Chemotherapy influences the pseudocapsule composition in soft tissue sarcomas

Abstract

Background: Soft tissue sarcomas are a heterogeneous group of malignant tumors. Standard treatment for soft tissue sarcoma of the extremity is surgical excision and adjuvant therapy; however, the role of neoadjuvant chemotherapy is controversial.

Questions/purposes: We sought to (1) define the histologic characteristics of the pseudocapsule in soft tissue sarcomas; (2) compare the appearance of this structure in chemotherapy-treated versus untreated soft tissue sarcomas; and (3) evaluate the effect of chemotherapy on the presence and viability of tumor cells at the host-sarcoma interface.

Methods: Twenty-eight patients with biopsy-proven, deep, high-grade extremity soft tissue sarcomas greater than 5 cm (AJCC stage III) treated with chemotherapy and surgical excision were compared histologically with 47 matched control subjects treated with surgery alone.

Results: A pseudocapsule was identifiable in the majority of tumors and consisted of two identifiable layers, each with specific histological characteristics suggesting the biologic processes occurring in these layers are different. The pseudocapsule was more frequently observed in the group treated with chemotherapy and it was more frequently continuous, thicker, and better developed in this group. Chemotherapy decreased the number of tumors with malignant cells identified within and beyond the pseudocapsule.

Conclusions: Neoadjuvant chemotherapy contributed to the development of a pseudocapsule and decreased the number of tumors with malignant cells identified within and beyond the pseudocapsule.

Clinical relevance: These findings may provide a histological explanation for the clinical effect of chemotherapy in soft tissue sarcoma.

Level of evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Trial registration: ClinicalTrials.gov NCT00346125.

Fig. 1A–B

A cartoon that shows the handling and analysis of the pathological specimens. (A) Specimens were sectioned along the longest axis. (B) The complete tumor-normal tissue interface in this slice was submitted for histologic evaluation.

Fig. 2

Undifferentiated pleomorphic sarcoma without neoadjuvant chemotherapy. The tumor (lower left, ^#) is surrounded by a delicate outer layer of pseudocapsule (*). Please note the absence of the inner layer (Stain, hematoxylin and eosin; original magnification, × 200).

Fig. 3

Pseudocapsule in undifferentiated pleomorphic sarcoma after neoadjuvant chemotherapy. Outer fibroblastic layer is seen at right (*); inner hyalinized hypocellular layer at left (^#) contains rare tumor cells with regressive changes and dilated capillaries (Stain, hematoxylin and eosin; original magnification, × 100).

Fig. 4

Synovial sarcoma after neoadjuvant chemotherapy; the external pseudocapsule layer contains numerous foamy macrophages (left, ^#). Undifferentiated pleomorphic sarcoma after neoadjuvant chemotherapy; external pseudocapsule layer contains numerous hemosiderin-laden macrophages (right, *) (Stain, hematoxylin and eosin; original magnification, × 100).

Fig. 5

Undifferentiated pleomorphic sarcoma without neoadjuvant chemotherapy. Tumor (right, *) infiltrates skeletal muscle (left, ^#); note absence of pseudocapsule (Stain, hematoxylin and eosin; original magnification, × 100).

Fig. 6

Fibrosarcoma after neoadjuvant chemotherapy. Residual viable tumor cells (*) in hyalinized inner layer show prominent degenerative changes (Stain, hematoxylin and eosin; original magnification, × 600).