10.14639/0392-100X-N1912
Laryngeal chondrosarcomas (LCS) are rare lesions that behave as locally aggressive tumours, producing symptoms such as dysphonia, dyspnoea, dysphagia and hoarseness. Different approaches for the treatment of LCS have been described in the literature. The main purpose of this investigation was to find all cases of LCS published to date and analyse management data and survival outcomes. In December 2020, a systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Provider Enrollment, Chain, and Ownership System (PECOS) method including articles published up to this date on different aspects of LCS. The search included the terms larynx, laryngeal, chondrosarcoma. A total of 148 articles were included in this systematic review describing 381 cases of LCS. Dyspnoea was the most reported symptom followed by hoarseness and neck mass sensation. Cricoid cartilage was the most usual location. Survival rate was influenced by both surgical technique (logrank = 11.7; p = 0.008) and the degree of tumour histologic differentiation (log-rank = 18.3; p = 0.003).
text/xml
1827-675X
1912
en
Cintia Micaela Chamorro-Petronacci
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
systematic review
Survival outcomes in laryngeal chondrosarcoma: a systematic review
Text.Serial.Journal
https://www.actaitalica.it/
42
Reviews
2022-12-29
2021-11-11
2022-12-29
2023-01-16
502-515
1
Cintia Micaela Chamorro-Petronacci
2022/12/29
10.14639/0392-100X-N1912
502
Oral Medicine, Oral Surgery and Implantology Unit, MedOralRes Group, Universidade de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
1827-675X
systematic review
en
515
Survival outcomes in laryngeal chondrosarcoma: a systematic review
https://www.actaitalica.it/article/download/1912/889
42
ACTA OTORHINOLARYNGOLOGICA ITALICA 2022;42:502-515; doi: 10.14639/0392-100X-N1912




Review


Survival outcomes in laryngeal chondrosarcoma:
a systematic review
Le stime di sopravvivenza nel condrosarcoma laringeo: una revisione sistematica
Oscar Álvarez-Calderón-Iglesias1, Mario Pérez-Sayáns2, Rafael Hurtado-Ruzza3, Alejandro Lorenzo-Pouso4,
Cintia Chamorro-Petronacci5
1
  Department of Health Sciences; Faculty of Nursing and Podiatry; Research, Health and Podiatry Group - Universidade da Coruña;
HM Hospitals Research Foundation, Madrid, Spain; 2 Oral Medicine, Oral Surgery and Implantology Unit, MedOralRes Group,
Universidade de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain;
3
  Department of Otorhinolaryngology, Complexo Hospitalario Universitario de Ourense, Province of Ourense, Spain; Research,
Health and Podiatry Group, Department of Health Sciences, Faculty of Nursing and Podiatry, Universidade da Coruña, Spain;
4
  Oral Medicine, Oral Surgery and Implantology Unit, MedOralRes Group, Universidade de Santiago de Compostela, Instituto de
Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; 5 Oral Medicine, Oral Surgery and Implantology Unit,
MedOralRes Group, Universidade de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de
Compostela, Spain


