Atypical Teratoid Rhabdoid Tumor: Two Case Reports and an Analysis of Adult Cases with Implications for Pathophysiology and Treatment

Abstract

We present the first quantitative analysis of atypical teratoid rhabdoid tumors (ATRT) in adults, including two patients from our own institutions. These are of interest as one occurred during pregnancy and one is a long-term survivor. Our review of pathological findings of 50 reported cases of adult ATRT leads us to propose a solely ectodermal origin for the tumor and that epithelial–mesenchymal transition (EMT) is a defining feature. Thus, the term ATRT may be misleading. Our review of clinical findings shows that ATRT tends to originate in mid-line structures adjacent to the CSF, leading to a high rate of leptomeningeal dissemination. Thus, we hypothesize that residual undifferentiated ectoderm in the circumventricular organs, particularly the pituitary and pineal glands, is the most common origin for these tumors. We note that if growth is not arrested soon after diagnosis, or after the first relapse/progression, death is almost universal. While typically rapidly fatal (as in our first case), long-term remission is possible (as in our second). Significant predictors of prognosis were the extent of resection and the use of chemotherapy. Glial differentiation (GFAP staining) was strongly associated with leptomeningeal metastases (chi-squared p = 0.02) and both predicted markedly worse outcomes. Clinical trials including adults are rare. ATRT is primarily a disease of infancy and radiotherapy is generally avoided in those aged less than 3 years old. Treatment options in adults differ from infants in that cranio-spinal irradiation is a viable adjunct to systemic chemotherapy in the adult population. Given the grave prognosis, this combined approach appears reasonable. As effective chemotherapy is likely to cause myelosuppression, we recommend that stem-cell rescue be available locally.

Embryonal Tumors

“…Multimodal treatment by GTR, RT, intrathecal CTx, as well as HDCT with or without stem cell rescue seems to be mandatory, although the relative role of each treatment component is difficult to be precisely evaluated. In accordance with the findings in the pediatric population, onset of AT/RT in adults also shows dismal prognosis with an OS of only 23 months (14-56 months) and a median time to progression of 5 months (3-18 months) (Dardis et al 2017). Studies indicate that adults with AT/RT with leptomeningeal dissemination have even a considerably poorer prognosis (Dardis et al 2017).…”

“…14-21% of the patients show cerebrospinal fluid (CSF) dissemination of the tumor at time of diagnosis already (Buscariollo et al 2012;Tekautz et al 2005;Athale et al 2009;Hilden et al 2004). In adults, AT/RT is even more uncommon with an estimated incidence rate of <1 per 1,000,000 per year (Dardis et al 2017). Consequently, experience in this population is extremely limited and is derived from case reports and small case series only.…”

A Systematic Review of Atypical Teratoid Rhabdoid Tumor in Adults

“…From our systematic review, we found 50 adult patients who were diagnosed with AT/RT from the 39 articles included in this study (Table 1 ). The Supplementary Table 1 will include all the patients included in the pooled analysis ( 1 , 2 , 4 – 9 , 11 – 42 ). Of the 50 patients, the average age was 36.69 ( SD = 15.19) years with range from 18 to 59 years.…”

Intra-operative cerebrospinal fluid sampling versus post-operative lumbar puncture for detection of leptomeningeal disease in malignant paediatric brain tumours

“…Although there are no definite numbers on the risk of LMD based on tumour type, historical series have demonstrated that medulloblastoma, ETMR and pineoblastoma (previously known as the entity ‘primitive neuroectodermal tumour’ or ‘PNET’) made up the majority of these cases [ 6 , 20 ]. Atypical teratoid rhabdoid tumour (ATRT)—a rare and hence, lesser understood malignant paediatric brain tumour, has also notoriety for LMD [ 10 , 21 ]. Others such as ependymoma and germ cell tumours are also associated with LMD [ 20 ].…”