—  SPECIALTY CONFERENCE  —

Pulmonary Pathology

Case 3 - Inflammatory Myofibroblastic Tumor (IMT)

Cheryl M. Coffin
University of Utah
Salt Lake City, Utah


Click on each slide thumbnail image for an enlarged view
Clinical History:
A six-year-old girl had a right lower lobe lung mass. Wedge resection revealed a 2.6x2.5x1.5 cm firm nodule with a grey-white whorled surface.

Diagnosis - Inflammatory myofibroblastic tumor (IMT)


Case 3 - Figure 1 - Inflammatory myofibroblastic tumor displays interlacing fascicles of spindle cells with a prominent lymphoplasmacytic infiltrate.
Case 3 - Figure 2 - Inflammatory myofibroblastic tumor with myxoid and spindle cell areas.
Case 3 - Figure 3 - Inflammatory myofibroblastic tumor demonstrates spindle cells with elongated nuclei and eosinophilic nucleoli resembling ganglion cells accompanied by a lymphoplasmacytic infiltrate.

Discussion/Differential Diagnosis:
Inflammatory myofibroblastic tumor is a distinctive lesion composed of myofibroblastic spindle cells accompanied by an inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils 14. IMT occurs primarily in the lungs, soft tissue, and viscera of children and young adults. Synonyms include plasma cell granuloma 31, 42, 48, 50, plasma cell pseudotumor 38, inflammatory myofibrohistiocytic proliferation 46, and inflammatory pseudotumor 1, 6, 7, 10, 32, 39, 47, 50. Omental mesenteric myxoid hamartoma 21 and inflammatory fibrosarcoma 33 are other terms which have been used for similar lesions.

The age range of IMT extends from early childhood through adulthood with a median age of nine years and a mean age of ten years. The peak frequency is in the first two decades of life and there is a slight female predominance. The etiology is unknown. Human herpesvirus-8 DNA sequences and overexpression of human interleukin 6 and cyclin D1 have been observed 19, 20. The most common sites are the lung, mesentery, and omentum. Other sites include soft tissue, mediastinum, gastrointestinal tract, pancreas, genitourinary tract, oral cavity, skin, breast, nerve, bone, and central nervous system 11, 14, 37. Pulmonary IMT is associated with chest pain and dyspnea, but may be asymptomatic. A mass, fever, weight loss, and pain are frequent complaints. In up to one-third of patients, a syndrome of fever, growth failure, malaise, weight loss, anemia, thrombocytosis, polyclonal hyperglobulinemia, and elevated erythrocyte sedimentation rate is observed 14, 41, 43. A case with progression from bronchopneumonia has been reported 18.

Grossly, IMT is a circumscribed or multinodular firm white or tan mass with a whorled, fleshy, or myxoid cut surface. Hemorrhage, necrosis, and calcification are unusual macroscopic variants. In some lesions, a zonal pattern with central scarring and a softer red or pink periphery is observed. Multinodular tumors are generally restricted to the same anatomic region and may be contiguous or separate. The spindled myofibroblasts, fibroblasts, and inflammatory cells form three basic histological patterns 12, 14. The myxoid vascular pattern consists of loosely arranged plump or spindled myofibroblasts in an edematous background with abundant blood vessels and infiltrative plasma cells, lymphocytes, and eosinophils. This pattern resembles granulation tissue, nodular fasciitis, or other reactive processes. The compact fascicular pattern is characterized by a spindle cell proliferation with variable myxoid and collagenized regions and a distinctive inflammatory infiltrate with a diffuse inflammation, small aggregates of plasma cells, or lymphoid nodules, and prominent cellularity. Ganglion-like myofibroblasts with vesicular nuclei, eosinophilic nucleoli, and abundant amphophilic cytoplasm are often seen in the first two patterns. The second pattern resembles a fibromatosis, fibrous histiocytoma, or other spindle cell neoplasms including rhabdomyosarcoma or smooth muscle neoplasms. The third pattern simulates a scar or desmoid fibromatosis with plate-like collagen, lower cellularity, and relatively sparse inflammation. Coarse or psammomatous calcifications and osseous metaplasia are unusual histologic variants.

Rare examples of IMT undergo histologic malignant transformation characterized by highly atypical polygonal cells with oval vesicular nuclei, prominent nucleoli, and variable mitoses, including atypical forms 11, 14. Large ganglion-like cells and Reed-Sternberg-like cells are also seen 35. A round cell histiocytoid pattern may develop in recurrences.

The immunohistochemical profile of IMT is variable. Strong diffuse cytoplasmic reactivity for vimentin is typical. Smooth muscle actin and muscle-specific actin expression vary from a focal to a diffuse pattern in the spindle cell cytoplasm, and desmin is identified in many cases. Focal cytokeratin reactivity is seen in about a third. Cytoplasmic immunohistochemical positivity for ALK is detectable in about half of IMTs and correlates well with the presence of ALK rearrangements detected by fluorescent in situ hybridization 9, 13, 15, 22, 51. p53 immunoreactivity is rare and may portend recurrence and malignant transformation 24.

IMT in children and young adults often harbors clonal cytogenetic rearrangements that activate the ALK receptor tyrosine kinase gene on the chromosome 2 short arm 4, 16, 22, 29, 40, 44. Some evidence suggests that such rearrangements may be uncommon in IMT diagnosed in adults greater than 40 years old. A subset of IMT lack ALK oncogenic activation but contain chromosomal rearrangements targeting the HMGIC gene on chromosome 12 26. Immunohistochemistry is the most efficient method for identifying ALK oncoproteins in IMT 13 15 and has sensitivity comparable to in situ hybridization. However, several other neoplasms including rhabdomyosarcoma and anaplastic large cell lymphoma can express ALK oncoproteins 8.

The recurrence rate for IMT is approximately 25% and is related to location, resectability, and multinodularity. A combination of atypia, ganglion-like cells, p53 expression, and aneuploidy may help to identify IMT with a more aggressive potential 2, 3, 24, 27, 30, 39. Unfortunately, histopathological findings alone do not provide reliable predictors of recurrence or malignant transformation in an individual case. At present, surgery is the principal treatment, although regression and response to corticosteroids and nonsteroidal anti-inflammatory agents have been reported in individual cases 5, 11, 12, 23, 25, 34, 36, 45.

The differential diagnosis includes reactive processes, dendritic cell neoplasms, fibromatoses, nodular fasciitis, fibrous histiocytoma, smooth muscle neoplasms, sarcomatoid carcinoma, rhabdomyosarcoma, and other spindle cell neoplasms 10, 14, 17, 49. Inflammatory pseudotumor of lymph nodes and spleen is a distinct entity from IMT 28.

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