SUMMARY
Laryngeal chondrosarcomas (LCS) are rare lesions that behave as locally aggressive tu-
mours, producing symptoms such as dysphonia, dyspnoea, dysphagia and hoarseness.
Different approaches for the treatment of LCS have been described in the literature. The
main purpose of this investigation was to find all cases of LCS published to date and ana-
lyse management data and survival outcomes. In December 2020, a systematic review was
performed following Preferred Reporting Items for Systematic Reviews and Meta-Anal-
yses (PRISMA) guidelines and the Provider Enrollment, Chain, and Ownership System
(PECOS) method including articles published up to this date on different aspects of LCS.
The search included the terms larynx, laryngeal, chondrosarcoma. A total of 148 articles
were included in this systematic review describing 381 cases of LCS. Dyspnoea was the
most reported symptom followed by hoarseness and neck mass sensation. Cricoid cartilage            Received: November 11, 2021
was the most usual location. Survival rate was influenced by both surgical technique (log-         Accepted: September 27, 2022
rank = 11.7; p = 0.008) and the degree of tumour histologic differentiation (log-rank = 18.3;
p = 0.003).                                                                                        Correspondence
                                                                                                   Cintia Micaela Chamorro Petronacci
KEY WORDS: larynx, chondrosarcoma, systematic review                                               C/ entrerrios S/N, CP: 15706, Santiago de Compo-
                                                                                                   stela, Spain
RIASSUNTO                                                                                          Tel.: +34 651011815
                                                                                                   E-mail: cintiamica.chamo@yahoo.es
Il condrosarcoma laringeo (LCS) è un tumore raro caratterizzato da un comportamento
localmente aggressivo, che determina l’insorgenza di sintomi quali la disfonia, la dispnea,
la disfagia e la raucedine. Diversi approcci terapeutici sono stati descritti in letteratura per     How to cite this article: Álvarez-Calderón-
la cura di questo tumore. Lo scopo principale di questo lavoro è stato quello di revisionare         Iglesias O, Pérez-Sayáns M, Hurtado-Ruzza
tutti i casi di LCS pubblicati in letteratura e analizzare la gestione terapeutica e i risultati     R, et al. Survival outcomes in laryngeal chon-
di sopravvivenza.                                                                                    drosarcoma: a systematic review. Acta Otorhi-
Nel dicembre 2020, è stata effettuata una revisione sistematica in accordo con le linee gui-         nolaryngol Ital 2022;42:502-515. https://doi.
                                                                                                     org/10.14639/0392-100X-N1912
da “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) e il
metodo “Provider Enrollment, Chain, and Ownership System” (PECOS), includendo tutti
                                                                                                   © Società Italiana di Otorinolaringoiatria
gli articoli pubblicati su LCS fino a tale data per caratterizzare i diversi aspetti di questo
                                                                                                   e Chirurgia Cervico-Facciale
tumore. La ricerca ha compreso i termini “Laringe, Laringeo, Condrosarcoma”. Un totale
di 148 articoli e 381 casi di LCS sono stati inclusi in questa ricerca. La dispnea è stato il
                                                                                                                  OPEN ACCESS
sintomo più frequente, seguito da raucedine e riscontro di una massa nel collo. La cricoide
è stata la sede d’insorgenza più frequente. La sopravvivenza è stata influenzata sia dal tipo      This is an open access article distributed in accordance with
                                                                                                   the CC-BY-NC-ND (Creative Commons Attribution-Non-
di chirurgia (log-rank = 11,7; p = 0,008) che dal grado di differenziazione tumorale (log-
                                                                                                   Commercial-NoDerivatives 4.0 International) license. The
rank = 18,3; P = 0,003).                                                                           article can be used by giving appropriate credit and mentio-
                                                                                                   ning the license, but only for non-commercial purposes and
PAROLE CHIAVE: laringe, condrosarcoma laringeo                                                     only in the original version. For further information: https://
                                                                                                   creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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Introduction                                                     Exclusion criteria: letters to the editor, meetings proceed-
                                                                 ings and articles with no abstract or full text available.
Chondrosarcomas (CS) are cartilaginous tumours that com-
                                                                 A comprehensive literature search was performed using the
monly affect bones including the pelvis, ribs and femur 1.
                                                                 PubMed, Web of Science, Scopus and Embase databases
