Novel fusion sarcomas including targetable NTRK and ALK.

BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.

Giant periosteal aggressive epithelioid osteoblastoma: 21-year-old male presents case in the midshaft of his femur.

We report a rare case of giant periosteal osteoblastoma in the femur of a 21-year-old male. The patient presented with a painful, firm, non-tender mass in his left thigh. The pain was worse at night and was temporarily relieved with NSAIDS. He had no fevers, night sweats, or weight loss. The patient underwent preoperative radiological studies including plain radiographs, MRI, bone scan, and CT scan. An open biopsy was subsequently performed that was consistent with an aggressive, epithelioid osteoblastoma. Pathology demonstrated a neoplasm characterized by cohesive sheets of epithelioid osteoblasts, mixed with areas of conventional osteoblastoma displaying prominent osteoblastic rimming of woven bone trabeculae in a fibrovascular stroma. The patient subsequently underwent resection, cryosurgery, fixation, and bone grafting with cortical strut allografts. At final follow-up, 32 months postoperatively, there was no evidence of local recurrence. The patient had resumed all his normal activities. He could run without pain and had no restrictions with activities. The goal of this case report is to aid professionals in the diagnosis and treatment of highly uncommon aggressive osteoblastomas.

Distal femoral replacement with the MML system: a single center experience with an average follow-up of 86 months.

BACKGROUND: The aim of this study was to compare the functional outcomes and complication rates after distal femoral replacement (DFR) performed with the modular Munich-Luebeck (MML) modular prosthesis (ESKA/Orthodynamics, Luebeck, Germany) in patients being treated for malignant disease or failed total knee arthroplasty. METHODS: A retrospective review of patient charts and a functional investigation (involving Musculoskeletal Tumor Society Score [MSTS], American Knee Society Score [AKSS], Oxford Knee Score [OKS], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], Toronto Extremity Salvage Score [TESS], the 12-Item Short-Form [SF-12] Health Survey, and a failure classification system developed by Henderson et al.) of DFR cases from 2002 to 2015 were conducted. The indications for DFR were malignant tumor resection in the femur (n = 20, group A) or failure of revision total knee arthroplasty without a history of malignant disease (n = 16, group B). RESULTS: One-hundred and twenty-nine patients were treated during the study period. Of these, 82 were analyzed for complications and implant-survival. Further, 36 patients were available for functional assessment after a mean follow-up of 86 months (range: 24-154). There were 75 complications in total. The overall failure rate for DFR was 64.6% (53/82 patients). The most common failure mechanisms were type III (mechanical failure), followed by type I (soft tissue) and type II (aseptic loosening). The mean MSTS score (out of 30) was 17 for group A and 12 for group B. All the clinical outcome scores revealed an age-dependent deterioration of function. CONCLUSION: DFR is an established procedure to restore distal femoral integrity. However, complication rates are high. Post-procedure functionality depends mainly on the patient's age at initial reconstruction.

Bone lymphoma with multiple negative bone biopsies.

This article describes a 71-year-old man with right knee pain, prerenal azotemia, hypercalcemia, and a mass in the distal femur. Although testing, including bone marrow biopsy, initially ruled out myeloma, an open surgical biopsy eventually confirmed the diagnosis as lymphoma involving the bone with classic histologic findings of mature B-cell neoplasm of germinal cell origin.

Tumour-induced osteomalacia: a literature review and a case report.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterised by severe hypophosphataemia and osteomalacia, with renal phosphate wasting that occurs in association with tumour. The epidemiology likewise aetiology is not known. The clinical presentation of TIO includes bone fractures, bone and muscular pains, and sometimes height and weight loss. TIO may be associated with mesenchymal tumours which may be benign or malignant in rare cases. Mesenchymal tumour itself may be related to fibroblast growth factor 23 (FGF23), which is responsible for hypophosphataemia and phosphaturia occurring in this paraneoplastic syndrome. Hypophosphataemia, phosphaturia and elevated alkaline phosphatase are the main laboratory readings that may lead to more precise investigations and better diagnosis. Finding the tumour can be a major diagnostic challenge and may involve total body magnetic resonance imaging, computed tomography and scintigraphy using radiolabelled somatostatin analogue. The treatment of choice for TIO is resection of a tumour with a wide margin to insure complete tumour removal, as recurrences of these tumours have been reported. We provide here an overview on the current available TIO case reports and review the best practices that may lead to earlier recognition of TIO and the subsequent treatment thereof, even though biochemical background and the long-term prognosis of the disease are not well understood. This review also includes a 4-year-long history of a patient that featured muscular pains, weakness and multiple stress fractures localised in the hips and vertebra with subsequent recovery after tumour resection. Because the occurrence of such a condition is rare, it may take years to correctly diagnose the disease, as is reported in this case report.

