Broder's Grading Research Articles

Immunohistochemical study of CD44s expression in oral squamous cell carcinoma-its correlation with prognostic parameters.

Background and Objectives:The study aims at the observation of the immunohistochemical expression of CD44s in Oral Squamous Cell Carcinoma (OSCC) and to correlate its expression with prognostic parameters.Materials and Methods:A total of 30 cases of OSCC, - 10 cases of each well differentiated (WD SCC), moderately differentiated (MD SCC) and poorly differentiated squamous cell carcinomas (PD SCC) were included in the study. The sections were subjected to immunohistochemical study using CD44s antigen marker. The degree of intensity and distribution of CD44s immunostaining was assessed and correlated with prognostic markers such as tumor stage (tumor size), tumor grade (Broder's histological grading), tumor site, tumor thickness (histological depth of invasion) and nodal status.Results:CD44s expression by tumor cells in OSCCs is statistically correlated with tumor grade i.e. Higher mean of CD44s immunoexpression was observed in WD SCC group (10.80 ± 3.97), followed by MD SCC group (5.90 ± 3.38) and PD SCC group showed least CD44s immunoexpression (3.70 ± 4.64). There was no statistical significance observed with respect to the other prognostic markers.Conclusion:Based on these observations it can be suggested that the decrease in expression of CD44s in OSCC cells may be due to the reduced cell-to-cell and cell-to-matrix adhesion, resulting in easy detachment from the rigid constitution. Low expression of CD44s in OSCC tissues may be an indicator of tumor invasion and high metastatic potential.

A case of recurrent malignant fibrous histiocytoma with marked response to combined chemotherapy with gemcitabine and carboplatin.

A case of recurrent malignant fibrous histiocytoma with marked response to combined chemotherapy with gemcitabine and carboplatin.

Diagnosis and treatment of low-grade osteosarcoma: experience with nine cases

Low-grade osteosarcoma, including low-grade central osteosarcoma and parosteal osteosarcoma, is an extremely rare variant, and the diagnosis is occasionally difficult. In this article we present cases of low-grade osteosarcomas that should be reviewed by a clinical oncologist. Nine cases of histologically diagnosed Broder grade 1 osteosarcoma were retrospectively reviewed. The pathological diagnoses included parosteal osteosarcoma, low-grade central osteosarcoma, and low-grade chondroblastic osteosarcoma in four, four, and one cases, respectively. Duration from initial surgical intervention including biopsy to final diagnosis as low-grade osteosarcoma was a mean of 9.4 months. The initial benign diagnoses on biopsy specimens included fibrous dysplasia in three cases, chondroblastoma in one case, and a giant cell tumor in one case. The average number of histological examinations was 1.8. Low-grade osteosarcomas are well suited for biological reconstruction: seven cases were reconstructed by frozen autografts, distraction osteogenesis, or vascularized bone grafts. Low-grade osteosarcomas can be misdiagnosed as benign lesions, especially fibrous dysplasia. If the diagnosis of a low-grade osteosarcoma is not established on the basis of radiologic findings, care should be exercised, even when a biopsy suggests a benign lesion. Low-grade osteosarcomas should be treated with wide excision, even after an intralesional excision. Biological reconstruction might be a better option for low-grade osteosarcomas.

Assessment and Correlation of Single Stranded DNA Damage in Oral Squamous Cell Carcinoma with Broder's Histopathological Grading

