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Smooth Muscle Tumor of the Pleura.

A Case Report and Review of the Literature

Primary intrathoracic soft tissue tumors are unusual. They can originate from the upper or lower respiratory tract or from the mediastinum.[1-5] The differential diagnosis for pleural spindle cell neoplasms includes smooth muscle tumors, malignant mesothelioma, thymoma, spindle cell carcinoma, and other soft tissue tumors arising in the adjacent organs, as well as solitary fibrous tumor in cases of circumscribed masses.

Leiomyomas and leiomyosarcomas originating in the serosal membranes represent controversial entities.[6-8] Some researchers classify these tumors as sarcomatous types of mesothelioma when they are diffuse, or as variants of solitary fibrous tumors when they are localized.[8] A leiomyoid form of mesothelioma that coexpresses cytokeratin, desmin, and smooth muscle actin has been documented.[9]

To date, only 1 published study has reported a series of 5 pleural smooth muscle tumors (3 leiomyosarcomas and 2 smooth muscle tumors of undetermined malignant potential).[6,7] Since only a few cases have been reported and the follow-up time for these cases was short, the malignant potential of pleural smooth muscle tumors has not yet been defined. We report an additional case of smooth muscle tumor of the pleura documented by light microscopy, immunohistochemistry, and electron microscopy.


A 32-year-old asymptomatic white man presented in 1994 with a left intrathoracic mass diagnosed incidentally by routine preemployment chest radiography. The radiologic examination showed a left pleural-based mass with a benign appearance and no destruction of adjacent ribs or indentation of the lung. The differential diagnosis suggested by both chest radiography and magnetic resonance imaging included fibroma, neuroma, and leiomyoma. The mass measured 3.0 x 5.2 cm by magnetic resonance imaging, and there was no invasion into the muscle or bone. A computed tomography-guided transthoracic biopsy of the tumor revealed a bland smooth muscle proliferation. Due to the lack of malignant features and significant obesity of the patient, it was elected that the lesion be followed rather than excised.

A chest computed tomographic scan performed 4 years later revealed a well-defined mass in the left thoracic wall at the level of the third and fourth ribs. The lesion had both an intrathoracic and an extrathoracic component; the intrathoracic part measured 4.3 x 7.0 cm and the extrathoracic part measured 4.0 x 6.0 cm. Figure 1 shows the computed tomographic scan demonstrating the intrathoracic component. The tumor displaced a portion of left upper lobe and appeared to extend through the chest wall, displacing the pectoralis minor muscle laterally. Coarse irregular calcifications with sclerosis and remodeling of the underlying ribs were also visualized. No adenopathy was present. No other masses were identified on physical examination or by radiologic studies. A biopsy of the pleural lesion was performed, and the histology was similar to that seen in the previous specimen from 1994. The tumor was resected with part of the anterior chest wall and a segment of the third rib. The patient had a unremarkable postoperative course and was alive and free of tumor 12 months postoperatively.



Representative formalin-fixed, paraffin-embedded tissue blocks from the pleural-based tumor and the intramuscular mass were cut at 3 [micro]m, dried for 1 hour at 60 [degrees] C, deparaffinized in xylene, and rehydrated through graded alcohol. Hematoxylin-eosin-stained sections and immunohistochemical studies were performed. Endogenous peroxidase activity was quenched by immersion in absolute methanol containing 3% (vol/vol) hydrogen peroxide for 5 minutes. Staining was performed on a Dako Autostainer (Dako Corporation, Carpinteria, Calif). Tissue sections were incubated with antibodies for cytokeratin cocktail (AE1/ AE, 1124-161, Boehringer-Mannheim, Indianapolis, Ind, 1:1000; MAK-6, 92-0005, Becton-Dickinson, San Jose, Calif, 1:20; CAM 5.2, 28-0001, Zymed, San Francisco, Calif, 1:100); vimentin (M0725, Dako, 1:50); desmin (M0724, Dako, 1:15); [Alpha]-smooth muscle actin (A2547, Dako, 1:75); muscle actin (HHF-35) (C34931, Enzo Diagnostics Inc, New York, NY, 1:20 000); smooth muscle myosin-heavy chain (M3558, Sigma, St Louis, Mo, 1:1000); CD34 (M236UC, Immunotech, Marseille, France, 1:75); CD99 (O13) (8810, Signet, Dedham, Mass, 1:30); S100 (20311, Dako, 1:3000); and Bcl-2 (M0887, Dako, 1:5) using the avidin-biotin peroxidase complex technique. Sections were counterstained with Harris hematoxylin and coverslipped using synthetic mounting medium. Mouse non-immune serum was substituted for negative controls, and appropriate positive controls were run for all antibodies tested. For electron microscopy, formalin-fixed tissue blocks were routinely processed for ultrastructural examination. Thin sections were stained with lead citrate and uranyl acetate, and examined with an electron microscope.


