Two-tier Grading System Research Articles

Low-Grade Ductal Carcinoma In Situ.

We aimed to determine the interobserver reproducibility in diagnosing low-grade ductal carcinoma in situ (DCIS). We also aimed to compare the interobserver variability using a proposed two-tiered grading system as opposed to the current three-tiered system. Three expert breast pathologists and one junior pathologist identified low-grade DCIS from a set of 300 DCIS slides. Months later, participants were asked to grade the 300 cases using the standard three-tiered system. Using the two-tiered system, interobserver agreement among breast pathologists was considered moderate (κ = 0.575). The agreement was similar (κ = 0.532) with the junior pathologist included. Using the three-tiered system, pathologists' agreement was poor (κ = 0.235). Pathologists' reproducibility on diagnosing low-grade DCIS showed moderate agreement. Experience does not seem to influence reproducibility. Our proposed two-tiered system of low vs nonlow grade, where the intermediate grade is grouped in the nonlow category has shown improved concordance.

Multi-institutional re-evaluation of prognostic factors in chromophobe renal cell carcinoma: proposal of a novel two-tiered grading scheme.

A histological grading system of chromophobe renal cell carcinoma (chRCC) is highly desirable to identify approximately 5-10% of tumors at risk for progression. Validation studies failed to demonstrate a correlation between the four-tiered WHO/ISUP grade and outcome. Previous proposals with three-tiered chromophobe grading systems could not be validated. In this study, the presence of sarcomatoid differentiation, necrosis, and mitosis was analyzed in a Swiss cohort (n = 42), an Italian cohort (n = 103), a German cohort (n = 54), a Japanese cohort (n = 119), and The Cancer Genome Atlas cohort (n = 64). All 3 histological parameters were significantly associated with shorter time to tumor progression and overall survival in univariate analysis. Interobserver variability for identification of these parameters was measured by Krippendorff's alpha coefficient and showed high concordance for the identification of sarcomatoid differentiation and tumor necrosis, but only low to medium concordance for the identification of mitosis. Therefore, we tested a two-tiered tumor grading system (low versus high grade) based only on the presence of sarcomatoid differentiation and/or necrosis finding in the combined cohorts (n = 382). pT stage, patient's age (> 65 vs ≤ 65), lymph node and/or distant metastasis, and the two-tiered grading system (low versus high grade) were significantly associated with overall survival and were independent prognostic parameters in multivariate analysis (Cox proportional hazard). This multi-institutional evaluation of prognostic parameters suggests tumor necrosis and sarcomatoid differentiation as reproducible components of a two-tiered chromophobe tumor grading system.

Low-grade epithelial ovarian cancer: what a radiologist should know.

Ovarian cancer accounts for the death of over 100,000 females every year and is the most lethal gynecological malignancy. Low-grade serous ovarian carcinoma (LGSOC) and high-grade serous ovarian carcinoma (HGSOC) have been found to represent two distinct entities based on their molecular differences, clinical course, and response to chemotherapy. Currently, all ovarian cancers are staged according to the revised staging system of the International Federation of Gynecology and Obstetrics (FIGO). Imaging plays an integral role in the diagnosis, staging, and follow-up of ovarian cancers. This review will be based on the two-tier grading system of epithelial ovarian cancers, with the main emphasis on serous ovarian cancer, and the role of imaging to characterize low-grade vs high-grade tumors and monitor disease recurrence during follow-up.

Should Pass/Fail Grading Be Used Instead of Traditional Letter Grades in Dental Education? Two Viewpoints: Viewpoint 1: Pass/Fail Grading Improves Learning Experiences for Students and Viewpoint 2: Traditional Letter Grading Provides Objective Evaluation for Dental Education.

Discussions about which grading system (letter grade or pass/fail) is more effective in dental education have been occurring for several decades. As more institutions continue to consider the change from the traditional five-tier letter grading system (A/B/C/D/F) to a two-tier grading system (pass/fail), this debate will likely continue. This point/counterpoint article examines arguments for and against each type of grading system, taking into consideration academic performance, learning outcomes, psychological well-being, learning environment, acceptance/performance in postgraduate educational programs, and student motivation. Viewpoint 1 supports the position that a pass/fail system improves learning experiences for dental students, whereas Viewpoint 2 argues that the traditional letter grading system provides for more objectivity and reliability in student evaluation.