Intra-articular osteoid osteoma as a differential diagnosis of diffuse mono-articular joint pain.

BACKGROUND: The aim of this retrospective study was to investigate the frequency of intra-articular osteoid osteoma (iaOO) in a large study cohort and to demonstrate its clinical relevance as an important differential diagnosis of non-specific mono-articular joint pain. METHODS: We searched the registry for bone tumours of the University Medical Centre Hamburg-Eppendorf for osteoid osteomas in the last 42 years. Herein, we present three selected iaOO which were detected in the three major weight-bearing joints. Computed tomography (CT) or magnetic resonance imaging (MRI) scans were performed for initial diagnosis. RESULTS: Out of a total of 367 osteoid osteomas, 19 (5.2 %) tumours were localized intra-articularly. In all three presented tumours, a history of severe mono-articular pain was reported; however, the mean time to correct diagnosis was delayed to 20.7 months. Clearly, the nidus seen in CT and MRI images in combination with inconsistent salicylate-responsive nocturnal pain led to the diagnosis of iaOO. CONCLUSIONS: Rarely, osteoid osteoma can occur in an intra-articular location. In cases of diffuse mono-articular pain, iaOO should be considered both in large and smaller joints to avoid delays in diagnosis and therapy of this benign bone tumour.

Management of extremity arterial pseudoaneurysms associated with osteochondromas.

Arterial pseudoaneurysms associated with osteochondromas are rare and most publications on this topic are case reports. The management of this double entity is not standardized. We wanted to update it. Literature searches on MEDLINE and EMBASE were performed using the keywords "artery pseudoaneurysm" and "osteochondroma". Patient demographics, clinical presentations, diagnostic and therapeutic modalities were reviewed. In sum, 101 cases were analyzed. Overall, young adults represented the majority of the affected population with a masculine preponderancy (86%). Painful swelling (51%) was the most commonly physical finding. Distal femur was the most common site of the osteochondroma (86%). Multiple hereditary exostosis was seldom reported (36%). Diagnostic confirmation was dominated by arteriography (55%). Popliteal artery (77%) was the most commonly injured vessel. The treatment was open surgery with vascular repair and optimal exostectomy. Arterial repair was performed with saphenous vein grafting (40%) or lateral suture (39%). Postoperative courses were often uneventful (97%). Arterial pseudoaneurysms resulted from osteochondromas were dominated by those involving the popliteal artery. The use of arteriography to confirm the diagnosis may be limited to the benefit of non-invasive radiological methods because endovascular treatment is not relevant in the setting of osteochondroma-induced arterial pseudoaneurysm.

Case of a Missed Giant Cell Tumor of Bone: An Opportunity to Observe its Natural History Disease.

Giant cell tumor of bone (GCT) is a benign neoplasm that most commonly presents with pain and is rarely diagnosed as an incidental finding. We present the report of a young woman whose pre-operative MRI was only noted to have a tear of the anterior cruciate ligament (ACL). Subsequently, the patient underwent anACL reconstruction. A second MRI, performed four years later, demonstrated an enlarged mass in the same location. A retrospective evaluation of the initial MRI revealed an eccentric metaphyseal lesion. Histology obtained from the lesion demonstrated a giant cell tumor of bone. We present the case of an asymptomatic GCT discovered retrospectively as an incidental finding and reevaluated four years later. 'Ihis case serves as a reminder of the importance for the critical review of routine preoperative imaging and also offers a unique perspective on the natural history of giant cell tumor of bone.

Osteoid Osteoma of the Femoral Neck: Use of the Half-Moon Sign in MRI Diagnosis.

