Pediatric Parosteal Osteosarcoma of the Distal Radius with Destruction of the Adjacent Ulna: A Case Report

doi:10.21203/rs.3.rs-3211188/v1

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Case Report

Pediatric Parosteal Osteosarcoma of the Distal Radius with Destruction of the Adjacent Ulna: A Case Report

https://doi.org/10.21203/rs.3.rs-3211188/v1

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Journal Publication

published 06 Dec, 2023

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Introduction:Parosteal osteosarcomas are low-grade bony malignancies that are treated primarily with surgical resection and reconstruction. We report a unique case of a pediatric patient who presented with a parosteal osteosarcoma of the distal radius with local invasion into the ulna. Likely due to their slow-growing nonaggressive nature, parosteal osteosarcomas have not been previously described to invade adjacent bony structures through direct contact. Our patient presented in a significantly delayed manner due to social circumstances, allowing us to inadvertently describe this novel behavior. We review this rare case and describe the current understanding of this tumor.

Case presentation:Our patient is a 13-year-old male who presented with a parosteal osteosarcoma of his distal radius. He presented with a palpable wrist mass and wrist stiffness. He presented in a delayed manner with advanced local disease due to social factors. Imaging revealed an osseous radial mass that effaced the ulna and likely stunted its growth. The patient ultimately underwent complex resection and allograft reconstruction of both his distal radius and ulna. Intraoperative pathology confirmed tumor pathology with erosion of the adjacent ulna. Allograft reconstruction of the radius and ulna was performed utilizing patient-specific custom cutting guides. At the 6-month postoperative visit, the patient had no recurrence of the mass, minimal pain, and had almost regained range of motion of the extremities. Clinical radiographs at the 6-month postoperative visit demonstrated allograft incorporation.

Conclusions: We present a previously unreported case of pediatric parosteal osteosarcoma of the distal radius with erosion of the adjacent ulna through direct contact. We describe the challenges in and emphasize the importance of arriving at a definitive diagnosis in a timely manner for the proper treatment of this malignancy.

Parosteal Osteosarcoma

Pediatric

Distal Radius

Ulna

MDM2 gene amplification

Parosteal osteosarcomas are low-grade bony malignancies that typically occur on the surface of metaphyseal long bones. They occur more commonly in women in the third decade of life. They carry a small risk of dedifferentiation and metastatic spread and are managed primarily with wide surgical resection and reconstruction [1]. Although other more aggressive bony malignancies have been shown to directly invade adjacent bony structures, parosteal osteosarcomas have not been described to behave this way prior to our report.

There are several diagnostic challenges present in identifying parosteal osteosarcomas. The histopathology of a parosteal osteosarcoma can appear benign. Both imaging and pathology can mimic other benign processes such as an osteochondroma. Molecular testing such as MDM2

gene amplification is crucial in making the correct diagnosis. Furthermore, aberrant gene signaling is only detectable at the active margins of the tumor, making it essential to utilize meticulous biopsy techniques and obtain samples from multiple areas of the tumor.

We report an unusual case of a 13-year-old skeletally immature male with a parosteal osteosarcoma involving the distal radius. Due to social factors, the patient presented to our institution in a delayed manner. Treatment was further delayed due to difficulties diagnosing the lesion. The patient ultimately underwent successful wide resection with negative margins and reconstruction with a strut allograft, plates and screws.

