Malignant Solitary Fibrous Tumor of the Pleura With Liposarcomatous Differentiation.
Although malignant SFTs are well recognized histologically, to our knowledge, cases with liposarcomatous differentiation have not been reported. We describe herein an unusual malignant SFT of the pleura intermixed with well-differentiated liposarcoma.
MATERIALS AND METHODS
Routine hematoxylin-eosin-stained sections for light microscopy were generated from formalin-fixed and paraffin-embedded tissue. Immunohistochemical stains were performed on formalin-fixed and paraffin-embedded tissue using an avidin-biotin immunoperoxidase and strepavidin horseradish peroxidase. The antibodies used included CD34 (1:2, BioGenex, San Ramon, Calif), vimentin (1:2000, BioGenex), cytokeratin (AE1/AE3, 1:2000, Boehringer-Mannheim, Indianapolis, Ind), desmin (1:100, Accurate Chemical and Scientific Corp, Westbury, NY), smooth muscle actin (IA4, 1:4000, Sigma Diagnostic, St Louis, Mo), and S100 protein (1:1500, Dako Corporation, Carpinteria, Calif). Appropriate positive and negative controls were set up at the same time.
REPORT OF A CASE
The patient was a 66-year-old man who presented to Rhode Island Hospital with a large right pleural mass in February 1999. He was found to have a mass at the right lower aspect of the pleura 22 years previously when he had a chest x-ray examination following presentation with acute heartburn. This mass was thought to be a benign lesion and was followed annually. It grew slowly on subsequent computed tomography (CT) scans. In the past few years, however, it has progressively enlarged. Chest CT scans at the time he presented to Rhode Island Hospital revealed a large pleural-based mass of the right lower lobe of the lung (Figure 1). Two fine needle aspirations from the mass were inconclusive for a diagnosis due to necrotic tissue. The patient complained of an intermittent nonproductive cough. He denied any shortness of breath, pleuritic chest pain, abdominal pain, or weight loss.
[Figure 1 ILLUSTRATION OMITTED]
His medical history was remarkable for a 30-year history of cigarette smoking, stable coronary artery disease after a myocardial infarction in 1989, and carcinoma of colon, status post resection in 1990. There was no history of tuberculosis or asbestos exposure. He previously had a part-time job working with chemicals and was, therefore, exposed to uncertain types of fumes.
The patient then underwent a right thoracotomy and a right lower lobe lobectomy. A large multilobulated bulky mass, which occupied most of the basal portions of the lower lobe, was excised. Malignant SFT of the pleura was diagnosed. The patient's postoperative course was unremarkable, and he was discharged to home a few days later.
He developed back pain after his operation and was found to have metastatic disease in the lower spine 3 months after the surgical resection of the tumor. Seven months after his operation, he developed a pleural effusion. Fine needle aspiration of the right pleura was positive for tumor cells that were consistent with recurrent malignant SFT. Currently, approximately 10 months after resection, the patient is alive with disease.
MACROSCOPIC AND MICROSCOPIC FINDINGS
The surgically resected specimen consisted of an entire right lower lobe of lung. A pleural-based tumor was found at the superior and medial basal segment of the right lower lobe. The tumor measured 13.5 x 10.3 x 8.5 cm. It was well circumscribed, and the external surface appeared intact and glistening. The cut surface was gray, tan to yellow, and predominantly solid with a slightly whorled and nodular appearance. The solid area had small areas with traversing gray-yellow bands throughout the center of the specimen. The tumor involved the pleural surface and appeared to arise from this area with a small amount of adjacent, compressed, dense, tan, brown pulmonary parenchyma noted especially in the inferior portion of the tumor. The remaining lung tissue was soft, tan, and gray, with a small amount of anthracosis without any additional mass lesions.
Microscopically, the tumor exhibited a classic histologic appearance of an SFT (Figure 2, A through D). It was composed of spindle and plump-shaped cells embedded in a dense collagenous stroma. These cells were loosely arranged in interlacing fascicles or had a short storiform pattern. Vascular clefts and branching, which mimicked hemangiopericytoma, were seen. Most of the tumor showed marked nuclear atypia and a high mitotic rate (21 mitoses per 10 high-power fields). Approximately 40% of the tumor showed prominent necrosis. In addition, numerous adipocytes mixed with typical lipoblasts were seen scattered throughout portions of the tumor. This liposarcomatous component was estimated to be approximately 15% of the total tumor. The needle biopsy specimen of the recurrence revealed foci of the malignant SFT with no obvious liposarcomatous differentiation.
[Figure 2 ILLUSTRATION OMITTED]
Immunohistochemistry revealed the tumor cells from the malignant SFT area were uniformly and strongly positive for CD34 (Figure 3) and vimentin. They were negative for cytokeratin, desmin, smooth muscle actin (IA4), and S100. In addition, scattered spindle cells from the liposarcomatous areas were also positive for CD34 and vimentin. The lipoblasts were negative for CD34 and S100.
[Figure 3 ILLUSTRATION OMITTED]
In this report, we described an unusual case of a high-grade malignant SFT of the pleura with liposarcomatous differentiation. Although liposarcomatous differentiation has been reported in diffuse mesothelioma of the pleura, it has not been previously reported in SFT of the pleura.