OBJECTIVE: Osteoid osteoma is a benign bone tumor that is commonly located in the proximal femur. Although CT is helpful in the diagnosis of osteoid osteoma, patients in whom the clinical presentation of the tumor is atypical are first referred to undergo MRI, which yields a high percentage of false-negative or inconclusive results. We sought to explore the association between a half-moon sign of bone marrow edema and the presence of osteoid osteoma of the femoral neck. SUBJECTS AND METHODS: The MRI examinations of 11 consecutive patients with osteoid osteoma (group 1) were prospectively included in the study. In addition, 950 consecutive hip MRI examinations of 485 patients were retrospectively analyzed for the presence of bone marrow edema of the femoral neck, with 19 patients identified as having bone marrow edema resulting from causes other than osteoid osteoma (group 2). Patients in both study groups were evaluated for the presence of the half-moon sign. RESULTS: The half-moon sign of bone marrow edema was significantly associated with the presence of osteoid osteoma (p < 0.0001), having been seen on the MR images of all 11 patients in group 1 and only one of 19 patients in group 2. MRI examination was therefore 94.7% specific and 100% sensitive for the detection of osteoid osteoma, with positive and negative predictive values of 91.7% and 100%, respectively. CONCLUSION: The half-moon sign is an MRI finding that is highly specific and sensitive for an accurate diagnosis of osteoid osteoma of the femoral neck.

False Arterial Aneurysm due to Long Bone Exostosis: Presentation of Two Cases and Update on Proper Management.

Osteochondromas are the most common benign bone tumors. Vascular complications are unusual, with false arterial aneurysms being the majority among them. Although there are several reports of false aneurysms because of an exostosis in the femoro-popliteal region, cases presenting with a false aneurysm of the brachial artery are quite rare. Many suggestions have been made regarding prevention, diagnosis, and treatment of these false aneurysms, although there are no official guidelines. Therefore, this report aims to present 2 unusual cases of patients with a false aneurysm in the femoral and brachial artery, respectively, because of an exostosis. Literature data are discussed and useful conclusions regarding optimal management are made.

Osteoma of long bone: an expanding spectrum of imaging findings.

Osteoma of long bone is an extremely rare, benign bone-forming surface lesion with the largest published case series consisting of only 14 patients. The most important and often most difficult lesion to differentiate from osteoma of long bone radiographically is parosteal osteosarcoma, which is a rare, low-grade surface osteosarcoma with the potential for dedifferentiation. Reports of imaging studies of osteoma of long bone depict a well-defined ossified mass arising from the surface of the diaphysis or metadiaphysis of a long bone. A characteristic feature is the homogeneity of the mass, with uniform density near or equal to that of cortical bone from the base of the lesion to its periphery. The 45-year-old female in this case presented with left hip fullness and was subsequently found to have a proximal femoral osteoma, which was unique in that it contained large fatty marrow spaces that corresponded to bands of relatively low density on plain radiography and computed tomography, giving it a heterogeneous appearance atypical of osteoma of long bone. Furthermore, the osteoma reported here was associated with a small but separate nodular focus of ossification in the adjacent soft tissue. These findings led to a presumptive diagnosis of parosteal osteosarcoma with a local soft tissue metastasis or satellite nodule resulting in radical resection of the tumor. Definitive diagnosis of osteoma was made on histology of both the parent lesion and ossified nodule as no neoplastic spindle cell proliferation was present to establish a diagnosis of low-grade osteosarcoma. This represents, to the best of our knowledge, the first such presentation of osteoma of long bone.

Complementary roles of bone scintigraphy and MR imaging in the detection and long-term follow-up of primary non-Hodgkin's bone lymphoma in a child-case report.

The aim of our report is to demonstrate the complementary roles of bone scintigraphy (BS), magnetic resonance imaging (MR), and positron emission tomography using 2-deoxy-2-[18F]fluoro-D-glucose (F-18-FDG PET/CT) in the diagnosis and treatment monitoring of a child with primary non-Hodgkin's lymphoma of bone (PLB). Increased blood flow, high tissue accumulation, and markedly increased uptake on the late BS pointed toward an active bone process in the left femoral region. Bone marrow infiltration of the left femur and cortical sclerosis, which were both demonstrated by MR imaging, were later confirmed as PLB by bone marrow biopsy. The normalizations of the flow and tissue phases of BS a year after treatment and during the entire follow-up were in keeping with inactive disease and clinical remission. However, even 8 years after treatment and complete remission, MR imaging demonstrated persistent unmodified bone marrow alteration and appreciable cortical involvement. A slightly increased metabolic activity of the left femoral epiphysis demonstrated by F-18-FDG PET/CT and mild activity in the same region on delayed BS were demonstrated in the late follow-up. Our results strongly suggest that BS and MR imaging should be included in the diagnostic algorithm of children with undefined bone symptoms. However, mild metabolic activity on the F-18-FDG PET/CT scan could not reliably differentiate between the presence or absence of disease in a patient with PLB in clinical remission.

