Embryonal rhabdomyosarcoma masquerading as a left vocal cord granuloma
- 1 ENT, Central Manchester University Hospitals NHS Foundation Trust, Manchester, Greater Manchester, UK
- 2 Anaesthesia, Central Manchester University Hospitals NHS Foundation Trust, Manchester, Greater Manchester, UK
- Correspondence to Mr Stefan Linton; Stefan.Linton@mft.nhs.uk
Abstract
Embryonal rhabdomyosarcoma (ERMS) of the larynx in adults is an extremely rare diagnosis with insidious onset and progression. Only six reports (including this one) have been documented in the literature. Clinical presentation is dependent on the site, size, subtype of ERMS and growth rate. Hoarseness is the usual first symptom, followed by stridor and dyspnoea, with dysphagia being late in onset. Accurate staging and risk stratification is necessary to avoid overtreating/undertreating patients and should be guided by local Head and Neck/Sarcoma Multidisciplinary Teams. Treatment has moved away from radical therapeutic regimens to less-invasive, organ-preserving therapies. Long-term follow-up is required due to the risk of late recurrence.
Background
Rhabdomyosarcomas (RMSs) are the most common soft tissue sarcomas in children/adolescence, accounting for 4.5% of all cases of childhood cancers.1 They arise from rhabdomyoblast and are divided into four distinct histological subtypes: embryonal, alveolar, anaplastic (previously known as pleomorphic) and sclerosing.2 Of the four subtypes, embryonal accounts for the majority (60%–75%) of cases, followed by alveolar (25%–30%), anaplastic and sclerosing.1 3 Embryonal rhabdomyosarcomas (ERMSs) can further be subdivided into ‘Botryoid’ and ‘Spindle cell’ variants.
The occurrence of RMSs in adults is rare, accounting for just 3% of all soft tissue sarcomas.4 RMSs can occur at any site but different subtypes are more common in certain areas of the body. ERMSs most commonly arise from the genitourinary region or the head and neck region. Alveolar RMSs are seen most commonly in the extremities, the trunk and the perianal region.3
Within the head and neck region, anatomical sites of RMSs have been grouped into orbital, parameningeal and non-parameningeal (which includes the larynx).5 The occurrence of RMS within the larynx is extremely rare in adults, with only 25 cases being described in the English-speaking literature. Of the 25 cases, only 5 were diagnosed as ERMSs. In this study, we present the first known case in the UK of an ERMS arising from the true vocal cord.
Case presentation
A 48-year-old woman was referred by the emergency department to the Ear, Nose and Throat (ENT) on-call team with worsening stridor and mild respiratory distress. Her medical history included anxiety, chronic obstructive pulmonary disease (COPD), fixed vocal cords and subglottic stenosis. Her laryngeal pathology was secondary to an inhalation injury incurred during a house fire in 2014. During that fire, she also suffered severe burns to the head and neck region, resulting in extensive scarring to these areas. Due to her laryngeal pathology, she suffered with a raspy voice and stable biphasic stridor. She had been recently discharged from the ENT inpatient service 3 weeks prior to this presentation, for similar symptoms which had been diagnosed as an exacerbation of her COPD. During that hospitalisation, a CT scan of her neck was done to assess the severity of her subglottic stenosis. The report measured the calibre of her subglottic stenosis to be 13 mm×14 mm in the anteroposterior and transverse diameters. This was a slight improvement compared with a previous CT neck done in December 2018 where the calibre measured 10 mm×15 mm.
