The initial database search resulted in 2,081 articles. After removing duplications, 1,623 articles remained. After reading the titles and abstracts, we assessed 33 articles. A flowchart describing the study selection phase is shown in Fig. 1.

The three selected studies were observational; published in English in 1986⁶, 2015³, and 2018⁴; and conducted in Germany, Japan, and India, respectively. A total of 380 patients was included in the meta-analysis study. The mean age of the patients was 13 years 6 months, and 67.4% (256 patients) of the patients were male. Of the included patients, 159 were diagnosed with embryonal type, 141 were diagnosed with alveolar type, 71 were diagnosed with spindle cell/sclerosing type, and 9 were diagnosed with pleomorphic type. Diagnoses were based on histopathology and immunohistochemistry in all included studies. Treatment protocols consisted of chemotherapy and radiotherapy, which were usually administered in combination with surgery. The follow-up period was at least 25 months in all studies. The mean survival rate was greater than 50%^3,4,6. Detailed information and data on follow-up, relapse, mean survival, and outcomes are shown in Table 1.

All studies achieved at least 15 points on the STROBE checklist, which indicates that they are good studies.(Table 2)

Schmidt et al.⁶ suggested division of embryonic RMS into three subtypes of primitive with predominantly undifferentiated cells (<10% rhabdomyoblasts), intermediate with 10%-50% rhabdomyoblasts, and well-differentiated with more than 50% rhabdomyoblasts. The study did not show any significant differences between subtypes, although they did show different body locations of origin. The primitive and intermediate subtypes occurred predominantly in the head and neck regions, while the well-differentiated subtype was most commonly recurrence at other sites. Expression of vimentin and desmin was positive in all three subtypes, with vimentin being the most significant in the primitive embryonic rhabdomyosarcoma subtype. Myoglobin expression was positive only in the well-differentiated embryonic rhabdomyosarcoma subtype. In addition, the primitive and intermediate embryonic rhabdomyosarcoma subtypes were usually diagnosed earlier than the well-differentiated type. At the time of diagnosis, intermediate embryonic rhabdomyosarcoma presents a better response to chemotherapy compared to the well-differentiated subtype.

Yasui et al.³ presented 16 cases of embryonic spindle/sclerosing cell RMS and 10 cases of primary tumors in the head and neck region. Regarding immunohistochemistry, the study showed that expression of focal myogenin (10%) and diffuse MYOD1 (>50%), associated with the discrete presence of desmin, can confirm diagnosis. The results suggest that fusiform/sclerosing RMS in pediatric patients has a worse prognosis than embryonic RMS since more than half of these tumors experience local or distant recurrence. The data obtained were not subjected to statistical analysis because of the small sample size.

Rekhi et al.⁴ performed a study involving 300 patients diagnosed with RMS. Regarding location, 42% occurred in the head and neck region, with a higher frequency of alveolar RMS. Among patients younger than 20 years, the embryonic type was most frequent. The study established a correlation between inhibition of markers, such as desmin, myogenin, and MYOD1, and RMS subtype. Myogenin expression is strongly related to the alveolar type. The expression of MYOD1 correlated with the predominance of spindle/sclerosing cell type. Tumor sizes smaller than 5 cm and absence of metastasis significantly contributed to longer disease-free and overall survival.

The total number of subjects observed in the selected studies was 380, of which 256 were male (67.4%) and 124 were female (32.6%), with a male/female ratio of 2:1^3,4,6. These values are comparable with those observed individually in each study included in this review, as reported by Lyos et al.⁹. The mean age of included patients was 13 years 6 months^3,4,6. This is different from other studies, possibly because approximately 21% of cases reported in the included studies were sclerosing and pleomorphic RMS variants with a greater prevalence in adults¹⁰.

Among the types of RMS, embryonic was the most prevalent, comprising 159 diagnosed cases (41.8%). Alveolar type was the second most common, with 141 cases (37.1%), followed by 71 cases of sclerosing RMS (18.7%) and 9 cases of pleomorphic RMS (2.4%)^3,4,6.

For location, soft tissues were most commonly affected, observed in 170 cases (44.7%). Sixty-three cases (16.6%) involved the extremities, while the head and neck region was affected in 157 cases (41.3%)^3,4,6. These values are proportional to those observed by Dillon et al.¹¹ and Radzikowska et al.¹².

Tumors can be identified by computed tomography or magnetic resonance imaging, and diagnoses can be confirmed by biopsy of altered and healthy cells. Immunohistochemistry is useful in determining the subtypes of RMS and choosing treatment^3,4,6,13. Embryonic and alveolar RMS were the two main histological subtypes observed^3,4,13.

Markers of desmin, myogenin, and MYOD1 expression may be viable indicators of tumor subtype. In the study by Rekhi et al.⁴, desmin had a positive expression greater than 90% (292/299), myogenin was observed in >70%, and MYOD1 in 65.3% of myoglobin. MYOD1 is the most indicated marker for reliable diagnosis in cases of sclerotic and spindle cell RMS^3,4. However, use of myogenin alone can lead to misdiagnosis, as its expression also can be related to alveolar RMS, which was reported in 72.3% (34/47) of cases in the study by Rekhi et al.⁴.

Schmidt et al.⁶ proposed the establishment of embryonic RMS subtypes based on the correlation between presence and predominance of rhabdomyoblasts. However, the results presented did not show significant differences based on this criterion. The presence and proportion of these cells in immunohistochemical studies showed no correlation with clinicopathological features³.

The head and neck region is the most common anatomical site for sclerosing and fusiform RMS. MYOD1 mutations have been reported in 3 of the 13 investigated cases of sclerosing-type RMS¹⁴. Another study identified the MYOD1 mutation in 30 cases of sclerosing and/or spindle cell RMS in patients aged 2-94 years, including 15 children¹⁵.

The sclerosing type of RMS is commonly diagnosed at an advanced stage because of its primary site (or extremities) and tumor size at initial diagnosis³. Alveolar RMS also showed a significant correlation with metastasis¹⁶, and patients with tumors <5 cm and those free from metastasis had better overall survival and disease-free survival⁴.

Surgery has demonstrated that local metastasis is a possibility, albeit rarely³. When possible, the suggested treatment involves complete tumor resection in addition to adjuvant therapy (chemotherapy and radiotherapy) to reduce the chances of local and distant metastases^3,4. When the MYOD1 mutation is present, 83% of pediatric patients died from the disease, even with multimodal treatment¹⁵.