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BACKGROUND: Ulcerative colitis is a well-known inflammatory bowel disease. Patients have an increased risk of developing colitis associated carcinoma (CAC). It is important for patient management to be able to distinguish between ulcerative colitis associated carcinoma and sporadic carcinoma (sCRC). However, this distinction is frequently very challenging. It is not readily possible to differentiate this histologically. However, the diagnosis is crucial for the patient's further treatment and follow-up. An attempt was therefore made to develop a diagnostic regime that would enable a reliable distinction between sCRC and CAC. METHODS: We screened 96 patients analyzing more than 850,000 methylation hotspots, to detect distinct epigenetic patterns between both types of carcinomas. Patients with sporadic carcinoma and colitis-associated carcinoma as well as patients with normal colon and patients with confirmed ulcerative colitis without neoplasia were used for the analysis. By extensively filtering the results, methylation sites relevant to distinguish between CAC and sCRC were identified. RESULTS: After the results were filtered, three methylation sites relevant to distinguish between CAC and sCRC were identified. For this purpose, methylation limit values were defined, which favor the samples as CAC or sCRC up to a certain methylation value of the methylation sites. The combination of three methylation sites allows a correct assignment to CAC or sCRC in 94.5% of the cases. CONCLUSION: The results show that these three methylation sites are promising markers in the diagnosis of CAC vs sCRC. Nevertheless, the diagnosis should always be made in conjunction with histomorphological analyses.
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Colite Ulcerativa , Neoplasias Associadas a Colite , Neoplasias Colorretais , Metilação de DNA , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Colite Ulcerativa/complicações , Neoplasias Colorretais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Associadas a Colite/patologia , Neoplasias Associadas a Colite/genética , Neoplasias Associadas a Colite/diagnóstico , Masculino , Feminino , Epigênese GenéticaRESUMO
Background: Endoscopic resection for early neoplastic lesions of the gastrointestinal tract is nowadays the accepted and feasible method also in non-tertiary reference centers. The main clinical advantage is the preserved quality of life compared to larger surgical procedures. Summary: Clinical colleagues need to have basic knowledge of factors that may influence the outcome of histopathology. This article discusses issues connected to the histopathological work-up of endoscopic resection specimens within in the gastrointestinal tract. Key Messages: Besides the clinical technical prerequisites, standardized histopathology is the key element of the pathology laboratory work-up of endoscopic resection specimens. Overdiagnoses of reactive lesions as low-grade neoplasia lead to incomparable study data and although criteria to overcome this situation exist, they are not accepted worldwide, calling for further efforts in harmonization.
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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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Fusobacterium nucleatum is supposed to play a critical role in the development of colorectal cancer. The species has also been associated with ulcerative colitis (UC) that can progress into colorectal cancer, however, the involvement of bacteria in this process remains unclear. We analysed 177 colon biopsies obtained from patients during screening, including 20 healthy controls, 56 UC cases and 69 cases at different stages of progression to colitis-associated cancer (CAC); 32 samples of sporadic colorectal carcinoma (sCRC) were also included. The presence of F. nucleatum was detected by quantitative real-time PCR (qPCR). Our data show an association between the presence of the bacteria and the progression of carcinogenesis in UC patients. In 39.5% of CAC samples F. nucleatum was detected, compared to only 1.8% in UC cases. The bacteria were detected in 6.3% of samples with initial neoplastic transformation, so-called low-grade dysplasia (LGD), whereas high-grade dysplasia (HGD) resulted in 33.3% of samples positive for F. nucleatum. The fraction of F. nucleatum-positive samples from sCRC cases was 56.3%, which was not significantly different to the CAC group. We conclude that F. nucleatum is associated with the occurrence and progression of colon carcinogenesis, rather than with UC itself.