The patient was a 13-year-old male, right hand dominant football player who was referred to our institution for a left wrist mass. He was brought in by his step-mother, who had noticed the mass and was concerned about the patient’s progressive decrease in wrist range of motion. Upon chart review, the patient had radiographs of the forearm documenting a left distal radius mass one year prior to his initial visit at our institution. Further history revealed that after presenting the previous year, the patient was lost to follow-up and did not obtain further imaging or treatment during the interim. Physical exam revealed a large solid volar mass at the wrist without any sensorimotor deficits. The radial and ulnar pulses were both 2+. He had limited range of motion at the wrist with approximately 15 degrees of supination and 10 degrees of pronation. He lacked approximately 15 degrees of flexion and extension compared to the contralateral wrist. New radiographs demonstrated that the mass had grown approximately 3 mm in width, 5 mm in length, and increased in radiopacity compared to imaging one year prior (Fig. 1). MRI with IV contrast was obtained, which showed an approximately 3.5 x 3.2 x 6.3 cm heterogeneous expansile corticomedullary mass arising from the ulnar aspect of the radial metadiaphysis that appeared hyperintense on T2 and hypointense on T1 sequences. The mass extended into the syndesmosis, eroding into the ulna causing thinning and breakdown of the adjacent ulnar cortical bone (Fig. 1).

Significant negative ulnar variance was noted on the affected wrist. It appeared as though the tumor abutment caused growth delay of the distal ulnar physis. We utilized the Hafner method to determine the degree of negative ulnar variance. The difference between the most proximal point to the radial and ulnar metaphysis (PRPR) and the difference between the most distal point of the radial and ulnar metaphysis (DIDI) were measured to be approximately 1.35 and 1.6 cm on initial presentation one year prior. Similarly, more recent radiographs demonstrated approximately 1.15 cm to 1.68 cm of ulnar shortening.

Differential diagnosis at this time included osteochondroma, melorheostosis, osteosarcoma, and secondary chondrosarcoma. We proceeded with an open surgical biopsy targeting the ulnar aspect of the mass under fluoroscopic guidance. Intraoperative frozen sections revealed lesional tissue with benign fibrous tissue and bone. Biopsied tissue was decalcified for permanent histology preparation. Therefore, we were unable to perform molecular studies on the samples obtained at that time. Permanent tissue histology demonstrated hyaline cartilage merging with bony trabeculae and associated bland fibrovascular and fatty tissues. The biopsy was ultimately deemed nondiagnostic.

At following clinical visits there was persistent suspicion for malignancy. Multiple discussions were had with the patient and family to perform a repeat biopsy of the mass. 3 months following the initial procedure we performed a repeat biopsy. Tissue was sent to an outside institution for consultation with molecular studies. The outside facility found the biopsy to be MDM2 positive on stain, and the patient was diagnosed with a low-grade parosteal osteosarcoma (Fig. 2).

We attempted to expediently schedule the patient for operative resection of the mass. However, the patient and family expressed the desire to complete his school football season despite inherent risks.

The patient ultimately underwent wide resection and reconstruction of his left distal radius and ulna approximately 18 months after the mass was first found. Due to the tumor’s close proximity to the wrist joint, the necessity for margin-negative wide resection and to maximize postoperative function, we elected to use a custom 3D printed patient-specific cutting guide developed from preoperative CT scans (Fig. 1).

Intraoperatively, the distal radius was resected en bloc salvaging the distal articular segment. Frozen sections of the ulnar periosteum and ulna were obtained to evaluate intraoperative margins. These sections were inconclusive at the time of the operation. Due to the direct involvement of the ulna on preoperative imaging and concerning histology on these frozen sections, we proceeded with resection of the ulna as well. The resected tumor measured 7.6 cm by 4.3 cm (Fig. 2). All neurovascular structures were identified and confirmed to be intact after resection. Matching distal radius and ulna allografts were cut to shape using 3D printed cutting guides. The allografts were fixed onto the proximal segments of the patient’s radius and ulna using plates and locking screws, respectively.

The patient had a normal neurovascular exam postoperatively. He was placed in a cast and made nonweight bearing to the extremity for three months. Final pathology returned with negative margins for malignancy and confirmed the diagnosis of low-grade parosteal osteosarcoma of the distal radius and erosive changes of the resected ulna. At his six-month postoperative appointment, the patient had almost regained full range of motion (Fig. 3). Radiographs show bony union at the allograft junction. At this six-month visit imaging of the contralateral forearm was taken showing neutral ulnar variance (Fig. 3). He has been overall satisfied with his progress and plans on playing football this fall.

