Productive research in patients with peritoneal carcinomatosis has moved slowly over several decades. In large part this was due to lack of standardized assessments by which cancer responses could be quantitated in a reliable and statistically evaluable manner. Recently, both laboratory and clinical assessments have been developed. Clinical research has shown that the prognosis of patients with peritoneal carcinomatosis is dependent upon preoperative and intraoperative variables [1]. These are the histologic grade of the malignancy, the preoperative tumor volume as assessed at surgery, the distribution of tumor at surgery, and the completeness of cytoreductive surgery. Also the preoperative abdominal and pelvic computed tomography (CT) scan has shown predictive value in assessment of the completeness of cytoreduction in patients with mucinous carcinomatosis [2]. The clinical research tools that are currently used in peritoneal carcinomatosis studies are reviewed in this manuscript.

Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis

TGFβ1 Inhibits the Formation of Benign Skin Tumors, but Enhances Progression to Invasive Spindle Carcinomas in Transgenic Mice

This chapter deals with neoplasms of the uterus in which there is mesenchymal differentiation. Purely mesenchymal tumors, such as those derived from smooth muscle and endometrial stroma, are considered, as are benign and malignant neoplasms in which there are mixtures of epithelium and connective tissue.

Mesenchymal Tumors of the Uterus

BACKGROUND. Angiosarcomas (AS) are rare, aggressive tumors. Optimal treatment has not been well defined. The authors undertook a retrospective review of patients seen at their institution with the intent of identifying prognostic factors and optimal treatment strategies. METHODS. Between 1955 and 1990, 67 patients with AS were seen at the University of California, at Los Angeles Medical Center. Follow-up ranged from 1 to 173 months with a median of 30 months. RESULTS. The overall prognosis was poor. The actuarial 2- and 5-year disease free survivals (DFS) were 44% and 24%, respectively. Of 52 recurrences after primary treatment, 81% (42 of 52) had a component of local failure. Twenty-eight patients had developed distant metastases at last follow-up. Of patients who received surgery (S) and radiation therapy (RT), with or without chemotherapy (CT), 5-year actuarial DFS was 43%, compared with 17% for patients who underwent S+/-CT as initial treatment (P = 0.03). Only 9% of patients (1 of 11) treated with RT+/-CT were rendered free of disease. CONCLUSIONS. Patients with AS usually present with high grade histology, and with multifocal disease. There is a propensity for both local recurrence and distant metastases. Our results and a review of the literature, suggest that S plus RT offers the best chance for long term control of this aggressive tumor. The role of CT remains undefined.

Angiosarcoma: A report of 67 patients and a review of the literature

To examine the natural history of lymph node metastasis from sarcomas and the utility of therapeutic lymphadenectomy, clinical histories of all adult patients identified by a prospective sarcoma database for the 10-year period July 1982 to July 1991 were examined. Of the 1772 sarcoma patients, 46 (2.6%) were identified with lymph node metastasis. Median follow-up of all patients from diagnosis of lymph node metastasis was 12.9 months (range, 0 to 100 months). Median survival for nonsurvivors was 12.7 months (range, 0 to 40.7). The tumor types with the highest incidence of lymph node metastasis are angiosarcoma (5/37 total cases; 13.5%), embryonal rhabdomyosarcoma (ERMS) (12/88 total cases; 13.6%), and epithelioid sarcoma (2/12 total cases; 16.7%). Lymph node metastasis from visceral primary (p = 0.004) and malignant fibrous histiocytomas (p = 0.006) were associated with particularly poor prognosis. Thirty-one patients underwent radical, therapeutic lymphadenectomy with curative intent, whereas 15 patients had less than curative procedures, in most cases biopsy only. Patients not treated with radical lymphadenectomy had a median survival of 4.3 months (range, 1 to 32) whereas radical lymphadenectomy was associated with a 16.3 month median survival and the only long-term survivors (46% 5-year survival by Kaplan-Meier). The authors conclude that lymph node metastases from sarcoma are rare in adults, but vigilance is warranted, especially in angiosarcoma, ERMS, and epithelioid subtypes. Radical lymphadenectomy is appropriate treatment for isolated metastasis to regional lymph nodes and may provide long-term survival.

Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients.

Forty-four cases of skin and soft tissue angiosarcoma seen at M. D. Anderson Hospital before 1976 were reviewed. The cases fell into six different clinical groups: scalp-face, 17 cases; postmastectomy, 14 cases; postradiation, 5 cases; leg with vascular stasis, 2 cases; breast, 2 cases; and miscellaneous, 4 cases. In all cases in the first four groups, the tumors involved primarily the dermis and subcutis and showed similar blends of vasoformative and solid histologic patterns. Two tumors in the miscellaneous group closely resembled those in the larger groups, but the other two in that group (both located in deeper soft tissue sites) and the two breast angiosarcomas had a somewhat different microscopic appearance. Survival was generally poor in all groups, owing to frequent local recurrence and early metastasis; median survival for the entire series was 20 months. Findings of significantly favorable prognostic importance were tumor size less than 5 cm (in the scalp-face group) and a moderate or marked lymphoid infiltrate in and around the tumor. Less significant favorable factors were a distal location ( in the postmastectomy group) and a low degree of pleomorphism. Only nine patients had long-term, disease-free survival.

