Malignant salivary tumors—analysis of prognostic factors and survival

A group of 113 patients with malignant salivary gland tumors was retrospectively reviewed to analyze the association of clinical and histologic factors with survival. These factors were patient sex and age, tumor site, clinical stage, histologic diagnosis, tumor grade, and whether or not final surgical margins were clear. There were 57 parotid, 40 minor salivary, and 16 submandibular gland cancers. The histologic groups were mucoepidermoid carcinoma (49 patients), adenoid cystic carcinoma (31), adenocarcinoma not otherwise specified (18), acinic cell carcinoma (7), malignant mixed tumor (5), squamous cell carcinoma (2), and undifferentiated carcinoma (1). Univariate analysis of clinical factors showed that age and clinical stage significantly influenced survival. At 10 yr the predicted cumulative survival rates for Stage I, II, III, and IV tumors were 74%, 56%, 32%, and 10%, respectively. Tumor grade was the only significant histologic factor. This was most obviously reflected among patients with mucoepidermoid carcinomas. Cumulative survival at 5 yr was 94% for those with low-grade tumors and 26% for high-grade tumors. By multivariate analysis, clinical stage, age, and tumor grade remained highly significant. Analysis of patients with only Stage I and II disease demonstrated that the significant factors were patient age, tumor site, tumor grade, and whether or not surgical clearance was achieved. These results suggest that clinical stage should not be the exclusive determinant of the extent of surgery and that the selection of patients, for adjuvant therpay may be improved by an awareness of these prognostic factors.     

Malignant salivary tumors--analysis of prognostic factors and survival

A group of 113 patients with malignant salivary gland tumors was retrospectively reviewed to analyze the association of clinical and histologic factors with survival. These factors were patient sex and age, tumor site, clinical stage, histologic diagnosis, tumor grade, and whether or not final surgical margins were clear. There were 57 parotid, 40 minor salivary, and 16 submandibular gland cancers. The histologic groups were mucoepidermoid carcinoma (49 patients), adenoid cystic carcinoma (31), adenocarcinoma not otherwise specified (18), acinic cell carcinoma (7), malignant mixed tumor (5), squamous cell carcinoma (2), and undifferentiated carcinoma (1). Univariate analysis of clinical factors showed that age and clinical stage significantly influenced survival. At 10 yr the predicted cumulative survival rates for Stage I, II, III, and IV tumors were 74%, 56%, 32%, and 10%, respectively. Tumor grade was the only significant histologic factor. This was most obviously reflected among patients with mucoepidermoid carcinomas. Cumulative survival at 5 yr was 94% for those with low-grade tumors and 26% for high-grade tumors. By multivariate analysis, clinical stage, age, and tumor grade remained highly significant. Analysis of patients with only Stage I and II disease demonstrated that the significant factors were patient age, tumor site, tumor grade, and whether or not surgical clearance was achieved. These results suggest that clinical stage should not be the exclusive determinant of the extent of surgery and that the selection of patients, for adjuvant therapy may be improved by an awareness of these prognostic factors.     

Clinical prognostic factors in malignant parotid gland tumors.

OBJECTIVE: To analyze the factors in parotid malignant epithelial tumors influencing recurrences and disease-specific survival. METHODS: We retrospectively reviewed the files of 150 patients treated at our institution, from 1974 to 1998. Twenty-four patients were not treated by surgery and were excluded from this study. The remaining 126 patients were treated with surgery and 74 patients had postoperative radiotherapy. Thirty-three patients were treated with parotidectomy plus neck dissection. Neck lymph node metastasis was found in 22 patients, 5 patients had occult neck metastasis, and 4 periparotid lymph nodes metastasis. The mean age was 49 years old. According to the UICC/1997 TNM Classification, 49 patients were stage I, 27 stage II, 22 stage III, and 28 stage IV. The influence of selected factors on the 10 year disease-specific survival was analyzed using the Kaplan-Meier actuarial method and the log-rank test. RESULTS: Forty patients had mucoepidermoid carcinoma, 18 patients adenocarcinoma NOS, 18 patients acinic cell carcinoma, 15 patients adenoid cystic carcinoma, 11 patients malignant mixed tumor, 11 patients salivary duct carcinoma, and 13 patients other pathology. Twenty-five patients had recurrences: 17 had local recurrences, 4 patients had neck recurrences, and 4 were loco-regional recurrences. Five factors influenced negatively the prognosis: 1) T stage (p.00001), 2) grade (p.00001), 3) + lymph nodes (p.0007), 4) facial nerve dysfunction (p.0001), and 5) age (p.004). Patients with high-grade tumors and high-stage tumors had the worst prognosis according to the multivariate analysis. The 10-year disease-specific survival was 97% for stage I, 81% for stage II, 56% for stage III, and 20% for stage IV. CONCLUSION: The grade of the tumor and stage were the most important prognostic factor. EBM RATING: C.     

