Primary Pulmonary Leiomyosarcoma: An Extremely Rare, Difficult-to-Manage Case of Lung Cancer

Background: Primary Pulmonary Leiomyosarcoma (PPL) known as <0.5% of total lung cancer. Histopathological examinations are the pillars of PPL diagnosis as clinical manifestations and radiological features are usually not specific. Treatments of PPL include surgical resection, radiotherapy, and chemotherapy. Case Illustration: A 51-year-old male, smoker, with a productive cough for 2 weeks, accompanied by chest pain, weight loss, and loss of appetite. Imaging studies showed a solid mass in the right lung, which was confirmed through bronchoscopy, cytology, histology, and immunohistochemistry evaluations. Bronchoscopy showed an intraluminal mass in the right main bronchus suggesting malignancy. Immunohistochemistry of Desmin and Smooth Muscle Actin, which were positive, confirmed the diagnosis of PPL of the right lung stage T4N1M1a IVA. Discussion: Surgical resection is the gold standard treatment for PPL whose clinical conditions and tumor spread still allowed for safe operation. Surgical resection did not undergo because already in stage IVA. Radiotherapy and chemotherapy can be added for patients who are unable to have surgery. There are no guidelines regarding chemotherapeutic regimens that are recommended for PPL. Cisplatin/carboplatin and etoposide are two chemotherapeutic agents that are commonly used in other variants of lung cancer. Cisplatin is successful in 5-23% of patients and etoposide is successful in 8%. Doxorubicin and ifosfamide are


Introduction
Primary pulmonary sarcomas (PPS) is a mesenchymal type of tumor that usually rare neoplasm that accounts for <10% of all soft tissue sarcomas.Most of primary pulmonary sarcomas are leiomyosarcomas, followed by fibrosarcomas and hemangiopericytomas.The prevalence of primary pulmonary leiomyosarcoma (PPL)   has been reported to be less than 0,5% of all lung malignancies.Primary pulmonary leiomyosarcoma (PPL) may arises from interstitial smooth muscle cells of the lung, bronchi, and vessels.This type of tumor most commonly affects individuals over 50 years of age, with the median age of 51 years.Men have 2-fold higher risk of developing PPL than women.
[3][4][5] We report a case of pulmonary leiomyosarcoma in a 51-year-old male with the chief complaint of cough in the past 2 weeks before admission.This report will discuss how pulmonary leiomyosarcoma is being treated using Carboplatin/Etoposide chemotherapy based on the existing literatures.

