Pediatric atypical teratoid/rhabdoid tumor in the cauda equina with rapid tumor progression: illustrative case

Abstract

BACKGROUND

Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon malignant neoplasm and rarely occurs in the spinal space, especially in the cauda equina. Only 8 cases of pediatric AT/RT of the cauda equina have been reported. Therefore, its clinical behavior and optimal treatment remain unclear.

OBSERVATIONS

The authors describe the case of a 9-year-old boy who presented with progressive back and left leg pain. Initial magnetic resonance imaging showed an intradural extramedullary lesion at the L3–4 level, which progressed rapidly to the L2–5 level within a month. He underwent partial resection of the tumor with an L2–5 laminectomy. The histopathological diagnosis was AT/RT. He received adjuvant chemotherapy and radiotherapy, and his gait disturbance improved postoperatively. At 6 months’ follow-up, disease recurrence was not observed.

LESSONS

Although extremely rare, AT/RT should be included in the differential diagnosis for prompt therapeutic intervention. Safe resection with minimal functional impairment, followed by postoperative chemoradiation, can lead to tumor control and improve neurological function.

https://thejns.org/doi/10.3171/CASE24219

Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon malignant neoplasm of the central nervous system (CNS), accounting for 1%–2% of all pediatric tumors.^1–3 AT/RT most frequently occurs in children aged < 3 years, with 16.5 months as the median age at diagnosis.⁴ AT/RT is highly aggressive and associated with a poor prognosis; even with adjuvant radiotherapy and/or chemotherapy after surgery, the median survival is approximately 9 months.^{5, 6}

The majority of AT/RTs occur intracranially, with 55%–75% of the lesions encountered in the posterior fossa and 25%–40% located supratentorially.^7–11 They rarely occur in the spinal space, accounting for 1.5%–2% of pediatric AT/RT cases.^{8, 10} Additionally, pediatric AT/RT of the cauda equina is extremely rare, with only 8 cases reported in the English-language literature.^11–18 Because of its rarity, the clinical behavior and optimal treatment, including the timing of treatment initiation and surgical strategy, are poorly understood. Herein, we report a case of AT/RT of the cauda equina in a 9-year-old boy showing rapid tumor progression in a short period before surgery.

Illustrative Case

A 9-year-old boy with no underlying medical history was referred to our hospital due to progressive back and left leg pain for 2 months. Upon presentation, the patient had no difficulty in walking. Magnetic resonance imaging (MRI) of the spine performed at the referring hospital revealed an intradural extramedullary lesion at the L3–4 level (Fig. 1A). Based on the tumor’s location and the patient’s age, our initial diagnosis was myxopapillary ependymoma. Subsequent preoperative MRI conducted at our hospital showed an increase in the tumor size, extending to the L2–5 level within a 19-day interval (Fig. 1B). The tumor showed an iso- to hyperintense signal on T2-weighted images (Fig. 1B upper) and heterogeneous enhancement on contrast-enhanced images (Fig. 1B center); ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed accumulation at the lesion site (Fig. 1B lower). Brain MRI findings were normal. At this juncture, the patient retained the ability to walk, and we scheduled an operation for 2 weeks later.

FIG. 1.

MRI of the spine performed at the referring hospital showed an intradural extramedullary lesion at the L3–4 level. A: Preoperative MRI at our hospital showed that the tumor had increased to the L2–5 level within a 19-day interval. B: The tumor showed an iso- to hyperintense signal on T2-weighted imaging (T2WI; upper) and heterogeneous enhancement on contrast-enhanced images (center). FDG-PET revealed accumulation at the lesion (lower). C: Spinal MRI performed 3 days before the operation showed further tumor enlargement, which was more than 3-fold greater in maximum length compared to the initial MRI study obtained 30 days prior (upper). MRI also revealed a disseminated lesion at the L1 level (lower, white arrow). BLE = bilateral lower extremity; Gd-T1WI = gadolinium-enhanced T1-weighted imaging.

