Oncologic Management for Liquid and Solid Tumors in Pediatric Oculoplastic Surgery

Fig. 13.1
Orbital rhabdomyosarcoma. Coronal T2-weighted with fat suppression (a) and axial post-contrast T1-weighted (b) and axial ADC map (c) images through the orbit showing an enhancing right orbital mass (black*) with restricted diffusion within the medial extraconal space causing flattening of the globe (white arrow) and mass effect upon the medial rectus muscle. This orbital mass was consistent with a rhabdomyosarcoma


Fig. 13.2
Another orbital rhabdomyosarcoma . Coronal T2-weighted with fat suppression (a) and axial post-contrast T1-weighted (b) and axial post-contrast T1-weighted coronal (c) images through the orbits showing mass lesion (black*) in the right superior medial orbit which is predominantly hyperintense on T2 and demonstrates avid enhancement. Inferior and lateral displacement (single white arrow) of the optic globe and proptosis (double white arrow) of the right globe. The imaging features are consistent with orbital rhabdomyosarcoma

The majority of pediatric rhabdomyosarcomas occur spontaneously. A small fraction are associated with genetic syndromes, such as Li-Fraumeni syndrome [2], neurofibromatosis type 1 [3], Costello syndrome [4], Beckwith-Wiedemann syndrome [5], and Rubinstein-Taybi syndrome [6]. It is important to assess for any stigmata of these syndromes, as their diagnoses may carry implications for long-term screening.

Evaluation of Pediatric Rhabdomyosarcoma

With any suspicion of malignancy, a referral to a pediatric oncology center should be considered. Initial imaging and decisions about approach to biopsy/resection are critical, as violation of tissue planes may have implications for staging, treatment, and further local control.

The primary tumor should be imaged preoperatively with MRI, including evaluation of regional nodes. A metastatic evaluation will be guided by the histology/fusion status and presence or absence of nodal involvement. This may include chest CT for pulmonary metastases and a PET to detect distant bone, lymph node, or soft tissue disease.

Risk Group Classification of Pediatric Rhabdomyosarcoma

Rhabdomyosarcomas are designated with a group and a stage. The group and stage are used together to assign a risk group – low, intermediate, and high. Selection of a treatment protocol is based on the risk group designation.

The clinical group is determined by the extent of tumor when chemotherapy begins. Group I tumors have been fully resected, group II tumors have microscopic residual disease, group III tumors have macroscopic residual disease, and group IV tumors have metastases.

The stage for patients with rhabdomyosarcomas depends on the site of disease (orbit is favorable), size of the primary tumor (less than five centimeters is favorable), and the presence or absence of lymph node involvement.

Rhabdomyosarcoma can be divided into two histologic subtypes – embryonal and alveolar. Embryonal rhabdomyosarcoma tends to occur in the head/neck and genitourinary tract and is associated with a favorable prognosis. Alveolar rhabdomyosarcoma more commonly develops in the extremities and carries a less favorable prognosis.

More important than the histologic subtype is the presence (unfavorable) or absence (favorable) of a 1;13 or 2;13 translocation [7]. The genes rearranged by these translocations are PAX3 and PAX7, respectively. The fusion transcripts encode novel transcription factors, which are more potent than their wild-type counterparts. Assays for the presence of these fusion transcripts can be detected by RT-PCR.

Treatment of Pediatric Rhabdomyosarcoma

Enormous progress has been made over the past 50 years, improving both short- and long-term outcomes for patients with rhabdomyosarcoma. This has been a collaboration of surgical oncologists, medical oncologists, and radiation oncologists. Effective therapy combines both systemic multi-agent chemotherapy and local control, either surgery or radiation.

The current chemotherapy backbone includes vincristine, actinomycin D, and cyclophosphamide. A large cooperative group trial has allowed us to decrease the cumulative cyclophosphamide dose for low-risk patients, in hopes of preserving their fertility in the long term [8]. The addition of irinotecan to the backbone for patients with intermediate-risk disease has maintained their ~70% overall survival rate, while allowing for reduction in the cumulative cyclophosphamide dose. Various attempts at augmenting the intensity of therapy for high-risk patients have largely been futile to date, and the prognosis for this group remains grim [9].

