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Second Malignancies in Pediatric Patients: Imaging Findings and Differential Diagnosis¹

¹ From the Department of Pediatric Radiology and Institut de Diagnòstic per la Imatge (E.V., A.C., J.P., P.O., J.L.), the Department of Pediatric Oncology (J.S.T.), and the Department of Pediatric Neurosurgery (P.N.), Hospital Materno-Infantil Vall d’Hebron, Psg Vall d’Hebron 112-119, Barcelona E-08035, Spain. Recipient of a Cum Laude award for an education exhibit at the 2002 RSNA scientific assembly. Received February 21, 2003; revision requested April 8 and received June 6; accepted June 6. Address correspondence to E.V. (e-mail: evazquez@cs.vhebron.es).

	Abstract

Top Abstract Introduction Patients and Procedures Pathogenic Factors Types of SMNs Implications for Imaging... Conclusions References

 
Therapeutic advances in the treatment of pediatric neoplasms have improved the prognosis but have also increased the risk of developing rare second malignant neoplasms (SMNs). Primary neoplasms that are often associated with SMNs include lymphoma, retinoblastoma, medulloblastoma, neuroblastoma, and leukemia. The most common SMNs are central nervous system (CNS) tumors, sarcomas, thyroid and parotid gland carcinomas, and leukemia, particularly acute myeloblastic leukemia. Genetic predisposition, chemotherapy, and especially radiation therapy are implicated as pathogenic factors in SMN. All survivors of childhood cancer should have lifelong follow-up, preferably with magnetic resonance imaging, which does not require ionizing radiation and provides greater anatomic detail and resolution in the head and neck region and the CNS. A new or progressive lesion may represent recurrence of the primitive neoplastic process, late radiation injury, or, more infrequently, an SMN. Differential diagnosis can be very difficult, and outcome is often fatal. Treatment protocols should be modified to reduce the risk for SMN without compromising the effectiveness of initial therapy. Clinicians should individualize treatment for patients who are genetically predisposed to SMN. In addition, radiologists should be familiar with the long-term consequences of antineoplastic therapy to facilitate diagnosis and anticipate adverse outcomes.

© RSNA, 2003

Index Terms: Chemotherapy, complications • Neoplasms, CT, _**.1211² • Neoplasms, in infants and children, _**.32 • Neoplasms, MR, _**.1214 • Radiations, injurious effects, neoplastic, _**.47

	Introduction

Top Abstract Introduction Patients and Procedures Pathogenic Factors Types of SMNs Implications for Imaging... Conclusions References

 
Increasingly effective therapies for childhood cancer developed over the past decades have revolutionized the practice of pediatric oncology. As cure rates increase, however, more children are at risk for long-term toxicity (1,2). Among the most dreaded late sequelae is the development of a second malignant neoplasm (SMN). In previous reports with long follow-up times, 5%–10% of all children treated for a first malignancy developed an SMN (3–5). Several recent reports have attempted to identify patient characteristics or therapy-related risk factors that might play a role in the development of SMN following treatment for childhood cancer. Genetic predisposition, chemotherapy, and especially radiation therapy have been implicated as pathogenic factors (4,5). Radiation-induced neoplasms occur at the edges of the irradiated field, where the radiation does not cause cell death but is sufficient to induce malignant transformation (6,7).

Primary neoplasms that may be associated with SMN include leukemia, lymphoma, bilateral retinoblastoma, medulloblastoma, craniopharyngioma, and neuroblastoma. The most commonly seen SMNs are brain tumors, sarcomas, carcinomas, and leukemia. Vigilant surveillance and long-term follow-up should be emphasized in all survivors of childhood cancer (3).

In this article, we describe our study in terms of patients and procedures; pathogenic factors in SMNs; clinical and imaging characteristics of various types of SMNs, especially those affecting the brain, head, and neck; and imaging strategies and therapy in patients with SMN.

	Patients and Procedures

Top Abstract Introduction Patients and Procedures Pathogenic Factors Types of SMNs Implications for Imaging... Conclusions References

 
We reviewed 19 SMNs in 16 patients who were referred to our pediatric hospital over the past 10 years after having previously undergone treatment for childhood cancer (medulloblastoma [n = 6], acute lymphoblastic leukemia [n = 5], bilateral retinoblastoma [n = 2], osteosarcome [n = 1], craniopharyngioma [n = 1], renal tumor [Wilms tumor] [n = 1]) (Table 1). The 19 SMNs included six cerebral gliomas, three meningiomas, three osteosarcomas, one primitive neuroectodermal tumor, and six head and neck carcinomas (Table 2). All patients underwent computed tomography (CT) and magnetic resonance (MR) imaging, and two underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Medical records and imaging studies were reviewed to identify the frequency of occurrence of SMNs, to assess possible risk factors for their development, and to identify specific CT or MR imaging features of these tumors.

	Pathogenic Factors

Top Abstract Introduction Patients and Procedures Pathogenic Factors Types of SMNs Implications for Imaging... Conclusions References

Therapy-related Factors
Radiation Therapy and Radiation-induced Neoplasms.— Cranial irradiation is widely used for treating neoplastic diseases. Such treatment results in longer survival of patients, although long-term toxicity such as late delayed radiation necrosis and irradiation-related arteriopathy can occur in the brain (2,7–10). The induction of SMNs is a rare but well-documented serious sequela of therapeutic irradiation (3,11).

The initial disease is most frequently acute leukemia (lymphoblastic leukemia), lymphoma (particularly Hodgkin disease), or primary brain tumor (eg, medulloblastoma, craniopharyngioma, astrocytoma, germ cell tumor, pituitary adenoma). Although craniopharyngioma, pituitary adenoma, and low-grade astrocytoma are all considered benign tumors and surgical resection is the treatment of choice, radiation therapy is widely used in cases of a postoperative residual mass, and SMNs have been described in the follow-up of these primary tumors. Reported radiation-induced tumors of the central nervous system (CNS) include meningioma, sarcoma, glioma (often high grade), ependymoma, and, more rarely, primitive neuroectodermal tumor. Head and neck carcinoma and soft-tissue or bone sarcoma can also be radiation induced (12,13).

