Medical and Pediatric Oncology 19:310-317 (1991)
PROCEEDINGS OF THE TUMOR BOARD OF THE CHILDREN’S HOSPITAL OF PHILADELPHIA Ciulio J.D’Angio, MD, Series Editor, and Audrey E. Evans, MD, Associate Editor
Rhabdoid Tumor of the Central Nervous System Ciorgio Perilongo, MD, Leslie Sutton, MD, Dannette Czaykowski, Debra Gusnard, MD, and Jaclyn Biegel, PhD
MSN, CPNP,
Key words: rhabdoid tumors, central nervous system, Wilms’ tumors
Dr. Ciorgio Perilongo, Neuro-Oncologist)
MD
(Pediatric
The topic of the tumor board this week regards central nervous system (CNS) rhabdoid tumors (RHTs). We chose this topic, first of all, to try to elaborate a rational therapeutic plan for the patient who will be presented and, second, to highlight the unique biological phenomena that appear to link RHTs with CNS tumors. The existence of extrarenal RHTs as an entity has recently been questioned by Weeks et al. [ 13, who argued that many neoplasms can mimic the light microscopic appearance of RHT of the kidney (RHTK). They suggest that RHTs represent merely a phenotype and not an entity and that extrarenal RHTs will eventually “emerge as a phenotypic concept encompassing a spectrum of histogenetic and clinical diversity.” It is important to recall these statements before opening the discussion and to take a more critical view of the biological and clinical problems of RHTs. So much for introduction; we can now proceed with the presentation of the case. The patient is a 5-year, 11-month-old white girl who was well until early April 1990, when she developed headache and photophobia. Two to 3 days before admission, the patient developed worsening headache, vomiting, and right disconjugate gaze. Her neurological examination on admission revealed bilateral papilledema, right homonymous hemianopsia, decreased visual acuity and mild bilateral sixth nerve palsy. A brain tumor was suspected, and a magnetic resonance image (MRI) of the brain was requested. Dr. Gusnard, will you please discuss the findings? Dr. Debra Cusnard,
MD
(Pediatric Neuro-Radiologist)
T2- and TI-weighted images before the administration of the contrast agent gadolinium-DTPA reveal a very large, lobulated neoplasm of inhomogeneous signal in0 1991 Wiley-Liss, Inc.
tensity in the left occipital lobe. It extends into the posterior portion of the temporal lobe and is surrounded by a moderate amount of vasogenic edema (Fig. 1A). After contrast administration, the tumor markedly enhances and shows signs suspicious for tentorial invasion (Fig. 1B). There is moderate mass effect, including some compression and distortion of the brain stem. The signal intensity inhomogeneity before contrast administration is at least partly attributable to foci of hemorrhage within the mass, including some small cystic areas. Those portions of the tumor that are not hemorrhagic, however, appear nearly isointense to brain parenchyma on the T2-weighted images. This is in contrast to the usual bright signal intensity of most tumors on T2-weighted images. It is noteworthy, because it suggests that this tumor has less free water content than many other tumors because of dense cellularity and a high nuclear to cytoplasmic ratio, reminiscent of the primitive neuroectodermal tumors (PNET-medulloblastoma). This is also suggested by the tumor’s hyperdense appearance on the computed tomography (CT) scan (Fig. 2), an appearance characteristic also of PNET. Dr. Perilongo. In view of these findings the child was then seen by the neurosurgeons and brought to the operating room for removal of the tumor. Leslie Sutton,
MD
(Pediatric Neurosurgeon)
The tumor was massive, filling most of the occipital lobe, and was approached by a large occipital craniotFrom the Neuro-Oncology Program, Division of Oncology (G.P., D.C.), Neurosurgery (L.S.), Neuroradiology (D.G.), Human Genetics, (J.B.), Children’s Hospital of Philadelphia, Philadelphia. Received February 6, 1991; accepted February 21, 1991. Address reprint request to Giulio J. D’Angio, MD, Department of Radiation-Oncology ,Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104.
Rhabdoid Tumor of the CNS
Fig. 1. Rhabdoid tumor. MR images. A:Axial 3000/90 (T2weighted) image reveals a large lobulated mass (small arrowheads) in the left temporo-occipital region abutting the tentorium (large arrowhead) and demonstrating mass effect with distortion of the upper brain stem. Though inhomogeneous in signal intensity, the bulk of the mass is nearly isointense to normal brain parenchyma. Small cysts and foci of blood products account for most of the inhomogeneity; a fluid-blood
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level is seen within a cystic region (small arrow). High signal intensity corresponding to vasogenic edema is seen in the surrounding white matter. B: Coronal 600122 (TI-weighted) image after administration of gadolinium-DPTA reveals marked enhancement of the tumor as well as prominent asymmetrical enhancement along the adjacent tentonal margin (arrowheads), highly suspicious for its invasion.
omy. It was quite vascular and received a large blood in the kidney of infants but that are known to occur in supply from the tentorium, which was invaded by tumor. other organs as well. Dr. Perilongo. At this point, we were faced with how It proved possible to remove all of the gross tumor, but there was obviously microscopic disease left on the dura. to stage a patient with an extrarenal RHT. Because the tumor invaded the tentorium, the spinal cord and cereLucy Rorke, MD (Pediatric Neuro-Pathologist) brospinal fluid pathways were examined by myelograAll histological sections of the tumor were similar and phy, a gadolinium-enhanced MRI of the cord, and spinal composed of large cells with distinct cytoplasmic board- fluid cytology. All these tests were negative. Because ers. The cytoplasm was either clear or bright pink, and RHTK disseminates hematogenously, we also obtained a nuclei were round or bilobar and eccentrically placed bone scan and CT of the chest. No remote metastases (Fig. 3). Nucleoli and mitotic figures were prominent, were found. Finally, because of the known association between and there were many foci of necrosis. A battery of immunoperoxidase stains was done that included the RHTK and brain tumors, a renal ultrasound was obfollowing: glial filament acid protein, neurofilament tained, even though the association of RHTK and RHT of proteins, synaptophysin, desmin, AElK (low molecular the brain is exceedingly rare. The first report of six cytokeratin), vimentin, and epithelial membrane antigen childhood RHTKs associated with primary brain tumors (EMA) (Fig. 4). Of these only the EMA was strongly list these as medulloblastoma, pineoblastoma, PNET, positive, although a small percentage of cells was also and malignant subependymal giant cell astrocytoma [2]. positive for vimentin. The histological features are those A review of 111 patients with RHTK by Weeks et al. [3] of an RHT similar to those that were originally described discerned that 15 (13.5%) developed a brain tumor. They
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Perilongo et al.
