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