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Osteosarcoma as a primary bone tumor in the adult foot: A case report

Open AccessPublished:October 05, 2022DOI:https://doi.org/10.1016/j.fastrc.2022.100248

      Abstract

      A 50-year-old male presented with left hallux pain and swelling that was treated for infection. Initial imaging studies were inconclusive, but further evaluation led to a diagnosis of high-grade primary osteosarcoma. Despite surgery and chemotherapy, the disease progressed rapidly, and 7 months after toe amputation multiple lung metastases were discovered. The patient died 15 months after diagnosis. Foot osteosarcomas are extremely rare malignant neoplasms that are often misdiagnosed, resulting in delayed or inappropriate treatment. It is imperative to maintain a high index of suspicion of any destructive bone lesions in the foot, regardless of size and symptom severity.

      Keywords

      Introduction

      Osteosarcomas are osteoid-producing malignant tumors of mesenchymal origin and are among the most common primary bone malignancies during childhood and adolescence. Most cases are high-grade malignancies originating in the metaphyseal region of long bones and are diagnosed in individuals aged 10–25 years. In adults, osteosarcomas are often secondary to preexisting bone pathology, most commonly radiation-induced osteitis
      • Picci P.
      • Picci P
      • Manfrinii M
      • Fabbri N
      • Gambarotti M
      • Vanel D
      Classic osteosarcoma.
      . The limited literature suggests that osteosarcomas of the foot are rare, accounting for 1–6% of cases. The foot bones most commonly affected are the calcaneus, followed by the tarsals and the small tubular bones; the phalanges are rarely involved.
      • Picci P.
      • Picci P
      • Manfrinii M
      • Fabbri N
      • Gambarotti M
      • Vanel D
      Classic osteosarcoma.
      ,
      • PosthumaDeboer J
      • Graat HC
      • Bras J
      • Saouti R.
      Small cell osteosarcoma of a toe phalanx: a case report and review of literature.
      Primary osteosarcoma of the short tubular bones of the foot in adults is exceedingly uncommon (<2% of all adult cases); mean age at diagnosis is 34 years, significantly later than the classic peak age of incidence during adolescence. The rarity of such cases often contributes to misdiagnosis and delayed or inappropriate treatment, facilitating disease spread.
      • PosthumaDeboer J
      • Graat HC
      • Bras J
      • Saouti R.
      Small cell osteosarcoma of a toe phalanx: a case report and review of literature.
      • Biscaglia R
      • Gasbarrini A
      • Böhling T
      • Bacchini P
      • Bertoni F
      • Picci P.
      Osteosarcoma of the bones of the foot—an easily misdiagnosed malignant tumor.
      • Wu KK.
      Osteogenic sarcoma of the tarsal navicular bone.
      In a retrospective study of 12 cases, Biscaglia et al. reported that the average time from patients’ onset of pain and swelling to diagnosis was 28 months.
      • Biscaglia R
      • Gasbarrini A
      • Böhling T
      • Bacchini P
      • Bertoni F
      • Picci P.
      Osteosarcoma of the bones of the foot—an easily misdiagnosed malignant tumor.
      Half of cases were misdiagnosed. Of the 7 patients with histologically identified high-grade lesions, 4 died of metastatic disease, on average 50 months after diagnosis. Prognosis was poorer in patients with delayed diagnosis, which often led to amputation rather than foot-sparing surgery. Older age, high-grade histologic malignancy, and delayed diagnosis were associated with disease progression and decreased survival.
      The clinical and radiographic findings may resemble those of conventional osteosarcoma, and include pain, swelling, and bone destruction. However, they may be nonspecific (e.g., redness, dystrophic nail, superimposed superficial infection) to a degree that hinders diagnosis and delays treatment.
      In this report, we present the case of a patient with high-grade osteosarcoma of the left hallux. Our goals are to highlight the highly malignant nature of foot osteosarcomas, to underscore the risk of delayed diagnosis and treatment, and to promote prompt recognition of this very rare condition. The patient provided informed consent for his health information to be used for research and educational purposes, including publication in the medical literature.