Surgical and radiation oncology considerations in rhabdomyosarcoma are quite complex. Patients with a complete upfront excision (group I) fare best, although this is almost never feasible with an orbital tumor. Given the location, an initial, limited biopsy allows confirmation of the diagnosis and may allow the radiation oncologist to treat a much smaller field than had the entire orbit been contaminated.

Ewing Sarcoma

Epidemiology of Pediatric Ewing Sarcoma

Ewing sarcoma is an aggressive form of childhood cancer. The majority (~75%) arise from bone, with the remainder arising from soft tissues. While the long bones are most commonly affected, Ewing sarcoma can arise in the bones of the orbit as well (Fig. 13.3).


Fig. 13.3
Ewing sarcoma of the orbit sagittal T2 (a); post-contrast T1-weighted axial (b) and coronal (c) images through the orbit demonstrate a large mass with solid component (white arrows) and large cystic component (black*), arising from the superior orbital wall with extension into the orbit and into the intracranial compartment in an extra-axial pattern into the left frontal region. Enhancement is seen within the solid portion of the mass and around the rim of the cystic portion. Diffusion restriction (not shown) was also noted in the solid portion of the mass. These findings indicate a malignant tumor such as a small blue cell tumor – Ewing sarcoma

Ewing sarcoma is the second most common primary bone tumor of childhood. Ewing sarcoma is more common in the Caucasian population and has a slight male predominance [10]. The majority of patients (~75%) present with localized disease. The lungs are the most common site of metastases, followed by bone and bone marrow.

Clinical Presentation of Pediatric Ewing Sarcoma

Symptoms at presentation depend on the location of the mass. Most patients present with pain or a palpable mass. Fever, weight loss, and night sweats may also be present. Careful assessment of the involved fields, including lymph nodes, is critical for ultimate planning of local control.

Evaluation of Pediatric Ewing Sarcoma

With any suspicion of malignancy, a referral to a pediatric oncology center should be considered. Initial imaging and decisions about approach to biopsy/resection are critical, as violation of tissue planes may have implications for staging, treatment, and further local control. Ewing sarcomas are often quite necrotic, so the surgeon must be careful to obtain adequate tissue for histologic and molecular testing.

Imaging of the primary tumor site, usually with MR, allows for a clear assessment of the extent of tumor involvement. Metastatic evaluation should include a non-contrast chest CT, whole-body PET scan, and bilateral bone marrow aspirates and biopsies.

Molecular Diagnosis of Pediatric Ewing Sarcoma

The majority of Ewing sarcomas carry a t(11;22) chromosomal translocation. This results in an EWS-FLI1 gene fusion, which activates a family of transcription factors involved in cellular proliferation and tumorigenesis. Identification of this translocation has become an integral part of the diagnosis of Ewing sarcoma [11], although it has not been convincingly linked to prognosis.

Risk Groups and Prognosis of Pediatric Ewing Sarcoma

The Children’s Oncology Group defines three risk groups for Ewing sarcoma – patients with localized disease, patients with lung metastases only, and patients with bone and/or other metastases. Various groups have identified male sex, older age, larger tumor size, and histologic response as adverse prognostic signs, although these are not uniformly accepted.

Treatment of Pediatric Ewing Sarcoma

Cytotoxic chemotherapy has significantly improved prognosis for patients with localized Ewing sarcoma. Patients with metastases, unfortunately, continue to fare quite poorly. Effective therapy combines chemotherapy with primary tumor treatment. Primary tumor treatment involves surgical resection, radiation therapy , or a combination of both modalities.

Current chemotherapy for Ewing sarcoma uses a backbone of alternating cycles of vincristine, doxorubicin, and cyclophosphamide with ifosfamide and etoposide. A recent Children’s Oncology Group study showed improved survival when chemotherapy cycles are delivered on an every 2-week cycle as compared to an every 3-week cycle [12].

Primary tumor treatment decisions are quite complex. Complete, en bloc surgical resection with negative margins is preferred. In some circumstances, this is not possible, or the ensuing disability is unacceptable. In those cases, or in those having undergone a surgical resection with positive margins, radiation therapy should be used, with consideration of proton radiotherapy, to spare surrounding tissues as much as possible.


