Abstract.

ANTICANCER RESEARCH 27: 2925-2930 (2007)
Chondrosarcoma of the Larynx and Review of the Literature
ALEXANDER SAUTER1, CLAUS BERSCH2, KATHERINE L. LAMBERT3, KARL HÖRMANN1 and RAMIN NAIM4
1Department
of Otolaryngology, Head and Neck Surgery, and
University Hospital Mannheim, Mannheim, Germany;
3Warwick Medical School, University of Warwick, Coventry, West Midlands, United Kingdom;
4Department of Otolaryngology, Head and Neck Surgery, Saarland University Hospital, Homburg, Germany
2Pathology,
Abstract. Chondrosarcoma (CS) of the larynx was first
described in 1935. Cartilaginous tumours of the larynx are
largely rare and there is little literature concerning them.
Laryngeal CS manifest with a different pathological behaviour
to other malignancies of the larynx and as such the treatment
of these neoplasias are different. The purpose of this review is
to present a detailed report of the laryngeal CS in recent
literature. We present a case of laryngeal CS of the cricoid
cartilage and a case of a sarcomatous neoplasm of the vocal
cord as a potential differential diagnosis. Although representing
a rare malignancy, the last decade has brought new insights in
surgical treatment of laryngeal CS and subsequent reduction
in recurrence rates, whereas progress in tumour biology and
etiological agents is still scarce. We concentrate on new insights
in classification, radiologic and pathologic features, and
treatment modalities in the last two decades. Based on the
literary evidence the authors recommend a conservative
laryngeal function-preserving surgery. Total laryngectomy
should be reserved to recurrent CS and rare cases of
voluminous high-grade CS of the larynx.
Chondrosarcomas (CSs) are uncommon malignant
neoplasms of the cartilage that occur anywhere in the body
but are most commonly seen in the long bones and pelvis.
Laryngeal CS account for less than 0.2% of all head and
neck tumors and up to 1% of all laryngeal malignancies (13, 4). In 1816, Travers (5) reported the first case of a
laryngeal chondroma as "a case of bony growth of the
cartilage of the larynx" to the Medico-Surgical Society of
London. The term chondrosarcoma of the larynx was
introduced in literature by New in 1935 (6). In the previous
Correspondence to: Dr. Alexander Sauter, Universitäts-HNOKlinik, Klinikum Mannheim, Theodor-Kutzer-Ufer, D-68135
Mannheim, Germany. Tel: +496213831600, Fax: +496213831972,
e-mail: alexander.sauter@googlemail.com
Key Words: Chondrosarcoma, laryngeal neoplasm, conservative
surgery, case report, laryngectomy.
0250-7005/2007 $2.00+.40
century, the term chondroma was used to describe all
cartilaginous tumours. Chondroma and CS are closely
related, either synchronously or metachronously. As a result
several cases of low-grade CS have been misinterpreted as
low grade laryngeal chondromas (7). Although a number of
broader studies of laryngeal CS have been published, a
recent review showed that many cases have been reported
several times or are rare single case reports (3). In fact the
actual number of CS of the larynx might indeed be smaller
than suggested. Although CSs of the larynx are rare, they
are of great clinical relevance as their management is largely
different from other malignancies of the larynx. We report
two cases of histopathologically confirmed CS of the larynx
and provide a comprehensive analysis of current advances
in basic research and clinical management of laryngeal CS.
Case Reports
Case 1. A 93-year-old male patient presented with a twoyear history of increasing stridor and dyspnoea. A left-sided
large bulging of the intact subglottic mucosa, occluding 95%
of the tracheal lumen, was visible with a flexible
nasopharyngoscope. In a first step, tracheostomy was
performed. Computed tomography (CT) of the neck showed
a 3 x 3.5 cm tumour of the posterolateral lamina of the
cricoid just inferior to the left vocal cord (Figure 1). The CT
scan excluded enlarged lymph nodes of the neck. The
patient underwent a flexible endoscopy and tumour
resection with a CO2 laser under general anaesthesia. The
majority of the tumour was removed, which on biopsy was
consistent with a low-grade chondrosarcoma (Figure 2 a and
b). Immunohistochemical staining showed expression of
S100 protein. Antibody staining against p53 revealed that
there was no staining of the nucleus of the tumour cells, this
indicating a low Ki-67 proliferation rate and therefore a low
chance of malignancy. In view of the patient’s age and the
histopathological results, a laryngectomy was declined and
the patient scheduled for an endoscopy three months later.
