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02 March 2024: Articles  Indonesia

Right Thigh Mass Metastasis from Lung Cancer Mimicking Primary Soft Tissue Sarcoma: A Case Report

Unusual clinical course, Challenging differential diagnosis

Yuni Artha Prabowo Putro12ABEF*, Thomas Edison Prasetyo32CDEF, Rahadyan Magetsari32DEF, Amri Wicaksono Pribadi24EF, Ery Kus Dwianingsih25EF, Ahmad Faiz Huwaidi2AEF

DOI: 10.12659/AJCR.942416

Am J Case Rep 2024; 25:e942416

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Abstract

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BACKGROUND: Soft tissue metastases (STMs) are less common than bone metastases and sometimes misdiagnosed as primary soft tissue malignancies. Skin, lungs, and breast are the most common primary lesions of STMs and rarely the presenting symptoms. We present an STM from lung adenocarcinoma that became a presenting symptom in nonsmoking woman.

CASE REPORT: A 47-year-old woman presented to our hospital with a painful mass in her right thigh and weight loss of 10 kg for 4 months. Femoral radiograph revealed a lesion suggestive of bone sarcoma. However, magnetic resonance imaging (MRI) showed it was more likely a primary soft tissue sarcoma. A small mediastinal mass was noticed on preoperative chest radiograph, and the patient denied any symptoms except the mass in the right thigh. Our clinicopathological conference team decided to perform a biopsy of mediastinal and right thigh masses. Histopathology examinations confirmed the right thigh mass as soft tissue metastasis from mediastinal mass, confirmed as lung adenocarcinoma. We treated the patient with palliative care with zoledronic acid and gefitinib. At the 6-month follow-up, the patient’s symptoms significantly improved, and MRI showed a marked size reduction.

CONCLUSIONS: Diagnosis of STM can be difficult when presenting as the primary manifestation. Failure to identify promptly can lead to rapid disease progression and unfavorable prognosis. Failure to diagnose primary malignancy during biopsy occurs in approximately 28% of cases. This report has the potential to facilitate the avoidance of unnecessary procedures and highlight the importance of using a multidisciplinary approach in managing cases with malignancy.

Keywords: case reports, lung neoplasms, Neoplasm Metastasis, Soft Tissue Neoplasms

Background

Soft tissue metastases (STMs) are less common than bone metastasis and are often misdiagnosed as primary soft tissue malignancies despite requiring differentiated treatment approaches [1–3]. STMs tend to predominantly occur in the abdomen, scapular region, and limbs, with primary sources often originating from the skin, lungs, and breasts [1].

In lung cancer, it is estimated that approximately 50% of cases have already metastasized at the time of diagnosis, affecting various organs such as the liver, brain, bone, and kidney [4]. STM in carcinoma is uncommon due to an unsuitable environment that suppresses tumor cell proliferation. Skeletal muscle, despite its considerable size and vascularity, is an uncommon site for lung cancer metastasis, partly due to the constant trauma inflicted on tumor cells through muscle mobility, contraction, and the production of lactic acid, free oxygen radicals, and low pH [5,6].

The most typical initial symptom of STM is pain and a palpable mass, frequently coupled with extremity swelling. In most cases, STM develops late, following the diagnosis of the primary malignancy. However, in rare instances, it can manifest around the same time or even before the primary lesion is detected [4,6,7]. Lung cancer metastasizing to soft tissue generally carries a poor prognosis compared with other primary sites, with adenocarcinoma being the most common type among metastasized cases. This study presents a unique case of a giant mass on the right thigh, an STM from lung adenocarcinoma that mimicked a primary malignancy in a nonsmoking woman. The STM became the primary concern, posing a diagnostic challenge. This report also underscores the importance of a multidisciplinary team approach.

