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Descriptions of the various dysplastic crypt phenotypes occurring in TA have remained unattended in the literature. Recently, new crypt-phenotypes, characterized by crypt rings in tandem (CRT), and by dysplastic crypt rings in tandem (DCRT) were described in IBD, and in in IBD-associated dysplasia, respectively. Here, we report the occurrence of DCRT in 40.4 % (n = 59) out of 146 consecutive tubular adenomas of the colorectum (TA). The number of DCRT varied: 10 TA had two DCRT, seven TA had three DCRT, two TA, four DCRT and the remaining two TA had ≥ five DCRT. The frequency of DCRT was influenced by TA-size; larger TA (≥ 5 mm) had significantly more DCRT than smaller TA (<5 mm). Conversely, the frequency of TA with DCRT was not influenced by age, gender, or localization. Since only 1 or 2 sections were available per TA, the number of DCRT in the entire TA should be higher than those shown in Results. Historical controls in human and rodent normal colorectum showed no CRT. Moreover, DCRT were not found in 781 historical non-polypoid colorectal adenomas. The present finding might encourage searching for DCRT, the final goal being to achieve a more elaborated microscopic narrative of TA, the most prevalent of all colorectal adenomas.
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Adenoma , Neoplasias Colorretais , Humanos , Feminino , Masculino , Neoplasias Colorretais/patologia , Adenoma/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Mucosa Intestinal/patologiaRESUMO
Dysplastic crypt branching (DCB) was recently found in ulcerative colitis-associated dysplasia. The aim was to assess the frequency and the branching phenotype of DCB in polypoid colorectal tubular adenomas (TA). A total of 3956 DCB were found in the 139 TA: 98% were in asymmetric branching (DCAB) and the remaining 2% in symmetric branching (DCSB). A linear correlation was found between DCB frequency and the increasing digital size in TA (p < .05). Using a digital ruler, adenomas were divided into small TA (<5 mm) and larger TA (≥5 mm). The difference between the frequency of DCB in small TA (n = 75) vs. larger TA (n = 64), was significant (p < .05). DCB frequency was not influenced by age, gender or TA localization. In the normal colorectal mucosa (≈2 m2 ), only occasional CSB is found and no CAB. And yet, multiple DCB (mean 16.7 DCB), mostly DCAB, was found in small TA, occupying <5 mm of the mucosal area. In larger TA, as many as 42.1 DCB (mean), mostly DCAB, occurred in merely 7.8 mm (mean) of the colon mucosa. Thus it is suggested that DCB is a standard histologic element of TA. The natural expansion of the adenomatous tissue in larger TA appears to be follow on from newly produced, mostly DCAB, by DCSB and by the accumulation of their dysplastic offspring's progenies. The findings strongly suggest that DCB is a central microstructure in the histological events unfolding in polypoid colorectal TA.
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Adenoma , Colite Ulcerativa , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Adenoma/patologia , Fenótipo , Hiperplasia/patologia , Mucosa Intestinal/patologiaRESUMO
BACKGROUND: Pathological TNM staging (pTNM) is the strongest prognosticator in colorectal carcinoma (CRC) and the foundation of its post-operative clinical management. Tumours that invade pericolic/perirectal adipose tissue generally fall into the pT3 category without further subdivision. METHODS: The histological depth of invasion into the pericolic/perirectal fat was digitally and conventionally measured in a training cohort of 950 CRCs (Munich). We biostatistically calculated the optimal cut-off to stratify pT3 CRCs into novel pT3a (≤3 mm)/pT3b (>3 mm) subgroups, which were then validated in two independent cohorts (447 CRCs, Bayreuth/542 CRCs, Mainz). RESULTS: Compared to pT3a tumours, pT3b CRCs showed significantly worse disease-specific survival, including in pN0 vs pN+ and colonic vs. rectal cancers (DSS: P < 0.001, respectively, pooled analysis of all cohorts). Furthermore, the pT3a/pT3b subclassification remained an independent predictor of survival in multivariate analyses (e.g. DSS: P < 0.001, hazard ratio: 4.41 for pT3b, pooled analysis of all cohorts). While pT2/pT3a CRCs showed similar survival characteristics, pT3b cancers remained a distinct subgroup with dismal survival. DISCUSSION: The delineation of pT3a/pT3b subcategories of CRC based on the histological depth of adipose tissue invasion adds valuable prognostic information to the current pT3 classification and implementation into current staging practices of CRC should be considered.
