A rapidly enlarging swelling of the left orbit
BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h799 (Published 25 February 2015) Cite this as: BMJ 2015;350:h799
- Rachel S Varughese, foundation doctor1,
- Elliott Ridgeon, foundation doctor1,
- Anna Mathew, consultant paediatrician2,
- David Sola-Del Valle, senior ophthalmology resident3
- 1University of Oxford Medical School, Oxford OX1 2JD, UK
- 2Department of Paediatrics, Worthing Hospital, Worthing, UK
- 3Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA
- Correspondence to: R S Varughese rachel.varughese{at}btinternet.com
A previously well 16 year old girl presented to acute medical admissions (walk-in assessment clinic) with a one week history of swelling of her left eyelid. She was prescribed amoxicillin for a presumed folliculitis.
She re-presented one week later to the emergency department because the swelling had steadily worsened over the past two weeks. It was tender to palpation but there was no pain with movement. Visual acuity was reduced in the left eye to 6/9 (previously 6/6), and although the swelling appeared to push her left eye “down and to the side” she denied diplopia. Pupils were equal and reactive, and the conjunctiva on the left was mildly injected superonasally. Her eye movements were normal. She had no history of trauma, insect bites, fever, or fatigue. Blood test results were unremarkable.
Her medical history consisted of two right eyebrow cysts removed six years earlier. Family history included a mother with three basal cell carcinomas and a maternal grandmother with chronic lymphocytic leukaemia.
She had no history of alcohol, smoking, or illicit drug use. In the emergency department she was given a second course of systemic antibiotics and scheduled for a follow-up appointment in the ophthalmology clinic nine days later.
In clinic, her visual acuity had drastically decreased to 6/60, the mass had increased in size and felt fluctuant, and her upgaze was now restricted (fig 1⇓).
Questions
1. What differential diagnoses should have been considered at first presentation?
2. What is the most likely diagnosis in this age group?
3. What important investigations are needed?
4. What are the management options?
5. What is the prognosis of this condition?
Answers
1. What differential diagnoses should have been considered at first presentation?
Short answer
An orbital mass carries a wide differential diagnosis, with three main categories: infectious causes, orbital tumours, and inflammatory lesions.
Long answer
Eye “lumps” are poorly understood by non-specialists so important diagnoses can be missed. To be able to instigate proper referral and treatment, all postgraduates must have an understanding of general differential diagnoses of orbital masses (box).
Differential diagnosis of orbital masses
Orbital tumours
Malignant
Rhabdomyosarcomas: Account for 10% of all rhabdomyosarcomas1
Lymphomas: Account for up to half of all primary orbital malignancies. Typically seen in patients aged 50-70 years
Metastases: Tumours that commonly metastasise to the orbit include breast tumours, prostate cancers, neuroblastoma, Ewing’s sarcoma, thyroid carcinoma, renal cell carcinoma, and lymphoma
Benign
Dermoid cysts: Cystic structures lined by stratified squamous epithelium, with epidermal appendages such as hair follicles and sebaceous glands
Capillary haemangiomas: Usually found anterior to the globe in the eyelid and often present in infancy
Lipomas: Rare well circumscribed lesions
Neurofibromas: Soft unencapsulated peripheral sheath tumours that make up 2-4% of orbital tumours. Can undergo malignant transformation
Infections
Bacterial
Abscesses: Associated with sinusitis, superficial infection, bacterial septicaemia, orbital surgery, and penetrating injury
Orbital cellulitis: Inflammation of eye tissues posterior to the orbital septum
Fungal
Aspergillosis: Can cause orbital cellulitis, with poor prognosis. Ocular involvement is often the result of spread from elsewhere
Mucormycosis: Rare fungal infection associated with immunocompromise, poorly controlled diabetes, and poor nutrition
Inflammatory processes
Idiopathic orbital inflammatory syndrome (pseudotumour): Diagnosis of exclusion with no known local or systemic cause. Benign, non-granulomatous orbital inflammatory lesion characterised by extraocular orbital and adnexal inflammation2
Sarcoidosis: Non-caseating granulomatous disease
Infectious causes can be divided into bacterial (abscess or orbital cellulitis), fungal (aspergillosis or mucormycosis), and parasitic (trichinosis or echinococcosis). A travel history is useful.
