Introduction
Malignant polyps are histologically characterized by the infiltration of invasive carcinoma into the underlying colorectal polyps, predominantly adenomas [1]. The carcinoma in malignant polyps has invaded beyond the muscularis mucosae into the submucosa but does not penetrate the muscularis propria, even if lymph nodes are affected [1]. These polyps are considered as pT1 in the TNM staging system and are high-grade neoplasms, which present a considerable risk for regional lymph node involvement and distant metastasis [1]. The morphological and histopathological characteristics of colorectal adenocarcinomas originating from adenomatous polyps are essential prognostic factors, significantly influencing the anticipated outcomes for patients with such malignancies [1]. Regula et al. [2] revealed that 5.9% of asymptomatic individuals aged ≥ 50 years who underwent a colonoscopy were diagnosed with adenocarcinoma arising from colorectal polyps. In another comprehensive study by Bokemeyer et al. [3], which examined 269,144 individuals who underwent colonoscopy, 7.1% were identified as having advanced adenomas. Additional studies have provided insights into the incidence rates of malignant colorectal polyps following endoscopic removal, estimated to range from 0.2% to 11% [4–7]. The increased implementation of colorectal cancer screening programs has contributed to increased detection and subsequent removal of malignant colorectal polyps, thereby facilitating the identification of individuals with such polyps.
The histopathological characteristics of malignant colorectal polyps, including polyp type, degree of differentiation, depth of invasion, and the presence or absence of lymphatic, venous, or perineural invasion, along with the status of margins involving the distance from invasive foci, are pivotal for assessing the likelihood of residual disease or recurrent carcinoma [8]. These characteristics serve as valuable guides for determining the most suitable strategies for managing and monitoring colorectal cancer [8]. Despite the notable emergence of malignant colorectal polyps in recent years, significant knowledge gaps persist regarding their histopathological characteristics. To address this knowledge deficit, a comprehensive 5-year analysis was performed to examine malignant polyps’ morphological and histological features. Additionally, demographic factors, such as age, sex, and location of occurrence, were investigated to gain insights into the epidemiological aspects of this disease.
Aim
The objective of this study was to characterize the pathological features of malignant polyps and investigate the correlation between the Haggitt level and various parameters.
Material and methods
Study setting
This retrospective study was conducted at Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University.
Patient selection
Patients who underwent colonoscopy followed by polypectomy between January 2018 and December 2022 were investigated. The primary focus was on patients histopathologically diagnosed with adenocarcinomas originating from pedunculated adenomatous polyps.
Inclusion and exclusion criteria
The inclusion criteria required completing histopathological reports confirming adenocarcinoma arising in pedunculated tubular, villous, tubulovillous adenomas, or other adenomatous polyps. Patients with histopathological results inconsistent with adenocarcinoma despite undergoing colonoscopy and polypectomy and those with incomplete documentation of adenocarcinoma originating in adenomatous polyps were excluded from the study.
Pathological evaluation
To ensure the accuracy of the diagnosis, all cases were independently re-evaluated by two experienced gastrointestinal (GI) pathologists using the 5th edition of the WHO Classification of Gastrointestinal and Hepatobiliary Tumors. The conflicting diagnoses were discussed by both GI pathologists to reach a consensus and establish the final diagnosis.
Data collection
Extensive data collection encompassed crucial patient characteristics such as age and sex, as well as pertinent tumor information, including location, histological type, differentiation grade, extent of invasion (Haggitt level), presence or absence of lymphatic space invasion (LSI), venous invasion (VI), perineural invasion (PNI), and details regarding the base or stalk margin of the tumor.
Anatomical classification
Each malignant polyp was assigned an anatomical level of invasion based on the classification system proposed by Haggitt et al. [9]. Level 1 denotes invasive adenocarcinoma confined solely to the polyp head. Level 2 included cases where the invasion extended to the neck of the polyp. Level 3 indicates adenocarcinoma infiltration of the stalk, whereas level 4 corresponds to submucosal invasion at the level of the adjacent intestinal wall.