Adenoid cystic carcinoma of the trachea and main-stem bronchus. A clinical, histopathologic, and immunohistochemical study

Twelve cases of adenoid cystic carcinoma of the trachea and main-stem bronchus were histologically analyzed, and the results were examined with reference to the growth pattern of the tumor and the prognosis. The tumors were histologically classified into tubular, cribriform, and solid subtypes. Three histologic grades were established: grade I, tumors with tubular and cribriform subtypes but without solid subtype; grade II, tumors with tubular and cribriform subtypes in which the solid subtype comprised less than 20% of the area; grade III, tumors in which the solid subtype comprised more than 20% of the area. Three gross infiltrating types were established: type I, entirely intraluminal; type II, predominantly intraluminal; type III, predominantly extraluminal. In most cases histologic grade correlated with gross tumor type; that is, grades, I, II, and III were grossly types I, II, and III, respectively. The tumors infiltrating along the tracheobronchial wall were of the tubular or cribriform subtype, but not of the solid subtype. In two patients who died of distant metastasis, the histologic studies revealed the solid subtype. Immunohistochemical analysis demonstrated that the tubular subtype was the most differentiated form and the solid subtype, the most undifferentiated form. The histologic subtype of adenoid cystic carcinoma of the tracheobronchial tree was an important factor in the growth pattern of the tumor and the prognosis.     

Multimodality Treatment of Thymoma: A Prospective Study

Background. Thymomas are a heterogeneous group of tumors. Treatment of invasive lesions is not well standardized. The aim of this study is to propose a clinicopathologically based protocol for multimodality therapy.

Methods. Between 1965 and 1988, we operated on 83 patients with thymoma who did not receive standardized adjuvant therapy. In 1989, on the basis of the retrospective analysis of the data, we started a multimodality therapy protocol and used it for 65 patients. Twelve patients had medullary thymoma (11 stage I and 1 stage II), 13 had mixed type (6 stage I and 7 stage II), and 40 had cortical thymoma (4 stage I, 11 stage II, 12 stage III, and 13 stage IV). We considered three groups. Group I (n = 18 patients), benign thymoma, included stage I and II medullary and stage I mixed thymomas; radical resection with no adjuvant therapy was performed. Group II (n = 22), invasive thymoma, included stage I and II cortical and stage II mixed thymomas; postoperative chemotherapy plus radiotherapy was always administered. Group III (n = 25), malignant thymoma, comprised stage III and IV cortical thymomas and stage III mixed thymomas; resectable stage III lesions were removed, and highly invasive stage III and stage IV lesions underwent biopsy, neoadjuvant chemotherapy, and surgical resection; postoperative chemotherapy and radiotherapy was administered to all patients.

Results. The 8-year survival rate for patients in stages I, II, III, and IV was 95%, 100%, 92%, and 68%, respectively. Patients with medullary thymoma had a 92% 8-year survival rate; those with mixed type, 100%; and those with cortical thymoma, 85%. Group I had an 8-year survival rate of 94%; group II, 100%; and group III, 76%. Survival was compared with that of patients operated on before 1989: differences were not significant for group I; survival improved in group II (100% versus 81%; p = not significant); and group III showed significant improvement (76% versus 43%; p < 0.049).

Conclusions. Multimodality treatment with neoadjuvant chemotherapy and adjuvant chemotherapy plus radiotherapy may improve the results of radical resection and the survival of patients with invasive and malignant thymoma.     

