New morphological risk factors for metastasis to regional lymph nodes in rectal cancer with invasion into the submucosa

AIM to assess prognostic significance of pathologic features of T1 rectal carcinoma in relation to regional lymph nodes involvement (N+).MATERIAL AND METHODS: surgical specimens (n = 66) from rectal resection for carcinoma pT1 were investigated. Following prognosticators were evaluated: depth of submucosal invasion, grade of differentiation, lymphovascular invasion (LVI), tumor budding (Bd), poorly differentiated clusters (PDC) of tumor and rupture of cancer glands (CGR).RESULTS: lymph nodes metastases were found in 13 (19.7%) specimens. LVI was associated lymphatic spread in great possibility OR 38.0 95% CI 2.1-670 (p < 0.0001). Tumor budding of high grade (Bd3) OR 6.2 95% CI 1.2-31 (p < 0.0001) and poorly differentiated clusters (p = 0,03) also increased risk of lymph node metastases. Depth of submucosal invasion, grade of differentiation, and rupture of cancer glands failed to demonstrate significant association with N+. Logistic regression analysis allowed to determine LVI as independent prognostic factor of lymph node tumor involvement.CONCLUSION: lymphovascular invasion, tumor budding and poorly differentiated clusters of tumor are risk factors of T1 rectal carcinoma lymph node metastases.

Poorly differentiated clusters and tumor budding are important prognostic factors in colorectal carcinomas

The aim of our study was to assess the prognostic value of the two new grading systems based on the quantification of tumor budding - TB (GBd) and poorly differentiated clusters - PDCs (PDCs-G) in colorectal carcinomas (CRC). We performed a retrospective study on 71 CRC patients who underwent surgery at the Emergency County Hospital, Timișoara. CRC cases were classified based on haematoxylin-eosin slides, using the conventional grading system, GBd and PDCs-G, respectively. We used two-tier and three-tier grading schemes for each system. Subsequently, we evaluated associations with other prognostic factors in CRC. Based on the three-tier GBd (GBd-3t) most cases (34/69, 49.27%) were classified as G3Bd-3t, while based on the conventional grading system, the majority of the cases (55/69, 79.71%) were considered G2. On the other hand, based on the three-tier PDCs-G system (PDCs-G-3t), most cases (31/69, 44.93%) were PDCs-G2-3t. We also noted a more significant association of GBd-3t with other prognostic parameters analyzed, as compared to the conventional grading system. Nodal status, tumor stage, and lymphovascular invasion were strongly correlated with GBd-3t (p=0.0001). Furthermore, we noted that PDCs-G-3t correlated more significantly than the conventional grading system with nodal status (p<0.0001), tumor stage (p=0.0003), lymphovascular invasion (p<0.0001), perineural invasion (p=0.005) and the tumor border configuration (p<0.0001). High GBd and PDCs-G grades correlate directly with other negative prognostic factors in CRC.Thus, these new parameters/classification methods could be used as additional tools for risk stratification in patients with CRC.

A Case of Colonic Micropapillary Carcinoma With a High Frequency of Apoptosis

Purpose: Colorectal micropapillary carcinoma (MPC) exhibits aggressive biological characteristics, with empty spaces and reversed polarity, similar to the poorly differentiated clusters (PDCs) formed from detached cancer cells. Epithelial–mesenchymal transition, which is involved in the cancer cell acquisition of apoptosis resistance, is closely linked with histological findings of MPC, PDCs, and tumor buds (TBs), with MPC and TBs considered as apoptosis-resistant features. However, we encountered a case of colonic MPC with frequent apoptosis.Methods: We examined the case using immunohistochemistry and compared it with two cases of conventional colonic cancer with high PDC and TB presence.Results: In many of the tumor glands (TGs) of the MPC, empty spaces and tumor cell detachment toward the gland interior were observed. Moreover, TG ruptures were scattered, with PDCs adjacent to them. Apoptosis occurred mainly at the TG and PDC peripheries in the middle and deep tumor layers, and transforming growth factor beta 1 (TGF-β1) positivity was evident in those tumor cells. Cells positive for apoptosis-related M30 were distributed mainly in the deep layer with a significant PDC and TB presence. However, apoptosis and M30 positivity were low in the TBs. In the control cases, apoptosis hardly occurred. Furthermore, M30 positivity in the TGs was scattered and barely evident in the PDCs. Aberrant β-catenin positivity was found. In MPC, non-tumorous bud components, especially those in the deep layer, had poor abilities to promptly acquire apoptosis resistance. Conclusion: Apoptosis has the potential to reciprocally produce MPC, PDCs, and TBs, with TGF-β1 involvement.