They may also affect the larynx, with the cricoid cartilage
                                                                 for studies published from January 1968 to December 2020.
being the most common site of appearance. Nevertheless,
                                                                 The search included the terms “Larynx [MeSH terms] OR
CS can also originate in thyroid or arytenoid cartilages, epi-
                                                                 Laryngeal [MeSH terms] OR Larynx [Title/Abstract] OR
glottis or even hyoid bone 2.
                                                                 Laryngeal [Title/Abstract] AND Chondrosarcoma [MeSH
Laryngeal chondrosarcomas (LCS) are extremely rare tu-
                                                                 terms] OR Chondrosarcoma [Title/Abstract]”.
mours, representing less than 1% of all malignancies of
the larynx 3. LCS behave as locally aggressive tumours,
                                                                 Study selection and data collection process
producing symptoms such as dysphonia, dyspnoea, dys-
                                                                 Two independent researchers (OACI and MPS) analysed
phagia and hoarseness. In other cases, they can also appear
                                                                 the articles. First, they read the abstracts and excluded those
as a neck mass. Computed tomography (CT) and magnetic
                                                                 not fulfilling inclusion criteria. After that, both authors ana-
resonance imaging (MRI) are the imaging modalities pre-
                                                                 lysed the full-text and decided whether they should be in-
ferred to make a presumptive diagnosis 4, although F-18
fluorodeoxyglucose-positron emission tomography (PET)            cluded or excluded. A third investigator (ALP) acted as a
may be used for grading, and for detection of local recur-       mediator in case of dispute. Agreement was calculated us-
rence or metastases 5. Fine needle aspiration (FNA) or in-       ing Cohen’s kappa coefficient (obtaining a k value of 0.92).
cisional/excisional biopsies may support initial diagnosis 6.
As surgical treatment may be necessary in most cases, his-       Data items
topathological report of tissues will determine the final di-    The following information was extracted from each study:
agnosis. CS are classified in 3 grades; Grade I, (low-grade,     first author, year of publication, journal, sex and age of the
well-differentiated), Grade II (intermediate grade, mod-         patient, symptoms, imaging technique, treatment modality,
erately differentiated) and Grade†III (high-grade, poorly        histopathological diagnosis, location, tumour size, recur-
differentiated). There are different subtypes of CS such as      rence, and follow-up data. References of the selected arti-
clear cell, mesenchymal, extra-skeletal and dedifferenti-        cles were also checked.
ated (also considered as Grade IV) CS 7.
Different approaches for the treatment of LCS have been          Risk of bias in individual studies
described in the literature 8-11. Treatment varies depending     The methodological quality of the included studies and
on the grade of differentiation of the tumour and anatomi-       the possibility of bias were assessed using the modified
cal involvement, from organ preservation techniques to           Newcastle–Ottawa, Pierson and Bradford Hill scales for
total laryngectomy. Radiotherapy (RT) can be considered          case and case series reports 14. The authors of this scale
in some inoperable patients, for recurrences or in case of       recommend assessing the quality of studies according to
aggressive tumours 5. Disease-specific survival of LCS is        four categories, selection, ascertainment, causality, and
higher compared with other laryngeal tumours 3,12. The           reporting, with eight specific questions to answer giving
main purpose of this research was to find all the cases of       low (1-3 questions), medium (4-6 questions) and high (7-
LCS published to date and analyse management data and            8 questions) quality values. This analysis was carried out
survival outcomes.                                               independently by each of the two investigators, and in case
                                                                 of disagreement, the third acted as a mediator.
Materials and methods
                                                                 Results
Systematic review. Protocol and registration
The systematic review was carried out by OACI and was            Systematic review
registered in PROSPERO (Ref. CRD42021224412). The                A total of 148 articles were included in this systematic re-
review was designed following PRISMA guidelines 13 and           view (Flowchart, Fig. 1) (Tab. I and continuation in Sup-
the PECOS method: patients with LCS (P = patient); histo-        pl. Material), describing a total of 381 cases of LCS. In
pathologic analysis (E = exposure); non-laryngeal location       terms of quality, the articles were classified within medium
(C = comparator); clinical-pathological aspects (O = out-        quality values. From articles where gender was specified
come); case reports (S = type of study).                         (342/381), 74% percent were men and 25% women, with a
Eligibility criteria: studies describing cases of LCS written    mean age of 61.1 ± 12 years.
in Spanish or English language.                                  Regarding symptoms, a total of 325 patients (85.3%) de-