Early detection of oral squamous cell carcinoma OSCC can prevent significant morbidity and can also increase the life expectancy of patients. Many methods have been devised to this effect but most are time consuming and expensive. Since DNAdamage is one of the principle features in cancer development assessment of DNA damage is an important prognostic indicator in patients with cancer. Single cell gel electrophoresis SCGE assay also known as Comet assay is a sensitive quick and cost effective method of detecting single stranded DNA damage in cells.The present study was carried out on the assumption that oral mucosal cells could show the DNA damage in OSCC. For this study smears were taken from lesion proper of 30 patients with OSCC and from the buccal mucosa of 30 normal healthy volunteers. This study was undertaken to evaluate the extent of DNA damage in oral smears of patients with OSCC and to determine correlation if any of the extent of DNA damage to Broders histopathological grading of OSCC. The mean DNA damage levels of both the groups were measured and statistically analyzed with students t test. A high statistical significance of p lt 0.0001 was found in DNA damage levels of oral mucosal cells between normal subjects and patients with OSCC. AStepwise increase in DNAdamage levels was also seen between the different grades of OSCC and statistical significance at p lt 0.0001 was found between all the grades by employing the one way Anova F technique.The findings of statistically significant increased DNA damage levels in oral mucosal cells in OSCC patients and their correlation to Broders histopathological grading suggest that comet assay may be used effectively to assess the prognosis of OSCC.

A study on histological grading of oral squamous cell carcinoma and its co-relationship with regional metastasis

Background:Histological grading is an important diagnostic tool to predict the clinical and biological behaviour of cancer. Cervical lymph node metastasis indicate poor prognosis of oral cancer. Considering economical status of a third world country, Anneroth's grading system is less expensive, more informative than TNM staging and Broder's grading system. Anneroth's grading system also shows co-relationship with lymph node metastasis. So we are trying to evaluate the Anneroth's grading as a standard one among these three system.Objective:To study the grading of histological malignancy according to Anneroth's classification of biopsy specimens in relation to metastasis in the cervical lymph nodes and comparing the Anneroth's with the other two recognized classifications.Materials and Methods:Fifty(50) patients with oral squamous cell carcinoma was included in the study. Specimen of 35 non-metastatic tumors were compared with 15 metastatic cases. All of the patients were graded to TNM, Broder's and Anneroth's system. TNM is clinical assessment and Broder's is based on only differentiation of cells. On the other hand, six parameters of Anneroth's gives a detail about the morphology of the tumor, invasion criteria in the host tissue and show its correlation with lymph node metastasis. Scoring system of Annearoth's grading indicates demarcation points of worseness of tumor and signifies the possibility of lymph node metastasis.Results:Both Anneroth's(P=0.002) and Broder's grading(P=0.012) have been significant but Anneroth's one is more significant then Broder's.Conclusion:Anneroth's classification can be taken as a standerd diagnostic factor and predictive factor of lymph node metastasis.

P55 Cutaneous squamous cell carcinoma (SCC) of the head and neck: risk factors of overall and recurrence-free survival

Background Head and neck cutaneous squamous cell carcinoma (HNCSCC) although rarely fatal has significant adverse public health effects due to high medical costs, compromised quality of life, functional impairment, and other serious consequences. The present longitudinal cohort study of HNCSCC was designed to determine whether certain clinical-pathologic features of HNCSCC are associated with reduced overall and recurrence-free survival, as suggested by previous data. Patients The cohort sample consisted of 315 consecutive patients presenting with primary only HNCSCC of the head and neck. Life-table analysis and Kaplan-Meier survival analysis were performed. Multivariate Cox's proportional hazards regression models were used to assess the effects of covariates on the length of the interval. Results There were 145 male and 170 female Caucasian patients. At the time of analysis, 222 patients were alive. The mean follow-up time of a patient after enrolment has been 46.1 months (range, 12–115 months). Broder's differentiation grade, perineural involvement, presence of inflammation and T-stage were independent adjusted predictors for overall survival. pT and N-stage, inflammation and perineural involvement were significant predictors for recurrence-free survival while adjuvant irradiation was associated with a 92% reduced risk for recurrence. Life-table analysis showed that 87 and 69% study patients were free from recurrence at years 3 and 5 respectively. Conclusion Patients with cutaneous HNCSCC should be enrolled in a long-term follow-up protocol. After excision in negative margins, patients with HNCSCC should be referred to specialized multidisciplinary oncology clinics for counseling on adjuvant radiotherapy and follow-up.