Fig. 2. CT scan without contrast. Note the nearly diffuse hyperdensity of the tumor, which suggests its highly cellular nature. Areas of particularly high density represent foci of hemorrhage (arrowheads).
were all histologically different from RHTK. More commonly they were diagnosed medulloblastoma, ependymoma, or gliomas. They tended to occur in or near the midline, either in the posterior fossa or just above the tentorium cerebelli. There was no consistent temporal relationship to the diagnosis of the renal tumor. Interestingly, brain metastases of RTK were randomly distributed, usually in the cerebrum. An association between renal and CNS RHT seems to exist, however. There is an abstract describing these tumors coexisting in two children [4], and we also have seen such a case [S] . The occurrence of a renal and brain RHT in the same patient could of course be explained as one of the two lesions being a metastasis from the other. Dr. D’Angio, perhaps you could tell us of the experience of the National Wilms’ Tumor Study (NWTS) in regard to RHTK.
Fig. 3. Photomicrograph of typical field from tumor composed of cells with prominent cytoplasmic membrane, clear or eosinophilic cytoplasm, and large nuclei with prominent nucleoli. Some cells are binucleated. Hematoxylin and eosin stain.
data. Table I shows the 2 and 4 year survival rates for favorable histology Wilms’ tumors, the anaplastic form, and the two non-Wilms’ tumors that occur relatively frequently in the kidneys of children, namely, the clear cell sarcoma of the kidney (CCSK) and the RHTK. As can be seen, survival is the worst for RHTK. It does not appear to be responsive to the triple attack that is so successful with the other forms of primary renal cancers of childhood. Also note that both the CCSK and the RHTK can affect the brain. Table I1 shows the distribution of metastases at diagnosis and Table 111 at first relapse. Clearly, the lung is the most frequently affected site for both tumor types, but the brain usually is not Ciulio D’Angio, MD (Pediatric Radiation Therapist) involved at diagnosis. It is, however, one of the relatively RHTKs are very aggressive lesions. Just how aggres- common sites of recurrence. A careful search during sive and lethal is clear from a review of the NWTS-3 follow-up for evidence of disease both in the thorax and
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313
TABLE I. National Wilms’ Tumor Study: Outcomes by Histology*
Survival Tumor typea
No.
2 year
4 year
FH 1,667 90 87 48 67 65 Ana 19 93 71 CCSK RHTK 48 24 24 *All stages. aFH, favorable histology Wilms’ tumor; Ana, anaplastic Wilms’ tumor; CCSK, clear cell sarcoma of kidney; RHTK, rhabdoid tumor of kidney.
rarely metastasize outside the CNS, and isolated liver metastases also are rare in RHTK patients. One other 2-month-old boy who had an RHT of the headheck region with a “medulloblastoma” was described by Schmidt et al. [7]. Dr. Biegel, do you have any data on the genetics of these tumors that could help in understanding their biology? Jaclyn Biegel, PhD (Cytogenetist)
Fig. 4. Section of tumor stained by the immunoperoxidase method for presence of epithelial membrane anitgen (EMA). Cytoplasm and/or all membranes of many cells are positive (black-staining material). Immunoperoxidase stain for EMA.
in the brain but not the skeleton is therefore warranted in RHTK patients. The implications of all this for children with RHT of the brain is the following: Unless there are other typical signs of RHTK such as young age and hypercalcemia, it is probably unnecessary to undertake a long and expensive search for a possible primary kidney tumor. The rare RHT of the brain would seem to be a separate and distinct entity. Dr. Perilongo. In regard to the relationship between RHTK and CNS tumors, the case published by Chang et al. [6] of a 14-day-old boy with a PNET of the left cerebral hemisphere and a solitary RHT of the liver incidentally found at autospy is of great interest. Cells resembling the liver RHT were observed in the brain tumor, suggesting that the liver lesion was a metastatis from the cerebral neoplasm. However, brain tumors
Cytogenetic studies of the brain tumor from this patient were performed in our laboratory. The tumor cells displayed an abnormal karyotype, with several changes including an abnormal chromosome 22. This finding is significant in light of our studies of three rhabdoid or atypical teratoid tumors of the brain that demonstrated monosomy 22 as the only change [8]. By contrast, abnormalities of chromosome 22 are rarely seen in PNETs; rather, i(17q) is seen in a large percentage of them. Cytogenetics may thus be used as an additional means of diagnosing RHTs of the brain. Studies of RHTs of the brain and kidney from the same patients are needed to help establish a common etiology for these tumors, if one exists. Dr. Perilongo. Moving forward in the discussion, we would like to consider the therapeutic options available to this child. Dr. Goldwein, do you think this child should be treated with radiation therapy (RT)? JoelColdwein, MD (Pediatric Radiation Therapist)
I believe this child should be treated with craniospinal RT and would recommend 3,600 cGy to the craniospinal axis, with a “boost” to the site of the primary tumor. what do you think Dr. D’Angio? Dr. D’Angio. I agree, even though I am not confident that RT is of much value for this kind of tumor. Dr. Perilongo. In order to find some possible therapeutic recommendations, and stimulated by the hypothesis advanced by Weeks et al. [I], we reviewed the experience accumulated at the Children’s Hospital of
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Perilongo et al. TABLE 11. National Wilms’ Tumor Study-3: Metastases Present at Diagnosis by Site and Tumor Type*
Site
FH (N = 173) No. Percent
Ana (N = 16) No. Percent
Lung only Liver only Bone only Brain only Lung other Other
142 10 21 -
13
+
82 6 -
1 -
12
2
-
-
-
CCSK (N = 4) No. Percent
50
-
2 2 -
13
-
-
-
-
-
81 6
-
-
50 -
RHTK (N = 10) No. Percent
5
50
-
-
-
-
-
-
3 2
30 20
*More than one site might be involved. N = total number of patients who relapsed. Columns give number who relapsed at that site and the total who relapsed. FH, favorable histology; Ana, anaplastic Wilms’ tumor; CCSK, clear cell sarcoma; RHTK, rhabdoid tumor of the kidney.
TABLE 111. National Wilms’ Tumor Study-& Sites of First Relapse by Tumor Type*
Site Lung Liver Bone Brain Flank /abdomen Opp. kidney Other
CCSK (N = 21) Percent
No.
RHTK (N = 24) No. Percent
5 I 13 5 2 0
24 5 62 24 10
14 3 I 3 13 0
58 13 4 13 54
4
19
4
17
*More than one site might be involved. N = total number of patients who relapsed. Columnsgive number who relapsed in that site and the percentage of the total who relapsed. Total numbers of stage 1-111 patientson study were72 for CCSK and 36 for RHTK. CCSK,clear cell sarcoma of the kidney; RHTK, rhabdoid tumor of the kidney.
