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doi:10.1510/icvts.2007.173476

Interactive CardioVascular and Thoracic Surgery 7 (2008) 629–633

� 2008 Published by European Association for Cardio-Thoracic Surgery

Institutional report - Thoracic general

Clinical spectrum of pulmonary inflammatory myofibroblastic tumorShin-ichi Takeda *, Yasuyo Onishi , Tomohiro Kawamura , Hajime Maedaa, b a a

Department of General Thoracic Surgery, Toneyama National Hospital, Toneyama 5-1-1, Toyonaka City, Osaka 560-8552, Japana

Department of Surgery Ootemae Hospital, Ootemae, Chuou-ku, Osaka 540-0008, Japanb

Received 17 December 2007; accepted 6 April 2008

Abstract

We retrospectively describe clinicopathological characteristics of five patients with surgically resected pulmonary inflammatory myofi-broblastic tumor (IMT), and discuss in the light of present-day concepts regarding this disease entity. During the past 15 years, five patientswith an age ranging from 21 to 74 years underwent surgery for IMT of the lung, and the resected lesions were studied histologically andimmunohistochemically. Three asymptomatic patients referred as X-ray suspicious lung cancer, one patient complained of recurrenthemoptysis, and one presented with fever and dyspnea. The three patients were treated by lobectomy (ns3) including chest wall resection,one segmentectomy and one wedge resection, two of whom were diagnosed as pulmonary sarcoma by frozen section at surgery. The tumorsize ranged from 1.5 to 5.5 cm in diameter and histologically characterized by myofibroblasts that are mixed with chronic inflammatorycells, including plasma cells, lymphocytes, and histiocytes. There was no recurrence in these patients, and all of them are in good health.Complete surgical resection can be chosen for both diagnostic and therapeutic for IMTs, which remains the best treatment.� 2008 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

Keywords: Inflammatory myofibroblastic tumor (IMT); Inflammatory pseudotumor; Rare pulmonary neoplasm

1. Introduction

Inflammatory myofibroblastic tumors (IMTs) are challeng-ing lesions with respect to classification, differential diag-nosis, and biologic potential w1, 2x. They present histol-ogically, presenting spindle cell proliferation with a distinc-tive fibroinflammatory and even pseudosarcomatousappearance w2x. IMT has been described by various termsbecause of its variable cellular components, which includeplasma cell granulomas w1, 3x, inflammatory pseudotumorw1, 4x, xantogranuloma w5x, and fibrous histiocytoma w6x.

The term ‘pseudotumor’ came about because of its pro-pensity to mimic clinically and radiologically a malignantprocess. However, the pathogenesis whether IMT is aninflammatory reactive lesion or neoplasm is still controver-sial. Recent detailed studies w2, 6x suggested that IMT is aneoplasm with benign or low-grade malignancy. The exactincidence of this disease is unclear. Furthermore, littleinformation has been reported regarding the natural his-tory, clinical presentation, and effective treatment. Diag-nostic dilemma exists in the fact that even the frozensection did not reach the differential diagnosis. The pur-pose of this retrospective analysis is to describe five addi-tional cases of pulmonary IMT and to review thosepreviously reported in the light of concept regarding thedisease entity and clinical significance.

*Corresponding author. Department of General Thoracic Surgery, OsakaGeneral Medical Center, 3-1-56 Bandaihigashi, Sumiyoshi-Ku, Osaka 558-8558, Japan. Tel.: q81-6-6692-1201; fax: q81-6-6606-7032.

2. Materials and methods

We retrospectively reviewed the charts of five patients(0.15%) who were diagnosed as inflammatory myofibroblas-tic tumors (IMTs) among 3486 general thoracic proceduresthat were performed at our institution between 1992 and2006. Clinical characteristics as well as clinicopathologicalfeatures, and including case presentation weredocumented.

Clinical characteristics of the five cases are presented inTable 1. Preoperative work-up included laboratory exami-nations, bronchofiberscopy, transthoracic fine needle aspi-ration cytology (FNAC), chest X-ray, and computedtomographic (CT) scans. For pathological examination ineach case, the tissue was fixed in 10% buffered formalin,and embedded in paraffin. The sections were cut thenstained with routine hematoxylin and eosin as well asimmunohistochemistry. Follow-up was complete for allpatients ranging from 18 months to 7 years.

