Spindle cell tumors of the pleura: differential diagnosis

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Spindle cell tumors that arise in or metastasize to the pleura must be thoroughly evaluated to arrive at a definitive diagnosis. Malignant mesothelioma is the most common tumor arising in the pleura, but metastatic tumors to the pleura occur more frequently. Additionally, many tumors arising in the lung and surrounding tissues involve the pleura. It is crucial to arrive at a correct diagnosis since many of these neoplasms show different prognoses and require varying treatment modalities. Sarcomatoid malignant mesothelioma is a rare tumor that arises in the pleura, and can be confused with numerous tumors arising in or metastasizing to the pleura, including synovial sarcoma, metastatic sarcomatoid carcinoma, metastatic melanoma, thymoma, renal cell carcinoma, localized fibrous tumor, leiomyosarcoma, and other types of sarcoma. Desmoplastic malignant mesothelioma is a fibrous sarcomatoid variant of malignant mesothelioma, and is occasionally mistaken for chronic fibrous pleurisy. Here, we review morphological, clinical, histological, immunohistochemical, ultrastructural, and molecular methods that aid in the diagnosis of spindle cell tumors of the pleura, and we provide specific examples of patients in which this multi-modal approach proved to be helpful.

Section snippets

Clinical history and morphology

Clinical data are extremely important in the diagnosis of pleural tumors. Clinical features can help to determine whether the condition is malignant or benign, as well as the origin of the malignancy. For example, when a patient presents with the differential diagnosis of DMM versus CFP, clinical evidence of distant metastases and invasion of the chest wall is diagnostic for malignancy. Instead, a history of pneumonia alerts the pathologist that the lesion may be benign CFP. Age is also an

Histology

Histologically, SMM mimics other spindle cell tumors. In highly cellular tumor areas, pleomorphic spindle cells may grow in a storiform pattern as often seen in malignant fibrous histiocytoma. Other areas may also arrange in herringbone fascicular pattern as seen in soft tissue fibrosarcoma.

Renal cell carcinomas can differentiate into a variety of histological patterns, including spindle cell, making them difficult to distinguish from SMM. Leiomyosarcomas are some of the more commonly occurring

Immunohistochemistry

One single specific marker to identify SMM or other spindle cell tumors of the pleura does not exist. Use of a diverse panel of immunohistochemical markers can lead to a definitive diagnosis when the data are considered collectively and in parallel with the clinical and histological evidence (Table 1). It is problematic to establish a unique immunoprofile for an inherently variable tumor such as MM, i.e., MM can show epithelioid, sarcomatoid, or biphasic characteristics. As a consequence of its

Electron microscopy

MM shares some ultrastructural similarities with adenocarcinoma, such as desmosomal junctions, external lamina, and elongated surface microvilli. Long branching microvilli are diagnostic of MM, whereas adenocarcinomas show short microvilli. Although microvilli are not seen in SMM cells, when these tumors have a small epithelial component, this tumor component should be sampled for EM, and if long branching microvilli are found, they are diagnostic of MM. SS is ultrastructurally defined by

Case 1

A 51-year-old female was hospitalized with a diagnosis of left pleural effusion and pneumonia. Two weeks later, she checked into the hospital again due to difficulty breathing. Radiology revealed a left pleural thickening, and a biopsy was interpreted as DMM. She was given a 6-month prognosis. The patient refused chemotherapy when she learned that chemotherapy usually does not influence the natural course of this disease. She sold her house, retired into a nursing home, and made funeral

Conclusion

The diagnoses of spindle cell tumors of the pleura are challenging because these malignancies show similar clinical presentation, histology, and immunoreactivity. Clinically, they may present with a localized mass or a diffuse pleural thickening. Histology generally shows poorly differentiated and pleomorphic tumors with a variable fibrous component and cellularity. MM is the most common primary tumor of the pleura, and SMM comprises approximately one-third of all MM. However, metastatic

Acknowledgments

This work was partially supported by grants from the Butitta Mesothelioma Foundation, the NCI (IPO1CA114047, RO1CA092657-05, RO1CA106567-02), and the Riviera Country Club (to M.C.).

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