Philadelphia (CHP) on CNS and extrarenal RHTs along with all the cases so far published. This includes only those cases in which: 1) the light microscopy features fit the criteria described by Weeks et al. [ 13; 2) there was a positive vimentin stain; and 3) whorls of filamentous cytoplasmatic inclusions were identified on ultrastructural study. In presenting these cases, RHTs of the CNS will be kept separate from all other extrarenal RHTs. We reviewed seven cases of primary RHTs of the CNS, four published in the literature and three observed in this institution [9-121.’ All occurred in children aged between 6 months and 13 years (median, 3 years). Four of the seven tumors were in males. The tumor was located infratentorially in five and supratentorially in two; two patients with a posterior fossa tumor also had evidence of subarachnoidal seeding of the tumor, with a large spinal metastatic lesion in one of the CHP children. One other ‘The discussion has been modified to include the index case because
of the interval between the case presentation and publication.
child presented with two intracerebral masses, the larger in the posterior fossa and the other, more discrete lesion, in the suprasellar region [ 121. A 6-month-old boy seen at CHP had a concurrent RHTK. When last reported, one child was alive with no evidence of disease (NED) at 5 months from diagnosis after gross-surgical resection, craniospinal RT, and “8-in- 1” systemic chemotherapy. The index case was treated similarly but had cyclophosphamide, cisplatin, VP 16,and vincristine instead and is alive NED at 6 months. The remaining five patients died of disease, one soon after diagnosis and the others at 2 112, 3, 3, and 5 months after diagnosis despite craniospinal RT in two and chemotherapy alone in the others. Subarachnoidal seeding of the tumor was documented in three cases at autopsy. None of these patients had extra-CNS disease at death. For comparison, we reviewed 43 cases of extrarenal, non-CNS RHTs reported in the literature [ 13-35].Thirtythree (77%) occurred in patients less that 19 years of age. Sixteen of 33 childhood RHTs (48%) occurred in children less than l year of age and 21 (64%) in patients under 5 years. A stillborn product of a normal pregnancy was reported to be affected by a chest RHT [9]. Male predominance is observed in both age groups, with a ma1e:female ratio in children of 1.5: 1 and 4:l in adults (Table IV). The primary sites of extrarenal non-CNS RHTs have been: trunk (six children, three adults), extremities (six children), headheck (three children, two adults), paravertebral region (three children, one adult), pelvis (four children), genitourinary tract (three children, one adult), liver (four children) and orbit (one child), heart (one child), thymus (one child), adrenal gland (one child), perineum (one adult), uterus (one adult), and skin (one adult). Two cases of extrarenal RHTs in association with PNET of the CNS have been reported as already discussed [6,7].Seven of the 33 children (21%) with RHT and 1 of the 10 occurring in adults had metastases at presentation. Pulmonary metastases were the most frequent (seven cases), followed by liver (three cases) and bone (one case).
Rhabdoid Tumor of the CNS
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TABLE IV. Comparison of Some Clinical Characteristics of Patients With Rhabdoid Tumor by Primary Site (Renal Vs. Central Nervous System Vs. Other Sites)* RHT
Ages Range Median Sex Male Female Patient status No. of PtsC Alive NED FOIIOW-UP Range Median Alive NED Range Dead of disease Survival timed Rangea Median
RHTKa ( N = 111)
RHT-CNS (N = 7)
Children (N = 33)
NB- 106 11
6-156 36
NB-228 12
Adults (N = 10) 25-59 years 41 years
63b 43
4 3
20 13
8 2
84 15 (18%)
7 2 (29%)
32 9 (28%)
9 1(11%)
Not known Not known
5-6
1-96 18 2 3-6 21 (66%) 2-28 5
-
-
-
69 (82%)
5 (71%)
Not known Not known
2.5-5 3
10 1
5 7 (78%)
2-84 7
*All times in months unless otherwise noted; NB, newborn; RHTK, rhabdoid tumor of the kidney; RHT-CNS, rhabdoid tumor of the central nervous system; RHT, rhabdoid tumors arising elsewhere. aData from Weeks et al. 131. bGender not known in five. CFor patients whose follow-up is known. dlncludes only patients who survived more than 14 days after diagnosis.
Regional lymph nodes were positive in patients who had RHT of the heart, skin, and spermatic cord (one each) and in two others, both with a tumor of the trunk. A case of RHT of the left inguinal region in a 3 1-year-old man associated with hypercalcemia (- 11.O mgldl) was described by Uchida et al. [27]. The hypercalcemia decreased toward a normal level just after tumor debulking, but apparently rose soon afterward; and, at autopsy, metastatic calcifications were seen in the lungs and kidneys. The parathyroids were not enlarged. No data on treatment and follow-up were available for 2 of 43 RHTs (one in a child and one in an adult). At the time of the reports, 9 of the 32 children (28%) and 1 of the 9 adults (1 1%) with RHT were alive apparently with NED. The follow-up ranged from 1 month to 8 years (median, 18 months) for the 10 children with RHT. The only adult alive with NED had a follow-up of 10 months. Twenty-one children (66%) and seven adults (78%) died of disease; two children and one adult were reported alive with tumors at 3, 6, and 5 months, respectively, from diagnosis. Five children died of disease within the first 2 weeks from diagnosis. The overall survival time of the remaining patients who died of disease varied from 2 to 28 months (median, 5 months) for the 16 children and from 2 months to 7 years (median, 7 months) for the 7
adults. Thirteen of the 16 children (81%) and 4 of the 7 adults (57%) died within 1 year of diagnosis. Six of the 3 1 patients for whom the surgical procedure is known had a grossly complete resection. Three of those (two children and one adult) at the time of the report were alive with NED at 5 , 10, and 105 months from diagnosis, respectively. The other three patients suffered lung metastases associated with regional lymph node relapses in two and local recurrence in one. Sixteen patients received RT with doses varying from 2,000 to 5,400 cGy; eight (50%) apparently failed at the primary site and died of disease. Thirty had systemic chemotherapy consisting mainly of vincristine, cyclophosphamide, doxorobucin, and/or dactinomycin. No complete responses to chemotherapy have been documented, but at this time it is impossible to make firm statements on the impact of different modalities on outcome. The metastatic sites are known for 20 patients (clinical and or autopsy reports). Pulmonary metastases were the most frequent (12 cases [60%]); followed by distant lymph nodes, 7 cases; CNS, 4; liver, 3; and bone, 3. Other metastatic sites have been heart, retro-orbital tissue, bladder, adrenal, pancreas, larynx, and bone marrow. Three patients had epidural metastases; another with a paravertebral RHT also had a brain stem tumor at
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death (histologically not documented) [ 131. Otherwise, isolated intraparenchymal CNS metastases have not been reported. This literature survey does not allow us to draw any concrete conclusions. The CNS seems to be a quite common location for RHT, ranking second in the extrarenal primary sites of RHT after trunk. RHT of the CNS seems to occur in young children but probably with a later peak of incidence than RHTK (Table IV). No cases of CNS RHT were documented in adults. It appears that for CNS RHTs, and particularly for extrarenal non-CNS RHTs, the age span of the affected patients is much wider than for RHTK. There was a male prevalence (M/F ratio 1.3:1) among the CNS tumors we collected, as is true for both RHTK and extrarenal RHT (1.5:l in children for both). As expected, none of the patients developed disease outside the CNS during the clinical course, but one child treated here had a concurrent RHTK. Interestingly, no CNS metastases have yet been reported at presentation for either RHTK or extrarenal RHT, CNS involvement having been described only at the time of recurrence or death. The tendency of these tumors when they occur in the brain to seed the subarachnoidal pathways has been clearly documented. None of the seven patients with a CNS RHT had hypercalcemia, as sometimes reported in RHTK patients and apparently described also in one case of nonrenal RHT [27]. Five of the seven patients with CNS tumors succumbed to the disease, as did most of the RHTK and extrarenal RHT patients (Table IV). Actually, it seems that RHTs, regardless of their primary location, have a very poor prognosis and a quite rapid clinical coursethis despite multimodality therapy as Dr. D’Angio has already pointed out for RHTK. A literature survey cannot, of course, settle the issues concerning the heterogenicity of tumors identified by the term rhabdoid. This remains open to further biological, histological, and genetic study, which may also clarify the fascinating relationship between kidney and other RHTs, including those of the CNS. All the foregoing leaves unsolved the problem of how to treat a child affected by this aggressive albeit rare tumor. There is little in the literature to guide us, and we have elected to treat this patient with intensive systemic chemotherapy and craniospinal RT, as proposed by Dr. Goldwein. The chemotherapy chosen is the one currently in use on the “Baby Brain Tumor protocol,” including cisplatin, cyclophosphamide, vincristine, and etoposide. According to Weeks et al. [3], the completeness of surgical resection and the absence of lymph node involvement are probably favorable prognostic factors for RTKs. If an analogy can be drawn, it could be that the gross complete removal of the tumor achieved in this child augurs a favorable outcome.