Low-grade Serous Ovarian Carcinoma.

In the early 2000s a two-tier grading system was introduced for serous ovarian cancer. Since then, we have increasingly come to accept that low-grade serous ovarian carcinoma (LGSOC) is a separate entity with a unique mutational landscape and clinical behaviour. As less than 10% of serous carcinomas of the ovary are low-grade, they are present in only a small number of patients in clinical trials for ovarian cancer. Therefore the current treatment of LGSOC is based on smaller trials, retrospective series, and subgroup analysis of large clinical trials on ovarian cancer. Surgery plays a major role in the treatment of patients with LGSOC. In the systemic treatment of LGSOC, hormonal treatment and targeted therapies seem to play an important role.

Tu1944 - Grading, Budding, Tumor Infiltrating Lymphocytes – Proposal for a Combined, Two-Tier Grading System in Colorectal Cancer with Impact on Clinical Course and Patient Outcome

Tu1944 - Grading, Budding, Tumor Infiltrating Lymphocytes – Proposal for a Combined, Two-Tier Grading System in Colorectal Cancer with Impact on Clinical Course and Patient Outcome

The new classifications of ovarian, fallopian tube, and primary peritoneal cancer and their clinical implications

The roles of histologic characterization and staging are to provide reproducible metrics for cancer classification with which to direct the most appropriate clinical care and to yield the most stable reliable system to allow both prospective and retrospective data analysis. Both the histologic and staging classifications of malignant ovarian/tubal/peritoneal cancers have recently changed. The World Health Organization sponsored a review and reclassification of the pathology of cancers of the ovaries, fallopian tubes, and peritoneum, and published these updates in 2014. In so doing, they codified the two-tiered grading system that has been in use in serous ovarian cancers for nearly a decade. In parallel, FIGO reviewed and updated the surgical staging system, applied to all histotypes of ovarian, tubal, and peritoneal cancers, also published in 2014. In both cases, the changes made are meant to encompass a better understanding of disease, but both have important merits and drawbacks. Changes in staging complicate analysis of retrospective data against current data. Though in some aspects controversial, the changes overall are meant to represent a better biologic understanding of disease that we hope will lead to an improvement in patient care and directed therapy.

Immunohistochemical Expression of Human Epididymis 4 (He4) in Ovarian Serous Carcinoma in Hospital Serdang from the Year 2006- 2013

Ovarian cancer is the fifth most common cause of cancer death in women worldwide and is the fourth leading cause of cancer related deaths in Malaysia. Ovarian cancer are classified based on histological types, because it is an important surrogate for genetic, prognostic, and predictive information about response to treatment. The malignant epithelial tumor, that is ovarian carcinoma (OC) is the most common group and the four most common subtypes of OC are serous, endometrioid, clear cell and mucinous. Among the OC, ovarian serous carcinoma (OSC) is the most common subtypes. Most of the women with OC presented with locally advanced disease or distant metastasized at the time of diagnosis. The two-tier grading system (also known as MDACC [M.D Anderson Cancer Center] grading system) has been accepted worldwide. Human epididymis 4 (HE4) is a new protein which is frequently overexpressed in ovarian neoplastic tissue. Previous studies have shown that there is significant difference of HE4 expression in low grade serous carcinoma (LGSC) and high grade serous carcinoma (HGSC). The aim of this study is to further evaluate the HE4 tissue expression in 2 different grades of OSC in Hospital Serdang. This is a retrospective, cross-sectional study, of 71 cases histopathologically diagnosed as OSC comprising of 48 cases of HGSC and 23 cases of LGSC. Cases were collected from Hospital Serdang, from 1st January 2006 to 31st December 2013. All cases were examined for HE4 expression by immunohistochemistry using anti-HE4 (Polyclonal rabbit antibody dilution 1:40, Abcam).

Do pathological variables have prognostic significance in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and surgery?

AIMTo clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery.METHODSTumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses.RESULTScN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables.CONCLUSIONOur data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.

Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients.

New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p=0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p=0.025). The MDACC grading system (p=0.008) but not the FIGO system (p=0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95% CI 1.007-2.449; p=0.047, and HR 0.712; 95% CI 0.476-1.066; p=0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95% CI 1.207-3.835; p=0.009, and HR 1.258; 95% CI 0.801-1.975; p=0.319, respectively). We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system.