Results
Patient demographics
Among the 53 patients included in this study, 35 (66.04%) were male and 18 (33.96%) female. The age range of the patients varied considerably, with the youngest participant being 42 years old and the oldest 88 years old. Specifically, 10 (18.87%) patients were aged ≤ 60 years, with most of the cohort comprising 43 patients aged > 60 (81.13%) years. The mean patient age was 66 years, with a standard deviation of 11.30.
Anatomical distribution
Regarding anatomical location, the distribution of colorectal malignant polyps within the study was as follows: 1 (1.89%) case occurred at the anal verge, while 20 (37.74%) cases were identified in the rectum. Similarly, the sigmoid colon accounted for 20 (37.74%) cases, the descending colon for 5 (9.43%) cases, the transverse colon for 4 (7.55%) cases, and the ascending colon for 3 (5.66%) cases. Table I provides a detailed representation of the distribution of adenocarcinomas arising from adenomas across different anatomical sites and sexes.
Table I
Distribution of different anatomical sites for adenocarcinoma arising in adenoma
Polyp sizes
According to the polyp sizes in this study, 15 (28.30%) polyps were found to have a diameter of ≤ 1 cm. In contrast, 28 (52.83%) polyps fell within the range of 1.1 to 3 cm in diameter. Furthermore, 7 (13.21%) polyps measured between 3.1 and 5 cm, whereas 3 (5.66%) exceeded 5 cm in size. The distribution of these polyp sizes and their correlation with the adenomatous background are outlined in Table II.
Table II
Relative frequency between the background of a malignant polyp and its size
Histopathological characteristics
All identified cases of colorectal polyp-associated carcinomas were adenocarcinomas. Further analysis revealed that 33 adenocarcinomas had originated from tubular adenomas, four from villous adenomas, 15 from tubulovillous adenomas, and one from a traditional serrated adenoma, representing the less common polyp type reported as “other” in the study findings. The distribution of malignant polyps relative to the site is shown in Table III. Additionally, the study observations revealed that among the 53 cases examined, 48 (90.57%) of the adenocarcinomas were well differentiated, while 4 (7.55%) exhibited moderate differentiation. Only 1 (1.89%) case showed poor differentiation.
Table III
Distribution of malignant polyps in relation to the site
Tumor invasion and margins
The depth of tumor invasion was classified according to the Haggitt level, and the findings of this study indicated that 17 (32.08%) cases were categorized as having Haggitt level 0. Eight (15.09%) cases were classified as Haggitt level 1, 5 (9.43%) cases as Haggitt level 2, 15 (28.30%) cases as Haggitt level 3, and the remaining 8 (15.09%) cases as Haggitt level 4. Furthermore, 44 (83.02%) displayed no evidence of LSI among the total cases examined, whereas LSI was observed in 9 (16.98%) cases. Similarly, 49 (92.45%) cases exhibited no VI, whereas it was present in 4 (7.55%) cases. Likewise, PNI was absent in 49 (92.45%) cases, whereas it was present in 4 (7.55%) cases. Regarding evaluation of surgical or base margins, 41 (77.35%) polyps demonstrated negative margins, including both polypectomy and colectomy specimens, whereas 12 (22.64%) showed positive base margins.
Correlation analysis
Table IV presents the correlation between sex, age, differentiation, adenomatous background, location, size, LSI, VI, and PNI and their association with the Haggitt levels. The analysis revealed a significant relationship between lymphatic invasion and higher Haggitt levels (p = 0.004). Moreover, patients with perineural invasion had higher Haggitt scores (p = 0.009).
Table IV
Association of Haggitt level with gender, age, differentiation, adenomatous background, location, size, lymphatic invasion, venous invasion, and perineural invasion
Discussion
Malignant colorectal polyps are unequivocally characterized by invasive carcinoma within the precursor adenomatous colorectal polyps [1]. This distinctive feature categorizes them as high-grade neoplasms with the inherent potential for regional nodal involvement and distant metastasis [8]. This salient attribute underscores their aggressive nature and the importance of timely detection and implementation of appropriate management strategies. The invasive nature of these polyps signifies a pivotal stage in the development of colorectal cancer, emphasizing the importance of surveillance and treatment approaches to mitigate the risk of further disease progression and associated adverse outcomes [1].