Clinical and Histopathologic Independent Prognostic Factors in Oral Squamous Cell Carcinoma: A Retrospective Study of 334 Cases

This retrospective hospital-based study reviewed and evaluated the outcome of patients with oral squamous cell carcinoma (OSCC) with the aim of identifying factors affecting the clinical course and survival rate. Patients with a follow-up of at least 12 months were included. The data collected were statistically analyzed for the presence of factors valuable for prognosis; survival curves were processed in accordance with the Kaplan-Meier method. Differences in the expression of variables in different grading levels were investigated. Cox's proportional hazard model for Z(i) covariates (grading, age, T, N) also was calculated. Mean patient age was 67.7 years in women (n = 152) and 62.4 years in men (n = 182). A total of 98 patients were identified with Broder's/World Health Organization grade 1 histology, 176 with grade 2, and 55 with grade 3; 5 patients were identified as grade 4 (carcinoma in situ). Gender and risk factors seemed to be unrelated to prognosis, whereas a significant increase in mortality was seen in patients over age 70. Histological grading, tumor size, and neck involvement were related, as independent factors, in predicting survival in patients with OSCC (QM-H > 3.9). Gender, age, and risk factors had no statistical relationship with cancer histological differentiation. Our analysis reveals a statistically significant relationship among histological Broder's grading of malignancy, tumor size, locoregional involvement, and survival rates, underscoring the utility of tumor differentiation in predicting the clinical course and outcome of OSCC.

How accurate are present risk group assignment tools in penile cancer?

To evaluate the accuracy of the predictive models available to estimate the risk of lymph node metastases and cancer-specific survival in patients with squamous cell carcinoma of the penis. A nonsystematic review of the literature was performed searching MEDLINE in January 2008. Most of the authors select patients for early inguinal lymphadenectomy according to the pathologic extension of the primary tumor and its histologic grade, as recommended by the EAU Guidelines and the Solsona risk groups. Although the Solsona risk groups performed slightly better, both risk groups had low predictive accuracy. A nomogram including eight clinical and pathologic variables (tumor thickness, microscopic growth pattern, Broder's grade, presence of vascular or lymphatic embolization, infiltrations of the corpora cavernosa, corpus spongiosum or urethra, and the clinical stage of groin lymph nodes) was developed to estimate the risk of lymph node involvement at follow-up. Two nomograms are currently available able to estimate the 5-year cancer-specific survival probabilities of the patients. The first nomogram included the clinical lymph node stage and the same pathological variables of the primary tumor at penectomy, while the pathological stage of the lymph nodes replaced the clinical one in the second model. All the 3 nomograms had good prognostic accuracy. Both the Solsona and EAU risk group assessment had low prognostic accuracy, although the Solsona risk groups performed slightly better. The nomograms designed to predict the risk of lymph node metastases showed and cancer-specific survival had good prognostic accuracy but their external validation is still lacking.

DNA histochemical analysis in oral squamous cell carcinoma

Recent years have witnessed an increasing emphasis on the role of nuclear DNA and its application in experimental pathological diagnosis to predict prognosis and management of certain neoplasm. to establish objective criteria for the degree of differentiation and histochemical quantitative of nuclear DNA of oral squamous cell carcinoma (OSCC) using microspectrophotometric analysis. The study was conducted on histologic materials from patient with OSCC. Two histological grading systems were used; Broder's and invasive front grading system were recorded. Microspectrophotometry was applied on Feulgen-stained sections to determine the quality of tumour nuclear DNA content in two different histological grading systems of OSCC. Nuclear DNA content increased significantly with decreasing tissue differentiation as well with increasing tumour size. The grading system and DNA content provides more objective and accurate criteria which relate the morphologic finding to biologic activity and growth patterns of oral cancer as compared to histologic differentiation alone.

