Primary Conjunctival Embryonal Rhabdomyosarcoma in an 8-Year-Old Girl

Abstract

Introduction

Rhabdomyosarcoma is a rare paediatric cancer, with the head and neck region representing a major anatomical site for rhabdomyosarcoma. In particular, orbital rhabdomyosarcoma is the most common region among children. However, rhabdomyosarcoma originating from the conjunctiva in paediatric population is a rare disease, and this knowledge is essential in order to ensure prompt treatment and early intervention.

Case Presentation

We discuss a rare case of primary conjunctival rhabdomyosarcoma in an 8-year-old Caucasian girl. She presented to a paediatric ophthalmology clinic with a 5-day history of a rapidly growing conjunctival lesion in the superior fornix of the right eye. An urgent excisional biopsy was performed which yielded a large 30-mm multilobulated, vascular, and papillomatous specimen with histopathological features consistent with embryonal rhabdomyosarcoma. She was urgently referred to oncology and was treated with systemic chemotherapy.

Conclusion

Therapeutical options and prognosis of rhabdomyosarcomas are based on clinical findings, tumour staging, and grouping, combined with histopathological and molecular features. Although rare, it is important to note that in the paediatric population, rhabdomyosarcoma can originate from the conjunctiva. Knowledge of its clinical, histopathological, and imaging characteristics is essential in order to achieve early diagnosis and timely treatment.

Introduction

Rhabdomyosarcoma is a rare cancer of childhood that has received significant attention in the literature. Rhabdomyosarcoma can occur in any soft tissue but is primarily found in the head, neck, orbit, genitourinary tract, and extremities [1, 2]. In particular, the orbit is a major anatomical location for rhabdomyosarcoma [1, 2]. Orbital rhabdomyosarcoma accounts for about 25–35% of head and neck rhabdomyosarcomas and for about 10–20% of all rhabdomyosarcomas [1–3]. In cases of orbital rhabdomyosarcoma, the involvement of conjunctival tissue is rare and accounts for only 12% of these cases [3]. Furthermore, rhabdomyosarcoma appears to be more common in males with a roughly 5:3 male-female ratio [3]. However, primary conjunctival rhabdomyosarcomas are very rare, particularly in a female child, with only few cases reported in the literature [1–10]. In this case report, we describe a unique case of primary conjunctival embryonal rhabdomyosarcoma, with no orbital extension in a young Caucasian girl.

In 2020, the WHO classification system identified 4 different histological subtypes of rhabdomyosarcoma: embryonal, alveolar, undifferentiated, and spindle-cell/sclerosing subtypes [2]. A study looking at 264 orbital rhabdomyosarcoma cases showed 84% of cases classifying as embryonal subtype, 9% as alveolar, and 4% as undifferentiated [1]. Moreover, the embryonal subtype has a more favourable prognosis in terms of 10-year survival rates [9].

There are various factors that are considered to guide risk stratification and prognosis for rhabdomyosarcoma. This includes clinical findings and histological characteristics [2], and more specifically, molecular data indicating the presence of the PAX3/FOX01 gene have proven highly effective in rhabdomyosarcoma risk stratification [2]. Rhabdomyosarcoma is a life-threatening disease, and early recognition with prompt treatment leads to best outcomes.

Case Report

We present a case of an 8-year-old Caucasian girl referred to the Pediatric Ophthalmology Clinic for a 5-day history of a rapidly growing conjunctival mass of the right eye (OD). On initial presentation, the uncorrected visual acuity was 6/15 bilaterally with normal intraocular pressures and pupillary examination. On motility assessment, there was a −1 abduction deficit of the affected eye (OD) with no significant proptosis noted using an exophthalmometer. However, the OD revealed fullness of the upper eyelid with approximately 3-mm blepharoptosis without eyelid erythema or tenderness (shown in Fig. 1). On eyelid eversion, there was a large 30-mm × 10-mm × 4-mm multilobulated, vascularised, and papillomatous lesion arising within the superior conjunctival fornix and some parts of the bulbar conjunctiva (shown in Fig. 1, 2). The remainder of the anterior and posterior segment examination was unremarkable. The left eye (OS) was also examined to be normal. The differential diagnoses based on the clinical findings included pyogenic granuloma, papilloma, lymphoma, and rhabdomyosarcoma.

Fig. 1.

Large vascularised papillomatous lesion arising within the superior conjunctival fornix and some parts of the bulbar conjunctiva with approximately 3-mm blepharoptosis without eyelid erythema or tenderness.