The incidence of malignant colorectal polyps in patients undergoing endoscopic removal varies across studies. In a seminal investigation conducted by Cranley et al. [10], the examination of 1523 adenomatous polyps revealed a modest proportion of 41 (2.7%) cases among 39 patients with invasive adenocarcinoma within the polyp structures. Conversely, Colacchio et al. [11] documented a higher prevalence, wherein 86 (11.7%) patients out of 729 who underwent endoscopic removal of pedunculated adenomatous polyps were found to have polyps containing carcinoma. These contradictory findings highlight the inherent heterogeneity prevalent in the incidence of malignant polyps, which may be attributed to differences in patient demographics, clinical characteristics, and methodological approaches among the cohorts analyzed. However, coping with colorectal polyps requires conducting a comprehensive evaluation and implementing a meticulous management strategy, as highlighted by these findings. Malignant colorectal polyps can occur anywhere in the colorectum.
The existing literature on the frequency of site involvement in malignant polyps remains limited. However, a study conducted by Bujanda et al. [8] contributed valuable insights by demonstrating that over 25% of advanced polyps and colon cancers manifest predominantly in the region proximal to the splenic flexure. In contrast, the current study’s findings emphasize that the sigmoid and rectal regions are common sites for malignant polyps, accounting for approximately 75.48% of observed cases. Therefore, considering their heightened potential for malignancy, it is imperative to prioritize complete endoscopic removal and comprehensive histopathological assessment of polyps arising in these areas. Adhering to meticulous examination practices and adopting appropriate management strategies tailored to these regions are critical for effectively mitigating the risk of undetected or inadequately treated malignant polyps.
The possibility of malignant polyps increases considerably with size, particularly when their diameter exceeds 1 cm. This correlation between polyp size and the likelihood of developing carcinoma emphasizes the need for vigilant monitoring and prompt intervention since larger polyps pose a greater risk of malignant transformation [8]. The investigation conducted in the present study revealed notable variation in the size of the polyps removed during endoscopy, with dimensions ranging from 0.2 to 8.5 cm. Remarkably, the majority of polyps observed in this study measured > 1 cm in diameter, with most in the range 1.1 to 3 cm, representing approximately 52.83% of cases. However, this study did not yield any significant evidence of an association between the Haggitt level and tumor size. These findings indicate the lack of a statistically significant correlation between the Haggitt level, which is used as a marker for invasion depth, and the size of the polyps excised during endoscopic procedures. It is worth noting that further investigations and larger sample sizes may be necessary to elucidate potential relationships or uncover any nuanced associations between tumor size and the Haggitt level in the context of malignant polyps. Additional research is warranted to deepen understanding of the complex interplay among polyp characteristics, tumor invasiveness, and clinical implications.
Assigning distinct anatomical levels of invasion facilitates a comprehensive understanding of the pathological features and prognostic implications associated with such cases. According to Kyzer et al. [12], colonic resection is required only in patients with level 4 invasion.
The determination of LSI in cancer is predicated on identifying tumor cells within an endothelial-lined channel devoid of red blood cells [10]. The limited extent of lymphatic penetration beyond the muscularis mucosa suggests that cancer cells that do not infiltrate through this specific layer pose minimal to no risk of lymphatic space invasion and subsequent lymph node metastasis [13]. A study conducted by Bujanda et al. [8] revealed that approximately 12% to 16% of malignant polyps showed LSI, with a significant association between the histopathological presence of invasive malignant cells within the deep submucosa of colorectal polyps and an increased risk of regional lymphatic involvement, in contrast to cases where only mild penetration was observed. These findings align with the results of this current study, demonstrating that approximately 17% of malignant polyps display microscopic evidence of LSI, and all are consistently classified as Haggitt level 3 or higher (p = 0.004). The correlation between the extent of invasive growth in the submucosa and lymphatic involvement emphasizes the importance of precise histopathological assessment to determine the aggressiveness and potential metastatic spread of malignant colorectal polyps.