Benign orbital tumours should be considered, especially when there are no systemic symptoms of cancer. Capillary haemangioma, orbital cyst (for example, dermoid cyst), reactive lymphoid hyperplasia, osteoma, lipoma, and neurofibroma are the main tumours to consider in young people.
Rhabdomyosarcoma is the most common malignant orbital tumour in childhood.3 Other possibilities include metastatic neuroblastoma, lymphoma, and more rarely extraosseous Ewing’s sarcoma.
Inflammatory lesions, such as idiopathic orbital inflammatory syndrome or sarcoidosis, should also form part of the differential diagnosis.
2. What is the most likely diagnosis in this case?
Short answer
The rapid growth of the lesion, superonasal position, and non-response to antibiotics favours the diagnosis of a malignant orbital tumour—the most common primary orbital tumour in children.
Long answer
Although infection is the most likely cause of an orbital mass, in the absence of raised inflammatory markers and a lack of response to antibiotics, a diagnosis of malignancy should be considered early.
Orbital rhabdomyosarcoma is the most common primary orbital cancer in children, accounting for 10% of all rhabdomyosarcomas.1
Rhabdomyosarcoma is a rapidly growing highly malignant tumour that arises from primitive mesenchymal cells committed to development into striated muscle.4 It can appear virtually anywhere in the body. It typically presents between the ages of 0 to 15 years and is slightly more common in males and white people.
Clinical features of orbital rhabdomyosarcoma include ptosis, proptosis, marked chemosis, globe displacement, eyelid swelling, and a palpable mass. The mass is usually painless, although the presence of pain is not an exclusion factor. About 70% of orbital rhabdomyosarcomas have a superior or superonasal location, resulting in downward and lateral displacement of the globe.4 5
3. What important investigations are needed?
Short answer
Computed tomography and magnetic resonance imaging of the orbit and surgical biopsy (not fine needle aspiration), followed by staging investigations—computed tomography of the chest, a bone scan, and bone marrow biopsy. Detailed ophthalmological evaluation is advised.
Long answer
Once the patient has undergone simple ophthalmological evaluation, including fundus examination, cross sectional imaging is the first step. This should provide the most valuable information in any orbital mass that does not respond to antibiotics in which cancer is suspected.
On computed tomography, rhabdomyosarcomas appear as homogeneous soft tissue masses that are isodense to normal muscle (fig 2⇓).6 7 Extension into bone, eyelid, sinuses, or anterior cranial fossa should be investigated.
Fig 2 (A) Horizontal computed tomogram without intravenous contrast of the orbit and (B) coronal view. Both scans show a rounded mass lesion in the medial canthal area, which flattens the medial aspect of the globe. There is no evidence of underlying osseous destruction, erosion, or invasion
Having performed initial cross sectional imaging to identify a likely orbital rhabdomyosarcoma, further studies can be obtained to assess local bone involvement (best seen on computed tomography) and soft tissue disruption (best seen on magnetic resonance imaging).6 7
Diffusion weighted magnetic resonance imaging can be used to describe lesions further, particularly to separate out haemangioma from rhabdomyosarcomas, which can appear similar on T1 and T2 weighted magnetic resonance imaging.8
Detailed ophthalmological evaluation is also advised, given the risk to the eye from the mass effect of the tumour.
Biopsy is crucial, because there are several histological variations, which carry different prognoses.1 The most common paediatric subtypes are embryonal and alveolar, with the embryonal subtype making up 50-70% of such tumours. Embryonal tumours are more common in the orbit, although—regardless of location—the alveolar variant is more common in teenagers.9 Fine needle aspiration should not be used because the tissue yield is usually insufficient.10
Rhabdomyosarcoma is a malignant tumour, so staging should be undertaken. This will require computed tomography of the chest, a technetium bone scan, and bilateral bone marrow aspiration and trephine biopsies.
