Discussion
IMT is a benign and uncommon mesenchymal tumor.1,2 IMT occurs most commonly in the lungs, gastrointestinal tract, and liver, but rarely arises in the larynx.1-3 Laryngeal IMT has been reported most commonly in the vocal folds although a few cases in the aryepiglottic folds have been reported.4 Lesions are usually 0.4 - 3.5cm in size.3,4 IMT primarily affects children and younger adults (mean age of 43).1-4
IMT originates from an inflammatory response and is related to smoking, immune responses, and trauma.1-4 IMT has also been linked to infectious agents including Epstein-Barr virus, Human Immunodeficiency Virus, human herpesvirus-8 as well as bacteria such asEscherichia coli, and Nocardia .1,4
Clinical presentation with IMT is often non-specific. Constitutional symptoms including weight loss, fever, and fatigue occur in 15-30% of patients. IMTs are usually painless, but may present with swelling, induration, or obstructive symptoms and/or voice changes.1-3 Laboratory values can show microcytic anemia, elevated erythrocyte sedimentation rate (ESR), thrombocytosis, and polyclonal hypergammaglobulinemia.2,3 These laboratory findings have not been demonstrated in laryngeal IMT, and were not found in this current case although an ESR was not measured.2,3
IMT has a variable radiographic appearance that can be nonspecific, suggestive of an infiltrative/malignant lesion, or granulomatous disease.1 It ranges from an ill-defined infiltrating lesion to a well-circumscribed mass with inflammatory and fibrotic regions.2 Fibrotic sections display delayed and persistent contrast enhancement, but attenuation on CT is variable as is echogenicity on ultrasound.2 Laryngeal IMT has been reported on CT showing uneven enhancement or as a subglottic mass not invading the laryngeal skeleton.3 Laryngeal IMT has not been well described on Magnetic Resonance Imaging (MRI), but any fibrosis will produce a low signal intensity region.2Additionally, in one case, fat saturated T1 gradient-echo images showed a mild spontaneously hyperintense vocal fold, and on fat-saturation T2-weighted images showed relative hyperintensity.3Strong contrast enhancement was also present.3
Histologically, IMT demonstrates myofibroblastic proliferating spindle cells with infiltrating plasma cells, lymphocytes, and eosinophils.3 Other patterns include compact fascicular spindle-cells with myxoid and collagenized regions with an inflammatory cell background, and a denser collagen pattern with plate-like collagen and less cellularity.4Immunochemistry staining of IMT shows reactivity to vimentin, SMA, muscle-specific actin, and desmin while being negative for myoglobin and S100.1,3 Additionally, ALK-1 gene translocations are present in about half of IMTs resulting in overexpression of ALK. Fusion partners have been identified including tropomyosin, clathrin heavy chain, and RAN-binding protein 2.1,2 ALK-1 positivity is relatively specific for IMT, and is frequent in laryngeal IMT, although bears no morphologic correlation.1,4 IMTs without ALK-1 translocations still show the presence of other fusion proteins involving platelet-derived growth factor, ROS1, tropomyosin 3 and 4, cysteinyl tRNA synthetase, and/or Ran binding protein.1,2
Squamous cell carcinoma, papilloma, and leiomyosarcoma were considered in the differential, but the histopathology findings supported IMT.
The leading treatment for laryngeal IMT is surgical excision, which offers a low recurrence rate and good prognosis.2-4Chemotherapy, or radiotherapy are considered when morbidity of surgery or patient co-morbid conditions preclude surgery.2,3
The ALK inhibitor Crizotinib is a novel treatment for ALK+ IMT. Crizotinib therapy has shown complete or partial remission in cases where only partial tumor resection was possible.5 In four cases Crizotinib therapy resulted in remission without surgical intervention.5 However these data are limited by publication bias, complex treatment regimens, and variable follow-up time – thus further study is needed.5