Case Report

For 4 months, a 47-year-old nonsmoking woman felt stiffness and pain in her right thigh while walking. She denied any history of trauma or malignancy. She went to a neurologist and was treated with painkillers. Two months later, she reported worsening pain, and a 5-cm palpable mass was found on her right thigh. Ultrasonography screening of the breasts, thyroid, and abdomen revealed no abnormalities or suspected metastases; therefore, she was referred to our center. In our center, she reported severe right thigh pain, low back pain, and weight loss of around 10 kg over the past 4 months. She had controlled type II diabetes mellitus, managed with routine glimepiride for 8 years. A physical examination revealed an inability to bear weight on her right extremity, a visible large mass, and swelling without deformity or sign of inflammation. Lower back tenderness was noted during the spine examination, without neurologic deficits or palpable masses (Figure 1).

A femur radiograph showed cortical erosion with a permeative pattern, a wide zone of transition, and a linear periosteal reaction involving soft tissue (Figure 2). Laboratory examination indicated mild anemia, leukocytosis with relative neutrophilia, thrombophilia, and a significant increase in erythrocyte sedimentation rate and C-reactive protein level. The blood glucose level was 141 mg/dL; therefore, we concluded that the patient’s weight loss was attributable to a malignant process. This determination was grounded in the observation that the patient’s blood sugar levels were within the normal range, and the substantial weight loss aligned with the onset of symptoms in the patient’s right thigh. This finding supported the suspicion of bone sarcoma.

Magnetic resonance imaging (MRI) of the right femoral area showed a pathologic signal that was not spread out evenly. It had solid and cystic parts over the vastus medialis, vastus intermedius, and vastus lateralis muscles. The size of the signal was 9.4×8.5×16.2 cm (Figure 3). This finding raised the suspicion of a primary malignant soft tissue sarcoma of the right femoral region. Other MRI slices showed pathologic lesions in the bilateral iliac bones, suggesting bone metastasis.

A core biopsy confirmed the suspicions by showing pieces of fibrous tissue and muscles, with tumor cells arranged in patterns that looked like hobnails: papillary, tubular, and cribriform. Immunohistochemistry examination of cytokeratin 7, cytokeratin 20, paired box gene 8, and TTF-1 confirmed the metastatic adenocarcinoma likely originated from the lung (Figure 4).

A clinicopathological conference with a multidisciplinary team was conducted, because clinical, radiological, and histopatho-logical findings did not align. It was agreed to investigate the possible primary lesion further with chest workup. A plain chest radiograph, which we had done before as a routine examination before surgery, revealed a well-demarcated, opaque lesion indicative of a mediastinal mass. Therefore, we decided to do a contrast-enhanced computed tomography (CT) scan, which showed a lung mass in the trachea, nodular and subpleural metastases in both lungs, and lytic lesions at the 7th cervical, and 5th, 6th, and 10th thoracic vertebrae (Figure 5).

A CT-guided transthoracic needle aspiration with rapid on-site evaluation confirmed that the main lesion was a soft tissue tumor that had spread from the lung and was consistent with adenocarcinoma. A malignant soft tissue tumor of the right femur region due to metastasis from lung adenocarcinoma was diagnosed (Figure 6). After the clinicopathological conference, palliative care was chosen. A non-surgical approach was initiated, combining zoledronic acid and targeted therapy (gefitinib).

The patient received chemotherapy. After 6 months of therapy, she reported no pain during rest, even without analgesics.

The visual analog scale score decreased from 6–7 to 1–2. The patient gained around 10 kg but remained unable to walk. During follow-ups and therapies, no chest symptoms developed. Examination of the thigh revealed reduced swelling and a soft, smooth mass with an unclear margin, measuring around 15×12×3 cm. MRI showed a significant reduction in the lesion, mainly in the vastus medius (Figure 7). Nine months after therapy, the pulmonary lesion showed a partial response (Figure 8).

Discussion

The lung is the most common site for developing malignancies, maintaining its status as the primary cause of cancer-related deaths. Lung carcinoma is frequently identified in its metastatic stage (IV) in approximately 50% of patients, with metastasis occurring through lymphatic or vascular routes. Studies indicate that spreading via blood vessels can occur earlier for distant metastases. Surgical resection of lung carcinoma has revealed that vascular invasion is common in early-stage tumors. Certain sites, such as the brain, bones, and adrenal glands, are more prone to lung cancer metastasis, especially in the case of lung adenocarcinoma, which often spreads to the brain and soft tissues [3,8].