4. What are the management options?
Short answer
Management takes into account patient age, tumour size, site, histology, and staging of disease. Presurgical staging (TNM—tumour, node, metastasis), open surgical biopsy, and postsurgical staging are the first steps. Chemotherapy is always needed. Radiotherapy can be added on the basis of the response.
Long answer
US and European guidelines for treatment of rhabdomyosarcoma differ. European protocols (for non-metastatic disease) are discussed here.11
Radiological investigations provide a presurgical TNM (clinical) staging. Open surgical biopsy is then undertaken, and postsurgical classification is based on the completeness of excision. Management always requires chemotherapy, and methods of local control (further surgery or radiation) may also be needed. The intensity of chemotherapy, the need for radiation, and the radiation dose depend on the site of disease, tumour size, the patient’s age, and tumour histology. In the United Kingdom, localised orbital rhabdomyosarcomas are eligible for proton therapy.
Extensive surgery is not recommended at diagnosis. If full surgical resection is considered, the functional and cosmetic consequences and the likelihood of residual disease after the procedure must be taken into account.
Patients with favourable TNM, surgical excision, and site are usually treated with vincristine and dactinomycin. Those with unfavourable staging or site may be treated with ifosfamide, vincristine, and dactinomycin or other combinations, including etoposide or carboplatin. The therapeutic efficacy of various regimens is under investigation. Patients who do not respond well to initial chemotherapy are considered for further cycles, with the possible addition of other agents.11
Continued poor response may necessitate local disease control with repeat surgery or radiotherapy. Because radiotherapy has serious adverse effects, such as corneal opacity cataracts, secondary tumours, and neovascular glaucoma, in the UK radiotherapy is avoided whenever possible. Orbital radiotherapy in young children is also associated with appreciable facial asymmetry, which can have adverse psychological effects.12
Alveolar variants are more likely to recur, and patients with this subtype are treated more aggressively. The site of the tumour is also important, with the orbital site being considered favourable.11
It is also important to monitor for recurrence and secondary tumours. This can be achieved with magnetic resonance imaging at three month intervals alongside ocular examination and lung imaging, decreasing in frequency to six monthly and then yearly.10
Future research directions include brachytherapy and wider use of fractionated proton radiotherapy.13 14 Dialogue is ongoing between European and American groups to establish the most effective method of stratifying and managing patients with the minimum of adverse treatment effects.12
5. What is the prognosis of this condition?
Short answer
Five year survival is good (84.3%) in localised orbital disease. Recurrence is seen in about 17% of cases, at a median of 18 months from diagnosis, although it is possible beyond five years.
Long answer
Orbital rhabdomyosarcomas are more likely to be localised (60.6% present this way), embryonal, and chemosensitive, so these tumours have good five year survival rates (84.3%).15 16
The histological subtype of the tumour is also important—patients with alveolar rhabdomyosarcomas have a worse prognosis than those with embryonal ones. Female patients and those under 10 years old also fare better.9 15
Metastasis is less likely with orbital rhabdomyosarcoma, although metastasis to the lung, bone, or bone marrow can occur through the haematogenous route. Recurrence is seen in about 17% of cases, a median of 18 months from diagnosis, although it can occur beyond five years.10 Recurrence can be local as well as metastatic. Recurrence is monitored with magnetic resonance imaging and lung imaging.
Patients require long term ophthalmological follow-up to assess for recurrence of disease and to manage sequelae of treatment.12
Patient outcome
Histological examination of a biopsy showed that the patient had the embryonal subtype of rhabdomyosarcoma. She was treated with the vincristine, dactinomycin, and cyclophosphamide chemotherapy regimen, during which she experienced mucositis, nausea and vomiting, weight loss, and fatigue. She also developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and myelosuppression (which was treated with granulocyte-colony stimulating factor). She required radiotherapy and is currently undergoing ophthalmology follow-up. She has not experienced any recurrence of disease.
Notes
Cite this as: BMJ 2015;350:h799
Footnotes
We would like to thank Sucheta J Vaidya, consultant paediatric oncologist, Royal Marsden Hospital, for her valuable specialist insight into the management of rhabdomyosarcoma.
Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: none.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent obtained.