                                                                                                                               503
O. Álvarez-Calderón-Iglesias et al.




Figure 1. Flow chart of the systematic review.


scribed some symptom before diagnosis, with dyspnoea            vant therapy with RT was delivered in 28 patients (7.34%)
being the most reported (42.8%), followed by hoarseness         and chemotherapy in 2 patients (0.52%). The size of the
(35.7%) and neck mass sensation (10.8%). Most of the pa-        tumour was reported in 135 patients (35.4%), with a mean
tients reported more than one symptom. Impairment of at         size of 3.8 ± 1.7 cm. Histological information was found
least one vocal cord mobility was reported in 66 patients       in 323 patients (84.7%). Pathological grading was report-
(17.3%). Imaging studies were described in 213 patients         ed as Grade I (well-differentiated) in 210 cases (70.5%),
(55.9%). CT scan was the most used (n = 209) followed by        Grade II (moderately differentiated) in 62 cases (20.8%),
MRI (n = 46). Other techniques such as ultrasound or X-ray      Grade III (poorly differentiated) in 8 cases (2.7%) and
were also described. In Table II, categorical data reported     Grade IV (dedifferentiated) in 18 cases (6.0%). Other cases
in the included studies are summarised.                         were reported as clear cell CS, or myxoid CS. Distant me-
Tumour site was reported in 340 patients (89.2%). The           tastases were infrequent, and reported in 21 patients (5.5%)
cricoid cartilage was the most affected with 271 cases          in different locations including the lungs, soft tissue, bone
(79.9%), followed by the thyroid cartilage in 67 cases          or peritoneum. Lung metastasis was the most frequent lo-
(19.7%). In 41 patients (10.8%), the tumour involved more       cation, being present in 15 cases (71.4 %).
than one anatomical site.                                       The mean follow-up time was 57.7 ± 53.4 months. In this
Different treatment modalities were used. Total laryngec-       period, tumour recurrence was reported in 62 cases (16.3%).
tomy was reported in 131 patients (34.4%), tumour exci-         Forty-two percent of recurrences corresponded to grade I
sion in 104 cases (27.3%), partial laryngectomy (hemic-         CS, 14.5 % to grade II CS, 8% to grade III CS and 9.6 % to
ricoidectomy, cricoidectomy, cricotracheal resection, or        grade IV or dedifferentiated CS. Total laryngectomy was the
vertical, supraglottic, supratracheal, supracricoid laryngec-   treatment of choice in 25 of the recurrences (40%). Local
tomy) in 92 (24.1%), and laser surgery (Carbon Dioxide,         excision and laser were used in 18 patients (29%) while par-
Nd Yag or KTP laser) in 34 patients (8.9%). Radiotherapy        tial laryngectomy was described in 8 patients (13%). Death
was used in 7 patients (1.8%) as the first treatment. Adju-     was reported in 47 patients (12.3%), mostly as “not related



504
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Table I. Studies included in the systematic review.
 Author                                               Year               Journal                                 Cases
 Düzcü et al. 47                                      2020                Turk J Pathol                            1
 Ghandi et al. 16                                     2020   Ind J Otolaryngol Head Neck Surg                      1
 Krawczyk et al. 48                                   2020             Ear Nose Throat J                           1
 Dogan et al. 49                                      2019         Braz J Otorhinolaryngol                         2
 Elktaibi et al. 50                                   2019          Case Rep Oncol Med                             1
 Galletti et al. 51                                   2019              BMJ Case Rep                               1
 Mantilla et al. 52                                   2019             Head Neck Pathol                            4
 Saraydaroglu et al. 53                               2019       Eur Arch Otorhinolaryngol                         3
 Abdullgaffar et al. 54                               2018             Ann Diagn Pathol                            1
 Akbaba et al. 11                                     2018                   Cancers                               7
 Bian et al. 55                                       2018            Int J Clin Exp Med                           1
 Chan et al. 56                                       2018             Ear Nose Throat J                           1
 Chen et al. 57                                       2018                Postgrad Med                             1
 Choi et al. 58                                       2018                    J Voice                              1
 Guthrie et al. 9                                     2018             Am J Otolaryngol                            1
 Hendriks et al. 59                                   2018              BMJ Case Rep                               1
 Hernandez-Brito et al. 30                            2018               Int J Case Rep                            1
 Hinther 60                                           2018          Int J Cell Sci Mol Biol                        1
 Tuite et al. 61                                      2018                 Irish Med J                             1
 Waters et al. 62                                     2018             J Surg Case Rep                             1
 Gao et al. 63                                        2017               Skeletal Radiol                           1
 Hasnaoui et al. 64                                   2017            Ann Clin Case Rep                            1
 Krishnan et al. 65                                   2017                     ORL                                 1
 Lame et al. 66                                       2017   Otorhinolaryngol Head Neck Surg                       1
 Magliocca et al. 35                                  2017             Ann Diagn Pathol                            1
 Maki et al. 67                                       2017            Auris Nasus Larynx                           1
 Moghimi et al. 68                                    2017                Act Med Iran                             1
 Pacheco et al. 69                                    2017     Rev Otorrin Cir Cabeza Cuello                       1
 Rovo et al. 70                                       2017                Laryngoscope                             4
 Vahidi et al. 71                                     2017             Diagn Cytopathol                            1
 Abdel-Fattah et al. 25                               2016             Alexandria J Med                            1
 Banaszewski et al. 72                                2016       Eur Arch Otorhinolaryngol                         4
 Dolinaj et al. 73                                    2016              Acta Clin Croat                            1
 Fidai et al. 74                                      2016         Head and Neck Pathol                            1
 Karatayli-Ozgursoy et al. 75                         2016          Am J Otolaryngology                            6
 Loos et al. 19                                       2016              Ann Surg Oncol                             7
 Rich et al. 76                                       2016                 Head Neck                               3
 Semmar et al. 77                                     2016              J Clin Case Rep                            1
 Sun et al. 78                                        2016                  Oncol Lett                             1
 Zhou et al. 79                                       2016                   Medicine                              1
 Ciolofan et al. 80                                   2015        Rom J Morphol Embryol                            1
 Horta et al. 81                                      2015              BMJ Case Rep                               1
 Jackson et al. 82                                    2015                Laryngoscope                             1
 Mundhe et al. 83                                     2015       Int J Otorhinolaryngol Clin                       1
 Righi et al. 84                                      2015             J Craniofac Surg                            1
 Wang et al. 85                                       2015           Int J Clin Exp Pathol                         2
                                                                                                                 continues u



