Primary Pulmonary Alveolar Rhabdomyosarcoma in a Pediatric Patient: A Case Report With Literature Review

Rhabdomyosarcoma (RMS) is a rare soft tissue tumor originating from skeletal muscle that is mostly reported in children. The most common sites of involvement are the head, neck, and extremities. The 2020 WHO classification divide RMS into four types: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing. Reports of RMS with primary lung origin are rare. We present a case of RMS in a 16-month-old boy who presented with a lung mass and microscopic examination with fluorescence in situ hybridization confirmed the diagnosis of alveolar RMS. In conclusion, RMS should be considered in the differential diagnosis of any lung mass with small round blue cell morphology in the microscopic evaluation and should be distinguished from metastatic RMS of other sites, pleuropulmonary blastoma, lymphoma, neuroblastoma, primitive neuroectodermal tumor (PNET)/EWING, and malignant peripheral nerve sheet tumors (MPNST).


Introduction
Rhabdomyosarcoma (RMS) is a malignant soft tissue neoplasm having skeletal muscle differentiation [1]. It is the most commonly occurring tumor in the pediatric age group and has a higher prevalence in males [1,2]. RMS is most frequently found in the head and neck area, followed by the genitourinary tract and extremities [3]. The World Health Organization (WHO) of soft tissue tumors has identified four subtypes: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing [4]. The embryonal type is the most common type in children, with a favorable prognosis compared with other types [5]. Alveolar RMS has a high rate of metastasis and unfavorable prognosis; it is characterized by a chromosomal alteration -a fusion between the FKHR (also known as FOXO1) gene and either the PAX3 or PAX7 gene [6]. RMS rarely originates in the lung and only 32

cm). (B) A longitudinal CT cut shows the extension through the diaphragm.
A pathological examination revealed six cores of lesioned tissue composed of nests of small round blue cell tumors, with some cells having little cytoplasm. The nuclei were round with euchromatin and focal cytoplasmic striation was noted. Necrosis was rare (Figures 2A, 2B). An immunohistochemistry panel was performed to label the following markers: desmin, pan-cytokeratin (CKpan), myogenin, synaptophysin, MyoD1, chromogranin, CD99, and CD45 S100. The tumor cells showed diffuse positivity for desmin, myogenin, MyoD1, and focal positivity for S100. The cells were negative for CD99, CKpan, CD45, chromogranin, and synaptophysin ( Figures 2C, 2D). FISH revealed rearrangement of the FOXO1 gene at 13q14 (FOXO1 [13q14]), which is characteristic of alveolar RMS. Based on the clinical history of no other primary in other sites of body and radiology in addition to microscopic features, immunohistochemistry, and the FISH study, the final diagnosis was primary pulmonary RMS, alveolar type. The patient received chemotherapy and radiotherapy for 10 months, demonstrating improvement at a follow-up imaging study. The patient showed complete remission at oneyear post-treatment follow-up.

Discussion
RMS is a primitive mesenchymal tumor with skeletal muscle differentiation. RMS is common in children and has a poor prognosis. Alveolar RMS has the worst prognosis due to its unique PAX3-FOXO1 fusion gene molecular phenotype [4].
RMS is associated with a congenital cystic adenomatoid malformation (CCAM) but may also occur in a healthy lung. The etiology of primary pulmonary RMS is still unknown, but there are two main hypotheses for its origin: first, the tumor may arise from heterotopic islets of striated muscle, which could explain the frequent association of RMS with pulmonary malformations such as cystic adenomatosis; and second, the tumor may arise from metaplastic changes in uncommitted mesenchymal cells in the absence of congenital abnormalities [3]. Like other lung neoplasms, RMS can present as a cough, respiratory distress, hemoptysis, chest pain, and/or recurrent pneumonitis [7]. Spontaneous pneumothorax has also been reported, especially in RMS cases that grow in the background of CCAM [8].
The main differential diagnosis is pleuropulmonary blastoma, lymphoma, neuroblastoma, primitive neuroectodermal tumor (PNET)/EWING, and malignant peripheral nerve sheet tumors (MPNST). Pleuropulmonary blastoma has blastema, anaplastic and epithelial components that are not present in RMS. The nuclear positivity for MyoD1 and myogenin is specific for RMS among other differential diagnoses.
An extensive search of English research literature (including PubMed, Google Scholar, and OVID) identified 32 cases reported as primary pulmonary RMS in the pediatric age group ( Table 1) . Fallon et al. diagnosed the first pediatric case of primary RMS in 1970 in a six-year-old girl [8]. Among the other cases, the ages of the patients ranged from five months to 16 years old. Nine of the cases developed in a background of CCAM, while the others-including our case-developed in a normal lung. Twenty-five of the cases were embryonal, two were pleomorphic, two were undifferentiated, and one had alveolar morphology. Our case represents the second reported case of alveolar RMS. Most patients received a chemotherapy regimen (vincristine, actinomycin, ifosfamide, and doxorubicin, in combination) according to the Intergroup Rhabdomyosarcoma Study (IRS) V protocol. Chemotherapy was combined with radiotherapy in several cases.

Conclusions
Primary pulmonary RMS is a rare disease that exhibits aggressive behavior. RMS should be included in the differential diagnosis of any lung mass with small round blue cell morphology. Clinical and radiological assessment is necessary to exclude metastatic RMS from other sites. In addition to RMS, other differential diagnoses that should be considered for a lung mass are pleuropulmonary blastoma, lymphoma, neuroblastoma, PNET/EWING, and MPNST.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.