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Colite Ulcerativa , Neoplasias Associadas a Colite , Humanos , Fusobacterium nucleatum , Colite Ulcerativa/complicações , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , CarcinogêneseRESUMO
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
PURPOSE: To study the relationship between standardized 18F-FDG PET/CT radiomic features and clinicopathological variables and programmed death ligand-1 (PD-L1) expression status in non-small cell lung cancer (NSCLC) patients. METHODS: 58 NSCLC patients with preoperative 18F-FDG PET/CT scans and postoperative results of PD-L1 expression were retrospectively analysed. A standardized, open-source software was used to extract 86 radiomic features from PET and low-dose CT images. Univariate analysis and multivariate logistic regression were used to find independent predictors of PD-L1 expression. The Area Under the Curve (AUC) of receiver operating characteristic (ROC) curve was used to compare the ability of variables and their combination in predicting PD-L1 expression. RESULTS: Multivariate logistic regression resulted in the PET radiomic feature GLRLM_LGRE (Odds Rate (OR): 0.300 vs 0.114, 95% confidence interval (CI): 0.096-0.931 vs 0.021-0.616, in NSCLC and adenocarcinoma respectively) and the CT radiomic feature GLZLM_SZE (OR: 3.338 vs 7.504, 95%CI: 1.074-10.375 vs 1.382-40.755, in NSCLC and adenocarcinoma respectively), being independent predictors of PD-L1 status. In NSCLC group, after adjusting for gender and histology, the PET radiomic feature GLRLM_LGRE (OR: 0.282, 95%CI: 0.085-0.936) remained an independent predictor for PD-L1 status. In the adenocarcinoma group, when adjusting for gender the PET radiomic feature GLRLM_LGRE (OR: 0.115, 95%CI: 0.021-0.631) and the CT radiomic feature GLZLM_SZE (OR: 7.343, 95%CI: 1.285-41.965) remained associated with PD-L1 expression. CONCLUSION: NSCLC and adenocarcinoma with PD-L1 expression show higher tumour heterogeneity. Heterogeneity-related 18F-FDG PET and CT radiomic features showed good ability to non-invasively predict PD-L1 expression.
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Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos RetrospectivosRESUMO
The treatment of infections by the gastric pathogen Helicobacter pylori (H. pylori) has become more difficult due to increased rates of resistances against various antibiotics. Typically, atriple therapy, employing a combination of at least two antibiotics and a proton pump inhibitor, is used to cure H. pylori infections. In case of first-line therapy failure, quinolones are commonly applied in a second-line therapy. To prevent second-line treatment failures, we developed an improved method to detect the most common quinolone-resistance mutations located in the quinolone-resistance-determining region (QRDR) of the bacterial gyrA gene. Biopsy material from the gastric mucosa of infected patients was used to identify quinolone-resistant strains before the onset of drug administration. Two different wild-type and six mutant QRDR sequences were included. Melting curve analyses were performed with corresponding gyrA plasmid DNAs using a real-time polymerase chain reaction (RT-PCR) assay. By applying a combination of only two different fluorescent probes, this assay allows wild-type sequences to be unambiguously distinguished from all known mutant QRDR sequences of H. pylori. Next, the Tm values of patient DNAs were established, and the genotypes were confirmed by sequencing. Thus, quinolone-resistant H. pylori strains can be easily and quickly diagnosed before treatment, which will help to avoid the administration of ineffective drug regimes.
