Primary intracranial rhabdomyosarcoma: report of two cases

Child's Nerv Syst (1989)5:246-249

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© Springer-Verlag 1989

Case report

Primary intracranial rhabdomyosarcoma: report of two cases* G i u s t i n o T o m e i 1 N a d i a G r i m o l d i 1 E n r i c o C a p p r i c c i 1, E r i k P. S g a n z e r l a 1 Sergio M . G a i n i 1, R o b e r t o Villani ~, a n d B a t t i s t i n a M a s i n i 2 1Institute of Neurosurgery and z Department of Pathology, University of Milan, Via F. Sforza, 35, 1-20122 Milan, Italy

Abstract. Primary intracranial r h a b d o m y o s a r c o m a (RMS)

is a rare tumor in infancy and childhood that is found in various locations in the central nervous system. The clinical course worsens rapidly, and the final outcome is poor, with a median survival time of 8 - 1 0 months. Invasion of the meninges, spontaneous intratumoral bleeding, spinal leptomeningeal CSF spreading of tumor cells, and early recurrence of the mass are the distinctive features of RMS. Diagnosis of R M S may be missed: immunohistochemical staining using specific markers (myoglobin, myosin, desmin, vimentin, enolase), along with ultrastructural studies, provide the basis for making the final diagnosis. Treatment of R M S includes surgical excision, craniospinal radiation therapy, and chemiotherapy. We report two cases of primary RMS in the CNS located in the posterior fossa and frontotemporal area. Both children underwent total surgical removal of the mass. Early recurrence of the tumor mass was noticed in both patients 2 months after surgery. Both children died shortly thereafter. Key words: Intracranial r h a b d o m y o s a r c o m a - Intratumoral hemorrhage - Immunochemistry.

from neuroectoderm, the true mesenchymal or neuroectodermal origin of R M S is still a matter of debate [2]. The immunohistochemical aspects of RMS are very important: the presence of myoglobin, myosin, desmin, enolase and other enzyme staining are valuable in demonstrating RMS. Children with R M S do not present clinical signs and symptoms that are different from other brain tumors; unfortunately, the clinical course worsens rapidly and the final outcome is poor. We report two cases of R M S treated at out Institute over the last 2 years.

Case reports

Case 1

A 14-month-old girl did well until 2 months before admission to the hospital when she began to be apathetic and somnolent. Two days before admission she was vomiting and showed ataxia, strabism, right hemiparesis, and lethargy. A C T scan demonstrated a remarkable lateral and III ventricle dilation and the presence of a mass in the pineal area that extended to the upper part of the IV ventricle. The tumor was a slightly round, irregular mass that was almost uniformly hyperdense with a further enhancement after injection of contrast medium (Fig. 1).

R h a b d o m y o s a r c o m a (RMS) or embryonal sarcoma or mixed mesenchymal tumor is a sarcoma variant [7]. Its most c o m m o n location in childhood is the head and neck. Primary intracranial R M S is rare since only 35 cases have so far been reported [2, 4]. Diagnosis of intracranial R M S is difficult. The presence of striate muscle fiber differentiation and/ or an association with neuroepithelial elements can be interpreted as teratomas or medullomyoblastomas. True R M S does not show evidence of such cell differentiation [2]. The presence of pleomorphic cells in R M S may be interpreted as an expression of "multipotential divergent differentiation on the part of a highly plastic embryonic type of mesenchymal tissue" [7, 8]. Since mesenchymal cells of the central nervous system (CNS) capillaries may be derived * Presented at the llth Meeting of the European Society for Paediattic Neurosurgery, Naples 1988

Fig. 1. Case 1: preoperative CT scan. A large hyperdense mass is located in the posterior part of III ventricle. Lateral and III ventricle dilation

Offprint requests to: G. Tomei

Fig. 2. Case 1 : recurrence of the tumor 2 months after surgery

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Fig. 3. Case 1 : photomicrograph of the tumor (autopsy material). Round and pleomorphic cells with abundant cytoplasm scattered in a myxoid matrix (hematoxylin and eosin, x 100)

ventricle and posterior fossa (Fig. 2). Twelve days later she died. A complete autopsy was performed.