Upon admission 3 days before the operation, the patient developed bilateral lower-extremity weakness with left-sided dominance and experienced difficulty walking. Spinal MRI performed 3 days before the operation revealed further tumor enlargement, which had increased more than 3-fold in maximum length compared to an initial MRI study obtained 30 days prior (Fig. 1C upper). Additionally, MRI revealed a disseminated lesion at the L1 level (Fig. 1C lower). This observation of rapid progression and disseminated lesions raised suspicions of malignant tumors other than myxopapillary ependymoma. However, since the patient had no preoperative bladder or rectal disturbances and considering the necessity of intraoperative neuromonitoring, we opted for a scheduled operation over an urgent one.

Tumor resection was performed with an L2–5 laminectomy under the monitoring of motor evoked potentials and bulbocavernosus reflex. Upon dural incision, the intradural pressure was so high that the tumor bulged out from the intradural space. The tumor exhibited a bleeding tendency, necessitating meticulous coagulation. The tumor was tightly attached to the nerve roots of the cauda equina, rendering occasional difficulties in detachment. The tumor was debulked and removed in a piecemeal manner using an ultrasonic aspirator, while intraoperative neuromonitoring ensured that the waveform was maintained. A tight attachment to the cauda equina did not allow total removal; however, decompression of the cauda equina was achieved.

Histological examination of the tumor showed densely packed, uniform atypical cells with a high nuclear/cytoplasmic ratio (Fig. 2A). Rhabdoid cells, which are cells with a large eosinophilic cytoplasm and eccentrically located nuclei, were rarely seen (Fig. 2B). Tumor cells were partially positive for GFAP, αSMA, and EMA. The tumor cells showed a loss of INI1 expression (Fig. 2C) and cytokeratin (AE1/AE3). The diagnosis of AT/RT was made.

FIG. 2.

The tumor consists of densely packed atypical cells with a high nuclear/cytoplasmic ratio (A, hematoxylin and eosin [H&E] stain, original magnification × 100). Rhabdoid cells, which are cells with a large eosinophilic cytoplasm and eccentrically located nuclei, are rarely seen (B, H&E stain, original magnification × 200; inset demonstrates rhabdoid cells, original magnification × 400). The tumor cells showed loss of INI1 expression (C, integrase interactor 1 stain, original magnification × 200), which is a characteristic finding of AT/RT.

Postoperative MRI revealed a residual tumor around the nerve roots of the cauda equina (Fig. 3A). Adjuvant chemotherapy and radiation to the whole brain and spine were initiated 18 and 22 days after surgery, respectively. At the time of adjuvant therapy, there was further enlargement of the disseminating lesion at the L1 level (Fig. 3B); however, following postoperative treatment, the disseminating lesion shrank remarkably (Fig. 3C). The bilateral lower-extremity weakness in the patient improved postoperatively, and he was discharged after rehabilitation. He showed no urinary disorders. Despite slight weakness in the left lower extremity, the patient was able to walk without a cane. Currently, he is undergoing chemotherapy, with no evidence of tumor recurrence 6 months postoperatively (Fig. 3D).

FIG. 3.

Postoperative MRI revealed a residual tumor around the nerve roots of the cauda equina (A). At the time of adjuvant therapy, there was further enlargement of the disseminating lesion at the L1 level (B, arrow); however, following postoperative treatment, the disseminating lesion shrank remarkably (C). The patient is currently undergoing chemotherapy, with no evidence of tumor recurrence 6 months postoperatively (D).

