Sellar atypical teratoid/rhabdoid tumor in adults: survival analysis of treatment strategies. Illustrative case

Abstract

BACKGROUND

Atypical teratoid/rhabdoid tumor (ATRT) is a rare, highly aggressive central nervous system tumor predominantly found in children. Limited information exists on ATRT in adults, posing challenges in diagnosis and treatment. This study presents the case of an adult patient with ATRT in the sellar region and explores the impact of different treatment regimens on patient survival.

OBSERVATIONS

A 60-year-old female with an ATRT underwent resection of the tumor, followed by adjuvant chemoradiotherapy. Molecular genetic analysis revealed compound heterozygous SMARCB1 point mutations. Survival analysis was performed on previously published adult ATRT cases, comparing treatment approaches. The cohort’s overall median survival was 6 months, with patients receiving combined chemoradiotherapy showing the longest median survival of 23.5 months. Statistical analysis demonstrated a significant difference in survival between patients treated with surgery alone and those receiving surgery followed by chemoradiotherapy (p < 0.001). However, no significant difference was observed between patients treated with surgery alone and those with postoperative radiotherapy (p = 0.105).

LESSONS

Early initiation of adjuvant chemoradiotherapy following surgery improves survival outcomes in adult patients with ATRT. Because of limited data on standardized treatment protocols for adults with ATRT, further research and larger-scale studies are needed to establish effective treatment guidelines for this population.

Atypical teratoid/rhabdoid tumor (ATRT) is a rare and highly aggressive embryonal tumor of the central nervous system, primarily affecting children.¹ The incidence of adult ATRT cases is relatively low, with fewer than 100 cases reported in the medical literature.^2,3 These tumors predominantly occur in females and are usually located in the supratentorial region, particularly affecting midline structures such as the sellar region,^2,4 whereas nonmidline tumors are more commonly found in males between the ages of 18 and 40 years.⁴ The median overall survival for adults with ATRT is approximately 20 months; in the pediatric population, survival ranges from 6 to 17 months.^1,5

Given its rarity and aggressive nature, ATRT presents significant challenges for clinicians in terms of diagnosis and treatment. Surgery is typically the initial approach, but the role of radiotherapy and chemotherapy has also been explored.^3,6 Chemotherapy protocols for ATRT in adults are mainly adapted from those used in pediatric patients. However, the optimal treatment strategy for adult ATRT remains uncertain, highlighting the need for further research to determine the most effective approach.

In this study, we present the case of a 60-year-old female patient diagnosed with an ATRT in the sellar region. The patient underwent resection followed by combined chemoradiotherapy. Additionally, we conducted a survival analysis of previously published cases of adult ATRT to evaluate the impact of different treatment strategies on patient survival. The aim of this study was to provide valuable insights into the efficacy of various treatment regimens and support clinical decision making for the management of ATRT.

Illustrative Case

A 60-year-old female presented with a 2-month history of right eye pain and binocular oblique diplopia. Clinical examination revealed that she had a right cranial nerve (CN) III palsy, which spared the pupil, and a right CN IV palsy. The patient denied any constitutional symptoms or any family history of pituitary tumors. Magnetic resonance imaging (MRI) revealed a 1.3-cm mass located in the sellar region. The mass involved the right cavernous sinus but did not displace the optic apparatus (Fig. 1). The patient did not exhibit any manifestations of endocrinal dysfunction, and hormone profiles, including morning cortisol, thyroid-stimulating hormone, free thyroxine, follicle-stimulating hormone, luteinizing hormone, growth hormone, and prolactin, were all within the normal range.

FIG. 1.

Sagittal (A) and coronal (B) T1-weighted magnetic resonance (MR) images at clinical presentation revealed a 1.3-cm mass in the sella with involvement of the right cavernous sinus.

After receiving dexamethasone, the patient underwent resection of the tumor via an endoscopic endonasal approach. Pathology results indicated that the tumor was a malignant neoplasm with an embryonal morphology. The tumor consisted of sheets of cells exhibiting open chromatin, varying prominent nucleoli, and limited eosinophilic cytoplasm. The lesion displayed high vascularity and areas of hemorrhage (Fig. 2A and B). Immunohistochemistry results showed positive staining for CAM5.2, synaptophysin, and EMA, while there was no INI1 expression (Fig. 2C, B, E). Molecular genetic testing revealed 2 variants of clinical significance: SMARCB1 L135fs c.403delC and SMARCB1 Q260* c.778C > T.