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Carcinoma , Neoplasias Retais , Humanos , Carcinoma/patologia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/patologia , Estudos RetrospectivosRESUMO
Histologic sections from patients with inflammatory bowel disease (IBD) usually exhibit crypts with architectural distortions and branching crypts. It has been postulated that crypt branching should be assessed only in well-oriented, upright crypts. However, those crypts are mostly found in sections from colectomy specimens and colon mucosectomies. Sections from endoscopic biopsies are fortuitously cut in a horizontal plane, a procedure mostly revealing cross-cut crypt rings. In endoscopic biopsies from UC patients we previously detected cross-cut crypts heralding the crest domain of branching crypts. Recently, the scrutiny of biopsies from IBD patients revealed that branching-crest domains concurred either with crypts in symmetric branching, typified by twin, amalgamating back-to-back isometrics crypt-rings, or with crypts in asymmetric branching, characterized by ≥2 amalgamating anisometric crypt-rings; both symmetric and asymmetric branching-crest domains were encased by a thin muscularis mucosae. Quantitative studies in biopsies from Swedish and German patients with IBD showed that crypts in asymmetric branching outnumbered those in symmetric branching. Because crypt-branching seldom occurs in the normal colon in adults and considering that colon crypts typically divide once or twice during a lifetime, the accruing of asymmetric branching crypts in IBD biopsies emerges as a significant histologic parameter. Although the biological significance of asymmetric crypt-branching in IBD remains at present elusive, their occurrence deserves to be further investigated. The future policy will be to include in our pathologic reports, the number of crypts in asymmetric branching, in order to monitor their frequency in prospective surveillance biopsies in patients with IBD.
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Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/patologiaRESUMO
PURPOSE: To analyze the influence of adjuvant chemotherapy on the combination of tumor budding and tumor-infiltrating lymphocytes (TILs) in stage II and III colon cancer and to elucidate its potential value for adjuvant treatment decisions. METHODS: 306 patients with stage II and 205 patients with stage III colon cancer diagnosed between 2005 and 2016 who had undergone surgery in a curative setting were enrolled. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and the criteria of the International TILs Working Group (ITWG). Combinations of budding and TILs were analyzed, and the influence of adjuvant chemotherapy was assessed. RESULTS: In stage II colon cancer, stratification into the four budding/TILs groups showed no significant differences in overall survival (OS) between the chemotherapy and the surgery-alone group, not even in cases with high-risk features. In stage III colon cancer, patients with low budding/high TILs benefited significantly from chemotherapy (p=0.005). Patients with high budding/low TILs as well as high budding/high TILs showed a trend to benefit from adjuvant treatment. However, no chemotherapy benefit was seen for the low budding/low TIL group. CONCLUSIONS: The budding/TIL combination identified subgroups in stage II and III colon cancer with and without benefit from adjuvant treatment. The results this study suggest that the combination of budding and TILs as tumor-host antagonists might be an additional helpful tool in adjuvant treatment decisions in stage II and III colon cancer.