ACKNOWLEDGMENTS
We are grateful to Donna R. Spratley for excellent secretarial assistance and to the National Wilms’ Tumor Study group for the data provided and permission for its use. This work was supported in part by USPHS grant CA-42326. REFERENCES 1. Weeks DA, Beckwith JB, Mierau GW: Rhabdoid tumor: An
entity or a phenotype? Arch Pathol Lab Med 113: 113-1 14, 1989. 2. Bonnin JM, Rubinstein LJ, Palmer NF, Beckwith J F The association of embryonal tumors originating in the kidney and in the brain-A report of seven cases. Cancer 54:2137-2146, 1984. 3. Weeks DA, Beckwith JB, Mierau GW, Luckey BW: Rhabdoid tumor of‘ the kidney: Report of I 1 I cases from National Wilms Tumor Study Pathology Center. Am J Surg Pathol 13:439-458, 1989. 4. de Chadarevian JP, Russo P: Central nervous system renal neoplasia: A puzzling emerging association in young children, abstracted. Lab Invest 50:2, 1984. 5 . Malik R: Rhabdoid tumor of the kidney. Med Pediatr Oncol 161203-205, 1988. 6. Chang C-H, Ramirez N , Sakr WA: Primitive neuroectodermal tumor of the brain associated with malignant rhabdoid tumor the A histologic, immunohistochemical and electron microc study. Pediatr Pathol 9:307-319, 1989. 7. Schmidt D, Leuschner 1, Harms D, Sprenger E, Schafer HJ: Malignant rhabdoid tumor: A morphological and flow cytometric study. Pathol Res Pract 184:202-210, 1989. 8. Biegel JA, Rorke LB, Packer RJ, Emanuel BS: Monosomy 22 in rhabdoid or atypical tumors of the brain. J Neurosurg 73:710-714, 1990. 9. Sotelo-Avila C, Gonzalez-Crussi F, deMello D, Vogler C, Gooch WM, Gale G, Pena R: Renal and extra-renal rhabdoid tumors in children: A clinicopathologic study of 14 patients. Semin Diagn Pathol 3:151-163, 1985. 10. Biggs PJ, Garen PD, Powers JM, Garvin AJ: Malignant rhabdoid tumor of the central nervous system. Hum Path01 18:332-337, 1987. 11. Jakate SM, Marsden HB, Ingram L: Primary rhabdoid tumor of the brain. Virchows Arch [Pathol Histopathol] 412:393-397, 1988. 12. Chi Y-W, Lee WH, Hwang RC, Liao HB, Cheng SN, Chu ML, Chou TY, Ho PS: Intracranial malignant rhabdoid tumor: Report of one case. Acta Paediatr Sin 30:316322, 1989. 13. Lynch HT, Shurin SB, Dahms BB, Izant RJ, Lynch J, Danes BS: Paravertebral malignant rhabdoid tumor in infancy: In vitro studies of a family tumor. Cancer 52:290-296, 1983. 14. Tsuneyoshi M, Daimaru Y, Hashimoto H, Enjoji M: Malignant soft tissue neoplasm with the histologic features of renal rhabdoid tumors: An ultrastructural and immunohistochemical study. Hum Pathol 16:1235-1242, 1985. 15. Ekfors TO, Aho HJ, Kekomaki M: Malignant rhabdoid tumor of the prostatic region: Immunohistochemical and ultrastructural evidence for epithelial origin. Virchows Arch 406:381-388, 1985. 16. Small EJ, Gordon GJ, Dahms BB: Malignant rhabdoid tumor of the heart in an infant. Cancer 55:2850-2853, 1985. 17. Parham DM, Peiper SC, Robicheaux G, Ribeiro RC, Douglass EC: Malignant rhabdoid tumor of the liver: Evidence for epithelial differentiation. Arch Pathol Lab Med 1 1 2 : 6 1 4 , 1988. 18. Frierson HF, Mills SE, Innes DJ: Malignant rhabdoid tumor of the pelvis. Cancer 55:1963-1967, 1985. ‘
Rhabdoid Tumor of the CNS 19. Blatt J, Russo P, Taylor S: Extrarenal rhabdoid sarcoma. Med
Pediatr Oncol 14:221-226, 1986. 20. Robson DB, Akbarnia BA, deMello D, Connors RH, Crafts DC: Malignant rhabdoid tumor of the thoracic spine. Spine 12:620621, 1987. 21. Kent AL, Mahoney DH, Gresik MV, Steuber CP, Fernback DJ: Malignant rhabdoid tumor of the thoracic extremity. Cancer 60:105&1059, 1987. 22. Hams M, Eyden BP, Joglekar VM: Rhabdoid tumor of the bladder: A histological ultrastructural and immunohistochemical study. Histopathology 11:1083-1092, 1987. 23. Dervan PA, Cahalane SF, Kneafsey P, Mynes A, McCallister K: Malignant rhabdoid tumor of soft tissue: An ultrastructural and immunohistological study of a pelvic tumor. Histopathology 11:183-190, 1987. 24. Balaton AJ, Vaury P, Videgrain M: Paravertebral malignant rhabdoid tumor in adult: A case report with immunocytochemical study. Pathol Res Pract 182:713-718, 1987. 2s. Batsakis JG, Manning JT: Malignant rhabdoid tumor. Ann Otol Rhino1 Laryngol 97:690-691, 1988. 26, Dabbs DJ, Park HK: Malignant rhabdoid skin tumor: An uncommon primary skin neoplasm. Ultrastructural and immunohistochemical analysis. J Cutan Pathol 15:109-115, 1988. 27. Uchida H, Yokoyama S, Nakayama I, Zeze K: An autopsy case of malignant rhabdoid tumor arising from soft parts in the left inguinal region. Acta Pathol Jpn 38: 1087-1096, 1988. 28. Patron M, Palacios J, Rodrigues-Peralto JL, Burgos E, Contreras F: Malignant rhabdoid tumor of the tongue: A case report with immunohistochemical and ultrastructural findings. Oral Surg Oral Med Oral Pathol 65:67-70, 1988. 29. Tsokos M, Kouraklis G, Chandra RS, Bhagavan BS, Tnche TJ: Malignant rhabdoid tumor of the kidney and soft tissues: Evidence for a diverse morphological and immunocytochemical phenotype. Arch Pathol Lab Med 113:115-120, 1989. 30. Carter RL, McCarthy KP, Al-Sam SZ, Monagham P, Agrawal M, McElwain TJ: Malignant rhabdoid tumor of the bladder with immunohistochemical and ultrastructural evidence suggesting histiocytic origin. Histopathology 14:17%190, 1989.
