Soft-tissue and bone sarcoma histopathology peer review: the frequency of disagreement in diagnosis and the need for second pathology opinions. The Southeastern Cancer Study Group experience.

Histopathologic peer review of specimens from 216 consecutive patients with soft-tissue or bone sarcomas on Southeastern Cancer Study Group protocols was performed by a panel of three pathologists. Subtype of sarcoma, degree of confidence in diagnosis, and grade were compared with agreement or disagreement in pathologic opinion from the primary member institution v the pathology review panel. The most common soft-tissue sarcoma was leiomyosarcoma, followed by malignant fibrous histiocytoma, fibrosarcoma, liposarcoma, malignant schwannoma, and rhabdomyosarcoma. There was total agreement between the primary pathologist and reviewer in 66% of cases. However, 12 cases (6%) were considered on review to not be sarcomas. In 27% of cases the subtype of sarcoma was felt to be incorrect by reviewers. Discordant diagnoses were more common when the confidence of the pathologist was less and when the tumor was of higher grade. There was no improvement in frequency of agreement in the second half of the study, despite educational workshops. We conclude that histologic peer review is important in sarcoma studies and is essential in many patients with presumed sarcomas.

Recurrence-free survival time for surgically treated soft tissue sarcoma patients. Multivariate analysis of five prognostic factors.

A staging system, based upon the experience of 1215 patients, was published by the American Joint Committee Task Force on Soft Tissue Sarcoma in 1977. A subset of these patients, 594, was selected to study recurrence-free survival time. The authors found 331 patients with a recurrence within 5 years (100 local only, 123 metastatic only, and 108 local + metastatic); median months to recurrence was 9.7. Within 5 years, recurrence was clearly associated with mortality: among the 331 patients who experienced a recurrence, 245 died, whereas only 31 died among the 263 who had no recurrence. To further evaluate the utility of the published staging system, a multivariate analysis of five factors was carried out for 297 of the 594 patients (patients with unknown information for any one of these factors were excluded). Factors in addition to grade that exerted a significant influence on recurrence were: direct extension, symptoms, and location of tumor when survival was measured to the first of any recurrence, and tumor size, measuring survival to the first metastatic recurrence. It is therefore recommended that these factors be taken into account in staging this disease. Estimates of probable recurrence-free survival time based upon the multivariate model (Weibull) are also presented.

An evaluation of reports of dioxin exposure and soft tissue sarcoma pathology among chemical workers in the United States.

A review of employment records and tissue specimens of seven workers, reported previously as having occupational dioxin exposure and soft tissue sarcomas, confirms that four workers had employment of 2 to 19 years in the production of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) or trichlorophenol, products contaminated with 2,3,7,8-tetrachlorodibenzodioxin, the most toxic dioxin isomer. Of these individuals, two have confirmed soft tissue sarcomas. In addition three individuals who worked for companies which made 2,4,5-T also have confirmed soft tissue sarcomas. Their employment records do not show specific assignment to 2,4,5-T or trichlorophenol departments; however, one individual worked for 10 d in the production of pentachlorophenol, which is contaminated with different isomers of dioxin. Methodological problems are discussed which must be addressed in the epidemiologic evaluation of the outcome of soft tissue sarcoma.

A clinical and pathological staging system for soft tissue sarcomas.

A system for staging the clinical status of patients with soft tissue sarcomas is presented, based on the clinical characteristics of the primary tumor (size, extension), the involvement of lymph nodes, the presence of metastases, and the grade of the tumor. This represents the TNM system with grade of tumor (G) added. The system evolved was based on examination of 1215 cases of 13 types of soft tissues sarcomas, primarily in the extremities (fibrosarcoma, liposarcoma, etc.). Nine stages are described, and they are correlated with survival in the cases reviewed. The staging system now can be used for case evaluation for therapy determination and for intercomparison of series of patients as to incidence of different kinds of tumors, effects of treatment, and survival.

Primary osteosarcoma of bone. Clinicopathologic investigation of 243 cases, with necropsy studies in 54.