Thymoma needs a new staging system

Despite the wide use of the Masaoka staging system for thymoma, the distribution of survival by stage group is not well balanced. The new staging systems for testing were defined as follows: stage I was created by merging Masaoka's stages I and II, and stage IV remained unchanged. Stages II and III were defined as thymomas with invasive growth and the following combinations of tumor diameter and number of involved structures/organs. Scheme 1: stage II included tumors less than 10 cm in diameter and involving one neighboring structure/organ. Stage III included tumors with all combinations of diameter and number of involved structures/organs other than those in stage II. Scheme 2: stage II included tumors of all combinations other than those in stage III. Stage III included tumors 10 cm or more in diameter and involving two or more structures/organs. The survival curves were assessed for 138 patients treated at the National Cancer Center, Tokyo. The 10-year survival rates for each stage according to the Masaoka, Scheme 1, and Scheme 2 systems were as follows: stage I (100%, 100%, 100%), stage II (100%, 86%, 83%), stage III (70%, 64%, 34%), and stage IV (34%, 34%, 34%), respectively. The survival curves for Scheme 1 gave the most balanced distribution of survival in each staging group. By considering both tumor diameter and number of involved structures/organs, Masaoka's stages I-III could be rearranged with more balanced distribution of survival.     

The importance of clinical staging of minor salivary gland carcinoma.

We reviewed a 45-year experience with 459 patients who had previously untreated minor salivary gland neoplasms, 378 (82%) of which were malignant. Data were adequate for retrospective clinical staging in 353 of the 378 patients with malignant tumors using criteria identical to those for squamous carcinoma in the same sites. Five-, 10-, and 15-year survival rates for the patients with malignant tumors treated after 1966 were 75%, 62%, and 56%, respectively, a significant improvement compared with results reported previously. Multivariate analysis confirms that survival was significantly influenced by the clinical stage and the histologic grade, but the applicability of grading was limited to patients with mucoepidermoid carcinoma or adenocarcinoma. Ten-year overall survival was 83%, 53%, 35%, and 24% for patients with stage I through stage IV, respectively. Results in these patients are similar to those we have recently reported in patients with major salivary gland carcinomas, but we are unable to demonstrate that postoperative radiotherapy improved survival.     

Clinical outcome of epithelial tumors of the thymus

OBJECTIVE AND METHODS: We retrospectively reviewed treatment and clinical outcome of thymic epithelial tumors of 64 patients over a 20-year period. Clinical staging of the tumor was done by according to Masaoka classification. Histological diagnosis of the tumors was done by according to the second edition of the WHO histologic classification system for thymic epithelial tumors. Survival rate was calculated after Kaplan-Meire method. RESULTS: Median age of patients was 53.7 years (ranged from 16 to 81). There were 30 men and 34 women. Eighteen patients had auto-immuno diseases. Sixty-two patients underwent surgery. In 57 patients resection was complete (extended thymo-thymectomy), but in the other five incomplete. The operative approach was median sternotomy in 51 patients and video-assisted thoracoscopic surgery in 6. Stage II to IV patients had postoperative mediastinal irradiation. Stage III to IV patients had postoperative cisplatin (CDDP) based chemotherapy. Inoperable patients were treated by chemo-radiotherapy. There were 42 stage I, 7 stage II, 11 stage III, 3 stage IV a, 1 stage IV b. The 5-year/10-year survival rates were 93%/89%, 71%/71%, 68.5%/--in patients with stage I, II and III. There were 5 type A tumors, 8 type AB tumors, 11 type B1 tumors, 11 type B2 tumors, 9 type B3 tumors, 11 type C tumors, the respect 5-year survival rates were 100%, 100%, 87.5%, 60%, 85.7% and 90%. Masaoka stage II to IV patients classified in B2, B3 and C type except one case. CONCLUSION: Histologic type B2, B3 and C tumors may reflect the invasive nature. Masaoka staging system and the WHO histologic classification may help the assessment and treatment of patients with thymic epithelial tumor.     

