European Journal of Cardiovascular Medicine

Colorectal carcinoma (CRC) is a significant global health burden, ranking as the third most common cancer in men (10.0%) and the second in women (9.2%), with approximately 55% of cases occurring in more developed countries. In India, CRC accounts for about 6.3% of all cancers among both sexes combined [1,2]. Over the past few years, a notable increase in CRC incidence has been observed in Asian countries, attributed to westernized diets high in red meat and low in fibre. Other established risk factors include obesity, smoking, alcohol consumption, physical inactivity, and genetic predisposition. Geographic disparities in CRC incidence suggest strong environmental and dietary influences [3].

Approximately 5% of CRC cases are hereditary, mainly associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer), familial adenomatous polyposis (FAP), and MUTYH-associated polyposis (MAP). Additionally, 10–15% of patients report a positive family history, indicating a combination of genetic and environmental contributions to disease development [4]. Clinical presentation and prognosis depend heavily on the stage at diagnosis. Around 55% of patients are diagnosed with localized disease (stage I or II), while 25% have regional lymph node involvement, and 20% present with distant metastasis [5].

With the advent of personalized medicine, the pathologist’s role has evolved beyond diagnosis to include accurate pathological staging, surgical margin evaluation, and assessment of prognostic factors such as lymphovascular and perineural invasion. One histopathological feature of emerging interest is desmoplasia—a fibrotic stromal reaction surrounding the tumor. While in some cancers like breast, pancreas, and lung, desmoplasia is associated with tumor invasion and poor prognosis, its role in CRC remains debatable [6,7]. It may either act as a physical barrier limiting tumor spread or contribute to tumor progression. This study aims to grade desmoplasia in colorectal carcinoma and correlate it with established prognostic parameters to better understand its clinical significance.

Aim And Objectives

1. To grade tumor desmoplasia in colorectal carcinomas.
2. To correlate tumor desmoplasia with known prognostic factors like tumor site, tumor size, tumor extension, histologic type, histologic grade, lymphovascular invasion, perineural invasion, tumor budding and regional lymph nodes.

This study was conducted on excised specimens of colon and rectum received at the Department of Pathology, NRI Medical College and Hospital, Chinakakani, Guntur, from the Departments of General Surgery, Surgical Gastroenterology, and Surgical Oncology. The study period spanned two years, from June 2018 to May 2020. All primary colorectal carcinoma (CRC) specimens were included, while specimens from patients who received presurgical chemotherapy/radiotherapy and core needle biopsies were excluded.

Clinical details, including age, sex, symptoms, and signs, were recorded. Specimens were fixed in 10% formalin and processed routinely. Gross features such as tumor site, size, growth pattern, margin involvement, and infiltration into adjacent structures were documented. Sections were taken from the tumor proper, adjacent mucosa, resection margins, lymph nodes, and other suspicious areas following the College of American Pathologists (CAP) protocol. Paraffin-embedded blocks were sectioned at 3–5 microns and stained with Hematoxylin and Eosin (H&E). Slides were examined under light microscopy at magnifications of 40x, 100x, and 400x.

Tumors were classified based on the WHO classification of gastrointestinal tract tumors, considering site, histologic type and grade, tumor extension, lymphovascular invasion (LVI), perineural invasion (PNI), tumor budding, and tumor deposits.

Desmoplastic reaction (DR) was assessed qualitatively on H&E-stained slides, focusing on the extramural desmoplastic front. DR was categorized histologically into three types:

• Mature: Stroma with only fine, layered collagen fibres and no keloid-like collagen or myxoid stroma.
• Intermediate: Presence of keloid-like collagen—broad, hyalinized eosinophilic bundles—in mature stroma.
• Immature: Presence of myxoid stroma—amphophilic or basophilic extracellular matrix—with or without keloid-like collagen. Immature DR was identified using a 40x objective field as the minimum criterion.

Statistical analysis was done using the Chi-square test to assess the association between DR categories and clinicopathological variables with JAMOVI software. A p-value <0.05 was considered statistically significant.