[Cardiac fibromyxosarcoma with bone metastases : palliative surgical treatment]. / Ossär metastasierendes Fibromyxosarkom des Herzens : Palliative operative Therapie.

This article presents the unusual case of a 58-year-old woman with a low-grade cardiac fibromyxosarcoma which was primarily surgically resected and treated with adjuvant chemotherapy. A pulmonary metastasis as well as osteolytic metastatic destruction of the right iliac crest occurred 3 years after primary diagnosis and 2 years later a bone metastasis of the left distal femur was detected. Applying a palliative treatment concept resection of the pulmonary metastasis and an extralesional resection of the bone metastasis of the right iliac crest with plastic reconstruction were performed. Afterwards resection of the left distal femur metastasis and prosthetic reconstruction with distal femur replacement could also be realized. Despite an initial poor prognosis a high quality of life without essential functional limitations could be maintained for more than 6 years in this individual case.

Coccidiomycosis infection of the patella mimicking a neoplasm - two case reports.

BACKGROUND: Coccidioidomycosis is an endemic fungal infection in the southwestern of United States. Most infections are asymptomatic or manifest with mild respiratory complaints. Rare cases may cause extrapulmonary or disseminated disease. We report two cases of knee involvement that presented as isolated lytic lesions of the patella mimicking neoplasms. CASE PRESENTATION: The first case, a 27 year-old immunocompetent male had progressive left anterior knee pain for four months. The second case was a 78 year-old male had left anterior knee pain for three months. Both of them had visited general physicians without conclusive diagnosis. A low attenuation lytic lesion in the patella was demonstrated on their image studies, and the initial radiologist's interpretation was suggestive of a primary bony neoplasm. The patients were referred for orthopaedic oncology consultation. The first case had a past episode of pulmonary coccioidomycosis 2 years prior, while the second case had no previous coccioidal infection history but lived in an endemic area, the central valley of California. Surgical biopsy was performed in both cases due to diagnostic uncertainty. Final pathologic examination revealed large thick walled spherules filled with endospores establishing the final diagnosis of extrapulmonary coccidioidomycosis. CONCLUSIONS: Though history and laboratory findings are supportive, definitive diagnosis still depends on growth in culture or endospores identified on histology. We suggest that orthopaedic surgeons and radiologists keep in mind that chronic fungal infections can mimic osseous neoplasm by imaging.

What are the results using the modified trapdoor procedure to treat chondroblastoma of the femoral head?

BACKGROUND: Treatment of chondroblastoma in the femoral head is challenging owing to the particular location and its aggressive nature. There is little published information to guide the surgeon regarding the appropriate approach to treating a chondroblastoma in this location. We developed a modified trapdoor procedure to address this issue. The primary modification is that the window surface of the femoral head is covered by the ligamentum teres rather than cartilage as in the traditional procedure. QUESTIONS/PURPOSES: We assessed (1) the clinical presentation of chondroblastoma of the femoral head and treatment results with the modified trapdoor procedure in terms of (2) the frequency of local recurrence, (3) complications, and (4) functional outcomes using the Musculoskeletal Tumor Society (MSTS) score. METHODS: Between 1999 and 2010, we treated 14 patients for chondroblastoma of the femoral head. All patients received the modified trapdoor procedure. Of those, 13 were available for followup at a minimum of 36 months (mean, 66 months; range, 36-117 months) and one patient was lost to followup. There were nine males and four females, with a mean age of 18 years (range, 9-29 years). Clinical features were ascertained by chart and radiographic review, and recurrence, complications, and functional outcomes (MSTS score) were recorded from chart review. Patterns of bone destruction were evaluated using the Lodwick classification, which ranges from IA (geographic appearance with sclerotic rim) to III (permeative appearance). RESULTS: The symptoms at diagnosis were pain in nine patients and discomfort in four. The mean duration of symptom was 11 months (range, 1-36 months). The physis was open in two patients, closing in one, and closed in 10. The patterns of bone destruction were evaluated as Lodwick Class IA in six patients, Lodwick Class IB in five, and Lodwick Class IC in two. At latest followup, no local recurrence was observed. Two patients had postoperative complications. One had avascular necrosis of the femoral head and was treated with prosthesis replacement. The other had asymptomatic heterotopic ossification in the surgical field. The mean MSTS score was 29.6 (range, 28-30). CONCLUSIONS: Based on this small series, we believe our modified trapdoor procedure is a safe, effective means of treating a chondroblastoma in the femoral head, but additional clinical evaluation with more patients is necessary to confirm our findings. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Limb function and quality of life after various reconstruction methods according to tumor location following resection of osteosarcoma in distal femur.