Gross Examination

The intrathoracic tumor was well circumscribed, encapsulated, and measured 7.0 x 5.5 x 4.0 cm. It appeared to originate from the parietal pleura and involved neither the ribs nor the skeletal muscle. The mass had a pink, shiny, and slightly lobulated cut surface with focal, punctate, light yellow calcifications and irregular, white, fibrous streaks (Figure 2). A second smaller tumor was identified embedded in the skeletal muscle, external to the third rib. This ovoid, well-defined lesion measuring 6.0 x 4.0 x 2.6 cm had a capsule and a variegated cut section with focal calcifications that appeared similar to the intrathoracic neoplasm. The 2 masses were completely separate from each other, on opposite sides of the ribs. All surgical margins were grossly free of tumor.



Sections of the tumors showed a proliferation of bland spindle cells (Figure 3) with rare mitotic figures (1-2 mitoses/10 high-power fields) and focal areas of increased mild cellularity and atypia. Scattered calcifications were noted. The intramuscular mass was less cellular, but otherwise histologically similar to the intrathoracic lesion. The 2 tumors were separated by intervening connective tissue, bone, and muscle. The resection margins were negative for tumor.



Immunohistochemical stains performed to further characterize the neoplasm showed reactivity for vimentin, [Alpha]-smooth muscle actin, HHF-35, smooth muscle myosin-heavy chain (Figure 4), and desmin, and showed focal weak positivity with CD34. No staining was seen with S100 protein, Bcl-2, CD99 (O13), and cytokeratin cocktail. The pattern of staining for the antibodies was similar in both lesions.


Electron Microscopy

Electron microscopy of the pleural-based mass showed discohesive spindle cells with elongated nuclei displaying margination of chromatin and indentation of the nuclear membrane. Parallel arrays of intracytoplasmic actin micro-filaments with interspersed fusiform dense bodies, discontinuous external lamina, and occasional cell junctions were also seen. No microvilli, tonofilaments, or desmosomes were present. These findings confirmed smooth muscle differentiation.


Leiomyomas and leiomyosarcomas are encountered commonly in the urogenital tract,[10,11] occasionally in the gastrointestinal tract,[12-14] and rarely in the respiratory tract.[1-5,15] Smooth muscle neoplasms originating in the serosal membranes are even more unusual.[6-8,16-19]

To the best of our knowledge, only 5 smooth muscle tumors of the pleura have been described in the literature to date.[6,7] Table 1 contains patient and tumor information for the 5 previously described cases and for the case described here. Three of the published cases were conventional leiomyosarcomas, while the other 2 had a bland histology suggestive of a leiomyoma. However, these 2 tumors were large and unresectable, and therefore were regarded to be of undetermined malignant potential. Interestingly, both tumors of undetermined malignant potential occurred in young women (aged 21 and 23 years), whereas the other 3 leiomyosarcomas presented in older adults. Radiographically, 4 of the neoplasms presented as solitary pleural masses (2 of them also involved the diaphragm), and the fifth encased the lung, similar to a mesothelioma. Histological immunohistochemical, and electron microscopic studies confirmed smooth muscle differentiation for all 5 tumors.

Table 1. Clinical and Histopathologic Features of Pleural Smooth Muscle Tumors
Patient No. y Symptoms Histology(*)

1 F/21 Asymptomatic SMT of UMP([dagger])
2 M/49 Asymptomatic Leiomyosarcoma,
3 F/23 Asymptomatic SMT of UMP([dagger])
4 F/44 Empyema Leiomyosarcoma,
 intermediate grade
5 M/69 Chest pain Leiomyosarcoma,
 high grade
Present patient M/32 Asymptomatic SMT of UMP

 Sex/Age, Follow-up,
Patient No. y mo

1 F/21 4
2 M/49 8
3 F/23 6
4 F/44 2
5 M/69 12
Present patient M/32 12

(*) SMT indicates smooth muscle tumor; UMP, undetermined malignant potential.

([dagger]) Tumors were unresectable and only debulked at surgery.

We describe a primary smooth muscle neoplasm that arose in the parietal pleura and over a period of 4 years increased in size and metastasized into the adjacent skeletal muscle. The second tumor, located in the pectoral muscle, most likely represents a metastasis from the primary neoplasm, but could also have resulted from dissemination of tumor cells through the needle biopsy tract.