The patient was discharged with tracheotomy and a speech
valve. The patient presented one month later with
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all laryngeal chondromas as misdiagnosed low-grade CS (7,
8). The mean age at diagnosis is between 64 and 66 years, and
the tumor affects three times more men than women (3).
However CS accounts for up to 1% of all head and neck
benign and malignant tumors in a review of a pediatric
population (9). CS of the larynx is seven times more common
in whites than in blacks (10). Approximately 80% of the cases
of laryngeal CS are situated in the cricoid cartilage (3). The
posterior lamina of the cricoid cartilage accounts for most of
the malignancies arising in the midline (3). The thyroid
cartilage, especially the inferolateral wall, is affected in about
20% of cases (11), followed by the arytenoid cartilage, which
accounts for about 3% of CS malignancies (3). Vocal cords
and the epiglottis are less frequently affected (7).
Etiology
Figure 1. Computed tomography (CT) of the neck showed a 3 x 3.5 cm
tumour of the posterolateral lamina of the cricoid with "popcorn-like"
calcification within the neoplasm.
granulations and a progressive growth of the residual
tumour. The residual tumour obstructed 50% of the
subglottic tracheal lumen. The CS was resected again using
a CO2 laser. The patient was discharged and followed up in
an outpatient setting. Three months on from the operation,
the patient is doing well and the tracheostoma was closed
without any evidence of further regional or distant disease.
In the scientific literature to date, there has not been a
detailed overview of etiological factors influencing CS
formation. There have been case reports of CS occurrence
following teflon injections (12) and radiotherapy (13). In a
larger study, about one third of the patients suffering from
CS reported tobacco abuse (3), thus smoking seems to be
an associated finding. The majority of the CS cases are
diagnosed in the seventh decade of life thus coinciding with
maximum cartilage ossification. The ossification of laryngeal
cartilage starts at the insertion sites of the laryngeal
muscles, which represent the predilection sites for CS
formation (3). Cases of recurrence of chondroma to CS as a
transition over time is a further aetiological factor. (14).
Pathology
Case 2. A 66-year-old male patient presented with increasing
hoarseness over several months. The patient denied
symptoms of dyspnoea or stridor. On rigid endoscopy, it was
noted that the mobility of the right vocal cord was reduced
and a 1 cm tumour at the posterior portion of the right vocal
fold was visible (Figure 3 a). Histopathology revealed an
undifferentiated chondrosarcoma, which was diagnosed as
non-classified sarcomatous neoplasm. Two weeks after the
histological diagnosis, the patient underwent chordectomy
with CO2 laser of the right vocal fold and adjacent tissue
under general anaesthesia. Further investigations showed no
evidence of progressive regional or distant metastatic disease.
The patient attended a follow-up endoscopy three months
after surgery. Endoscopy showed no evidence of recurrence
(Figure 3 b).
Epidemiology
Approximately 400 to 600 cases of laryngeal chondroma and
CS have been reported in the literature. Worldwide, laryngeal
chondromas are extremely rare and some authors consider
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Diagnosis of CS is based on the criteria described for
malignant cartilaginous tumours of extralaryngeal bone origin
first described by Lichtenstein and Jaffé in 1943 (15). Their
definition depends upon the finding of any of the following in
a cartilaginous tumour: (i) pronounced irregularity in the size
of the cells and their nuclei; (ii) presence of numerous cells
and their nuclei; (iii) pronounced hyperchromatism of the
nuclei; and (iv) any large or giant cartilage cells with single or
multiple nuclei or with clumps of chromatin. As these criteria
refer to extralaryngeal bones, some authors question if the
criteria of Lichtenstein and Jaffé is still appropiate for
laryngeal CS (16). In 1977, Evans et al. (17) grouped CS of the
long bones according to mitotic rate, cellularity and nuclear
size into grades I, II and III, a higher histological grading
being associated with a poorer prognosis. The criteria
according to Evans et al. is still the most widely accepted
classification for laryngeal CS. However, in the case of
phalangeal CS some authors raise the question if this
classification is still appropiate; this is because both laryngeal
CS and phalangeal CS seldom metastasize, unlike malignant
Sauter et al: Chondrosarcoma of the Larynx
Figure 2. Low-grade chondrosarcoma arising in the cricoid cartilage of a 93-year-old man. (a) The tumour has a multilobular growth pattern and cords
of eosinophilic cells are deposited within the abundant myxoid matrix. HE stain and x150. (b) Partially, aggregates of tumour cells with fibroblastic
features are evident within the epitheloid strands. HE stain and x250.
