Indolent Multinodular Synovial Sarcoma of Peripheral Nerves Mimicking Schwannoma: A Case Report and Literature Review.

BACKGROUND/AIM: Most cases of synovial sarcoma (SS) are aggressive and large-sized; only few show indolent behavior, having a small size. Nerves are rare sites of SS occurrence. An atypical case of SS can lead to its misdiagnosis as a benign tumor and delay its treatment. CASE REPORT: Here, we report a case of primary SS of indolent multinodular synovial sarcoma of peripheral nerves. Considering the clinical and imaging findings at the first visit, we suspected a benign tumor and continued careful follow-up. Three years later, marginal resection was performed and SS was suspected. We then performed an additional wide resection using a free flap. Histopathologically, the proximal tumor showed a diffuse proliferation of spindle cells without pleomorphism, whereas the distal tumor showed a similar histology with more hypercellularity. Additional wide-resection specimens showed remnant tumors derived from the peripheral nerve. Immunohistochemistry (IHC) showed positive staining for SS18:SSX and SSX in both tumors and fluorescence in situ hybridization showed positive staining for the SS18 split in both tumors. Finally, SS of the peripheral nerve was diagnosed. Owing to FNCLCC grade 2 tumor and tumor size, adjuvant chemotherapy was not performed. CONCLUSION: In cases of SS or other sarcomas with atypical clinical courses, with imaging findings mimicking benign tumors, we recommend marginal resection along with pathological examination for correct diagnosis.

Delirium in patients with musculoskeletal tumours: incidence and risk factors - single-centre prospective study.

OBJECTIVES: Delirium, a neurocognitive disorder, typically occurs in older patients and those with advanced cancer. Although there have been numerous reports on delirium in patients with cancer in various conditions, there are no reports that specifically focus on patients with musculoskeletal tumours. This prospective study aimed to investigate the incidence, risk factors and prognostic implications of delirium in patients with musculoskeletal tumours. METHODS: In this single institutional study, 148 patients with musculoskeletal oncology were enrolled. The estimated risk factors included age, sex, alcohol abuse, performance status (PS), dietary status, admission route, tumour malignancy, oncological stage and blood test results. The significance of delirium in survival was also examined. RESULTS: Only 18 patients with malignant tumours had delirium (12.2%). Based on univariate analysis, older age, poor PS, dietary status, admission from another hospital, malignant tumour, carcinoma rather than sarcoma, anaemia and some laboratory abnormalities were found to be significant risk factors for delirium. Multivariate analysis showed that poor PS was significantly correlated with delirium. Additionally, delirium was significantly correlated with poor survival. CONCLUSIONS: The incidence of delirium among patients with musculoskeletal tumours was 12.2% and was observed only in patients with malignant tumours. PS is a significant risk factor for delirium. Delirium is correlated with poor prognosis.

Case Report: Extraskeletal osteosarcoma with preceding myositis ossificans.

Extraskeletal osteosarcoma (EO) is a soft tissue sarcoma characterized by the production of bone matrix by neoplastic cells. Benign osteoid in EO, leading to a diagnostic dilemma, is rarely encountered. Herein, for the first time, we present a case with cytogenetically confirmed EO combined with or preceding myositis ossificans (MO). A 21-year-old man had a mildly painful swelling in his left knee. Imaging studies demonstrated a 39-mm mass with peripheral mineralization and cystic change on the posterolateral side of the left fibular head. He was clinically suspected of having either MO or a malignancy, such that wide resection was performed. Macroscopically, the mass was grayish to brown. In the cut section, multiple cystic lesions in addition to solid components were noted. Histopathologically, the solid components demonstrated diffuse proliferation of pleomorphic tumor cells with osteoclast-like giant cells. The malignant tumor cells formed osteoid. In the periphery, the mass was benign, showing mature bone tissue and focally non-malignant woven bone with fibroblasts, compatible with zonation. Fluorescence in situ hybridization (FISH) demonstrated split signals of the USP6 gene. These findings suggested EO with preceding MO. Although the pathogenesis remains to be elucidated, the observed USP6 rearrangement might contribute to both the diagnosis of EO with preceding MO and an understanding of the underlying histopathology.