Carcinoma of the gallbladder--a clinical appraisal and review of 40 cases

Prognosis of 40 patients with gallbladder carcinoma who had undergone curative resection was investigated. Five-year survival rate calculated from Kaplan & Meier's method was 67% in 16 cases in Stage I, 43% in 8 cases in Stage II and 22% in 10 cases in Stage III, respectively. In 6 cases, classified as Stage IV, no case survived more than 2 years postoperatively. Most patients in Stage I had the tumors of papillary type in macroscopic appearance, papillary adenocarcinoma, and negative vascular and perineural invasions and showed better prognosis. In Stages II, III and IV, in contrast, most tumors were infiltrative or nodular type, tubular adenocarcinoma, and positive vascular and perineural invasions and demonstrated poorer prognosis. Patients in Stage I who had undergone simple cholecystectomy showed 5-year survival rate of 57%, and who underwent cholecystectomy with wedged resection of the gallbladder bed of the liver and regional lymphadenectomy (extended cholecystectomy) showed that of 100%. Extended cholecystectomy, therefore, is the procedure of choice in patients in Stage I. In patients in Stages II, III and IV, extended cholecystectomy yielded 5-year survival rate of 33%. More radical procedure or combined modality therapy must be indicated in advanced stage of the disease.     

Correlation of histopathological variants, cellular DNA content, and clinical outcome in adenoid cystic carcinoma of the salivary glands.

OBJECTIVE: To study the correlation between flow cytometrically measured DNA ploidy with prognostically important histopathologic groups and clinical outcome in patients with adenoid cystic carcinoma of the salivary glands. STUDY DESIGN: 46 tumor specimens were analyzed flow cytometrically for DNA content and assessed for histological grade. Correlations were made between tumor DNA ploidy and histopathological grade, and disease-free and overall survival of these patients. RESULTS: Of the 46 patients, 31 had a cribiform/tubular histologic pattern, and 15 had a solid pattern. 84% of the tumors with cribriform/tubular pattern were DNA diploid, compared with 33% of tumors that were graded solid. This difference proved to be statistically significant (chi(2)11.75, P = 0.0006). Overall and disease-free survival periods were longer for patients with DNA diploid tumors in both groups, 63% vs. 36% and 62% vs 38%, respectively. CONCLUSIONS: Tumor DNA ploidy correlates with prognostically important tumor histopathology as well as overall and disease-free survival in patients with adenoid cystic carcinoma of the salivary gland. EBM rating: B-3.     

Prognostic factors in patients with renal cell carcinoma: retrospective analysis of 675 cases

OBJECTIVES: To identify independent predictors of cause-specific survival in patients affected by renal cell carcinoma (RCC). MATERIAL AND METHODS: We evaluated retrospectively 675 patients who underwent in our department from 1976 to 1999 radical nephrectomy for RCC. Pathological stage of the primary tumor (TNM, 1997) was pT1 in 326 cases (48%), pT2 in 133 (20%), pT3a in 66 (10%), pT3b in 138 (20%) and pT4 in 12 (2%). According to TNM classification (Union International Contre le Cancer (UICC), 1997) the pathological stage was I in 303 cases (45%), II in 119 (18%), III in 150 (22%) and IV in 103 (15%). Histological grading was assigned according to Fuhrman's classification in only 333 cases: G1 in 25%, G2 in 35%, G3 in 33% and G4 in 7%. RESULTS: Cause-specific survival was 77% at 5 years, 69% at 10 years, 64% at 15 years and 57% at 20 years. Five and 10 year cause-specific survival was, respectively 91.4 and 88.5% in pT1 tumors, 84.8 and 72.7% in pT2, 57.4 and 35.6% in pT3a, 47.2 and 33.6% in pT3b-c, and 29.6% in pT4 (P < 0.0001). In relation to the pathological stage according to TNM classification, 5 and 10 year cause-specific survival was, respectively 94 and 91.6% in stage I tumors, 89.7 and 78% in stage II, 63.4 and 46.4% in stage III and 28 and 16.3% in stage IV (P < 0.0001). In relation to the nuclear grade of the primary tumor 5 and 10 year cause-specific survival was, respectively 94 and 88% in G1 tumors, 86 and 75% in G2, 59 and 40% in G3 and 31% in G4 (P < 0.0001). At multivariate analysis pathological stage of the primary tumor, lymph nodes involvement, presence of distant metastases at diagnosis and nuclear grading resulted all independent predictors of cause-specific survival in patients with RCC. CONCLUSION: Pathological stage of primary tumors, lymph nodes involvement, presence of distant metastases at diagnosis and nuclear grading according to Fuhrman resulted all independent predictors of cause-specific mortality in patients with RCC.     