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Table I. Studies included in the systematic review (follows).
 Author                                                         Year                      Journal                         Cases
 Alexander et al. 86                                            2014               Head and Neck Pathol                     1
 Damiani et al. 18                                              2014              Eur Arch Otorhinolaryngol                 6
 Dominguez-Duran et al. 36                                      2014             Acta Otorrinolaringol Espan                1
 dos Santos et al. 5                                            2014               Braz J Otorhinolaryngol                  6
 Hu et al. 87                                                   2014                       J Voice                          1
 Iravani et al. 88                                              2014                  Am J Otolaryngol                      1
 Kokoglu et al. 89                                              2014                Case Rep Otolaryngol                    1
 Leong et al. 90                                                2014              Eur Arch Otorhinolaryngol                 1
 Miyamaru et al. 91                                             2014                  Am J Otolaryngol                      1
 Pantazis et al. 92                                             2014                        B-Ent                           1
 Pelliccia et al. 17                                            2014                   Ann Surg Oncol                       7
 Piazza et al. 8                                                2014                    Laryngoscope                        16
 Potochny et al. 93                                             2014                  Head Neck Pathol                      1
 Purohit et al. 94                                              2014                    Laryngoscope                        1
 Tsai et al. 95                                                 2014                   Case Rep Oncol                       1



or other cause” (74%), or “distant metastasis” (17.4%). Only           CS are the most common, with a slow-growing tumour
8.7% were reported as “died of disease”.                               pattern. In some cases, biopsies may misdiagnose Grade
Using Kaplan-Meier curves, a mean survival of 207.5                    I LCS as chondromas. Intermediate and high-grade LCS
months (95% confidence interval, CI 176.4-238.7 months)                are less common and usually have the worst prognosis. The
is estimated for the entire series.                                    results of this systematic review show that survival rate in
Regarding survival in relation with tumour location, the es-           grade IV LCS was lower than in Grade I LCS.
timate is lower for cases with combined location, with 98.5            Symptoms depend on the site and extent of the tumour,
months (95% CI 73-124 months) compared to those affect-                generally appear insidiously, and may persist for years be-
ing only one location, with a mean of 191.6 months (95%                fore a final diagnosis is made 16. Due to this indolent behav-
CI 163.1-220 months) (log-rank = 6.6, p = 0.01).                       iour and, to the usual submucosal growth, diagnosis may
Survival was also affected by histological differentiation,            be delayed in time. Dysphonia and hoarseness are the most
being the lowest for grade IV (dedifferentiated) with 118.7            frequent complaints of the patients with LCS. Most cases
months (95% CI 64.8-172.6 months) and the longest for                  arise from cricoid cartilage, mainly involving the poste-
grade I (well-differentiated) with 253.8 months (95% CI                rior lamina and cricoarytenoid joint. It is not uncommon
215-292.5 months) (log-rank = 18.3; p = 0.003) (Fig. 2).               that LCS may affect different locations at the same time
Regarding treatment modality, the estimate for survival was            (referred to as combined location herein). In fact, the sur-
lower for those who underwent total laryngectomy with                  vival estimate is lower in those patients with involvement
156.6 months (95% CI 127.5-185.6 months) compared                      in more than one site, compared to those with a tumour
with those who were treated with laser excision with 276.1             involved in only one 5.
months (95% CI 229.4-322.9) (log-rank = 11.7; p = 0.008)               Surgery is the treatment of choice for LCS. The selection
(Fig. 3). Death was found to be more frequent in patients              of the surgical technique will depend on different factors
with recurrence who were treated with total laryngectomy               such as anatomical involvement, mobility of the cricoar-
(55.3%, p = 0.001).                                                    ytenoid joint or histological grade of the tumour. The key
                                                                       to choose the appropriate technique is to balance the onco-
                                                                       logical (loco-regional cancer control) with functional out-
Discussion                                                             comes 17. Since these tumours are generally associated with
A total of 148 articles were included in our study. The re-            good prognosis, the goal should be to remove the tumour
sults of this systematic review, in general, agree with the            with adequate margins avoiding local recurrences or distant
main previously published series 3,15. Thus, LCS are rare              metastasis and trying to preserve as much laryngeal func-
tumours, with a male predominance and an average age of                tion as possible. For this reason, surgeons have described
appearance between 60-70 years. Histologically, low-grade              different conservative surgical techniques, including mini-