Rare Case of BCOR::CCNB3 Sarcoma of Bone.

BACKGROUND BCOR: CCNB3 sarcoma is a rare mesenchymal tumor that was formerly included in the undifferentiated/unclassified sarcoma group and was recently reclassified as one of undifferentiated small round cell sarcomas with a genetically distinct subtype in the WHO 2020 classification. Because of its rarity, still not much is known, especially about its clinical features. CASE REPORT A 15-year-old boy presented with almost 1-year intermittent thigh pain. On the first visit, a pathologic fracture of the femur and a big mass expanding through the femoral cortex with lobular shape and homogenous appearance were recognized on radiography and magnetic resonance imaging. Plain radiography, which was taken 6 months before at a local clinic, showed an expansion and thickening of the right proximal femoral shaft. Biopsy specimen of the lesion revealed a proliferation of round to spindle tumor cells with diffuse and strong immunohistochemical nuclear positivity for BCOR and CCNB3. Under the diagnosis of BCOR::CCNB3 sarcoma of the femur, a chemotherapy based on a protocol of Ewing sarcoma, followed by a wide resection and total femoral replacement surgery, were conducted. The effect of chemotherapy was favorable, showing no microscopic residual tumor. Although postoperative chemotherapy was not completed because of a minor infection detected on the surgical site, the patient was doing well, without any recurrence, for 26 months. CONCLUSIONS BCOR: CCNB3 sarcoma of the bone is a quite rare tumor with much lower incidence than Ewing sarcoma. Notable clinical characteristics of the current case were a 1-year-long symptomatic period and homogenous appearance on MRI.

Cytological features of BCOR-CCNB3 sarcoma: Comparison with Ewing sarcoma and synovial sarcoma.

INTRODUCTION: BCOR-CCNB3 sarcoma (BCS) is one of the histological types classified as an undifferentiated small round cell sarcoma of bone and soft tissue. This sarcoma frequently develops in males under 20 years of age. Histologically, a delicate capillary network has been reported as a conspicuous finding. In this study, the cytological findings of BCS were observed in two cases of primary lesions and one case of a lung metastatic lesion. The cytological findings of BCS were compared with its histological mimics, and the characteristic findings of BCS were examined. METHODS: Three cases of BCS were studied, and a cytological comparison was performed with 8 cases of Ewing sarcoma (ES) and 10 cases of synovial sarcoma (SS; monophasic type: 7 cases, biphasic type: 2 cases, poorly differentiated: 1 case). RESULTS: In all BCS cases, small clusters with thin and delicate vascular cores and tiny vascular fragments were conspicuous. In ES and SS cases, although small clusters with vascular cores were observed, the vascular cores were thicker than in BCS, and no tiny vascular fragments appeared in most cases. Cytomorphological differences of tumour cells were also observed among BCS, ES, and SS. Predominantly rounded nuclei with fine chromatin and inconspicuous nucleoli can be cytological clues for BCS. CONCLUSIONS: BCS shows characteristic cytological findings that make the diagnosis of BCS more likely than that of ES and SS. Cytological evaluation is a useful tool for appropriate differential diagnosis that leads to a more accurate final diagnosis and rapid treatment.

Oncologic emergency in patients with skeletal metastasis of unknown primary.

AIM: Patients with skeletal metastasis from prediagnosed primary malignancy sometimes have concurrent oncologic emergency (OE) during the first visit. This study aims to investigate the types of OEs and treatment outcome in such patients. METHODS: We have experienced 359 patients with skeletal metastasis from unknown primary malignancy. Among them, 130 patients required immediate admission for OE treatment (OE group), 229 patients had no OE and did not required immediate admission (non-OE group). RESULTS: The recognized types of OE were spinal cord compression in 60 patients, cancer pain in 30, hypercalcemia in 19, delirium in 16, deep vein thrombosis in 13, acute renal failure in 6, respiratory failure in 3, gastrointestinal hemorrhage in 3, and disseminated intravascular coagulation in 1. The overall 5-year survival rates were 28% and 37% in the OE and non-OE groups, respectively (P < 0.001). The multivariate analysis revealed that delirium (hazard ratio 4.2; 95% confidence interval, 1.6-12.5; P < 0.005) and respiratory failure (hazard ratio 22.6; 95% confidence interval, 4.5-92.8; P < 0.001) were significant prognostic factors in patients with OEs, whereas other OEs did not confer a significant risk for patient outcomes. CONCLUSION: In this study, OE was observed in as many as 36% of patients with skeletal metastasis from unknown primary malignancy. Delirium and respiratory failure were only two significant prognostic risk factors, which suggest that many of the OEs in untreated advanced cancer patients have probable chance to resolve. Early detection followed by appropriate treatment of such OEs is recommended.