Figure 3. Non-classified sarcomatous neoplasm in the right vocal fold of a 66-year-old man. (a) Endoscopy revealed a 1 cm tumour of the posterior
portion of the right vocal fold. (b) Endoscopic control three months after prior surgery.
cartilaginous tumours of most extralaryngeal origin which do.
(18). In CS localised to the larynx and phalanx, there are very
few tumour related deaths described. In our case of laryngeal
CS, the low expression of Ki-67 accurately indicated a low
proliferation rate of the malignant cells (18). This result could
describe the improved clinical outcome of laryngeal and
phalangeal CS compared to CS of the long bones.
There are two other variants of laryngeal CS described in
the literature. In 1971, the histological diagnosis of an
undifferentiated CS was first described (19). In
undifferentiated CS, high-grade spindle cell sarcomatous
tissue is associated with low (I) to intermediate (II) grade
CS. Undifferentiated CS have a poorer clinical prognosis.
The second variant of laryngeal CS is clear cell CS. Clear
cell CS is mainly characterized by rounded cells having
conspicuous, clear cytoplasm with sparse intervening matrix,
and by additional criteria such as osteoclast-like cells, bone
trabeculae, aneurysmal bone cyst-like giant cells, and also
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foci of conventional CS (20). To our knowledge no reports
of metastases have been described in the literature. In CS,
regional metastasis is a poor prognostic sign (3). Distant
metastases are rare but have been observed more than
regional neck metastases (7). Metastatic disease has only
been reported in cases of poorly differentiated and
undifferentiated tumours. Metastases can occur as long as
20 years after initial diagnosis (7).
Radiographic Features
CT scanning is a reliable method of evaluating CS of the
larynx, escpecially in preoperative planning of partial laryngeal
resection (1). A calcified mass involving one or more
cartilages of the larynx or trachea that moderately enhances
after the application of contrast medium is a typical CT
finding for a cartilaginous tumour (7). A mass lesion
demonstrating a fine, punctate stippled to coarse "popcornlike" calcification within the tumour is a typical radiological
feature in laryngeal CS. CT scans can determine the size and
extent of the laryngeal tumour. They may also show invasion
of surrounding structures and metastasis of lymph nodes. In
the majority of cases, focal expansion and displacement of
adjacent tissue will be demonstrated. MRI may improve
preoperative evaluation of the extent of the lesion by depicting
the tumour-soft tissue more clearly than can a CT scan. The
common lateral soft tissue radiographs and anteroposterior
tomography study of the larynx used in the past to define the
location and extent of the tumour have been replaced today
by CT and MRI scanning.
Treatment Modalities
Laryngeal CS can be considered as a relatively low-grade
tumour, both histologically and by clinical aggressiveness. As
a result, conservative surgery is the treatment of choice. The
majority of the cases in the literature received a conservative
laryngeal function-preserving surgical treatment. The choice
of conservative surgical options is determined by the
localization of the primary neoplasm. While radical removal
is the aim, the margin of safe excision is difficult to determine,
especially in function-preserving resections. Endoscopic
removal, laryngofissure, thyrotomy or partial laryngectomy
have been described in order to achieve an excision with a
sufficient margin of normal, uninvolved cartilage. Most
laryngeal CS affect the cricoid cartilage, which is considered
crucial to normal laryngeal function. The thyrotomy approach
permits precise excision and preserves the cricoarytenoid, as
well as the posterior cricothyroid muscle and the recurrent
laryngeal nerves. The external approach permits excision with
preservation of the internal perichondrium (21) which is
crucial in order to prevent granulations and cartilage
affections. Extensive resection beyond the midline may lead
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to significant airway narrowing. Hemicricoidectomy followed
by implantation of a modified Montgomery stent in 8 patients
achieved the best voice function following surgery (22). Cohen
et al. (22) also emphasize the surgical preservation of the inner
perichondrium and subglottic mucosa. The inability to
reconstruct laryngeal defects often leads to the
recommendation of total laryngectomy. Laryngeal
reconstruction using local flaps or autogenic transplants can
be used for neoplasms that involve large parts of the cricoid in
order to permit laryngeal function-preserving surgery (16). In