Two hundred forty-three patients who had pathologically verified primary osteosarcomas of bone, treated at The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute over a 24-year period, form the basis of this study. These cases provide a basis for comparison of those patients currently receiving adjuvant chemotherapy with those who did not receive such treatment. Anatomic findings in 54 cases subjected to complete postmortem examinations were analyzed. Three significant findings emerged: pulmonary metastases were observed in all but one case, lymph-node metastases were found in only four cases, and in all metastases the histologic pattern reproduced that of the primary lesion. In addition, patients less than 26 years old had a significantly earlier appearance of pulmonary metastases than patients past this age. Patients with osteoblastic tumors had the poorest survival rate, followed by those with chondroblastic lesions. Those with fibroblastic tumors survived longest. In the overall study of 243 cases, tumors in the distal end of the femur and the proximal end of the tibia accounted for 147 cases, representing 60.5% of the cases. The highest incidence of the tumor was in the second decade of life, with 76.5% of the cases occurring in patients less than 25 years old. Three-year survival for the series was 21.7%, with only 12.6% surviving five years. Persons with primary lesions in the facial bones had the highest survival rate. Those with lesions in the humerus, tibia, and distal end of the femur had decreasingly lower survival rates. The lowest survival rates were for patients with lesions of the torso. In the femoral cases, size was a factor in survival; no patient with a tumor larger than 10 cm survived longer than five years. The surgery, irradiation, and chemotherapy employed--individually or in combination--did not alter appreciably the mortality rate for this tumor; only 12.6% of the patients survived five years or longer. Survivals were directly attributable to surgical procedures, including resection of pulmonary metastases. The data analyzed in this study provide a firm baseline of experience in analyzing results of treatment for osteosarcoma prior to the use of adjuvant chemotherapy, which is currently producing a vastly improved therapeuttic response.

Prognostic significance of vascular invasion in colorectal cancer of Dukes' B class.

To further characterize important prognostic factors in colorectal cancer of the Dukes' B class the pathologic material from 143 Dukes' B patients was reviewed for the presence of lymphatic and/or blood vessel invasion and correlated with the postoperative tumor-free interval and overall length of survival. In 27 patients with vascular invasion within the bowel wall, both the tumor-free interval and the overall survival time were not significantly different from the same parameters in 116 patients without vascular invasion (P = 0.28, P = 0.12 respectively). These data suggest that vascular invasion within the bowel wall per se is not an important prognostic factor among patients with colorectal cancer of the Dukes' B class.

Soft part tumors.

Results of management of rhabdomyosarcoma of childhood have improved in a dramatic manner during the recent 10 years as a consequence of the treatment by three modality approach which relies on an intensive multi-drug multicycle chemotherapy regimen combined with radiation therapy and or surgery. Both local results and total disease-free survival rates are markedly better with this more comprehensive approach. A staging system for sarcoma of soft tissue has just been developed by the A.J.C. Histopathological grade is the important parameter: stage 1,2, and 3 are tumors of histological grades 1, 2, and 3 respectively (an outline of the system is presented). Treatment results of 100 patients with sarcoma of soft tissue (extremities 89, torso 11) treated by radical dose radiation therapy (less than 6300 rad) and limited surgery at M.D. Anderson Hospital are presented. For both local control and disease free survival, results decreased with advancing stage and anatomic site was not a factor per se. Radiation therapy under tourniquet induced hypoxia was not found to be significantly more effective than conventional radical dose therapy. The necessity of planning treatment such that if subsequent surgery is required, the fields will provide the best distribution of unirradiated or low dose tissue for preparation of flaps, etc.

Radiation therapy of soft tissue sarcomas.

Recent advances in radiation therapy in the clinical management of patients with sarcoma of soft tissue are discussed. Radical dose radiation therapy combined with limited surgery has been shown to be highly effective as treatment of early to moderately advanced sarcomas of the extremities. Desmoid tumors which are nonresectable have been treated with moderate to high radiation doses with regular success. The multimodality treatment of rhadbomysarcoma of childhood has yielded a dramatic improvement in 2-year survival figures. This approach includes radiation therapy, multidrug and multicycle chemotherapy, and surgery. Finally, the dominant importance of the histologic grade of sarcoma to the prognosis is discussed in terms of a proposed clinical staging system.

Sarcoma of soft tissue: clinical and histopathologic parameters and response to treatment.

Radical dose radiation therapy alone or combined with limited surgery has been employed in the management of 100 patients with primary (71) and recurrent (29) sarcoma of soft tissue. Results of this experience show that a combination of conservative surgery and radiation therapy, based upon radical dose levels and sophisticated techniques, is effective: only 13 of 100 patients showed local regrowth during a followup of 2-12 years. This may be compared with an expected congruent to 25 recurrences had treatment been radical surgery (wide resection or amputation). For lesions located on the distal extremities (elbow-hand, knee-foot) there were local failures in only 3 of 59 (5 percent). Further, 75 percent of patients treated by the improved techniques utilized in the recent 8 years retained a useful limb which is free of pain or edema. Histopathologic grade is demonstrated to be an important indicator of prognosis of local recurrence and of disease-free survival. Local recurrence rates were 0/23, 9/53, and 4/24 for Grades 1, 2, and 3. Disease-free survival rates were 19/23 (86 percent), 27/53 (51 percent), and 4/24 (17 percent) for Grades 1, 2, and 3, respectively. Invasion of skin appeared to be a sign of poor prognosis; 8 of 9 such patients developed distant metastases.