological spectrum of premalignant and malignant colorectal lesions. Cancer Res Stat Treat 2021;4:472-8
|How to cite this URL:|
Tahiliani HT, Purohit AP, Desai SC, Jarwani PB. Retrospective analysis of histopathological spectrum of premalignant and malignant colorectal lesions. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Dec 9];4:472-8. Available from: https://www.crstonline.com/text.asp?2021/4/3/472/327802
| Introduction|| |
The colorectal region is the site for various malignant and premalignant lesions. Colorectal adenoma is the most frequent premalignant lesion. Other premalignant lesions including chronic inflammatory bowel diseases (IBDs) and hereditary syndromes, such as familial adenomatous polyposis, Peutz − Jeghers syndrome, and juvenile polyposis, involve different sites of the gastrointestinal tract with an overall incidence of <5%. Colorectal cancers (CRCs) arise due to the progression of acquired or hereditary premalignant lesions. Developed countries like North America, Australia, New Zealand, Europe, and Japan have reported a high incidence of colorectal adenocarcinomas. Contrarily, developing countries like India, Africa, and South-Central Asia have reported a lower incidence of colorectal adenocarcinomas. However now the incidence of colorectal adenocarcinoma is consistently increasing due to changes in lifestyle and food habits. Nevertheless, it is the most curable form of carcinoma of the gastrointestinal tract. Histopathology is the gold standard for the diagnosis of colorectal tumors. Hence, an early diagnosis of premalignant and malignant colorectal lesions through histopathological examination can help improve disease management, prognosis, and long-term survival.
This study is focused on the analysis of biopsies and resected specimens to obtain insights into the pathology of CRC. This study was aimed at determining the prevalence and distribution of premalignant and malignant colorectal lesions and to assess their histopathological features.
| Materials and Methods|| |
General study details
This retrospective observational study was conducted in the Department of Pathology of the Gujarat Cancer Society Medical College, Hospital and Research Center, a tertiary care hospital in Ahmedabad, Gujarat, between August 2018 and July 2020. Our sample population included patients from Gujarat and Rajasthan. The study was approved by the Institutional Ethics Committee for biomedical and health research on July 16, 2020 (approval number 186) [Supplementary Appendix 1: Study protocol]. As this was a retrospective study, informed consent from the participants was not required. The study was conducted according to the ethical guidelines outlined in the declaration of Helsinki, Good Clinical Practice guidelines and the Indian Council of Medical Research guidelines. No financial support was obtained for this study.
We included patients with malignant or premalignant lesions in the region from the terminal ileum to the rectum who underwent biopsy and surgical resection of the lesions, regardless of their age and sex. We excluded biopsies and resected specimens of lesions other than premalignant and malignant lesions in the colorectal region. In addition, inadequate biopsies in terms of lack of mucosal glands, presence of only fibrocollagenous tissue, etc., were excluded. We also excluded inadequately preserved specimens with handling artifacts.
The primary aim of the study was to assess the prevalence of premalignant and malignant colorectal lesions and to determine the distribution of various premalignant and malignant lesions according to the age, according to the age, sex, and, and anatomical site. Our secondary aim was to assess the histopathological spectrum of colorectal lesions.
All the biopsies and resected specimens from the colorectal region that underwent histopathological examination were analyzed. The specimens were fixed using 10% formalin. Gross findings were recorded and representative sections were taken from the resected specimens; small biopsies were embedded in paraffin. The sections were positioned in cassettes placed in a fixative, and paraffin tissue blocks were prepared using a tissue processor. Thereafter, 3–4-μm thick sections were cut from the paraffin tissue blocks and stained with hematoxylin and eosin. The diagnosis was established after detailed histopathological examination. Immunohistochemical and special stains were used, whenever required.
Based on the histopathological examination, the colonoscopic biopsies and resected specimens were categorized as premalignant or malignant lesions. Any evidence of dysplasia in the premalignant lesions was noted. The clinical history and details related to the age, sex, and anatomical site were obtained from the patients' case files retrieved from the Medical Record Department.
