An IMT of the lung is rare, with an incidence of 0.04% [4] to 0.3% [1]. Gender, race, and geographical location appear to play no role in its occurrence [1]. Cerfolio et al. reported that the median age of their case was 47 years (range, 5 to 77 years) [1]. They also reported that the invasive cases were more significantly symptomatic and required more extensive surgery than noninvasive cases. In our case, the patient had no complaint, but the tumor possessed aggressive features. Symptoms may depend on their location, and thus careful analysis on the extensive area of the IMT should be done.
It is unclear whether the etiology of an IMT is the result of non-specific inflammatory reaction or neoplastic change. There were some cases where expression of the ALK gene elevated [5] and others where there was rearrangement of the ALK gene on chromosome 2p23 [6]. In addition, the ALK gene expression was reported to be associated with local recurrence [5]. These reports suggest that an IMT is a neoplastic tumor rather than a result of an inflammatory reaction. On the other hand, IgG4-related sclerosing disease (IgG4SD) has been reported as a steroid-responsive multi-organ disorder with chronic inflammation, and it demonstrates many clinical features, including autoimmune pancreatitis, sclerosing cholangitis, and inflammatory pseudotumor of the lung [7, 8]. The diagnostic criteria of this disease are IgG4/IgG > 0.1 in tissue samples and serum IgG4 concentration > 135 mg/dl [2]. Between IgG4SD and IMT, there are some overlaps including abundance of plasma cells. Recently, IMT demonstrating both ALK high gene expression and highly positive IgG4 cases were reported [2]. This suggests that there may be more etiology and clinical features of IMT.
The 5-year survival rate of IMT was reported 74–91% [1, 4]. Complete resection was recommended [4, 9], and the recurrent cases were related to incomplete resection [1]. Other treatments besides surgery include radiation [1, 10] and chemotherapy [3, 11,12,13]. Dishop et al. reported a case treated with vincristine and etoposide as the first line and cisplatin, adriamycin, and methotrexate as the second line after incomplete resection [11]. In addition, complete remission was reported using vincristine, ifosfamide, doxorubicin, and celecoxib [12]. However, Trojan reported aggressive IMT case which infiltrated the central nerve system with mediastinal metastases despite chemotherapy including vincristine [13], suggesting the neoplastic feature of IMT. Steroid and non-steroidal anti-inflammatory drugs [3, 11, 12] have also been reported as effective for IMT. Especially, steroids have been reported as effective for IMT containing IgG4SD features [7]. However, steroid was effective even for the case without IgG4SD features [2]. On the other hand, Cerfolio et al. [1] reported two cases where the remaining tumor showed no growth after incomplete resection during 4 to 9 years follow-up and the cases did not receive any additional treatment, although the biological features of those cases were not explained in their article. These findings would make the choice of treatment strategy for IMT complicated. However, since some cases of IMT have shown no malignant feature, observation could be carefully selected based on clinical and molecular biological features of each case. In the present case, because of the possibility of malignancy as well as a risk of massive bleeding or tumor embolism based on the location of the tumor, we performed the surgical resection.
Recently, clinical trial of crizotinib for ALK-positive IMT was reported [3]. In that report, crizotinib administration combined with surgical resection resulted in complete remission in the IMT with ALK rearrangement. However, they also reported that crizotinib was not effective for an ALK-negative case, suggesting that crizotinib might be effective only for ALK-positive IMT cases. In light of the report above, a treatment strategy with or without surgery should be considered carefully based on each feature, especially for invasive cases.
