Inflammatory Myofibroblastic Tumor Mimicking a Cavitary Lesion in the Lung: A Case Report and a Comprehensive Literature Review

Inflammatory myofibroblastic tumors (IMTs) are a group of soft tissue neoplasms with a predilection for the lungs and abdominopelvic cavity, characterized by a mixture of fasciitis-like, compact spindle cells, hypocellular fibrous histologic patterns, and distinctive molecular features. Due to their unspecified symptoms and non-specific radiologic presentation, the histopathologic and immunohistochemical analysis of a biopsy specimen is crucial for the diagnosis. We present a case of a 30-year-old man with intermittent hemoptysis diagnosed with a pulmonary IMT. We aim to review the literature regarding its definition, clinical findings, diagnosis, treatment, and prognosis. The treatment for an IMT is based on its location and extent, including complete surgical resection, which has a good prognosis compared to corticosteroids, chemotherapy, radiotherapy, and non-steroidal immunomodulation in patients who are not good surgical candidates. Further investigative studies with larger sample sizes and longer meticulous follow-ups are needed to demonstrate this neoplastic disease's natural history and find appropriate management for it.


Introduction
Inflammatory myofibroblastic tumors (IMTs) were first described by Brunn in 1937. They represent an extremely rare type of inflammatory pseudotumor that appears most commonly in children and young individuals, with a global prevalence ranging from 0.04% to 0.7%, irrespective of gender or race [1]. IMTs are a group of soft tissue neoplasms formed by spindle-shaped myofibroblasts and inflammatory cells (eosinophils, plasma cells, and lymphocytes) with a predilection for the lungs and abdominopelvic region [2]. Although they account for about 50% of benign pulmonary masses in children, they represent less than 1% of adult lung tumors [2,3]. Unspecified symptoms, such as cough, chest pain, dyspnea, hemoptysis, and non-specific inflammatory symptoms like fever, malaise, and weight loss, are the presenting features most commonly seen in IMTs of the lungs [2]. The radiographic presentation of pulmonary IMTs is also nonspecific. They can be solitary or multiple well-circumscribed peripheral lung masses. Because of their similar radiological appearance to other malignant lung masses and aggressive behavior with the invasion of adjacent structures, histopathologic and immunohistochemical analysis of a biopsy specimen is the mainstay for diagnosis [2,4].
Here, we discuss the case of a 30-year-old male who reported hemoptysis and was diagnosed with a pulmonary IMT. The aim of this report is to present a case of an inflammatory myofibroblastic tumor diagnosed by immunochemistry and review the literature on its definition, clinical findings, diagnosis, treatment, and prognosis.

Case Presentation
A 30-year-old man with a history of nephrolithiasis presented to the emergency room with complaints of flank pain and an episode of small-volume hemoptysis (two to three teaspoonfuls of blood a day) before presentation. He denied fever, chills, chest pain, night sweats, or weight loss. The patient reported intermittently experiencing episodes of non-massive hemoptysis for the last six years. There was no known history of tuberculosis or valley fever exposure, and he did not have a history of recent travel. On admission, computed tomography angiography (CTA) of the chest revealed a lesion initially interpreted by radiologists as a cavity. However, it was concluded that the lesion was a solid nodule containing rounded soft tissue mass, with a dilated airway mimicking a cavitary change. It was seen to be arising adjacent to the right posterior basal segmental bronchus along with adjacent ground-glass airspace opacities, likely reflecting pulmonary hemorrhage ( Figure 1). This lesion appeared to have progressed since a prior CT scan was done five months earlier. Differential diagnoses of the lesions included fungal infection, bacterial superinfection of a preexisting right lung cystic lesion, or a neoplasm such as bronchial carcinoid. Bronchoscopy and bronchoalveolar lavage (BAL) of the posterior basal segment of the right lower lobe (RLL) were notable for some fresh blood emanating from the posterior basal segment of the RLL but no endobronchial lesion. A biopsy was not done. BAL cultures were negative for bacteria, fungus, or acid-fast bacilli (AFB).
The patient was subsequently discharged home with plans to follow up on an outpatient basis. An Ion protocol CT chest scan was done three weeks later, which showed a right infrahilar mass measuring 2.4 x 1.7 x 2.4 cm in size, showing an increase in size. Three weeks later, a robot-assisted navigational bronchoscopy with radial endobronchial ultrasound (r-EBUS) and fluoroscopy-assisted transbronchial needle aspiration and brushing of the RLL lung nodule were performed ( Figure 2).  including eosinophils and lymphocytes ( Figure 4).