BACKGROUND: We tried to compare the functional and psychosocial outcomes after various reconstruction methods according to tumor location following resection of osteosarcoma in distal femur. METHODS: We retrospectively reviewed 51 patients who underwent limb-salvage surgery of osteosarcoma in distal femur in our institution, 30 males and 21 females with an average age of 21 years (range 13-51 years). We classified osteosarcoma in distal femur into 3 types, and organized affected limb reconstruction methods after wide resection. MSTS and QOL scores were used to analyze the functional and psychological outcomes. RESULTS: After a mean follow-up of 43 months (12-225 months), there is no difference on functional results and QOL scores among three reconstruction groups (p > 0.05) and among three types groups (p > 0.05). No difference could be noticed on tumor-free survival and total survival among three reconstruction groups (p > 0.05) and three type groups (p > 0.05). In ≤2-year, better functional scores could be found in prosthesis group, rather than the other two inactivated-bone groups (p < 0.05). CONCLUSIONS: Biological reconstruction with alcohol-inactivated autograft replantation could avoid prosthesis related complications and achieved comparable results with prosthesis following resection of osteosarcoma in distal femur. Different reconstruction options could be chosen according to tumor location, such as the distance to Insall line.

Intracortical schwannoma of the femur.

Schwannomas are benign nerve sheath tumors most commonly found in soft tissue. Intraosseous schwannomas are rare, and account for <0.2 % of primary bone tumors. The typical radiologic findings, a lytic lesion with a thin peripheral rim of sclerosis, are nonspecific. In all reviewed case reports, the diagnosis was made only after microscopic examination. Among previously described intraosseous schwannomas, there have been no reports of tumors arising within cortical bone. It is important to note that while schwannomas are benign tumors, they can be misdiagnosed clinically and radiographically can be potentially mistaken for metastases or other serious skeletal diseases such as osteomyelitis. Tissue sampling is critical for definitive diagnosis as well as to avoid unnecessary treatment. We present the first reported case of an intracortical schwannoma in a 42-year-old man who presented with an incidental radiographic lesion of the diaphyseal femoral cortex.

Giant cell tumor of bone with secondary aneurysmal bone cyst-like change producing ß-human chorionic gonadotropin.

Giant cell tumor of bone is a benign, locally aggressive neoplasm that is composed of sheets of neoplastic mononuclear cells interspersed amongst non-neoplastic, uniformly distributed, osteoclast-like giant cells. They represent approximately 4-5% of primary bone tumors. Rarely, bone tumors have been noted to produce human chorionic gonadotropin, a finding most often reported in osteosarcoma. We present the case of a young woman who presented with a low-level human chorionic gonadotropin level which, after resection of her recurrent giant cell tumor of bone with secondary aneurysmal bone cyst-like change, became undetectable in her blood. Furthermore, cells within the aneurysmal bone cyst component were immunohistochemically positive for ß-human chorionic gonadotropin. This is the first report of such a finding in the literature.

Spontaneous hip dislocation secondary to intraarticular neurofibroma: a case report.

Spontaneous hip dislocation due to intraarticular neurofibroma in patients with neurofibromatosis type 1 is extremely rare. We describe the imaging features of spontaneous dislocation of hip due to histologically proven intraarticular neurofibroma in young woman with neurofibromatosis type 1, and review the literature.

Diagnosis of osteosarcoma in a patient previously treated for Ewing sarcoma.

Primary malignant bone tumors, whether Ewing sarcoma or osteosarcoma, are a rare type of tumor. The sequential occurrence of two bone sarcomas, Ewing sarcoma and high-grade osteosarcoma, in the same patient at two different locations is an exceptionally rare phenomenon. We present the case of a 13-year-old girl who presented with a high-grade osteoblastic osteosarcoma of the distal femur, 7 years after treatment for Ewing sarcoma of the left pelvis. She did not receive radiation therapy. Following the recent developing multidisciplinary therapy, long-term follow-up for monitoring latent treatment-related adverse effects may be necessary for survivors of primary malignant bone tumors.