Pathology. The initial postoperative histological diagnosis was a Fig. 4. Case 1: immunochemical positive staining for myoglobin ( x 250) Fig. 5, Case 2: photomicrograph of the tumor. Two types of cells are present: large pleomorphic cells with eosinophilic cytoplasm and small cells with scant cytoplasm and dark nuclei (hemotoxylin and eosin x 65) Fig. 6, Case 2: immunochemical positive staining for actin ( x 100)

MR imaging outlined a tumor mass extending toward the IV ventricle and cerebellar vermis and invading the posterior part of the III ventricle. The patient underwent an extrathecal CSF shunt and then received external radiation therapy, with 2000 rads given in 10 fractions. A C T scan performed shortly after the radiation therapy did not show any evidence of tumor shrinkage. The patient was then admitted to our institute and submitted to surgery. A suboccipital craniectomy was performed. Exposure of the IV ventricle revealed the presence of a mass occupying its upper portion. The cerebellar vermis was incised and a friable, necrotic and somewhat calcific tumor located in the upper part of the IV ventricle and reaching the posterior part of the III ventricle was totally removed. The postoperative course was characterized by rapid neurological improvement, and the patient was discharged with moderate strabism. She did well during the following 2 months and then suddenly deteriorated and was readmitted in decerebrate coma. CT scan showed the presence of a huge recurrent mass that was nonhomogeneously hyperdense and largely occupied the III

teratoma. At autopsy, gross examination of the brain showed the presence of a large, .partly hemorrhagic mass that occupied the posterior part of the III ventricle and was encased in the IV ventricle. Nodular masses were found in the cerebral and spinal meninges. There was no tumor outside the CNS. Histology revealed a tumor with superficial invasion o f the cerebellar structures, large necrotic areas, and pleomorphic cells ranging from medium to large. Most tumor cells had eosinophilic cytoplasm with round eosinophilic bodies. The nuclei were usually round and pleomorphic with prominent nucleoli and clear chromatin. The nuclear membrane was usually sharply defined (Fig. 3). Immunohistochemical stains were positive for striated muscle markers in some cells; other markers, including vimentin, cytokeratin (KL 1) and enolase, were seen in many other cells (Fig. 4). Histopathological findings were consistent with a diagnosis of primitive CNS RMS.

Case 2 A 14-year-old boy had the first orofacial sensorimotor seizure 6 months before hospitalization. Later on, he began having dysphasia and paresis of the right hand. A C T scan performed on admission showed a left frontotemporal tumor. The mass had irregular boundaries and was mildly hyperdense, with dyshomogeneous areas of hyperdensities. Contrast enhancement resulted in an almost homogeneous increase of tumoral density. The patient underwent a frontotemporal craniotomy and total resection of a firm, well-capsulated tumor attached to and infiltrating the dura mater. Postoperative neurological examination revealed

248 complete remission of right-hand paresis and the persistence of aphasia. The patient was discharged and referred to another hospital where he was submitted to external radiation therapy. One month later, lumbar CSF cytology showed the presence of neoplastic cells consistent with leptomeningeal metastasis. The patient worsened rapidly and died 60 days after surgery. No CT scan was performed before death. No autopsy findings were available.

Pathology. Histological studies of the frontotemporal mass revealed a tumor that invaded the dura mater and cerebral cortex and had large, necrotic areas. The population of neoplastic ceils was characterized by two forms: (a) medium-sized oval cells with eosinophilic cytoplasm, round hyperchromatic nuclei and large centrally-located nucleoli; (b) small cells with scant cytoplasm and hyperchromatic nuclei (Fig. 5). Immunohistochemical stains were negative for myoglobin, desmin, and panleucocyte antigens and postive for actin, vimentin, and other muscle markers (Fig. 6). The histological findings were suggestive of primitive CNS RMS. Discussion An extensive review of primary intracranial RMS reported in the literature was published by Dropcho and Allen in 1987 [2]. The authors emphasized the aggressiveness and poor prognosis of RMS and the relevance of histological, immunohistochemical, and ultrastructural studies as definitive methods of diagnosing RMS. Primary intracranial RMS is a tumor that is mostly observed in infancy and childhood, as 73% of the reported cases have been patients younger than 18 years of age. The location of the tumor is in the posterior fossa (mostly involving the vermis and/or IV ventricle) in 54% of the cases. In the remainder, the fi'ontotemporal area in the supratentorial compartment was the site most often found. Only in rare instances was tumor found in the basal ganglia, brain stem, clivus, and in the region of the sella turcica [4]. The clinical picture of patients with RMS does not differ from other brain tumors. Unfortunately, the clinical course worsens rapidly, and the median survival time after diagnosis in the reported cases is 7 months, with a range of 1-67 months. In our cases, the survival period was 2 months. Neuroradiological findings, i.e., hyperdense tumor that enhances after contrast medium injection and the location (prevailing in the region of the vermis and frontotemporal areas), may mimic other intracranial tumors such as primitive neuroectodermal tumors, lymphomas, and medulloblastomas. Spontaneous intratumoral hemorrhage was suspected in the tumor recurrence in our first case and was subsequently confirmed at autopsy. Thus intratumoral hemorrhage must be considered a probable cause of death in patients with CNS RMS [2]. The histological findings of primary CNS RMS usually reveal two cellular forms: (a) pleomorphic cells with a variety of shapes (round, oval, spindle) and abundant eosinophilic cytoplasm indicative of rhabd0myoblasts [2]; (b) small cells with scant cytoplasm and hyperchromatic nuclei, defined as poorly differentiated "embryonal" or "mesenchymal cells" [2]. The presence of cross-striations within tumor cells that represent the rhabdomyoblastic differentiation is demon-