3. Results

The following five case reports illustrate some importantfeatures of IMTs in terms of surgical management andoutcome.

3.1. Patient 1

A 74-year-old female presented with an abnormal shadow1.5 cm in size in the left lung field when she underwentan annual check-up following an implantation of a cardiac

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Table 1Chemical profiles and outcome of five patients with inflammatory myofibroblastic tumors

Case Ageysex Symptom Locationysize Preoperativesyfrozen Surgery Subtype ALK Outcome

1 74yF None LULy1.5 cm –yOP Wedge resection OP type – 7 years alive2 50yF Hemoptysis RLLy3.5 cm –ysarcoma Sleeve lobectomy LP type qqq 54 months alive3 31yF None LLLy1.6 cm –ysarcoma Segmentectomy FH type q 49 months alive4 55yF None RMLy5.5 cm OP/OP Lobectomy CW OP type – 41 months alive5 58yM Fever cough LULy4.8 cm –yFH Lobectomy FH type qqq 24 months alive

OP, organizing pneumonia; LP, lymphoplasmacytic; FH, fibrous histiocytic; ALK, anaplastic lymphoma kinase activity; LUL, left upper lobe; RLL, right lowerlobe; LLL, left lower lobe; RML, right middle lobe; CW, chest wall resection.

pacemaker. Since the bronchofiberscopy did not reach adiagnosis, exploratory video-assisted thoracic surgery(VATS) wedge resection was employed. The frozen sectionrevealed being compatible with organizing pneumonia.Final histologic diagnosis was IMT, and the patient wasfollowed-up for seven years without relapse. This case wassimilar to the organized pneumonia type according to theclassification by Matsubara et al. w7x.

3.2. Patient 2

A 50-year-old female was transferred to our hospital withrecurrent hemoptysis of 50–100 ml, occurring two or threetimes per week. Chest CT showed the endobronchial tumor(Fig. 1a), and bronchofiberscopy revealed a protrudingmass in the right lower lobe with a total obstruction of theB7, however, repeated biopsies did not reach a definitehistological diagnosis. Then, a right lower lobectomy withbronchoplasty was employed, and the frozen sectionrevealed a possible highly malignant sarcoma during thesurgery. There was no lymph node metastasis, and the finaldiagnosis of IMT with lymphohistiocytic type was obtainedfrom the resected specimen. Immunohistochemistryrevealed a strong staining for anaplastic lymphoma kinase(ALK) (Fig. 1b,c). The patient is doing well 54 months aftersurgery.

3.3. Patient 3

A 31-year-old female was admitted to our hospital withsuspicious diagnosis of lung cancer, radiologically presentingwith an irregular margin mass with pleural indentation inchest CT. Then a VATS exploration and diagnostic left S6segmentectomy was employed, and a frozen sectionrevealed a suspected sarcoma. However, there was nolymph node metastasis by intraoperative sampling of thelymph nodes. Further extensive resection was not per-formed because of the previous experience in patient 2, ofwhich clinical and histological features mimicked. The finaldiagnosis was IMT with a histologically fibrous histiocyticpattern. Immunohistochemistry revealed a weak stainingfor ALK. This case was similar to the lymphocyte predomi-nant type w7x. The patient is doing well 45 months aftersurgery.

3.4. Patient 4

A 55-year-old female was admitted to our hospital forclose examination for a lung tumor 2 cm in size in the rightmiddle lobe (Fig. 2a). Transbronchial lung biopsy (TBLB)

revealed organized pneumonia without malignancy. Thenthe patient was followed up in the outpatient clinic. Justtwo months later in the outpatient clinic, repeated chestX-ray revealed a large tumor 5 cm in size, invading intothe chest wall (Fig. 2b). The surgery was achieved by rightmiddle lobectomy and combined chest wall resection (4thand 5th ribs). The final histological diagnosis was IMT thatwas similar to the organized pneumonia type w7x.