STM from the lung involves skeletal muscle, subcutaneous tissue, and skin. Regarding the epidemiology of metastatic carcinomas, autopsies have shown that less than 9% of patients die from STM. This percentage is even lower for lung cancer metastasizing to muscle (0–0.8%) and skin (1.3–4%). STM in lung cancer is considered a grave prognostic indicator, with a median survival of less than 6 months, even with chemotherapy [9]. In a review by Pop et al, among 16 such patients, the 5-year survival rate was 11.5%, with a median survival duration of 6 months [10].

The mechanism of metastasis to soft tissue can occur hematogenously or lymphatically. Theories posit that muscle contractions, which increase pressure in the tissues around them and fluctuate local blood flow, prevent tumor cells from implanting, accounting for STM’s rarity. Other limiting factors include specific homeostatic conditions that suppress tumor cell proliferation, constant trauma to cells due to muscle contraction, lactic acid production by skeletal muscle, and high tumor cell permeability [5,9,11].

Pop et al presented a total of 130 cases of skeletal muscle metastases from non-small cell lung cancer (NSCLC; 16 of which were their own cases, and 114 were from available literature). Pain and a palpable mass were the most prevalent symptoms, at 83% and 78%, respectively. The size of the mass varied considerably between 1 and 20 cm, with a median of 6 cm. Combined survival rates were low, with 1-year and 5-year rates of 32.6% and 11.5%, respectively. Age, sex, presenting symptoms, site and size of metastasis, histology, and tumor/node/metastasis staging of the carcinoma did not significantly influence survival. Significantly higher survival rates were found in patients with a single site of metastasis vs multiple (13.6% vs 0% at 5 years) and an interval between diagnosis of NSCLC and STM >6 months vs ≤6 months (16.9% vs 9.1% at 5 years) [10].

Imaging, histopathological, and immunohistochemical examinations are crucial for diagnosing and managing STM, and are typically performed after the detection of the primary tumor. However, STM can be identified through incidental findings on CT as symptomless disease or even as the primary concern. The most common appearance on the CT scan is a rim-enhancing mass with central hypoattenuation. MRI is the most sensitive and specific imaging modality, allowing assessment of tissue characteristics, tumor extent, and areas of reactivity. Ilag et al conducted retrospective studies of image-guided soft tissue biopsies, either after ultrasound or CT scan, and found that image-guided biopsy had a high diagnostic yield. They also observed a significant predilection of lesions in the trunk and intramuscular areas. STM is challenging to diagnose when it is the initial cancer manifestation, and when missed or neglected, it can rapidly progress. Detection of STM can alter patient management, workup, and prognosis. Studies have shown as many as 28% of patients did not have a known primary malignancy at the time of biopsy. The findings made it possible to avoid more invasive procedures, and many shifted to chemotherapy, immunotherapy, and/or radiotherapy [12–14].

Given the unusual nature of metastasis to soft tissue and its poor prognosis, and recognizing that early detection could impact management, there is a crucial need for thorough physical examination and diagnostic workup. Early detection can lead to better survival and quality of life. Signs such as the rapid growth of skin nodules, weight loss, and a history of chronic smoking are crucial in the clinical setting [4]. The strength of this study lies in implementing the clinicopathological conference to resolve the rare case. Without the clinicopathological conference, the correct diagnosis could have been significantly delayed, and the patient may have been treated ineffectively. One limitation of this study is the short duration, and a longer follow-up study may be necessary to draw more valid conclusions.

Conclusions

STM as the initial symptom is uncommon, but surgeons should be cautious because STM can mimic primary cancers. As a result, STM must be included in the differential diagnosis. Surgery is not always the first line of intervention. A clinicopathological conference is critical in assuring quick and correct diagnosis and proper patient treatment to improve the patient’s quality of life and survival. A clinicopathological conference should be incorporated into the tumor diagnosis and care procedure on a consistent basis.

