Chondrosarcomas (ChSs) of the larynx are malignant tumours with a mesenchymal origin that most commonly originate from the hyaline cartilage. These tumours represent 0.1% of all tumours of the head and neck region and may occur in the nasal cavity, maxilla, and mandible in addition to the larynx. In regard to the larynx, ChS accounts for 1% of all laryngeal neoplasms[2,3]. Although these tumours rarely occur in the larynx, they have the second highest frequency after tumours originating from epithelial tissue, squamous cell carcinoma and adenocarcinoma. Although high-grade ChS of the larynx has also been described, low-grade tumours are the most common form of the disease[1,5].
These tumours most commonly occur in the cricoid cartilage. The tumours most commonly present on the anterior surface of the posterior lamina of the cricoid cartilage. Cases of occurrence in the epiglottis have also been described (3%)[7,8]. ChS of the larynx often occurs in elderly individuals, usually in the seventh decade of life (average age of 63 years). These tumours are much more common in Caucasians and men (male-to-female ratio = 3.2:1). These tumours rarely progress to regional and distant metastases, even in the T4 stage. Symptoms depend on the location and size of the tumour. Most often, the clinical symptoms are dominated by dyspnoea, dysphasia, dysphonia, and cough with hoarseness. The aetiology of tumour formation remains unclear[1,2]. In addition to clinical examinations, computed tomography and magnetic resonance imaging are recommended as diagnostic imaging methods. A definitive diagnosis is made by histopathological analysis of the tumour tissue. In terms of differential diagnosis, it is necessary to exclude chondroma in cases of low-grade ChS. In cases of high-grade ChS, other types of poorly differentiated malignant tumours (primarily other sarcomas and poorly differentiated cancers) should be excluded.
Chondromas and ChSs are known to be found synchronously in the same tumour or metachronously as a consequence of the malignant transformation of chondroma into ChS, suggesting the enormous importance of adequate sampling of tumour tissue during a pathologic analysis. Surgery is the treatment method of choice. It is important to describe rare cases in clinical practice for the purpose of differential diagnostic assessment, with the aim of making an accurate diagnosis and selecting the proper treatment. Here, we present a case study of a patient treated for low-grade ChS of the larynx.
We present a case of a 60-year-old female patient who developed progressive hoarseness and shortness of breath.
History of present illness
Hoarseness and shortness of breath developed progressively over a 2-mo period.
History of past illness
The patient underwent resection of a laryngeal tumour 14 years before the aforementioned symptoms developed, and histopathological analysis indicated that it was a chondroma.
Personal and family history
The patient had suffered from hypertension for many years, with no significant hereditary diseases. She worked in administrative jobs and never smoked cigarettes or consumed alcohol.
Palpatory examination of the neck during patient assessment revealed an oval-shaped tumour, which was predominantly located on the left side, approximately 6 cm in size, and fixed to the larynx wall. No enlarged lymph nodes were found.
By indirect laryngoscopy, the left hemilarynx was found to be immobile and displaced medially, and the respiratory space was reduced. The mucous membrane was unchanged.
Laboratory analyses were within the reference values.
A computed tomography examination of the neck found a hypodense tumour, permeated with calcifications, up to 5.6 cm in diameter on the left, in the laryngeal wall in the subglottic segment, with no clear boundaries. The tumour infiltrated and partially destroyed the cricoid and thyroid cartilage. The tumour asymmetrically and significantly narrowed the lumen of the subglottic laryngeal segment (Figure 1). On computed tomography, no enlarged and pathologically altered lymph nodes were found, and there were no pathological changes in bone structure.
Computed tomography of laryngeal chondrosarcoma.
A lung X-ray and abdominal ultrasound were performed, and no distant metastases were found.
A portion of the larynx wall and a resected portion of the trachea were submitted for pathohistological analysis, with tumour tissue with a lobulated appearance, 6 cm × 4 cm × 2 cm in size, a whitish colour, homogeneous structure, and moderately solid consistency.
The histology of the tumour tissue was dominated by a moderately abundant basophilic extracellular matrix, part of which had a myxoid appearance. The cellularity of the tumour tissue was moderately focal, with atypical, individual or organized smaller clusters and smaller chondrocytes with rare mitoses present in extracellular matrix lacunae (Figure 2). The tumour growth was nodulo-infiltrative.
Fields with different cellularity and degrees of atypia of chondrosarcoma (hematoxylin-eosin, × 10).
Here, we present a case of a 60-year-old female patient who was diagnosed with low-grade ChS 14 years after the diagnosis of laryngeal chondroma of the cricoid cartilage. Considering that these tumours are extremely rare, it is of the utmost importance to recognize these types of cartilage-origin neoplasms. These facts should be taken into account when considering the differential diagnosis in cases of intramural pathological processes with a preserved laryngeal mucosa.