FIG. 2.

Histological examination of the tumor. Hematoxylin-and-eosin staining, original magnification ×20 (A) and ×40 (B), showed sheets of cells with open chromatin, variably prominent nucleoli, and scant eosinophilic cytoplasm. Immunohistochemistry, original magnification ×40, with immunoperoxidase staining: CAM5.2-positive staining (C) and synaptophysin-positive staining (D). INI-1 immunostaining shows loss of nuclear staining in the tumor nuclei and positive in the endothelial cells and residual pituitary tissue (E, original magnification ×40).

Further diagnostic workup, including chest computed tomography (CT) and spinal MRI, did not reveal any evidence of metastatic disease. Additionally, lumbar puncture was performed to stage the disease, and it showed no signs of metastasis.

Despite initial symptom improvement following surgery, the patient developed right-sided CN III palsy and numbness along the distribution of the CN V1 3 weeks later. Follow-up brain and spine MRI indicated tumor regrowth in the sellar region with extension into the right cavernous sinus (Fig. 3). The tumor was deemed Knosp grade 4 on the right side and grade 1 on the left. There was no indication of spinal metastasis. Subsequently, the patient received radiotherapy with a total dose of 54 Gy administered over 30 fractions. She is currently undergoing chemotherapy with cyclophosphamide, doxorubicin, vincristine, and etoposide.

FIG. 3.

Sagittal (A) and coronal (B) T1-weighted MR images obtained 3 weeks postoperatively, showing a 2.2 × 2.0 × 3.0–cm enhancing mass extending to the right cavernous sinus and encasing the right internal carotid artery, indicating tumor regrowth.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

ATRT is an uncommon and highly aggressive tumor that is predominantly diagnosed in children under the age of 3.⁷ In infants, ATRTs typically arise in the posterior fossa; in adults, they more commonly occur in the supratentorial region.^2,3,8,9 Among adults, approximately 60 cases of ATRT have been reported in the sellar region.

Molecular genetic analysis of the ATRT case presented in this study revealed compound heterozygous SMARCB1 point mutations, specifically the SMARCB1 L135fs c.403delC and SMARCB1 Q260* c.778C > T variants. These mutations, affecting different alleles, are considered to have strong clinical significance. Interestingly, these specific mutations are rare in pediatric SMARCB1-deficient tumors, with only 1 tumor of 50 ATRTs and none of 150 ATRTs examined exhibiting these mutations.^10,11 However, they have been previously reported in sellar region ATRTs in adults.¹² This rarity of mutations in pediatric ATRT suggests the existence of different underlying mechanisms contributing to the development of ATRTs in adults and children.

The divergence in the genetic characteristics between adult and pediatric ATRTs raises the question of whether adapting pediatric treatment regimens is the most effective approach for treating adult ATRT. The typical treatment for sellar ATRT in adults involves resection, followed by chemotherapy, radiotherapy, or a combination of the 2. However, there is currently no consensus regarding the optimal adjuvant therapy for these patients.

In the reported case, the patient initially underwent resection of the tumor, followed by a decision to initiate adjuvant therapy with chemoradiotherapy. The optimal chemotherapeutic regimen for ATRT in adults is still unknown, and there is a lack of standardized chemotherapy protocols specifically tailored for this population. However, commonly used chemotherapeutic agents for ATRT include ifosfamide, cisplatin, etoposide, doxorubicin, cyclophosphamide, vincristine, methotrexate, and temozolomide, administered in various combinations.^13,14

To evaluate the impact of different treatments on adult ATRT patient survival, we conducted a survival analysis of previously reported adult ATRT cases (Table 1, Fig. 4). The overall median patient survival was 6 months, with an interquartile range (IQR) of 2–25.5 months. Patients who underwent resection alone had a median survival of 2.5 months (IQR: 1–4.75 mos), whereas those who received postoperative radiotherapy had a median survival of 7.5 months (IQR: 1.75–24.25 mos). Patients who underwent both radiotherapy and chemotherapy after surgery had a median survival of 22.5 months (IQR: 8.25–29.75 mos). Only 3 patients received chemotherapy alone after surgery.

TABLE 1.