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

The frequency of AT/RT occurrence in the lumbar spine involving the cauda equina is extremely low. To the best of our knowledge, only 8 other cases have been reported in the English-language literature (Table 1),^11–18 with a slight male predominance (66.7%) and a median age of 18 months at diagnosis. All patients underwent surgery, with subtotal resection in 3 cases, partial resection in 1, and biopsy in 1, suggesting that gross-total resection is not always achieved in cases of cauda equina AT/RT. Postoperative treatment included chemotherapy in 6 cases, radiotherapy in 4, and a combination of chemotherapy and radiotherapy in 3. Postoperative functional outcomes were reported in 3 cases, including ours, all of which showed improvement in gait disturbance after surgical intervention. With the exception of our case, there have been no reports on preoperative tumor progression based on serial imaging findings. Our case is unique, as it shows the rapid tumor progression proven by multiple consecutive imaging findings before tumor resection for AT/RT of the cauda equina.

TABLE 1.

Nine cases of pediatric AT/RT of the cauda equina

Authors & Year	Sex	Age	Symptom	Tumor Location	Surgery	Extent of Resection	Chemo	Radiotherapy	Recurrence/Metastasis	Functional Outcome	Outcome
Yang et al., 200718	M	7 yrs	Back pain, unstable gait	L2–4, IDEM	L2–4 laminectomy	NA	Yes	Yes	5 mos	NA	7 mos, DOD
Makis et al., 201115	M	8 mos	BLE weakness, hyporeflexia, loss of motor milestones	L4–SC, IDEM	NA	Biopsy	Yes	No	No	NA	3 wks, NED
Dhir et al., 201513	M	30 mos	Inability to ambulate, encopresis, urinary dribbling, decreased rectal tone, bilat foot drop	L3–S2, IDEM	L3–S2 laminoplasty	NA	Yes	No	No	NA	8 mos, NED
Garling et al., 201814	F	15 yrs	BLE weakness, decreased sensation, weight loss, back pain, progressive bowel & bladder incontinence	L3–S2, IDEM	L3–5 laminectomy	STR	NA	NA	NA	Improvement in gait disturbance	NA
Song et al., 201817	M	16 mos	BLE weakness	L1–3, IDEM	L1–4 laminoplasty	NA	No	Yes	NA	NA	NA
Buccoliero et al., 201912	M	18 mos	Pain, weakness of lt lower extremity	L1–5, IDEM	NA	STR	Yes	No	No	NA	3 mos, DOD
Shiflett et al., 202016	F	17 mos	Complete plegia, absent reflexes, & paralysis of BLE, decreased rectal tone	T11–L5, IDEM	T11–L5 laminectomy	GTR	No	No	1 wk	NA	3 wks, DOD
Syed et al., 202311	F	15 mos	BLE weakness	L3–4, IDEM	L1–4 laminoplasty	STR	Yes	Yes	No	Improvement in gait disturbance	2 yrs, NED
Present case	M	9 yrs	BLE weakness, lt lower-extremity pain	L2–5, IDEM	L2–5 laminectomy	PR	Yes	Yes	No	Improvement in gait disturbance w/o urinary disorder	6 mos, NED

BLE = bilateral lower extremity; DOD = died of disease; GTR = gross-total resection; IDEM = intradural extramedullary; NA = not applicable; NED = no evidence of recurrent/progressive disease; PR = partial resection; SC = sacrococcygeal region; STR = subtotal resection.

As AT/RT in the cauda equina is rare, preoperative diagnosis is difficult.^{17, 19, 20} In the present case, since the tumor occurred in the cauda equina at a young patient age, the preoperative diagnosis was myxopapillary ependymoma. Myxopapillary ependymoma is a benign tumor (World Health Organization grade 1), which is inconsistent with the malignant course, rapid growth, and dissemination observed in our case. As 20%–40% of all AT/RTs reportedly present with cerebrospinal fluid (CSF) dissemination from their primary source at initial presentation,^{21, 22} the findings of preoperative CSF dissemination were consistent with those of AT/RT. Other differential diagnoses included chordoma and schwannoma, which are often difficult to diagnose preoperatively.^{17, 19} Moreover, other rapidly progressing CNS tumors of the cauda equina in the pediatric population include metastatic, malignant peripheral nerve sheath, and Ewing tumors.^23–25 The characteristics of AT/RT on MRI include hypo- to isointensity on T1-weighted sequences, iso- to hyperintensity on T2-weighted sequences, and variable gadolinium enhancement with no enhancement in some cases. Reflecting the high cell density of the tumor, hyperintensity on computed tomography and diffusion-weighted imaging is characteristic. Although infrequent, AT/RT occurs anywhere in the CNS. Therefore, AT/RT should be considered as a differential diagnosis especially in rapidly progressing cauda equina tumors in children.