Clinical pattern and pathologic stage but not histologic features predict outcome for bronchioloalveolar carcinoma

BACKGROUND: The histologic criteria defining bronchioloalveolar carcinoma (BAC) were recently revised, but it is unclear whether these criteria predict clinical behavior. This study determined the outcome of resected BAC in relationship to clinical and radiologic disease pattern, and pathologic features. METHODS: Between 1989 and 2000, 100 consecutive surgically treated patients with adenocarcinomas exhibiting various degrees of BAC features were retrospectively studied. Histology was reviewed; tumors were classified as pure BAC, BAC with focal invasion, and adenocarcinoma with BAC features. Clinical and radiologic pattern were classified as unifocal, multifocal, or pneumonic. Demographic data, tumor stage, and outcome were recorded. Survival was analyzed by the Kaplan-Meier method, and prognostic factors were determined by the log-rank test. RESULTS: Patient median age was 65, and 74% of the patients were female. Pure BAC, BAC with focal invasion, and adenocarcinoma with BAC features occurred in 47, 21, and 32 patients, respectively. Unifocal disease occurred in 64 patients, multifocal in 29, and pneumonic in 7. Seventy-one patients had stage I/II tumors, 22 had stage III/IV, and 7 patients had Stage X tumors. Overall 5-year survival was 74%. There was no significant difference in survival among the three histologic subtypes. The pneumonic pattern had significantly worse survival compared with unifocal and multifocal patterns. Pathologic stage predicted survival, with 5-year survivals for I/II and III/IV of 83.7% and 59.6%, respectively. CONCLUSIONS: Clinical pattern and pathologic stage, but not the degree of invasion on histologic examination predict survival. Multifocal disease is associated with excellent long-term survival after resection. The favorable survival of stage III/IV BAC indicates that the current staging system does not fully describe this disease in patients undergoing resection because of its distinct tumor behavior.     

Prognostic relevance of Masaoka and Müller-Hermelink classification in patients with thymic tumors

BACKGROUND: To compare the prognostic relevance of Masaoka and Müller-Hermelink classifications. METHODS: We treated 71 patients with thymic tumors at our institution between 1980 and 1997. Complete follow-up was achieved in 69 patients (97%) with a mean follow up-time of 8.3 years (range, 9 months to 17 years). RESULTS: Masaoka stage I was found in 31 patients (44.9%), stage II in 17 (24.6%), stage III in 19 (27.6%), and stage IV in 2 (2.9%). The 10-year overall survival rate was 83.5% for stage I, 100% for stage IIa, 58% for stage IIb, 44% for stage III, and 0% for stage IV. The disease-free survival rates were 100%, 70%, 40%, 38%, and 0%, respectively. Histologic classification according to Müller-Hermelink found medullary tumors in 7 patients (10.1%), mixed in 18 (26.1%), organoid in 14 (20.3%), cortical in 11 (15.9%), well-differentiated thymic carcinoma in 14 (20.3%), and endocrine carcinoma in 5 (7.3%), with 10-year overall survival rates of 100%, 75%, 92%, 87.5%, 30%, and 0%, respectively, and 10-year disease-free survival rates of 100%, 100%, 77%, 75%, 37%, and 0%, respectively. Medullary, mixed, and well-differentiated organoid tumors were correlated with stage I and II, and well-differentiated thymic carcinoma and endocrine carcinoma with stage III and IV (p < 0.001). Multivariate analysis showed age, gender, myasthenia gravis, and postoperative adjuvant therapy not to be significant predictors of overall and disease-free survival after complete resection, whereas the Müller-Hermelink and Masaoka classifications were independent significant predictors for overall (p < 0.05) and disease-free survival (p < 0.004; p < 0.0001). CONCLUSIONS: The consideration of staging and histology in thymic tumors has the potential to improve recurrence prediction and patient selection for combined treatment modalities.     

