DISCUSION:
Head and neck cancer comprises malignant lesions affecting the oral
cavity, pharynx, larynx, salivary glands, as well as the nasal cavity
and paranasal sinuses. Worldwide, it ranks seventh among malignant
neoplasms. In the USA, there are more than 54,000 new cases per year
with an incidence of around 15/100,000 inhabitants and 12,000 deaths
attributable to this disease (14). According to data from the Spanish
Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC),
about 10,000 new cases are detected each year in Spain (15), mainly in
men between 45 and 65 years of age. The most common histology is
epidermoid carcinoma, which is related to alcohol and tobacco
consumption. Laryngeal tumours with histology other than squamous cell
carcinoma are rare with an incidence of <1%. Most of these
are mesenchymal tumours (10). Inflammatory myofibroblastic tumour (IMT)
is an extremely rare subtype in the larynx but more frequent in other
areas of the head and neck. Clinically it mimics other more common
laryngeal neoplasms, requiring a differential diagnosis.
Clinically they behave as asymptomatic masses or may cause symptoms of a
space-occupying lesion, causing dysphonia, dyspnoea, dysphagia or
pharyngeal-laryngeal foreign body sensation. Locally, the inflammatory
and expansive behaviour of the lesion can cause great clinical
variability, mimicking other neoplastic processes. Primary involvement
at the laryngeal level with systemic symptoms including constitutional
syndrome, fever, anaemia or thrombocytopenia has been described
(16)(17), which reflects the variability and morbidity associated with
this pathology. The definitive diagnosis is eminently
anatomopathological.
Histologically is composed of lymphocytes, plasma cells, histiocytes,
fibroblasts and myofibroblasts in variable proportion, forming four
basic histological patterns: predominant lymphoplasmocytic infiltrate,
predominant lymphohistiocytic infiltrate, myofibroblastic infiltrate and
lymphocytic infiltrate with collagen deposition (3).
Immunohistochemistry is characteristic of a soft tissue tumour with ALK
cytoplasmic positivity in most cases, without being a specific finding
for this type of tumour. Variable cytoplasmic positivity for vimentin,
smooth muscle actin, muscle specific actin and desmin, and negativity
for myoglobin, myogenin and S100 protein is characteristic (2,18).
Characteristic is the finding of genetic rearrangements on chromosome
2p23 with activation of the ALK receptor tyrosine kinase gene leading to
overexpression and activation of the ALK protein, without being a
specific finding, which occurs in approximately 50% of cases and
appears to have an age-dependent distribution, with this finding being
more common in adults under 40 years of age. This overexpression also
appears to have a morphological distribution within the tumour itself,
with activation occurring in the myofibroblastic component without
expression of this genetic alteration in the inflammatory cells of the
tumour itself. In any case, if there is no genetic alteration in ALK,
genetic rearrangements have been observed in the HMGIC gene (also known
as HMGA2) on chromosome 12, t(2, 17), (p23, q23), tropomyosin 4 (TPM 4),
TPM 3, t(p25, p23), cysteinyl tRNA synthetase and Ran binding protein.
In addition, TP53 positivity has been demonstrated in some cases, which
could have prognostic influence, being more common in recurrent cases,
with transformation to malignant histological types or production of
metastases (2,7,13,19).
Despite being very infrequent lesions in the larynx, IMT is a pathology
to be taken into account, which requires the same management as
laryngeal neoplasms, with biopsies taken to establish the definitive
anatomopathological diagnosis and define a treatment plan. The
first-line treatment is surgery, either with cold instruments or
resection with laser surgery, the fundamental prognostic factor being
radical excision with free edges. Radiochemotherapy is reserved for
cases with positive margins or a formal contraindication to surgery.
Close clinical follow-up of this pathology is essential, with most
series requiring close follow-up of the patient for at least 12 months,
given the variable risk of recurrence and distant metastasis
(7,13,16,17,20,21).
Given the marked inflammatory component of the lesion, second-line
corticosteroid therapy is validated as an alternative therapy in cases
with contraindications for surgery or tumour recurrence and is also used
for head and neck IMT in locations other than the larynx (1).
Genetic alterations also influence new lines of treatment, with
published series of treatment with the ALK inhibitor crizotinib in cases
of ALK-positive ITM as second-line therapy in cases of contraindication
to surgery, partial resection or positive surgical margins (13, 22).