Epidemiology of Pediatric Osteosarcoma

Osteosarcoma is the most common primary tumor of the bone in childhood and represents about 5% of all childhood cancers. Osteosarcoma can occur in any bone in the body, and while orbital presentations are rare, they have been reported. The ability to cure osteosarcoma depends on the ability to achieve a complete resection, so orbital tumors present a particular challenge. The majority of patients present with localized disease. Lungs are the most common site of metastases, when they occur. There are also cases of osteosarcoma metastasizing to the orbital wall (Fig. 13.4).


Fig. 13.4
MRI study images of a 13-year-old female patient with osteosarcoma metastasis involving the left lateral orbital wall. Axial T2-weighted (a), STIR (b), and post-contrast axial T1-weighted (c) images through the orbit demonstrate an expansile, destructive, enhancing mass (white arrows) involving the left lateral orbital wall and the greater wing of the sphenoid bone encroaching into the left retro-orbital space with displacement of the left optic globe anteriorly and medially and medial displacement of the left optic nerve sheath. Restricted diffusion (not shown) was noted within the mass. Also noted is contiguous extension into the left anterior temporal region (black*)

Osteosarcoma has a bimodal age distribution. There is a peak in adolescence and a second peak in adults greater than 65 years old. Osteosarcoma is more common in the African-American population and has a slight male predominance [13]. Risk factors for the development of osteosarcoma include prior radiation, Li-Fraumeni syndrome, history of retinoblastoma, and Bloom syndrome.

Clinical Presentation of Pediatric Osteosarcoma

Osteosarcoma typically presents with pain and/or a palpable mass. Systemic symptoms such as fever, weight loss, and night sweats are usually absent. Physical examination often reveals a palpable mass. Nodal involvement is rare.

Evaluation of Pediatric Osteosarcoma

With any suspicion of malignancy, a referral to a pediatric oncology center should be considered. Initial imaging and decisions about approach to biopsy/resection are critical, as violation of tissue planes may have implications for staging, treatment, and further local control.

Imaging of the primary tumor site is best achieved with MR. Metastatic evaluation includes a CT chest, to assess for pulmonary disease. PET or bone scan is used to evaluate for bony metastases or skip lesions.

Risk Group and Prognosis of Pediatric Osteosarcoma

The most important prognostic factor in osteosarcoma is the ability to fully resect the primary tumor and metastatic sites. Other adverse prognostic factors include poor histologic response following chemotherapy, male sex, tumor in the axial skeleton, and tumors greater than 10 cm.

Treatment of Pediatric Osteosarcoma

Chemotherapy is critical to our ability to cure osteosarcoma, even in those with localized disease, supporting the presence of micrometastases not visible even with modern staging techniques. The long-standing backbone of chemotherapy includes cisplatin, doxorubicin, and methotrexate. This provides cure in about 75% of patients with localized disease. Efforts to intensify therapy have, to date, not yielded an improved outcome. For those with unresectable tumors or unresectable metastases, the prognosis is far worse.

As with all sarcomas, primary tumor treatment is a difficult decision. Osteosarcomas are not radiation sensitive, so we rely solely on surgery to achieve local control. Osteosarcomas can rarely be treated without some long-term disability. The goals of the patient must be seriously considered when proposing options for local control. Although limb salvage techniques have improved significantly over time, for a very active teenager committed to participation in sports, amputation may provide a more acceptable outcome.


Epidemiology of Pediatric Neuroblastoma

Neuroblastoma represents an extraordinarily broad spectrum of disease, from spontaneously regressing tumors to high-risk, widely metastatic disease with a poor prognosis. Improved understanding of molecular and genetic features of these tumors has allowed for more detailed clinical classification.

Neuroblastoma can arise from any site along the sympathetic nervous chain. Metastases can involve the periorbital bones, leading to proptosis and periorbital ecchymoses. Tumors high in the thoracic region or in the neck can also cause a Horner’s syndrome.

Neuroblastoma is the most common extracranial solid tumor of childhood, representing between 8% and 10% of childhood cancers. Neuroblastoma is largely a disease of infants and young children, although diagnosis of an adolescent or young adult is possible.

Clinical Presentation of Pediatric Neuroblastoma

Clinical presentation varies with the spectrum of disease. Low-risk tumors are often incidentally discovered, while children with high-risk disease are usually ill appearing at presentation. Fevers, bone pain, pallor, and fatigue are common for those with high-risk disease. Orbital metastases can present as “racoon eyes” (Figs. 13.5, 13.6, and 13.7). Genetic analysis of the tumor is critical for risk group assignment. The diagnostic biopsy should be generous, if possible, to ensure adequate specimen. Children presenting with orbital ecchymoses should undergo imaging in search of a primary tumor mass. In the absence of a primary tumor, the orbital lesion may need to be biopsied. There is no role for complete resection, only a diagnostic specimen.