Previously published adult ATRT cases

Authors & Year	Age (yrs)	Gender	MRI Findings	Treatment*	Outcome
Kuge et al., 200015	32	F	Contrast-enhancing sellar lesion	Resection; RT; chemo: cisplatin, etoposide, interferon-gamma, methotrexate	Death at 28 mos
Raisanen et al., 200516	20	F	2.0 × 1.9–cm, partially cystic, heterogeneously enhancing mass in sellar region	Resection; RT; chemo	Alive at 28 mos
	31	F	1.6-cm enhancing mass	Resection; RT	Death at 9 mos
Arita et al., 200817	56	F	Heterogeneously enhancing mass invading rt CS & displacing pituitary gland	Resection; RT: 17 Gy to periphery & 34 Gy to center of residual tumor	Death at 23 mos
Las Heras et al., 201018	46	F	NR	NR	NR
Schneiderhan et al., 201119	61	F	Heterogeneously enhancing sellar/suprasellar mass w/ parasellar expansion; edema of adjacent brain parenchyma & bilat optic tracts	Resection	Death at 3 mos
	57	F	Heterogeneously enhancing sellar lesion w/ rt-sided parasellar expansion	Resection; RT; chemo: 3 cycles of doxorubicin & cisplatin	Alive at 6 mos
Chou et al., 201320	43	F	Isointense/hypointense sellar lesion w/ heterogeneous enhancement; invasion into lt CS	Resection; RT	Alive at 0.5 mo
Moretti et al., 201321	60	F	Heterogeneously enhancing sellar lesion w/ extrasellar; lt CS invasion; encasing ICA	Resection; chemo: doxorubicin & vinorelbine	Death at 30 mos
Park et al., 201422	42	F	Heterogeneously enhancing solid & cystic sellar/suprasellar mass	Resection; RT; chemo: 10 mos of vincristine, cisplatin, adriamycin, etoposide, & cyclophosphamide alternating w/ vincristine, etoposide, ifosfamide, & carboplatin	Alive at 27 mos
Shitara et al., 201423	44	F	Heterogeneously enhancing mass	Resection; RT; chemo: ifosfamide, cisplatine & etoposide	Death at 17 mos
Lev et al., 201524	36	F	3.3 × 3.2 × 2.3–cm heterogeneously enhancing sellar lesion; compression of optic chiasm, lt CS invasion	Multiple resections; RT; chemo: cytoxan, adriamycin, vincristine, & cisplatin	Death at 29 mos
Biswas et al., 201525	48	F	Sellar lesion w/ “malignant characteristics”	Neoadjuvant chemo: vincristine, doxorubicin; resection; chemo: cyclophosphamide alternating w/ ifosfamide, carboplatin, etoposide; RT	Death at 2 mos
Regan et al., 201526	45	F	Hypointense sellar lesion w/ extension into lt CS	Resection; stereotactic RT to CS & parasellar region	Death at 6 mos
Nobusawa et al., 201627	69	F	2.8 x 1.6–cm isointense sellar lesion, extension into lt CS surrounding ICA	Resection; chemo: temozolomide; focal RT	Alive at 24 mos
Almalki et al., 201628	36	F	Heterogeneously enhancing sellar/suprasellar lesion; bilat invasion of CS & clivus w/ posterior destruction of clinoid	Resection; chemo: vincristine; fractionated RT: total 60 Gy; chemo: ifosfamide, cisplatin, & etoposide	Alive at 37 mos
Larran-Escandon et al., 201629	43	F	2.0 x 2.3–cm sellar/suprasellar lesion w/ subacute hemorrhage	Resection	Death at 1 mo
Elsayad et al., 201630	66	M	2.2 × 1.6 × 1.4–cm heterogeneously enhancing sellar lesion	Resection; RT: 59.4 Gy	Alive at 48 mos
Nakata et al., 201712	31	F	NR	Resection; chemo: cisplatin & etoposide, followed by methotrexate (intrathecal); local & posterior fossa RT	Death at 28 mos
	56	F	NR	Resection; stereotactic radiosurgery; craniospinal RT	Death at 23 mos
	44	F	NR	Resection; chemo: ifosfamide, cisplatin, & etoposide; RT	Death at 17 mos
	26	F	NR	Resection; chemo: methotrexate (intrathecal), ifosfamide, cisplatin, & etoposide; local spine RT	Death at 33 mos
	21	F	NR	Resection; chemo: ifosfamide, cisplatin, etoposide; local RT	Death at 35 mos
	69	F	NR	Resection; chemo: temozolomide; local RT	Alive at 37 mos
Dardis et al., 201731	35	M	Mixed cystic/solid heterogeneously enhancing suprasellar & interpeduncular lesion	2 resections; fractioned craniospinal RT w/ localized boosts w/ cisplatin sensitizer (total 66 Gy); chemo: high-dose cyclophosphamide & vincristine, followed by autologous stem cell transplant	Alive at 30 mos