Clinical Significance of Preoperative Inflammatory Markers in Prediction of Prognosis in Node-Negative Colon Cancer: Correlation between Neutrophil-to-Lymphocyte Ratio and Poorly Differentiated Clusters

Although stage I and II colon cancers (CC) generally show a very good prognosis, a small proportion of these patients dies from recurrent disease. The identification of high-risk patients, who may benefit from adjuvant chemotherapy, becomes therefore essential. We retrospectively evaluated 107 cases of stage I (n = 28, 26.2%) and II (n = 79, 73.8%) CC for correlations among preoperative inflammatory markers, histopathological factors and long-term prognosis. A neutrophil-to-lymphocyte ratio greater than 3 (H-NLR) and a platelet-to-lymphocyte ratio greater than 150 (H-PLR) were significantly associated with the presence of poorly differentiated clusters (PDC) (p = 0.007 and p = 0.039, respectively). In addition, H-NLR and PDC proved to be significant and independent survival prognosticators for overall survival (OS; p = 0.007 and p < 0.001, respectively), while PDC was the only significant prognostic factor for cancer-specific survival (CSS; p < 0.001,). Finally, the combination of H-NLR and PDC allowed an optimal stratification of OS and CSS in our cohort, suggesting a potential role in clinical practice for the identification of high-risk patients with stage I and II CC.

Comment on Jun, S.Y.; et al. “Tumor Budding and Poorly Differentiated Clusters in Small Intestinal Adenocarcinoma” Cancers 2020, 12, 2199

We read with interest the paper by Jun S [...]

Reply to Comment on “Jun, S.Y.; et al. Tumor Budding and Poorly Differentiated Clusters in Small Intestinal Adenocarcinoma” Cancers 2020, 12, 2199

We thank Giuffrida et al [...]

Tumor Budding and Poorly Differentiated Clusters in Small Intestinal Adenocarcinoma

The clinicopathologic and prognostic significances of tumor budding (TB) and poorly-differentiated clusters (PDC) have not been investigated in small intestinal adenocarcinomas (SIACs). In 236 surgically-resected SIACs, we counted TB (single cells or clusters ≤4 tumor cells) and PDC (clusters ≥5 tumor cells) at the peritumoral-invasive front (p) and in the intratumoral area (i) independently to classify as grade-1 (≤4), grade-2 (5–9), or grade-3 (≥10). Consequently, grades-2 and -3 were considered high-grade. High-pTB, -iTB, -pPDC, and -iPDC were observed in 174 (73.7%), 129 (54.7%), 118 (50.0%), and 85 (36.0%) cases, respectively. High-TB/PDCs were more frequently observed in tumors with high-grade, higher T- and N-categories and stage grouping, and perineural or lymphovascular invasion. Patients with high-TB/PDC had a shorter survival than those with low-TB/PDC. In a multivariate analysis, high-pTB, nonintestinal type, high N-category, retroperitoneal seeding, and microsatellite-stable were worse independent-prognostic predictors. Subgroup analysis demonstrated that patients with high-pTB showed worse survival (median: 42.5 months) than those with low-pTB (133.7 months; p = 0.007) in the lower stage (stages I–II) group. High-TB/PDC, both in peritumoral and intratumoral localizations, were associated with aggressive behaviors in SIACs. High-pTB can be used as an adverse prognostic indicator in SIAC patients, especially when patients are in early disease stages.