CSF dissemination at diagnosis, an age < 2 years, and delayed radiotherapy have been reported as poor prognostic factors for AT/RT.^{5, 20} Therefore, prompt diagnosis and initiation of postoperative adjuvant therapy are extremely important. Histopathological examination, whose most important finding is confirmation of the loss of INI1 immunoexpression, is the gold standard for AT/RT diagnosis. In our case, the loss of INI1 staining was observed, and the patient was diagnosed with AT/RT. Subsequently, prompt postoperative chemotherapy and radiation to the whole brain and spine were initiated, and tumor control was achieved for at least 6 months.

Aggressive resection is generally recommended for AT/RT, although the survival benefit of gross-total resection has not been fully proven.²⁶ However, resection of cauda equina tumors is challenging because the involvement of nerve roots by the tumor enhances the risk of postoperative neurological dysfunction, such as gait or urinary disturbance.¹¹ Intraoperative neuromonitoring, such as motor and somatosensory evoked potentials and bulbocavernosus reflex monitoring, is useful in the resection of cauda equina tumors to determine the appropriate degree of resection.^{27, 28} In this case, neuromonitoring was useful in determining the extent of tumor resection, leading to the minimization of postoperative functional impairment and improvement in walking after rehabilitation. Based on the observed favorable functional outcomes, we recommend safe resection plus adjuvant chemoradiotherapy, with the preservation of neurological function, as a therapeutic strategy in cases of AT/RT occurring in the cauda equina.

Lessons

Although extremely rare, pediatric AT/RT can occur in the cauda equina. AT/RT should be included in the differential diagnosis for prompt therapeutic intervention, especially in cases of rapid clinical and/or radiological progression of cauda equina tumors in children. Safe resection with minimal functional impairment, followed by postoperative chemoradiation, can achieve tumor control and improve neurological function.

Disclosures

Dr. Igaki reported grants from AstraZeneca, CICS Inc., Elekta KK, and Merck Biopharma; and personal fees from Itochu, HIMEDIC, Accuray, Nippon Medi-physics, Daiichi Sankyo, Eisai, EA Pharma, and ZAP Surgical Japan outside the submitted work. Dr. Yoshida reported grants from Daiichi Sankyo and Chugai and personal fees from Eisai outside the submitted work. Dr. Narita reported grants from Sumitomo Pharm, Daiichi Sankyo, Eisai, Ono Pharm, Servier, MBL, and Incyte outside the submitted work.

Author Contributions

Conception and design: Ohno, Watanabe, Yanagisawa. Acquisition of data: Tsuchiya, Sugino, Igaki, Yoshida, Ogawa. Analysis and interpretation of data: Ohno, Tsuchiya, Sugino, Yoshida. Drafting the article: Ohno, Tsuchiya, Yanagisawa. Critically revising the article: Watanabe, Miyazaki, Igaki, Yoshida, Takahashi, Yanagisawa, Ogawa, Narita. Reviewed submitted version of manuscript: Ohno, Watanabe, Miyazaki, Sugino, Igaki, Yoshida, Takahashi, Osawa, Narita. Approved the final version of the manuscript on behalf of all authors: Ohno. Administrative/technical/material support: Yanagisawa. Study supervision: Watanabe, Narita. Patient management and treatment: Fujita.

Correspondence

Makoto Ohno: National Cancer Center Hospital, Tokyo, Japan. mohno@ncc.go.jp.