ChS is characterized primarily by the infiltration of surrounding tissues, although lymphogenic and haematogenous metastases have been reported in approximately 10% of cases. Metastases to the lymph nodes, lungs, bones, kidney, spleen and spinal cord have been described.
The risk factors are unknown. Recurrent laryngeal trauma, radiotherapy, Teflon injections and irregular ossification of the laryngeal cartilage are reported as possible causes. Recurrent ischaemia in chondroma has also been reported as a possible cause for the onset of this tumour. In addition to abnormal cartilage ossification, Gao and co-workers proposed two additional theories: that the tumour is caused by congenital cartilage residues or that chondroplasia occurs due to chronic inflammation. In the literature review, this group of authors cited a case of the malignant transformation of chondroma into ChS within 6 years. Wang et al stated that no correlation between alcohol consumption and cigarette smoking with the onset of this tumour has been demonstrated.
The patient described in this study had been treated for hypertension for many years. She was a non-smoker and did not consume alcohol.
The clinical manifestations of laryngeal ChS may be nonspecific. Symptoms of laryngeal ChS include dyspnoea (if intraluminal tumour growth is dominant), dysphagia (if pharynx infiltration is dominant), and progressive hoarseness. Considering that this is a slow-growing tumour, the patient can tolerate the narrowing airways for a long time, and therefore acute respiratory failure may be the first symptom to occur. In ChS with a thyroid cartilage origin, the clinical picture may also be dominated by a painless tumour mass.
The clinical manifestations of this patient were dominated by hoarseness and respiratory problems.
When a submucosal mass is found during endoscopic examination, most commonly infraglottic and posterior, soft tissue laryngeal tumours should be considered. Although the mucosa is usually smooth, it can be ulcerated in the case of larger tumours. Computed tomography and magnetic resonance imaging are recommended as radiological examinations. Each of these methods has advantages in the analysis of tumour tissue, as well as in the evaluation of the relationship of tumour tissue to the surrounding structures of the laryngeal wall[5,7]. Surgical excision is the treatment method of choice for ChS. Tumour resections must have clear margins. Based on the fact that cervical lymph node metastases are rare, neck dissection should be reserved for clinically or radiologically suspected lymph node metastases. The complex function of the larynx depends on the conservation of the cricoid cartilage. Surgery that preserves laryngeal function is recommended whenever possible. Since 75% of laryngeal ChS forms in the cricoid cartilage, which is considered crucial for laryngeal function, its preservation is often not possible. Total laryngectomy is recommended in cases where more than half of the cricoid cartilage is destroyed by tumour tissue, as well as in cases involving relapse[2,7]. Nonsurgical treatment modalities are rarely used for the treatment of this tumour. Radiotherapy does not seem to play a significant role in the treatment of laryngeal ChS. In the past, it was used to provide local disease control in cases of unresectable or recurrent disease. Chemotherapy has not been shown to be effective for laryngeal ChS, especially low-grade ChS[5,10]. Most authors report relapses in 16% to 50% of cases[1,2]. Regarding the prognosis of this disease, the expected one-year survival rate is 96.5%, the five-year survival rate is 88.6% and the ten-year survival rate is 84.8% of patients. Definitive diagnosis is made by histopathological analysis. The histology of the tumour is dominated by a basophilic acellular matrix (on haematoxylin-eosin stained preparations) containing lacunae with cells. Cell characteristics, nuclear characteristics, cellularity, and the mitotic index are important for histological analysis[1,7]. Macroscopic tumour tissue is solid and hard in consistency. However, it is possible to find softer and even cystic parts due to degenerative changes. In cases of resection of the laryngeal wall, smooth mucosa is often located above the tumour tissue.
Since most laryngeal ChSs are tumours with low-grade differentiation, they are characterized by a lobular-infiltrative growth pattern with cartilage destruction. Given that the most common case in practice is low-grade laryngeal ChS, the differential diagnosis of chondroma and low-grade ChS is very important. Microscopic chondromas are hypocellular (30 to 40 nuclei/HPF), with a homogenous structure and lobular growth pattern, with no cellular atypia or mitosis. Increased cellularity, cellular atypia, binucleation in lacunae, hyperchromasia, a prominent nucleolus, mitoses, and pleomorphism all suggest ChS. It is especially important to analyse parts of the tumour in the border zone compared to the preserved portions of the laryngeal wall[1,5,7]. Immunohistochemical analysis is rarely required. ChS tumour cells are positive for vimentin, S100 and D2-40[1,5]. In less differentiated ChS, cellularity increases and nuclear pleomorphism, hyperchromasia, and mitotic activity are increased. In cases of poorly differentiated laryngeal ChSs, chondroblastic osteosarcoma, fibrosarcoma, myxoid liposarcoma, embryonic rhabdomyosarcoma, spindle cell squamous cell carcinoma with cartilaginous metaplasia should be included in differential diagnosis.