The risk of SMN is higher in patients who undergo radiation therapy at an early age, particularly those under 5 years old, with a prevalence of 2.6%–38.8%, which is six to 10 times higher than in the general population (3,4). The cumulative probability in long-term survivors of childhood cancer is reported to be 12% from 5 to 24 years after the primary diagnosis is made, which is 20 times greater than in the general population. Imperfect repair of radiation-induced DNA strand breakage in tumor suppressor genes has been suggested as the genetic basis; for example, radiation-associated sarcomas and glioblastomas may show somatic p53 gene mutations (14,15). The period of latency varies from 8 to 15 years after radiation therapy. Latency has been noted to be inversely proportional to radiation dose, with shorter latency periods often seen following administration of higher doses (3).

Medulloblastoma represents one of the most common brain tumors in children. As survival time increases with use of intensive therapy, there is also an increased risk of an SMN—particularly a radiation-related tumor—mainly salivary and thyroid gland carcinomas, CNS solid tumors, or acute lymphoblastic leukemia (16).

Chemotherapy and Bone Marrow Transplantation.— The role of chemotherapeutic agents is difficult to discern due to the use of multiple agents in childhood cancer therapy. For example, cyclophosphamide has a well-recognized association with transitional cell carcinoma of the bladder, and the topoisomerase II inhibitors are associated with secondary acute myelogenous leukemia (AML), also known as topoisomerase II inhibitor–related leukemia. Chemotherapy-related tumors tend to plateau after 5 years from diagnosis of the primary malignancy, in contrast to radiation therapy–related tumors, which have an increased prevalence over time (4,17). Because of this short latency period, secondary AML is the most likely SMN to occur during the first 5 years after treatment, although it should be differentiated from primary leukemia relapse, which is much more common. Most patients with secondary AML do not survive, even after bone marrow transplantation (18).

Bone marrow transplantation, which combines intensive therapy with alkylating agents and total body irradiation, is often associated with SMN, particularly with brain tumors and with carcinomas of the tongue, thyroid gland, and parotid gland. The high degree of immunosuppression in affected patients has been considered responsible for Epstein-Barr virus–associated lymphoproliferative disease and some SMNs such as melanoma and carcinoma of the tongue (4,19).

Genetic Predisposition to Multiple Neoplasms
Patients who develop multiple primary cancers at an early age may be genetically predisposed. Familial aggregation of early-onset cancer has been recognized as a good indicator of the presence of genetic mutations, and these individuals are at high risk for developing cancer (4,5). Recent reports also suggest that a substantial proportion of early-onset cancers are associated with the inheritance of predisposing genes of low penetrance (20). Susceptibility genes are present in Wilms tumor (WT1), adenomatous polyposis coli (APC), ataxia-telangiectasia (ATM), and other syndromes. For example, childhood leukemia, brain tumors, and sarcoma are cardinal features of Li-Fraumeni syndrome, an autosomal dominant disorder (21,22). Most patients with this syndrome have a germline p53 mutation and are at high risk for additional cancers. Approximately 50% of neoplasms in families with reported Li-Fraumeni syndrome occur before 30 years of age, manifesting as soft-tissue sarcomas in the first 5 years of life and to osteosarcomas in adolescence. In addition, adrenocortical carcinoma can occur in infancy and breast cancer in young adults. Germline p53 mutations in Li-Fraumeni syndrome and other rare cancer groups can be considered a biomarker of increased risk for cancer development and should trigger preventative measures. Early detection should be pursued in affected families.

There are at least nine major cancer susceptibility syndromes that infer an increased risk for colorectal cancer or colorectal polyposis: heredi-tary nonpoliposis colorectal cancer syndrome (HNPCC), Muir-Torre syndrome, Turcot syndrome, the I1307K polymorphism of the APC gene, familial adenomatous polyposis (FAP), attenuated FAP, Peutz-Jeghers syndrome, juvenile polyposis, and the PTEN (tumor suppressor gene) hamartoma tumor syndrome (23). Turcot syndrome is characterized by the concurrence of a primary brain tumor and multiple colorectal adenomas and can represent a variant of either HNPCC or FAP. Medulloblastomas are associated with FAP and are seen in two-thirds of Turcot syndrome cases, whereas glioblastoma is associated with HNPCC. Occasionally, medulloblastoma occurs in children with other genetically linked disorders, such as Gorlin syndrome (basal cell nevus syndrome). Several genes have been implicated in the development of medulloblastoma in these children, including Patched-1 and Smoothened. The protein products of these genes function within the sonic hedgehog molecular signaling pathways, which are important in neural development and disease.

Ataxia-telangiectasia is a multisystem disease with an autosomal recessive inheritance that is characterized by progressive ataxia, oculocutaneous telangiectasia, humoral and cellular immunodeficiencies, and a high prevalence of neoplastic development and radiosensitivity. Recurrent sinopulmonary infections, absent or low serum levels of immunoglobin A, and lymphopenia may also be seen. Patients with ataxia-telangiectasia have a 100-fold higher risk of cancer than does the general population, particularly lymphoma (usually B-cell type) and leukemia. The responsible gene, ATM, encodes a large protein kinase with a phosphatidylinositol 3-kinase–like domain (24). Incontinentia pigmenti is another rare hereditary disorder that, together with Fanconi anemia and ataxia-telangiectasia, is now classified as a chromosomal instability syndrome that predisposes to cancer (25). Failure to diagnose ataxia-telangiectasia in an infant with lymphoma or leukemia may lead to radiation therapy with conventional dosages, which is contraindicated due to the radiosensitivity of these patients.