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Neoplasias do Colo , Linfócitos do Interstício Tumoral , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Humanos , Linfócitos do Interstício Tumoral/patologia , Estadiamento de Neoplasias , PrognósticoRESUMO
PURPOSE: To analyze the role of programmed death ligand 1 (PD-L1) immunohistochemisty in the context of tumor microenvironment in colon cancer (CC) with focus on the interaction between tumor budding and tumor-infiltrating lymphocytes (TILs) and to elucidate its potential value for immunooncologic treatment decisions. METHODS: Three hundred forty seven patients with CC, stages I to IV, were enrolled. PD-L1 immunohistochemistry was performed using two different antibodies (clone 22C3 pharmDx, Agilent and clone QR1, Quartett). Tumor proportion score (TPS) as well as immune cell score (IC) was assessed. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and International TILs Working Group (ITWG). Correlation analyses as well as survival analyses were performed. RESULTS: PD-L1 positivity significantly correlated with TILs > 5% and MMR deficiency, and PD-L1-positive cases (overall and IC) showed significantly longer overall survival (OS) with both antibodies.The parameters "high grade," "right-sidedness," and "TILS > 5% regardless of MMR status" evolved as potential parameters for additional immunological treatment decisions. Additionally, TPS positivity correlated with low budding. More PD-L1-positive cases were seen in both high TIL groups. The low budding/high TIL group showed longer disease-free survival and longer OS in PD-L1-positive cases. CONCLUSION: Overall, PD-L1 positivity correlated with markers of good prognosis. PD-L1 immunohistochemistry was able to identify parameters as additional potential candidates for immune therapy. Furthermore, it was able to stratify patients within the low budding/high TIL group with significant prognostic impact.
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Antígeno B7-H1 , Neoplasias do Colo , Linfócitos do Interstício Tumoral/imunologia , Microambiente Tumoral , Biomarcadores Tumorais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Humanos , PrognósticoRESUMO
BACKGROUND/AIM: Tubular adenomas of the colon (TA) are neoplastic polyps composed of dysplastic tube-like crypts. Nondysplastic crypts, mostly in asymmetric branching have been previously reported, both beneath and bordering TA. In the present article, intercalated nondysplastic crypts (INDC) amidst dysplastic crypts in TA are showcased. PATIENTS AND METHODS: The occurrence of INDC was recorded in 139 TA. RESULTS: Out of the 139 TA, 31% exhibited INDC; of these, 58% were in asymmetric branching (INDCAB), 35% were single intercalated crypts without branching (INDSNB), and 7% were in symmetric branching (INDCSB). Luminal dysplasia occurred in 53% out of the 43 TA: in 37% TA with INDCAB, in 16% TA with INDSNB, but in none of the TA with INDCSB. Thus, INDCAB predominated. CONCLUSION: The finding of INDC in TA domain contrasts with the infrequency of INDCSB and with the absence of INDCAB in the normal colorectal mucosa. Hence, INDC emerge as integral components in TA. Since only 1 or 2 sections were available per TA, the total number of INDC in the entire TA is likely higher. INDC in TA may be remnants of acquired nondysplastic mucosal cores of abnormal cryptogenesis that were subsequently replaced by top-down growing dysplastic epithelium. The present and previous findings support the concept of field cancerization in the human colorectum.
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Adenoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/patologia , Adenoma/patologia , Colo/patologia , Mucosa Intestinal/patologia , Transformação Celular Neoplásica/patologiaRESUMO
Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E-cadherin loss. Focal activation of P-cadherin expression in tumor cells that are deficient for E-cadherin occurs in a subset of ILCs. Switching from an E-cadherin deficient to P-cadherin proficient status (EPS) partially restores cell-cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52-year-old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E-cadherin and P-cadherin. CDH1/E-cadherin mutations were determined by next-generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1/E-cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E-cadherin-negative and P-cadherin-negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter-cryptal ILC cells switched to a P-cadherin-positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment-induced EPS and conversion to cohesive growth.
