Leiomyosarcoma

Leiomyosarcoma

Primary leiomyosarcomas of the lung are rare; however, they are more common than their   benign counterparts (leiomyomas). Essentially the same principles are applied to the diagnosis of  these tumors; a careful clinical history and physical examination are necessary to rule out metastatic disease. The diagnostic criteria are similar to those for soft tissue leiomyosarcomas. ost of the information regarding pulmonary leiomyosarcomas has been p resented as single case reports or short series of cases, with only a few larger series. !n some reported series, however,  pulmonary leiomyosarcomas have been included in the general context of smooth muscle tumors or with other sarcomas, such as fibrosarcomas. Clinical Features

Primary leiomyosarcomas in the lung are more common in adult patients; however, several cases occurring in children as young as newborns also have been described. These tumors may appear  as intrap intrapare arenchy nchymal mal masses masses or may arise arise in an endobro endobronchi nchial al locati location. on. "linic "linical al signs signs and symptoms may be related to the anatomic location of the tumor. Patients with tumors in a central location may present with symptoms of bronchial obstruction, including cough, shortness of   breath, chest pain, and hemoptysis. Patients with peripheral tumors may present with more systemic complaints such as weight loss, or they may be completely asymptomatic, with the tumor discovered on a routine chest radiograph. #ther presenting manifestations may include clubbing of the fingers, pleural effusion, or Pancoast tumor. $ uni%ue case of a renin&producing leiomyosarcoma has been reported. #n radiologic evaluation, no specific diagnostic hallmar's for leiomyosarcomas in the lung have been recognied. Macroscopic Features

Tumor sie may range from  cm to more than * cm in greatest dimension. !ntraparenchymal tumors appear to be well&demarcated masses that may be encapsulated or surrounded by a thin covering of fibroconnective tissue. The cut surface may app ear a bit +whorly and whitish, with a firm consistency ( -ig. &* ). $reas of hemorrhage and necrosis may be seen, and it is important to document such findings. Endobronchial tumors may manifest as pedunculated masses or may

 be firmly adherent to the bronchial wall. They are smaller than intraparenchymal tumors but may have the same gross features in terms of necrosis and hemorrhage.

Figure 7-10 Pulmonary leiomyosarcoma, gross specimen, with focal areas of hemorrhage and necrosis. istopathologic Features

The morphologic features of primary leiomyosarcomas of the lung are similar to those seen in soft tissue tumors. The microscopic appearance is characteried by a spindle cellular   proliferation arranged in broad fascicles of tumor cells that intersect at right angles, replacing normal lung parenchyma or protruding into the bronchial lumen. The cells have light eosinophilic cytoplasm, elongated +cigar&shapednuclei, and inconspicuous nucleoli. #n the  basis of their cytoarchitectural features, pulmonary leiomyosarcomas have been separated into three distinct histologic grades/ •

Low-grade leiomyosarcomas:  !umors are composed of a spindle cell proliferation, which on higher magni"cation shows mild cytologic atypia and a mitotic count of 1 to # mitotic "gures per 10 high-power "elds $ Figs. 7-11 to 7-1# %. Cellular pleomorphism and hemorrhage and necrosis are a&sent.

Figure 7-11 Low-grade pulmonary leiomyosarcoma. ' spindle cell proliferation can &e seen replacing lung parenchyma.

Figure 7-1( Low-grade pulmonary leiomyosarcoma with ectatic )essels.

Figure 7-1# igh-power )iew of a low-grade leiomyosarcoma showing mild nuclear atypia and scattered mitotic "gures. •

Intermediate-grade leiomyosarcoma:  !he fascicular pattern of growth is preser)ed* howe)er, the tumors show more prominent cellularity and increased mitotic acti)ity in the range of + to  mitotic "gures per 10 highpower "elds $ Figs. 7-1+ to 7-1 %. Cytologic atypia is present &ut not mared, and

occasionally,

pleomorphic

hemorrhage are a&sent.

Figure 7-1+

cells

may

&e

present.

/ecrosis

and

ntermediate-grade leiomyosarcoma with more o&)ious cellular atypia.

Figure 7-1 ntermediate-grade leiomyosarcoma showing a focal infarcted area.

Figure 7-1 ntermediate-grade leiomyosarcoma with readily identi"a&le mitotic "gures. •

High-grade leiomyosarcoma: ' more solid spindle cell proliferation is displayed, with areas still preser)ing the fascicular pattern of growth, which may ac2uire a storiform or hemangiopericytic pattern. 'reas of necrosis or hemorrhage are readily identi"ed. 3egenerati)e changes, such as my4oid change and stromal hyalini5ation, can &e seen. Cellular pleomorphism is

mared, with larger cells that ha)e prominent nucleoli* mitotic "gures are easily identi"ed and num&er more than  per 10 high-power "elds $ Figs. 7-17 to 7-(1 %. n some cases, )ascular in)asion is identi"ed.

Figure 7-17 igh-grade leiomyosarcoma with mared cellular atypia.

Figure 7-1 igh-grade leiomyosarcoma with a hemangiopericytic pattern.

Figure 7-16 igh-grade leiomyosarcoma with e4tensi)e areas of necrosis.

Figure 7-(0 igh-grade leiomyosarcoma showing my4oid changes.

Figure 7-(1 igh-grade leiomyosarcoma showing mitotic "gures and nuclear atypia. mmunohistochemical Features

The tumor cells show positive staining for smooth muscle actin, desmin, and vimentin. $s the tumor loses differentiation, however, variability in the staining pattern for these muscle mar'ers may be noted. !n high&grade tumors, the staining may be only focal, whereas in low&grade tumors, the staining may be stronger and diffuse. 0eiomyosarcomas also may coexpress positive staining for 'eratin antibodies, so a wider than usual panel of immunohistochemical studies will  be necessary to properly evaluate these neoplasms. Molecular tudies

1chneider and associates reported a case of a primary pulmonary leiomyosarcoma in a child. 2aryotypic studies demonstrated consistent abnormalities of chromosomes , 3, 4, and ; relative gain of chromosomes 5 and ; and relative loss of chromosomes 6, 6, 5*, and 55. 3i8erential 3iagnosis

#ne of the most important considerations in the differential diagnosis is metastatic disease. The only way to distinguish between primary and metastatic disease is by careful analysis of findings on the clinical history and physical examination. #n morphologic grounds, other spindle cell

sarcomas may enter into the differential diagnosis, including monophasic synovial sarcoma, intrapulmonary solitary fibrous tumor, and neurogenic sarcoma. !n this setting, positive immunostaining for muscle mar'ers (smooth muscle actin and desmin) and negative staining for  1&** protein and "789 should indicate the correct interpretation. !n high&grade tumors,  pleomorphic carcinoma may enter into the differential diagnosis. $lthough pleomorphic carcinoma also may show focal staining for actin, it usually does not show positive staining for  desmin and negative staining for 'eratin. !n the same context, malignant melanoma also may be a consideration; the use of 1&** protein, :&93, and elan $ may be helpful in these cases.  !reatment and Prognosis

The initial treatment for patients with pulmonary leiomyosarcoma usually is surgical excision of  the tumor. #nce that is accomplished, the patient may be a candidate for ad