Fig. 13.5
One-year-old presenting with bilateral proptosis, fussiness, and bilateral temporal masses. Axial T2-weighted (a), axial post-contrast T1-weighted (b), and axial ADC map (c) through the orbits show mass lesions (black*) with extensive periosteal reaction (thick white arrows) seen involving the bilateral temporal bones and lateral walls of the orbits with mass effect upon the bilateral optic nerve sheaths (thin white arrows). The bilateral masses demonstrate intracranial extension and mass effect upon the anterior portions of the temporal lobes. These mass lesions demonstrate restricted diffusion (white*) and nearly homogeneous enhancement. Mild proptosis of the optic globes is evident. With the history of abdominal mass, these represent neuroblastoma metastases


Fig. 13.6
Another metastatic neuroblastoma. Images from enhanced CT study of the orbit with coronal soft tissue (a) and axial bone (b) window images demonstrate mass lesion at the superolateral orbit (black*) with spiculated periosteal involvement along the lateral orbital walls


Fig. 13.7
MRI images of the orbit on the same patient as shown in Fig. 13.5. Coronal (a) and axial (b) T2-weighted with fat suppression and post-contrast axial T1-weighted (c) and axial diffusion (d) images through the orbit which show expansion of the left sphenoid bone and subperiosteal masses which involve both the lateral aspect of the bilateral, left greater than right orbits resulting in mass effect on the left ocular globe. This metastatic disease to the skull was consistent with the patient’s known history of stage IV neuroblastoma

Evaluation of Pediatric Neuroblastoma

The primary tumor should be imaged with cross-sectional imaging. Metastatic evaluation includes an MIBG scan and bilateral bone marrow aspirates and biopsies. A rare subset of neuroblastomas (~10%) is MIBG non-avid. In this case, a PET scan should be considered to definitively rule out metastases. Urinary catecholamines should also be evaluated.

Risk Group Classification of Pediatric Neuroblastoma

In an effort to standardize risk group classification, the International Neuroblastoma Risk Group (INRG) was developed. INRG establishes pretreatment risk grouping. Staging via INRG relies on presence of image-defined risk factors (i.e., extent of tumor infiltration, encasement of surrounding vessels, infiltration of adjacent organs, or intraspinal extension). L1 tumors lack image-defined risk factors, while L2 tumors do not. Stage M tumors have spread to other parts of the body. Stage MS includes tumors in children, < 18 months old, with a particular pattern of metastases – skin, liver, and/or bone marrow (<10% bone marrow involvement). In addition to the INRG classification, age of the patient, histology, level of differentiation, ploidy, and presence/absence of MYCN amplification are used to assign a risk group – very low, low, intermediate, or high.

Treatment of Pediatric Neuroblastoma

Low- and intermediate-risk tumors are treated with observation, surgery alone, or surgery plus chemotherapy. Treatment of high-risk neuroblastoma is multimodal and includes induction chemotherapy, surgical resection, stem cell transplant, radiation, and immunotherapy. With this intensive approach, long-term survival has reached ~50%. Disease evaluation prior to stem cell transplant determines the approach to “local” control. Patients with persistent sites of MIBG-avid disease, including the orbit, will have those sites irradiated posttransplant.

Liquid Malignancies


Epidemiology of Pediatric Leukemia

Pediatric acute leukemia is the most common malignancy of childhood. Leukemia is a malignancy of the hematopoietic stem cells. The two main types of pediatric acute leukemia are acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) . ALL accounts for approximately 75–80% of acute leukemia in children, and AML accounts for most of the remaining 25–80% [14].

The incidence of ALL is approximately 30 cases per million in children younger than 20 years of age annually [15]. The peak incidence of ALL is between ages 3 and 5, but it can occur at all ages [15]. Boys are more likely to develop ALL than girls (55% of children with ALL are male), and Hispanic and white children are more likely to develop ALL than black children [15].

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Dec 19, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Oncologic Management for Liquid and Solid Tumors in Pediatric Oculoplastic Surgery

Full access? Get Clinical Tree

Get Clinical Tree app for offline access