When examining VI in malignant polyps, it is pertinent to note the substantial variation in the overall incidence among different studies [14], ranging from 3.5% to 39.0%. The present investigation identified VI in approximately 8% of the malignant polyps. However, the findings did not reveal any statistically significant correlation between Haggitt level and the presence of VI. Furthermore, Talbot et al. [15] investigated and reported that the VI in malignant polyps did not significantly correlate with poor prognosis. This finding adds to existing knowledge, suggesting that venous invasion may not be an independent prognostic factor in this clinical context.
In their systematic review and meta-analysis, Bosch et al. [16] analyzed 17 studies and found that lymphatic invasion was the strongest predictor of lymph node metastasis (LNM), with a relative risk (RR) of 5.2 (95% CI: 4.0–6.8), while vascular invasion was a less significant predictor (RR = 2.2, 95% CI: 1.4–3.2). When both factors were combined, they indicated an intermediate relative risk, which provided less clarity [16]. Consequently, it is essential to evaluate and report lymphatic and vascular invasions as separate variables to enhance the prediction of LNM and support therapeutic decisions.
PNI has emerged as a significant prognostic marker in colorectal carcinoma (CRC), as evidenced by several studies in which multivariate analysis confirmed its independent association with an unfavorable prognosis [17–19]. In a study conducted by Liebig et al. [20], PNI was defined as the presence of tumor cells within any of the three layers of the nerve sheath (epineurium, perineurium, and endoneurium) or tumor foci outside the nerve, involving at least 33% of its circumference. The incidence of PNI in CRC varies between 6% and 31% [21]. Despite its significance in CRC, literature on PNI in malignant colorectal polyps is limited. The present study identified PNI in approximately 8% of the cases, with statistical significance established using the Haggitt test (p = 0.009). These findings underscore the relevance of assessing PNI in malignant colorectal polyps and its potential implications for prognostication.
A strong correlation has been observed between the distance of the invasive adenocarcinoma from the deep resection margin and the subsequent risk of recurrence, as documented in several studies. In the context of malignant polyps, the risk of disease recurrence remains minimal, ranging from 0% to 2%, when the distance between the invasive adenocarcinoma and resection margin exceeds 1 mm. Conversely, when the resection margin is involved, or the distance between the tumor and the resection margin is less than 1 mm, the risk of tumor recurrence significantly increases, with reported rates ranging from 21% to 33% [14, 22]. Recent studies suggest that defining a positive margin as the presence of tumor at the cautery line may be appropriate. Berg et al. [23] found that the occurrence of tumor at the cautery line significantly raises the risk of lymph node metastases when compared to margins greater than 0 mm, which exhibited no residual carcinoma and minimal risk of lymph node metastasis. Furthermore, in the study of Brown et al. [24], none of the surgical margins between 0.1 mm and 1 mm contained residual adenocarcinoma in the resected specimens. However, it is important to note that the current study did not specifically focus on assessing the resected margin status and its direct impact on tumor recurrence. Consequently, further investigations are warranted to comprehensively understand the correlation between the local recurrence rate and margin status to inform clinical decision-making and refine treatment approaches.
Conclusions
This study of malignant colorectal polyps revealed a significant correlation between the level of invasion (Haggitt) and lymphatic and perineural invasion. These findings underscore the critical importance of carefully evaluating and considering tumor size, location, LSI, and PNI for optimal management and treatment decision-making in patients with malignant polyps. Although further research is warranted to elucidate the impact of these factors on patient outcomes fully, the findings of this study underscore the importance of thorough evaluation and careful consideration of tumor size, location, LSI, and PNI for effective management and treatment decision-making.