Case
A 51-year-old male was admitted to our department with cough and whitish sputum for the past 2 weeks.These symptoms T4N1M1a (Figure 2).The patient also underwent bronchoscopy that showed a white intraluminal mass in the right main bronchus suggesting malignancy (Figure 3).
(Progressive disease) and a non-target lesion on the right lung segment 10 nodule with a size of 5mm and a segment 3 left lung nodule with a size of 9.4mm (stable disease).No new lesions were found.Overall Response: Progressive disease.
Our patient was planned to receive the combination of chemotherapy carboplatin 350 mg and etoposide 180 mg for 6 cycles.or pulmonary arteries (10%).Pulmonary sarcomas are extremely rare, accounting for less than 10% of all soft tissue sarcomas. 1,2,5st of PPS are leiomyosarcomas, followed by fibrosarcomas and hemangiopericytomas. 4 Until 2006, there were only 300 cases of PPS that had been reported in the literature.
This includes 0.2-0.5% of all primary lung malignancies. 2,4The prevalence of PPL was reported to be less than 0.5% of all types of lung cancer. 1,2This type of tumor mostly occurs in the age over 50 years, with the median age of 51 years.Men are reported to have 2-fold higher risk to develop PPL than women. 3,4,6This is in concordance with our case where the patient was a 51 years old male.
According to its location, PPL can be classified into intraluminal (endobronchial), intrapulmonary, or pulmonary vascular.
Intrapulmonary is the most common subtype, while endobronchial is less commonly found.
To date, there are only 14 patients aged over 20 years which have been diagnosed with endobronchial primary pulmonary leiomyosarcoma. 3,4,6Primary pulmonary leiomyosarcoma (PPL) is a very aggressive tumor that has the capability to grow and to cause symptoms promptly. 3Around 25% of PPS patients show manifestation of lymph node metastasis. 5oking is a risk factor for lung cancer, where 1 of 9 heavy smokers are reported to develop lung cancer. 7In contrast, smoking is rarely found as a risk factor in PPL patients.Less than 50% of PPL patients had a history of being a heavy smoker.The risk factors associated with PPL are similar to those of other sarcomas, such as history of radiation, chemical, occupational and environmental exposure. 5,8The patient in our case had a history of smoking for 15 years with the Brinkman index of 150.
Patients with PPL often represent with mild and non-specific respiratory symptoms, and may even remain asymptomatic for a long time.Surgery is the most common treatment approach in PPL, especially in cases with no evidence of metastasis. 1,3,4,18rgery is considered as the only curative therapy option, with lobectomy as the gold standard therapy in PPL. 5,6Wedge resections may be performed if the tumor is small and peripherally located, although this approach has shown a higher local recurrence rate.
Meanwhile, pneumectomy was reported to cause high morbidity.This approach can still be performed if needed to achieve a better local control. 5Lobectomy and pneumectomy that is performed in early disease was reported to produce a 5-year survival rate of >50%.Complete resection of the entire tumor mass is recommended if the patient can tolerate.Complete surgical excision results in a higher median survival (17-24 months) compared to incomplete surgical excision (6-10 months). 3Only one-third of PPL patients can undergo surgery because the tumor is often found at an advanced stage. 16Partial resection of the chest wall, diaphragm, or vascular structures is also necessary in some cases to achieve R0 resection. 6,8diotherapy can be performed if the patient has contraindications to surgery or cannot undergo a complete resection.
However, radiotherapy is not associated with an increased survival in patients with PPL. 4,8stoperative adjuvant radiotherapy can be performed to improve locoregional tumor control, especially for patients with known regional lymph node metastases. 5Therefore, radiotherapy is only a palliative treatment approach. 6oadjuvant chemotherapy is used for patients with unresectable tumors and lymph node metastases to achieve better operability and local control. 5 In general, the prognosis of PPL is still poor. 1 In a cohort study with 60.4% of patients undergoing treatment and 14.1% undergoing radiotherapy, the median overall survival was reported to be 14 months, with 1-, 3-, and 5-year overall survival are 52.7%,29.0% , and 22.2% respectively.Surgery has shown to increase the overall survival by 29 months and reduce risk of death by 57%. 8,18ctors that may reduce overall survival in PPL patients include age, tumor size (>5 cm), presence of lymph node metastases, tumor TNM stage, and higher histological grade.In addition, the prognosis was reported to be worse in endobronchial tumors or tumors that show a high mitotic rate. 5,6Compared with soft tissue sarcomas of the extremities, PPL has a poorer prognosis with a higher proportion of lymph node metastases. 5This case is interesting because primary pulmonary leiomyosarcoma is a type of lung cancer that is very rarely found and reported.

Conclusion
Management of primary pulmonary leiomyosarcoma is challenging because the prevalence of this cancer is rare and there are no guidelines in the management approach.
Surgery, radiotherapy and chemotherapy are the treatment approach that have been used in patients with primary pulmonary leiomyosarcoma in some literatures.
However, there are still no recommendation regarding the type of chemotherapeutic agent that should be used in primary pulmonary leiomyosarcoma.

Consent
Written informed consent was obtained from the patient for publication of this case report.
were accompanied with right chest pain which occurred only when the patient coughed.The patient also complaint decreased of appetite and weight loss for the last 3 months.An uncontrollable cough drove the patient to seek for medical treatment in the local hospital.A nodule appearance showed up from the chest radiography examination.The patient then was referred to our hospital.Patient had a history of smoking for 15 years with 10 cigarettes per day (Brinkman index : 150).There was no history of lung cancer in the family.The patient worked as a fish seller.The patient had stable vital signs with normal findings on the lung examination.Other physical examinations revealed unremarkable results.Initial laboratory tests showed mild hypokalemia (potassium 3.41 mmol/L, reference range 3.5 -5.0 mmol/L), azotemia (creatinine 1.68 mg/dL, reference range < 1.2 mg/dL), and increased neuron specific enolase (NSE, 57.29 ng/mL, reference range < 16.3 ng/mL).Chest radiography revealed a lung nodule on the anterior segment of the right lobe (Figure 1).Chest computed tomography (CT) with contrast showed right endobronchial mass of the posterior segment in anterior superior lobe that attached to the branch of right pulmonary artery.Chest CT also revealed bilateral lung nodule in accordance with

Figure 1 .
Figure 1.Chest radiograph PA and lateral view showing right lung nodule.

