A Case of Mistaken Identity: The Importance of Recognizing Red Flag Symptoms

Case report

A 10-year-old female patient was referred to the local oral and maxillofacial (OMF) department owing to a large left-sided facial swelling. The patient gave a history of pain and tingling to the left lower lip starting 1 week prior to presentation, with the swelling beginning soon after. There were no reports of complaints of dental pain and no history of dental treatment. The patient initially attended an out-of-hours general dental practitioner (GDP) who suspected an odontogenic infection and prescribed a course of amoxicillin with no effect. Her own GDP continued the course of antibiotics and reviewed her 1 week later with no observed change, therefore referred her to the nearest emergency OMF services.

Preliminary diagnoses indicated dental infection with no response to antimicrobial treatment and no improvement. On her presentation at the University Hospital South Manchester, extra-oral examination identified left facial swelling and trismus. Intra-oral examination, although limited, revealed a large firm swelling of the left buccal mucosa extending from the buccal sulcus to the palate and oropharynx, and surrounding the upper left first molar. A degree of molar–incisal hypomineralization was observed, but no evidence of caries. The patient was admitted as an inpatient with the working diagnosis of an odontogenic infection with associated buccal space collection. Further investigations of bloods and a dental panoramic tomograph (DPT) were taken (Figure 1). Inflammatory markers were unremarkable and there was no irregularity found on the DPT, raising suspicions that this was not a dental infection.

The patient was listed for urgent incision and drainage of the buccal swelling with extraction of the upper left first molar if needed. Once under anaesthesia, the mass appeared firm, non-fluctuant and non-pulsatile, extending into the buccal, retromolar and parapharyngeal spaces. The mass was aspirated to reveal minimal blood, no pus and on incision was found to be firm, pale soft tissue. At this point the team became highly suspicious that the swelling was unlikely to be related to an odontogenic cause, but perhaps something more sinister. A soft tissue biopsy was taken, which was sent to histopathology for urgent investigation.

Following a conversation with the patient and her parents, contrast magnetic resonance imaging (MRI) was performed, which showed a large heterogeneous abnormally enhancing mass lesion originating from the left masticator space with marked local aggressive features (Figure 2). A computed tomograph (CT) of the facial bones showed the mass extended from the left mandibular ramus, left maxillary sinus with extension to the left pterygoid plate and bony floor of the middle cranial fossa (Figure 3). The radiological investigation was completed with a CT of the abdomen, thorax and pelvis to check on distant metastases, which in this case were not present. Histology showed the tissue was predominantly a malignant tumour, composed of sheets of tumour cells of varying morphological and immunohistochemical features evident of an embryonal RMS.

The patient was transferred to the Royal Manchester Children's Hospital where the official diagnosis of an embryonal parameningeal RMS of the left buccal/retromolar site was made. The patient's tumour was staged at T2N0M0 and was treated with chemotherapy followed by proton beam therapy in Germany. Surgery at this point was not planned, but was a possibility in the future.

Discussion

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood accounting for over 50% of all sarcomas.⁵ RMS is infrequently encountered and its incidence is 4.5 per 1 million children,² representing 5% of all childhood cancers.⁶ It is the third most prevalent solid tumour following tumours of the central nervous system and neuroblastomas.⁷ The head and neck region sees around 30% of paediatric RMS.⁸ RMS is less commonly encountered in adults. RMS is malignant, unlike its benign counterpart rhabdomyoma. The most common sites of metastasis are to the lungs, bone marrow, lymph nodes and bone.⁹ Of all cases, 50% are diagnosed in the first decade of life, decreasing into adulthood.

RMS is associated with tumours of skeletal muscle, originating from primitive mesenchymal cells.⁶ These multipotent stem cells can differentiate into numerous cell types including osteocytes, adipocytes, chondrocytes and myocytes.¹⁰ These cells develop into a variety of tissues and organs and RMS can occur in a number of anatomical sites not restricted to skeletal muscle. RMS can be divided into embryonal and alveolar categories. Embryonal RMS is characterized by anaplastic mesenchymal cells resembling developing skeletal muscle cells of the embryo. Alveolar RMS resembles mesenchymal cells destined for differentiation to skeletal muscle cells.⁹ Alveolar RMS is most commonly seen in skeletal muscle of the extremities, but is also encountered in other sites including the head and neck. In contrast, the embryonal subtype is predominantly seen in the head and neck and genitourinary tract.¹¹ RMS can be further divided into different subtypes characterized by histopathology: embryonal; alveolar; pleomorphic; and sclerosing/spindle cell.

Most cases of RMS are spontaneous without genetic predisposition. However, some individuals with tumour protein 53 (TP53) gene mutations are predisposed to developing childhood RMS.¹². Multiple syndromic conditions can be associated with RMS including Li-Fraumeni syndrome¹³ and Noonan syndrome.¹⁴

Long-term prognosis is closely related to the behavioural characteristics of the tumour, as well as the size of tumour, number of affected lymph nodes and evidence of metastases (TNM staging). Patients in the low-risk category have an over 90% 5-year survival rate, while high-risk individuals have an approximately 40% survival rate. Rates of survival are significantly lower in adults with tumours at the same sites as children, and factors including age, histological subtype, stage and location are all predictors of survival.¹⁵

RMS can often be a late presentation due to its rarity and other conditions mimicking similar symptoms. Symptoms of RMS vary according to the extent of the primary tumour and the presence of metastases. Symptoms can include an asymptomatic mass, dysphagia, sinusitis, and epistaxis. Symptoms are often non-specific and, in the head and neck region, can present as enlarged lymph nodes or facial swellings associated with odontogenic infections, leading to difficulties in diagnosis. Suspicion of RMS should prompt timely referral to appropriate services to allow for biopsy. Often, open biopsy or trocar is required to aid diagnosis, and care must be taken to ensure surgical sites are not contaminated and malignant cells are not seeded. Additional diagnostic investigations include CT of primary site and MRI.

Treatment is often with chemotherapy, radiotherapy and surgery. All treatments can lead to significant side effects owing to damage to normal surrounding tissues.¹⁶ Surgery is often difficult due to the anatomical constraints of a parameningeal tumour and, therefore, this is often not the treatment of choice. The effects of radiotherapy can include endocrine deficits, facial hypoplasia, visual or orbital complications, hearing loss and other radiation-induced malignancies. Proton beam therapy (PBT) is the ideal choice over conventional photon radiotherapy due to the dosimetric advantage enhancing normal tissue sparing and reduction of side effects.¹⁶ PBT has only been available since 2019 at the Christie Foundation Trust. At the time of this case, patients requiring this treatment were sent abroad. However, with new PBT sites planned to open in the UK, this may no longer be required.

Conclusion

The authors hope that this case will increase awareness for clinicians to identify abnormal signs and symptoms of facial swellings. The patient had been seen by clinicians and treated with multiple courses of antibiotics with no clinical improvement. Clinical presentations that do not follow a regular pattern, or respond to treatment, should raise alarm bells. If a sinister diagnosis is suspected, patients should be discussed and referred in a timely manner to aid in a quick, effective diagnosis and treatment.