      Case report

      A 50-year-old male with an unremarkable medical history presented to the emergency room in April 2017 with pain, redness, and swelling in his left hallux. He stated that the symptoms had been present for four weeks but reported no fever, chest pain, or shortness of breath. Because he had clinical signs of infection, he was treated with cephalexin 500 mg bid. After initial radiographic imaging (no official radiologist readback was done), the patient was discharged and advised to visit our podiatry office for outpatient follow-up.
      At the follow-up visit one week later he reported that the pain was radiating and pulsating and kept him awake at night; he rated its severity as 10 on a 10-point scale. Physical exam revealed a large bulbous deformity at the distal aspect of the left great toe, with partially absent hallux nail and swelling of the entire toe (Fig. 1A). No ulceration or cellulitis was evident. The patient had palpable pedal pulses bilaterally with a temperature gradient within normal limits. Neurological protective and epicritic sensation was grossly intact bilaterally. Pain on palpation was noted to the distal aspect of the left great toe. The hallux interphalangeal joint had limited range of motion. There were no regional or distant palpable lymph nodes.
      Fig 1
      Fig. 1A. Clinical picture. -B Anteroposterior view of the left foot. -C Oblique view of left foot. -D Zoomed-in anteroposterior view of left hallux. Note cystic changes with periosteal reaction and permeative destruction of cortex of the first distal phalanx.
      Radiographs showed a permeative destructive lesion with some periosteal reaction of the cortex and soft tissue expansion of the distal phalanx of the great toe (Fig. 1B-D). After reviewing the radiographs and clinical presentation, we ordered magnetic resonance imaging (MRI) to further assess the pathology. MRI confirmed the presence of a destructive and expanding mass that had peripheral nodular enhancing borders with internal fluid-like signal intensity (Fig. 2A-D). The lesion measured 2.0 × 1.2 × 0.8 cm and was associated with extensive inflammatory changes of the adjacent fat, including skin thickening and stranding of subcutaneous tissue. Cartilage loss of the first interphalangeal joint with a small enhancing joint effusion was evident, though no obvious degenerative changes were noted. These findings raised suspicions of malignancy; the differential diagnosis also included subacute/chronic bacterial osteomyelitis and a granulomatous necrotizing process (e.g., fungal infection). An in-office biopsy was scheduled to provide tissue-based diagnosis.
      Fig. 2
      Figs. 2A-D Magnetic resonance imaging of the left foot. Note the destructive, expansile lesion disrupting the first distal phalanx and the peripheral nodular enhancing borders with fluid-like signal intensity.
      The biopsy was performed the following week. After 5 cc of 1% lidocaine plain was injected for local anesthesia, a small stab incision was made on the dorsal aspect of the left hallux; the incision was then deepened to the bone. A Jamshidi needle was used to obtain a biopsy of the distal phalanx, and the specimen was sent out for culture and pathology. Results of culture and sensitivity tests were negative and revealed no aerobic or anaerobic growth. However, the biopsy results indicated a high-grade osteosarcoma.
      The patient was advised to take acetaminophen for pain, was prescribed cephalexin 500 mg, and was transferred to [blinded for peer review]. The pathology report was sent for review, and a musculoskeletal pathologist confirmed the diagnosis of conventional high-grade osteosarcoma. The distinctive pathologic features were marked cellular pleomorphism and nuclear atypia in a background of osteoid matrix (Fig. 3, Fig. 4).
      Fig 3
      Fig. 3Biopsy of conventional high-grade osteosarcoma of the left first distal phalanx. Green box: neoplastic cells in a background of osteoid. Red box: residual trabeculae (40x).
      Fig 4
      Fig. 4Amputated specimen. Neoplastic cells with high-grade atypia and pleomorphism (blue arrow) (40x).
      The tumor staging workup comprised a 99m-Tc-MDP whole-body bone scan and computed tomography (CT) scan of the chest, abdomen, and pelvis. While bone scan showed no abnormal uptake outside of the left hallux, the CT scan revealed multiple bilateral lung metastases. A treatment plan consisting of en-bloc excision with negative margins followed by multidrug chemotherapy was recommended. The patient underwent a left partial first-ray amputation in May 2017 and had an uneventful postoperative course. The amputated specimen (Fig. 5) was sent to the pathology lab, which again confirmed the diagnosis and noted tumor infiltration and destruction of the left hallux. Tumor size was 4 × 2.8 × 2.6 cm.
      Fig 5
      Fig. 5Amputated specimen. Postamputation gross pathology images of tumor infiltrating and destroying the left hallux.
      Three weeks postsurgery, the patient started a chemotherapy regimen that included 7 cycles of cisplatin and doxorubicin. The patient quickly resumed ambulation and returned to nearly normal activity 6 weeks after surgery. Postoperative pain and chemotherapy-related symptoms and side effects were effectively addressed by medical management. The patient tolerated treatment well and there were no major deviations from the intended chemotherapy regimen and dose/intensity ratio.
      In July 2017, the patient reported onset of thoracic rib, spine, and testicular pain. Chest imaging demonstrated clear disease progression and increased size of the lung metastases. Further increase in lesion size was noted on a CT scan in September. Moreover, transesophageal echocardiography revealed a right atrium thrombus, and the patient was placed on rivaroxaban 20 mg daily. In December 2017, the patient underwent a right thoracotomy and multiple wedge resections; plans were made to address the left lung. However, the disease progressed rapidly, resulting in multiple unresectable lung lesions, and palliative care was progressively implemented to provide support.
      During treatment and follow-up, patient was also seen regularly to assess the primary tumor site. His left foot remained functional, with no pain or evidence of local recurrence, until he died of disease 15 months after diagnosis.