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BACKGROUND AND AIMS: Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett's oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation. METHODS: This hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE. Subsequently, a prospective histocytological analysis of endoscope channels and accessories was performed in 2 phases (cytohistological analysis; test for cell viability) in 22 different oesophageal carcinoma patients undergoing endoscopy. Finally, cultures from two oesophageal adenocarcinoma cell lines were incubated with different triamcinolone concentrations (0.625-10 mg/mL); cell growth was determined on a Multiwell plate reader. RESULTS: Cancer regrowth in the two suspicious cases (male, 78/71 years) occurred 7 and 1 months, respectively, after curative tumour resection. Subsequent surgery showed advanced tumours (T2) with lymph node metastases; one patient died. On cytohistological examinations of channels and accessories, suspicious/neoplastic cells were found in 4/10 superficial and in all 5 advanced cancers. Further analyses in seven further advanced adenocarcinoma cases showed viable cells in two channel washing specimens. Finally, cell culture experiments demonstrated enhanced tumour cell growth by triamcinolone after 24 hours compared with controls. CONCLUSIONS: Tumour cell reimplanation from contaminated endoscopes and accessories is a possible cause of local recurrence after curative endoscopic therapy for superficial Barrett carcinoma; also, corticosteroid injection could have promoted tumour regrowth in these cases.
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Esôfago de Barrett/cirurgia , Carcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagoscopia/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Inoculação de Neoplasia , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/patologia , Carcinoma/etiologia , Carcinoma/patologia , Estudos de Coortes , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Fatores de RiscoRESUMO
In non-small cell lung cancer (NSCLC), approximately 1-3% of cases harbor an increased gene copy number (GCN) of the MET gene. This alteration can be due to de novo amplification of the MET gene or can represent a secondary resistance mechanism in response to targeted therapies. To date, the gold standard method to evaluate the GCN of MET is fluorescence in situ hybridization (FISH). However, next-generation sequencing (NGS) is becoming more relevant to optimize therapy by revealing the mutational profile of each NSCLC. Using evaluable n = 205 NSCLC cases of a consecutive cohort, this study addressed the question of whether an amplicon based NGS assay can completely replace the FISH method regarding the classification of MET GCN status. Out of the 205 evaluable cases, only n = 9 cases (43.7%) of n = 16 high-level MET amplified cases assessed by FISH were classified as amplified by NGS. Cases harboring a MET GCN > 10 showed the best concordance when comparing FISH versus NGS (80%). This study confirms that an amplicon-based NGS assessment of the MET GCN detects high-level MET amplified cases harboring a MET GCN > 10 but fails to detect the various facets of MET gene amplification in the context of a therapy-induced resistance mechanism.
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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
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
BACKGROUND: We aimed to provide insight into the actual frequencies of gastric adenoma types and their association with gastritis status and associated mucosal changes with a focus on Helicobacter infection and the operative link on gastritis assessment (OLGA)/operative link on gastric intestinal metaplasia assessment (OLGIM) staging. METHODS: From the archive of the Institute of Pathology in Bayreuth, we collected a consecutive series of 1058 gastric adenomas diagnosed between 1987 and 2017. Clinicopathological parameters retrieved from diagnostic reports included adenoma type and localization, associated mucosal changes in antrum and corpus (i.e., type of gastritis, the extent of intestinal metaplasia and atrophy), gender, date of birth, and date of diagnosis. RESULTS: Intestinal-type adenoma was the most frequent adenoma (89.1%), followed by foveolar-type adenoma (4.3%), pyloric gland adenoma (3.4%), adenomas associated with hereditary tumor syndromes (2.8%), and oxyntic gland adenoma (0.4%). Adenomas were found in the background of Helicobacter pylori (H. pylori) gastritis in 23.9%, Ex-H. pylori gastritis in 36.0%, autoimmune gastritis in 24.8%, chemical reactive gastritis in 7.4%, and others in 0.1%. More than 70% of patients with gastric adenomas had low-risk stages in OLGA and OLGIM. CONCLUSIONS: We found a higher frequency of foveolar-type adenoma than anticipated from the literature. It needs to be questioned whether OLGA/OLGIM staging can be applied to all patients.
