Sarcoma of the pulmonary artery: report of four cases with electron microscopic and immunohistochemical examinations, and review of the literature

Abstract

Herein we report the clinicopathological features of four cases of pulmonary artery sarcoma that appeared at our institution during a period of 30 years. The patients, 2 males and 2 females, were 50-62 years old. Tumour was found in the pulmonary trunk and right pulmonary artery in all cases, in the pulmonary valve and left pulmonary artery in three of the four cases, and in the right ventricular outflow tract in one case. There was direct extension or metastases to the lungs in two cases, the heart in one case, mediastinum or lymph nodes in two cases and the pleura in one case. Ultrastructural examination in one case revealed cells with features of smooth muscle cells and myofibroblasts. Immunohistochemical examination of three cases gave the following results: vimentin and smooth muscle specific actin was positive in all three cases, desmin in one case and cytokeratin in one case. No positivity was found for Factor VIII. This and other studies indicate that histologically most pulmonary artery sarcomas are leiomyosarcomas or "undifferentiated spindle cell sarcomas". Immunohistochemical and ultrastructural examinations favour an origin from myofibroblasts, probably derived from multipotent (undifferentiated) cells in the wall of the vessel. Most lesions show extensive intrathoracic growth although they rarely metastasize outside the thoracic cavity. They have a poor prognosis although some cases are currently being diagnosed during life.

Gains of 12q13-14 and overexpression of mdm2 are frequent findings in intimal sarcomas of the pulmonary artery

“…In accordance with the results of previous studies [5,6,12], the immunohistochemical expression of vimentin was very strong in contrast to less pronounced expression of alpha smooth muscle actin. Weak focal expression of desmin and epithelial markers were found in two and three tumors, respectively.…”

“…The two tumor types (including tumors classified as malignant fibrous histiocytoma and myxofibrosarcomas) comprise up to 80% of the reported tumors. The remaining tumors contained areas of osteosarcoma, chondrosarcoma, angiosarcoma, or rhabdomyosarcoma or, very rarely, liposarcoma [5,6,12,17,19]. No such elements were observed in representatively sampled tumors in our series.…”

“…Non-intimal, mural sarcomas of the pulmonary artery are exceedingly rare and are difficult to differentiate from primary sarcomas of the lung. In the literature, the majority of intimal sarcomas are described as poorly differentiated, often myxoid and pleomorphic sarcomas, often with immunohistochemical and ultrastructural signs of myofibroblastic differentiation [5,12,17]. The second most common category is a leiomyosarcoma.…”

“…Since the first intimal sarcoma of pulmonary artery reported by Mandelstamm in 1923 [14], approximately 150 further tumors have been described. Immunohistochemical and electron microscopic examinations suggest a myofibroblastic differentiation of the tumor cells, although an at least partial differentiation along other cell lineages was morphologically documented (chondrosarcomatous, osteosarcomatous, and angiosarcomatous) [8,11,12,17]. The molecular background of these tumors is largely unknown and, to the best of our knowledge, they have not yet been analyzed at the genetic level.…”

Primary pulmonary artery sarcoma resembling chronic thromboembolic pulmonary disease

“…The origin of PPAS is uncertain, but is thought to be linked to the malignant development of intimal or subintimal myofibroblasts [3].…”