Temporal hemiarthroplasty for distal femoral osteosarcoma in early childhood: a case report.

BACKGROUND: Prosthetic reconstruction for distal femoral osteosarcoma is challenging for younger children. We herein report a successful case of limb-sparing surgery for a younger patient with distal femoral osteosarcoma requiring osteo-articular resection. CASE PRESENTATION: A 5-year-old girl with high-grade conventional osteosarcoma in the left distal femur underwent a series of surgeries. After three cycles of neoadjuvant chemotherapy, limb-salvage surgery was planned because femoral rotationplasty had been refused. At 6 years and 2 months old, distal femoral resection and temporary spacer insertion using a 7-mm-diameter intramedullary nail and molded polymethylmethacrylate was performed. At 7 years and 8 months old, secondary surgery was performed because the first spacer had been dislocated and the residual femur became atrophic. The distal end of the residual femur was removed by 1 cm, but the periosteum and induced membrane around polymethylmethacrylate was preserved. In order to stabilize the spacer against the tibia, a custom-made ceramic spacer with a smooth straight 8-mm-diameter stem was utilized. The bone-spacer junction was fixed with polymethylmethacrylate and then covered with the preserved periosteum and induced membrane. After surgery, the bone atrophy improved. At 9 years and 7 months old, the second spacer was removed because it had loosened, and the knee joint was reconstructed using a custom-made growing femoral prosthesis with a curved porous 8.5-mm-diameter stem. Cancellous bone tips from the proximal tibia were grafted around the bone-prosthesis junction underneath the induced membrane. At 10 years and 5 months old, the patient was able to walk unsupported and a radiograph showed further thickening of the cortex of the residual femur without any stress shielding. Although having 5 cm of limb length discrepancy, the patient and her mother were satisfied with the function. The MSTS score was 24 out of 30 points. Repeated limb length extensions are planned. CONCLUSIONS: This case report provides an example of limb-salvage surgery after distal femoral resection in a small child. The use of a temporary spacer utilizing partial cementation and preservation of the periosteum and induced membrane appears to afford a viable limb-salvage option after distal femoral resection for younger children.

Navigation-assisted surgery for chondroblastoma arising in the femoral head: A case report.

INTRODUCTION: Surgery for chondroblastoma in the femoral head is challenging due to its inaccessibility, with high risk of local recurrence and poor functional outcomes reported. We herein report the first case of chondroblastoma in the femoral head treated by navigation-assisted surgery. PRESENTATION OF CASE: A 12-year-old girl presented with persistent left hip pain and limited hip range of motion. Imaging studies revealed a well-defined osteolytic lesion in the left femoral head accompanied by extensive intra-osseous oedematous change. The bone lesion was radiologically diagnosed as chondroblastoma. With navigation assistance, curettage was performed via the anterior approach. The tumor was fully accessible from the femoral neck. After curettage, the bony defect was filled with bone substitute. The pathological diagnosis was chondroblastoma. The post-operative course was uneventful. Thirty months postoperatively, the patient was free of pain with full hip range of motion, and MR images showed no evidence of recurrence or osteonecrosis. DISCUSSION: This case is the first to use a navigation system for the treatment of chondroblastoma in the femoral head. The navigation system can minimize damage to intact structures and increase the efficiency of curettage by visualizing access to the tumor. CONCLUSION: Navigation assistance is an optimal surgical option for chondroblastoma in the femoral head.