The present study included a total of 62 cases of colorectal carcinoma. The most affected age group was 51–70 years, comprising 35 cases (56.5%). Eighteen cases (29%) were reported in patients below 50 years of age, with the youngest being 17 years old. Nine cases (14.5%) occurred in individuals above 70 years, with the oldest patient aged 85 years. The mean age at diagnosis was 56 years. with 33 cases (53.2%) in females and 29 cases (46.8%) in males.

Figure 1: Site-wise distribution of CRC cases

That a majority of 53 cases (85.5%) were adenocarcinoma, followed by 8 cases (12.9%) of mucinous adenocarcinoma and 1 case (1.6%) of signet ring cell carcinoma.

Among the 62 cases, a majority of 58 cases (93.6%) were well differentiated tumors followed by 2 cases (3.2%) of moderately differentiated and poorly differentiated tumors each. There were no undifferentiated tumors.

Table 1: Incidence of tumor extension in 62 cases of CRC

Indicates the tumor extension into the underlying structures showing a majority of 46 cases (74.3%) with extension into the peri colorectal tissue (T3), followed by 11 cases (17.7%) into the muscularis propria (T2), 3 cases (4.8%) invading the submucosa(T1) and 1 case (1.6%) invading the visceral peritoneum(T4a). One case (1.6%) was seen in a female patient with tumor invading the adjacent structures, anal canal, endocervix and isthmus(T4b).

Among the 62 cases of colorectal carcinoma studied, lymphovascular invasion (LVI) was identified in 32 cases (51.6%), while it was absent in 30 cases (48.4%). Perineural invasion (PNI) was observed in 5 cases (8.1%) and was not found in the remaining 57 cases (91.9%). Tumor budding was assessed and scored in all cases. A majority of 55 cases (88.7%) demonstrated a low tumor budding score (0–4 buds), followed by 6 cases (9.7%) with an intermediate score (5–9 buds), and only 1 case (1.6%) with a high tumor budding score (≥10 buds). Tumor deposits were detected in 7 cases (11.3%), whereas 55 cases (88.7%) showed no evidence of tumor deposits. Regarding regional lymph node metastasis, 40 cases (64.5%) had no lymph node involvement (N0), 11 cases (17.7%) showed metastasis in 1–3 regional lymph nodes (N1), and 11 cases (17.7%) exhibited metastasis in four or more regional lymph nodes (N2).

Table 2: Incidence of histological grades of desmoplasia

A majority of 45 cases (72.6%) showed grade 1 or mature desmoplasia, followed by 13 cases (21%) with grade 2 or intermediate desmoplasia and 4 cases (6.4%) with grade 3 or immature desmoplasia.

Table 3: Desmoplasia grade in comparison with various variables

Table 3 presents the relationship between desmoplasia grade and various clinicopathological parameters in colorectal carcinoma patients (n = 62). The majority of cases across all age groups, sexes, tumor sites, sizes, and histological features showed mature desmoplasia (Grade 1). No statistically significant association was observed between desmoplasia grade and age (p=0.978), sex (p=0.384), tumor site (p=0.627), tumor size (p=0.069), tumor extension (p=0.900), lymphovascular invasion (p=0.722), tumor deposits (p=0.173), regional lymph node involvement (p=0.411), histologic type (p=0.180), or histologic grade (p=0.763).

However, statistically significant associations were found with perineural invasion (p=0.002) and tumor budding score (p=0.014). A higher proportion of immature desmoplasia (Grade 3) was seen in cases with perineural invasion and high tumor budding, indicating a possible link between aggressive tumor behavior and stromal response. This suggests that desmoplasia grade may reflect tumor aggressiveness, particularly in the presence of neural invasion and high tumor budding.

Figure 2: Gross photographs of an ulcero-proliferative growth in the sigmoid colon and ascending colon, respectively, followed by Gross photographs of an ulcero-proliferative growth in the descending colon and rectum.