Figure 2 .
Figure 2. Chest computed tomography (CT) with contrast before treatment showed an endobronchial mass at posterior segment of the right lung, anterior superior lobe, difficult to separate from the right perihilar lymph nodes, attached to the branch of right pulmonary artery, obliterating the 3 rd segment bronchial tree with partial atelectasis of 3 rd segment, bilateral lung nodules according to T4N1M1a.RECIST 1.1 (baseline) found target lesions: right lung mass measuring 51mm and non-target lesions: right lung segment 3 nodule measuring 6.6mm and left lung nodule segment 9 measuring 7.2mm.

Figure 3 .
Figure 3. Bronchoscopy suggesting malignancy of the right main bronchus During bronchoscopy, we performed washing and brushing for the histopathological analysis.The result was class III, with atypic cell focus.Biopsy results showed spindle mesenchymal tumor focus, with the differential diagnosis of leiomyosarcoma, malignant peripheral nerve sheath tumor, and carcinoma with sarcomatous appearance.Immunohistochemical (IHC) staining demonstrated positivity toward smooth muscle actin (SMA) (Figure 4) and desmin (Figure 5), which showed an immunophenotype indicating a leiomyosarcoma.This confirmed the diagnosis of PPL of the right lung stage T4N1M1a IVA.

Figure 4 .
Figure 4. Smooth muscle actin IHC staining showed fibrous connective tissue with spindleshaped atypical cells with oval, pleomorphic,

Figure 6 .
Figure 6.Serial chest radiograph during chemotherapy.(1) Chest radiograph PA/lateral January 10 th 2022 showed right hilar thickening with ground glass opacity in superior lobe of the right lung suspected right lung nodule with a component of right lung superior lobe atelectasis.(2) Chest radiograph PA/lateral January 25 th 2022 showed thickening of right hilar, suggesting right lung mass, with atelectasis of the superior and medium lobes of right lung.(3) Chest radiograph PA/lateral March 9 th 2022 showed a central stenoting right lung mass and bilateral lung nodule because of the metastatic process.

Figure 7 .
Figure 7. Chest CT with contrast after chemotherapy showed an endobronchial mass in the posterior segment of the right lung, anterior to the superior lobe, which completely obliterated the right main bronchus, causing atelectasis of the superior lobe of the right lung.Bilateral pulmonary nodules suspected the metastatic process.RECIST 1.1 found a target lesion on the right lung mass measuring 78mm

The chemotherapy cycle was 21
days.In every chemotherapy cycle, we performed a laboratory examination and dose adjustment based on toxicity degree.The patient also underwent chest radiography (Figure 6) and chest CT with contrast (Figure 7) to evaluate response toward chemotherapy.Due to the results from chest CT with contrast showed a progressive disease according to Recist 1.1, we discontinued the chemotherapy regimen of carboplatin/etoposide after the fourth cycle and replaced with a second line regimen of Docetaxel 120 mg every 21 days.After the administration of first cycle of Docetaxel, the patient decided to receive the best supportive care.The patient still survives until now.Discussion Primary pulmonary leiomyosarcoma (PPL) is a tumor that originates from the interstitial smooth muscle cells of the lungs, bronchi or blood vessels.Primary pulmonary sarcomas (PPS) are mesenchymal-type tumors that usually arise from the lung parenchyma (70%), bronchial walls (20%), negative results were shown in epithelial staining such as cytokeratin and S-100.

A
51-year-old man came with chief complaint of productive cough for the last 2 weeks.The symptom was also accompanied by chest pain, weight loss and decreased appetite.Radiological examination revealed a tumor mass in the right lung.Histopathological and immunohistochemical examination confirmed the presence of a tumor mass consistent with the diagnosis of PPL T4N1M1a Stage IVA.The patient is currently receiving supportive management.