Primary cutaneous localized/clearly-outlined true histiocytic sarcoma: Two long-term follow-up cases.

Histiocytic sarcoma (HS) is a rare hematopoietic tumor that mainly involves extranodal sites, including the intestinal tract, skin, soft tissues and other organs. It is well known as an aggressive neoplasm that shows a poor response to therapy. However, a subset of patients with resectable disease has shown a favorable outcome with surgical treatment. Primary cutaneous HS is exceedingly rare and, to date, its long-term prognosis has thus not been well described. Here, we highlight two cases of primary cutaneous HS that showed long-term survival. Case 1 was a healthy 47-year-old woman who found a 12-mm tumor on her forehead. Case 2 was a 66-year-old woman, under follow up of a myxoid liposarcoma in her leg, who presented with a 25-mm tumor in her hypothenar eminence. Histologically, the tumors in both cases had a smooth outline with proliferating atypical tumor cells that showed histiocytic differentiation as revealed by immunohistochemistry with antibodies to CD68 (KP-1) and lysozyme in case 1; and CD68, lysozyme and CD163 in case 2. Tumor cells in case 1 had a monotonous appearance. After complete resection, cases 1 and 2 have survived for 10 and 4 years, respectively, without recurrence. To date, such patients are relatively long follow-up cases of survival from HS and highlight how a clear outline of the primary cutaneous HS tumor may be associated with its resectability and be an important factor in the assessment of its curability.

"Phantom akathisia" in an amputated leg of a sarcoma patient: a case report.

BACKGROUND: Akathisia is a rather common extrapyramidal side effect of antipsychotic drugs and antidepressants, often resulting in severe discomfort for patients. However, due to the diversity of symptoms, it is often overlooked. We hereby report a case with akathisia that mainly appeared in an amputated leg. CASE PRESENTATIONS: A 60-year-old woman, who had undergone external hemipelvectomy for a recurrent soft tissue sarcoma, was referred to the Department of Psycho-Oncology due to worsening anxiety and restlessness. She was not unconscious or disoriented. Her chief complains included restlessness, an itching sensation in the area corresponding to the amputated left leg, and a feeling as if the lost left leg were raising itself. Detailed examination revealed that she had been administered 10 mg per day of oral prochlorperazine maleate for nausea induced by the oxycodone that had been prescribed to control post-operative pain. Akathisia was suspected and prochlorperazine maleate treatment was discontinued. All the symptoms were alleviated on the next day, and disappeared in 3 days. Eventually, she was diagnosed with akathisia. CONCLUSIONS: This case indicates that the symptoms associated with akathisia can occur in an amputated extremity. Considering two previous reports of "phantom dyskinesia", extrapyramidal syndromes may result in unusual presentations if occurring in an amputated extremity. Not only should the use of antipsychotic drugs and antidepressants be carefully considered, but also closer observation of psychological symptoms is required after prescription of these drugs because the clinical presentation of akathisia can be various and confusing due to modifications caused by other factors as in this case.

The impact of antecedent primary malignancy in soft tissue sarcoma patients.

BACKGROUND: It is unclear whether antecedent primary malignancies (APMs) have any negative impact on the prognosis of soft tissue sarcoma (STS). We retrospectively reviewed STS patients with APMs (STS-APM) and compared their survival to those of STS only (STS-O). METHODS: Twenty-one cases of STS-APM from 2008 to 2017 in our institution were analyzed. One hundred and seventy cases of STS-O at the same period were compared as a control group. Overall survival was estimated using Kaplan-Meier survival curves and prognostic factors were analyzed using logistic regression analyses and contingency table analyses. RESULTS: As the final status of STS-APM patients, 12 patients were in disease-free survival, 5 were alive with disease, 3 have died of disease, and 1 has died of another disease. There was no case that died of APM. The 5-year overall survival rates were 88% in STS-APM and 78% in STS-O, showing no statistical significant ( p = 0.65). The 5-year overall survival rates in each stage of STS-APM and STS-O were 100/100% in stage I, 100/85% in stage II, 86/72% in stage III, and the 3-year overall survival rates were 67/51% in stage IV, with no statistical significance. With regard to prognostic factor, histological grade of STS was the only significant factor. Although antecedent radiotherapy tended to show a high odds ratio, the association was not statistically significant. Antecedent chemotherapy did not show any estimated prognostic risk. CONCLUSIONS: Our study suggested that APM in STS patient would not be a negative prognostic factor.

Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma.

Objective: Eribulin, a microtubule dynamics inhibitor, is approved for the treatment of patients with breast cancer and soft tissue sarcoma. We investigated the efficacy and safety of eribulin in Japanese patients with soft tissue sarcoma. Methods: This open-label, multicenter, nonrandomized, Phase 2 study enrolled Japanese patients with measurable, advanced/metastatic soft tissue sarcoma of high/intermediate grade and ≥1 prior chemotherapy for advanced disease. Patients received eribulin mesilate 1.4 mg/m2 intravenously over 2­5 minutes on Days 1 and 8 of a 21-day cycle. The primary endpoint was progression-free rate at 12 weeks. Secondary endpoints included overall survival, progression-free survival and safety. Efficacy analyses were stratified by histology (liposarcoma or leiomyosarcoma, and other subtypes). Results: Overall, 52 patients were enrolled and 51 patients were treated. Patients with liposarcoma/leiomyosarcoma (n = 35) had similar characteristics to those with other subtypes (n = 16), except for a higher proportion of women (63% vs 38%, respectively) and patients with Eastern Cooperative Oncology Group performance status 0 (57% vs 44%). Progression-free rate at 12 weeks was 60% in liposarcoma/leiomyosarcoma patients, 31% in other subtypes and 51% overall. Median progression-free survival was 5.5 months in liposarcoma/leiomyosarcoma patients, 2.0 months in other subtypes and 4.1 months overall. Median overall survival was 17.0 months in liposarcoma/leiomyosarcoma patients, 7.6 months in other subtypes and 13.2 months overall. The most common Grade 3­4 adverse events were neutropenia (86%), leukopenia (75%), lymphopenia (33%), anemia (14%) and febrile neutropenia (8%). Conclusion: Eribulin showed clinical activity with a manageable safety profile in previously treated Japanese patients with advanced/metastatic soft tissue sarcoma.

Atypical and malignant granular cell tumors in Japan: a Japanese Musculoskeletal Oncology Group (JMOG) study.

BACKGROUND: Malignant granular cell tumors (MGCTs) are extremely rare neoplasms with only a limited number of studies published to date. The aim of this study is to elucidate the clinicopathological characteristics and prognostic factors of MGCTs. METHODS: This is a multi-institutional retrospective study of MGCTs with a central pathological review. A total of 18 cases were retrieved. Specimens were blindly reviewed by two pathologists based on the diagnostic criteria by Fanburg-Smith et al. Kaplan-Meier survival probabilities were calculated, and risk factors for poor prognosis were evaluated. RESULTS: Three and fifteen cases were diagnosed as atypical GCTs (AGCTs) and mGCTs according to the Fanburg-Smith et al. classification, respectively. Four (one atypical and three malignant) cases had metastasis at the first presentation, including lymph node metastasis. Three out of ten cases treated with wide resection developed local recurrence. Although prolonged static disease periods of ≥1 year were observed in four cases receiving chemotherapy, all cases with local recurrence or metastasis, including two atypical cases, eventually died of disease. The 5- and 10-year overall survival rates for localized MGCTs were 69.2 and 34.6 %, respectively. The presence of necrosis was revealed as a risk factor associated with adverse clinical outcomes. CONCLUSIONS: MGCTs have high rates of recurrence and metastasis including lymph node metastasis. As histologically atypical cases also have metastatic potential, close attention should be paid to AGCTs. The combination of histological evaluation and tumor size may lead to more accurate diagnosis of this rare neoplasm.

The effect of an external hip joint stabiliser on gait function after surgery for tumours located around the circumference of the pelvis: analysis of seven cases of internal hemipelvectomy or proximal femur resection.