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31. Tsujimura T, Wada A, Kawano K, Iwasa A, Mizutani S: A case of malignant rhabdoid tumor arising from soft parts in the prepubic region. Acta Pathol Jpn 39:677-682, 1989. 32. Molenaar WM, DeJong B, Dam-Meiring A, Postma A, DeVries 3, Hoekstra HJ: Epithelioid sarcoma or malignant rhabdoid tumor of soft tissue? Epithelioid immunophenotype and rhabdoid karyotype. Hum Path01 20:347-351, 1989. 33. Kawanishi Y, Tamura M, Akiyama K, Akiyama M, Tanaka T, Numata A, Yuasa M, Imagawa A: Rhabdoid tumor of the spermatic cord. Br J Urol 53:439440, 1989. 34. Rootman J, Damji KF, Dimmick JE: Malignant rhabdoid tumor the orbit. Ophthalmology 96: 1650-1654, 1989. 35. Cho KR, Rosenshein NB, Epstein JI: Malignant rhabdoid tumor of the uterus. Int J Gynecol Pathol 8:381-387, 1989.
SERIES EDITOR’S NOTE
The “rhabdo” (“rod” in Greek) part of the term rhubdomyosurcoma calls attention to the rod-shaped cell characteristic of that lesion. “Rhabdo” is used in other interesting word constructs, for example, “rhabdomancy,” or the discovery of hidden objects, usually well water, by divination using a rod or wand. Insofar as the word rhabdoid itself is concerned: there is such a word. It means “rod-shaped’ and is thus incorrectly used for tumors of that name. They neither grossly nor microscopically fit the description. Because the cell of origin of the lesion remains unknown, maybe our pathology colleagues should in the meantime do as is often done in medicine, that is, give the unknown a Latin name to cover our ignorance. Thus the rhabdoid tumor could become the “tumor ab origine ignota” or the TO1 for short. Sounds better than, “We don’t know,” but adds little more.
PROCEEDINGS OF THE TUMOR BOARD OF THE CHILDREN’S HOSPITAL OF PHILADELPHIA Ciulio J.D’Angio, MD, Series Editor, and Audrey E. Evans, MD, Associate Editor
Rhabdoid Tumor of the Central Nervous System Ciorgio Perilongo, MD, Leslie Sutton, MD, Dannette Czaykowski, Debra Gusnard, MD, and Jaclyn Biegel, PhD
MSN, CPNP,
Key words: rhabdoid tumors, central nervous system, Wilms’ tumors
Dr. Ciorgio Perilongo, Neuro-Oncologist)
MD
(Pediatric
The topic of the tumor board this week regards central nervous system (CNS) rhabdoid tumors (RHTs). We chose this topic, first of all, to try to elaborate a rational therapeutic plan for the patient who will be presented and, second, to highlight the unique biological phenomena that appear to link RHTs with CNS tumors. The existence of extrarenal RHTs as an entity has recently been questioned by Weeks et al. [ 13, who argued that many neoplasms can mimic the light microscopic appearance of RHT of the kidney (RHTK). They suggest that RHTs represent merely a phenotype and not an entity and that extrarenal RHTs will eventually “emerge as a phenotypic concept encompassing a spectrum of histogenetic and clinical diversity.” It is important to recall these statements before opening the discussion and to take a more critical view of the biological and clinical problems of RHTs. So much for introduction; we can now proceed with the presentation of the case. The patient is a 5-year, 11-month-old white girl who was well until early April 1990, when she developed headache and photophobia. Two to 3 days before admission, the patient developed worsening headache, vomiting, and right disconjugate gaze. Her neurological examination on admission revealed bilateral papilledema, right homonymous hemianopsia, decreased visual acuity and mild bilateral sixth nerve palsy. A brain tumor was suspected, and a magnetic resonance image (MRI) of the brain was requested. Dr. Gusnard, will you please discuss the findings? Dr. Debra Cusnard,
MD
(Pediatric Neuro-Radiologist)
T2- and TI-weighted images before the administration of the contrast agent gadolinium-DTPA reveal a very large, lobulated neoplasm of inhomogeneous signal in0 1991 Wiley-Liss, Inc.
tensity in the left occipital lobe. It extends into the posterior portion of the temporal lobe and is surrounded by a moderate amount of vasogenic edema (Fig. 1A). After contrast administration, the tumor markedly enhances and shows signs suspicious for tentorial invasion (Fig. 1B). There is moderate mass effect, including some compression and distortion of the brain stem. The signal intensity inhomogeneity before contrast administration is at least partly attributable to foci of hemorrhage within the mass, including some small cystic areas. Those portions of the tumor that are not hemorrhagic, however, appear nearly isointense to brain parenchyma on the T2-weighted images. This is in contrast to the usual bright signal intensity of most tumors on T2-weighted images. It is noteworthy, because it suggests that this tumor has less free water content than many other tumors because of dense cellularity and a high nuclear to cytoplasmic ratio, reminiscent of the primitive neuroectodermal tumors (PNET-medulloblastoma). This is also suggested by the tumor’s hyperdense appearance on the computed tomography (CT) scan (Fig. 2), an appearance characteristic also of PNET. Dr. Perilongo. In view of these findings the child was then seen by the neurosurgeons and brought to the operating room for removal of the tumor. Leslie Sutton,
MD
(Pediatric Neurosurgeon)
The tumor was massive, filling most of the occipital lobe, and was approached by a large occipital craniotFrom the Neuro-Oncology Program, Division of Oncology (G.P., D.C.), Neurosurgery (L.S.), Neuroradiology (D.G.), Human Genetics, (J.B.), Children’s Hospital of Philadelphia, Philadelphia. Received February 6, 1991; accepted February 21, 1991. Address reprint request to Giulio J. D’Angio, MD, Department of Radiation-Oncology ,Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104.