The neoplastic cells were histologically bland, spindle-shaped, and had elongated nuclei and a moderate amount of eosinophilic cytoplasm. Rare areas of increased cellularity, atypia, and mitotic activity were present. The tumor cells stained strongly positive for vimentin and all smooth muscle markers ([Alpha]-smooth muscle actin, smooth muscle myosin-heavy chain, HHF-35, and desmin) and stained focally and weakly with CD34. Immunostains for cytokeratin cocktail, S100, Bcl-2, and CD99 (O13) were negative. The histologic appearance of the masses, as well as the immunohistochemical pattern of staining and the smooth muscle differentiation confirmed by electron microscopy, was most consistent with a diagnosis of smooth muscle neoplasm.

The differential diagnosis for spindle cell tumors of the serosal membranes includes solitary fibrous tumor, metastatic spindle cell carcinoma, sarcomas extending from the adjacent mediastinal structures, sarcomatous mesothelioma, and thymoma.[9,15-9] Table 2 compares the typical pattern of immunoreactivity for these tumors.

Table 2. Immunohistochemical Pattern of Reactivity in Pleural Spindle Cell Tumors(*)
Tumor Vimentin SMA HHF-35 SMMS

Smooth muscle tumor + + + +
Solitary fibrous tumor + -/+ -/+ -/+
Metastatic spindle cell
 carcinoma +/- - - -
Synovial sarcoma + - - -
Fibrosarcoma + - - -
Malignant peripheral nerve
 sheath tumor + - - -
Sarcomatous mesothelioma + - - -
Spindle cell thymoma - - - -

Tumor Desmin CD34 S100

Smooth muscle tumor + +/- -
Solitary fibrous tumor - + -
Metastatic spindle cell
 carcinoma - - -
Synovial sarcoma - - -
Fibrosarcoma - - -
Malignant peripheral nerve
 sheath tumor - - -/+
Sarcomatous mesothelioma -/+ - -/+
Spindle cell thymoma - - -

Tumor Bcl-2 CD99 (O13) Cyto-keratin

Smooth muscle tumor - - -
Solitary fibrous tumor + + -
Metastatic spindle cell
 carcinoma - - +
Synovial sarcoma + +/- +/-
Fibrosarcoma -/+ - -
Malignant peripheral nerve
 sheath tumor -/+ - -
Sarcomatous mesothelioma -/+ -/+ +([dagger])
Spindle cell thymoma -/+ - +

(*) SMA indicates smooth muscle actin; HHF-35, muscle actin; SMMS, smooth muscle myosin-heavy chain; +, positive staining; +/-, usually positive; -/+, rarely positive; and -, negative.

([dagger]) Low molecular weight cytokeratin.

In sarcomatous mesothelioma, the histologic pattern is nonspecific and overlaps with that of many soft tissue tumors, including malignant fibrous histiocytoma, fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, and malignant schwannoma. Sarcomatous mesothelioma typically is immunoreactive with low-molecular-weight cytokeratin, whereas most sarcomas either do not express cytokeratin or do so only focally.[18] Other soft tissue tumors, such as synovial sarcoma, fibrosarcoma, malignant fibrous histiocytoma, and malignant or benign peripheral nerve sheath tumors, can be excluded by their histologic appearance and immunophenotypes.

In our case, the mass was solitary and well circumscribed, suggesting a diagnosis of solitary fibrous tumor or metastatic carcinoma rather than mesothelioma. Due to the cytokeratin negativity and the absence of a primary epithelial neoplasm, a metastatic carcinoma was unlikely. The main entity that remained in the differential diagnosis was solitary fibrous tumor of the pleura.

Solitary fibrous tumor is also known as localized mesothelioma or pleural fibroma, and it frequently presents as a pedunculated mass occupying the pleural cavity, but it can adhere to the pleural surface and, rarely, can project within the lung or can be entirely intrapulmonary. Histologic features characteristic for solitary fibrous tumor are spindle cells arranged in a "patternless pattern" and interlacing collagen bundles. Most tumors have fibrous areas with low to moderate cellularity and abundant bands of hyalinized collagen, but more cellular areas composed of spindle cells with scant intervening stroma are also present.[18-21]

