Rare Case of Recurrent Adamantinoma of the Tibia: Limited Efficacy of Pazopanib as a Standalone Treatment.

BACKGROUND Adamantinoma is a rare low-grade malignant bone tumor, usually found in the tibial diaphysis and metaphysis, with histological similarities to mandibular ameloblastoma. The most effective treatment of recurrent adamantinoma is not yet clear. This report is of a 22-year-old woman with recurrent tibial adamantinoma treated with the tyrosine kinase inhibitor pazopanib. CASE REPORT We report the case of a 22-year-old woman who was referred to our center for a suspicious bone lesion in the right tibia. Bone biopsy findings were consistent with an adamantinoma. En bloc resection was completed successfully, with no postoperative complications. Five years later, a positive emission tomography scan revealed mildly increased tracer uptake near the area of the previous lesion and in the right inguinal lymph node. Biopsies of the lesion and inguinal lymph node confirmed recurrence of the adamantinoma. Due to abdominal and pelvic metastasis, the patient underwent surgical debulking, along with an appendectomy, right salpingo-oophorectomy, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Subsequently, the patient was placed on pazopanib for 4 months; however, her tumor continued to worsen after 4 months of chemotherapy. Currently, the patient is receiving gemcitabine and docetaxel as second-line medical therapy. CONCLUSIONS This report showed that pazopanib as standalone treatment does not appear to have promising role on patient outcomes. To the best of our knowledge, this is the second report of pazopanib in the treatment of adamantinoma.

Clinical outcomes in patients with adamantinoma: Report from the bone and soft tissue tumor registry in Japan.

BACKGROUND: Adamantinomas are rare malignant bone tumors. Due to their low incidence, there are few reports on the clinical results of adamantinoma. OBJECTIVES: This study aims to clarify outcomes in patients with adamantinoma using data from the National Bone and Soft Tissue Tumor Registry. METHODS: From 2006 to 2019, 38 cases of tibial origin were included. Twenty-four were male and 14 were female, with a mean age of 37 (6-87) years and a mean follow-up of 35 (1-128) months. RESULTS: Surgery was performed in 33 cases (87%) (curettage: 4 cases, wide resection: 27 cases, amputation: 2 cases). Reconstruction was performed in 27 patients who underwent wide resection. A total of 12 additional surgeries were performed in 11 patients. The main reason for the additional surgeries was nonunion of grafting bone in 6 cases. Oncologic outcomes were DOC (death from other causes) in one case and NED (no evidence of disease) in 37 cases. CONCLUSIONS: The results of treatment of adamantinomas in Japan have been extremely favorable. This may be due in part to the large number of cases with wide resection.

Adamantinoma-Like Ewing Sarcoma Mimicking Merkel Cell Carcinoma in the Parotid Gland: A Diagnostic Pitfall.

Adamantinoma-like Ewing sarcoma (ALES) is a newly described rare entity, which shows EWSR1::FLI1 rearrangement characteristic of Ewing sarcoma. This can be diagnostically challenging as it manifests histologically with epithelial differentiation and has diffuse keratin expression as well as p40 and p60 positivity. We hereby report a case of ALES in a 33-year-old woman with a past medical history of breast carcinoma who presented with a right-sided parotid mass. CT scan of the neck showed a heterogenous mass within the superficial lobe, measuring 17 mm in diameter for which the patient underwent superficial parotidectomy. Histopathology of the mass revealed a malignant neoplasm formed of solid nests, cords and sheets of cells with minimal cytoplasm and monomorphic nuclei with granular chromatin and indistinct nucleoli. Brisk mitotic activity and tumor necrosis were also present. The tumor showed strong and diffuse reactivity for pankeratin (clone AE1/AE3) and keratin 20, both in a dot-like pattern, raising the suspicion of metastatic Merkel cell carcinoma; however, molecular studies showed EWSR1::FLI1 rearrangement, supporting the diagnosis of ALES. In summary, it is prudent to have knowledge about this entity to avoid its misdiagnosis as other malignancies of the head and neck region which exhibit a different clinical course, prognosis and hence treatment modalities.

Outcome for Neoadjuvant Treatment of Parotid Gland Adamantinoma-Like Ewing Sarcoma: Case Report and Review of Literatures.