On clinical examination by the emergency physician, the patient had biphasic stridor with mild respiratory distress with a respiratory rate of 27 breaths/min and an oxygen saturation (SpO2) of 99% on room air. The remainder of her vitals were stable. Her chest was clear aside from a slight expiratory wheeze and transmitted upper airway sound on auscultation. Intravenous access was set up and blood was taken for a full blood count, urea & electrolytes, C reactive protein (CRP), serum magnesium (Mg2+) and arterial blood gas (ABG). The ABG revealed hypoxia with a partial pressure of oxygen (pO2) of 8.9 kilopascal (kPa) and carbon dioxide retention with a partial pressure (pCO2) of 6.9 kPa. Her white cell count was normal with a mildly elevated CRP 25 mg/L. ECG showed sinus tachycardia of 112 beats/min. The diagnosis at this time was non-infective exacerbation of COPD and worsen stridor due to progression of her subglottic stenosis. She was started on oxygen via facemask and administered dexamethasone 10 miligrams (mg) intravenous, co-amoxiclav 1.2 g intravenous and 1:1000 epinephrine nebuliser. These measures improved the patient’s tachypnoea, allowing her to undergo flexible nasoendoscopy (FNE) by the on-call ENT clinical fellow. The examination showed limited vocal cord movement and subglottic stenosis but no laryngeal oedema. The critical care medical team also reviewed the patient. However, with her symptoms now improved, the decision was made to admit her to the ENT inpatient ward for observation and continued treatment for her COPD. She was switched from intravenous dexamethasone to oral prednisolone 30 mg for 5 days. The co-amoxiclav was also changed to doxycycline 100 mg two times per day for 5 days as per the medical team’s advice. Her regular inhalers were to be continued and consisted of salbutamol and Trimbow (a combination inhaler of beclometasone with formoterol and glycopyrronium). The plan at this time was to continue this treatment regimen until review by the respiratory inpatient team.
Her symptoms showed slight improvement over the next 48 hours, with decreasing use of ‘as needed (prn)’ salbutamol nebulisers and decreasing expiratory wheeze on clinical examination. On day 3 hospitalisation, the patient was rescoped via FNE by the ENT registrar as her breathlessness appeared worse compared with her admission 3 weeks prior. The examination revealed a ‘fleshy’ lesion appearing to arise from the left vocal cord. The lesion appeared to be ball-valving into the glottis during respiration. After discussion and review by the on-site consultant laryngologist, the decision was made to take the patient to theatre for microlaryngoscopy and debridement of the left vocal cord lesion.
Treatment
In preparation for a difficult intubation, the advance airway anaesthetic consultant was asked to review the patient. It was determined that a cannula cricothyroidotomy would be performed to avoid a ‘Can’t Intubate, Can’t Oxygenate’ (CICO) scenario. While receiving nasal high-flow oxygen therapy, a cannula cricothyroidotomy was performed under ultrasound guidance with the use of local anaesthesia (1% lidocaine). With the cannula cricothyroidotomy in place, the patient was anaesthetised and successfully intubated using a size 4.0 microlaryngotracheal tube.
Microlaryngoscopy was then performed by the on-call ENT consultant. This confirmed the origin of the ‘fleshy’ lesion to be arising from the left vocal cord along its medial surface (figure 1). The lesion was excised via a cold steel technique and sent for histology. The rest of the left vocal cord was debrided until an adequate glottic inlet was established (figure 2).
Microlaryngoscopic image showing ‘fleshy’ lesion arising from the left vocal cord.
Microlaryngoscopic image showing post debridement appearance of laryngeal inlet.
Outcome and follow-up
The patient was extubated successfully and spent an uneventful night in the extended recovery suite before being transferred back to ward level care. With her respiratory symptoms now resolved completely, the patient made an uncomplicated recovery from her surgery and was discharged on day 5 hospitalisation for followed up in the head and neck clinic in 2–3 weeks time for histology results (figures 3–6).
Histological image showing cellular tumour with ulcerations and poorly differentiated areas with focal necrosis (×100) (H&E stain).
Histological image showing myxoid areas with poorly differentiated tumour cells (×200) (H&E stain).
Histological image showing desmin positivity revealing muscle differentiation. ‘Arrows’ highlight cross striations within tumour cells showing muscle differentiation (×400).