Rhabdoid Tumor of the CNS
Fig. 1. Rhabdoid tumor. MR images. A:Axial 3000/90 (T2weighted) image reveals a large lobulated mass (small arrowheads) in the left temporo-occipital region abutting the tentorium (large arrowhead) and demonstrating mass effect with distortion of the upper brain stem. Though inhomogeneous in signal intensity, the bulk of the mass is nearly isointense to normal brain parenchyma. Small cysts and foci of blood products account for most of the inhomogeneity; a fluid-blood
311
level is seen within a cystic region (small arrow). High signal intensity corresponding to vasogenic edema is seen in the surrounding white matter. B: Coronal 600122 (TI-weighted) image after administration of gadolinium-DPTA reveals marked enhancement of the tumor as well as prominent asymmetrical enhancement along the adjacent tentonal margin (arrowheads), highly suspicious for its invasion.
omy. It was quite vascular and received a large blood in the kidney of infants but that are known to occur in supply from the tentorium, which was invaded by tumor. other organs as well. Dr. Perilongo. At this point, we were faced with how It proved possible to remove all of the gross tumor, but there was obviously microscopic disease left on the dura. to stage a patient with an extrarenal RHT. Because the tumor invaded the tentorium, the spinal cord and cereLucy Rorke, MD (Pediatric Neuro-Pathologist) brospinal fluid pathways were examined by myelograAll histological sections of the tumor were similar and phy, a gadolinium-enhanced MRI of the cord, and spinal composed of large cells with distinct cytoplasmic board- fluid cytology. All these tests were negative. Because ers. The cytoplasm was either clear or bright pink, and RHTK disseminates hematogenously, we also obtained a nuclei were round or bilobar and eccentrically placed bone scan and CT of the chest. No remote metastases (Fig. 3). Nucleoli and mitotic figures were prominent, were found. Finally, because of the known association between and there were many foci of necrosis. A battery of immunoperoxidase stains was done that included the RHTK and brain tumors, a renal ultrasound was obfollowing: glial filament acid protein, neurofilament tained, even though the association of RHTK and RHT of proteins, synaptophysin, desmin, AElK (low molecular the brain is exceedingly rare. The first report of six cytokeratin), vimentin, and epithelial membrane antigen childhood RHTKs associated with primary brain tumors (EMA) (Fig. 4). Of these only the EMA was strongly list these as medulloblastoma, pineoblastoma, PNET, positive, although a small percentage of cells was also and malignant subependymal giant cell astrocytoma [2]. positive for vimentin. The histological features are those A review of 111 patients with RHTK by Weeks et al. [3] of an RHT similar to those that were originally described discerned that 15 (13.5%) developed a brain tumor. They
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Perilongo et al.
Fig. 2. CT scan without contrast. Note the nearly diffuse hyperdensity of the tumor, which suggests its highly cellular nature. Areas of particularly high density represent foci of hemorrhage (arrowheads).
were all histologically different from RHTK. More commonly they were diagnosed medulloblastoma, ependymoma, or gliomas. They tended to occur in or near the midline, either in the posterior fossa or just above the tentorium cerebelli. There was no consistent temporal relationship to the diagnosis of the renal tumor. Interestingly, brain metastases of RTK were randomly distributed, usually in the cerebrum. An association between renal and CNS RHT seems to exist, however. There is an abstract describing these tumors coexisting in two children [4], and we also have seen such a case [S] . The occurrence of a renal and brain RHT in the same patient could of course be explained as one of the two lesions being a metastasis from the other. Dr. D’Angio, perhaps you could tell us of the experience of the National Wilms’ Tumor Study (NWTS) in regard to RHTK.
Fig. 3. Photomicrograph of typical field from tumor composed of cells with prominent cytoplasmic membrane, clear or eosinophilic cytoplasm, and large nuclei with prominent nucleoli. Some cells are binucleated. Hematoxylin and eosin stain.
data. Table I shows the 2 and 4 year survival rates for favorable histology Wilms’ tumors, the anaplastic form, and the two non-Wilms’ tumors that occur relatively frequently in the kidneys of children, namely, the clear cell sarcoma of the kidney (CCSK) and the RHTK. As can be seen, survival is the worst for RHTK. It does not appear to be responsive to the triple attack that is so successful with the other forms of primary renal cancers of childhood. Also note that both the CCSK and the RHTK can affect the brain. Table I1 shows the distribution of metastases at diagnosis and Table 111 at first relapse. Clearly, the lung is the most frequently affected site for both tumor types, but the brain usually is not Ciulio D’Angio, MD (Pediatric Radiation Therapist) involved at diagnosis. It is, however, one of the relatively RHTKs are very aggressive lesions. Just how aggres- common sites of recurrence. A careful search during sive and lethal is clear from a review of the NWTS-3 follow-up for evidence of disease both in the thorax and
Rhabdoid Tumor of the CNS
313
TABLE I. National Wilms’ Tumor Study: Outcomes by Histology*
Survival Tumor typea
No.
2 year
4 year
FH 1,667 90 87 48 67 65 Ana 19 93 71 CCSK RHTK 48 24 24 *All stages. aFH, favorable histology Wilms’ tumor; Ana, anaplastic Wilms’ tumor; CCSK, clear cell sarcoma of kidney; RHTK, rhabdoid tumor of kidney.
rarely metastasize outside the CNS, and isolated liver metastases also are rare in RHTK patients. One other 2-month-old boy who had an RHT of the headheck region with a “medulloblastoma” was described by Schmidt et al. [7]. Dr. Biegel, do you have any data on the genetics of these tumors that could help in understanding their biology? Jaclyn Biegel, PhD (Cytogenetist)
Fig. 4. Section of tumor stained by the immunoperoxidase method for presence of epithelial membrane anitgen (EMA). Cytoplasm and/or all membranes of many cells are positive (black-staining material). Immunoperoxidase stain for EMA.