Adamantinoma-like Ewing sarcoma typically shows t(11;22) EWSR1::FLI1 translocation and complex epithelial differentiation. It poses a diagnostic challenge, especially in the head and neck region, due to its under-recognition and significant histologic overlap with other malignancies. Neoadjuvant and adjuvant treatment information on head and neck Adamantinoma-like Ewing sarcoma is limited. Herein, we report a case of a 78-year-old female with Adamantinoma-like Ewing sarcoma of the parotid gland, including the imaging findings and clinical response to neoadjuvant therapy followed by surgery. The efficacy of neoadjuvant therapy in the treatment of Adamantinoma-like Ewing sarcoma is discussed in the context of a review of pertinent literature. Adamantinoma-like Ewing sarcoma in the head and neck is frequently misdiagnosed as poorly differentiated squamous cell carcinoma or a basaloid salivary gland carcinoma. Adamantinoma-like Ewing sarcoma is a EWS1::FLI1 translocation driven tumor; frequently misdiagnosed on head and neck biopsies as poorly differentiated carcinoma, or squamous cell carcinoma. Ewing sarcoma-specific chemoregimen appears effective for this entity. If diagnosed early, patient may be amenable to neoadjuvant therapy, which may improve surgical and cosmetic outcomes. This is especially important in head and neck regions.

Osteofibrous dysplasia and adamantinoma: A summary of diagnostic challenges and surgical techniques.

Osteofibrous dysplasia is an indolent benign fibro-osseous tumor, while adamantinoma is a locally aggressive biphasic malignancy with epithelial and fibro-osseous components. Predominantly arising in the tibial diaphysis of children and young adults, both tumors are resistant to chemotherapy and radiation. Wide surgical resection is regarded as the mainstay of therapy for adamantinoma, and limb-salvage reconstructive procedures can achieve good functional outcomes, albeit with non-negligible rates of complications. This review discusses emerging advances in the pathogenesis, histogenesis, and diagnosis of these entities and presents advantages and limitations of the most common surgical techniques used for their management.

Adamantinoma: metastatic disease masquerading as a gynaecological malignancy.

Adamantinoma is a rare low-grade malignancy of the appendicular skeleton with unclear histogenesis. We present the case of a 65-year-old woman with known recurrent and metastatic right tibial disease despite clear resection margins. On further investigation, a positron emission tomography-CT scan identified a primary breast lesion and an 11 cm mass in the right iliac fossa of suspected ovarian malignancy amenable to surgical resection. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and resection of a retroperitoneal mass arising from the pelvic sidewall encompassing the iliac vasculature. The patient made an uneventful recovery with histology confirming disease metastasising to the pelvis. Currently, clinical management guidelines are not available. We present an overview of adamantinoma and highlight a previously undocumented gynaecological oncology surgical approach to this novel disease location. Regarding metastases, we acknowledge the challenges of investigation pertaining to disease site and origin as well as a paucity of recommendations for surveillance and follow-up.

Adamantinoma-like Variant of Ewing Sarcoma in the Metatarsal Bone After Chemotherapy: Report of a Case Successfully Treated with Pedicled Osteocutaneous Fibular Transfer.

Adamantinoma-like Ewing sarcoma is a rare variant of Ewing sarcoma with histologic and immunohistochemical evidence of squamous differentiation. This variant most commonly occurs in the head and neck region with a few cases reported in the long bones of the limbs. It may be associated with poorer clinical outcome and could pose a diagnostic challenge, particularly if it occurs in older patients or as a metastatic lesion. We present a case of Ewing sarcoma in the metatarsal of an 11-year-old boy that manifested adamantinoma-like morphology after neoadjuvant chemotherapy. Chemotherapy has been reported to induce neuronal maturation and rhabdoid morphology in cases of Ewing sarcoma, but no reports of treatment-induced squamous differentiation with P40/P63 expression have been demonstrated. This is also the first documented case treated with a pedicled osteocutaneous fibular transfer in a metatarsal malignancy, which is usually treated by either ray or below-knee amputation.

Understanding The Rare Bone Tumor "ADAMANTINOMA".

Adamantinoma is a rare neoplastic bone tumor that has the potential to metastasize. The classic presentation is in the tibial region however; cases involving other bones of the body have been noticed. The tumour is very likely to be mistaken for other bone diseases and therefore it is important to investigate and study about its nature and thus differentiate it from other differentials. Nevertheless, literature on the presentation, findings, investigations and treatment options of adamantinomas are limited. In this case series, we report four cases from a local hospital in Karachi who were diagnosed, treated and followed up for adamantinoma. Studies regarding the disease will help us understand more about its features.

Recurrent adamantinoma of the mandible.

Adamantinoma is an extremely rare tumour originating from bone that can be divided into classical and osteofibrous dysplasia (OFD)-like adamantinoma. This low-grade malignancy almost exclusively occurs in long bones, and only few cases of mandibular adamantinoma have been reported. Here, we report the case of a 30-year-old female with a 2-year history of right mandible tenderness. Radiological examinations showed a lytic lesion involving the right mandible without a well-defined margin. Biopsy confirmed the diagnosis of adamantinoma. She underwent a segmental mandibulectomy and reconstruction with a fibula flap. The definitive diagnosis was OFD-like adamantinoma. However, the tumour recurred after 5 years. The residual mandible and fibula flap were widely involved. A total mandibulectomy was performed. Five years later, there is no evidence of recurrence or metastasis. We recommend that adamantinoma be treated by radical resection with clear margins, and long-term surveillance is necessary due to the likely high local recurrence rate and the potential for late tumour metastasis.