Neuroblastoma: an analysis of 160 cases

Neuroblastoma was observed in 160 patients from 1948–1978. Ninety-seven patients were boys and 63 were girls. At diagnosis, 74 patients were less than 2 years of age, 28 between 2–3 years, and 58 over 3 years. Sixty-two (38%) patients had localized disease, while 98 (62%) had metastases. Patients were grouped by extent of disease according to the staging criteria of Evans et al.: stage I (5), stage II (31), stage III (26), stage IV (82), stage IV-S (16). Tumors occurred in the neck (3), mediastinum (16), abdomen (136), and pelvis (3). Clinical findings often included abdominal mass, weight loss, anemia, bone pain, and proptosis. Six patients had diarrhea and 3 had cerebellar ataxia and nystagmus. Lesions were often calcified (>50%), and bone marrow aspirate frequently demonstrated tumor clumps (rosettes). Urinary VMA was elevated in 85% of cases. Therapy varied according to stage. Stage I patients received operative excision alone and stage II patients operative resection with radiation for residual tumor and/or positive lymph nodes. Stage III patients were managed aggressively with operative resection (when possible), irradiation, and combination chemotherapy (cyclophosphamide, vincristine, DTIC, Adriamycin®, VM-26). Patients with metastases (stage IV) were initially treated with multiagent chemotherapy with late “second-look” or delayed primary laparotomy for tumor resection done in clinical responders. Two-year disease-free survival occurred in 57 of 160 patients or 35.6%. Survival rates were best for infants under age 1 year (74%) and for patients with stage I (100%), stage II (74%) and stage IV-S (75%) tumors. There was improved survival in patients with tumors that occurred in the neck (100%), pelvis (100%), and mediastinum (75%). Survival rates were poor in patients over 2 years of age (13–17%), with abdominal tumors (28%), and with stage III (34%) and stage IV (10%) tumors. While chemotherapy and irradiation have improved tumor response, survival rate has not been improved. Immunotherapy has been disappointing. Unfortunately, at the present time, there is no specific chemotherapeutic agent that has a curative effect on this tumor.     

Proliferating cell nuclear antigen and c-erbB-2 oncoprotein expression in adenoid cystic carcinomas of the salivary glands.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the salivary gland shows a variable clinical course. It would be helpful to discover reliable biologic markers in the management of patients with ACC. METHODS: We examined proliferating cell nuclear antigen (PCNA) and c-erbB-2 oncoprotein expression on 30 cases of ACC of the salivary glands. The immunohistochemical results, and size, location, and histologic grade of the tumors were compared with the clinical outcome of the patients. RESULTS: Mean PCNA positivity of ACCs was 15%, and was higher in solid than in cribriform/tubular areas. High PCNA value was significantly correlated with shorter disease-free and overall survival of the patients with ACC. c-erbB-2 overexpression was observed in only five cases, focally in cribriform/tubular areas. High histologic grade, which was determined by the presence of solid components, showed a trend toward shorter survival. Size and location of ACC were not associated with patient outcome. CONCLUSIONS: The present study indicates that PCNA score may be one of the most useful prognostic factor of ACC.     

A population-based competing-risks analysis of survival after nephrectomy for renal cell carcinoma