Análise de sobrevida e fatores prognósticos de cães com mastocitoma cutâneo

O mastocitoma é a neoplasia cutânea maligna de maior frequência em cães. Apesar do estudo e do desenvolvimento de diversos marcadores prognósticos na tentativa de prever o comportamento biológico deste tipo de neoplasia, a graduação histológica continua sendo utilizada como principal delineador prognóstico para os animais acometidos, mesmo não conseguindo prever o comportamento de mastocitomas de diferenciação intermediária. Diferentes marcadores de proliferação e atividade celular vêm sendo testados com resultados promissores, entretanto, em sua maioria, demandam técnicas específicas de coloração e imuno-histoquímica que, ainda hoje, são de alto custo e muitas vezes não estão facilmente disponíveis. O índice mitótico é um método indireto de mensuração da atividade proliferativa celular, que pode ser contabilizado em uma lâmina comum de avaliação histológica e estudos vêm determinando-o como importante marcador prognóstico para o mastocitoma canino. Dada a recente publicação sugerindo nova graduação em dois graus (alto e baixo) e indisponibilidade das técnicas específicas utilizadas na determinação de outros fatores prognósticos, objetivou-se avaliar o poder prognóstico das diferentes classificações, associando-as à sobrevida destes animais e comparando com o índice mitótico. Apesar de isoladamente ambas as classificações histológicas apresentarem associação com a sobrevida (P<.001) dos animais acometidos, na análise multifatorial nenhuma foi significativamente associada com a sobrevida (P>0,05). O índice mitótico foi o fator prognóstico mais confiável para sobrevida, independente do ponto de corte utilizado (P<0,05), principalmente para os mastocitomas grau 2 de Patnaik et al. (1984), que apresentam comportamento biológico variado, sendo também associado à ocorrência de recidivas, tanto locais como distantes, e de síndromes paraneoplásicas (P<0,05). Conclui-se ser o índice mitótico o fator prognóstico mais significante, na ausência de técnicas específicas mais avançadas. Preconiza-se seu uso associado às graduações histológicas, visando maior poder prognóstico.

Is the two-tier ovarian serous carcinoma grading system potentially useful in stratifying uterine serous carcinoma? A large multi-institutional analysis

ObjectiveA subset of uterine serous carcinoma (USC) may have better clinical behavior bringing up the possibility that there may be morphologic features, which would help in their categorization. The aim of this study is to evaluate the potential use of the MD Anderson Cancer Center 2-tier grading system for ovarian carcinoma in USC. MethodsTumors assigned a combined score included in this analysis were 1) low-grade: tumors without marked atypia and 12 mitoses/10 high power field (HPF) and 2) high grade: tumors with severe nuclear atypia and >12 mitoses/10 HPF. Clinicopathologic parameters evaluated included patients' age, tumor size, myometrial invasion (MI), lymphovascular invasion (LVI), lymph node (LN), FIGO stage, and patient outcome. Results140 patients with USC were included, 30 low grade uterine serous carcinoma (LGUSC) and 110 high grade uterine serous carcinoma (HGUSC). Of all parameters only 2 (MI and stage IA) reached statistical significance. 67% of LGUSC cases showed myometrial invasion versus 93.6% HGUSC cases (p=0.003). A higher percentage of LGUSC (63.3%) versus HGUSC (32.7%) were in stage IA (p=0.01). However, by multivariate analysis including age, LVI, stage and tumor grade only stage was an independent prognostic factor. ConclusionThe presence of atypia and mitosis across a uterine serous carcinoma is notoriously variable in magnitude and extent, potentially making evaluation of these features difficult and subsequent grading subjective. Our findings thus show that actual prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma may not be applicable.

