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).