Pratt et al., 201732	47	F	2.6 x 3.9 x 3.2–cm heterogeneously enhancing sellar mass; erosion of surrounding bone & extension into bilat CSs, complete encasement of lt carotid artery	Resection; RT	NR
Johann et al., 201833	20	F	NR	Resection; chemo: ifosfamide, cisplatin, & etoposide, followed by autologous stem cell rescue	Death at 120 mos
Nishikawa et al., 201834	42	F	1.9 x 2.0 x 0.5–cm intrasellar mass, lt CS invasion, optic chiasm compression	Resection; chemo: temozolomide; stereotactic RT x2 (total 30 Gy); after recurrence: resection; chemo: paclitaxel; RT	Death at 11 mos
Paolini et al., 201835	31	F	Heterogeneously enhancing sellar/suprasellar lesion	Resection	Death at 2 mos
	36	F	NR	Resection; unspecified chemo; RT	Alive at 22 mos
	46	F	NR	2nd resection	Death (postop)
	47	F	NR	Resection; chemo: 3 agents (NR); fractionated RT: total 20 Gy	Alive at 62 mos
	65	F	NR	Resection; chemo: vincristine, cisplatin, doxorubicin, & cyclophosphamide; fractionated RT w/ cisplatin sensitizer (total 54 Gy)	Death at 23 mos
Barresi et al., 201836	59	F	2.3 x 1.2–cm heterogeneously enhancing sellar lesion; invasion into lt CS	Resection; RT	Death at 2 mos
Su et al., 201837	37	F	Heterogeneously enhancing, 2.57 x 1.96 x 3.63–cm sellar/suprasellar lesion	Resection	Death at 3 mos
Barsky et al., 201838	54	F	1.6 x 1.1 x 2.4–cm sellar/suprasellar lesion w/ edema	Resection	NR
Asmaro et al., 201939	62	F	Heterogeneously enhancing sellar/suprasellar hemorrhagic lesion, w/ SAH & IVH	Resection	Death at 2 mos
Voisin et al., 201940	51	F	Preop CT: lobulated heterogeneously enhancing suprasellar cystic lesion	Resection; chemo: temozolomide; fractionated craniospinal RT: total 54 Gy; chemo: 1 dose ifosfamide, carboplatin, & etoposide	Alive at 9 mos
Siddiqui et al., 201941	55	F	Hemorrhagic sellar mass w/ SAH & IVH	Resection	Death at 1.5 mos
Lawler et al., 201942	27	F	Enlarged pituitary fossa & gland w/ ill-defined lesion at floor of pituitary fossa	Resection	NR
Bokhari et al., 202043	40	F	2.9 × 1.7 × 2.3–cm, sellar, enhancing cystic lesion	Resection; chemo: NR; RT	Death at 1 mo
Peng et al., 20212	43	F	NR	Resection; stereotactic RT: total 60 Gy	Death at 4 mos
	52	F	NR	Resection	Death at 2 mos
	50	F	Cystic tumor	Resection	Death at 1 mo
	29	F	NR	Resection; chemo: cisplatin & dacabazide; RT: total 52 Gy	Death at 8 mos
	70	F	Tumor, hemorrhage	Resection	Death at 1 mo
Major et al., 20223	70	F	1.8 x 2.2 x 1.7-cm heterogeneously enhancing sellar/suprasellar mass w/ invasion into rt CS encasing rt ICA	Resection; chemo: carboplatin & etoposide; alternating intrathecal etoposide plus topotecan & intrathecal methotrexate, & thiotepa (3 cycles); fractionated external beam focal RT: total 30 Gy	Death at 5.5 mos
Duan et al., 202244	47	M	NR	Resection; RT: Gamma Knife	Death at 1 mo
	52	F	NR	2 resections	Death at 2.5 mos
	47	F	NR	2 resections	Death at 6 mos
	46	F	NR	Resection	Death at 6 mos
	45	F	NR	Resection	Death at 1 mos
	73	F	NR	Resection	Death at 3 mos
	26	M	NR	2 resections	Death at 3 mos
	41	F	NR	Resection	Alive at 12 mos
Baiano et al., 20228	32	F	Large sellar mass	Resection; chemo: bleomycin (3 cycles)	Death at 2 mos
	40	F	Intra- & lt parasellar lesion	Resection; chemo: bleomycin (3 cycles)	Death at 2 mos
	41	F	Intra-, infra-, supra-, & lt parasellar lesion w/ heterogeneous contrast enhancement, lt carotid artery encasement w/ extension to 3rd ventricle & lt tentorium of cerebellum infiltration	Resection	Death at 1 mo
	50	F	Intra-, supra-, & lt parasellar lesion endowed w/ heterogeneous contrast enhancement & lt carotid artery encasement	Resection; chemo: 6 cycles, 3 w/ vincristine, doxorubicin, cyclophosphamide alternating w/ 3 cycles of ifosfamide & etoposide	Alive at 18 mos
Present case	60	F	1.3-cm mass in sella w/ involvement of rt CS, no displacement of optic apparatus, Knosp grade 4 on rt & grade 1 on lt w/ no evidence of spinal metastasis	Resection; RT: total 54 Gy; chemo: cyclophosphamide, doxorubicin, vincristine, & etoposide	Alive at 6 mos