Pathology and pathobiology of the gastric carcinoma

Recent epidemiological studies in Serbia revealed that gastric carcinoma is the third and the fifth main cause of cancer morbidity in men and women, respectively. Despite the declining incidence of gastric cancer, it remains the second most common cause of cancer-related deaths as it is worldwide. A well-defined carcinogenic inflammation-metaplasia-dysplasia-cancer sequence typically precedes the development of most gastric adenocarcinomas. Alterations such as gastric mucosal atrophy and intestinal metaplasia are merely markers of increased risk, while gastric epithelial dysplasia (GED) represent a direct precursor of cancer. DNA damage and increased mucosal proliferation secondary to H pylori infection, combined with a suitable host susceptibility phenotype (eg, genetic polymorphisms in interleukin IL-1B, IL-1RN, and tumor necrosis factor a TNF-alpha genes), are important factors in this progression pathway. However, only a small minority of patients infected with H. pylori eventually develops gastric cancer, and eradication of H pylori in these patients does not seem to eliminate the risk of cancer completely. It has been shown that atrophy may be a better indicator of risk of cancer than intestinal metaplasia, and remains to be validated in routine clinical practice according to recent proposal for new quantitative methods. It is often associated with pseudopyloric gland metaplasia in the gastric corpus mucosa, which expresses a type of trefoil peptide, the spasmolytic polypeptide (termed spasmolytic polypeptide-expressing metaplasia or SPEM) and has been shown to be linked more closely to gastric cancer than intestinal metaplasia. Better histological characterization of adenomatous (or type I), hyperplastic (foveolar or type II) and tubule-neck (mucocellular or type III) GED, two-tiered grading system (low and high grade dysplasia) as well as the introduction of Padova and Vienna international classifications of dysplasia seem to be more helpful in GED surveillance and comparative studies. A combination of histopathological features, serum markers such as pepsinogen I, and molecular tests that analyze host susceptibility polymorphisms and bacterial virulence factors, may allow development of strategies for early detection of cancer in the future. At present, pathobiology of gastric cancerogenesis is far from known, despite the progressive knowledge on predisposing environmental conditions and genetic and epigenetic abnormalities, including tumour suppressor genes, oncogenes, microsatellite instability and hypermethylation or the significance of E-cadherin mutational status association with hereditary diffuse gastric cancer syndrome. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as resection margin status and lymph node metastases and their implications have also been discussed. We aim to review these aspects, with special relevance to gastric cancer specimen reporting.

Application of simplified Fuhrman grading system in clear‐cell renal cell carcinoma

To investigate the efficacy of simplified (two- or three-tiered) Fuhrman grading systems as prognostic indicators in clear-cell renal cell carcinoma (RCC). By reviewing records, various clinicopathological factors were assessed in 431 patients who received surgical management for clear-cell RCC. A conventional four-tiered Fuhrman grading system was compared with a modified two-tiered grading system (Fuhrman grades I and II were combined as one class, and grades III and IV as another) and also with a three-tiered grading system (only grades I and II were combined). Efficacies of grading systems were assessed via univariate analyses and multivariate models for prediction of cancer-specific survival. In univariate analysis, the four-tiered and three-tiered grading systems showed similar accuracies (76.5 vs 76.2%, P =0.614) for predicting cancer-specific survival, which were greater than that of the two-tiered system (72.5%; both P < 0.05). Of the three grading systems, only the three-tiered system was an independent predictor of cancer-specific survival in multivariate analysis (P = 0.046). When receiver operating characteristic-derived areas under the curve (AUCs) of multivariate models for predicting cancer-specific survivals were assessed, AUCs for models including the three-tiered Fuhrman grading system and the conventional four-tiered Fuhrman grading system were the same (95.3%), followed by that of a model incorporating the two-tiered grading system (95.1%). A modified, three-tiered Fuhrman grading system can be considered an appropriate option in the application of a nuclear grading system to the prognostication of clear-cell RCC in both univariate analysis and multivariate model setting.

Assessment of prognostic factors in pancreatic ductal adenocarcinoma: Focus on the retroperitoneal margin