In the present case, the tumor was composed of 2 entirely different tumor cell populations, malignant SFT and well-differentiated liposarcoma. Although the possibility of 2 coexisting primary malignant pleural tumors cannot be totally excluded, several features suggest that this is a single tumor. The tumor described in this report was a single mass lesion and not 2 adjacent abutting tumors and was mainly composed of spindle-shaped cells embedded in a dense collagenous stroma. Liposarcomatous areas were seen scattered throughout portions of the tumor and compromised relatively small portions (approximately 15%) of the tumor mass. Primary liposarcomas of the pleura, although reported, are extremely rare. These tumors usually present as typical liposarcomas, such as well-differentiated or myxoid, which are the most common types reported. An interlacing fascicular growth pattern or a patternless pattern of the tumor cells in a dense collagenous stroma are not the characteristics of these liposarcomas. Recently, a spindle cell variant of well-differentiated liposarcoma has been reported. These tumors share certain histomorphologic and immunohistochemical features with our case. These tumors, however, like other types of liposarcomas, were located in the extremities, shoulder, and upper back and arose predominantly in subcutaneous tissue. In addition, unlike the present case, these tumors frequently have myxoid change and a better-organized fascicular pattern. Although immunoreactivity for CD34 is found in lipomatous tumors, including the recently described spindle cell variant of liposarcoma,[12,13] only focal or scattered cells are positive for CD34. The uniform and strong positivity of tumor cells for CD34 in our case supports the diagnosis of malignant SFT of the pleura with liposarcomatous differentiation.
In the present case, the tumor cells are composed of spindle and plump-shaped cells, which are arranged in interlacing fascicles or a short storiform pattern. Focally, vascular clefts and branching are appreciated. These morphological features can mimic other benign or malignant lesions, such as malignant peripheral nerve sheath tumor (MPNST), malignant mesothelioma, sarcomatoid type, monophasic synovial sarcoma, malignant fibrous histocytoma, fibrosarcoma, leiomyosarcoma, and spindle cell carcinoma. In MPNST, the cells are usually arranged in sweeping fascicles. Densely hypercellular areas alternate with hypocellular myxoid areas. The cells may be arranged in a nodular or whorled pattern. One of the important features of the MPNST is the proliferation of the tumor cells in the subendothelial zones of the blood vessels. The presence of heterologous elements, such as cartilage, bone, and skeletal muscle, may be helpful for the diagnosis of the MPNST. The nuclear features of the tumor cells in MPNST are usually wavy or comma shaped. About 50% to 90% of the MPNST are S100 protein positive, although focally.
In diffuse mesothelioma, or malignant sarcomatoid-type mesothelioma, the tumor cells are spindle shaped and pleomorphic. They may be embedded in a fibrous and hyalinized stroma and may display a whorled or storiform pattern. However, most of the tumor cells, unlike SFT, are positive for high- and low-molecular-weight cytokeratin. The cells in the monophasic synovial sarcoma are spindle shaped. This tumor has a more uniform fascicular pattern. Calcified and hyalinized areas are often seen. The tumor cells, unlike SFT, are usually cytokeratin positive. Malignant fibrous histocytoma is a tumor with highly variable morphologic features. The tumor cells may have a spindle, plump, or pleomorphic appearance and may be arranged in short fascicles or in a storiform pattern. Immunohistochemically, the tumor cells are usually negative for CD34 and may be focally positive for cytokeratin or desmin.
Fibrosarcoma can be ruled out from the present case by its herringbone growth pattern and negativity for CD34 in the tumor cells. In leiomyosarcoma, the cells are elongated with abundant cytoplasm and centrally located with blunt-ended (cigar-shaped) nuclei. The cells are arranged in a more orderly fascicular pattern than SFT. Muscle-specific actin (HHF35) stains the tumor cells in about 50% to 100% of cases. Finally, spindle cell carcinoma can be ruled out by its positivity for cytokeratin and negativity for CD34.
Malignant SFT may occur de novo or by transformation from benign or low-grade tumors. A case of malignant recurrence of an SFT of the pleura developing 20 years after initial surgery has been reported. In the present case, the patient had the lesion for 22 years with recent rapid growth. This could represent a transformation from a benign pleural tumor to a more aggressive malignant tumor.
To the best of our knowledge, this is the first report of a malignant SFT of the pleura with liposarcomatous differentiation. Recognizing this heterogeneity of SFT of the pleura will be helpful in the accurate diagnosis and appropriate management of these patients. This also raises interesting suggestions about the relation between lipomatous tumors and SFT in general, and possibly the cell of origin, especially in light of the recent report on the reactivity of CD34 in lipomatous tumors. This should be addressed in future studies.
We thank Dr Sharon W. Weiss (Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Ga) for confirming the diagnosis.
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Accepted for publication July 18, 2000.
From the Departments of Pathology (Drs Bai, Aswad, and Gnepp) and Surgery (Dr Gaissert), Rhode Island Hospital, Brown University School of Medicine, Providence, RI.
Reprints: Douglas R. Gnepp, MD, Department of Pathology, Rhode Island Hospital, 593 Eddy St, Providence, RI 02903.