SMARCA4-UT is different from traditional lung cancer. There was controversy about whether it represented a true sarcoma and the 2021 WHO classification of thoracic tumors classified SMARCA4-UT as undifferentiated carcinoma within epithelioid tumors[9]. A review of the literature found that it is most commonly seen in young to middle-aged adults, ranging in age from 27 to 90 years, with a mean age of 58 years [10]. Patients were strongly associated with smoking and were predominantly male, and our cases fit these demographic characteristics. SMARCA4-UT is an aggressive tumor with a poor prognosis, often metastasizing to the lymph nodes, adrenal glands, brain, and so on [11–12].
The patient's symptoms are one of the most interesting aspects of this case and an important diagnostic challenge in the early stages. In general, because SMARCA4-UT lesions originate in the chest, patients may come to the hospital with thoracic-related symptoms such as chest pain, dyspnea, and cough, or sometimes they may only incidentally discover chest lesions through an examination without any discomfort themselves. Our search for the cause of this symptom is more of a logical inference. Four common clinical causes of fever and polyarthralgia are infection, rheumatic disease, hematologic disease, and cancer. Comprehensive molecular testing helped to rule out most rheumatic conditions, and the patient did not have a response to antibiotics, Bacterial and viral tests were negative, and a bone marrow aspirate revealed no abnormalities. We then proceeded to exclude infectious and hematologic lesions. Bacterial and fungal tests of the surgically removed tissue also showed no abnormalities ultimately, we concluded that the tumor was the primary cause of her symptoms, which was supported by her hormone sensitivity, Imaging findings, continued improvement in symptoms after treatment, and rapid reduction in inflammatory markers. Cancer is one of the most common causes of fever of unknown origin and joint inflammation. According to statistics, up to 30% of patients with malignant tumors have unexplained fever and polyarthralgia. This type of symptom may result from paraneoplastic syndrome because of elevated blood concentrations of interleukin-6, tumor necrosis factor-α, and interleukin-1[13]. Few cases of SMARCA4-UT with fever and polyarthralgia as initial symptoms have been reported in the present study. Nambirajan A previously reported a patient with chronic empyema who underwent thoracotomy due to dyspnea and fever. SMARCA4-UT was detected by postoperative histopathology, and no pathogenic microorganisms were detected by pleural effusion culture [14].
Histologically, SMARCA4-UT in the chest showed a solid, flaky growth pattern with prominent necrosis, rhabdoid nuclei, and abundant eosinophilic cytoplasm. Some may be epithelioid. The vast majority of cases lack evidence of cellular differentiation, but 5% of cases present poorly and highly differentiated non-small cell lung cancer .The immunophenotype of SMARCA4-UT was most typically BRG1-negative but weakly positive in 25% of cases. INI-1 was usually positive. CD34, SOX2, and SALL4 were positive in most cases. P53 is usually overexpressed. Syn may also be markedly positive, and CK is usually focally positive. A few cases were focally positive for TTF-1, p63, or p40[15]. The histology and immunophenotype of this case were mostly consistent with that described in previous literature, so it could represent a typical pathological and immunological feature of SMARCA4-UT.
SMARCA4-UT usually presents as a large mass with an ill-defined boundary, uneven density, and even necrosis, without obvious cystic degeneration or calcification. They involve the mediastinum, hilum, lung, pleura, etc, by invasive compression or even spread the lesion to more distant tissues by infiltration. Tumors are most commonly found in the mediastinum, followed by pleura and lung tissues, which is consistent with our case. PET-CT scan showed increased FDG uptake, and the background was emphysema caused by smoking. The SUVmax of the mediastinal lymph node lesion, in this case, was 9.5, which was consistent with the SUVmax range [16.6 ± 8.2 (9.1–33.8)] reported in the literature [6]. Some tumors with undifferentiated rhabdoid morphology can also show high metabolic activity, which easily causes misdiagnosis in the clinic. However, SMARCA4-UT is less likely to encase blood vessels than lymphoma. Germ cell tumors and thymic carcinomas are generally more likely to have calcified and cystic components. Solitary fibrous tumors (SFTs) have large peritumoral and intratumoral vessels, but a low SUVmax. Thymic carcinoma and small-cell lung cancer can cause specific paraneoplastic syndromes. In summary, the diagnosis of SMARCA4-UT needs to be based on imaging findings, pathology, and clinical data[16].
At present, there is no consensus on the treatment of SMARCA4-UT. The basic regimen is anthracycline-based chemotherapy, but the clinical effect is not ideal. It has been reported that the current immune checkpoint inhibitors represented by PD-1 have produced encouraging results in preclinical studies, but they are only limited to patients with some immune subtypes [17–19]. The patient received postoperative adjuvant chemotherapy after the postsurgical workup confirmed the absence of residual tumor. The patient's symptoms continued to improve after the first chemotherapy, and no adverse events occurred. Unfortunately, because of the loss of follow-up, we could not track the prognosis of the patient.
Although this case stands out with a rare disease type and atypical symptoms, there is always a limit to the power of a single case. Due to the limited understanding of this disease, the description in the pathological report is not detailed enough, and the explanation of the treatment decision also lacks professionalism. Finally, we were unable to follow up on subsequent visits.
In conclusion, SMARCA4-UT is an outstanding example of multidisciplinary collaboration in the diagnosis of rare tumors. Young and middle-aged men with a long history of heavy smoking are susceptible to SMARCA4-UT. In this case, we hope that clinicians will be aware of such atypical symptoms in the diagnosis and differential diagnosis of tumors, and not only in the diagnosis of SMARCA4-UT. Although the final diagnosis depends on pathological examination, the role of imaging, especially 18F-FDG PET/CT, in the diagnosis and evaluation of SMARCA4-UT cannot be ignored. Finally, the treatment of SMARCA4-UT may require more reliable clinical trials, including ICI therapy.