Unknown 9

The patient is a 7-year-old boy with severe left-sided chest pain for several weeks following minor trauma.

Chest Radiography

Figure 1

Frontal chest radiograph shows homogeneous opacity within the left chest, without evidence of rib fracture. The opacity was interpreted to represent pleural effusion, perhaps related to intercostal artery injury, given the history of trauma. A surgical chest tube was placed.

Several more procedures were performed to characterize this opacity. See Figures 2, 3, 4, 5, 6, 7, 8, and 9.


Pathology

The open biopsy was interpreted as granulation tissue on frozen section, but the diagnosis was changed on the permanent sections. Thoracotomy to remove the tumor was performed 2 weeks later after embolization to reduce bleeding. The operative report states that the predominantly mediastinal tumor was surrounded by dense adhesions and blood. It was dissected piecemeal from the diaphragm, pericardium, and lung where it involved part of the lower lobe and lingula. Removal was incomplete.

Gross: The specimen consisted of multiple fragments, 7 x 7 x 2 cm in aggregate, consisting of lung parenchyma and solid yellow-tan tumor.

Figure 10: The tumor was composed of interlacing bundles of spindled cells; scattered lymphocytes, plasma cells, and eosinophils; and areas of fibrosis.

 

This low-power view shows bundles of longitudinally cut spindled cells with elongate nuclei mixed with bundles of similar cells with round nuclei cut in cross section.

Note two arteries (one large and one small) and multiple very fine capillaries that help to supply this vascular tumor.

Figure 11

At higher magnification, in another area, the spindled cells with ill-defined borders and pale nuclei are separated by collagenous matrix. In the center is a cluster of lymphocytes without visible cytoplasm and plasma cells with eccentric nuclei and visible cytoplasm.

The spindled cell nuclei do not show enlargement or hyperchromaticity to suggest malignancy. Mitoses were rare.

Figure 12

Foamy macrophages, often in clusters and sometimes multinucleated, are a frequent finding. The cells on the right have large amounts of lipid-filled cytoplasm and those on the left side have considerably less.

What is the differential diagnosis? What is the diagnosis? Answers

What special stains would help to confirm the diagnosis? Answer

 

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Inflammatory Myofibroblastic Tumor (IMT)

(also called plasma cell granuloma, inflammatory pseudotumor)

Discussion: IMTs occur in all parts of the body, but the lung is probably the organ most frequently involved. A few tumors are localized to the airways [1]. Occurring at all ages and fairly equally in both sexes, IMTs are common among primary lung tumors in pediatric patients [2]. These lesions are often discovered incidentally, as in the present case. When symptomatic, patients may present with cough, chest pain, or hemoptysis; or symptoms related to endobronchial obstruction when the lesion presents in such a location. Systemic manifestations, occurring in 30 to 50% of patients include fever, thrombocytosis, anemia, clubbing, increased sedimentation rate, and increased serum immunoglobulins, probably manifestations of cytokines produced by the tumor. These symptoms usually disappear after the tumor is removed [3].

IMTs have not been described extensively in the radiographic literature. The largest series, from the AFIP, showed that the lesion usually presents as a peripheral nodule or focal consolidation, and less commonly as an endobronchial lesion with post-obstructive pneumonia [4]. Lesions are often less than 3 cm in size, but may become quite large and may occasionally be associated with hilar or mediastinal lymphadenopathy or pleural effusion. CT has been reported to show a smooth or lobulated mass, with or without enhancement, that occasionally calcifies. MR has been reported to show decreased T1 and increased T2 signal intensity. It has been asserted that pulmonary inflammatory myofibroblastic tumor is the most common cause of a calcified pulmonary mass on the radiograph of a child [4].

On long term follow-up, thoracic inflammatory myofibroblastic tumors tend to be stable in size, although they may demonstrate growth. In rare circumstances they have been shown to spontaneously regress, or they may regress with steroid or radiation treatment. However, some lesions show locally aggressive behavior, including chest wall invasion, invasion of adjacent vasculature, or mediastinal invasion [4]. Metastasis has been reported.

Mediastinal IMTs are rare. A tumor similar to that described here and supplied by an artery from the aorta was described in the right chest of a 12-year-old girl [2]. As with sequestration, the blood supply to these lesions is derived from an aberrant systemic artery.

Classification and genetics: Soft tissue tumors (tumors of the body's connective tissue) have been classified acording to histologic appearance and clinical behavior, and treatment has been developed accordingly. Recently, molecular genetic methods have shown that entities with a homogeneous morphologic pattern may differ in behavior or pathogenesis. Inflammatory pseudotumor is an example. Some tumors have been shown to contain organisms. In some of these tumors the proliferating cells have been shown to be histiocytes rather than myofibroblasts. These tumors may be designated histiocytic inflammatory pseudotumors [5].