The following colorectal lesions were considered premalignant:
- IBDs including ulcerative colitis and Crohn's disease
- Colorectal adenomas: benign, premalignant neoplasms comprising dysplastic epithelium. Types: tubular, tubulovillous, and villous adenomas with low-grade dysplasia or high-grade dysplasia
- Serrated colorectal lesions: sessile serrated polyp/sessile serrated lesion and traditional serrated adenoma
- Hereditary syndromes, such as familial adenomatous polyposis, Peutz − Jeghers syndrome, and juvenile polyposis.
For the malignant colorectal tumors: ,
- Histological typing of the tumors was done based on the World Health Organization (WHO) histological classification of tumors of the colon and rectum.
- Grading of the tumors was done according to the four-tier grading system for CRC suggested by the American Joint Committee on Cancer (AJCC).
- TNM staging was done according to the staging system suggested by the AJCC and the International Union against Cancer (UICC).
As this was a retrospective analysis, sample size calculation was not performed and all patients fulfilling the eligibility criteria within the time frame of the study were included. The findings were then analyzed using the descriptive statistical methods such as proportion and ratio. All statistical analyses were performed using the Statistical Package for the Social Sciences (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY, USA: IBM Corp.).
| Results|| |
A total of 10,384 biopsies and resections were performed at our center between August 2018 and July 2020. Of these, 150 (1.4%) biopsies/specimens of premalignant and malignant colorectal lesions were included in the study [Supplementary Appendix 2: [Figure S1]]. Out of the 150 specimens, 83 (55%) were colonoscopic biopsy specimens, and the remaining 67 (45%) were resected specimens. Malignancy was noted in 114 (76%) specimens, whereas the remaining 36 (24%) specimens were benign. The rectum was the most commonly involved site in 49 (32.7%) patients. The most common histology was adenocarcinoma not otherwise specified, as reported in 91 (60.7%) patients [Table 1].
|Table 1: Prevalence and pattern of pattern of distribution of premalignant and malignant colorectal lesions, n (%)|
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The age of the patients varied from 7–85 years. The majority (n = 52, 34.7%) of the patients were in their sixth decade of life; only 1 patient (0.7%) was in the first decade of life [Table 1]. Out of the total 150 patients, 98 were male, comprising 65.3% of the total cases. The male-to-female ratio was 1.9:1.
[Table 1] and [Figure 1] show the various premalignant colorectal lesions. Premalignant lesions were seen in patients of all age groups, ranging from 7–78 years. The lesions commonly occurred in the descending colon (n = 9, 25%), followed by the rectum (n = 7, 19.4%), with a predilection for the left side [Supplementary Appendix 2: [Figure S2]]. They were more common in male (n = 23, 63.9%) than female (n = 13, 36.1%) patients [Supplementary Appendix 2: [Figure S3]].
|Figure 1: (a) Ulcerative colitis (H and E, ×4), (b) Ulcerative colitis (H and E, ×10). (c) Ulcerative colitis (H and E, ×40). (d) Tubular adenoma (H and E, ×10). (e) Tubulovillous adenoma (H and E, ×10). (f) Peutz-Jeghers polyp (H and E, ×10)|
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Ulcerative colitis was the most common premalignant colorectal lesion seen in 23 (63.8%) cases. This occurred most commonly in patients between the ages of 31–40 years. All cases of ulcerative colitis ulcerative colitis showed the presence of cryptitis and crypt abscesses. Out of the total 23 cases, 19 (82.6%) showed no dysplastic changes, 2 (8.7%) had low-grade dysplasia, and in the remaining 2 (8.7%), the status of dysplasia was indefinite, i.e., the changes were too marked to be considered negative but insufficient to be labeled dysplasia.
There were 2 (5.6%) cases of Crohn's colitis. Microscopically, multiple small, non-caseating granulomas were observed in these lesions. The mucosa and submucosa showed lymphocytic infiltrates. In addition, the lesions showed pyloric gland metaplasia, along with preservation of the goblet cell population and maintenance of the architecture of the glands.
There were 9 (25%) cases of tubular adenoma in which microscopically more than 80% of the tumor area showed branching tubules surrounded by the lamina propria. Of these, six cases were of low-grade dysplasia and three were of high-grade dysplasia.