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BACKGROUND: Diagnosing low grade intraepithelial neoplasia (LGIN) in patients with ulcerative colitis (UC) is difficult. Distinguishing between sporadic adenoma (SA) and UC associated LGIN is even more challenging but has clinical impact. We aimed to examine, if the morphological distinction between both entities is reliably possible, how it influences patient's outcome and the role of the endoscopist in this decision with respect to current endoscopy classification schemes. METHODS: Seven pathologists retrospectively reevaluated 425 cases of LGIN in UC patients, diagnosed between 2009 and 2017 with preceding expert consensus and follow up in two separate readings, based on published morphological differentiation criteria. In the first evaluation, the observers were blinded to any clinical data. In the second evaluation, they knew patients' age as well as endoscopic features. They also rated their subjective diagnostic certainty. RESULTS: Diagnostic correctness improved significantly in the second assessment as did the pathologists' confidence in their diagnoses (p < 0.001 - p = 0.019). Knowledge of clinical and endoscopical data led to a higher percentage of SA (71.8% vs. 85.6%). UC associated LGIN showed significant earlier LGIN relapse as well as more high grade intraepithelial neoplasia and carcinoma during follow up (p < 0.001, p < 0.001, p = 0.005). CONCLUSIONS: Distinction between SA and UC associated LGIN is important as it has an impact on patients' follow up and treatment. Morphological distinction remains difficult with moderate interobserver variability. Adequate clinical information significantly improves pathologists' diagnoses as well as their confidence in their diagnoses.
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Adenoma/patologia , Carcinoma in Situ/patologia , Colite Ulcerativa/complicações , Neoplasias do Colo/patologia , Adenoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/diagnóstico , Neoplasias do Colo/diagnóstico , Endoscopia do Sistema Digestório , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Prognóstico , Estudos RetrospectivosRESUMO
Unfortunately we did not explain the type of sample collection in "materials and methods".
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BACKGROUND: Cytological analysis of ascitic fluid is an important tool for diagnosis, staging, and prognostic assessment in patients with cancer, but more detailed information is needed regarding malignancy rates and the time sequence in which ascites develops for different sites of cancer origin. Especially, an increased early tumor diagnosis may improve the acceptance for cytological examinations for the tumor patients in oncological practice. METHODS: Ascites specimens from patients who were treated at Bayreuth Hospital from 2006 to 2015 were reevaluated retrospectively and correlated with clinical reports. RESULTS: 580 of all 941 ascitis specimens (61.6%) were from patients with malignancies with predominant appearance of gastrointestinal and gynecological tumors in 516/580 (89%) patients. Histologically, 549 (94.6%) were carcinomas, 23 (4%) hematological malignancies, 5 (0.9%) mesotheliomas and 3 (0.5%) were melanomas. Malignant ascitic fluid was noted in 298 of the 580 (51.4%) patients with cancer, thus the overall malignancy rate in the ascites specimens examined was 298/941 (31.7%). The most frequent malignancy rate for gynecological tumors we obtained in ovarian cancer with 85.7% and in the upper gastrointestinal tract with 77.8% for Barrett's carcinoma and 61,4% for gastric carcinoma. Regarding time of detection, malignant ascitic fluid was noted as a separate finding, prior or simultaneous to the histological diagnosis of cancer in 225/298 patients (75.5%). An outstanding earliest occurrence was found in ovarian carcinoma in 94.9% and in the gastrointestinal tract in pancreatic carcinoma in 66.7%. CONCLUSIONS: Tumor staging was the main important clinical question in our single center study of ascitic fluid, especially for patients with gastrointestinal and gynecological malignomas. The highest malignancy rate and earliest time of tumor detection caused the leading importance for ovarian tumors in malignant ascitic fluid. Moreover, the application of immunostains in our study allowed in 75.5% of all tumor patients a correct initial diagnosis, which is important for further clinical therapy.
