Malignant Rhabdoid Tumor of the Mediastinum: A Case Report and Literature Review.

Malignant rhabdoid tumor (MRT) of the mediastinum is an aggressive tumor that is extremely rare. To date, only 24 cases of the mediastinal MRT have been reported in adults and 9 cases in the pediatric age group under the age of 18 years. We report a rare case of such tumor and review the literature on its clinical and imaging features as well as its treatment and prognostic outcomes.

INTRODUCTION

The rhabdoid tumor (RT) was originally described by Beckwith and Palmer in 1978.[1] It is one of the most aggressive childhood neoplasms associated with high mortality, commonly arising in kidneys of young children before the age of 1 year.[2] The most common site of tumor outside the kidney is the central nervous system, which are called the atypical teratoid/rhabdoid tumors is (AT/RT).[3,4] Other extrarenal malignant RTs (MRTs) are relatively rare and have been described in locations such as the head and neck region, thorax and mediastinum, liver, ileum, adrenal gland, spine, genitourinary tract, retroperitoneum, trunk, and extremities.[5-21] They occur predominantly in the pediatric population. Here, we describe a case of MRT of the anterior mediastinum in a young adult.

CASE REPORT

A 35-year-old male patient presented to the accident and emergency department with worsening central chest pain for 1 day. He experienced chest pain that was not related to exertion for 1 month, associated with night sweats. There was no history of fever, palpitations, or weight loss. He was a chronic smoker and had a history of childhood asthma. On admission, the patient was in respiratory distress, however, was hemodynamically stable.

The initial chest radiograph [Figure 1] revealed a large soft-tissue opacity over the medial aspect of the left upper zone. In view of the clinical possibility of acute aortic dissection, urgent computed tomography (CT) angiography was performed. CT showed no evidence of dissection or an aneurysm in the thoracic aorta. There was, however, a lobulated heterogeneously enhancing soft-tissue mass seen in the anterior mediastinum, partially encasing the aortic arch, almost completely encasing the left common carotid artery and fully encasing the left subclavian artery [Figure 2]. No calcifications or fat densities were noted within the mass. The mass displaced the left upper lobe pulmonary artery laterally. No thrombus was seen within the pulmonary artery. This mass also displaced the trachea and esophagus to the right [Figure 2b and c]. Blood tests including tumor markers were all unremarkable. Radiological differential diagnoses of anterior mediastinal mass including lymphoma, germ cell tumor, and invasive thymoma were made. Subsequently, an 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan was performed, showing the anterior mediastinal mass to be hypermetabolic with maximum standardized uptake values measuring 19.8 [Figure 3a]. A hypermetabolic left cervical lymph node metastasis was also detected [Figure 3b].

Figure 1

Chest X-ray revealed a large soft-tissue opacity over the medial aspect of the left upper zone.

Figure 2

Sagittal (a), coronal (b), and axial (c) computed tomography images showed a lobulated heterogeneously enhancing soft-tissue mass in the anterior mediastinum in the left upper hemithorax, partially encasing the arch of the aorta, almost completely encasing the left common carotid artery and fully encasing the left subclavian artery. This mass also displaced the trachea and esophagus to the right. No calcification or fat densities were noted within the mass.

Figure 3

Pre- (a and b) and post-chemotherapy (c and d) positron emission tomography/computed tomography images of the mediastinal mass and left cervical lymph node metastasis, showing persistent high grade 18 F-fluorodeoxyglucose uptake of the tumor mass, as well as multiple new hypermetabolic bilateral cervical, supraclavicular and mediastinal lymph nodes metastases, suggestive of disease progression.

The mediastinal tumor was considered unresectable since it encased the aorta and its branches. The patient underwent video-assisted thoracoscopic surgery and biopsy of the mediastinal mass was taken. Histopathological examination [Figure 4] revealed sheets of tumor cells composed of large, eccentric nuclei with abundant eosinophilic cytoplasmic inclusion. The evidence of tumor necrosis was noted. On immunohistochemistry, the tumor cells showed strong and diffuse staining for CD34, and negative for MNF 116, synaptophysin, leukocyte common antigen, and desmin. The tumor cells also showed a lack of INI-1 protein expression. The final diagnosis of an extra-renal MRT was made.

Figure 4

Pathological examination: (a) hematoxylin and eosin stained section revealed tumor cells arranged in sheets and were large, round to oval with eccentric nuclei and deep eosinophilic cytoplasm concordant with rhabdoid morphology. The tumor cells also demonstrated malignant cytological features of pleomorphic hyperchromatic nuclei and brisk mitosis. (b) Similar features were demonstrated in the cytological imprint of H and E section. (c) On immunohistochemistry, the tumor cells showed loss of INI-1 immunostaining; the stained cells were normal cells mixed within blood vessels or inflammatory cells.