There was 1 (2.8%) case of tubulovillous adenoma. Microscopically, more than 20% of the tumor area had both tubular and villous architecture and showed features of low-grade dysplasia.
There was 1 (2.8%) case of Peutz − Jeghers polyp, which manifested as a polypoidal lesion made up of branching bands of smooth muscles and covered by normal colonic mucosa.
[Table 1] and [Figure 2] show the various malignant colorectal lesions. Malignant lesions were seen in patients aged 22–85 years and majority of the patients were in the sixth decade of life. They showed a male predominance. Out of 114 malignant lesions, 79 (69.3%) were seen in male patients, with a male-to-female ratio of 2.3:1. The site most commonly involved by malignancy was the rectum (n = 42, 36.8%) [Supplementary Appendix 2: [Figure S2] and [Figure S4]].
|Figure 2: (a) Mucinous adenocarcinoma (H and E, ×10). (b) Signet ring cell adenocarcinoma (H and E, ×40). (c) Gastrointestinal stromal tumor (H and E, ×10). (d) Metastatic papillary serous cystadenocarcinoma from ovary (H and E, ×10)|
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The majority of the malignant lesions were adenocarcinomas; adenocarcinoma not otherwise specified was observed in 91 (79.8%) cases. Among these, there were 20 (22%) cases of well-differentiated adenocarcinoma, with well-formed malignant glands extending beyond the mucosa in which some of the glands showed a papillary configuration. The glands were lined by columnar cells, with nuclei showing hyperchromatism, stratification, and mitoses. There were 67 (73.3%) cases of moderately differentiated adenocarcinoma, with malignant tubules and simple/complex/irregular outlines. The lesions showed an absence of nuclear polarity and presence of nuclear pleomorphism. There were 4 (4.5%) cases of poorly differentiated adenocarcinoma, and they displayed <50% well-formed glandular structures. Sheets of tumor cells showed marked variation in the nuclear size, nuclear hyperchromatism, and prominent nucleoli. Very little cytoplasm was visible in these cells.
There were 16 (14%) cases of mucinous adenocarcinoma, with more than 50% of the lesion comprising pools of extracellular mucin-containing clumps, sheets, and individual tumor cells.
There were 3 (2.6%) cases of signet ring cell carcinoma, with groups of tumor cells showing a signet ring component. The signet ring cells had intracellular mucin pushing the nucleus to the periphery, and nuclear molding was also observed. They made up more than 50% of the tumor volume.
There were 2 (1.7%) cases of gastrointestinal stromal tumor (GIST), and both were overtly histologically malignant (high risk) with marked cytologic atypia, necrosis, prominent mitotic activity, and mucosal invasion. They showed strong and diffuse expression of c-KIT and DOG1.
There was 1 (0.9%) case of adenosquamous carcinoma, which showed features of both adenocarcinoma and squamous cell carcinoma.
There was 1 (0.9%) case of metastasis from papillary serous carcinoma of the ovary.
Out of the total 53 cases, majority were Stage IIIB disease (n = 15, 28.3%). There were 11 (20.7%) cases of Stage I disease, 13 (24.5%) cases of Stage IIA disease, 3 (5.7%) cases of Stage IIC disease, 2 (3.8%) cases of Stage IIIA disease, and 9 (17%) cases of Stage IIIC disease.
| Discussion|| |
In the present study, out of 150 colorectal biopsies and resected specimens, 114 (76%) were malignant, whereas the remaining 36 (24%) were benign. The majority of the patients were in the sixth decade of life and were male. The rectum was the most commonly involved site. The patients' ages varied from 7–85 years. There was a clustering of cases (52.7%) in the fifth and sixth decades of life. Our findings correlate well with those of Umana et al. who also reported that the majority of their patients (58.4%) were in the same age group. The most common colorectal lesion that we encountered was adenocarcinoma not otherwise specified in 60.6% of the cases, which is comparable to the findings reported by other similar studies [Table 2].
