Brain metastasis in soft-tissue sarcoma is an uncommon event. It usually follows lung metastasis, with a lag period between the occurrences of the two events. We present such a case of soft-tissue sarcoma with lung and brain metastases, with the intention of drawing attention toward this rare occurrence and need of anticipation of brain metastasis in patients who are asymptomatic for the same and have already developed lung metastasis.

Introduction

Brain metastasis is a relatively uncommon occurrence in the natural history of soft-tissue sarcoma, accounting for 1–6% of total patients, and usually follows lung metastasis.[1],[2],[3] Among different histological subtypes, it is more frequently seen in leiomyosarcoma, rhabdomyosarcoma, and malignant fibrous histiocytoma.[1] The purpose of this case report is to increase the index of suspicion and a more vigilant workup to detect brain metastasis in these patients and an early intervention to improve the outcome of therapy and overall survival.

Case Report

A 31-year-old male with a cystic swelling of the second toe of left foot was operated in October 2013 in rural setup and was sent to our department for further management with a histopathological report which was suggestive of malignancy. Slide review and immunohistochemistry reports confirmed the diagnosis of epithelioid sarcoma of large cell type

(vimentin strongly positive, S-100 focal positive and negative for P63, HMB45, CD20, CD30, CD34, desmin, and epithelial membrane antigen). Abdominal and pelvic ultrasonography and chest X-ray studies were normal. However, computed tomography (CT) scan of thorax revealed multiple lung metastases [Figure 1]. Imaging for brain metastasis was not performed at that time due to the absence of any sign or symptom of central nervous system (CNS) involvement. In view of the metastatic status, six cycles of ifosfamide with doxorubicin were planned. He defaulted the treatment after three cycles only and was lost to follow-up. He returned 6 months later when a fresh CT scan of thorax showed that the lung metastases have partially responded to the therapy and, thus, chemotherapy was resumed. During the fourth cycle of chemotherapy, the patient had an episode of convulsions. CT scan of brain was suggestive of brain metastasis [Figure 2]. He was treated with palliative whole-brain radiotherapy (30 Gy in 10 fractions) with parallel opposed fields on a 6 MV linear accelerator. The patient showed progressive disease at the end of chemotherapy and was advised best supportive care.{Figure 1}{Figure 2}

Discussion

In soft-tissue sarcoma, metastasis to brain is an unusual occurrence and mostly follows secondary in the lung with a considerable lag period (average 49.5 weeks).[1],[2] The incidence of brain metastasis is estimated to be <1–6% by various authors.[2],[3],[4] The increased incidence of brain metastasis in soft-tissue sarcomas in these later studies may be attributed to the prolonged survival achieved by successful systemic chemotherapy and the poor penetration of the blood–brain barrier by these agents.[5] This predisposes the brain to secondary while the patient lives with the benefits of chemotherapy. Higher probability of brain metastasis is associated with leiomyosarcoma, liposarcoma, malignant fibrous histiocytoma, and rhabdomyosarcoma of the extremities.[2] Furthermore, the histological grade is considered an independent risk factor for the development of lung and brain metastases.[6] It is imperative to be more vigilant in patients with these histological subtypes and grades, and these groups should be screened for lung metastasis as soon as the diagnosis is confirmed by histopathology. These patients should also be screened for brain metastasis at the first appearance of signs and symptoms of CNS involvement or 6–8 months (lag period) after the appearance of lung metastasis, whichever is the earliest. The management options of a case with brain metastasis are metastasectomy, palliative whole-brain radiotherapy, or gamma knife surgery.[7] On postmetastasectomy, survival benefit of 7–8 months has been shown in case series.[2] A good performance score and parenchymal metastasis are candidates for surgical resection while the presence of lung metastasis is not a contraindication for cranial surgery.[8] Leptomeningeal metastases, which are three times less frequent than parenchymal metastases, are not amenable to surgical resection.[2] For these cases, gamma knife surgery is another option. For patients who are not suitable candidates for craniotomy or gamma knife surgery, whole-brain radiation therapy is a commonly used modality of palliation. Therapy in soft-tissue sarcoma with brain metastasis increases the medial survival to 4–6 months from that of 1–2 months in case of untreated patients.[9] Considering the long lag period between the appearance of lung and brain metastases, prophylactic chemotherapy using BCNU, CCNU, MeCCNU, or prophylactic cranial irradiation could be an interesting approach to prevent CNS involvement.[1] Pazopanib, a multitargeted tyrosine kinase inhibitor, has shown to be effective in increasing progression-free survival in metastatic disease after failure of standard chemotherapy.[10] However, the overall outcome is poor even with the best intervention.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.