ObjectivesVariability in survival after surgical treatment is observed in patients with renal cell carcinoma (RCC), thereby affirming the heterogeneity of the disease. The aim of our study was to provide a clinically relevant and detailed assessment of survival following surgical excision in patients with RCC of all stages according to age, stage, and grade.Materials and methodsA retrospective population-based analysis of 42,090 patients in the United States who were treated with partial nephrectomy (PN) or radical nephrectomy (RN) for RCC of all stages between the years 1988 and 2008 was performed. Competing-risks Poisson regression analyses focusing on cancer-specific mortality (CSM) or other-cause mortality (OCM) were executed. Stratification was performed according to age groups (≤59, 60–69, 70–79, and ≥80 y), the American Joint Committee on Cancer stage (I, II, III, and IV), and the Fuhrman grade (I–II and III–IV).ResultsIncreasing stage was associated with higher CSM rates (from 2%–9% to 54%–79% for stage I and IV), regardless of age. Similarly, high tumor grade was associated with higher CSM rates (from 2%–64% to 6%–79% for low and high grade). However, OCM was nonnegligible amongst persons aged 70 to 79 years (11%–24%) and ≥80 years (17%–44%), regardless of stage and grade. In subanalyses focusing on stage I RCC, CSM (3%–10%) rates were slightly higher for RN-treated patients, regardless of age and grade. However, in individuals aged 70 to 79 years with high-grade RCC, OCM rates were slightly higher for PN relative to RN (25.5% vs. 23.5%). In those aged ≥80 years, OCM rates were higher for PN compared with RN, both for low-grade (39.4% vs. 32.7%) and high-grade disease (52.0% vs. 42.8%).ConclusionsTumor grade and American Joint Committee on Cancer stage represent important prognostic factors for the prediction of CSM, despite adjustment for patient age. However, OCM rates were nonnegligible in elderly individuals (≥70 y) with low-grade and stage I to III RCC.     

Grading of human urothelial carcinoma based on nuclear atypia and mitotic frequency. II. Prognostic importance

A grading system was applied in a retrospective study of 124 patients with transitional cell carcinoma of the bladder using a modified Bergkvist system. The intermediate World Health Organization (WHO) grade II tumors were divided into supposedly benign and malignant forms of grades IIa and IIb, respectively. The 5-year survival was 92% for patients with grade IIa urothelial carcinoma, compared to 43% for patients with grade IIb tumors. The corresponding figures for grades I and III tumors were 100 and 44%, respectively. When excluding carcinoma in situ (5-year survival 50%) no patient with a noninvasive tumor (stage Ta) died of bladder carcinoma within 5 years, compared to 50% of those with invasive cancers (stages T1 to T4). We propose a new grading system in which grades I and IIa are embraced as grade A, grades IIb and III as grade B, and grade IV as grade C. The 5-year survival rate in the 3 grades was 94, 44 and 27%, respectively. Grade A seems to represent a type of tumor with universally favorable prognosis, in contrast to grades B and C. This offers practical advantages, since the former can be treated conservatively, whereas the latter need more urgent radical intervention, especially in patients in whom invasive growth is recorded.     

Molecular profile of grade 3 endometrioid endometrial carcinoma: is it a type I or type II endometrial carcinoma?