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Neoplasias da Mama , Carcinoma Lobular , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Lobular/genética , Neoplasias da Mama/genética , Caderinas/genética , Biópsia , Colo , Microambiente TumoralRESUMO
BACKGROUND: To date, little is known regarding human epithelial growth factor receptor (HER2) low-expressing colorectal cancer (CRC). Due to promising rising therapies with HER2-antibody-drug conjugates we aimed to analyze the frequency of HER2-low in patients with CRC. Additionally we characterized the clinicopathologic background of this group and its potential relationship with the tumor microenvironment represented by budding and tumor infiltrating lymphocytes (TILs). METHODS: 319 patients with CRC, stages I-IV, were enrolled. HER2-immunohistochemistry (IHC) as well as fluorescence in situ hybridization (FISH) were performed on tissue microarrays. IHC was evaluated semiquantitatively and software-assisted using the HERACLES Diagnostic Criteria for CRC. HER2-low was defined as IHC 1 + or 2 +/FISH negative. HER2-IHC results were compared with budding, TILs and their combinations. RESULTS: The HER2 low-expressing subset represented almost one half of all CRC (47.1 %). Assessment was highly reproducible with different methods. HER2-low cases were significantly more often lower T-, N-, and tumor stage and had less L1 compared with HER2-0. Additionally, they showed more often TILs > 5 % (p = 0.001). The difference between HER2-0 and HER2-low was highly significant between the four budding/TILs-groups (p < 0.001). Cases with low budding/high TILs were more often HER2-low. The highest difference was seen between the low budding/high TILs-group and the low budding/low TILs-group (p < 0.001). CONCLUSIONS: HER2-low expression in CRC is frequent and involves nearly one half of all patients. We could show a relationsship between HER2-low expression and the tumor microenvironment. Special attention should be paid to the low budding/high TILs group in future research.
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Neoplasias Colorretais , Microambiente Tumoral , Humanos , Prognóstico , Hibridização in Situ Fluorescente , Neoplasias Colorretais/patologia , Oncogenes , Linfócitos do Interstício Tumoral/patologiaRESUMO
AIMS: Recently, eight novel histologic structures in colon mucosa with inflammation were described. Here, we assessed the frequency of one of them: crypt rings in tandem (CRT), in patients with infectious colitis (IC), IBD (ulcerative colitis; UC or Crohn colitis; CrC) and UC in remission (UCR). In addition, the frequency of dysplastic CRT (DCRT) in IBD-associated noninvasive neoplasia (IBDNIN) were also calculated. METHODS: Colon biopsies in 578 cases were reviewed: 42 cases with IC, 280 with IBD (180 UC and 100 CrC), 100 UCR and the remaining 156, IBDNIN. RESULTS: The proportions of CRT in IC was 16.7%, in IBD 14.3% %, in UCR 3%, and of DCRT in IBDNIN, 20%. No differences were recorded between the proportions of CRT in IC, UC and CrC. Conversely, the difference in CRT frequency between UC and UCR, and between CRT and DCRT were significant (P = 0.006, and p = 0.05, respectively). CONCLUSIONS: CRT evolved in IC and in IBD. The finding of CRT in IC strongly suggest that those characteristic crypts were shaped at the early stages of mucosal inflammation. CRT persisted in IBD with protracted inflammation but plummeted in UCR, that is when the mucosal inflammation waned. The proportion of DCRT was significantly higher than that of CRT. It is submitted that DCRT might had developed in IBDNIN using CRT as scaffolds. This is the first study in which a characteristic pathologic aberration of cryptogenesis was tracked in colon biopsies from patients with IBD and with IBD-associated neoplastic transformation.
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Colite Ulcerativa , Doença de Crohn , Neoplasias , Humanos , Colo/patologia , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Doença de Crohn/complicações , Doença de Crohn/patologia , Neoplasias/patologia , Inflamação/patologiaRESUMO
BACKGROUND/AIM: For many years, it was empirically estimated that the majority of the routine colon biopsies in Swedish patients with ulcerative colitis (UC), exhibited cross-cut crypts. The aim of the present study was to assess the frequency of cross-cut crypts (CCC) and well-oriented crypts in routine colon biopsies in German patients with UC. PATIENTS AND METHODS: In total, 447 colon biopsies: 376 with UC and 71 controls were investigated. RESULTS: Out of 376 colon biopsies with UC, 73% exhibited ≥60% CCC. Out of the 237 biopsies showing ≥80% CCC, as many as 71% exhibited 100% CCC in individual biopsies. Similar percentages were found in control biopsies. CONCLUSION: The majority of the routine colon biopsies with UC, as well as control biopsies in German patients displayed CCC. Thus, an unnoticed, consequent, and systematic cutting technical hitch was introduced during the laboratory processing of colon biopsies. The reason(s) behind the similar histologic processing mode of colon biopsies at the two geographically disparate laboratories (Sweden and Germany) remains elusive. The cross-cutting mode influenced the narrative of biopsies in UC, inasmuch as some histological parameters listed among well-oriented colon sections were not present in sections displaying CCC.