Fig. 2.

A 30-mm × 10-mm × 4-mm multilobulated, vascularised, papillomatous lesion excised from the superior conjunctival fornix.

An urgent subtotal excision of the lesion was performed in the theatre, and histopathological assessment was conducted. This demonstrated an infiltrate of mitotically active spindled cells positive for desmin, myoD1, and myogenin, therefore highly suggestive of rhabdomyosarcoma (shown in Fig. 3). The fluorescent in situ hybridisation assay demonstrated no rearrangement of the FOX01 gene consistent with the embryonal variant of rhabdomyosarcoma.

Fig. 3.

Demonstrating an infiltrate of mitotically active spindled cells positive for desmin (left), myoD1 (middle), and myogenin (right), highly suggestive of rhabdomyosarcoma.

Following the diagnosis, a systemic staging process was conducted including CT chest, MRI brain, orbits, and spine in addition to a PET scan. This revealed stage 1, group 2 disease with no evidence of metastatic disease. The patient was treated with vincristine, actinomycin, cyclophosphamide, as per protocol ARST0331. Six months post treatment, the patient remains tumour-free with no ocular complications.

Discussion

The major anatomical location for rhabdomyosarcoma is the head and neck, and 25–30% of the tumours originating in this anatomical area appear in the orbit [2]. Moreover, rhabdomyosarcoma is the most common cancer of the orbit within the paediatric population, representing approximately 5% of all paediatric tumours [1, 2]. Nevertheless, its origin from the conjunctiva is rare with only a few cases reported in the literature, primarily of young boys [1–10].

A study conducted by Meza et al. [11] demonstrated that rhabdomyosarcoma can be divided in to 4 stages prior to the onset of treatment based on anatomical origin and the presence of metastasis. They identified stage I as disease involving the head or neck and biliary or genitourinary tract (excluding the bladder or prostate); stage II as disease involving the bladder, prostate, extremities, or cranial parameningeal involvement without nodal spread; stage III as disease involving all anatomical regions mentioned in stage II but with nodal involvement; and finally, stage IV as the presence of metastasis [11].

There are 4 different histopathological subtypes of rhabdomyosarcoma with the most common subtype and the one with more favourable prognosis being embryonal followed by alveolar, spindle-cell/sclerosing, and undifferentiated [2]. Once surgical excision and histopathological assessment are completed, Meza et al. [11] demonstrated that patients can be classified into 4 groups based on amount of residual tumour tissue post-operatively: group I being no residual tissue, group II being the presence of microscopic residual tissue, group III being the presence of macroscopic residual tissue, and group IV being the presence of metastasis.

Based on this information, our patient exhibited stage I, group II rhabdomyosarcoma. An important molecular feature regarding the presence of the PAX3/FOXO1 fusion gene was negative in our patient. Considering these features, the estimated 5-year overall survival rate is 97%.

Over the years, the prognosis for rhabdomyosarcoma has significantly improved with a >90% survival rate [2, 3]. This is based on a combination of therapies including surgical excision, chemotherapy, and radiotherapy [2, 3]. Our case emphasises the importance of a careful histopathological review of all conjunctival masses in children in order to achieve timely diagnosis and treatment.

Conclusion

This case report describes an 8-year-old girl with a right rapidly growing papillomatous conjunctival lesion which was diagnosed with primary embryonal rhabdomyosarcoma. The patient was treated with radical therapy, and there was no evidence of disease or ocular complications at her 6-month follow-up visit.

Although rare, it is essential to know that in the paediatric population, rhabdomyosarcoma can originate from the conjunctiva. Knowledge of its clinical, histological, molecular, and imaging characteristics is essential in order to achieve early diagnosis and prompt treatment. Additionally, it is essential to propose a multidisciplinary approach for treatment where the risks and benefits of the different therapies/interventions are evaluated.

The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000536382).

Statement of Ethics

Written informed consent was obtained from the parents for publication of this case report and any accompanying images. Ethical approval is not required for this study in accordance with local or national guidelines.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

The first author S.B. contributed to data collection, data analysis and interpretation, drafting of the article, conception/design of the work, and critical revision of the article. Additionally, the second author M.B. contributed to data analysis and interpretation and final approval of the version to be published. Both authors S.B. and M.B. declare that the contributions to the paper fulfil the ICMJE Criteria for Authorship.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analysed during this study are included in this article and its supplementary material files. Further enquiries can be directed to the corresponding author.