The patient was started on chemotherapy with vincristine, dactinomycin, and cyclophosphamide. After completion of one course of chemotherapy, follow-up PET/CT scan showed persistent avid FDG uptake of the tumor mass as well as multiple new hypermetabolic bilateral cervical, supraclavicular, and mediastinal lymph nodes and new pleural metastases [Figure 3c and d], suggestive of disease progression. The patient’s condition deteriorated despite aggressive chemotherapy, and he succumbed 4 months after diagnosis.

DISCUSSION

RT was originally described in the kidneys by Beckwith and Palmer and was thought to be a sarcomatous variant of classical renal Wilms tumor.[1] Later, it was regarded as a separate clinicopathological entity.[22] MRT of the mediastinum are rare; to the best of our knowledge, only 33 cases have been reported in the literature [Table 1].[6,12-18,23-25] The previously available literature is mainly case reports and small series of 1–3 patients, except for the retrospective review by Sauter et al.,[24] which included 18 patients with mediastinal RT. However, in their review, detailed information was only available for the seven patients with BRG1 (SMARCA4)-deficient tumors, which is a distinct subset of the tumor with undifferentiated rhabdoid morphology that shows aggressive behavior and poor prognosis.

Table 1

Summary of reported cases of mediastinal rhabdoid tumor.

Author	n	Age (years)	Sex	Clinical findings	Imaging features	Treatment	Metastasis/local invasion	Clinical outcome
Gururangan et al., 1993[12]	1	13	Female	Chest pain, Horner syndrome	NR	B, C	Lungs	DOD, 12 months
Parham et al., 1994[17]	3	0.8-13	Male=3	NR	NR	NR	Posterior auricular region	DOD=1, 7 years NR=2
Perlman et al., 1998[18]	1	Newborn	Male	Hydrops and respiratory distress	Pericardial effusion and cardiac compression, mass encasing great vessels focally involved the right atrial free wall	C	NR	DOD, 2 months
Falconieri et al., 2005[13]	2	40 and 46	Male=2	Chest pain, fever, vomiting, joint pain, prostration	Mass	B, C, R=1 S, C, R=1	NR	DOD=1, 8 months AWD=1, ? duration
Garcés-Iñigo et al., 2009[6]	3	0.4-0.8	Male=3	Chest wall mass	CT: Heterogeneous enhancement MRI: T1W hypointense, T2W heterogeneous hyperintense, Gd: Heterogeneous enhancement US: Heterogeneous mass	NR	Skull	DOD, 4-62 months
Oh KJ et al., 2009[15]Report in Korean language	1	35	Female	Cough, loss of weight, loss of appetite, generalized weakness	Mass	B, C, R	Supraclavicular LN, muscles, ribs	DOD, 3 months
Thomson et al., 2011[14]	2	7.5 and 26	Male=1 Female=1	NR	NR	FNA, B=1 FNA=1	Infraumbilical, back	DOD, 3 and 9 months
Le Loarer et al., 2015[25]	1	48	Male	NR	NR	NR	NR	DOD, 7 months
Kuwamoto et al., 2017[23]	1	30s	Female	Chest pain	Slight enhancing compressive mass on CT marked FDG uptake on PET	B, C	Left axillary LN	NR
Farber et al., 2017[16]	1	3.9	Male	NR	NR	B, C	Lung	DOD, 10 months
Sauter et al., 2017[24]	18[^]	44-69	Male=5 Female=2	Dyspnea, weight loss, fatigue, reflux, chest pain, metastatic bony pain	Mass, encasing major vessels, trachea and bronchus, severe midline shift, jugular vein thrombosis, lymphadenopathy, echogenic area in pericardium, PET avid	B, C=2 S, C=3 S, C, R=1 NA=1	Brain, bone, lungs, axilla	DOD=6, 1-4 months NR=1
Ng et al.,* 2018	1	35	Male	Chest pain, night sweat, respiratory distress	Lobulated enhancing mass, encasing major vessels, displaces trachea and esophagus, PET avid	B, S, C	Cervical and mediastinal LN, pleural metastasis	DOD, 4 months

Seven patients with BRG1-deficient tumors and 11 patients with BRG1-retained tumors. Information was only available for the seven patients with BRG1-deficient tumors,

Present case. NR: Not reported, S: Surgery, R: Radiation therapy, C: Chemotherapy, FNA: Fine-needle aspiration, B: Biopsy only, LN: Lymph nodes, DOD: Died of disease, CT: Computed tomography, PET: Positron emission tomography, FDG: 18F-fluorodeoxyglucose, MRI: Magnetic resonance imaging, US: Ultrasonography, AWD: Alive with disease, ? duration: unsure of duration