Parosteal osteosarcomas are rare low-grade bony malignancies with a slight female preference found in the second to fourth decades of life [1]. Okuda et al. reported a female to male ratio of 1.28:1 in their report of 228 patients [1]. Parosteal osteosarcomas arise from the periosteum of metaphyseal long bones, most commonly in the distal femur, proximal tibia, and proximal humerus [1, 2]. However, there have been reports of parosteal osteosarcomas arising from various locations, such as the distal radius, talus, cranium, mandible, ribs, clavicle, and tarsal bones [3, 4, 8].

Although they were once thought to be a subtype of intramedullary osteosarcomas, the World Health Organization (WHO) now recognizes parosteal sarcomas as a distinct entity with its own unique clinical course and pathologic characteristics [5]. On presentation, patients most commonly complain of a painless growing mass and range of motion limitations in cases in which the tumor arises adjacent to a joint [6]. Radiographically, the tumor appears as a cortically based exophytic ossified mass without extension into the medullary canal [7]. They can often be mistaken for osteochondromas, which also appear as cortically based bony masses, but present with continuity of the medullary space between the mass and the native bone.

Histological and immunochemical analysis showed a fibro-osseous lesion with hypocellular spindle cell stroma containing trabeculae of bone. Spindle cells usually have minimal cytologic atypia and limited mitotic activity [1]. Okuda et al delineated guidelines for identifying parosteal osteosarcomas that involve radiographic evidence of bony origin and histology showing well-formed osteoid, spindle-cell stroma and overall well-differentiated low-grade appearance. They also noted that in cases with medullary involvement, there must be less than 25% involvement of the cavity [1]. Molecular studies can aid in the diagnosis of this malignancy over its benign imitators. Yoshida et al examined MDM2 and CDK4 gene amplifications to differentiate parosteal osteosarcoma from osteochondroma. The authors found that all of the parosteal osteosarcoma samples demonstrated positivity to CDK4 gene amplification, and the majority showed positivity to MDM2 gene amplification [9]. Duhmel et al reported that MDM2 could be utilized to distinguish parosteal osteosarcoma from conventional osteosarcoma, as 85% of parosteal osteosarcomas in their sample were MDM2 amplification positive [10].

Parosteal osteosarcomas are well-differentiated malignant tumors with low local recurrence rate and metastatic potential. Treatment consists of wide resection without chemotherapeutic intervention. Ruengwanichayakun et al demonstrated that the degree of dedifferentiation of these tumors had the largest inverse effect on long-term survival. They reported 96% 5-year survival in parosteal osteosarcomas compared to 65% in cases with dedifferentiation. Similarly, they reported the 10-year survival rates of the two groups to be 96% and 60%, respectively [11].

In this case, there was a significant delay in treatment due to various social factors. The patient initially presented with advanced local disease and was lost to follow-up for an additional year. Surgical resection was further delayed following diagnosis due to the patient's desire to participate in his high school sports season. Fortunately, despite the delayed presentation, the patient’s lesion did not worsen significantly on repeat plain radiographs. This reflects the slowly evolving natural history of this tumor.

Direct local invasion of adjacent bone has been reported in aggressive bony malignancies and has been associated with a higher likelihood of local recurrence and poorer outcomes [12]. In our case, both preoperative imaging and intraoperative histology demonstrated tumor invasion causing erosion of the adjacent ulna. This phenomenon has not been characterized previously in parosteal osteosarcomas of the distal radius in skeletally immature patients. This may be due to the fact that these lesions more commonly arise in the distal femur, proximal tibia, or humerus, where direct bony abutment to an adjacent bone is far less likely. The delay in presentation also played a role in allowing the tumor to grow to a sufficient size to allow for adjacent bony invasion. It may be that in previously reported cases, the tumor was resected prior to reaching a size to abut and efface an adjacent bone. We feel that this is likely a phenomenon only seen in later stages of the disease. Although this demonstrates the slow-growing nature of parosteal osteosarcomas, we recommend expedited treatment, as local bony invasion may require more aggressive resection and complex reconstruction endeavors.