Figure 3A: Microphotograph of well differentiated adenocarcinoma showing well-formed glands (H&E x100). Figure 3B: Microphotograph showing a gland with basally oriented nuclei (H&E x400).

The present study demonstrated comparable demographic patterns with established literature. The mean age of 56 years (range 17–85) aligned closely with Ueno et al. (59.9 years, range 23–88) and Elzouki et al. (57.4 years, range 21–87) (8,9). However, a female preponderance was noted in contrast to the male predominance reported by Ueno et al. and Elzouki et al. (9–11).

 In terms of tumor location, this study confirmed that colorectal carcinomas were more common in the colon than the rectum, consistent with findings by Ueno et al. (62.1% colon), H. Ueno et al. (69.2% colon), and Elzouki et al. (57.89% colon) (8,9,11). Adenocarcinoma emerged as the predominant histologic type (85.5%), comparable to the findings of Laohavinij et al. (96.0%) (12). A notable observation was the predominance of well-differentiated tumors (Grade 1: 93.5%) in the current study, a finding that significantly differed from other investigations. While Laohavinij et al. reported 62% Grade 1 tumors (12), most other studies observed a predominance of Grade 2 tumors: Ueno et al. (49.5%), H. Ueno et al. (65.2%), and B Sis et al. (56.2%) (8,10,11). This discrepancy may reflect regional differences in tumor biology or patterns of detection. No statistically significant correlation was found between tumor desmoplasia and tumor site, consistent with Ueno et al. (9) but contrasting with other studies reporting significant associations: Ueno et al. and H. Ueno et al. (8,11). Similarly, tumor size did not show a significant correlation, which aligned with Ueno et al. (8) but differed from studies that reported significant size correlations (8,11). No significant correlation was observed between tumor desmoplasia and histologic grade, echoing B Sis et al. (11), but in contrast to multiple studies showing strong correlations: Ueno et al., Ueno et al., and H. Ueno et al. (8,9,11).

Furthermore, there was no significant correlation between desmoplasia and lymphovascular invasion, which contrasted sharply with existing literature where Ueno et al. and B Sis et al. found significant correlations for both lymphatic and venous invasions (8,11,15). However, two parameters showed statistically significant associations. Perineural invasion showed a strong correlation, indicating that mature desmoplasia was associated with a reduced risk of perineural invasion, a finding that contrasted with B Sis et al. (11) and suggested possible prognostic importance. Tumor budding also showed significant correlation, with mature desmoplasia linked to lower budding scores, aligning with the results of Ueno et al. and H. Ueno et al. (8,10), reinforcing the prognostic relevance of desmoplastic grading. Regarding lymph node involvement, there was no significant correlation, in agreement with B Sis et al. (11), but differing from Ueno et al. and H. Ueno et al. (8,11).

Nonetheless, 72.5% of node-negative (N0) cases showed mature desmoplasia, comparable to Ueno et al. (72.3%) (8). These findings suggest that desmoplastic grading, particularly about perineural invasion and tumor budding, may hold prognostic value in colorectal carcinoma. The predominance of mature desmoplasia in node-negative cases further supports its clinical relevance. Variations from international studies may be attributed to differences in population demographics, sample sizes, or regional tumor characteristics, highlighting the need for larger, multi-institutional studies to validate the role of desmoplastic grading in diverse populations.

Colorectal carcinoma is a leading cause of cancer-related morbidity and mortality. Prognosis post-surgery depends on factors like patient age, tumor site, size, histologic type and grade, lymphovascular and perineural invasion, tumor budding, and lymph node metastasis. Tumor desmoplasia, the fibrotic stroma at the tumor’s invasive edge, can be histologically graded as mature, intermediate, or immature. This study found that mature desmoplasia correlates with a lower risk of tumor spread, indicating its role as a significant prognostic factor. Further molecular studies could enhance its clinical utility in guiding treatment and improving survival.

Conflict Of Interest: No

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