Predictive Markers for Late Cervical Metastasis in Stage I and II Invasive Squamous Cell Carcinoma of the Oral Tongue

Patients with oral tongue carcinoma treated by intraoral excision only should be followed up carefully for cervical lymph node metastasis and salvaged immediately if found, because some patients have a more aggressive clinical course. The purpose of this study was to find useful markers for predicting late cervical metastasis in patients with stage I and II invasive squamous cell carcinoma of the oral tongue. We investigated clinicopathologic factors and immunohistochemical biomarkers predicting late cervical metastasis in surgical specimens from 56 patients with T(1-2)N(0)M(0) invasive squamous cell carcinoma of the oral tongue who did not undergo elective neck dissection. Histopathologic factors including tumor thickness, mode of invasion, Broders grade, total score of three different malignancy grading systems, eight other clinicopathologic parameters, and immunohistochemical expression of p53, cyclin D1, Ki-67, epidermal growth factor receptor, microvessel density, cyclooxygenase-2, MUC1, laminin-5 gamma2, E-cadherin, and beta-catenin were examined. All of the clinicopathologic factors and immunohistochemical expression of biomarkers were compared in terms of survival. In the univariate analysis, tumor thickness (P = 0.009), Broders grade (P = 0.017), nest shape (P = 0.005), mode of invasion (P < 0.001), Anneroth score (P = 0.029), Bryne score (P < 0.001), and E-cadherin expression (P = 0.003) were correlated with late cervical metastasis. Multivariate analysis on late cervical metastasis revealed that tumor thickness >4 mm, mode of invasion grade 3 or 4, and E-cadherin expression were independent factors. Late cervical metastasis was the only prognostic factor for overall survival (P = 0.002). Our results indicate that patients with stage I and II invasive squamous cell carcinoma of the oral tongue with tumor thickness >4 mm, mode of invasion grade 3 or 4, and low expression of E-cadherin should be considered a high-risk group for late cervical metastasis when a wait-and-see policy for the neck is adopted.

Tumor biologic prognostic parameters in T1N0M0 squamous cell carcinoma of the oral cavity

Conventional prognostic factors in squamous cell carcinomas are tumor stage, tumor size, evidence of lymph node metastases, extracapsular spread of lymph node metastases, and Broder's grading. Unfortunately these parameters are only of limited value in predicting the biological behavior and ultimately the prognosis of a particular tumor. The present study was conducted for determining objective prognostic factors based on tumor biologic examinations in patients with squamous cell carcinomas of the oral cavity. These parameters were compared to the conventional prognostic factors. Operative specimens of fourty-two patients who underwent surgery for a squamous cell carcinoma of the oral cavity with clinical TNM stage T1N0M0 were examined. All tumors were radically excised with histologic clear margins, which were confirmed by serial sections. The examinations included morphologic multifactorial tumor front grading, quantitative DNA analysis, and immunohistochemical assessment of proliferation markers (i.e. proliferating cell nuclear antigen [PCNA] and MIB1) and of oncogene products (i.e. p53; nm23). Prognostic significance of particular parameters was evaluated by univariate and multivariate Cox regression models. In clinical follow-up of 70 months on average, 6 patients developed local recurrences and 5 patients lymph node metastases. Three patients died of disease. Tumors which recurred had increased values for 2 c Deviation Index, 5 c Exceeding Rate along with high tumor front grading scores and proliferation scores. Using multivariate Cox regression analysis, parameters which were highly significant for prognosis were 5 c Exceeding Rate, tumor front grading score and PCNA score. None of the clinical parameters achieved statistical significance in the multivariate model. Tumors which recurred had also increased expression rates for p53 and nm23. Nevertheless this was statistically not significant. Tumor biologic examinations provide important informations about the clinical aggressiveness and ultimately about the prognosis of a particular tumor. Tumors with aggressive behavior can already be identified during initial diagnosis, which has consequences for the therapeutic management of the patients.

High grade surface osteosarcoma: a clinicopathologic study of 46 cases.