in the brain but not the skeleton is therefore warranted in RHTK patients. The implications of all this for children with RHT of the brain is the following: Unless there are other typical signs of RHTK such as young age and hypercalcemia, it is probably unnecessary to undertake a long and expensive search for a possible primary kidney tumor. The rare RHT of the brain would seem to be a separate and distinct entity. Dr. Perilongo. In regard to the relationship between RHTK and CNS tumors, the case published by Chang et al. [6] of a 14-day-old boy with a PNET of the left cerebral hemisphere and a solitary RHT of the liver incidentally found at autospy is of great interest. Cells resembling the liver RHT were observed in the brain tumor, suggesting that the liver lesion was a metastatis from the cerebral neoplasm. However, brain tumors
Cytogenetic studies of the brain tumor from this patient were performed in our laboratory. The tumor cells displayed an abnormal karyotype, with several changes including an abnormal chromosome 22. This finding is significant in light of our studies of three rhabdoid or atypical teratoid tumors of the brain that demonstrated monosomy 22 as the only change [8]. By contrast, abnormalities of chromosome 22 are rarely seen in PNETs; rather, i(17q) is seen in a large percentage of them. Cytogenetics may thus be used as an additional means of diagnosing RHTs of the brain. Studies of RHTs of the brain and kidney from the same patients are needed to help establish a common etiology for these tumors, if one exists. Dr. Perilongo. Moving forward in the discussion, we would like to consider the therapeutic options available to this child. Dr. Goldwein, do you think this child should be treated with radiation therapy (RT)? JoelColdwein, MD (Pediatric Radiation Therapist)
I believe this child should be treated with craniospinal RT and would recommend 3,600 cGy to the craniospinal axis, with a “boost” to the site of the primary tumor. what do you think Dr. D’Angio? Dr. D’Angio. I agree, even though I am not confident that RT is of much value for this kind of tumor. Dr. Perilongo. In order to find some possible therapeutic recommendations, and stimulated by the hypothesis advanced by Weeks et al. [I], we reviewed the experience accumulated at the Children’s Hospital of
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Perilongo et al. TABLE 11. National Wilms’ Tumor Study-3: Metastases Present at Diagnosis by Site and Tumor Type*
Site
FH (N = 173) No. Percent
Ana (N = 16) No. Percent
Lung only Liver only Bone only Brain only Lung other Other
142 10 21 -
13
+
82 6 -
1 -
12
2
-
-
-
CCSK (N = 4) No. Percent
50
-
2 2 -
13
-
-
-
-
-
81 6
-
-
50 -
RHTK (N = 10) No. Percent
5
50
-
-
-
-
-
-
3 2
30 20
*More than one site might be involved. N = total number of patients who relapsed. Columns give number who relapsed at that site and the total who relapsed. FH, favorable histology; Ana, anaplastic Wilms’ tumor; CCSK, clear cell sarcoma; RHTK, rhabdoid tumor of the kidney.
TABLE 111. National Wilms’ Tumor Study-& Sites of First Relapse by Tumor Type*
Site Lung Liver Bone Brain Flank /abdomen Opp. kidney Other
CCSK (N = 21) Percent
No.
RHTK (N = 24) No. Percent
5 I 13 5 2 0
24 5 62 24 10
14 3 I 3 13 0
58 13 4 13 54
4
19
4
17
*More than one site might be involved. N = total number of patients who relapsed. Columnsgive number who relapsed in that site and the percentage of the total who relapsed. Total numbers of stage 1-111 patientson study were72 for CCSK and 36 for RHTK. CCSK,clear cell sarcoma of the kidney; RHTK, rhabdoid tumor of the kidney.
Philadelphia (CHP) on CNS and extrarenal RHTs along with all the cases so far published. This includes only those cases in which: 1) the light microscopy features fit the criteria described by Weeks et al. [ 13; 2) there was a positive vimentin stain; and 3) whorls of filamentous cytoplasmatic inclusions were identified on ultrastructural study. In presenting these cases, RHTs of the CNS will be kept separate from all other extrarenal RHTs. We reviewed seven cases of primary RHTs of the CNS, four published in the literature and three observed in this institution [9-121.’ All occurred in children aged between 6 months and 13 years (median, 3 years). Four of the seven tumors were in males. The tumor was located infratentorially in five and supratentorially in two; two patients with a posterior fossa tumor also had evidence of subarachnoidal seeding of the tumor, with a large spinal metastatic lesion in one of the CHP children. One other ‘The discussion has been modified to include the index case because
of the interval between the case presentation and publication.
child presented with two intracerebral masses, the larger in the posterior fossa and the other, more discrete lesion, in the suprasellar region [ 121. A 6-month-old boy seen at CHP had a concurrent RHTK. When last reported, one child was alive with no evidence of disease (NED) at 5 months from diagnosis after gross-surgical resection, craniospinal RT, and “8-in- 1” systemic chemotherapy. The index case was treated similarly but had cyclophosphamide, cisplatin, VP 16,and vincristine instead and is alive NED at 6 months. The remaining five patients died of disease, one soon after diagnosis and the others at 2 112, 3, 3, and 5 months after diagnosis despite craniospinal RT in two and chemotherapy alone in the others. Subarachnoidal seeding of the tumor was documented in three cases at autopsy. None of these patients had extra-CNS disease at death. For comparison, we reviewed 43 cases of extrarenal, non-CNS RHTs reported in the literature [ 13-35].Thirtythree (77%) occurred in patients less that 19 years of age. Sixteen of 33 childhood RHTs (48%) occurred in children less than l year of age and 21 (64%) in patients under 5 years. A stillborn product of a normal pregnancy was reported to be affected by a chest RHT [9]. Male predominance is observed in both age groups, with a ma1e:female ratio in children of 1.5: 1 and 4:l in adults (Table IV). The primary sites of extrarenal non-CNS RHTs have been: trunk (six children, three adults), extremities (six children), headheck (three children, two adults), paravertebral region (three children, one adult), pelvis (four children), genitourinary tract (three children, one adult), liver (four children) and orbit (one child), heart (one child), thymus (one child), adrenal gland (one child), perineum (one adult), uterus (one adult), and skin (one adult). Two cases of extrarenal RHTs in association with PNET of the CNS have been reported as already discussed [6,7].Seven of the 33 children (21%) with RHT and 1 of the 10 occurring in adults had metastases at presentation. Pulmonary metastases were the most frequent (seven cases), followed by liver (three cases) and bone (one case).
Rhabdoid Tumor of the CNS
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TABLE IV. Comparison of Some Clinical Characteristics of Patients With Rhabdoid Tumor by Primary Site (Renal Vs. Central Nervous System Vs. Other Sites)* RHT
Ages Range Median Sex Male Female Patient status No. of PtsC Alive NED FOIIOW-UP Range Median Alive NED Range Dead of disease Survival timed Rangea Median
RHTKa ( N = 111)
RHT-CNS (N = 7)
Children (N = 33)
NB- 106 11
6-156 36
NB-228 12
Adults (N = 10) 25-59 years 41 years
63b 43
4 3
20 13
8 2
84 15 (18%)
7 2 (29%)
32 9 (28%)
9 1(11%)
Not known Not known
5-6
1-96 18 2 3-6 21 (66%) 2-28 5
-
-
-
69 (82%)
5 (71%)
Not known Not known
2.5-5 3
10 1
5 7 (78%)
2-84 7
*All times in months unless otherwise noted; NB, newborn; RHTK, rhabdoid tumor of the kidney; RHT-CNS, rhabdoid tumor of the central nervous system; RHT, rhabdoid tumors arising elsewhere. aData from Weeks et al. 131. bGender not known in five. CFor patients whose follow-up is known. dlncludes only patients who survived more than 14 days after diagnosis.