Two types of endometrial carcinoma (EC) have been delineated on the basis of clinicopathologic studies. Low-grade endometrioid carcinoma (EEC) is the prototype of type I EC and is characterized by microsatellite instability and PTEN, K-ras, and/or β-catenin gene mutations, whereas type II EC is typically represented by serous and clear cell carcinomas (SCs/CCCs), the former frequently showing p53 mutations and c-erb-2 overexpression; however, the molecular profile of grade 3 EEC has not yet been well characterized. The goal of this study was to define the immunohistochemical and molecular profile of grade 3 EEC. We studied 25 patients with grade 3 EEC ranging in age from 35 to 87 (mean 61) years. At the time of initial diagnosis, 16 patients had stage I tumors, whereas 3, 5, and 1 had stages II, III, and IV tumors, respectively. Only 1 patient with stage IV tumor had disease in the peritoneum because of direct extend of tumor through the uterine wall. Two tissue microarrays were constructed from paraffin-embedded blocks and stained for MLH-1, MSH-2, p16, cyclin D1, C-erb-B2, WT-1, and p53. Loss of MLH-1 and MSH-2 was seen in 3 of 25 and 1 of 24 tumors, respectively; none showed loss of both. Diffuse p16 nuclear expression was found in 7 of 23 cases; diffuse and strong nuclear immunostaining for p53, cyclin D1, and Her-2 was seen in 9 of 24 neoplasms, 9 of 25, and 3 of 25 carcinomas, respectively. WT-1 was negative in all 25 tumors. One of the 3 grade 3 EECs with Her-2 overexpression showed gene amplification by fluorescence in situ hybridization analysis. No gene amplification for cyclin D1 was found. Follow-up information was available for all patients. Sixteen had stage I tumors. Of these patients, 11 were alive and well (AW), 3 died of disease (DOD), and 2 died of unrelated causes (DUC), with a mean follow-up time of 56 months (range, 24 to 96 mo); 2 of 3 patients with stage II tumors DOD, and 1 was AW with a mean follow-up time of 81 months (range, 6 to 66 mo); of the 5 patients with stage III tumors, 2 DOD, 1 was AW, 1 was alive with lung metastases, and 1 DUC [mean follow-up of 29 months (range, 12 to 74 mo)]; the only patient who had a stage IV tumor DOD 12 months later. Interestingly, patients with grade 3 EECs showing loss of MLH-1/MSH-2 had stage I tumors, and all were AW (60 to 84 mo). Seventy-seven percent (7 of 9) of patients with tumors showing cyclin D1 overexpression were stage I, and none died of disease, whereas 85% (6 of 7) of patients with p16-positive tumors were high stage (2 stage II, 3 stage III, and 1 stage IV), and 5 DOD. All but one of these patients had tumors that also had p53 overexpression. All 3 patients with Her-2 overexpression DOD (stages I, III, and IV). In conclusion, this study shows that grade 3 EEC shares with low-grade EEC the overexpression but not amplification of cyclin D1 and low frequency of Her-2 overexpression and amplification. Grade 3 EEC shares with SC the relatively common p53 and p16 overexpression and low frequency of loss of mismatch repair genes. However, in contrast to SC ECs, which often show WT-1, cyclin D1 amplification, and Her-2 overexpression and/or amplification, grade 3 EECs rarely overexpressed any of these markers. Moreover, in this study, patients with tumors showing loss of MLH-1/MSH-2 or cyclin D1 overexpression were more likely to have low-stage tumors (stage I), whereas patients with tumors that overexpressed p53, p16, or Her-2 were frequently associated with high-stage tumors.     

Diagnosis and Therapy for Ampullary Tumors: 63 Cases

n = 11) or bypass ( n = 10). The mean duration of hospital stay was 20.6 days. Operative mortality was 12.7% for the whole series and 7.5% after PD (2.5% for the last 10 years). Overall survival was 40% at 5 years (85% for stage I, 65% for stage II, 44% for stage III, and 8% for stage IV). Survival was better for stages I, II, and III after PD than after ampullectomy. For stage IV patients survival was 70% after PD versus 20% after bypass at 1 year and 25% versus 0% after 2 years. In our opinion, PD should be proposed even for benign lesions because two of our patients had to undergo repeat operation (PD) 4 and 22 years later, respectively, for stage IV disease. PD is our choice for all tumors of the ampulla.     

A better prognostic value from a modification of lung cancer staging

This prospective study analyzes the survival rate, according to TNM and staging, of 538 patients who underwent curative pulmonary resection for non-oat cell tumors and who survived the operative period. A total of 279 patients had Stage I disease, 113 Stage II, and 146 Stage III. The overall survival rates were 72% at 1 year, 54% at 2 years, 47% at 3 years, 43% at 4 years, and 39% at 5 years. The survival curves of Stages I, II, and III are significantly different. Nevertheless, in Stage I, T1 N0 tumors presented the best survival rate (71% at 5 years), and this was significantly different from those of all other groups. For Stage II, the survival curves were significantly different according to hilar or lobar location of N1. The survival rate of T2 N1 hilar tumors was similar to that of T2 N2 tumors. In Stage III, the survival of T3 N2 tumors was the worst of all classifications. These results may contribute to a reappraisal of the surgical classification. T1 N0 tumors are worthy, on their own, of forming Stage I. T2 N0, T1 N1 lobar, and T2 N1 lobar can constitute Stage II. Stage III or IIIa would comprise carcinomas classified T2 N1 hilar, T1 N2, T2 N2, and perhaps T3 N0 and T3 N1. T3 N2 should probably be isolated in a IIIb or IV stage.