Immunohistochemistry revealed a negative staining forALK. The patient is doing well 41 months after the surgery.

3.5. Patient 5

A 58-year-old female was transferred to our hospital withcoughing and fever. Chest X-ray revealed a irregular mass5 cm in size. Bronchofiberscopy did not reach a histologicaldiagnosis, however, positron emission tomography (PET)confirmed an abnormal metabolic activity with a highstandardized uptake value (SUV) of 8.4 in the lesion,suggestive of malignancy (Fig. 3). Therefore, a left upperlobectomy was employed, and frozen section revealed asuspicious diagnosis of IMT. Immunohistochemistry revealeda strong staining for ALK. The patient is doing well24 months after surgery. This case was similar to thehistiocytoma type (44%), and fibrohistiocytic type w7x.

Three patients were asymptomatic and referred becauseof radiologically suspicious lung cancer, and one patientcomplained of a cough and the other patient presentedwith recurrent hemoptysis, and dyspnea. The three patientswere treated by lobectomy, one segmentectomy, and onewedge resection (Table 1). Intraoperatively two patientswere diagnosed as pulmonary sarcoma by frozen section,and one organizing pneumonia. The resected tumor sizeranged from 1.5 to 5.5 cm in diameter. Histologically, avariety of inflammatory and spindle cells were observed.Three of five patients (60%) showed ALK, abnormalitieswere found in five patients, which further supported adiagnosis of IMT. Despite a short follow-up period, therewas no recurrence in these patients, and all of them are ingood health without recurrence at the time on writing.

4. Discussions

Inflammatory myofibroblastic tumors (IMTs) or inflamma-tory pseudotumor, the name implies its propensity to mimicclinically and radiologically a malignant process. Initially,IMTs arise through a non-neoplastic process due to anunregulated growth of inflammatory cells, and this down-regulation remains unknown w1, 4x. The incidence reportedin the literature ranged from 0.04 w4x to 1.2% w8, 9x of all

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Fig. 1. Chest CT image showing the protruding endobronchial tumor in theright lower lobe (a). The histological diagnosis of the frozen section wasinconclusive, and the diagnosis of IMT with lymphohistiocytic type wasobtained by the resected specimen (b). Immunohistochemistry revealed astrong staining for anaplastic lymphoma kinase (ALK) that was characteristicof this disease (c).

Fig. 2. At first chest X-ray revealed a lung tumor 2 cm in size in the rightmiddle lobe (a). Transbronchial lung biopsy (TBLB) revealed organized pneu-monia without any malignancy. However, the tumor increased in size up to5 cm, invading to the chest wall within four months (b).

lung tumors. In addition to the rarity in pulmonary tumors,the important issue exists in that they can demonstratecharacteristics that mimic malignant lesions, such as inva-

sion of pleural mediastinal and chest wall structures seenin patients 4 and 5.

Histopathologically, the lesions may range from a primarilymyofibroblastic or fibroxahanthomous appearance to onethat has a heavy infiltrate of plasma cells, which may bethe reasons why they were named later as plasma cellgranulomas w3x, inflammatory pseudotumor w1, 4x, xanto-granuloma w5x, and fibrous histiocytoma w6x. Namely, theyinclude a spectrum of myofibroblastic proliferation withvarying infiltrate of inflammatory cells as a histologicfeature.

IMTs occur at any age, however, they are a relativelycommon lung mass in pediatric patients compared toadults. There was no sex predilection w2, 4, 5x, half of the

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Fig. 3. Chest CT image showing an irregular mass 5 cm in size, and positronemission tomographyyCT (PETyCT) confirm an abnormal metabolic activitywith a high standardized uptake value (SUV) of 8.4 in the lesion (a). A cutsurface of the resected specimen (b).

patients have been reported asymptomatic, and the tumoris seen as an incidental finding in the chest X-ray that wasseen in patient 1, 3, 4. Symptom related to bronchialobstruction and hemoptysis that was seen in patient 2, andpatient 5 presented with respiratory symptom of cough andfever. In particular, rapid growing in size was observed inCase 4. Others were non-specific constitutional symptoms,and no consistent identifiable risk factors. On the chest X-ray, usually solitary, well demarcated mass, sometimesirregular in the periphery w10, 11x, and positive uptake inthe FDG-PET w12x similar to the malignancies. In one reportfrom Korea w11x, IMTs were more commonly derived fromtracheobronchial airways, than those in the peripheralorigin.