Smooth muscle neoplasms and solitary fibrous tumors are both negative for cytokeratin, epithelial membrane antigen, and S100. Solitary fibrous tumors are generally negative for actin and desmin, and do not typically show strong positive reactions to other muscle antibodies. Solitary fibrous tumors exhibit strong and consistent positive staining with CD34 and Bcl-2.[18-24] Bcl-2 is generally negative in benign and malignant smooth muscle tumors, except for uterine leiomyomas.[23,24] Recently, CD99 (O13) has been described as a marker that is often useful in the diagnosis of solitary fibrous tumors in conjunction with CD34 and Bcl-2.[20-25] In our case, immunoreactivity for CD99 (O13) and Bcl-2 was negative, but reactivity for CD34 was weakly and focally positive. CD34 is a myeloid progenitor cell antigen and is present in endothelial cells and most vascular tumors, as well as in most gastrointestinal stromal tumors, dermatofibrosarcoma protuberans, and solitary fibrous tumors.[26-29] Occasional positivity has been described in benign nerve sheath tumors, epithelioid sarcomas, and spindle cell lipomas.[27-30] CD34 reactivity has also been described in some uterine smooth muscle neoplasms, as well as in spindle and epithelioid leiomyosarcomas arising elsewhere.[30-34] Therefore, weak immunoreactivity for CD34 in our case is nonspecific and does not help limit the differential diagnosis. The appearance with hematoxylin-eosin staining and the immunohistochemical pattern of staining in our case are most consistent with a smooth muscle neoplasm.

The addition of our case to the literature offers new clinicopathologic data useful for better defining the diagnosis and biological behavior of pleural smooth muscle tumors. We present a pleural-based neoplasm that fulfilled all criteria for smooth muscle differentiation, but that showed weak, focal staining with CD34. Focal CD34 immunoreactivity has been reported occasionally in leiomyosarcomas from different locations, as well as in leiomyomas and leiomyosarcomas of the uterus, but has not been demonstrated previously in smooth muscle tumors of the pleura. Our case documents a metastatic site or, less likely, needle tract seeding in a tumor that was well circumscribed and histologically bland, emphasizing that these neoplasms have a low, but definite malignant potential and should be completely resected when possible.

In summary, smooth muscle tumor of the pleura is a well-defined clinicopathologic entity. Despite its bland histologic appearance, this tumor has a low, but definite malignant potential, and therefore complete resection and follow-up of patients is advised. Additional cases with long-term follow-up are necessary to better define the prognosis.


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[21.] Hasegawa T, Matsuno Y, Shimoda T, Hirohashi S, Hirose T, Sano T. Frequent expression of bcl-2 protein in solitary fibrous tumors. Jpn J Clin Oncol. 1998;28: 86-89.

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[23.] Miettinen M, Sarlomo-Rikala M, Kovatich AJ. Cell-type- and tumour-type-related patterns of bcl-2 reactivity in mesenchymal cells and soft tissue tumours. Virchows Arch. 1998;433:255-260.

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[28.] Weiss SW, Nickoloff BJ. CD-34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors and related lesions. Am J Surg Pathol. 1993;17:1039-1045.

[29.] Katenkap D, Mentzel T, Kosmehl H. CD34 detection: an immunohistochemical contribution to the differential diagnosis of soft tissue tumors. Pathologe. 1996;17:195-201.

[30.] Templeton SF, Solomon AR, Jr. Spindle cell lipoma is strongly CD34 positive: an immunohistochemical study. J Cutan Pathol. 1996;23:546-550.

[31.] Arber DA, Kandalaft PL, Mehta P, Battifora H. Vimentin-negative epithelioid sarcoma: the value of an immunohistochemical panel that includes CD34. Am J Surg Pathol. 1993;17:302-307.

[32.] Ikeda T, Yoshida Y, Satoh M, Sawada N, Mori M. Oesophageal sarcoma with CD34 positivity. Histopathology. 1998;33:284-286.

[33.] Sirgi KE, Wick MR, Swanson PE. B72.3 and CD34 immunoreactivity in malignant epithelioid soft tissue tumors: adjuncts in the recognition of endothelial neoplasms. Am J Surg Pathol. 1993;17:179-185.

[34.] Rizeq MN, Van De Rijn M, Hendrickson MR, Rouse RV. A comparative immunohistochemical study of uterine smooth muscle neoplasms with emphasis on the epithelioid variant. Hum Pathol. 1994;25:671-677.

Accepted for publication April 19, 2000.

From the Departments of Pathology (Drs Proca and Frankel) and Surgery (Drs Ross and Pratt), The Ohio State University Medical Center and Arthur G. James Cancer Hospital and Research Institute, Columbus, Ohio.

Reprints: Wendy L. Frankel, MD, The Ohio State University Medical Center, Department of Pathology, E401 Doan Hall, 410 W 10th Ave, Columbus, OH 43210.
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Author:Proca, Daniela M.; Ross, Patrick Jr.; Pratt, Jerry; Frankel, Wendy L.
Publication:Archives of Pathology & Laboratory Medicine
Geographic Code:1USA
Date:Nov 1, 2000
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