Histological image showing myogenin positivity in keeping with muscle differentiation (×400).
With the diagnosis of ERMS confirmed by histological analysis, the patient was sent for further imaging to investigate for local and regional metastasis. CT neck did not show any lymphadenopathy. CT thorax showed upper lobe predominant centrilobular and paraseptal emphysema but no evidence of metastasis or lymphadenopathy.
Her case was discussed at the local sarcoma MDT, with the outcome being to take the patient back to theatre for microlaryngoscopy and laser resection of the left vocal cord. This procedure was carried out 4 weeks after her diagnosis. There were no complications from this procedure. Follow-up histology revealed no further evidence of malignancy. She continues to be followed up in the head and neck clinic for recurrence surveillance and to plan adjuvant treatment, that is, radiotherapy.
Discussion
The occurrence of laryngeal sarcomas is rare, accounting for less than 1% of all laryngeal cancers.6 Histological subtypes include fibrosarcomas, chondrosarcomas, osteosarcomas, leiomyosarcomas, liposarcomas and rhabdomyosarcomas. The first known case of RMS of the larynx was described in a child by Glick in 1944.7 The occurrence of such cancers of the larynx in adults is extremely rare, with only 25 cases documented in the English literature. Of those 25 cases, there are only 5 embryonal RMSs documented (table 1). This report will be the first documented ERMS of the true vocal cord in the UK.
Adult case reports of embryonal rhabdomyosarcoma of the larynx
| Author | Age, sex | Laryngeal site | Treatment | Outcome |
| Rodriguez and Ziskind, 197017 | 57, M | Right true vocal cord | Total laryngectomy | No follow-up required |
| Hall-Jones, 197518 | 54, M | Posterior vestibular wall of larynx | Total laryngectomy | No recurrence at 16 months |
| Libera et al, 199919 | 66, M | Vestibule | Partial laryngectomy | No recurrence after 10 years |
| Dikbas et al, 200515 | 28, M | Ventricle | Induction chemotherapy plus radiotherapy | No recurrence after 22 months |
| Li et al, 201520 | 22, F | Right true vocal cord | Cordectomy and selective neck dissection | No recurrence after 5 years |
Clinical presentation of laryngeal sarcomas are variable and depends on the site, its size and growth rate. Hoarseness appears to be the first symptom reported. Stridor and dyspnoea soon follow as the tumour continues to grow. Dysphagia is usually a later symptom, only becoming present when the tumour extends into the hypopharynx.8 In the current clinical report, the patient already suffered with hoarseness, biphasic stridor (due to fixed vocal cords and subglottic stenosis) and dyspnoea (due to her COPD). She only complained of worsening shortness of breath. As the lesion was not seen during her last admission 3 weeks prior, it may have emerged within that timeline.
The histological examination of RMSs reveal high cytologic and morphologic variability representing different stages of skeletal muscle morphogenesis. Desmin, myogenin, MyoD1 and muscle-specific actin are the common immunohistochemical stains used to diagnose RMSs. ERMSs have specific molecular characteristics differentiating them from the other subtypes of RMSs. These include a loss of genomic material from the short arm of chromosome 11 and the lack of gene amplification.3 In the current report, the patient’s histological analysis showed a range of differentiation; ranging from undifferentiated/primitive cells showing a mild degree of nuclear pleomorphism, to well-differentiated rhabdomyoblasts and strap cells. Immunohistochemical staining was positive for MyoD1, myogenin, desmin and negative for S-100, thereby confirming the lesion as an RMS. The presence of multiple copies of FOXO1 gene raised the possibility of chromosomal gain classifying it as an embryonal RMS.
Radiological investigations for staging of RMSs of the larynx include CT or MRI. Evaluation of regional and distant lymphadenopathy should be carried out either by clinical or radiological imaging.