Multiple endocrine neoplasia (MEN) syndromes, previously called familial endocrine adenomatosis, are disorders that affect the thyroid gland and other endocrine glands. There are three types of MEN, all of which are inherited as autosomal dominant disorders: MEN 1, 2A, and 2B. MEN 1 is characterized by hyperparathyroidism, pancreatic tumors (gastrinomas), and pituitary gland hyperplasia and is caused by a mutation in the PYGM, a tumor suppressor gene, MEN 2A and 2B are characterized by medullary thyroid cancer and pheochromocytoma and are caused by mutations in RET. Since 1994, genetic screening with DNA technology has been available for both MEN 1 and 2, allowing earlier diagnosis prior to the onset of symptoms. Children in families with MEN 2 can develop medullary thyroid cancer at a very young age; consequently, several authors advocate performing prophylactic thyroidectomy in the 1st year of life in children with MEN 2B and at age 2 years in children with MEN 2A to achieve an optimal cure rate (26).

Because the NF1 gene is a tumor suppressor gene in some cells, children with neurofibromatosis-1 are at risk for developing a variety of benign and malignant tumors. The most common tumors are optic pathway gliomas and neurofibromas; neurofibrosarcomas and malignant peripheral nerve sheath tumors are exceedingly rare. Brain tumors tend to have a more indolent course than in the general population; thus, they should be managed conservatively, administering radiation therapy only sparingly due to the very high relative risk of developing a CNS SMN (27). Children with neurofibromatosis-1 are also predisposed to develop pheochromocytomas, juvenile chronic myeloid leukemia, and, more rarely, rhabdomyosarcomas. In fact, 10% of the spontaneous cases of myeloproliferative syndrome seen in children affect patients with neurofibromatosis-1. The NF1 gene is considered a tumor suppressor of myeloid cells, and germline NF1 mutations are associated with preleukemia and myeloblastic leukemia.

Retinoblastoma may be either sporadic or hereditary. In all retinoblastomas, the tumor suppressor gene Rb, located on the long arm of chromosome 13, is functionally defective. Familial cases carry a germline deletion of one of the two Rb alleles, so that a single spontaneous mutation of the other one is sufficient to cause tumor development, usually at a younger age and bilaterally. Retinoblastoma is often associated with SMNs—particularly osteosarcoma—and other less common tumors such as melanoma, brain tumors, and soft-tissue sarcomas (4,28).

Wilms tumor is the fifth most common pediatric malignancy and the most common renal tumor in children, with a survival rate of nearly 90% in recent years. As in the model described for retinoblastoma, Wilms tumor results from two mutational events related to the loss of function of tumor suppressor genes, particularly the WT1 gene located at chromosome 11p13. Prezygotic mutations are present in all body cells and predispose to familial or multiple Wilms tumors (29). SMNs may result from the inherited disposition and the coadjuvant therapy used. These neoplasms mainly correspond to bone, breast, and thyroid tumors, with a prevalence of 1.6% after 15 years, which is five times the expected prevalence (30).

	Types of SMNs

Top Abstract Introduction Patients and Procedures Pathogenic Factors Types of SMNs Implications for Imaging... Conclusions References

 
SMNs of the Central Nervous System
CNS SMNs are relatively rare, are mainly related to radiation therapy, and account for 3%–12% of all SMNs. Among intracranial SMNs, approximately 70% are meningiomas, 20% are gliomas, and 10% are sarcomas (3,6,8). The latency period between treatment and development of these tumors varies. Children who underwent cranial radiation therapy at 5 years of age or younger, those with a genetic predisposition to tumors, and survivors of bone marrow transplantation have a markedly increased risk. Unfortunately, these treatment-induced tumors are often more aggressive than primary tumors and are highly refractory to therapy (6,8). The risk of CNS SMNs is both dose- and age dependent. A strong dose-response correlation is reported, with a relative risk approaching 20 after therapy with estimated doses of approximately 2.5 Gy, although radiation doses on the order of 1–2 Gy, as used in the treatment of tinea capitis, are enough to significantly increase the risk. Lower doses may increase the risk in very young patients due to their greater sensitivity to ionizing radiation (4).

Survivors of childhood acute lymphoblastic leukemia form a large population at risk for developing SMN. Brain tumors are frequently seen in survivors of acute lymphoblastic leukemia. Outcome is drastically different for patients who develop low-grade tumors (primarily meningiomas) than for those with high-grade tumors (high-grade gliomas). The incidence of SMNs that develop after therapy for acute lymphoblastic leukemia is 62.3 per 100,000 persons annually (31). Cranial irradiation in particular has been implicated, although CNS SMNs have been reported in survivors of childhood leukemia with no history of prophylactic irradiation. Other proposed mechanisms include loss of immune surveillance and genetic factors. The cumulative incidence of both low- and high-grade brain neoplasms is related to the presence of CNS leukemic or lymphomatous infiltration at diagnosis due to the more intensive CNS-directed chemotherapy and radiation therapy given to these patients (2,32).

Secondary meningiomas are characterized by a younger patient age at presentation, a higher male-to-female ratio, and more aggressive histologic variants compared with primary spontaneous meningiomas (Figs 1–3). The latency period is longer for benign meningiomas and shorter for malignant subtypes (10,32,33). In our experience, these tumors appear within the margins of the irradiated area, that is, near the tentorium or in the posterior fossa in cases of previous medulloblastoma (Figs 1, 2). Despite a previous description of a possible good clinical outcome (5), all of our cases showed aggressive histologic features, and outcome was poor in two cases, with numerous recurrences after surgery. Malignant histologic features and multiplicity of meningeal tumors have also been reported (34).