FIGURE 4: On the cell block, the lesion was composed of spindle cells with inflammatory cells in the background including eosinophils and lymphocytes
On immunohistochemical staining, the spindle cells showed cytoplasmic staining with smooth muscle actin (SMA) and anaplastic lymphoma kinase (ALK) (Figures 5, 6). The spindle cells did not express S-100, SOX-10, cytokeratin AE1/3, CAM 5.2, CD56, synaptophysin, chromogranin, TTF-1, desmin, and HHV-8. The morphology and immunoprofile together support the diagnosis of an inflammatory myofibroblastic tumor. The patient was referred to an oncologist as well as a thoracic surgeon for further management, and was lost to follow-up.

Discussion
An inflammatory myofibroblastic tumor is a unique tumor with predominantly benign potential, with a few reports of distant metastasis [5]. It varies significantly in clinical and histological findings, progression, and prognosis. The diagnosis is primarily histological. However, it is challenging to diagnose the disease in such a manner because the histological characteristics of the tumor are similar to other neoplasms, such as lowgrade sarcoma and lymphoma, all of which are characterized by infiltration of varying polymorphic cells [6].
IMTs are also difficult to diagnose by imaging, as was demonstrated in this case. The rarity of this tumor, along with its non-preference for a specific bodily location, makes the process of diagnosis arduous. However, IMTs grow and can start invading adjacent organs. Hence, the need for an accurate and speedy diagnosis is of the greatest importance. The rate of growth, as well as the nature of the tumor, can be determined by its associated biological markers [7]. It was found that tumors with absent ALK expression are of a more aggressive nature, with higher mortality rates due to distant metastases. The absence of p53 nuclear expression was also noted in 75% of the IMTs of metastatic nature in the same study [8].
When involving the lungs, the tumor presents with non-specific respiratory and systemic symptoms, and therefore chest imaging is crucial in identifying lung lesions early. Patients with a similar presentation require a biopsy of the lung lesions either via CT-guided biopsy or bronchoscopy with endobronchial ultrasound and fine needle aspiration for a histological diagnosis. As discussed above, histological examination alone is inconclusive. To differentiate it from various benign and malignant tumors conclusively, immunohistochemistry for ALK expression, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) are assistive [8].
The treatment for IMT depends mainly on the site and extent of the tumor. Complete surgical resection is associated with a better long-term prognosis. However, lobectomy and pneumonectomy are preferred over wedge resection or endobronchial resection, as these decrease the risk of local recurrence and metastasis more effectively [8]. A good prognosis was seen in patients undergoing complete resection of the pulmonary inflammatory myofibroblastic tumor (PIMT), with 5-and 10-year survival rates of 91% and 77%, respectively [9]. The recurrence rate of PIMTs can be up to 60%, but complete resection reduces it to less than 2% [9,10]. Although the recurrence rate after surgical management remains low, a long-term follow-up is advised as cases of recurrence have been reported even after 11 years [1,9,11]. Corticosteroids can be used when the mass has invaded adjacent structures or has multifocal involvement, making it unresectable. If ALK-1 is positive, like in our patient, crizotinib, a competitive inhibitor of ALK tyrosine kinase, has been found to be effective in some cases [12].
Chemotherapy, radiotherapy, and non-steroidal immunomodulation have been attempted in patients who were not good candidates for surgery. However, these treatment methods were found to be ineffective against this aggressive tumor [13].

Conclusions
Inflammatory myofibroblastic tumors are an uncommon subgroup of benign soft tissue neoplasms for which an exhaustive clinical exam, as well as investigative procedures, must be conducted first. In short, inflammatory myofibroblastic tumors may be considered per exclusion. Competitive inhibitors of ALK tyrosine kinase, such as crizotinib, may be used with a variable response if ALK-1 markers are positive. Because of the rarity and non-specific presentation of the pulmonary inflammatory myofibroblastic tumor, as seen in our case, we strongly suggest including the disease as a differential diagnosis when patients present with unclassifiable respiratory signs and symptoms. Histopathological evaluation is necessary for diagnosis and should be done early, given the aggressive nature of the tumor. For higher diagnostic rates and favorable outcomes, further investigative studies with larger sample sizes and longer follow-ups are needed to establish the natural history of this neoplastic disease and discover appropriate medical management.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.