Inflammatory myofibroblastic tumour of the lung

Definition

An inflammatory "pseudotumour" composed of collagen, inflammatory cells and bland spindle cell of myofibroblastic differentiation.

Synonyms

Inflammatory pseudotumour, plasma cell granuloma, plasma cell/histiocytoma complex, fibroxanthoma, xanthogranuloma, fibrous histiocytoma, organising pneumonia, invasive fibrous tumour of the tracheobronchial tree.

Similar lesions occur in the mediastinum, intestinal mesentery, bone and urinary bladder.

Epidemiology

Occurring at any age, inflammatory myofibroblastic tumour is most common before the age of 40 years.

Etiology

There is increasing evidence that these tumours should be subdivided into those that are non-neoplastic inflammatory lesions (inflammatory pseudotumour) and those that are true neoplasms, showing cytogenetic abnormalities and gene mutation, with the associated potential for more aggressive behavior3, designated as inflammatory myofibroblastic tumour. The true neoplasms may be aneuploid and show p53 mutations. Cytogenetic abnormalities have been shown on chromosome 2 at 2p2310, in proximity to the ALK gene, with formation of fusion products incorporating the ALK gene and immunohistochemical expression of ALK. ALK positivity is less common in pseudotumour of the lung than at other sites2.

A second subset of inflammatory pseudotumours appear to be reactive and associated with various infective agents, including Epstein-Barr virus, Actinomyces, Pseudomonas species, mycoplasma and human herpes virus-82,8. The principle cell in this type appears to be the follicular dendritic cell.

Clinical features

80% of patients are symptomatic5, with endobronchial lesions resulting in cough, wheeze or haemoptysis4. Constitutionally, there may be weight loss, fever or fatigue5. Invasion of the chest wall by peripheral lesions results in pleuritic or chest wall pain.

Radiology

There is a solitary mass which may have spiculated margins. If endobronchial, there may be postobstructive pneumonia or atelectasis. The lesion may be radiologically indistinguishable from pulmonary sequestration11.

Macroscopic appearance

The tumour forms a rubbery mass which is not encapsulated. There may be calcification. Cavitation is not common.

Histopathology

Matsubara proposed three forms, with overlap9:

organising pneumonia type: a presumed postpneumonic inflammatory mass with central scarring and peripheral air space granulation tissue.
fibrous histiocytoma type: storiform proliferation of bland spindle cells with admixed lymphocytes, plasma cells and histiocytes.
plasma cell granuloma/lymphoplasmacytic type: fascicles of benign spindle cells associated with an intense lymphoplasmacytic infiltrate. There may be lymphoid follicles6 or Touton type giant cells.

Immunohistochemistry

smooth muscle actin	9/91, 4/46
vimentin	9/91, 4/46
desmin	0/91, 0/46
cytokeratin	focally positive in one third of cases0, 0/91, 0/46
ALK-1	positive in 40% of cases0, 3/91
Myoglobin	negative0
Myogenin	negative0
CD117	negative0
S-100	negative0, 0/46

The extrapulmonary cases more often show positivity for cytokeratins.

Differential diagnosis

inflammatory fibrosarcoma
sarcomatoid variant of anaplastic large cell Ki-1 lymphoma
malignant fibrous histiocytoma7

Management

Complete resection4. If incompletely resected, the residual tumour will continue to grow5.

Prognosis

Complete excision is commonly curative5. Recurrences7 and metastases are rare. Local invasion, vascular invasion, increased cellularity and pleomorphism, a high mitotic rate (greater than 3 per 50 HPF) and necrosis are associated with poor prognosis7.