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  Meningioma after medulloblastoma. (a) CT scan of a 4-year-old child shows a posterior mass. Follow-up CT over the next several years was unremarkable. (b) CT scan obtained 7 years later shows a high-attenuation, asymptomatic extraaxial mass. (c, d) T2-weighted (c) and contrast-enhanced T1-weighted (d) MR images show a well-defined, extraparenchymal left occipital mass that is isointense relative to gray matter (c) and anterior hyperintense white matter edema and homogeneous enhancement (d), findings that are consistent with meningioma. Surgery and posterior histologic analysis revealed anaplastic tumor foci with a typical whorl of bland meningothelial cells. (e) Follow-up MR image demonstrates tumor recurrence with dural venous sinus invasion and transcalvarial extension. Two other resections were performed, but the tumor progressed and the patient died.

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  Meningioma after medulloblastoma. (a) CT scan of a 4-year-old child shows a posterior mass. Follow-up CT over the next several years was unremarkable. (b) CT scan obtained 7 years later shows a high-attenuation, asymptomatic extraaxial mass. (c, d) T2-weighted (c) and contrast-enhanced T1-weighted (d) MR images show a well-defined, extraparenchymal left occipital mass that is isointense relative to gray matter (c) and anterior hyperintense white matter edema and homogeneous enhancement (d), findings that are consistent with meningioma. Surgery and posterior histologic analysis revealed anaplastic tumor foci with a typical whorl of bland meningothelial cells. (e) Follow-up MR image demonstrates tumor recurrence with dural venous sinus invasion and transcalvarial extension. Two other resections were performed, but the tumor progressed and the patient died.

View larger version (138K): [in this window] [in a new window] [Download PPT slide]   Figure 1c.  Meningioma after medulloblastoma. (a) CT scan of a 4-year-old child shows a posterior mass. Follow-up CT over the next several years was unremarkable. (b) CT scan obtained 7 years later shows a high-attenuation, asymptomatic extraaxial mass. (c, d) T2-weighted (c) and contrast-enhanced T1-weighted (d) MR images show a well-defined, extraparenchymal left occipital mass that is isointense relative to gray matter (c) and anterior hyperintense white matter edema and homogeneous enhancement (d), findings that are consistent with meningioma. Surgery and posterior histologic analysis revealed anaplastic tumor foci with a typical whorl of bland meningothelial cells. (e) Follow-up MR image demonstrates tumor recurrence with dural venous sinus invasion and transcalvarial extension. Two other resections were performed, but the tumor progressed and the patient died.

View larger version (107K): [in this window] [in a new window] [Download PPT slide]   Figure 1d.  Meningioma after medulloblastoma. (a) CT scan of a 4-year-old child shows a posterior mass. Follow-up CT over the next several years was unremarkable. (b) CT scan obtained 7 years later shows a high-attenuation, asymptomatic extraaxial mass. (c, d) T2-weighted (c) and contrast-enhanced T1-weighted (d) MR images show a well-defined, extraparenchymal left occipital mass that is isointense relative to gray matter (c) and anterior hyperintense white matter edema and homogeneous enhancement (d), findings that are consistent with meningioma. Surgery and posterior histologic analysis revealed anaplastic tumor foci with a typical whorl of bland meningothelial cells. (e) Follow-up MR image demonstrates tumor recurrence with dural venous sinus invasion and transcalvarial extension. Two other resections were performed, but the tumor progressed and the patient died.

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 1e.  Meningioma after medulloblastoma. (a) CT scan of a 4-year-old child shows a posterior mass. Follow-up CT over the next several years was unremarkable. (b) CT scan obtained 7 years later shows a high-attenuation, asymptomatic extraaxial mass. (c, d) T2-weighted (c) and contrast-enhanced T1-weighted (d) MR images show a well-defined, extraparenchymal left occipital mass that is isointense relative to gray matter (c) and anterior hyperintense white matter edema and homogeneous enhancement (d), findings that are consistent with meningioma. Surgery and posterior histologic analysis revealed anaplastic tumor foci with a typical whorl of bland meningothelial cells. (e) Follow-up MR image demonstrates tumor recurrence with dural venous sinus invasion and transcalvarial extension. Two other resections were performed, but the tumor progressed and the patient died.

View larger version (116K): [in this window] [in a new window] [Download PPT slide]   Figure 2a.  Meningioma after medulloblastoma. (a) CT scan of a 3-month-old boy shows a hypoattenuating mass in the cerebellar vermis with associated hydrocephalus. Surgical resection helped confirm medulloblastoma. (b) Contrast-enhanced CT scan obtained 12 years later shows an enhancing mass with calcifications and increased size posteriorly. (c) Sagittal T1-weighted MR image shows two hypointense masses of different sizes (arrows). (d) Axial contrast-enhanced T1-weighted MR image shows the larger mass with heterogeneous enhancement and peripheral cystic or necrotic areas (arrow) that represent meningioma. (e) Coronal T2-weighted MR image shows the smaller mass with heterogeneous intensity (arrow). The mass proved to be basal cell carcinoma. Several resections were performed for recurrence of meningioma, but the patient died.

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 2b.  Meningioma after medulloblastoma. (a) CT scan of a 3-month-old boy shows a hypoattenuating mass in the cerebellar vermis with associated hydrocephalus. Surgical resection helped confirm medulloblastoma. (b) Contrast-enhanced CT scan obtained 12 years later shows an enhancing mass with calcifications and increased size posteriorly. (c) Sagittal T1-weighted MR image shows two hypointense masses of different sizes (arrows). (d) Axial contrast-enhanced T1-weighted MR image shows the larger mass with heterogeneous enhancement and peripheral cystic or necrotic areas (arrow) that represent meningioma. (e) Coronal T2-weighted MR image shows the smaller mass with heterogeneous intensity (arrow). The mass proved to be basal cell carcinoma. Several resections were performed for recurrence of meningioma, but the patient died.