      Discussion

      Osteosarcomas occur most commonly in the long bones and are extremely rare in the foot. Awareness and early recognition, though difficult, are critical to successful management and survival. Conversely, misdiagnosis and inappropriate treatment—or even appropriate but delayed treatment—are often associated with disease progression and a fatal outcome.
      Biscaglia et al. noted that the average time between initial symptoms and diagnosis was more than 2 years (28 months) in their series, and that half of the cases had been misdiagnosed.
      • Biscaglia R
      • Gasbarrini A
      • Böhling T
      • Bacchini P
      • Bertoni F
      • Picci P.
      Osteosarcoma of the bones of the foot—an easily misdiagnosed malignant tumor.
      Other work has established a clear negative relationship between time to diagnosis and survival, showing also that metastatic disease at diagnosis is the main prognostic factor for high-grade osteosarcoma.
      • Colding-Rasmussen T
      • Thorn AP
      • Horstmann P
      • Rechnitzer C
      • Hjalgrim LL
      • Krarup-Hansen A
      • Peterson MM.
      Survival and prognostic factors at time of diagnosis in high-grade appendicular osteosarcoma: a 21 year single institution evaluation from east Denmark.
      Among patient-related factors, age has a significant effect on prognosis, with older patients having worse outcomes.
      • Anderson ME.
      Update on survival in osteosarcoma.
      Lesion size is also a prognostic factor. In the recently revised staging manual of the American Joint Committee on Cancer,
      which uses TNM classification, the size of a bone sarcoma arising in the appendicular skeleton is categorized as T1 (≤8 cm), T2 (>8 cm) or T3 (discontinuous tumors in the primary bone site). Notably, our patient had a relatively small tumor at diagnosis—4 cm in diameter, well below the cutoff for higher staging and risk—yet presented with bilateral lung metastases, reflecting an extremely aggressive tumor biology.
      Awareness of epidemiologic, clinical, radiographic, and histologic features can facilitate early recognition of this rare malignancy. It is imperative to maintain a high index of suspicion of any bone lesions in the adult foot, even if patients present with mild symptoms. Thorough clinical assessment, biopsy, and prompt referral to a musculoskeletal cancer surgeon are critical for successful diagnosis and treatment. Referral to an experienced musculoskeletal oncology group for multidisciplinary management—including workup, staging, diagnosis, and multimodal treatment—remains critical for cure. Advances in molecular profiling and cancer biology are needed to understand aggressive clinical course and metastatic potential, as well as to provide novel treatment opportunities.
      This case also highlights the important role of podiatric surgeons in the overall health of patients. They are trained to identify, prevent, diagnose, and address (in this case by referral to a specialized center) disease, including conditions rarely affecting the pedal extremity. They may also profoundly impact the life of a patient, such as in the case of a primary malignancy at high risk for metastatic progression and fatal outcome.

      Declaration of Competing Interests

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      Acknowledgement

      We would like to thank Dr. Parul Gheewala, MD, for her support and contributions to this project.

      Funding

      This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. The funding source had no role in the collection, analysis, or interpretation of data, the preparation of this case report, or the decision to submit the case for publication.

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