Angiosarcoma of skin and soft tissue: A study of forty-four cases

U.T.M.D. Anderson Hospital cases filed as endometrial sarcoma were reviewed. Malignant mixed Mullerian tumors, Mullerian adenosarcomas, and poorly differentiated sarcomas of uncertain origin were excluded, and a minimum of 36 months follow-up was required. On pathologic examination, the remaining cases fell into two distinct groups: endometrial stromal sarcoma (11 cases) and poorly differentiated endometrial sarcoma (seven cases). The former were characterized histologically by small to medium-sized uniform cells and distinctive arterial vasculature resembling the spiral arteries of the normal endometrium; they were thus considered to exhibit endometrial stromal differentiation. The latter showed topographic configurations indicative of endometrial origin but did not demonstrate endometrial stromal differentiation; they were composed of generally larger cells with nuclear hyperchromatism and pleomorphism and had no distinctive vascular pattern. The mitotic rate was usually low in endometrial stromal sarcoma and high in poorly differentiated endometrial sarcoma, although two examples of the former had more than 20 mitoses per 10 high-power fields. All but one of the patients with endometrial stromal sarcoma were less than 50 years of age, whereas all of those with poorly differentiated endometrial sarcoma were older than 50 years. One patient with endometrial stromal sarcoma died of tumor, two were living with tumor at latest follow-up, and eight were clinically tumor-free. By contrast, six of those with poorly differentiated endometrial sarcoma died of tumor, all within 34 months. The extent of tumor was the major prognostic factor in both groups; the three patients with endometrial stromal sarcoma who were dead or living with tumor all had extrauterine extension at the time of hysterectomy (only one of the other eight did so) and all six who died with poorly differentiated endometrial sarcoma had myometrial invasion (the one survivor had a tumor limited to the endometrium). Other pathologic factors, including mitotic rate, had no prognostic significance in either category; of particular interest was that both patients who had endometrial stromal sarcomas with high mitotic rates were tumor-free. It is concluded that endometrial stromal sarcoma is a distinct tumor entity whose diagnosis should not depend on mitotic rate, and it is suggested that poorly differentiated endometrial sarcoma is closely related to malignant mixed Mullerian tumor, in view of clinical and pathologic similarities.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819821115%2950%3A10%3C2170%3A%3AAID-CNCR2820501033%3E3.0.CO%3B2-K

Endometrial stromal sarcoma and poorly differentiated endometrial sarcoma

The case records and histologic material of 28 patients with leiomyosarcoma of soft tissue treated at M. D. Anderson Hospital between 1948 and 1975 were reviewed. These included patients in whom the tumors arose in the retroperitoneum (16), major blood vessels (3), and other soft-tissue sites, collectively designated peripheral soft tissue (9). Follow-up was complete in all cases. A striking preponderance of female patients was observed in the group with retroperitoneal tumors, in contrast to the male preponderance in the vascular and peripheral soft tissue tumor groups. Tumor size and location were the major prognostic factors; large size (greater than 5 cm) and retroperitoneal origin were associated with a much poorer clinical outcome than smaller size (less than 5 cm) and origin elsewhere than the retroperitoneum. These factors were related, since all retroperitoneal tumors were large. Microscopic appearance did not correlate significantly with clinical course. The clinical approach to these tumors is discussed in light of the findings of this study.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819810815%2948%3A4%3C1022%3A%3AAID-CNCR2820480429%3E3.0.CO%3B2-5

Leiomyosarcoma of soft tissue: A clinicopathologic study

Twenty cases of head and neck mucosal squamous cell carcinoma containing a prominent sarcomatoid element were reviewed with special attention to possible prognostic factors. Patients whose tumors invaded muscle, minor salivary or accessory respiratory glands, or bone had very poor survival rates, whereas those whose tumors were superficial and did not extend into any of these structures had excellent survival rates. A history of irradiation to the tumor site and tumor location in the oral cavity rather than the larynx, pharynx, nasal cavity, or nasal-associated structures were associated with invasiveness and thus with poorer survival. Aside from invasion, histologic features and gross configuration were not found to be of significant prognostic importance.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819810815%2948%3A4%3C994%3A%3AAID-CNCR2820480424%3E3.0.CO%3B2-M

Sarcomatoid squamous cell carcinoma of the mucous membranes of the head and neck: a clinicopathologic study of 20 cases.

Twenty-six cases of cystosarcoma phyllodes diagnosed at M. D. Anderson Hospital were reviewed. The following criteria were evaluated for possible correlation with local recurrence, uncontrolled local recurrence, metastasis, and tumor death: tumor size, stromal overgrowth, tumor necrosis, mitotic rate, stromal cellularity, nuclear size and pleomorphism, the presence of specialized stroma, and initial therapy. Of the 26 tumors, seven caused death. Five patients developed metastatic spread, and all of them died of tumor. Five patients had local recurrence, which was uncontrolled in three (two patients died with uncontrolled recurrence alone, and one with uncontrolled recurrence and metastasis). Stromal overgrowth was present in eight cases. Six of the seven patients who died of tumor had stromal overgrowth, including all five with metastasis. Correlation of stromal overgrowth with meta static spread and tumor death was significant at P levels of 0.0014 and 0.02, respectively. It is concluded that stromal overgrowth is a significant histologic indicator of malignant behavior in cystosarcoma phyllodes.

Harry L. Evans

Papers

Angiosarcoma of skin and soft tissue: A study of forty-four cases

Endometrial stromal sarcoma and poorly differentiated endometrial sarcoma

Leiomyosarcoma of soft tissue: A clinicopathologic study

Sarcomatoid squamous cell carcinoma of the mucous membranes of the head and neck: a clinicopathologic study of 20 cases.

Cystosarcoma phyllodes. A clinicopathologic study of 26 cases.