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 2c.  Meningioma after medulloblastoma. (a) CT scan of a 3-month-old boy shows a hypoattenuating mass in the cerebellar vermis with associated hydrocephalus. Surgical resection helped confirm medulloblastoma. (b) Contrast-enhanced CT scan obtained 12 years later shows an enhancing mass with calcifications and increased size posteriorly. (c) Sagittal T1-weighted MR image shows two hypointense masses of different sizes (arrows). (d) Axial contrast-enhanced T1-weighted MR image shows the larger mass with heterogeneous enhancement and peripheral cystic or necrotic areas (arrow) that represent meningioma. (e) Coronal T2-weighted MR image shows the smaller mass with heterogeneous intensity (arrow). The mass proved to be basal cell carcinoma. Several resections were performed for recurrence of meningioma, but the patient died.

View larger version (143K): [in this window] [in a new window] [Download PPT slide]   Figure 2d.  Meningioma after medulloblastoma. (a) CT scan of a 3-month-old boy shows a hypoattenuating mass in the cerebellar vermis with associated hydrocephalus. Surgical resection helped confirm medulloblastoma. (b) Contrast-enhanced CT scan obtained 12 years later shows an enhancing mass with calcifications and increased size posteriorly. (c) Sagittal T1-weighted MR image shows two hypointense masses of different sizes (arrows). (d) Axial contrast-enhanced T1-weighted MR image shows the larger mass with heterogeneous enhancement and peripheral cystic or necrotic areas (arrow) that represent meningioma. (e) Coronal T2-weighted MR image shows the smaller mass with heterogeneous intensity (arrow). The mass proved to be basal cell carcinoma. Several resections were performed for recurrence of meningioma, but the patient died.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 2e.  Meningioma after medulloblastoma. (a) CT scan of a 3-month-old boy shows a hypoattenuating mass in the cerebellar vermis with associated hydrocephalus. Surgical resection helped confirm medulloblastoma. (b) Contrast-enhanced CT scan obtained 12 years later shows an enhancing mass with calcifications and increased size posteriorly. (c) Sagittal T1-weighted MR image shows two hypointense masses of different sizes (arrows). (d) Axial contrast-enhanced T1-weighted MR image shows the larger mass with heterogeneous enhancement and peripheral cystic or necrotic areas (arrow) that represent meningioma. (e) Coronal T2-weighted MR image shows the smaller mass with heterogeneous intensity (arrow). The mass proved to be basal cell carcinoma. Several resections were performed for recurrence of meningioma, but the patient died.

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 3.  Meningioma after acute lymphoblastic leukemia in a 17-year-old girl who presented with headaches. The patient had undergone chemotherapy and craniospinal irradiation at 2 years of age. Coronal contrast-enhanced T1-weighted MR image demonstrates a posterior fossa mass. The tumor was resected, and no residual or recurrent meningioma was seen at follow-up MR imaging.

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  Primitive neuroectodermal tumor in a 17-year-old girl. The patient had been treated for acute lymphoblastic leukemia at 5 years of age. Axial contrast-enhanced CT scan (a), axial T2-weighted MR image (b), and coronal contrast-enhanced T1-weighted MR image (c) show a heterogeneous right hemispheric cerebral mass with cystic-necrotic components (arrow in a). Partial surgical resection demonstrated a primitive neuroectodermal tumor with posterior tumor progression. The patient did not survive.

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  Primitive neuroectodermal tumor in a 17-year-old girl. The patient had been treated for acute lymphoblastic leukemia at 5 years of age. Axial contrast-enhanced CT scan (a), axial T2-weighted MR image (b), and coronal contrast-enhanced T1-weighted MR image (c) show a heterogeneous right hemispheric cerebral mass with cystic-necrotic components (arrow in a). Partial surgical resection demonstrated a primitive neuroectodermal tumor with posterior tumor progression. The patient did not survive.

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 4c.  Primitive neuroectodermal tumor in a 17-year-old girl. The patient had been treated for acute lymphoblastic leukemia at 5 years of age. Axial contrast-enhanced CT scan (a), axial T2-weighted MR image (b), and coronal contrast-enhanced T1-weighted MR image (c) show a heterogeneous right hemispheric cerebral mass with cystic-necrotic components (arrow in a). Partial surgical resection demonstrated a primitive neuroectodermal tumor with posterior tumor progression. The patient did not survive.

View larger version (154K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Pontine glioma after medulloblastoma. (a) Sagittal T1-weighted MR image obtained in a 2-year-old girl shows a posterior fossa mass with homogeneous hypointensity (arrow), an enlarged Silvian aqueduct, and hydrocephalus. The postsurgical diagnosis was medulloblastoma. (b) Follow-up axial contrast-enhanced T1-weighted MR image shows postoperative deformity of the fourth ventricle with no residual tumor. (c) Contrast-enhanced T1-weighted MR image obtained 5 years later reveals a hypointense pontine mass with nodular enhancement. Biopsy revealed anaplastic glioma. The family decided against therapy, and the patient died.

View larger version (140K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Pontine glioma after medulloblastoma. (a) Sagittal T1-weighted MR image obtained in a 2-year-old girl shows a posterior fossa mass with homogeneous hypointensity (arrow), an enlarged Silvian aqueduct, and hydrocephalus. The postsurgical diagnosis was medulloblastoma. (b) Follow-up axial contrast-enhanced T1-weighted MR image shows postoperative deformity of the fourth ventricle with no residual tumor. (c) Contrast-enhanced T1-weighted MR image obtained 5 years later reveals a hypointense pontine mass with nodular enhancement. Biopsy revealed anaplastic glioma. The family decided against therapy, and the patient died.