The staging system for RMSs is complex and based on a combination of the ‘Tumour, Nodal and Metastasis’ (TMN) system and the ‘Clinical Grouping System’ developed by the Intergroup Rhabdomyosarcoma Study Group (IRSG).9 TNM system is used first to stage the extent of the tumour before any therapy is undertaken. The clinical grouping system then categorises patients based on pathological extent of tumour invasion after surgical resection of the primary tumour and nodal evaluation prior to the initiation of chemotherapy (table 2).
Clinical grouping system for rhabdomyosarcoma1
| Clinical group I | Local disease completely resected. No regional nodes. |
| Clinical group II | Total gross resection with evidence of regional spread:
|
| Clinical group III | Incomplete resection or biopsy with gross residual disease |
| Clinical group IV | Distant metastatic disease at time of diagnosis |
The two staging systems are combined and patients are risk stratified into three groups (low, intermediate and high) based on the ‘Children’s Oncology Group (COG)10’ risk stratification system (table 3). The COG classification has been shown to be an accurate predictor of outcome in the paediatric age group. Its application in adults is questionable due to the rarity of RMSs in this age group. However, in a large retrospective study of RMSs in adults, Ferrari et al 11 concluded that the prognosis of RMSs in adults may be similar to that of the paediatric population. Poor prognostic factors for RMSs in adults include advancing age, histological subtype (alveolar and pleomorphic), unfavourable site (extremities, bladder/prostate and biliary tract/liver) and disease stage.11 12
Risk group stratification classification1
| Risk group | Histology | Primary sites | Initial resection | Distant metastases | Proportion of patients (%) | Event-free survival (%) |
| Low | ERMS | Favourable Unfavourable |
Any Yes |
None None |
32 | 70–95 |
| Intermediate | ERMS ARMS |
Unfavourable Any |
No Any |
None None |
27 25 |
73 65 |
| High | ERMS ARMS |
Any Any |
Any Any |
Present Present |
8 8 |
35 15 |
-
ARMS, Alveolar Rhabdomyosarcoma ; ERMS, embryonal rhbdomyosarcoma.
Treatment of laryngeal ERMS has evolved over the last several decades (based on prognostic evidence from the IRSG and the COG) from more radical multiple modality therapies (eg, hemilaryngectomy, total laryngectomy±chemoradiation) to less-invasive, organ-preserving single modality treatments (laser cordectomy). ERMS of the larynx is seen to have a favourable treatment outcome in the literature in comparison to the alveolar subtype. They are also more sensitive to chemoradiation.13 Jain et al 14 successfully treated a subglottic ERMS in a teenage girl with chemoradiation alone. Dikbas et al 15 also described a similar outcome with chemoradiation alone in a young adult male with an ERMS of the laryngeal ventricle. However, it should be noted that single modality treatment is only used for small localised cancers (group 1, low risk) and that patients with locally advance and regional disease (II–IV, intermediate–high risk group) will require more extensive resection with adjuvant radiotherapy (RT) or chemoradiotherpy (XRT).9 In the current report, the patient is considered to be in group 1, low risk classification. As the evidence for adjuvant RT or XRT for patients within this group is lacking,16 the rationale to subject patients to such therapies may be questionable. Long-term follow-up is recommended for these patients due to the risk of late recurrence.
Learning points
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Embryonal rhabdomyosarcoma of the larynx in adults is extremely rare with insidious onset and progression.
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Accurate staging and risk stratification is necessary to develop individual treatment regimens to avoid overtreating/undertreating patients.
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Guidance should be sought wherever possible from local Head and Neck/Sarcoma Multidisciplinary Teams.
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Life-long follow-up is required due to late recurrence.
Acknowledgments
Dr Guy Betts, Consultant Head and Neck Histopathologist, Central Manchester University Hospitals NHS Foundation Trust, contributed the histology images used in the case report.
Footnotes
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Contributors SL contributed to the case presentation and discussion. SP reviewed the case report. ES and Dr SM-P contributed to the discussion and summary of the article.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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