Utilizing the mean distal ulnar growth rate and negative ulnar variance measurements, we were able to estimate when the tumor began impeding the distal ulnar growth and approximate how long the tumor had been growing. We utilized the Hafner method to calculate the ulnar variance for our patient. In short, this is a validated method of measuring negative ulnar variance in pediatric patients by measuring the difference between the most proximal point to the radial and ulnar metaphysis (PRPR) and the difference between the most distal point of the radial and ulnar metaphysis (DIDI). Even at initial presentation, our patient had approximately 1.35 to 1.6 cm of ulnar shortening. We assumed the mean growth rate of the distal ulna to be approximately 0.9 cm per year; the mean ulnar growth rate in skeletally immature males is reportedly 1.1 cm per year, with the distal ulna accounting for 85% of the growth [13]. Using these values, we estimated that the tumor had been impeding the growth of the ulna for approximately 1.5 to 1.9 years even prior to initial presentation. Of note, this only accounts for when the tumor was of sufficient size to start impeding the growth of the distal ulna. Although an estimate, this does give insight into the age of our patient’s tumor and how slow growing it is.

Finally, our case also demonstrated the common diagnostic difficulties associated with this malignancy. Pathology can often have a benign appearance, making molecular studies crucial in making the correct diagnosis. Aberrant gene signaling can only be detected at the active margins of the tumor, and as in our case, these can be prone to sampling errors. Adhering to careful biopsy techniques and sampling multiple areas of the tumor, making sure to include active borders of bony growth are paramount. Furthermore, communication with the pathology team regarding the differential diagnosis, clinical presentation, and molecular studies needed can shorten the time to diagnosis and treatment.

We present a case of low-grade parosteal osteosarcoma in the distal radius in a skeletally immature individual. We describe a unique phenomenon of local invasion through direct contact between adjacent bones. To our knowledge, this has not been previously described in the literature for this malignancy. In addition, we highlight our experiences and the challenges encountered during the management of this case. We were able to obtain a tissue diagnosis and proceed with limb salvage operation in part due to the advances made in molecular testing for this malignancy. Although the diagnosis and treatment were delayed in our case for various reasons, our patient thus far has had a positive outcome, which provides insight into the unique natural history of this tumor.

MDM2- Mouse double minute 2 homolog

MM– Millimeter

CM- Centimeter

MRI- Magnetic resonance imaging,

IV- Intravenous

T2- Transverse relaxation time

T1- Longitudinal relaxation time

PRPR- Proximal point to the radial and ulnar metaphysis

DIDI- distal point of the radial and ulnar metaphysis

CT- Computerized tomography

AP- Anterior posterior

WHO- World Health Organization

CDK4- Cyclin-dependent kinase 4

Acknowledgements

We are grateful for all the members of the University of Nevada, Las Vegas medical team involved in this patient's care.

Funding

There was no funding for the research for this manuscript for the authors.

Availability of data and materials

Written consent was obtained from the patient and parents for publication of the patient’s details. The data supporting this case report are from previously reported studies and datasets, which have been cited. The processed data are available upon request from the corresponding author.

Authors’ contributions

AP and SP wrote the initial draft of this manuscript and subsequent revisions. RP helped with obtaining consent from the patient and family along with submission of this manuscript. JD is the senior author who is treating the patient; he is responsible for the oversight of the report and editing the manuscript. All authors have read and approved the final manuscript.

Competing interests

The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.

Consent for publication

The authors have obtained the patient’s and family’s written informed consent for print and electronic publication of this case report.

Ethics approval and consent to participate

Not applicable.

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No competing interests reported.

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Journal Publication

published 06 Dec, 2023

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Editorial decision: Major revision
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Pediatric Parosteal Osteosarcoma of the Distal Radius with Destruction of the Adjacent Ulna: A Case Report

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