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 5c.  Pontine glioma after medulloblastoma. (a) Sagittal T1-weighted MR image obtained in a 2-year-old girl shows a posterior fossa mass with homogeneous hypointensity (arrow), an enlarged Silvian aqueduct, and hydrocephalus. The postsurgical diagnosis was medulloblastoma. (b) Follow-up axial contrast-enhanced T1-weighted MR image shows postoperative deformity of the fourth ventricle with no residual tumor. (c) Contrast-enhanced T1-weighted MR image obtained 5 years later reveals a hypointense pontine mass with nodular enhancement. Biopsy revealed anaplastic glioma. The family decided against therapy, and the patient died.

View larger version (156K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  Brainstem glioma after craniopharyngioma. (a, b) Sagittal (a) and axial contrast-enhanced (b) T1-weighted MR images obtained in a 10-year-old girl show an isointense, heterogeneously enhancing suprasellar mass (arrow), a finding that is suggestive of craniopharyngioma. The tumor was partially resected. (c) Follow-up sagittal T1-weighted MR image demonstrates no progression of the mass. Residual calcifications were seen at CT. (d) Axial contrast-enhanced T1-weighted MR image obtained 8 years later shows a heterogeneously enhancing mass that involves the upper brainstem. Stereotactic biopsy revealed high-grade glioma.

View larger version (136K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  Brainstem glioma after craniopharyngioma. (a, b) Sagittal (a) and axial contrast-enhanced (b) T1-weighted MR images obtained in a 10-year-old girl show an isointense, heterogeneously enhancing suprasellar mass (arrow), a finding that is suggestive of craniopharyngioma. The tumor was partially resected. (c) Follow-up sagittal T1-weighted MR image demonstrates no progression of the mass. Residual calcifications were seen at CT. (d) Axial contrast-enhanced T1-weighted MR image obtained 8 years later shows a heterogeneously enhancing mass that involves the upper brainstem. Stereotactic biopsy revealed high-grade glioma.

View larger version (152K): [in this window] [in a new window] [Download PPT slide]   Figure 6c.  Brainstem glioma after craniopharyngioma. (a, b) Sagittal (a) and axial contrast-enhanced (b) T1-weighted MR images obtained in a 10-year-old girl show an isointense, heterogeneously enhancing suprasellar mass (arrow), a finding that is suggestive of craniopharyngioma. The tumor was partially resected. (c) Follow-up sagittal T1-weighted MR image demonstrates no progression of the mass. Residual calcifications were seen at CT. (d) Axial contrast-enhanced T1-weighted MR image obtained 8 years later shows a heterogeneously enhancing mass that involves the upper brainstem. Stereotactic biopsy revealed high-grade glioma.

View larger version (139K): [in this window] [in a new window] [Download PPT slide]   Figure 6d.  Brainstem glioma after craniopharyngioma. (a, b) Sagittal (a) and axial contrast-enhanced (b) T1-weighted MR images obtained in a 10-year-old girl show an isointense, heterogeneously enhancing suprasellar mass (arrow), a finding that is suggestive of craniopharyngioma. The tumor was partially resected. (c) Follow-up sagittal T1-weighted MR image demonstrates no progression of the mass. Residual calcifications were seen at CT. (d) Axial contrast-enhanced T1-weighted MR image obtained 8 years later shows a heterogeneously enhancing mass that involves the upper brainstem. Stereotactic biopsy revealed high-grade glioma.

View larger version (167K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.  Osteosarcoma after bilateral retinoblastoma. (a, b) Axial T2-weighted (a) and contrast-enhanced fat-saturated T1-weighted (b) MR images obtained in an 8-month-old boy with leukocoria show extensive bilateral retinal tumors (arrows). (c) Follow-up contrast-enhanced CT scan obtained postoperatively shows residual soft tissue in the left orbit and an ocular prosthesis in the right orbit, without evidence of tumor. (d, e) CT scans obtained 4 years later (e obtained caudad to d) demonstrate a maxillary mass with bone destruction and matrix mineralization. Follow-up MR imaging performed after chemotherapy and radical surgery demonstrated no tumor recurrence.

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.  Osteosarcoma after bilateral retinoblastoma. (a, b) Axial T2-weighted (a) and contrast-enhanced fat-saturated T1-weighted (b) MR images obtained in an 8-month-old boy with leukocoria show extensive bilateral retinal tumors (arrows). (c) Follow-up contrast-enhanced CT scan obtained postoperatively shows residual soft tissue in the left orbit and an ocular prosthesis in the right orbit, without evidence of tumor. (d, e) CT scans obtained 4 years later (e obtained caudad to d) demonstrate a maxillary mass with bone destruction and matrix mineralization. Follow-up MR imaging performed after chemotherapy and radical surgery demonstrated no tumor recurrence.

View larger version (95K): [in this window] [in a new window] [Download PPT slide]   Figure 7c.  Osteosarcoma after bilateral retinoblastoma. (a, b) Axial T2-weighted (a) and contrast-enhanced fat-saturated T1-weighted (b) MR images obtained in an 8-month-old boy with leukocoria show extensive bilateral retinal tumors (arrows). (c) Follow-up contrast-enhanced CT scan obtained postoperatively shows residual soft tissue in the left orbit and an ocular prosthesis in the right orbit, without evidence of tumor. (d, e) CT scans obtained 4 years later (e obtained caudad to d) demonstrate a maxillary mass with bone destruction and matrix mineralization. Follow-up MR imaging performed after chemotherapy and radical surgery demonstrated no tumor recurrence.

View larger version (103K): [in this window] [in a new window] [Download PPT slide]   Figure 7d.  Osteosarcoma after bilateral retinoblastoma. (a, b) Axial T2-weighted (a) and contrast-enhanced fat-saturated T1-weighted (b) MR images obtained in an 8-month-old boy with leukocoria show extensive bilateral retinal tumors (arrows). (c) Follow-up contrast-enhanced CT scan obtained postoperatively shows residual soft tissue in the left orbit and an ocular prosthesis in the right orbit, without evidence of tumor. (d, e) CT scans obtained 4 years later (e obtained caudad to d) demonstrate a maxillary mass with bone destruction and matrix mineralization. Follow-up MR imaging performed after chemotherapy and radical surgery demonstrated no tumor recurrence.

