Answer: Inflammatory myofibroblastic tumor

Histology: The lung contains a spindle cell tumor, which has both a fascicular and storiform pattern. Intermixed within the spindle cell tumor are foamy macrophages containing hemosiderin, lymphocytes, and a population of multinucleate giant cells. The spindle cells are non-pleomorphic and lack significant mitotic activity. A focus of vascular invasion is identified. By immunohistochemistry, this lesion labeled intensely for vimentin, focally for actin and desmin, and not for cytokeratin or S100 protein. The lesion demonstrated strong cytoplasmic immunoreactivity for ALK (anaplastic lymphoma kinase).

Discussion: Synovial sarcomas can be primary to the lung, though more commonly they are metastatic. Similar to the above case, the monophasic spindle cell variant is composed of bland monomorphic spindle cells. However, synovial sarcomas do not typically contain multinucleated giant cells and admixed inflammation. Spindled synovial sarcomas are often focally immunoreactive for epithelial markers, and do not label for either desmin or ALK. Leiomyosarcomas also are more commonly metastatic when present in the lung. These lesions typically grow with a more purely fascicular pattern, have abundant eosinophilic cytoplasm, and show significant pleomorphism. They also do not stain for ALK. A significant portion of anaplastic large cell lymphomas are immunoreactive for ALK, usually in a nuclear and cytoplasmic pattern. However, these tumors are typically non-spindled and composed of pleomorphic, rounded cells with irregular convoluted nuclei.

Inflammatory myofibroblastic tumors go by several names in the literature, including plasma cell granuloma, inflammatory pseudotumor, and inflammatory fibrosarcoma. IMTs are myofibroblastic proliferations with an associated inflammatory infiltrate that preferentially occur in children or young adults. Up to 25% will recur and a few will “metastasize”, though it is not clear if the latter are examples of metastasis or multifocality. The histopathology can be separated into three types. The myxoid type resembles nodular fasciitis, the compact/spindle cell type resembles fibrous histiocytoma, while the hypocellular fibrous type resembles fibromatosis. While some of these lesions are likely reactive (for example, the pulmonary IMTs that are associated with bronchiolitis obliterans organizing pneumonia), a subset of IMTs appear to be neoplastic. These tumors have rearrangements involving chromosome 2p23, which is the location of the ALK gene. ALK is known to be rearranged in the t(2;5)(p23;q35) translocation of anaplastic large cell lymphoma (ALCL). Because of this translocation, ALK, which is normally not expressed in adult tissue, is over expressed in ALCL and the product becomes detectable by immunohistochemistry. A similar phenomenon occurs in a subset of IMTs. Translocations of the ALK gene to a number of partners, including the Tropomyocin 3 and 4 genes, result in ALK overexpression in IMTs.