e15670 Background: Pancreatic ductal adenocarcinoma (PDA) is a leading cause of cancer death in the West, with a nearly superimposable incidence and mortality. Resection is the only chance for cure, and various features in resection specimens correlate with outcome. While most consider the uncinate margin (UM) to be the true retroperitoneal margin, it has been suggested that the posterior pancreatic surface (PPS) may also be important. At another site with a retroperitoneal margin (i.e. rectum), 1 mm margins are significant. We thus evaluated margin status in various ways, focusing on the retroperitoneal region and emphasizing outcome. Methods: We identified all pancreaticoduodenectomies for PDA over a 6 year period in which the PPS was histologically evaluable. Tumors were assessed for the following: size, stage, grade, lymph node (LN) status, vascular and perineural invasion, and margin status. Margin status was evaluated in 3 ways: traditional margins (tumor at pancreatic neck, bile duct, and/or uncinate margins), 1 mm margins (traditional + tumor within 1 mm of UM), and PPS margins (traditional + tumor within 1 mm of PPS or UM). Kaplan-Meier survival curves were constructed with univariate factors compared by log rank analysis; multivariate analysis was done using the Cox proportional hazard model. Results: Fifty-one tumors exhibited the following features: size (mean 3.3 cm), stage (48 T3), grade (27 low, 24 high), LN status (11 neg, 40 pos), positive margins (13 traditional, 23 1 mm, and 32 PPS). Nearly all tumors exhibited at least focal vascular and perineural invasion. Grade influenced survival (p=0.0001), while size (p=0.417) and traditional and PPS margins did not (p=0.5 and 0.95). LN status and 1 mm margins trended toward significance (p=0.17 and 0.2). Conclusions: Use of a two-tiered grading system is highly correlated with survival. Neither tumor size, LN status, nor traditional or PPS margins are significant, while 1 mm margins trend toward significance. Although lack of significance of some features (i.e. size, LN status, and traditional margin status) may be attributable to modest sample size, lack of significance of the PPS may reflect its anatomic nature (i.e. not a true surgical margin). Additional study of 1 mm margins in a larger tumor set is warranted. No significant financial relationships to disclose.

Diagnostic concordance among dermatopathologists using a three‐tiered keratinocytic intraepithelial neoplasia grading scheme

The distinction between actinic keratosis (AK) and squamous cell carcinoma in-situ (SCCIS) is a subject of discussion among dermatopathologists. A previous study determined that there was excellent interobserver agreement among dermatopathologists using the current two-tiered grading system. Presently, we assessed concordance among dermatopathologists using a three-tiered keratinocytic intraepithelial neoplasia (KIN) diagnostic system. At the 2006 meeting of the American Society of Dermatopathology (ASDP), registration personnel solicited 125 registrants by randomly inserting an invitation into 125 registration packets. Participants reviewed 15 glass slides representing a spectrum of keratinocytic atypia from AK to SCCIS. Participants were asked to choose 1 or 2 but not 3 grades of KIN that best reflected the changes on each slide. Thirty-two of the 125 solicited enrollees participated in the study. There were 16 volunteers for a total of 48 participants. The inter-observer agreement for all participants was 0.575 (moderate agreement). The overall inter-observer agreement for anatomic pathologist-dermatopathologists (AP-DP), dermatopathologist-dermatologists (DP-D) and anatomic pathologist-dermatologist-dermatopathologists (AP-DP-D) was 0.665, 0.609 and 0.670 (substantial agreement), respectively. There is high concordance among dermatopathologists using a three-tiered diagnostic system for KIN. The observed agreement suggests that dermatopathologists are reliably able to categorize the continuum of keratinocytic atypia in a manner that may have diagnostic relevance.

Interobserver and Intraobserver Variability of a Two-tier System for Grading Ovarian Serous Carcinoma

Although grading has been demonstrated to be an important prognostic factor in ovarian serous carcinoma, there is no system universally used to perform this task. A few years ago, we proposed a two-tier system for grading ovarian serous carcinoma that is based primarily on the assessment of nuclear atypia (uniformity vs. pleomorphism) in the worst area of the tumor. Tumor grade in this two-tier system is correlated with survival. After being used by numerous pathologists and trainees at The University of Texas M.D. Anderson Cancer Center (MDACC) for 15 years, we have observed that this system is user-friendly and reproducible. We undertook this study to evaluate the interobserver and intraobserver variability among a group of 7 gynecologic pathologists and 2 general surgical pathologists using this grading system. A total of 80 cases of ovarian serous carcinoma, 40 low-grade and 40 high-grade, were circulated twice among these pathologists. Slides with examples of low-grade and high-grade serous carcinoma were sent with the unknowns. A website was used to provide diagnostic criteria, images of examples of ovarian low-grade and high-grade carcinoma, and a log form to facilitate data entry. Statistical analysis demonstrated an overall kappa statistic among the different observers of 0.909. The intergrader kappa's ranged from 0.717 to 1.000 in the first round of the review and from 0.701 to 1.000 in the second round. Eight of the participants had an intragrader kappa ranging from 0.775 to 1.000 (excellent agreement), whereas a single participant had an intragrader kappa of 0.725 (good agreement). This study demonstrates that the two-tier grading system (the MDACC grading system) for ovarian serous carcinoma on the basis of the assessment of nuclear atypia is easy to learn and is highly reproducible. These findings would support its universal use, which would be beneficial for the standardization of clinical trials and protocols, thus facilitating the understanding of this disease and investigation into the treatment of patients affected by these tumors.