High grade surface osteosarcoma is a rare subtype of osteosarcoma arising on the surface of bone, accounting for only 8.9% of surface osteosarcomas at the study institution. This study reviews 46 cases of high grade surface osteosarcoma, comprised of 13 cases from the Mayo Clinic files and 33 from the authors' files. Histologic features were reviewed in all cases, and radiographs were reviewed in 29 cases. There was a definite male predominance, and 70% of the patients were in the second and third decades of life. Forty-four of the 46 patients had lesions involving the long bones, the most common site being the midportion of the femur. Radiographically, the majority of lesions showed dense to moderate mineralization with a fluffy, immature appearance. Radiating spicules of bone perpendicular to the long axis of the bone, characteristic of periosteal osteosarcoma, were sparse. Histologic findings were identical to those of conventional osteosarcoma. Overall, survival at 5 years was 46.1%. Statistical analysis revealed that marginal excision was associated with an increased risk of local recurrence and that the patients with Broders Grade 3 tumors had a better prognosis than those with Grade 4 tumors. A good response to chemotherapy was associated with better clinical outcome. High grade surface osteosarcoma is a rare subtype of surface osteoscarcoma that has a prognosis similar to that of conventional osteosarcoma, in contrast to the more common type of osteosarcoma arising on the surface of bone. Wide excision and effective systemic chemotherapy are associated with better clinical results.

Morphologic criteria for the prognosis of serous cystadenocarcinoma of the ovary.

143 cases of serous ovarian cystadenocarcinoma were studied to establish the prognostic relevance of specific macroscopic and microscopic criteria. Significant differences in the survival rate were found depending on TNM classification, age, residual tumor mass, ascites, and degree of invasion. The prognosis was significantly better for normotypical or predominantly cystic tumors as well as for those with mononuclear infiltration, little histological atypia, or limited invasion. No prognostic relevance was found, however, for cytologic criteria such as Broder's grading and rate of mitosis.

Stage I ovarian epithelial carcinoma: Survival analysis following definitive treatment

Between 1977 and 1986, 55 patients with surgical stage I ovarian epithelial carcinoma were managed in a definitive fashion, which included surgical staging and adjuvant therapy in 51 of 55 patients (93%) and second-look laparotomy. The mean follow-up time from the date of reassessment surgery was 94 months, allowing sufficient time to facilitate the identification of one or more subgroups of patients at risk of having persistent disease or developing a recurrence. Treatment failures were detected at second-look laparotomy in 6 patients (11%), and an additional 5 patients (9%) subsequently had recurrences after being declared free of disease at second-look reassessment. Analysis of pathologic variables identified grade and substage as important prognostic factors, with 8 of the 9 deaths (89%) being associated with Broders grade 3 or 4 and/or stage IC. Within the bivariate model consisting of patients harboring poorly differentiated (grade 3 or 4) stage IC lesions, 6 of 14 patients (43%) are dead from disease, yielding a long-term survival rate that at best approximates the survival rate associated with optimally reduced (microscopic residual) stage III patients subjected to contemporary adjuvant therapy and reassessment surgery. These data suggest that intensive therapy as utilized in advanced disease, including platinum-based chemotherapy, second-look laparotomy, and innovative salvage or investigational consolidation therapy, is equally applicable to this “high-risk” stage I group.

Adjuvant whole abdominopelvic irradiation for high risk endometrial carcinoma

Fifty-six patients with surgical Stage III or IV endometrial carcinoma, or earlier stage disease with two or more risk factors for peritoneal recurrence, were given postoperative whole abdomino-pelvic irradiation (WAPI) with nodal and vaginal boosts between November 1981 and May 1989. Mean age at diagnosis was 63 years. Twenty-seven patients were surgical Stage I–II, 17 Stage III, and 12 Stage IV. Thirty-seven (66%) had deep myometrial involvement, 34 (61%) had positive peritoneal cytology, 31(55%) had high grade lesions, 20 (36%) had either serous-papillary or adenosquamous histologic variants, and 13 (23%) had up to 2 cm residual disease remaining after surgery. Mean overall follow-up was 45 months. The 7-year actuarial survival was 63.8% with a 7-year disease-free survival (DFS) of 60.9%. By surgical stage, the 7-year DIPS was 77.1% for Stage I–II, 57.8% for Stage III, and 25.0% for Stage IV ( p = 0.006). The 7-year DSF was 79.8% for those with lesions of Broder's grade 1 or 2, and 46.9% for grades 3 or 4 ( p = 0.001). Multivariate analysis demonstrated that of all covariates considered, only surgical stage and histologic grade had prognostic significance for survival and disease-free survival. Acute toxicity has been common but mild; chronic toxicity has been almost entirely subclinical with the exception of three cases of moderate to severe bowel toxicity. These results suggest that post-operative WAPI is a safe and efficacious treatment alternative for patients with surgical Stage I through III high-risk endometrial carcinoma.