Bimodal age distribution of the mediastinal MRT is observed in our review, having the first peak during childhood and the second peak between the 4th and 5th decades. It is more common in male patients, as observed in 16 out of 22 of the patients in this review [Table 1].[6,12-18,23-25] Indeed, for the pediatric patients <10-year-old, all were male patients.[6,14,16-18]

Mediastinal MRT usually presents with chest pain, dyspnea, cough, and respiratory distress,[12,13,15,18,23,24] which are nonspecific but are likely due to the mass effect of the tumor. However, some patients also had constitutional symptoms such as fever, loss of weight, loss of appetite, joint pain, and generalized weakness.[13,15,24] Our patient experienced chest pain and respiratory distress with the constitutional symptom of night sweats.

Radiologically, MRT of the mediastinum usually shows large masses with heterogeneous contrast enhancement on CT and magnetic resonance imaging,[6,18,23,24] similar to MRT in other locations.[2,7,26] They cause compressive mass effects to the heart and other mediastinal structures and can cause severe midline shift.[18,23,24] However, unique to the mediastinal compartment, these tumors may demonstrate infiltrative features encasing the great vessels, trachea, and bronchus.[18,24] One of the cases reported by Sauter et al.,[24] showed left jugular vein thrombosis. These tumors are hypermetabolic on 18 F-FDG PET/CT scan. Our patient demonstrated both compressive and infiltrative features, showing displacement of the trachea and esophagus as well as encasement of the great vessels and PET/CT avid.

The discovery of a solid anterior mediastinal mass usually raises the suspicion of a lymphoma, germ cell tumor or invasive thymoma. It may be very difficult to differentiate one from the other radiologically. The definitive diagnosis can only be made on histopathological examination. Although imaging features of MRT of the mediastinum are not specific, radiologists should include MRT in the differential diagnosis when dealing with aggressive anterior mediastinal masses with both compressive and infiltrative features, especially in children and young adults.

Microscopic analysis of RTs usually reveals the presence of eosinophilic cytoplasmic inclusions and large vesicular nuclei as well as prominent nucleoli.[6] Immunohistochemically, they show positivity for vimentin and often for keratin and epithelial membrane antigen, but generally not for skeletal muscle markers or S-100 protein.[6] Molecular analysis reveals mutation or alteration in the SMARB1/INI gene in most RTs, which results in loss of INI-1 expression.[6] Thus, lack of INI-1 protein expression on immunostaining seen in our patient, together with the morphological features on histology lead us to the diagnosis of MRT.

Due to its rarity, no standard or consistently effective chemotherapy or radiotherapy regimen for mediastinal MRT has been established. Mediastinal MRT usually presents at an advanced stage and is rendered unresectable. For renal and gluteal MRT, a few cases with the successful outcome of surgery and chemotherapy have been reported.[27-29] However, to date, only a few studies have been published featuring the efficacy of different treatment modalities for extracranial MRT.[8,10,12,16] The beneficial role of radiotherapy in MRT have been reported in a few studies.[16,30] However, its delivery is often limited by a young age at presentation. Although the outcomes are generally poor, Venkatramani et al. suggested treatment with high dose alkylator therapy followed by consolidation with high-dose chemotherapy and autologous bone marrow transplant for patients in radiographic remission. This appears to have a beneficial effect on survival.[10] Most patients in our review underwent chemotherapy[12,13,15,16,18,23,24] with some undergoing adjuvant radiotherapy.[13,15,24] A few new targeted strategies have been suggested to treat MRT, and the results seem promising.[31-33]

The prognosis of patients with MRT is generally very poor, and the clinical course is extremely aggressive. In a series of 100 children diagnosed with extracranial MRT from 2005 to 2014, 3-year overall survival was only 38.4%.[8] In a single-institution series of 14 cases of extracranial MRT diagnosed over a 20-year period, the median time to progression was only 2 months.[9] Similarly, a dismal outcome for mediastinal MRT was seen in our review in which the available data showed 17 out of 18 patients died of the disease on follow-up. Our patient showed disease progression despite chemotherapy and died of the disease 4 months after diagnosis.

CONCLUSION

Mediastinal MRT is a rare tumor with aggressive features and a grave prognosis. Although no specific imaging features were found in our review, a tendency toward a large mediastinal mass with both compressive and infiltrative features is described and should be considered in the differential diagnosis in young patients. A biopsy is required to establish the final diagnosis, providing histologic, and immunohistochemistry characterization and further potential targeted therapy.