Chemo = chemotherapy; CS = cavernous sinus; ICA = internal carotid artery; IVH = intraventricular hemorrhage; NR = not reported; RT = radiotherapy; SAH = subarachnoid hemorrhage.

^*Treatments administered to the patients are mentioned in the order they were given.

FIG. 4.

Kaplan-Meier survival curves comparing different treatment regimens in adult patients with atypical teratoid/rhabdoid tumor (ATRT). Log-rank test revealed a significant difference in survival time between patients treated with surgery alone and those treated with surgery followed by chemoradiotherapy (p < 0.001), but no significant difference between patients treated with surgery alone and those treated with surgery plus postoperative radiotherapy (p = 0.105). Cox proportional hazards analysis showed that patients undergoing surgery followed by chemoradiotherapy had a hazard ratio of 0.26 (95% confidence interval: 0.12–0.55, p < 0.001) compared to those who underwent only surgical intervention.

Statistical analysis using the log-rank test revealed a significant difference in survival time between patients treated with surgery alone and those treated with surgery followed by chemoradiotherapy (p < 0.001). However, no significant difference was observed between patients treated with only surgery and those treated with surgery plus postoperative radiotherapy (p = 0.105). Cox proportional hazards analysis was then used to calculate the hazard ratio (HR). The HR for patients undergoing surgery followed by chemoradiotherapy versus surgical intervention alone was 0.26 (95% confidence interval: 0.12–0.55; p < 0.001), indicating a significantly lower risk of death in patients who received combination therapy after surgery compared with those who only underwent surgical intervention. These findings suggest that the addition of postoperative chemoradiotherapy may improve survival outcomes in adult patients with ATRT. It should be noted that the choice of treatment, such as surgery with or without adjuvant therapy, is frequently determined based on the severity of the disease. However, in the cases reviewed, there was no clear indication of disease severity or the rationale behind treatment selection. This limitation is important to acknowledge when considering the survival analysis conducted in this study.

Patients who received chemoradiotherapy postoperatively demonstrated the longest median survival time of 22.5 months. Additionally, the results of the log-rank test revealed a significant difference in survival time between patients treated with only surgery and those treated with chemoradiotherapy, indicating that combination therapy may be the most effective treatment strategy for ATRT. These findings are consistent with previous reports in both children and adults, which have consistently shown that a combined radio-chemotherapy adjuvant approach is associated with better prognosis and longer survival.^3,4

Lessons

In conclusion, our study indicates that early initiation of adjuvant chemoradiotherapy following surgery in adult patients with ATRT improves survival outcomes. However, because of the limited data on standardized treatment protocols for adults with ATRT, further research and larger-scale studies are necessary to validate these findings and establish effective treatment guidelines for this patient population.

Author Contributions

Conception and design: Garzon-Muvdi, Zamudio-Coronado, Zohdy. Acquisition of data: Garzon-Muvdi, Zamudio-Coronado. Analysis and interpretation of data: Zamudio-Coronado, Zohdy. Drafting of the article: Garzon-Muvdi, Zamudio-Coronado. Critically revising the article: Garzon-Muvdi, Zamudio-Coronado, Zohdy, Pradilla. Reviewed submitted version of the manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Garzon-Muvdi. Statistical analysis: Zohdy. Administrative/technical/material support: Zamudio-Coronado, Pradilla. Study supervision: Zamudio-Coronado, Pradilla.