Diagnosis: Solitary fibrous tumor of pleura. Synonyms: Localized fibrous tumor, localized fibrous mesothelioma [1], benign fibrous tumor [2]


Solitary Fibrous Tumor of Pleura

Introduction: These rare tumors are composed of cells that have the phenotype of fibrous connective tissue of the subpleura (or subserosa). They also develop in other sites in the thorax (pericardium, anterior mediastinum, lung parenchyma), as well as in other locations in the body [3,4]. Their behavior is somewhat unpredictable. They are not associated with asbestos exposure. One case occurred after radiation therapy [5].

Clinical features: Solitary fibrous tumors occur at all ages but have a peak in the sixth and seventh decades; they occur equally in men and women. Symptoms of chest pain, cough, and dyspnea occur in about half of patients; others are asymptomatic. Larger tumors may be associated with effusion, hypoglycemia, and pulmonary osteoarthropathy [2]. One possible cause of hypoglycemia is overproduction of insulin-like growth factor-II [6]. Osteoarthropathy is very frequent in patients with benign tumors over 7 cm diameter [7].

Radiographic features: Most tumors are pleural-based, have sharply circumscribed borders and a round contour, and are less than 10 cm in diameter. A few are located in the fissures. Calcification is rare [1,3].

Gross features: Two-thirds of tumors are found on the visceral pleura and one-third on the parietal pleura. Some arise in fissures and a few grow into, or are entirely within, lung parenchyma. About 8% occur in the mediastinum [2,3]. Up to 39 cm in diameter, but usually 5 to 10 cm in diameter, the tumors may be sessile or pedunculated. Large tumors may adhere secondarily to contiguous surfaces, making their site of origin uncertain. Tumors are usually firm, rounded or lobulated, and sharply circumscribed from lung parenchyma. The cut surfaces are pale and lobulated but may have cysts, focal hemorrhage, or necrosis [1,2].

Histologic features: The patterns seen in these tumors often resemble those of other tumors. Two general patterns have been described: a solid, spindled cell growth and a sclerosing growth. Both are often present in the same tumor [1]. Cells have nuclei with fine, diffuse chromatin and small nucleoli [2]. In solid, cellular areas there is little or no collagen. In sclerosing areas, collagen varies from scant to marked. As collagen increases and then predominates, cells become compressed. Other areas may have a myxoid stroma. Gland-like structures represent inclusions of non-neoplastic epithelium. Other areas can resemble malignant fibrous histiocytoma, hemangiopericytoma, fibrosarcoma, or a neural tumor [1]. For example, bundles of spindled cells with a spoke-like arrangement characterize the storiform pattern seen in malignant fibrous histiocytoma. When thin-walled, dilated vessels become prominent, the pattern is hemangiopericytoma-like. A herringbone pattern resembles fibrosarcoma. Some areas have wavy fibers reminiscent of neural tumors [1]. The pattern has been called "patternless" when these distinct patterns are absent. Reactive multinucleate giant cells may be present occasionally, and a chronic inflammatory infiltrate is found in some tumors. There may be microscopic calcification or metaplastic bone or cartilage [2].

Histologic features of malignancy occur in about 40% of tumors. These features include crowded, overlapping nuclei, >4 mitoses/10 high power fields, cellular pleomorphism, or tumor giant cells [2]. Adequate sampling (1 section/centimeter diameter of tumor) is important to evaluate cellular features [2].

Immunohistochemical stains: Immunoperoxidase stains show consistent staining with antibodies to vimentin, a very non-specific connective tissue marker, but no staining with antibodies to keratin, an epithelial marker. Stains for smooth muscle actin are sometimes positive. Recently, it has been shown that these tumors usually react with antibody to CD34, a glycoprotein found in endothelial and myeloid precursor cells [8].

Summary of Histologic Features

Differential diagnosis: The patterns seen in localized fibrous tumors can mimic those of other benign or malignant tumors. Hemangiopericytoma, fibrosarcoma, and malignant fibrous histiocytoma are most difficult to separate from solitary fibrous tumor [8]. Hemangiopericytoma is usually a parenchymal tumor when it involves the lung. Malignant fibrous histiocytoma and fibrosarcoma usually have a more uniform histologic pattern and are not circumscribed [8].

Diagnosis: Needle biopsy can exclude most epithelial carcinomas, but the differential diagnosis of spindle-celled neoplasms is large, including carcinoma, and requires a large amount of tissue to recognize the patterns present and to perform special stains. Diagnosis is usually made after surgical excision.

Metastatic sites: Malignant lesions metastasize to lymph nodes and the opposite lung, CNS, liver, spleen, peritoneum, adrenal, gastrointestinal tract, kidney, or bone [2]

Therapy: Wide resection of the primary tumor is advocated because of possible local recurrence.

Prognostic factors: Large size (>10 cm diameter), location in fissures and growth into the lung, hemorrhage, necrosis, and histologic features of malignancy are correlated with aggressive behavior [2]. About 40% of the tumors are histologically malignant. Although almost all histologically benign, circumscribed tumors are cured by excision, only about 1/2 of histologically malignant tumors are cured. The other half recur or metastasize. Complete excision of the tumor is the most important factor in predicting a favorable clinical outcome for histologically malignant tumors [2].

References

1. Moran C, Suster S, Koss M. The spectrum of histologic growth patterns in benign and malignant fibrous tumors of the pleura. Sem Diagn Pathol 1992; 9:169-180.

2. England D, Hochholzer L, McCarthy M. Localized benign and malignant fibrous tumors of the pleura. A clinicopathologic review of 223 cases. Am J Surg Pathol 1989; 13:640-658.

3. Witkin G, Rosai J. Solitary fibrous tumor of the mediastinum. A report of 14 cases. Am J Surg Pathol 1989; 13:547-557.

4. Goodlad J, Fletcher C. Solitary fibrous tumour arising at unusual sites: analysis of a series. Histopathology 1991; 19:515-522.

5. Bilbey J, Müller N, Miller R. Localized fibrous mesothelioma of pleura following external ionizing radiation therapy. Chest 1988; 94:1291-1292.

6. Ron D, Powers A, Pandian M, Godine J, Axelrod L. Increased insulin-like growth factor II production and consequent suppression of growth hormone secretion: a dual mechanism for tumor-induced hypoglycemia. J Clin Endocrinol Metab 1989; 68:701-706.

7. Okike N, Bernatz P, Woolner L. Localized mesothelioma of the pleura. Benign and malignant variants. J Thorac Cardiovasc Surg 1978; 75:363-372.

8. Hanau C, Miettinen M. Solitary fibrous tumor: Histological and immunohistochemical spectrum of benign and malignant variants presenting at different sites. Hum Pathol 1995; 26:440-449.

Clinical summary

Comments: mw6825@itsa.ucsf.edu

Table of Contents

Last revised 5/10/97

Copyright 1997 Martha L. Warnock. All rights reserved.