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 7e.  Osteosarcoma after bilateral retinoblastoma. (a, b) Axial T2-weighted (a) and contrast-enhanced fat-saturated T1-weighted (b) MR images obtained in an 8-month-old boy with leukocoria show extensive bilateral retinal tumors (arrows). (c) Follow-up contrast-enhanced CT scan obtained postoperatively shows residual soft tissue in the left orbit and an ocular prosthesis in the right orbit, without evidence of tumor. (d, e) CT scans obtained 4 years later (e obtained caudad to d) demonstrate a maxillary mass with bone destruction and matrix mineralization. Follow-up MR imaging performed after chemotherapy and radical surgery demonstrated no tumor recurrence.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 8a.  Osteosarcoma after bilateral retinoblastoma in a 13-year-old girl who presented with a nasopharyngeal mass. The patient had undergone treatment for bilateral retinoblastoma at a young age. (a) CT scan shows a heterogeneous mass with areas of iso- and hypoattenuation that involves the maxillary antrum on the right side. Associated osseous destruction of the posterior maxillary sinus wall and nasopharyngeal protrusion are also seen (arrows). (b, c) Axial fat-saturated T2-weighted (b) and coronal contrast-enhanced fat-saturated T1-weighted (c) MR images demonstrate an extensive soft-tissue mass that arises from the right maxilla. Biopsy revealed undifferentiated osteosarcoma. Chemotherapy and surgery produced very good results, although the follow-up period has been very short.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 8b.  Osteosarcoma after bilateral retinoblastoma in a 13-year-old girl who presented with a nasopharyngeal mass. The patient had undergone treatment for bilateral retinoblastoma at a young age. (a) CT scan shows a heterogeneous mass with areas of iso- and hypoattenuation that involves the maxillary antrum on the right side. Associated osseous destruction of the posterior maxillary sinus wall and nasopharyngeal protrusion are also seen (arrows). (b, c) Axial fat-saturated T2-weighted (b) and coronal contrast-enhanced fat-saturated T1-weighted (c) MR images demonstrate an extensive soft-tissue mass that arises from the right maxilla. Biopsy revealed undifferentiated osteosarcoma. Chemotherapy and surgery produced very good results, although the follow-up period has been very short.

View larger version (133K): [in this window] [in a new window] [Download PPT slide]   Figure 8c.  Osteosarcoma after bilateral retinoblastoma in a 13-year-old girl who presented with a nasopharyngeal mass. The patient had undergone treatment for bilateral retinoblastoma at a young age. (a) CT scan shows a heterogeneous mass with areas of iso- and hypoattenuation that involves the maxillary antrum on the right side. Associated osseous destruction of the posterior maxillary sinus wall and nasopharyngeal protrusion are also seen (arrows). (b, c) Axial fat-saturated T2-weighted (b) and coronal contrast-enhanced fat-saturated T1-weighted (c) MR images demonstrate an extensive soft-tissue mass that arises from the right maxilla. Biopsy revealed undifferentiated osteosarcoma. Chemotherapy and surgery produced very good results, although the follow-up period has been very short.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Calvarial osteosarcoma after cerebral astrocytoma and surface femoral osteosarcoma. (a) Coronal T1-weighted MR image obtained in a 12-year-old girl shows a surface femoral osteosarcoma (arrow). The patient underwent surgery and chemotherapy. (b) Coronal contrast-enhanced T1-weighted MR image obtained 2 years later for seizures demonstrates a left hemispheric mass. The presumptive imaging diagnosis was a metastatic lesion, but surgical resection revealed anaplastic glioma. The patient underwent cranial irradiation. (c, d) Brain CT scans obtained 3 years later (d obtained at a lower level with bone windowing) reveal a calcified mass with new bone formation and a permeative pattern. (e, f) Axial T2-weighted (e) and coronal contrast-enhanced T1-weighted (f) MR images demonstrate the bone lesion with an accompanying soft-tissue mass. Histologic analysis demonstrated a highly atypical proliferation of mesenchymal cells with osteoid and trabecular bone differentiation.

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Calvarial osteosarcoma after cerebral astrocytoma and surface femoral osteosarcoma. (a) Coronal T1-weighted MR image obtained in a 12-year-old girl shows a surface femoral osteosarcoma (arrow). The patient underwent surgery and chemotherapy. (b) Coronal contrast-enhanced T1-weighted MR image obtained 2 years later for seizures demonstrates a left hemispheric mass. The presumptive imaging diagnosis was a metastatic lesion, but surgical resection revealed anaplastic glioma. The patient underwent cranial irradiation. (c, d) Brain CT scans obtained 3 years later (d obtained at a lower level with bone windowing) reveal a calcified mass with new bone formation and a permeative pattern. (e, f) Axial T2-weighted (e) and coronal contrast-enhanced T1-weighted (f) MR images demonstrate the bone lesion with an accompanying soft-tissue mass. Histologic analysis demonstrated a highly atypical proliferation of mesenchymal cells with osteoid and trabecular bone differentiation.

View larger version (90K): [in this window] [in a new window] [Download PPT slide]   Figure 9c.  Calvarial osteosarcoma after cerebral astrocytoma and surface femoral osteosarcoma. (a) Coronal T1-weighted MR image obtained in a 12-year-old girl shows a surface femoral osteosarcoma (arrow). The patient underwent surgery and chemotherapy. (b) Coronal contrast-enhanced T1-weighted MR image obtained 2 years later for seizures demonstrates a left hemispheric mass. The presumptive imaging diagnosis was a metastatic lesion, but surgical resection revealed anaplastic glioma. The patient underwent cranial irradiation. (c, d) Brain CT scans obtained 3 years later (d obtained at a lower level with bone windowing) reveal a calcified mass with new bone formation and a permeative pattern. (e, f) Axial T2-weighted (e) and coronal contrast-enhanced T1-weighted (f) MR images demonstrate the bone lesion with an accompanying soft-tissue mass. Histologic analysis demonstrated a highly atypical proliferation of mesenchymal cells with osteoid and trabecular bone differentiation.