Squamous Cell Carcinoma of the Lower Lip Involving a Large Cutaneous Surface

A 72-year-old white man complained of redness, soreness, and irritation of his lower lip for more than 10 years. Physical examination revealed a diffuse erythematous crusted patch involving the lower lip, with a 1.2-cm centrally located palpable area (Fig 1). Cervical adenopathy was not noted. A biopsy performed in 1981 showed actinic keratosis, and the area was treated with liquid nitrogen and fluorouracil. In 1985, two lip biopsy specimens showed squamous cell carcinoma in situ, and actinic keratosis with severe dysplasia, for which he was treated with liquid nitrogen. Several lip biopsy specimens obtained in 1988 demonstrated ulcerated squamous cell carcinoma, Broder's grade 1. The tumor was 0.9 cm at its greatest depth. At about the same time, a 2-cm noncalcified nodule in the right middle lobe was seen on a chest roentgenogram ordered as preoperative screening for cataract surgery, and it was feared that squamous cell carcinoma had metastasized

Predictive factors for long-term survival in patients with advanced ovarian cancer

A total of 107 patients with carcinoma of the ovary were entered in a study combining extensive primary surgery and intensive chemotherapy. Because of evidence supporting the effectiveness of both single agent platinum (P) and the combination of cyclophosphamide and doxorubicin (CA), patients were treated with alternating cycles of CA and CP. Primary surgery to remove the bulk of tumor to less than 2 cm was possible in 45% of the 85 eligible patients, and an additional 17% had similar surgery after two to four cycles of chemotherapy. Fifteen percent of patients progressed on chemotherapy. Of the 68 who were clinically and radiologically without disease at the completion of chemotherapy, 91% had second-look surgery. Forty-eight percent of these women had residual disease. All patients but one are at risk for >60 months, with a median follow-up of 86 months. Overall 5-year survival is 26%, with a median survival of 33 months. Twenty patients survived over 5 years with 11 continuing to be free of disease (13% of all eligible patients). Patients with modified Broder's grade I,II tumors have not yet reached a median survival. Grade, stage, and primary mass size were the only variables with independent prognostic value in a Cox multivariate analysis.

Staging in the treatment of maxillary carcinoma revisited

The site of origin of maxillary sinus carcinoma will not infrequently predetermine the varied neurological signs at presentation. Modifying Ohngren's division, the maxillary sinus can be divided into four quadrants based on anatomical nerve correlates, thus facilitating identification of the primary site. An inclusive classification of maxillary sinus carcinoma based on Broder's grading, site of origin, the TNM classification and the patient's general condition, serves as the basis for a correlative therapeutic regimen.

Evaluation of gleason classification system in prostate cancer

To compare the relative prognostic accuracy of the Gleason classification, the Whitmore staging, and the Broder grading systems, 111 patients with prostate cancer undergoing radical surgery were assessed utilizing these systems. The assessments were correlated with the presence or absence of disease six months to eight years after surgery. Of the three systems the Gleason classification system was the least accurate.

Radical Pancreatoduodenectomy for Cancer of the Papilla of Vater

Over a 22-year span, 87 patients with carcinoma of the papilla of Vater underwent radical pancreatoduodenectomy. No patient was lost to follow-up, and extended observation was possible in most cases: the definitive operation was at least five years earlier than this study in 87% and at least ten years earlier in 73%. Operative mortality was 11.5% among patients who had a single definitive operative procedure and 15.4% among those whose treatment involved reoperation after prior exploration elsewhere. Overall survival rates at two, five, and ten years were 56%, 34%, and 20% respectively. Factors associated with favorable survival were histologic differentiation (Broders grades 1 and 2), absence of nodal metastasis, and papillary histologic characteristics. Noteworthy is the fact that no patient having resection of an undifferentiated carcinoma (Broders grade 3 or 4) survived four years.