Surgical Outcome and Oncological Survival of Osteofibrous Dysplasia-Like and Classic Adamantinomas: An International Multicenter Study of 318 Cases.

BACKGROUND: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. METHODS: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. RESULTS: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. CONCLUSIONS: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Osteofibrous dysplasia-like adamantinoma treated via intercalary segmental resection with partial cortex preservation using pedicled vascularized fibula graft: a case report.

BACKGROUND: Morphologically, osteofibrous dysplasia-like adamantinoma is thought to be intermediate between osteofibrous dysplasia and adamantinoma. Its treatment is not well established owing to its rarity. CASE PRESENTATION: We report about of a 10-year-old girl with osteofibrous dysplasia-like adamantinoma initially diagnosed as osteofibrous dysplasia and treated via intercalary segmental resection with partial cortex preservation using a pedicled vascularized fibula graft for reconstruction. Bone union was observed 9 weeks after surgery. Twenty-two months after the definitive surgery, no recurrence was observed. CONCLUSION: This case illustrates the upgrade from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma. The surgical method may aid the treatment of osteofibrous dysplasia-like adamantinoma with incomplete cortex involvement of the tumor.

Outcome of osteofibrous dysplasia-like versus classic adamantinoma of long bones: a single-institution experience.

BACKGROUND: The clinical and molecular characteristics of osteofibrous dysplasia (OFD)-like adamantinoma (AD) differ from those of classic AD. Most reports about OFD-like AD are case reports or small case series. More cases from different centers are still warranted. METHODS: The orthopedic oncology database of our institution was searched to identify patients with AD. The cases of OFD-like and classic AD of the long bones were retrospectively analyzed. Between December 1999 and August 2016, 23 patients were treated for AD, comprising seven with OFD-like AD and 16 with classic AD. The outcomes were compared between AD subtypes. RESULTS: In the OFD-like AD group, four lesions were treated with extensive curettage, while three were treated with wide resection. The median follow-up duration in the OFD-like AD group was 66 months (range 43-131 months). At the end of follow-up, there was only one case of local recurrence (LR) in the OFD-like AD group, giving a LR rate of 14.3% (1/7). No distant metastasis or progression to classic AD was detected in the OFD-like AD group. In the classic AD group, the treatments were below-the-knee amputation in one patient with extensive tibial and fibular lesions, curettage with a bone graft in one patient who was diagnosed with OFD based on a core needle biopsy, hemi-cortical excision and reconstruction in two patients, and segmental resection and reconstruction in 12 patients. At the end of follow-up, there were three cases of LR in the classic AD group, giving a LR rate of 18.8% (3/16); two patients developed lung metastasis after LR and died of the disease at 88 and 126 months after the first surgery in our hospital, respectively. The classic AD group had a metastatic rate of 12.5% (2/16), a final limb salvage rate of 75%, and estimated 5- and 10-year survival rates of 88.9% and 77.1%, respectively. CONCLUSIONS: OFD-like AD has a better outcome than classic AD. For OFD-like AD, extensive curettage is suggested if the tumor extent allows. For classic AD, aggressive resection with wide margins is essential to achieve local control. A long-term follow-up is necessary due to the possibility of late complications.

Adamantinomatous tumors: Long-term follow-up study of 20 patients treated at a single institution.

BACKGROUND AND OBJECTIVES: Adamantinomas are primary, low-grade malignant tumors of the bone that have metastatic potential to the lungs, lymph nodes, and other regions. The rarity of this disease and its nonspecific symptoms complicate diagnosis. MATERIALS AND METHODS: Records for 20 patients who underwent treatment for adamantinoma from 1975 to 2018 were reviewed for demographic, clinical, and pathological data, treatment details, postoperative complications, and outcomes. RESULTS: Patients presented at a median age of 22 years (1-79 years): 14 patients had a localized primary tumor, three presented with local recurrence, and three with metastatic disease. Median tumor size was 5.7 cm (0.5-15.5 cm). Wide excision was performed primarily in 15 cases; the remaining five patients underwent intralesional curettage. At a median follow-up of 7.3 years, 14 patients had no evidence of disease; two patients were alive with disease, and four patients died from the disease. Local recurrence and distant metastasis occurred at a median of 11.4 years (6 month-19 years) and 15.8 years (4 month-23 years) after diagnosis. CONCLUSIONS: Adequate histopathological diagnosis is crucial to avoid misdiagnosis of this rare tumor. Local and distant recuAbs_Para_meprrence can occur more than 20 years after the initial diagnosis. Life-long follow-up with clinical examination and imaging is required.