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AIMS: Studying crypt branching in ulcerative colitis (UC) and in infectious colitis (IC), we detected previously unreported crypt-associated anomalies (CAAs). The objective was to describe, illustrate and assess the frequency of CAAs in inflamed colon mucosa in patients with UC and IC. METHODS: Sections from 100 consecutive biopsies with UC, in 50 with IC and in 27 with UC in remission (UCR) were reviewed. The following CAAs were identified: crypt eosinophilia, intracryptal epithelial hyperplasia, intracryptal epithelial budding, intracryptal supernumerary crypts, intracryptal epithelial bridges, crypt rings in rows and off-centre epithelial budding. RESULTS: The frequency of crypts with extensive crypt eosinophilia and with intracryptal epithelial budding was significantly higher in UC than in IC and UCR (p<0.05); the frequency in the remaining histological parameters was similar in UC, IC and UCR. CONCLUSIONS: CAAs were found interspersed with branching crypts. CAAs persisted in long-lasting UC mucosal inflammation, but declined when the inflammation waned. Since similar anomalies are not present in normal colon mucosa, the results suggest that CAAs had been boosted by the ongoing mucosal inflammation. The development of these previously unreported CAAs in the colon mucosa with inflammation might embody pathological aberrations of cryptogenesis.
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Colite Ulcerativa , Colo , Humanos , Colo/patologia , Colite Ulcerativa/patologia , Mucosa Intestinal/patologia , Inflamação/patologia , BiópsiaRESUMO
Background/Aim: It has been demonstrated that most routine biopsies from the colon and rectum display cross-cut crypts (CCC). The aim was to assess the number of CCC in microscopic isometric digital samples (0.500 mm2) from routine colon biopsies. Patients and Methods: Colon biopsies from 224 patients were investigated: 99 in patients with ulcerative colitis (UC), 31 UC in remission (UCR), 28 infectious colitis (IC), 7 resolved IC (RIC), 19 diverticular sigmoiditis (DS), and 40 normal colon mucosa (NCM). Results: A total of 8,024 CCC were registered: 2,860 (35.6%) in UC, 1,319 UCR (16.4%), 849 (10.6%) in IC, 340 (4.2%) in RIC, 795 (9.9%) in DS, and 1,861 (23.2%) in NCM. The CCC frequencies in UC and IC were significantly lower (p<0.05) than those in UCR, RIC, DS, and NCM. Conclusion: By the simple algorithm of counting CCC in standardized isometric microscopic digital circles measuring 0.500 mm2, it was possible to differentiate between UC (long-lasting inflammation) and IC (short-lasting inflammation) on the one hand, and UCR, RIC, DS (persistent inflammation), and NCM, on the other. The counting of CCC in the algorithm by five pathologists working in three disparate European Countries, was found to be reproducible.
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BACKGROUND/AIM: Nondysplastic crypt branching (NDCB), mostly asymmetric branching (NDCAB), was previously found beneath the dysplastic epithelium of colorectal tubular adenomas (TA) in Swedish patients. This study examined the frequency of NDCB and NDCAB beneath the dysplastic epithelium of TA, in German patients. PATIENTS AND METHODS: From a collection of 305 TA, 121 TA fulfilled the prerequisites for inclusion. All NDCB were registered. RESULTS: Of 673 NDBCs, 572 (85%) NDCABs and 101 (15%) NDCSs, were found beneath the neoplastic tissue in the 121 TA. When the frequency of NDCB was challenged against the TA size, a linear correlation was found in the 121 TA (p<0.05, p=0.020172). Most NDCB were NDCAB (p<0.05, p=0.00001). The frequency of NDCB correlated with increasing TA size, implying that the higher frequency of both NDCB, dysplastic crypt branching, and their dysplastic offspring crypts were the most probable sources of TA enlargement. The frequency of NDCB underneath TA was not influenced by increasing age, sex or TA localization. CONCLUSION: Similar findings as those reported here were previously found in TA in Swedish patients. The similarity between these two populations, located in disparate geographical areas and subjected to dissimilar microenvironmental conditions suggests that NDBC in TA might be a ubiquitous unreported phenomenon. According to the literature, normal colon cells often harbor somatic mutations. Consequently, NDCB underneath TA may be mutated nondysplastic branching crypts upon which the dysplastic epithelium in TA eventually develops.