Figures

A clinical picture of the right leg. The clinical picture shows a large mass on the right femoral region that felt elastic hard, smooth, and immobile, and measuring 23×20×2.0 cmFigure 1.. A clinical picture of the right leg. The clinical picture shows a large mass on the right femoral region that felt elastic hard, smooth, and immobile, and measuring 23×20×2.0 cm Plain radiograph of femur dextra in anterior-posterior and lateral projection. Radiograph of the right femur revealed a lytic lesion with a permeative pattern and wide zone of transition. A periosteal reaction was also noted, with soft tissue involvement, suggestive of bone sarcoma.Figure 2.. Plain radiograph of femur dextra in anterior-posterior and lateral projection. Radiograph of the right femur revealed a lytic lesion with a permeative pattern and wide zone of transition. A periosteal reaction was also noted, with soft tissue involvement, suggestive of bone sarcoma. Magnetic resonance imaging (MRI) of the right femur. (A) MRI of the right femur sagittal view shows an inhomogeneous pathologic signal with cystic solid components from vastus medialis, vastus intermedius, and vastus lateralis muscle with the size of 9.41×8.52×16.21 cm. The solid component gave an isohypohyperintense signal at T1 and T2. (B) MRI of the right femur in transverse view.Figure 3.. Magnetic resonance imaging (MRI) of the right femur. (A) MRI of the right femur sagittal view shows an inhomogeneous pathologic signal with cystic solid components from vastus medialis, vastus intermedius, and vastus lateralis muscle with the size of 9.41×8.52×16.21 cm. The solid component gave an isohypohyperintense signal at T1 and T2. (B) MRI of the right femur in transverse view. Histopathology results of the right femoral biopsy show metastatic adenocarcinoma. (A) Papillary form. (B) Tumor cells with variable size, lack of cytoplasm, with vacuoles. (C) Immunohistochemistry (IHC) staining showed positive result, with TTF 1. (D) IHC staining showed positive result, with cytokeratin 7. (E) IHC staining showed negative result, with thyroglobulin.Figure 4.. Histopathology results of the right femoral biopsy show metastatic adenocarcinoma. (A) Papillary form. (B) Tumor cells with variable size, lack of cytoplasm, with vacuoles. (C) Immunohistochemistry (IHC) staining showed positive result, with TTF 1. (D) IHC staining showed positive result, with cytokeratin 7. (E) IHC staining showed negative result, with thyroglobulin. Chest radiograph of the patient. (A) Chest radiograph, with opaque lesion indicative of a mediastinal mass (outlined by red line). (B) Chest computed tomography scan showed infiltration of the trachea (red dashed line).Figure 5.. Chest radiograph of the patient. (A) Chest radiograph, with opaque lesion indicative of a mediastinal mass (outlined by red line). (B) Chest computed tomography scan showed infiltration of the trachea (red dashed line). Result of needle aspiration shows polymorphic tumor cells of middle size, lack of cytoplasm, some vacuolized, with oval nuclei irregular membranes and hyperchromatic, consistent with adenocarcinoma of lung origin.Figure 6.. Result of needle aspiration shows polymorphic tumor cells of middle size, lack of cytoplasm, some vacuolized, with oval nuclei irregular membranes and hyperchromatic, consistent with adenocarcinoma of lung origin. Magnetic resonance imaging of the right femur 6 months after therapy shows significantly reduced lesion (around 59%), mainly on vastus medius.Figure 7.. Magnetic resonance imaging of the right femur 6 months after therapy shows significantly reduced lesion (around 59%), mainly on vastus medius. Thorax computed tomography scan 9 months after therapy shows the pulmonary lesion showed partial response to the therapy.Figure 8.. Thorax computed tomography scan 9 months after therapy shows the pulmonary lesion showed partial response to the therapy.