506
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Table II. Categorical variables reported in cases included.                                mally invasive local resections, transoral laser procedures,
                                                   N                   Percentage          and partial laryngectomies. Theoretically, less aggressive
 Symptoms                                                                                  techniques are indicated for low-grade, not extensive tu-
    Dyspnoea                                     163                       42.8            mours, and those that affect thyroid, arytenoids, and epi-
    Hoarseness                                   136                       35.7            glottis or less than a half of the cricoid cartilage. Neverthe-
    Dysphonia                                    105                       27.6            less, treatment of cricoid CS is still controversial. Trying to
    Dysphagia                                     55                       14.4            avoid radical, non-functional, management of cricoid CS,
    Neck Mass                                     41                       10.8            some authors reported their results with conservative tech-
    Stridor                                       25                        6.6            niques. In this sense, Damiani et al. 18, emphasised the use
    Foreign body sensation                         8                        2.1            of techniques like “Remodeling Transoral Laser Surgery”,
    Haemoptysis                                    2                        0.5            or “Supratracheal Partial Laryngectomy”, in low-to inter-
    Incidental                                     2                        0.5            mediate cricoid LCS, achieving good laryngeal function
    Weight Loss                                    1                        0.3
                                                                                           with minimal risk of recurrence. De Vincentiis et al. 10, in
    Vocal cord impairment                         66                       17.3
                                                                                           their series of 3 cricoid CS affecting more than 50% of the
 Site
                                                                                           cricoid ring, reported that “total cricoidectomy with thyro-
    Cricoid                                      271                       71.9
                                                                                           tracheopexy” is an effective alternative to total laryngecto-
    Thyroid                                       67                       19.7
                                                                                           my. Loos et al. 19, reported good oncological and functional
    Arytenoid                                     21                        6.2
    Hyoid Bone                                     9                        2.7
                                                                                           results in 7 patients with cricoid CS, after “hemilaryngec-
    Epiglottic                                     6                        1.8            tomy with tracheal autotransplantation”. Piazza et al. 8 also
    Trachea                                        5                        1.5            reported good results with “open partial laryngectomy”
    Subglottic area                                4                        1.2            and “cricotracheal resections and anastomosis”. Total lar-
    Transglottic area*                             2                       0.6             yngectomy used to be the preferred surgery for high-grade,
    Combined location**                           41                       10.8            extensive tumors, those affecting more than 50% of the
 Imaging                                         213                       55.9            cricoid cartilage and recurrences. The results of this sys-
    CT scan                                      167                       78.4            tematic review reflect that survival is lower in patients in
    MRI                                            4                       1.41            which a total laryngectomy was performed in comparison
    CT + MRI                                      42                       14.8            with those who underwent more conservative techniques.
 Treatment                                                                                 This may have an explanation, because patients with poor
    Total laryngectomy                           131                       34.4            prognosis (larger, dedifferentiated, and recurrent tumours)
    Local scission (removal of the tumour)       104                       27.3            are those in which laryngectomy was performed.
    Partial laryngectomy                          92                       24.1            The role of chemotherapy for these tumours is negligi-
    Laser surgery                                 34                        8.9            ble 20,21. Radiation therapy has been proposed to reduce tu-
    Neck dissection                               18                        4.7            mour volume, as adjuvant therapy in some cases of residual
    Radiotherapy                                   7                        1.8            tumours or in non-operable patients 6,11,22-24. Cervical me-
    Adjuvant therapy                              30                        7.8            tastases of CS are rare, and neck dissection should be per-
    Radiotherapy                                  28                        7.3            formed only if radiological or clinical evidence of disease
    Chemotherapy                                   2                       0.52
                                                                                           is present 25-27. In this review, some authors reported neck
 Histologic grading                              313                       82.2
                                                                                           dissection when pathological lymph node was present, as
    Grade I                                      210                       67.1
                                                                                           well as thyroidectomy when needed 20,26-31,32-34.
    Grade I-II                                    11                        3.5
                                                                                           Distant metastases are infrequent, and usually involve the
    Grade II                                      62                       19.8
    Grade II-III                                   4                        1.3
                                                                                           lungs 24,27,35-37. Tumour recurrence is common. The results
    Grade III                                      8                        2.6
                                                                                           of this systematic review found recurrence in 16% of cases.
    Grade IV                                      18                        5.8            This fact makes close follow-up of patients mandatory, es-
 Tumour size [cm]                                135                       35.4            pecially in those treated with conservative techniques.
 Follow-up [months]                              317                       83.2            The most debatable issue, to date, is what type of surgi-
 Recurrence                                       62                       16.3            cal technique is the most appropriate for LCS. Total laryn-
 Metastases                                       21                        5.5            gectomy should be the choice for large tumours or those
 Death                                            47                       12.3            with high grade or undifferentiated histology. On the other
*
  Transglotic tumours are those that crosses the laryngeal ventricle involving both the    hand, conservative techniques have the main advantage of
vestibular and vocal folds. **Combined location is considered when more than a cartilage   being less aggressive, but with a high risk of recurrence.
of area was involved.
                                                                                           This strategy may be useful for patients with a more favour-