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Adenoma , Neoplasias Colorretais , Humanos , Simbiose , Adenoma/genética , Epitélio , Neoplasias Colorretais/genética , HiperplasiaRESUMO
AIMS: Special histomorphological subtypes of colorectal low-grade intraepithelial neoplasia (LGIN) with variable prognostic impact were recently described in patients with inflammatory bowel disease (IBD) referred to as non-conventional dysplasia. However, they can also be found in patients without IBD. We aimed to analyse the reproducibility, frequency and prognostic impact of non-conventional colorectal LGIN in patients with and without IBD. METHODS: Six pathologists evaluated 500 specimens of five different LGIN-cohorts from patients with and without IBD. Non-conventional LGIN included hypermucinous, goblet cell-deficient, Paneth cell-rich and crypt cell dysplasia. A goblet cell-rich type and non-conventional LGIN, not otherwise specified were added. Results were compared with the original expert-consented diagnosis from archived pathology records. RESULTS: Four or more pathologists agreed in 86.0% of all cases. Non-conventional LGIN was seen in 44.4%, more frequently in patients with IBD (52%; non-IBD: 39.3%, p=0.005). In patients with IBD non-conventional LGIN associated with more frequent and earlier LGIN relapse (p=0.006, p=0.025), high-grade intraepithelial neoplasia (p=0.003), larger lesion size (p=0.001), non-polypoid lesions (p=0.019) and additional risk factors (p=0.034). Results were highly comparable with expert-consented diagnoses. In patients without IBD, non-conventional LGIN may indicate a higher risk for concurrent or subsequent colorectal carcinoma (CRC, p=0.056 and p=0.061, respectively). Frequencies and association with high-grade intraepithelial neoplasia or CRC varied between the different LGIN subtypes. CONCLUSIONS: Non-conventional histomorphology in colorectal LGIN is frequent and highly reproducible. Our results indicate an increased risk for CRC in patients with non-conventional LGIN, probably independent of IBD. We recommend reporting non-conventional LGIN in routine pathology reports.
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The tumor-stroma ratio (TSR) has been repeatedly shown to be a prognostic factor for survival prediction of different cancer types. However, an objective and reliable determination of the tumor-stroma ratio remains challenging. We present an easily adaptable deep learning model for accurately segmenting tumor regions in hematoxylin and eosin (H&E)-stained whole slide images (WSIs) of colon cancer patients into five distinct classes (tumor, stroma, necrosis, mucus, and background). The tumor-stroma ratio can be determined in the presence of necrotic or mucinous areas. We employ a few-shot model, eventually aiming for the easy adaptability of our approach to related segmentation tasks or other primaries, and compare the results to a well-established state-of-the art approach (U-Net). Both models achieve similar results with an overall accuracy of 86.5% and 86.7%, respectively, indicating that the adaptability does not lead to a significant decrease in accuracy. Moreover, we comprehensively compare with TSR estimates of human observers and examine in detail discrepancies and inter-rater reliability. Adding a second survey for segmentation quality on top of a first survey for TSR estimation, we found that TSR estimations of human observers are not as reliable a ground truth as previously thought.
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BACKGROUND/AIM: This study aimed to validate the inter-rater agreement of the assessment of crypt branching (also called crypt fission) in patients with ulcerative colitis (UC) and to elucidate its potential diagnostic and prognostic impact. PATIENTS AND METHODS: A total of 100 biopsies from patients with UC were analyzed. Two cohorts of 50 patients each served as controls [infectious controls/controls with low grade intraepithelial neoplasia (LGIN) in UC alio loco]. Three pathologists scored the number of total crypts in fission as well as the number of crypts in symmetric (CSF) and asymmetric fission (CAF). RESULTS: Inter-rater agreement ranged from good to excellent in the study cohort. The number of crypts in fission correlated significantly with UC-activity (p=0.001; p<0.001). The study cohort showed higher mean counts of crypts in fission and significant more total and CAF than the infectious controls (p=0.007 and p=0.008), especially in male patients (p<0.001) The LGIN-control cohort showed significant more CSF (p=0.012). CONCLUSION: Inter-rater agreement for crypt branching was reliable in the study cohort. Crypt branching proved as an additional histologic feature to distinguish active UC against infectious colitis. Higher amounts of CSF may help identifying patients at higher risk for neoplasia.