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Clustering in medicine is the subgrouping of a cohort according to specific phenotypical or genotypical traits. For breast cancer and lymphomas, clustering by gene expression profiles has already resulted in important prognostic and predictive subgroups. For non-small cell lung cancer (NSCLC), however, little is known. We performed a cluster analysis on a cohort of 365 surgically resected, well-documented NSCLC patients, which was followed-up for a median of 62 months, incorporating 70 expressed proteins and several genes. Our data reveal that tumor grading by architecture is significant, that large cell carcinoma is likely not a separate entity, and that an immune signature cluster exists. For squamous cell carcinomas, a prognostically relevant cluster with poorer outcome was found, defined by a high CD4/CD8 ratio and lower presence of granzyme B+ tumor-infiltrating lymphocytes (TIL). This study shows that clustering analysis is a useful tool for verifying established characteristics and generating new insights for NSCLC. Importantly, for one "immune signature" cluster, the signature of the TIL (especially the amount of CD8+ TIL) was more crucial than the histologic or any other phenotypical aspect. This may be an important finding toward explaining why only a fraction of eligible patients respond to immunomodulating anticancer therapies.
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Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Linfócitos do Interstício Tumoral , Idoso , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Malignant melanoma metastases are chameleons of histopathology. In 4 primary malignant melanomas and 20 melanoma metastases expression of S-100, HMB-45 and melan-A as melanoma markers and CD56, synaptophysin and chromogranin-A as neuroendocrine markers was retrospectively analyzed. While all primary tumors expressed all 3 melanoma markers 7/20 of melanoma metastases had lost at least one melanoma marker, one had lost all three markers. Conversely about half of the samples stained for CD56, only 6/20 metastases were negative for all 3 neuroendocrine markers. None expressed chromogranin-A. Partial loss of melanoma markers and expression of neuroendocrine markers seems not to be infrequent. In patients with a history of malignant melanoma and suspected metastases, losing melanoma markers while expressing neuroendocrine markers is a potential diagnostic pitfall. Therefore all 3 melanoma markers should be performed as well as chromogranin-A staining. In doubt, metastases of the melanoma should be assumed.
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Biomarcadores Tumorais/análise , Melanoma/diagnóstico , Melanoma/patologia , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Melanoma Maligno CutâneoRESUMO
Grading for colorectal carcinoma (CRC) is traditionally based on the percentage of gland formation. In recent years, high-grade CRC has become subject to more precise molecular grading strategies. Most, however, are low-grade cases according to the World Health Organization (WHO) with inhomogenous outcomes due to still insufficient characterization. On the other hand, budding and tumor-infiltrating lymphocytes have developed as interesting additive prognostic factors in CRC. Especially budding has been very well defined by the International Tumor Budding Consensus Conference recently. We analyzed a large collective of 576 WHO low-grade CRC cases, stages I to IV, diagnosed between 2005 and 2016 in terms of gland formation, budding, and tumor-infiltrating lymphocytes and developed a new, morphology-based risk score, taking into account each of the 3 parameters. For each parameter, 1 to 2 points were given, resulting in a sum score, dividing the CRC cases into a low-, an intermediate-, and a high-risk group. By our score, 179 (34.9%) of the cases were grouped as low risk, 241 (53.5) as intermediate risk, and 92 (35.5%) as high risk. The 3 groups differed significantly in pT, pN, and M as well as tumor stages, lymphatic vessel invasion, venous invasion, and overall survival (0.;P < .001 for low risk versus high risk, P = .038 for low versus intermediate risk, and P = .036 for intermediate versus high risk; log rank: median, 94.0 months [95% confidence interval {CI}, 74.9-113.1] for low risk; median, 63.0 months [95% CI, 44.0-82.0] for intermediate risk; and median, 40.0 months [95% CI, 23.4-56.7] for high risk) in Kaplan-Meier-analysis. Our proposed Bayreuth score enables separating the large group of WHO low-grade CRC cases into subgroups, which differ significantly in outcome.