order to preserve the laryngeal framework and function,
extensive excision of laryngeal tumours are followed by
thyrotracheal anastomosis with rib grafts. Endoscopic CO2
laser resections have been used in our cases and have recently
been reported as treatment for primary lesions and
recurrences (14, 16). Cricoid involvement is the critical
feature, especially concerning recurrences, and is the key to
the extent of resection. Primary lesions located in thyroid
cartilage or epiglottis are technically easier to remove by CO2
laser. In Case 1 we excised the tumour from the cricoid
cartilage by CO2 laser. Although we had to remove
granulation tissue after the first excision, the wound healing
was not impaired after revision surgery. When recurrences
develop, a further excision can again be used. A total
laryngectomy might then be necessary, depending on the
extent of the recurrent lesion or inability to reconstruct a
sufficient airway. The partial resections offer patients a better
quality of life with extra years of laryngeal function. This
benefit is of further importance when considering that the
majority of the cases are diagnosed at a high age. A larger
study showed that the approach of partial resection laryngeal
surgery did not impact on the long-term survival of patients
(3). Adjuvant radiotherapy or chemotherapy seems to be
ineffective in the management of laryngeal CS, similar to the
results in CS in other anatomic sites (2, 7, 23).
Primary radiotherapy is not recommended as surgery is
undoubtedly the best-studied form of laryngeal CS treatment.
A study involving 12 cases showed long-term remission
following irradiation in only two of the patients (24) laryngeal
CSs do not respond to chemotherapeutic agents, therefore
chemotherapy is not a recommended therapeutic option (3).
Larger studies report an overall recurrence rate of 16% to
18% (2, 3). The recurrence may develop if the primary
neoplasm was incompletely excised, especially in patients
whose initial treatment included partial or local excision. The
recurrence rate also depends on the grade of the tumour.
High-grade tumours are associated with a significantly higher
recurrence rate (3). A literature review showed that recurrent
laryngeal CS does not affect the overall patient outcome. The
curative rate of total laryngectomy after recurrent laryngeal
CS is comparable to that of initial total laryngectomy (25).
Thus there is no added survival advantage with total instead
of partial laryngectomy (2). Our 93-year-old patient with CS
Sauter et al: Chondrosarcoma of the Larynx
of the cricoid (case 1) developed recurrence despite
conservative surgery in order to maintain laryngeal function
due to the high age of the patient. However, although
conservative surgical treatment failed to eradicate the
neoplasm, we did not perform a total laryngectomy, instead
the patient underwent further laryngeal function-preserving
surgery. The fact that the patient could be decanulated after
the second procedure argues in favour of larynx preserving
procedures. Based on the good prognosis of these laryngeal
tumours, regardless of partial or total laryngectomy, quality of
life must be taken into account. Metastatic disease is
described in about 2% to 10% of the reported cases of
laryngeal CS (2, 3, 7). The development of metastases in the
lung, bone and liver have been reported. In contrast to the
good prognosis of laryngeal CS, a rapid clinical course with
tumour-related death within two years was reported in the
literature (2). Tumour-related death is nevertheless
uncommon and occurs in rare cases with uncontrollable
growth, recurrences, involvement of vital adjacent structures
and persistent aggressive tumour (2, 11). Thompson and
Gannon (3) observed that in laryngeal CS, only 4.5% of the
patients died as a direct result of the disease.
Conclusion
CSs of the larynx are rare. In most cases, CS is being detected
in older men complaining of stridor and hoarseness. This
cartilaginous neoplasm is staged into three grades depending
on histological analysis. Most tumours are low to intermediate
grade, with a poorer prognosis of higher grade CS. The
majority of CSs are located in the cricoid cartilage.
Conservative surgical excision is recommended due to the
good prognosis of larnygeal CS and the generally high age of
the patients. Recurrence should be treated with salvage
laryngectomy. Nevertheless, another conservative surgical
option might be preferred because of the high age of the
patient or concommitant serious disease.
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Received January 29, 2007
Revised April 4, 2007
Accepted May 3, 2007
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