Two-Tier Grading System for Ovarian Epithelial Cancer

Two-Tier Grading System for Ovarian Epithelial Cancer

PT classification, grade, and vascular invasion as prognostic indicators in urothelial carcinoma of the upper urinary tract

Clinicopathologic features predictive of patient outcome in upper urinary tract urothelial carcinoma are not well defined. The aim of this study was to assess the role of pT classification, tumor grade, and vascular invasion in predicting metastasis-free survival. A total of 190 consecutive invasive upper urinary tract urothelial cancers operated between 01/1984 and 12/2004 were re-evaluated with respect to pT classification, tumor grade (according to the three-tiered WHO 1973 and the recent two-tiered grading system following the WHO/ISUP consensus classification), as well as presence of lymph and/or blood vessel invasion. Prognostic impact was analyzed using the Kaplan–Meier method and the Log-Rank test. For multivariate testing, a Cox’s proportional hazards regression model was used. pT1 was present in 81 (43%), pT2 in 29 (15%), pT3 in 73 (38%), and pT4 in seven (4%) cases. There were 12 (6%) G1, 96 (51%) G2, and 82 (43%) G3 tumors or 84 (44%) low-grade and 106 (56%) high-grade tumors according to the two-tiered system. The presence of vascular invasion in 72/190 (38%) tumors was associated with high pT classification (P<0.001) and high tumor grade (P<0.001). Disease progression occurred in 39% of patients, with 5- and 10-year metastasis-free survival rates of 56 and 45%, respectively. On univariate analysis, all investigated parameters showed prognostic significance. The negative influence of vascular invasion on patient outcome was strikingly strong in high pT classification and high-grade cancers. On multivariate analysis, pT classification (P<0.001) and vascular invasion (P<0.001) proved to be independent prognostic factors, whereas tumor grade according to the two-tiered system missed statistical significance (P=0.06). In conclusion, pT classification and vascular invasion are independent prognostic factors with respect to metastasis-free survival and should be used to guide adjuvant therapy strategies in affected patients. Presence (or absence) of vascular invasion should be commented upon separately in the pathology report.

Grading of soft tissue sarcomas: the challenge of providing precise information in an imprecise world

By identifying patients at greatest risk for distant metastasis and, hence, most likely to benefit from adjuvant therapy, the grading of sarcomas has been one of the most important contributions pathologists have made to the treatment of sarcomas. Over the years, many grading schemes have been proposed and validated as efficacious. The three-tier system proposed by the French Federation of Cancer Centres is precisely defined, easy to use, and is the most widely employed. However, no system performs perfectly on all sarcomas. Sarcomas that do not lend themselves well to grading include (i) those in which grade provides no incremental information over histological subtypes (e.g. well-differentiated liposarcoma/atypical lipomatous neoplasm, Ewing's sarcoma); (ii) tumours traditionally considered "ungradable" (e.g. epithelioid sarcoma, clear cell sarcoma, angiosarcoma); and (iii) sarcomas that customarily have been graded but in which grade has recently been shown not to correlate well with outcome (e.g. malignant peripheral nerve sheath tumour). Consequently, several sarcoma-specific risk stratification schemes have been proposed. The future may well witness a synthesis of these two approaches. Nomograms, which incorporate clinical, histological and demographic findings, have proved accurate in predicting disease-specific survival in sarcomas. Diagnosis and grading are increasingly based on tissue obtained by core needle biopsy, which poses new challenges for pathologists, particularly if neoadjuvant therapy is to be given. Grading on needle biopsies may require a two-tier grading system (i.e. low versus high grade) and a close dialogue with clinicians to resolve ambiguities.