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O. Álvarez-Calderón-Iglesias et al.




Figure 2. Survival outcomes according to histological differentiation.




Figure 3. Survival outcomes according to surgical treatment.



508
                                                                                                   Laryngeal chondrosarcoma systematic review




able anatomy, low grade histology, or elderly patients in         analysis: MPS; investigation: RH-R; methodology: CC-P;
whom life expectancy makes tumour recurrence less likely.         Supervision: O-C-I; writing-review and editing: MPS and
Close follow-up and regular monitoring is needed in these         CC-P.
patients and in case of relapse, more aggressive techniques
will be needed. Brandwein et al. 38 state that given the          Ethical consideration
behaviour of LCS, initial management should encompass             This study was sent to the Ethics Committee of Clinical
conservative techniques. Salvage total laryngectomy in            Research of Galicia (Spain), which stated that ethical ap-
case of recurrence would be the option, without compro-           proval was not required.
mising survival.
Iandelli et al. 39 proposed a conservative approach rather than
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Supplementary material
Table SI. Studies included in the systematic review (continuation of Table I).
 Author                                           Year                                         Journal                                 Number of cases
 Maki et al. 96                                    2017                                    Auris Nasus Larynx                                  1
 Mantilla et al. 97                                2019                                  Head and Neck Pathol                                  4
 Maughan et al. 98                                 2012                                   Ann R Coll Surg Engl                                 1
 Medina-Banegas et al. 99                          2003                                Eur Arch Otorhinolaryngol                               1
 Merrot et al. 100                                 2009                                         Head Neck                                      7
 Mishell et al. 101                                1990                            Arch Otolaryngol Head Neck Surg                             1
 Miyamaru et al. 102                               2014                                     Am J Otolaryngol                                   1
 Moghimi et al. 103                                2017                                       Acta Med Iran                                    1
 Mohajeri et al. 104                               2013                                      Adv Biomed Res                                    1
 Mokhtari et al. 105                               2012                                     Head Neck Oncol                                    4
 Moran et al. 106                                  1993                                   Arch Pathol Lab Med                                 4
 Mundhe et al. 83                                  2015                                Int J Otorhinolaryngol Clin                             1
 Muñoz et al. 107                                  1990                                   AJR Am J Roentgenol                                 3
 Nakano et al. 108                                 1999                                    Auris Nasus Larynx                                  1
 Nakayama et al. 109                               1993                                 Ann Otol Rhinol Laryngol                              2
 Nao et al. 110                                    2011                         Eur Ann Otorhinolaryngol Head Neck Dis                         2
 Neis et al. 111                                   1989                                 Ann Otol Rhinol Laryngol                              3
 Nicolai et al. 112                                1990                                 Ann Otol Rhinol Laryngol                              8
 Nistal et al. 113                                 2005                                         Head Neck                                      1
 Obenauer et al. 114                               1999                                          Eur Radiol                                   1
 Obeso et al. 115                                  2010                                 Acta Otorrinolaringol Esp                              5
 Oestreicher-Kedem et al. 116                      2009                                       J Laryngol Otol                                 2
 Oliveira et al. 117                               2014                                  Braz J Otorhinolaryngol                               6
 Onorati et al. 118                                2013                                         Pathologica                                    2
 Ostberg et al. 119                                1979                                      Acta Otolaryngol                                  6
 Pacheco et al. 120                                2017                          Rev Otorrinolaringol Cir Cabeza Cuello                       1
 Pantazis et al. 121                               2014                                            B-Ent                                      1
 Pelliccia et al. 17                               2014                                      Ann Surg Oncol                                    7
 Perrot et al. 122                                 2013                         Eur Ann Otorhinolaryngol Head Neck Dis                         1