Another subset of these tumors that is composed of myofibroblasts and called IMT shows a clonal genetic abnormality consisting of one of several different translocations involving the short arm of chromosome 2 and another chromosome. Each of these translocations causes activation of the anaplastic lymphoma kinase (ALK) gene located at 2p23 [6]. This activation, which is believed to be oncogenic and which can be identified immunohistochemically, has been identified in about 35% of lung tumors and 50% of extrapulmonary IMTs. Tumors with these clonal translocations are considered to be neoplasms. Other chromosomal abnormalities have been detected in another subset of these tumors [6,7]. Still some IMTs have no known abnormalities [6].

Identical translocations involving the ALK gene were previously found in a subset of anaplastic large cell lymphomas, and their presence is associated with a more favorable outcome than lymphomas of similar appearance without ALK expression. Further, ALK expression has been found in several other soft tissue tumors usually not in the differential diagnosis of IMT [8]. The significance of ALK expression in all of these tumors is still under investigation.

Gross appearance: Lung tumors are circumscribed but not encapsulated and vary from 1 to 15 cm in diameter [3]. They are firm and sometimes gritty on sectioning due to calcification [9]. They obliterate bronchovascular structures. They may have a yellowish cast from the lipid-filled histiocytes. The tumors are locally invasive, sometimes multicentric, and recur unpredictably, especially if not completely excised [3]. As described in the above case, tumors involving the lung may present as a large mediastinal mass [2,9]. Rarely, metastasis has been reported [7], but distinguishing metastasis from multicentricity can be a problem.

Histology: IMTs are tumors composed of spindled fibroblasts and myofibroblasts, lymphocytes and plasma cells, foamy histiocytes, and collagen, all in varying amounts. The spindled cells stain with a marker of smooth muscle cells--smooth muscle actin--and are negative for epithelial markers [3,7]. Staining for the presence of ALK, while not diagnostic, can help to confirm the diagnosis of an otherwise typical IMT. The plasma cells are polyclonal and reactive.

Treatment and behavior: A few tumors have responded to radiation or corticosteroids when excision was not possible [10]. Patients with these usually static or slowly-growing tumors have an excellent prognosis if the tumor is completely removed [3].

Increased cellular crowding, atypia, and mitotic rate (>3/50 high power fields), and invasion of adjacent structures including the mediastinum, vertebrae, and chest wall may signify transition to inflammatory fibrosarcoma, a potentially more aggressive tumor [7].

Because the spindled cells and chronic inflammation resemble granulation tissue, diagnosis based on needle or forceps biopsies or on frozen section may be misleading, as in the above case [2].

Summary of radiographic features of IMT in the chest

Summary of pathologic features of IMT

Diagnosis: Inflammatory myofibroblastic tumor (IMT) in left mediastinum and left lung.

References: To return to reference section after viewing abstract, click here before clicking on "abstract".

1. Altman H, Pietra G, LiVolsi V, Kelley M, Unger M, Hayden R. Tracheobronchial inflammatory myofibroblastoma. A locally invasive, potentially recurrent neoplasm. Int J Surg Pathol 1994; 2:93-98.

2. Souid A, Ziemba M, Dubansky A, Mazur M, Oliphant M, Thomas F, Ratner M, Sadowitz P. Inflammatory myofibroblastic tumor in children. Cancer 1993: 72:2042-2048. Abstract

3. Pettinato G, Manivel J, De Rosa N, Dehner L. Inflammatory myofibroblastic tumor (plasma cell granuloma). Clinicopathologic study of 20 cases with immunohistochemical and ultrastructural observations. Am J Clin Pathol 1990; 94:538-546. Abstract

4. Agrons G, Rosado-de-Christenson M, Kirejczyk W, Conran R, Stocker J. Pulmonary inflammatory pseudotumor: radiologic features. Radiology. 1998; 206:511-518. Abstract

5. Dehner L. The enigmatic inflammatory pseudotumours: the current state of our understanding, or misunderstanding. J Pathol 2000; 192:277-279. Abstract

6. Coffin C, Patel A, Perkins S, Elenitoba-Johnson K, Perlman E, Griffin C. ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor. Mod Pathol 2001; 14:569-576. Abstract

7. Yousem S, Shaw H, Cieply K. Involvement of 2p23 in pulmonary inflammatory pseudotumors. Hum Pathol 2001; 32:428-433. Abstract

8. Cessna M, Zhou H, Sanger W, Perkins S, Tripp S, Pickering D, Daines C, Coffin C. Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases. Mod Pathol 2002; 15:931-938. Abstract

9. Kim I, Kim W, Yeon K, Chi J. Inflammatory pseudotumor of the lung manifesting as a posterior mediastinal mass. Pediatr Radiol 1992; 22:467-468. Abstract

10. Bando T, Fujimura M, Noda Y, Hirose J, Ohta G, Matsuda T. Pulmonary plasma cell granuloma improves with corticosteroid therapy. Chest 1994; 105:1574-1575. Abstract

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Histologic differential diagnosis