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 9d.  Calvarial osteosarcoma after cerebral astrocytoma and surface femoral osteosarcoma. (a) Coronal T1-weighted MR image obtained in a 12-year-old girl shows a surface femoral osteosarcoma (arrow). The patient underwent surgery and chemotherapy. (b) Coronal contrast-enhanced T1-weighted MR image obtained 2 years later for seizures demonstrates a left hemispheric mass. The presumptive imaging diagnosis was a metastatic lesion, but surgical resection revealed anaplastic glioma. The patient underwent cranial irradiation. (c, d) Brain CT scans obtained 3 years later (d obtained at a lower level with bone windowing) reveal a calcified mass with new bone formation and a permeative pattern. (e, f) Axial T2-weighted (e) and coronal contrast-enhanced T1-weighted (f) MR images demonstrate the bone lesion with an accompanying soft-tissue mass. Histologic analysis demonstrated a highly atypical proliferation of mesenchymal cells with osteoid and trabecular bone differentiation.

View larger version (162K): [in this window] [in a new window] [Download PPT slide]   Figure 9e.  Calvarial osteosarcoma after cerebral astrocytoma and surface femoral osteosarcoma. (a) Coronal T1-weighted MR image obtained in a 12-year-old girl shows a surface femoral osteosarcoma (arrow). The patient underwent surgery and chemotherapy. (b) Coronal contrast-enhanced T1-weighted MR image obtained 2 years later for seizures demonstrates a left hemispheric mass. The presumptive imaging diagnosis was a metastatic lesion, but surgical resection revealed anaplastic glioma. The patient underwent cranial irradiation. (c, d) Brain CT scans obtained 3 years later (d obtained at a lower level with bone windowing) reveal a calcified mass with new bone formation and a permeative pattern. (e, f) Axial T2-weighted (e) and coronal contrast-enhanced T1-weighted (f) MR images demonstrate the bone lesion with an accompanying soft-tissue mass. Histologic analysis demonstrated a highly atypical proliferation of mesenchymal cells with osteoid and trabecular bone differentiation.

View larger version (157K): [in this window] [in a new window] [Download PPT slide]   Figure 9f.  Calvarial osteosarcoma after cerebral astrocytoma and surface femoral osteosarcoma. (a) Coronal T1-weighted MR image obtained in a 12-year-old girl shows a surface femoral osteosarcoma (arrow). The patient underwent surgery and chemotherapy. (b) Coronal contrast-enhanced T1-weighted MR image obtained 2 years later for seizures demonstrates a left hemispheric mass. The presumptive imaging diagnosis was a metastatic lesion, but surgical resection revealed anaplastic glioma. The patient underwent cranial irradiation. (c, d) Brain CT scans obtained 3 years later (d obtained at a lower level with bone windowing) reveal a calcified mass with new bone formation and a permeative pattern. (e, f) Axial T2-weighted (e) and coronal contrast-enhanced T1-weighted (f) MR images demonstrate the bone lesion with an accompanying soft-tissue mass. Histologic analysis demonstrated a highly atypical proliferation of mesenchymal cells with osteoid and trabecular bone differentiation.

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Lingual epidermoid carcinoma after Wilms tumor in a 15-year-old boy. The patient had been treated for Wilms tumor with pulmonary metastases at the age of 5 years. Axial T2-weighted (a) and contrast-enhanced T1-weighted (b) MR images demonstrate a hyperintense enhancing mass (arrow) that involves the middle and posterior thirds of the right side of the tongue. The tongue carcinoma was surgically resected, and radiation therapy was administered. Follow-up MR imaging performed 5 years later showed no tumor recurrence.

View larger version (136K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Lingual epidermoid carcinoma after Wilms tumor in a 15-year-old boy. The patient had been treated for Wilms tumor with pulmonary metastases at the age of 5 years. Axial T2-weighted (a) and contrast-enhanced T1-weighted (b) MR images demonstrate a hyperintense enhancing mass (arrow) that involves the middle and posterior thirds of the right side of the tongue. The tongue carcinoma was surgically resected, and radiation therapy was administered. Follow-up MR imaging performed 5 years later showed no tumor recurrence.

View larger version (162K): [in this window] [in a new window] [Download PPT slide]   Figure 11a.  Parotid gland carcinoma after acute lymphoblastic leukemia in a 14-year-old boy. The patient had been treated for acute lymphoblastic leukemia with chemotherapy and radiation therapy at the age of 5 years. Axial T1-weighted (a) and fat-saturated T2-weighted (b) MR images demonstrate a left parotid gland mass (arrows in a). The lesion is well defined and hypointense in a, with conspicuously higher homogeneous signal intensity in b. Surgical resection and posterior histologic examination demonstrated a low-grade mucoepidermoid carcinoma. Follow-up MR imaging showed no tumor recurrence.

View larger version (149K): [in this window] [in a new window] [Download PPT slide]   Figure 11b.  Parotid gland carcinoma after acute lymphoblastic leukemia in a 14-year-old boy. The patient had been treated for acute lymphoblastic leukemia with chemotherapy and radiation therapy at the age of 5 years. Axial T1-weighted (a) and fat-saturated T2-weighted (b) MR images demonstrate a left parotid gland mass (arrows in a). The lesion is well defined and hypointense in a, with conspicuously higher homogeneous signal intensity in b. Surgical resection and posterior histologic examination demonstrated a low-grade mucoepidermoid carcinoma. Follow-up MR imaging showed no tumor recurrence.