Prolonged partial remission of malignant fibrous histiocytoma in posterior mediastinum by immunotherapy

Shinjiro Muneta

Malignant fibrous histiocytoma (MFH) is the most common type of soft-tissue sarcoma of late adult life. It occurs most frequently in deep fascia and skeletal muscle of the extremities and trunk, but mediastinal MFH is exceptionally rare.[1,2] Concerning the treatment of MFH, little information is available on immunotherapy. We report herein the case of a patient with the giant cell type of MFH in the posterior mediastinum who achieved a prolonged partial remission by immunotherapy with recombinant interferon alpha-2a and OK432 (streptococcal preparation).[3]

Case Report

A 16-year-old girl began to complain of dry cough and chest pain 10 months before the hospital admission. Since these symptoms steadily progressed with gradual weight loss, she visited a local hospital, where a chest roentgenogram revealed a giant posterior mediastinal tumor. A chest roentogenogram taken one year previously showed no abnormality.

On hospital admission, there was dullness to percussion with decreased breath sounds at the left upper lung posteriorly. Magnetic resonance imaging showed a spherical mass with regular margin measuring 10 cm in diameter in the left pleural cavity, which displaced the mediastinum in the right anterior direction and invaded the vertebrae (fifth, sixth) and the ribs (fourth to seventh).

Exploratory thoracotomy revealed that the tumor formed a gray spherical mass measuring 10 cm in diameter, which arose from the left posterior mediastinum and wedged between the two left lung lobes. Since the tumor was densely adherent to the pleural surface and involved the great vessels, its extirpation could not be carried out. Histologic examination of the excisional biopsy specimen showed that the main components of the tumor consisted of mononuclear histiocyte-like cells and osteoclast-type polynuclear giant cells, as shown in Figure 1. Spindle fibroblastic cells arranged in a focal storiform pattern and foamy cells were also observed in some places. The tumor section showed weakly positive reaction with anti-S-100 antibody. These histologic appearances were characteristic of the giant cell type of MFH.

After the operation, the patient received three courses of combination chemotherapy followed by a course of radiation therapy (42 Gy). The tumor, however, increased in size and worsening of clinical symptoms was observed (Fig 2). Treatment with interferon alpha-2a, therefore, was started and continued thereafter in a daily maintenance dose of 13.5 million units with subsequent combination with OK-432 (2.5 KE/day), which improved clinical symptoms strikingly and induced a marked reduction in tumor size with extensive necrosis (Figs 2 and 3). The patient currently remains well without evidence of metastasis.

General immunities before and one year after the immunotherapy were evaluated by lymphocyte blastogenesis assays and lymphocyte surface antigens. Lymphocyte blastogenesis was measured by incorporation of tritiated thymidine induced by mitogens such as phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). Stimulation indices, which were calculated by dividing the radioactivity in the presence of mitogen by that without mitogen, increased from 20.6 to 69.2 for PHA, from 14.2 to 33.6 for Con A, and from 2.7 to 7.5 for PWM after the immunotherapy. The percentage of CD-16 positive cells and that of CD-57 positive cells among peripheral blood lymphocytes increased from 10 percent to 19 percent and from 26 percent to 36 percent, respectively. The ratio of percentage of CD-4 positive cells to that of CD-8 positive cells decreased from 0.95 (38 percent/40 percent) to 0.26 (13 percent/50 percent) after the immunotherapy. The immunohistologic staining using the patients serum obtained after the immunotherapy, however, showed negative in the tumor section.

Discussion

MFH is the most common soft-tissue sarcoma in middle-to-late adult life with a definite preponderance and a predilection for the extremities.[1,2] A review of the literature disclosed only eight case reports of MFH originating from the mediastinum. Early and complete surgical removal of the tumor is an essential first step in the treatment of MFH because of its aggressive nature such as frequent local recurrences and distant metastases. Only a few investigators[4,5] have reported that partial remissions occurred in some patients after combination chemotherapy. Most of them, however, received surgical treatment prior to chemotherapy. Chemotherapy or radiation therapy alone, therefore, seems to have very limited effect on patients with MFH. Our patient was entirely resistant to both combination chemotheraphy and radiation therapy.

Thus, we tried immunotherapy based on the following knowledge. It is reported that interferon induces the expression of major histocompatibility complex class I antigens as well as tumor associated antigens on the surface of tumor cells,[6] which may enhance the immune recognition of tumor cells through the generation of cytotoxic T lymphocytes. OK-432, a potent immunopotentiating agent widely used in Japan, has been shown to augment the cytotoxicity of various effector cells, including macrophages, natural killer cells, and killer T cells.[3] Therefore, these two biologic response modifiers are expected to act in a synergistic manner for a tumoricidal effect.

Following the immunotherapy, our patient showed an increased capacity of lymphocyte blastogenesis and increased percentages of cytotoxic T cells (CD-8) and natural killer cells (CD-16, CD-57) among peripheral blood lymphocytes, suggesting the augmentation of cell-mediated immunity. This may be responsible for the tumoricidal effect of the combination immunotherapy in our patient who has a prolonged remission of MFH.

References

[1.] Weiss SW, Enzinger FM. Malignant fibrous histiocytoma: an analysis of 200 cases. Cancers 1978; 41:2250-66 [2.] Kearney MM, Soule EH, Ivins JC. Malignant fibrous histiocytoma: a retrospective study of 167 cases. Cancer 1980; 45:167-78 [3.] Uchida A, Hoshino T. Clinical studies on cell-mediated immunity in patients with malignant disease: I effect of immunotheraphy with OK-432 on lymphocyte subpopulation and phytomitogen responsiveness in vitro. Cancer 1980; 45:476-83 [4.] Leite C. Goodwin JW, Sinkovics JG, Baker LH, Benjamen R. Chemotherapy of malignant fibrous histiocytoma: a Southwest Oncology Group report. Cancer 1977; 40:2010-14 [5.] Tewfik HH. Tewfik FA, Latourette HB. Malignant fibrous histiocytoma: a retrospective evaluation of 24 patients. J Surg Oncol 1981; 16:189-97 [6.] Guadagni F, Schlom J. Johnston WW, Szpak CA, Goldstein D, Smalley R, et al. Selective interferon-induced enhancement of tumor-associated antigens on a spectrum of freshly isolated human adenocarcinoma cells. J Natl Cancer Inst 1989; 81:502-12

COPYRIGHT 1992 American College of Chest Physicians

COPYRIGHT 2004 Gale Group

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