Matsubara et al. w7x classified this entity into threesubtypes by analyzing 32 cases of clinicopathologic findingsof inflammatory pseudotumor of the lung, i.e. organizingpneumonia type (44%), fibrous histiocytoma type (44%),and lymphoplasmacytic type (12%). Organizing pneumoniatype has intraalveolar lymphohistiocytic inflammationwhich converts to intraalveolar fibrosis peripherally andinterstitial fibrosis centrally because of a proliferation offibroblasts. Fibrous histiocytoma type has a predominantproliferation of spindle cells and histiocytes in storiformpattern, with loss of alveolar architecture. Lymphoplasma-cytic type has a predominance of lymphocytes and plasmacells with little fibrosis w7x. There is considerable histologic

overlap among the three types. This concept derived fromthe idea that IMT was inflammatory origin. On the otherhand, Colby and associates w13x removed the type oforganizing pneumonia from this entity, and classified intofibrohistiocytic subtype and plasma cell granuloma subtype.The former consists of spindle cells (myofibroblasts andfibroblasts), collagen, macrophage, foamy macrophages,and Touton giant cells. The latter consists of spindle myofi-broblasts and inflammatory cells with abundant plasmacells. Immunohistochemical studies demonstrate vimentin,muscle specific actin, and focally desmin within the cyto-plasm of the spindle cells indicating myofibroblastic differ-entiation w13x.

Based on the findings of the published reports w1–4, 10x,IMT is a benign, non-metastasizing proliferation of myofi-broblasts with a potential for recurrence and persistentlocal growth, similar in some respects to the fibromatosesat the present stage. In the clinical setting that IMTdecreased in size with corticosteroid therapy w14x, and IMTassociated with IgG4 – positive lung tumor suggest IMT isinflammatory or immunoopathologic disease process, name-ly non-neoplastic, was postulated.

On the other hand, demonstration of ALK and p80 as wellas the evidence of crucial gene or chromosomal rearrange-ment of 2p23 that occur in IMT w15x is strongly suggestiveof neoplasm nature. Moreover, as to the clinical behavior,local recurrence or distant metastasis have been reportedw1, 4x, thus a complete surgical resection is mandatory. Wediagnosed them as malignant pulmonary sarcoma in twopatients by frozen section during surgery, may due to theclosely similar histological features compared to sarcoma,except that the IMTs lacked mitoses and invasiveness w7,13x.

As already stated, IMT are difficult to diagnose pre- orintraoperatively w1, 2, 4x, fine needle aspiration cytology(FNAC) sometimes shows a mixtures of inflammatory cells,and fibroblastic proliferation with mitoses may mimic mes-enchymal neoplasms. The differential diagnosis rangedfrom fibrohistiocytic neoplasms, lymphoma, primary lungcancer or sarcoma, and fibrosis. As we experienced inpatient 4, the indeterminate nodule was once diagnosed asorganized pneumonia of benign nature, however, the lesionrapidly increased in size associated with invasion to thechest wall, which showed a characteristic biological behav-ior of IMT. Thus, we recommended complete resection fordiagnosis and treatment for this disease and prevention ofrecurrence, since the patient management otherwise doesnot change w2, 4, 9x.

According to the literature reviews, the prognosis ofpatient wit IMT who undergo a complete resection wasexcellent, however, local and distance recurrence as wellas tumor deaths were reported. A collective review showeda 5 year and 10-year survivals of 91 and 77% w8x, whichalternatively suggestive of prognostic nature of low-grade-malignancy.

In conclusions, a IMT is a rare benign lesion that ischaracterized by myofibroblasts proliferation mixed withchronic inflammatory cells, which should be distinguishedfrom malignant tumors by surgical resection.

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