In our study, the most common premalignant lesion was ulcerative colitis, as has also been reported in a study by Padma et al., while in the studies by Umana et al. and Sheikh et al., the most common premalignant lesion was tubular adenoma [Table 2]. Colorectal adenoma has been reported to be the most frequent premalignant lesion; however, in our hospital, there were more cases of ulcerative colitis. The possible reason for this may be that ours is a tertiary care center, and patients present here with more advanced disease.
In our study, there were two cases each of low-grade and indefinite dysplasia, both of which were associated with ulcerative colitis. The most common morphological subtypes of dysplasia were adenomatous and serrated. In a study by Ullman et al., about 50% patients of ulcerative colitis developed high-grade dysplasia over a period of approximately 32 months. It has been observed that there is an increased risk of malignant transformation in patients with IBD. Colitis-associated cancer is a type of colon cancer that is preceded by clinically detectable IBD, such as Crohn's disease or ulcerative colitis. The risk of dysplasia and subsequent cancer is related to several factors, including the duration and extent of disease along with the nature of the inflammatory response. The risk increases sharply 8–10 years after disease onset. Patients with pancolitis are at a greater risk than those with only left-sided colitis. Patients of Crohn's disease without colonic involvement are not at an increased risk. More severe and active inflammation (characterized by the presence of neutrophils) confers an increased risk.
Adenomas have been less commonly reported in Asia in the past, but the numbers are on the rise along with CRC because of the consumption of low-fiber diet and change in lifestyle. Colorectal adenomas are considered as precursors of colorectal carcinomas. The classic adenoma-carcinoma sequence accounts for up to 80% of sporadic cancers and typically involves mutation in the adenomatous polyposis coli gene early in the neoplastic process. The incidence of CRC can be reduced by regular screening through colonoscopy and removal of polyps, if present. However, it is important to note that the most adenomas do not transform into a malignancy. According to a study done by Lieberman et al., the proportion of adenomas with advanced histology was 1.7% in the 1 − 5 mm group, 6.6% in the 6 − 9 mm group, 30.6% in the > 10 mm group, and 72.1% in the tumor group. Distal location was associated with advanced histology in the 6 − 9 mm group (P = .04) and in the >10-mm group (P = .002). Advanced histology was defined as an adenoma with villous or serrated histology, high-grade dysplasia, or an invasive cancer. There were 10 cases (6.7%) of colorectal adenoma in the present study, 3 of which showed high-grade dysplasia. They were most commonly seen in the sixth decade of life, which was similar to the findings from Sheikh et al.'s study.
CRCs account for 10% of all cancers, and 19,31,590 new cases of CRC were recorded in the year 2020 worldwide. In women, breast, colorectal, and lung cancers account for 43.9% of all cancers, CRC being the second most common malignancy. In men, lung, prostate, and CRCs account for 44.4% of all cancers, with CRC being the third most common malignancy., According to the latest report of the National Cancer Registry Program, Aizawl district in India leads with an age-adjusted incidence rate (AAR) of 15.9 in males and 11.4 in females for CRC. Mizoram has the second highest AAR (males: 12.2 and females: 8.6). Ahmedabad urban has a comparatively lower AAR of 4.8 in males and 2.5 in females. As per the study done by Shetty et al., in India, the incidence of lung, breast, prostate, and CRC is increasing. Also overall, there is a trend suggesting a transition to lifestyle-related cancers such as breast and CRC, while the incidence of infection-related cancers such as cervical and stomach cancers is declining.
The incidence of CRC is consistently increasing in individuals who consume high-calorie, animal-fat-rich food and are less physically active. Smoking and alcohol consumption are considered as risk factors for CRC, whereas healthy lifestyle, regular physical exercise, and eating green leafy vegetables confer protection against CRC. Long-term use of drugs such as non-steroidal anti-inflammatory drugs and estrogen hormone therapy also play a protective role against CRC. CRC commonly affects individuals in the age group of 60–70 years and is less common among those aged <50 years. The incidence is slightly higher among males than females., In the present study also, malignant colorectal lesions were most commonly observed in the sixth decade of life and had a male predilection which correlated well with Sheikh et al.'s  and Sharma and Dekha. The incidence of CRC appears to be increasing among the younger population, as 22.8% patients in our study were aged <40 years, which is comparable to the findings from Chaitanya et al.'s and Umana et al.'s studies in which, 23.6% and 17.1% of the cases of CRC, respectively, occurred in those aged <40 years. Increased consumption of fast food by the Indian youth has now replaced the traditional Indian diet. These foods are rich in carcinogenic compounds such as animal proteins and fats, leading to an increased risk of CRC.