 Piazza et al. 8                                   2014                                       Laryngoscope                                    16
 Policarpo et al. 123                              2008                                 Acta Otorhinolaryngol Ital                             1
 Poole et al. 124                                  1986                                      Aust N Z J Surg                                  1
 Potochny et al. 125                               2014                                  Head and Neck Pathol                                  1
 Purohit et al. 126                                2014                                       Laryngoscope                                     1
 Rich et al. 127                                   2016                                         Head Neck                                      3
 Righi et al. 128                                  2015                                     J Craniofac Surg                                   1
 Rinaggio et al. 129                               2004                    Oral Surg Oral Med Oral Pathol Oral Radiol Endod                   1
 Rinaldo et al. 130                                2000                                      Acta Otolaryngol                                 12
 Rovo et al. 131                                   2017                                       Laryngoscope                                     4
 Sakai et al. 132                                  2000                                  AJNR Am J Neuroradiol                                1
 Saleh et al. 133                                  2002                                Eur Arch Otorhinolaryngol                               5
 Saraydaroglu et al. 134                           2019                                Eur Arch Otorhinolaryngol                               3
 Sarma et al. 135                                  2011                                    Open J Anesthesiol                                 1
 Sauter et al. 136                                 2007                                       Anticancer Res                                   2
                                                                                                                                               continues u



                                                                                                                                                      513
O. Álvarez-Calderón-Iglesias et al.




Table SI. Studies included in the systematic review (continuation of Table I).
 Author                                           Year                                         Journal                                Number of cases
 Sears et al. 137                                  2012                                       Med Health RI                                  1
 Semmar et al. 77                                  2016                                     J Clin Case Rep                                   1
 Sheen et al. 138                                  1997                                        Head Neck                                      1
 Shinhar et al. 139                                2001                                    Ear Nose Throat J                                  1
 Stavrakas et al. 140                              2016                                      J Laryngol Otol                                  5
 Sun et al. 141                                    2016                                         Oncol Lett                                    1
 Tachino et al. 142                                2012                                     J Med Case Rep                                    1
 Timon et al. 143                                  1992                                       J Otolaryngol                                   4
 Tiwari et al. 144                                 1999                                Eur Arch Otorhinolaryngol                              5
 Tsai et al. 145                                   2014                                     Case Rep Oncol                                    1
 Tuite et al. 146                                  2018                                        Irish Med J                                    1
 Vahidi et al. 147                                 2017                                     Diagn Cytopathol                                 1
 Wang et al. 148                                   2015                                   Int J Clin Exp Pathol                              2
 Wang et al. 149                                   1999                                     Am J Otolaryngol                                  5
 Waters et al. 150                                 2018                                     J Surg Case Rep                                   1
 Windfuhr et al. 151                               2003                                      J Laryngol Otol                                  3
 Wippold et al. 152                                1993                                 AJNR Am J Neuroradiol                                10
 Zeiltels et al. 153                               2011                                 Ann Oto Rhino Laryngol                               10
 Zhang et al. 154                                  2014                                  Head Neck J Sci Spec                                 1
 Zhou et al. 155                                   2016                                          Medicine                                     1



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