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Adenocarcinoma/classificação , Adenocarcinoma/patologia , Neoplasias Colorretais/classificação , Neoplasias Colorretais/patologia , Gradação de Tumores/métodos , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Linfócitos do Interstício Tumoral , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Extramural venous invasion (EMVI) is prognostic for colorectal cancer; however, veins are only detected partially by normal perpendicular preparation. Therefore, reported findings are conflicting and standardization is required. A total of 239 resection specimens were examined by tangential preparation of the extramural veins at the invasive tumor front. Average follow-up was 39 months. The relationship of EMVI to metachronous hematogenic metastasis (MHM) was evaluated. With this method, a high prevalence of EMVI beginning in stage II is apparent. In stage I, 66% of patients with EMVI developed MHM; in stage II, 25%; and in stage III, 49%. In stage III, the number of tumor-invaded veins is crucial. In the absence of detection of EMVI, MHM occurred in 1 of 29 patients in stage II and in 2 of 13 patients in early stage III. By tangential sectioning at the invasive tumor front, we found a high incidence of EMVI beginning in stage II, which increases with tumor stage. Especially in stages II and III, the correct determination of absent EMVI has a high negative predictive value for MHM. In stage I, EMVI defines a patient group with increased risk for MHM. The quantification of EMVI is an important issue for standardization.
Assuntos
Neoplasias Colorretais/patologia , Invasividade Neoplásica/patologia , Veias/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Malignant ascites often develops in patients with ovarian cancer, but there is a lack of more detailed characterization of the different histological subtypes. METHODS: Ascites specimens from patients with ovarian cancer who were treated at Bayreuth Hospital from 2006 to 2015, with follow-up until December 2016, were reevaluated retrospectively. RESULTS: A total of 191 women (mean age 64 years, range 48-79) were included, of whom 180 (94.2%) had carcinoma, three (1.6%) had malignant mixed müllerian tumors (MMMTs), four (2.1%) had sex cord-stromal tumors (SCSTs), three (1.6%) had germ cell tumors (GCTs), and one (0.5%) had a sarcoma. The carcinoma group comprised 134 (70.1%) patients with high-grade serous papillary ovarian cancer, 17 (8.9%) with low-grade serous papillary ovarian cancer, 10 (5.3%) with mucinous carcinomas, nine (4.7%) with endometrioid carcinomas, six (3.1%) with clear cell carcinomas, and four (2.1%) with neuroendocrine tumors. The latter group consisted of two patients with mixed neuroendocrine-nonneuroendocrine tumors (MiNENs), one with only a small cell carcinoma (SCCO), and one with a mucinous carcinoid. The noncarcinomatous group of eight patients (4.2%) included three (1.6%) with Sertoli-Leydig cell tumor and mature cystic teratoma (MCT), one (0.5%) with a granulosa cell tumor, and one with a leiomyosarcoma. A statistically significant difference in the proportion of patients with malignant ascites was observed, at 17.7% (3/17) in those with low-grade serous papillary ovarian cancer and 91.8% (123/134) in those with high-grade serous papillary ovarian carcinomas. In both patients with MiNEN, the glandular tumor cell component was found in the ascites. Tumor cells were found in the ascitic fluid in 50% (5/10) of patients with mucinous ovarian carcinomas, 16.7% (1/6) of those with clear cell carcinomas, and 33.3% (1/3) of those with MMMTs. The two patients (2/3; 66.7%) with neoplastic squamous cell components in MCT and the only patient with a granulosa cell tumor in the SCST group (1/4; 25%) had malignant cell populations in the ascites, whereas patients with endometrioid cell carcinoma and leiomyosarcoma lacked tumor cells in the ascites. The malignant ascites was detected at the initial diagnosis in all 138 (100%) patients with ovarian neoplasms. CONCLUSIONS: High-grade serous papillary ovarian cancer was the main histological subtype most frequently found in ascites fluid in this series. The significant difference (P < 0.00001) in the malignancy rate in comparison with low-grade serous papillary carcinoma confirms the histological distinction between the two entities. Initial evidence of ovarian cancer in ascites fluid allows correct primary diagnosis in cytology specimens and is important for staging and prognosis.