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Biópsia/métodos , Colite Ulcerativa/patologia , Humanos , PrognósticoRESUMO
BACKGROUND/AIM: To report the frequency of crypts in asymmetric branching (CAB) in biopsies from all colorectal segments in patients with ulcerative colitis in remission (UCR). PATIENTS AND METHODS: Biopsies in 100 UC patients were investigated: 50 with UCR and 50 with ongoing long-lasting UC (LLU; i.e., controls). RESULTS: The frequency of CAB was significantly lower in UCR than in LLUC, both in the right colon and left colorectum. CAB frequency was not influenced by two important confounders: the age and sex of patients. CONCLUSION: CAB is a pathologic aberration of colorectal cryptogenesis evoked by chronic mucosal inflammation. When chronic inflammation waned in UCR, the production of CAB plummeted or ceased. Chronic inflammation and protracted disease-duration in LLUC increase the risk for colorectal dysplasia or carcinoma. Importantly, dysplastic CAB were recently detected in LLUC-associated dysplasia. Whether the abrogation of CAB is instrumental in reducing the neoplastic risk in UCR patients, deserves further investigation.
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Colite Ulcerativa , Neoplasias Colorretais , Biópsia , Colite Ulcerativa/patologia , Colo/patologia , Neoplasias Colorretais/patologia , Humanos , Hiperplasia/patologia , Inflamação/patologiaRESUMO
BACKGROUND/AIM: Nearly 70 years ago, Slaughter launched the hypothesis of field cancerization for oral carcinomas; that hypothesis was subsequently also claimed for carcinomas in other organs. We previously found in the colon mucosa adjacent to nonpolypoid adenomas, branching crypts lined by normal epithelium (BCNE). Here, we explored whether BCNE could also be found in the colon mucosa adjacent to sporadic polypoid tubular adenomas (TA), the most prevalent of all colon adenomas. PATIENTS AND METHODS: Nondysplastic mucosa adjacent to TA was found in 103 out of 131 TA. All BCNE adjacent to TA were recorded. RESULTS: In 98 (95.1%) out of 103 TA having nondysplastic adjacent mucosa, 645 BCNE were registered: 82.6% were in asymmetric branching and 17.4% in symmetric branching. Thus, BCNE in asymmetric branching predominated. The frequency of BCNE adjacent to TA was influenced by the adenoma size and degree of dysplasia severity. Contrarywise, the frequency of BCNE adjacent to TA was neither influenced by the age or sex of the patients, nor by the colon localization of TA. CONCLUSION: BCNE often occur in the normal mucosa adjacent to TA. BCNE emerge as integral components of TA. The majority of the BCNE were in asymmetric branching, considered as aberrations of cryptogenesis. We propose that the accretion of asymmetric BCNE adjacent to TA supports Slaughter's hypothesis of field cancerization.
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Carcinoma , Neoplasias do Colo , Humanos , Epitélio , HiperplasiaRESUMO
AIM: To report the detection of dysplastic crypts in asymmetric branching (DCAB) in biopsies from patients with ulcerative colitis (UC). PATIENTS AND METHODS: One hundred consecutive endoscopic biopsies from patients with UC undergoing surveillance were reviewed. RESULTS: Three biopsy/cases showed DCAB. The frequency of DCAB varied from two in one case, three in another case, and five in the remaining case. CONCLUSION: The final outcome of DCAB is to generate two or more dysplastic asymmetric offspring-crypts. Repeated DCAB offspring formation, together with new DCAB, would boost the pool of dysplastic crypts, resulting in an exponential expansion of the mucosal area occupied by dysplasia in UC.