strated in less than 50% of the cases. Therefore, the histological diagnosis should differentiate CNS RMS from lymphosarcoma, neuroblastoma, Ewing's sarcoma and other undifferentiated tumors. Misdiagnosis of RMS as primitive neuroectodermal tumors or other undifferentiated tumors is not rare [2]. In our first case, the initial diagnosis was a teratoma. The usefulness of immunohistochemical studies has recently been pointed out [1, 2, 4] and should address the mesenchymal or neuroectodermal origin of the tumor, in addition to aiding in the RMS diagnosis. A number of markers indicative of the presence of RMS have been identified. Among the striated-muscle markers, myoglobin and desmin are specific for striated muscle differentiation: myoglobin is present in 50% to 89% of RMS, including our cases, whereas desmin has only been demonstrated in a single case reported in the literature [2]. Myosin as an expression of early embryonal myoblastic differentiation is more often observed in poorly differentiated tumor cells [2]. Vimentin is a subunit protein of the cytoskeletal intermediate filament and is present early in embryological development. Vimentin staining is positive in meningiomas, sarcomas, and astrocytomas [1]. Cytokeratin is a specific marker of epithelial cells [1]. Both vimentin and cytokeratin alone cannot differentiate mesenchymal from neuroectodermal cells [1] and are not specific for RMS [2]. Enolase, although demonstrated in many neuronal and nonrelated neuron tumors [1], is present in up to 80% of RMS tumors [2]. The ultimate diagnosis of RMS is ultrastructural. Electron microscopy can identify actin and myosin filaments along with Z-band materials in the cytoplasms of pleomorphic cells of RMS [2, 4]. The recommended therapy for RMS in infancy and childhood is surgical resection of the tumor, followed by craniospinal radiation therapy (5000 rads) and chemotherapy. The rarity of this lesion, however, does not allow a conclusive therapeutic regimen: the median reported survival of patients submitted to partial or total surgical removal (with or without other therapies) has been 10 months; that for patients who underwent radiation therapy (with or without other therapies) has been 9 months. The median reported survival of patients who received surgical treatment, radiation therapy, and chemotherapy has been 9 months. In spite of that, 45% of the reported cases, including our two patients, died within 5 months of diagnosis; 18% showed a "short" survival and only 14% survived more than 20 months. In our experience, neither radiation therapy nor total excision of the mass were effective in preventing early recurrence of the tumor and prolonging the life span of the children. Spreading of tumor cells into the cranial and spinal meninges was noted in our two cases and has often been reported in the literature [2, 6]. This should lead to additional prophylactic intrathecal chemotherapy; however, methotrexate injection did not result in clearing CSF of tumor cells [61. Systemic chemotherapy is a matter of debate: as underlined by Dropcho and Allen [2], the debatable cellular origin of RMS in the CNS makes appropriate chemotherapy diffi-

249 cult to select. Should R M S be the counterpart o f systemic R M S , vincristine, actinomycin D and cyclophosphamide are more appropriate. On the other hand, if these tumors are o f neuroectodermal origin, vincristine during r a d i o t h e r a p y and C C N U , vincristine (with or without procarbazine) as maintenance treatment are the therapy o f choice [3].

Acknowledgements. The authors would like to thank Miss Rita Paglino and Mr. Antonio Ladislao for their technical support.

References 1. Bonnin JM, Rubinstein LJ (1984) Immunochemistry of central nervous system tumors. Its contribution to neurosurgical diagnosis. J Neurosurg 60:1121 1133

2. Dropcho EJ, Allen JC (1987) Primary intracranial rhabdomyosarcoma. Case report and review of the literature. J Neurooncol 5:139-150 3. Gaffney CC, Sloane JP, Bradley NJ, Bloom HJG (1985) Primitive neuroectodermal tumors of the cerebrum. J Neurooncol 3:23-33 4. Jalalah S, Kovacs K, Horvath E, Couldwell W, Weiss MH, Ezrin C (1987) Rhabdomyosarcoma in the region of the sella turcica. Acta Neurochir (Wien) 18:142-146 5. Matsukado Y, Yokota A, Marubayashi T (1975) Rhabdomyosarcoma of the brain. Case report. J Neurosurg 43:215-221 6. Olson JJ, Menezes AH, Godersky JC, Lobosky JM, Hart M (1985) Primary intracranial rhabdomyosarcoma. Neurosurgery 17:25-34 7. Rubinstein LJ (1972) Tumors of the central nervous system. Armed Forces Institute of Pathology, Washington, DC 8. Willis RA (1960) Pathology of tumors, 3rd edn. Butterworths, London Received December 5, 1988