Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system (CNS) neoplasm predominantly found in children under the age of 3, and is extremely rare in adults (1, 2). In the year 1987, it was described for the first time (3). AT/RT usually occurs in posterior fossa for pediatric patients, most commonly in the cerebellum. By contrast, the most common locations in adults are the cerebral hemisphere and the sellar region (2, 4, 5). The pathological features of AT/RT are peculiar, consisting primarily of rhabdoid cells and heterogeneous portions containing mesenchymal, epithelial, and neuroectodermal cells (6).

According to the 2021 WHO Classification of CNS tumors, medulloblastoma and AT/RT were classified as embryonal tumors, and all embryonal tumors (except for cribriform neuroepithelial tumor and CNS tumor with BCL6 corepressor internal tandem duplication) were classified as Grade 4 tumor (7). Using DNA methylation and gene expression profiling, the relevant reports showed that AT/RTs are comprised of three epigenetic subgroups with distinct enhancer landscapes: ATRT-TYR, ATRT-SHH, and ATRT-MYC (8). AT/RTs are often misdiagnosed as other types of brain tumors due to the lack of specific radiological features and the heterogeneous nature of the tumor cells (6). Differential diagnoses should be noted for embryonal tumor, medulloblastoma, choroids plexus carcinoma, and high-grade glioma (9). Therefore, a diagnosis of AT/RTs requires the confirmation of specific genetic aberrations such as a loss of integrase interactor 1 (INI1) tumor suppressor gene on chromosome 22 or BRG1 gene (10, 11).

In addition, the treatment criteria (including stratification criteria) for patients with AT/RT are a controversial topic (10). The prognosis is grim, even if the treatment generally consists of surgical resection in combination with chemotherapy and radiation therapy (RT) (6). In order to better diagnose and treat AT/RT, more cases should be included in the study. In this report, we describe two patients who presented with intracranial masses in the left cerebellum and right ventricle, respectively, and show the clinical, imaging, pathological, and immunohistochemical aspects of AT/RTs.

Case 1: The patient was a 19-month-old boy with a 1-month history of claudication before admission. Neurological examination verified that the left ankle clonus and the left Babinski sign were positive. Cerebral magnetic resonance imaging (MRI) revealed a mass in the right lateral ventricle with intraventricular extension. The size of the lump was about 6 × 5 × 2 cm, which was primarily isointense on both T1- and T2-weighted MRI. Additionally, the mass appeared hyperintense on enhanced MRI, with areas of calcification and heterogeneous contrast enhancement (Figures 1A–E). The patient underwent a right frontal approach for gross total resection in supine position. To observe the yellow and soft mass, we gently slit the epidermis, subcutaneous tissue, and other tissues to expose the skull, dissociated the skull with a milling cutter, and liberated the blood vessels. Grossly, the tumor had a tender fish flesh-like appearance with necrosis. However, the tumor was tightly connected to the lateral ventricle wall and the septum pellucidum and protruded into the third ventricle through the interventricular foramen. Then, piecemeal resection was performed on the tumor. Postoperative computed tomography (CT) showed that in the bilateral lateral ventricle walls, there were several irregular nodular, strip-like high-density foci with indistinct boundaries. The tumor was completely removed (Figures 1F–H). Postoperative pathological diagnosis showed embryonic tumors with multidirectional differentiation of immature small cells, epithelial, and neuron cells and revealed abundant eosinophilic cytoplasm and eccentric nucleus with prominent nucleoli. The tumors were negative for INI1 and positive for Synaptophysin (Syn) (Figures 3A–D). The Ki-67 labeling index was 50%. A case of AT/RT was ultimately diagnosed by histopathological examination of the resected specimens. Two months after the operation, the patient received two cycles of adjuvant chemotherapy including Vincristine, Methotrexate, Leucovorin, Cytoxan, Etoposide, and Cisplatin. Unfortunately, the patient died of tumor recurrence after 15 months.

Case 2: The patient was a 27-month-old boy, whose symptoms were unstable gait for a month, accompanied by nausea and vomiting for half a month. Physical examination did not reveal positive signs. An MRI revealed the presence of a mass measured 2.3 × 1.8 × 1.7 cm in the left cerebellum. MRI showed the isointense on T1-weighted images, heterogeneous iso/hyperintense on T2-weighted images and a pronounced enhancement after using an MR contrast agent (Figures 2A–E). The patient underwent a median suboccipital approach to the posterior fossa for tumor resection in the right lateral position. The epidermis and other tissues were slit progressively to reveal the tumor, just as we did in case 1. Then, we made a bone window along the squamous portion of the occipital bone. Unlike case 1, however, the tumor had a distinct capsule that separated it from the normal parenchyma. The tumor was red and soft, with abundant vascularity. A subtotal resection of the tumor was performed. Postoperative CT revealed that the left cerebellum was a low-density area, with an unclear boundary and sporadic pneumocephalus. The tumor was removed completely (Figures 2F–H). Tumor cells have eccentric nucleoli and abundant eosinophil cytoplasm. Brisk mitotic activity and apoptotic bodies are common. The tumors were partly positive for vimentin (Figures 3E–H) and the tumors were negative for INI1, Smooth Muscle Actin (SMA), and Glial Fibrillary Acidic Protein (GFAP). The Ki-67 labeling index was 40%. Postoperatively, the results of histopathological examinations demonstrated an AT/RT. After 2 months, the patient received four cycles of chemotherapy (cisplatin, cyclophosphamide, and vincristine). Despite these efforts, patient survival was less than 9 months. Notably, the two patients had no history of radiation or family history of hereditary diseases. Moreover, cerebrospinal fluid examinations for tumor markers were negative. Fortunately, no metastases occurred in the two patients. The relevant information on the patients is listed in Table 1.

As in prior cases, the pathology of tumors showed that cells had a prominent nucleus with eccentric nucleoli and abundant cytoplasm of a somewhat “rhabdoid” morphology (6). However, pathological features cannot diagnose AT/RT. The final diagnosis of the disease still depends on the loss of nuclear INI1 expression. However, INI1 expression may be retained in a small percentage of AT/RTs, and INI1 deletion may also occur in other tumors. In our case, postoperative immunohistochemistry of all patients showed that the tumor cells were negative for INI1, OLIG2, and GFAP. The SMA was positive in the first patient. Meanwhile, immunostaining of the two patients’ tumor tissue showed that the tumor cells were positive for epithelial membrane antigen (EMA). The Ki-67 labeling indexes were 40% and 50%. The results of immunohistochemical staining are listed in Table 2.

AT/RT is a rare disease condition, and a preoperative diagnosis is difficult without an adequate knowledge of the disease. To date, despite multiple advanced diagnoses and treatments being available, the prognosis of patients with AT/RT remains grim. More AT/RT case reports should be included, which will lead to greater diagnostic accuracy as well as improvement in treatment and prognosis. Due to its aggressiveness and poor prognosis, AT/RT cannot be ruled out in the differential diagnosis of intracranial lesions. The case reports replenish the existing literature with new knowledge and hopefully will draw the attention of doctors to the rare tumor.