In our study, carcinomas more commonly occurred in the left-sided colon (56.9%) as compared to the right-sided colon (43%); this is also comparable to the findings of Chaitanya et al.'s study in which 61% cases involved the left colon and 38% involved the right colon. The most commonly involved site of the lesion in our study was the rectum (36.8%). Similar findings have been reported in other studies.,,
According to the recent WHO histological classification of tumors of the colon and rectum, tumors are divided into four major categories-epithelial tumors, non-epithelial tumors, secondary tumors and polyps. Epithelial tumors include adenoma, IBD-associated dysplasia, carcinoma, carcinoid, mixed neuroendocrine-adenocarcinoma, and others. Non-epithelial tumors consist of GIST, lipoma, liposarcoma, leiomyoma, leiomyosarcoma, lymphoma, angiosarcoma, Kaposi sarcoma, and malignant melanoma. More than 90% of CRCs are adenocarcinomas that originate from the epithelial cells of the colorectal mucosa. In the present study as well, adenocarcinoma was the most common histology (96.4%) and moderately differentiated adenocarcinoma was the most common type which is comparable to the findings reported by other similar studies. Compared to other studies, fewer cases of poorly differentiated carcinoma were found in the present study [Table 3]. The majority of cases in our study (28.3%) had Stage IIIB disease, whereas in the study by Sharma et al. majority of the cases (38%) had Stage IIA disease which suggests that our patients had more advanced disease, possibly as ours is a tertiary care center.
The present study was based on a small sample population; hence, larger studies with a bigger sample size should be carried out for understanding the exact scenario in our country. Even though oral, breast, and cervical cancers constitute the major cancer burden in India, equal importance should be given to other emerging cancer types such as CRC to ensure early detection through screening.
| Conclusions|| |
Premalignant and malignant colorectal lesions usually develop in those with advanced age and have a male predilection, with the rectum being the most commonly involved site.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| Supplementary Appendixes|| |
Supplementary Appendix 1: Study protocol
Title of the Project: Histopathological spectrum of premalignant and malignant colorectal lesions.
Aims and objectives
- To find out the prevalence of premalignant and malignant colorectal lesions
- To determine the age, gender, anatomical site wise distribution of various premalignant and malignant lesions of colorectum
- To study the histopathological features of colorectal lesions
This will be an observational retrospective study conducted in the Pathology Department of GCSMCH and RC, Ahmedabad during the period from August 2018 to July 2020.
- All the received biopsies and resected specimens from terminal ileum to rectum and diagnosed as having malignant and premalignant lesions.
- Patients of both sexes and all age groups.
- Biopsies and resected specimens of lesions other than premalignant and malignant conditions of colorectal region.
- Inadequate biopsies in terms of no mucosal glands, only fibrocollagenous tissue etc.
- Inadequately preserved specimens with handling artifacts.
| Materials and Methods|| |
- All colonoscopic biopsies and resected specimens received in the department of Pathology, GCSMCH and RC, Ahmedabad will be subjected to histopathological study and data will be analyzed
- All tissues will be fixed in formalin, stained with hematoxylin and eosin and special stains like Periodic Acid Schiff, Reticulin etc., along with immunohistochemistry will be done as and when required.
Written informed consent
Not required as it is an observational retrospective analysis and no drugs/procedures are used on the study participants/patients.
Descriptive statistical analysis will be done using SPSS version 20.
- No extra financial support is required for this study
- There is no ethical issue related to this study.
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- Umana IO, Obasek DE, EkanemVJ. The clinicopathological features of lower gastrointestinal tract endoscopic biopsies in Benin City, Nigeria. Saudi Surg J 2017;5: 9-20.
Case record form (Sample copy)
Supplementary Appendix 2
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]