Regional lymph nodes were positive in patients who had RHT of the heart, skin, and spermatic cord (one each) and in two others, both with a tumor of the trunk. A case of RHT of the left inguinal region in a 3 1-year-old man associated with hypercalcemia (- 11.O mgldl) was described by Uchida et al. [27]. The hypercalcemia decreased toward a normal level just after tumor debulking, but apparently rose soon afterward; and, at autopsy, metastatic calcifications were seen in the lungs and kidneys. The parathyroids were not enlarged. No data on treatment and follow-up were available for 2 of 43 RHTs (one in a child and one in an adult). At the time of the reports, 9 of the 32 children (28%) and 1 of the 9 adults (1 1%) with RHT were alive apparently with NED. The follow-up ranged from 1 month to 8 years (median, 18 months) for the 10 children with RHT. The only adult alive with NED had a follow-up of 10 months. Twenty-one children (66%) and seven adults (78%) died of disease; two children and one adult were reported alive with tumors at 3, 6, and 5 months, respectively, from diagnosis. Five children died of disease within the first 2 weeks from diagnosis. The overall survival time of the remaining patients who died of disease varied from 2 to 28 months (median, 5 months) for the 16 children and from 2 months to 7 years (median, 7 months) for the 7
adults. Thirteen of the 16 children (81%) and 4 of the 7 adults (57%) died within 1 year of diagnosis. Six of the 3 1 patients for whom the surgical procedure is known had a grossly complete resection. Three of those (two children and one adult) at the time of the report were alive with NED at 5 , 10, and 105 months from diagnosis, respectively. The other three patients suffered lung metastases associated with regional lymph node relapses in two and local recurrence in one. Sixteen patients received RT with doses varying from 2,000 to 5,400 cGy; eight (50%) apparently failed at the primary site and died of disease. Thirty had systemic chemotherapy consisting mainly of vincristine, cyclophosphamide, doxorobucin, and/or dactinomycin. No complete responses to chemotherapy have been documented, but at this time it is impossible to make firm statements on the impact of different modalities on outcome. The metastatic sites are known for 20 patients (clinical and or autopsy reports). Pulmonary metastases were the most frequent (12 cases [60%]); followed by distant lymph nodes, 7 cases; CNS, 4; liver, 3; and bone, 3. Other metastatic sites have been heart, retro-orbital tissue, bladder, adrenal, pancreas, larynx, and bone marrow. Three patients had epidural metastases; another with a paravertebral RHT also had a brain stem tumor at
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Perilongo et al.
death (histologically not documented) [ 131. Otherwise, isolated intraparenchymal CNS metastases have not been reported. This literature survey does not allow us to draw any concrete conclusions. The CNS seems to be a quite common location for RHT, ranking second in the extrarenal primary sites of RHT after trunk. RHT of the CNS seems to occur in young children but probably with a later peak of incidence than RHTK (Table IV). No cases of CNS RHT were documented in adults. It appears that for CNS RHTs, and particularly for extrarenal non-CNS RHTs, the age span of the affected patients is much wider than for RHTK. There was a male prevalence (M/F ratio 1.3:1) among the CNS tumors we collected, as is true for both RHTK and extrarenal RHT (1.5:l in children for both). As expected, none of the patients developed disease outside the CNS during the clinical course, but one child treated here had a concurrent RHTK. Interestingly, no CNS metastases have yet been reported at presentation for either RHTK or extrarenal RHT, CNS involvement having been described only at the time of recurrence or death. The tendency of these tumors when they occur in the brain to seed the subarachnoidal pathways has been clearly documented. None of the seven patients with a CNS RHT had hypercalcemia, as sometimes reported in RHTK patients and apparently described also in one case of nonrenal RHT [27]. Five of the seven patients with CNS tumors succumbed to the disease, as did most of the RHTK and extrarenal RHT patients (Table IV). Actually, it seems that RHTs, regardless of their primary location, have a very poor prognosis and a quite rapid clinical coursethis despite multimodality therapy as Dr. D’Angio has already pointed out for RHTK. A literature survey cannot, of course, settle the issues concerning the heterogenicity of tumors identified by the term rhabdoid. This remains open to further biological, histological, and genetic study, which may also clarify the fascinating relationship between kidney and other RHTs, including those of the CNS. All the foregoing leaves unsolved the problem of how to treat a child affected by this aggressive albeit rare tumor. There is little in the literature to guide us, and we have elected to treat this patient with intensive systemic chemotherapy and craniospinal RT, as proposed by Dr. Goldwein. The chemotherapy chosen is the one currently in use on the “Baby Brain Tumor protocol,” including cisplatin, cyclophosphamide, vincristine, and etoposide. According to Weeks et al. [3], the completeness of surgical resection and the absence of lymph node involvement are probably favorable prognostic factors for RTKs. If an analogy can be drawn, it could be that the gross complete removal of the tumor achieved in this child augurs a favorable outcome.
ACKNOWLEDGMENTS
We are grateful to Donna R. Spratley for excellent secretarial assistance and to the National Wilms’ Tumor Study group for the data provided and permission for its use. This work was supported in part by USPHS grant CA-42326. REFERENCES 1. Weeks DA, Beckwith JB, Mierau GW: Rhabdoid tumor: An
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Rhabdoid Tumor of the CNS 19. Blatt J, Russo P, Taylor S: Extrarenal rhabdoid sarcoma. Med
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SERIES EDITOR’S NOTE
The “rhabdo” (“rod” in Greek) part of the term rhubdomyosurcoma calls attention to the rod-shaped cell characteristic of that lesion. “Rhabdo” is used in other interesting word constructs, for example, “rhabdomancy,” or the discovery of hidden objects, usually well water, by divination using a rod or wand. Insofar as the word rhabdoid itself is concerned: there is such a word. It means “rod-shaped’ and is thus incorrectly used for tumors of that name. They neither grossly nor microscopically fit the description. Because the cell of origin of the lesion remains unknown, maybe our pathology colleagues should in the meantime do as is often done in medicine, that is, give the unknown a Latin name to cover our ignorance. Thus the rhabdoid tumor could become the “tumor ab origine ignota” or the TO1 for short. Sounds better than, “We don’t know,” but adds little more.
