Due to the rarity of PPRMS in the middle-aged and elderly, information regarding its clinicopathological characteristics and prognosis is very limited. The large, multi-institutional trials have not been performed, and only reports from single institutions have been published. More importantly, so far the analyses on clinicopathological characteristics and prognosis of PPRMS in the middle-aged and elderly have not been performed.
RMS occurred in the lung, there was no specificity in clinical manifestation and serum laboratory examination. For our case, we found LDH, NSE and Pro-GRP in his blood were simultaneously elevated, these three markers useful in diagnosis and predicting the prognosis of SCLC[6–8]. Under microscopy, the tumor cells were small, deeply stained with extrusion deformation, which should be distinguished from some small round cell tumors occurred in lung: (1) For SCLC, both serological data, microscopic morphology and immunohistochemical results of neuroendocrine markers were easily misdiagnosed as it in this case, because it was more common than RMS in lung. Moreover, for RMS, immunohistochemical results also partially overlapped with SCLC, since 43% of acinar PPRMS expressed at least one specific neuroendocrine marker, 32% expressed Syn, 22% expressed CgA, 11% expressed both of them, and CD56 was expressed in almost all cases[9]. However, the epithelial markers usually were positive and TTF-1 was positively expressed up to 80-90% in SCLC[10]. (2) For some rare tumors such as soft tissue clear cell sarcoma, extraosseous Ewing sarcoma, non-Hodgkin lymphoma, and malignant melanoma, etc, microscopic morphology resembled acinar RMS, but immunohistochemical markers of those tumors such as HMB45, S-100, CD99, Fli-1, CD20, CD3 and Pax5 were all negative. (3) For secondary tumors, PET-CT showed no other lesions in his whole body.
To better characterize the clinical features and outcomes of PPRMS in the middle-aged and elderly, we searched all PPRMS in the middle-aged and elderly from 1958 to 2021 on PubMed and Elsevier websites and removed the repeated cases in these literatures. We performed an analysis of 36 PPRMS cases which consisted of 35 cases collected from PubMed and Elsevier websites[11–19] and one case in our own hospital (Table. 1). In a total of 36 cases, males were significantly more than females (P = 0.001). The incidence of 50-69 years old was higher than that of 45-49 years old and ≥ 70 years old (P = 0.000); Pleomorphic type was more common than embryonal and acinar type (P = 0.000) (Table. 2). 35 patients received different treatment methods. Among the 34 patients followed up, there was a significant correlation with the prognosis. The survival time of supportive treatment was short and the survival time of surgical resection was significantly prolonged (P = 0.010) (Fig. 3).
We found that there was a significant gender difference and notable age distribution in PPRMS with the middle-aged and elderly, most of them were men and often occurred between the ages of 50-69 years old. Due to the rarity and only some published reports of PPRMS in the middle-aged and elderly, there has been no similar opinion at present. A previous study found the ratio of men to women is 1.5:1 in 76 RMS patients ≥40 years old[5]. A recent study also showed 66 patients with embryonal and alveolar RMS in adults included 42 men and 24 women[20]. A large study analyzed data from RMS with 1,071 adults (age >19 years) and 1,529 children (age ≤19 years) and males were more than females too among both of these adults and children[3]. Some researchers found that male predominance (male/female of 1.5:1) was noticed for almost all types of soft tumor sarcomas and the age range 20–76, 25–71, 18–86, and 55–76 years old for head and neck primaries, genitourinary primaries, limbs, or other primary sites, respectively [21, 22].
There was a significant difference in histological type of PPRMS with the middle-aged and elderly, most of them were diagnosed as pleomorphic type. A large study pointed out that embryonal and alveolar subtype were the most and second common in children/adolescents, while embryonal and pleomorphic subtype other than not otherwise specified (NOS) subtype were the two most common in adults[3]. A previous study on 76 cases of RMS in the middle-aged and elderly also proposed that embryonal and pleomorphic subtype were the two most common[5]. Another present study found for pleomorphic RMS, the incidence was more frequently and the median age of 51 years was older than alveolar and embryonal RMS[22]. Pleomorphic RMS is an aggressive sarcoma, arising predominantly in the extremities of adult males usually 45 of older[23]. Similar with the above studies, PPRMS in the middle-aged and elderly were more males as well as pleomorphic predominant subtype.
The combination of surgery, chemotherapy and / or radiotherapy has achieved good results in children's RMS, and the prognosis of children's rhabdomyosarcoma has been significantly improved. The successful experience in the treatment of RMS in children has been widely used in the treatment of adult RMS (including middle-aged and elderly), but the effect is not good[5]. Polymorphic RMS is less sensitive to chemotherapy, and its treatment depends more on surgery. The unfavorable prognostic factors of RMS are anatomical location such as parameningeal, extremities, abdomen, chest and so on, histological subtypes including acinar and pleomorphic RMS, tumor size > 5cm, as well as metastasis[24]. In this study, although some of patients received surgery, and or chemotherapy, 26 of 36 cases were diagnosed as pleomorphic type and acinar type, and each case was located in lung, the prognosis of PPRMS in the middle-aged and elderly was poor.
Our analyses were not without limitations. First, as most of cases from literatures spanned a long period of time, progress in supplementary examination shifted the diagnosis of RMS from standard morphological detection to incorporate immunohistochemical staining, and now to molecular testing. It is possible that some of cases included in our analyses were not RMS, particularly those with pleomorphic type. Second, not every case had details of clinicopahtological features and prognosis such as tumor size, as a result, some clinicopathological features such as tumor size could not be statistically analyzed.