PURPOSE: Limb-sparing resection of malignant pelvic tumours provides the opportunity for patients to obtain better post-operative mobility. However, because few studies have examined in detail the gait function of patients following pelvic tumour resection, the factors affecting gait performance remain to be clarified. Here, with the laboratory-based computer-assisted gait analysis, we evaluated these patients' gait objectively and the impact of a hip-stabilising supporter on gait improvement was simultaneously examined. METHODS: Three-dimensional gait analysis was performed to obtain cross-sectional data for seven post-operative patients (mean age, 42.7 years; range, 20-61 years) who underwent various types of resection, including P1/4 internal hemipelvectomy (IH), P1/2/3 IH, and proximal femur resection with prosthetic reconstruction. To assess the immediate effects of a hip joint stabiliser, we instructed subjects to walk at their self-selected preferred speed and compared gait parameters with and without use of the hip stabiliser. RESULTS: At baseline, the average walking speed was 0.75 m/s (95% CI 0.53-0.97). As shown by the intra-subject comparison, the hip stabiliser increased walking speed in all but one subject, increasing both temporal and spatial parameters. Ground reaction force of operated limbs increased for some subjects, while step length increased on at least one side in all subjects. CONCLUSIONS: Improvement in the gait parameters is indicative of better control provided by the external hip stabiliser over the affected limb. Moreover, our findings show the potential of a biomechanical approach to improve gait function following pelvic tumour resection.

Type 3 internal hemipelvectomy: a report of two cases.

Type 3 internal hemipelvectomy involves resection of the pubis. We report on 2 patients who underwent type 3 internal hemipelvectomy. One patient developed a bladder hernia, tumour recurrence, and a pathological fracture of the proximal femur. These were resolved with external hemipelvectomy 7 months later. Another patient underwent additional fascia lata transplantation to prevent development of hernia. Both patients had a stress fracture in the contralateral posterior ilium mimicking bone metastasis.

Bilateral non-osteochondroma-related proximal tibiofibular synostosis.

We report the case of a 67-year-old male with bilateral proximal tibiofibular synostosis, presenting with unilateral symptoms. The patient complained of pain around the left fibular head, which was attributed to incomplete bone bridging between the proximal tibia and fibula; he underwent proximal fibular head resection, which alleviated the pain and improved knee mobility. Eleven months later, the patient continued to be pain-free and did not experience any adverse effects. An examination of this case and a review of similar cases revealed that participation in sport activities such as long-distance running may be one of the causes of proximal tibiofibular synostosis. In this report, we have also reconsidered the classification of proximal tibiofibular synostosis and provided information for a better understanding of this unusual condition.

A bone metastasis of non-small cell lung carcinoma with prominent clear cell features.

We report the case of a 78-year-old man with multiple bone tumours and three round, smooth nodules in the right lung. He was referred to our hospital because of the left femoral neck pathological fracture. The histological characteristics of the femoral tumour corresponded to clear cell carcinoma, and bone and lung lesions were regarded as metastatic from an unknown primary site, since there was no clinical evidence of renal carcinoma. His general conditions gradually declined, and he died 2 months after the operation. At autopsy, no neoplasia lesion was found in the kidneys. Although clear cell components were histologically dominant in the affected organs such as the lungs, bones and liver, neoplastic tubular structures also existed. Immunohistochemically, atypical cells were positive for napsin-A. The final diagnosis was adenocarcinoma of the lung origin with prominent clear cell features.

Pedicle freezing with liquid nitrogen for malignant bone tumour in the radius: a new technique of osteotomy of the ulna.

We describe a new technique of pedicle freezing of the distal radius with malignant bone tumour and osteotomy of the normal ulna. The distal radius was sufficiently elevated to enable freezing without damaging adjacent tissues by releasing the distal radio-ulnar and radio-carpal joint and cutting the middle third of the ulna. The distal radius (including the tumour) was soaked in liquid nitrogen and the defect filled with iliac grafts. The ulna was repaired with plate and screws and was united at month 2. There was no local recurrence and the postoperative function score was 93%. This technique decreases the risk of non-union of the osteotomy site of the tumorous bone.