Total Tibial Allograft Reconstruction for Adamantinoma: A Case Report With 2-Year Follow-up.

CASE: A 47-year-old woman with adamantinoma of the entire left tibia and distal fibula underwent resection and reconstruction using a total tibia allograft-prosthetic composite with rotating hinged knee replacement and ankle fusion. She is ambulating without tumor recurrence with 2-year follow-up. CONCLUSION: This case report offers a unique reconstruction option for extensive tibia bone primary malignancy. To our knowledge, this is the longest survival for total tibia allograft prosthetic composite reconstruction.

Microsurgical reconstruction with vascularized fibula and massive bone allograft for bone tumors.

INTRODUCTION: Combining massive bone allograft and vascularized fibula in intercalary reconstruction following resection of bone tumors represents a complex reconstructive procedure that requires specialists in microvascular surgery as well as orthopedic surgery. The purpose of our study was to examine the outcomes using this surgical technique in patients with bone tumors in terms of oncologic results, complications related to surgery, Musculoskeletal Tumor Society (MSTS) scores and duration of surgery. MATERIALS AND METHODS: We analyzed 81 patients with femoral or tibial sarcomas who underwent intercalary resection and microsurgical reconstruction with massive bone allograft and vascularized fibula. There were 56 boys and 25 girls with a mean age of 13.4 years at the time of surgery. The patients' medical records were reviewed for clinical and functional outcomes as well as postoperative complications. The study group was comprised of 33 patients who underwent reconstruction of the femur with massive bone allograft and free vascularized fibula and 48 patients who underwent reconstruction of the tibia with massive bone allograft and free or pedicle vascularized fibula. The mean length of resection was 15.9 cm (8-31 cm). The functional evaluation of the patients was done at the end of the follow-up using MSTS score for the lower limb. All patients had at least a 2-year follow-up. RESULTS: The overall limb salvage rate was 94%, although many patients required re-operation after the procedure. Complications occurred in 24 patients, 18 of which underwent additional surgical procedures. They included fractures of the massive bone allograft-vascularized fibula construct with or without implant failure (19) and deep infection (5). After surgical or conservative treatment, all the fractures successfully healed. The overall MSTS functional score was good to excellent in 91% of patients. CONCLUSIONS: The combination of massive bone allograft and vascularized fibula seems to be a reasonable option for reconstruction of diaphyseal defects following intercalary resection of bone tumors. Although there was a high rate of complications and therefore re-operations, the biology of vascularized fibula was able to save the reconstruction in most of the cases that had complications.

Adamantinoma of bone: Long-term follow-up of 46 consecutive patients.

BACKGROUND: Adamantinomas are rare bone tumors, commonly affecting the tibia. Due to the rare nature of disease, previous studies are small or from multiple centers. The purpose of this study is to investigate outcomes of patients with adamantinoma treated in a single institution. METHODS: Forty-six histological confirmed adamantinomas of the extremities were reviewed at our institution between 1939 and 2012. Follow-up data included clinical and radiographical information focusing on complications, local recurrence, metastasis, and overall survival after the treatment. The mean follow-up was 16 years (range 2-42 years). RESULTS: The most common location was the tibia (n = 31). Patients commonly presented with pain and swelling. The mean age was 24 years (7-79 years). Thirty-seven patients were treated with limb salvage. The 39% of patients required a reoperation. The 10-year disease specific- and recurrence free survival was 92% and 72%, with three patients having a recurrence over 15 years postoperative. Older (> 20 years) patients and males were at increased risk of local recurrence (P < 0.05). CONCLUSION: Treatment of adamantinoma of the long bone consists of limb-salvage surgery. Male patients should be cautioned on their increased risk of disease recurrence, and advocate for continued surveillance of patients even greater than 15-years postoperatively due to late tumor recurrence.

Adamantinoma-like Ewing sarcoma of the parotid gland: Cytopathologic findings and differential diagnosis.

Adamantinoma-like Ewing sarcoma (AES) is a rare variant of Ewing sarcoma family of tumors (EFTs), primarily affecting bone and soft tissue. AES has mixed features of Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) and adamantinoma with a complex immunoprofile and EWSR1 gene rearrangements. Herein, we report a 72-year-old male who presented with left parotid mass, right neck mass and thyroid nodules. Fine needle aspiration of the left parotid mass displayed nests of monotonous epithelioid cells with basaloid features in a background of small round blue cells and lymphocytes. AES can involve head and neck region and is characterized by groups of primitive small round blue cells admixed with groups of epithelioid cells with amphophilic cytoplasm and focal squamous differentiation. The proportion of these components can be variable, creating diagnostic challenges, particularly in unusual anatomic sites such as the parotid gland. However, when additional material is available, CD99 and/or FLI1 immunostains need to be included for diagnostic confirmation.