INTRODUCTION
Rhabdomyosarcoma (RMS), constitute a distinctive group of malignant tumours that share a tendency to undergo myogenesis (Parham et al. 2006). It is recognized as childhood and young adolescent malignancy. RMS is most frequently encountered soft tissue sarcoma in infant and children (Vankalakunti et al. 2006). It occurs in any sites of anatomical location where there is skeletal muscle differentiation present (Chu 2013). The vast majority of RMS occurs in head and neck region, extremities, genitourinary system and trunk. RMS bears variable histological pattern including poorly differentiated tumours that are very difficult to diagnose without the help of immunohistochemical or molecular study. RMS have distinct clinical, pathologic and molecular differences which varies in clinical outcome and approach to therapy. The most prevalent subtype is embryonal rhabdomyosarcoma (ERMS) accounting for about 60% of RMS cases. It occurs mainly in children younger than 10 years associated with a favourable prognosis (Marshall et al. 2012). The alveolar subtype (ARMS) constitutes another 20% of RMS cases and occurs predominantly in adolescents (Marshall et al. 2012). ARMS are more aggressive with poorer prognosis.
CASE REPORT
A 2-month-old girl presented with history of reduced left hand movement and progressive swelling of left neck region for two weeks associated with partial ptosis of the left eye. Physical examination revealed a hard and lobulated mass at the left neck measuring 10 x 5 cm (Figure 1). There was presence of left Horner syndrome and lower motor neuron symptoms of the left upper limb. An urgent magnetic resonance image (MRI) of the neck and thorax showed a soft tissue mass at the left neck which was homogenous and multilobulated, extending from C2 to T5 vertebral body. Multiple enlarged lymph nodes at the left axillary region were detected. The mass showed intraspinal extension and spinal cord compression, thus raising the possibility of a neurogenic or malignant nerve sheath tumour.
Histopathological examination of the biopsy of the mass revealed a primitive, small round cell tumour with no rhabdoid differentiation (Figure 2A). Based on the tumour morphology, the differential diagnoses include rhabdomyosarcoma, lymphoma, neuroblastoma and epithelial tumour. The tumour cells were positive for desmin with focal and weak nuclear positivity for myogenin and MyoD1 (Figure 2B & 2C). S100, chromogranin, neuron-specific enolase (NSE), synaptophysin, vimentin, pan-cytokeratin and leucocyte common antigen (LCA) were negative. Ki67 proliferative index was high (90%). The immunohistochemical studies were in favour of rhabdomyosarcoma. Further confirmation by fluorescent in situ hybridization (FISH) showed presence of translocation t(2;13)(q35;q14), thus supporting the diagnosis of alveolar rhabdomyosarcoma (Figure 2D).
The patient's condition rapidly deteriorated and had to be ventilated. Chemotherapy MT95 protocol (Strategy 953 (ARM B)) was commenced consisting of intravenous fosfamide, vincristine and actinomycin D. Unfortunately, the patient developed severe neutropenic sepsis and succumbed from septic shock.
DISCUSSION
The presenting signs and symptoms of RMS are variable and depending on the sites of origin of the primary tumour (Dagher & Helman 1999). The common sites include the head and neck, gastrointestinal, urinary tracts and the extremities (Parham et al. 2006). Head and neck RMS can arise from the orbit, parameningeal sites, scalp, parotid glands, oral cavity, pharynx, thyroid, parathyroid glands and neck region. There are two distinct types of RMS, namely the embryonal and the alveolar subtypes. The diagnosis of ARMS is considered when the histopathologic examination of the tumor tissue shows undifferentiated small round blue tumor cells lining up the spaces reminiscent of pulmonary alveoli. RMS may display cross-striation which is characteristic of skeletal or rhabdomyoblast differentiation (Dagher & Helman 1999). Ancillary studies that include a panel of immunohistochemical staining need to be carried out in diagnosing RMS (Parham et al. 2006). Muscle specific protein markers such as alpha-actin, myogenin, myosin, desmin, myoglobin, Z-band protein and Myo-D are very useful (Dagher & Helman 1999). In difficult cases, additional molecular study is important to confirm the diagnosis and subtypes of RMS. The majority of ARMS tumours carry a characteristic chromosomal translocations of t(2;13) (q35;q14) (Marshall et al. 2012). This chromosomal translocations produce an oncogenic (PAX3-FOX01) fusion protein and can be detected in 55% of ARMS cases. Another 22% of ARMS cases exhibit translocation of t(1;13)(p36;q14) with characteristic (PAX7-FOX01) fusion oncogene proteins (Marshall et al. 2012).
In cases of small round blue cell tumors of the head and neck, several differential diagnoses need to be considered, which include Ewing sarcoma/PNET, neuroblastoma and lymphoma (Reshma et al. 2013). Ewing sarcoma is group of highly malignant small round cells characterized by monotonous round blue cell tumour. It is common in children and young adult. Immunohistochemistry studies will show tumour cells positivity for CD99 and FLI-1expression. Cytogenetic studies exhibit EWSR-ETS fusions. It involves the EWS gene which also known as EWSR1 located on chromosome 22 and a member of ETS family including FLI1 and ERG (Pinto et al. 2011).
Neuroblastoma of head and neck is the second most common tumour after rhabdomyosarcoma. It can manifest as extracranial soft tissue tumour in infant less than 12 months (Sameer et al. 2017). The tumor originates from primitive neuroectodermal cells derived from neural crest cells. Histologically, it exhibits small round cells with features of neural or ganglionic cells depending on maturation and differentiation. Immunohistochemical studies show positivity for neuron specific enolase, synaptophysin and chromogranin (Reshma et al. 2013). Common lymphoma in paediatric patients include lymphoblastic lymphoma and Burkitt lymphoma and the immunohistochemistry studies performed, shows positivity for lymphoid markers. Thus, immunohistochemistry is very crucial in diagnosis of small round blue cell tumors to help reach to the specific diagnosis. Failure to give a specific diagnosis leads to different treatment modalities.
As seen in the current case, alveolar rhabdomyosarcoma behaves aggressively. It is prone to metastasis and carries poor prognosis. Management of RMS requires multimodality therapeutic approach including surgery, chemotherapy and radiotherapy (El Nadi et al. 2013). Many authors agree that management of infant less than one year should be a tailored therapeutic approach. The prognosis of RMS depends on the grade of the tumour, age, type of resection, histology, translocation and number of sites with metastases (Eguía-Aguilar et al. 2016). The prognosis is less favourable due to the physiologic immaturity of many organ systems in infants (Pinto et al. 2003).
CONCLUSION
Rhabdomyosarcoma is a highly aggressive mesenchymal neoplasm which may present with diagnostic difficulty. Correlation with clinical, radiological and histopathological examination along with immunohistochemical and molecular study are crucial for accurate diagnosis and appropriate chemotherapy.