References:

1.. Plaza JA, Perez-Montiel D, Mayerson J, Metastases to soft tissue: A review of 118 cases over a 30-year period: Cancer, 2008; 112; 193-203

2.. Torigoe T, Terakado A, Suehara Y, Metastatic soft tissue tumors: J Cancer Ther, 2011; 2; 746-51

3.. Perisano C, Spinelli MS, Graci C, Soft tissue metastases in lung cancer: A review of the literature: Eur Rev Med Pharmacol Sci, 2012; 16(14); 1908-14

4.. Baldeo C, Ali R, Seeram V, Lung cancer presenting as a soft-tissue metastasis: Case Rep Oncol, 2015; 8; 185

5.. Tsuchie H, Emori M, Miyakoshi N, Prognostic factors in patients with distant soft tissue metastasis of carcinoma: A clinicopathological study of 16 cases: Med Princ Pract, 2020; 29; 538-43

6.. Sariaydin M, Gunay E, Ulasli S, An unusual metastasis of lung adeno-carcinoma: Biceps brachii muscle: Lung India, 2016; 33; 669

7.. Wang B, Chen LJ, Wang XY, A Clinical model of bone angiosarcoma patients: A population- based analysis of epidemiology, prognosis, and treatment: Orthop Surg, 2020; 12; 3551-62

8.. Popper HH, Progression and metastasis of lung cancer: Cancer Metastasis Rev, 2016; 35; 75

9.. Lalchandani A, Shukla Y, Parwez MM, Carcinoma lung presenting with skeletal muscle metastasis: Case report with review of literature: Surg J (N Y), 2021; 7; e121-23

10.. Pop D, Nadeemy AS, Venissac N, Skeletal muscle metastasis from non-small cell lung cancer: J Thorac Oncol, 2009; 4; 1236-41

11.. Hashimoto K, Nishimura S, Akagi M, Lung adenocarcinoma presenting as a soft tissue metastasis to the shoulder: A case report: Medicina (Kaunas), 2021; 57; 1-5

12.. Wang J, Wu R, Liu F, Case report: Lung adenocarcinoma initially presenting with cutaneous and subcutaneous metastases: Front Oncol, 2022; 12; 3551

13.. Pretorius ES, Fishman EK, Helical CT of skeletal muscle metastases from primary carcinomas: Am J Roentgenol, 2000; 174; 401-4

14.. Ilag M, Burke C, Walter WR, Imaging features and biopsy yield of soft tissue metastatic lesions: 10-year single tertiary center experience: Skeletal Radiol, 2023; 52; 705-14

Figures

Figure 1.. A clinical picture of the right leg. The clinical picture shows a large mass on the right femoral region that felt elastic hard, smooth, and immobile, and measuring 23×20×2.0 cmFigure 2.. Plain radiograph of femur dextra in anterior-posterior and lateral projection. Radiograph of the right femur revealed a lytic lesion with a permeative pattern and wide zone of transition. A periosteal reaction was also noted, with soft tissue involvement, suggestive of bone sarcoma.Figure 3.. Magnetic resonance imaging (MRI) of the right femur. (A) MRI of the right femur sagittal view shows an inhomogeneous pathologic signal with cystic solid components from vastus medialis, vastus intermedius, and vastus lateralis muscle with the size of 9.41×8.52×16.21 cm. The solid component gave an isohypohyperintense signal at T1 and T2. (B) MRI of the right femur in transverse view.Figure 4.. Histopathology results of the right femoral biopsy show metastatic adenocarcinoma. (A) Papillary form. (B) Tumor cells with variable size, lack of cytoplasm, with vacuoles. (C) Immunohistochemistry (IHC) staining showed positive result, with TTF 1. (D) IHC staining showed positive result, with cytokeratin 7. (E) IHC staining showed negative result, with thyroglobulin.Figure 5.. Chest radiograph of the patient. (A) Chest radiograph, with opaque lesion indicative of a mediastinal mass (outlined by red line). (B) Chest computed tomography scan showed infiltration of the trachea (red dashed line).Figure 6.. Result of needle aspiration shows polymorphic tumor cells of middle size, lack of cytoplasm, some vacuolized, with oval nuclei irregular membranes and hyperchromatic, consistent with adenocarcinoma of lung origin.Figure 7.. Magnetic resonance imaging of the right femur 6 months after therapy shows significantly reduced lesion (around 59%), mainly on vastus medius.Figure 8.. Thorax computed tomography scan 9 months after therapy shows the pulmonary lesion showed partial response to the therapy.

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923