Clinicopathologic and genetic characterization of angiofibroma of soft tissue: a study of 12 cases including two cases with AHRR::NCOA3 gene fusion.

AIMS: Angiofibroma of soft tissue (AFST) is a benign tumour characterised by prominent arborizing blood vessels throughout the lesion. Approximately two-thirds of AFST cases were reported to have AHRR::NCOA2 fusion, and only two cases have been reported to have other gene fusions: GTF2I::NCOA2 or GAB1::ABL1. Although AFST is included in fibroblastic and myofibroblastic tumours in the World Health Organization's 2020 classification, histiocytic markers, especially CD163, have been reported to be positive in almost all examined cases, and it still remains the possibility of a fibrohistiocytic nature of the tumour. Therefore, we aimed to clarify the genetic and pathological spectrum of AFST and identify whether histiocytic marker-positive cells were true neoplastic cells. METHODS AND RESULTS: We evaluated 12 AFST cases, which included 10 cases with AHRR::NCOA2 and two with AHRR::NCOA3 fusions. Pathologically, nuclear palisading, which has not been reported in AFST, was detected in two cases. Furthermore, one tumour resected by additional wide resection revealed severe infiltrative growth. Immunohistochemical analysis indicated varying levels of desmin-positive cells in nine cases, whereas CD163- and CD68-positive cells were diffusely distributed in all 12 cases. We also performed double immunofluorescence staining and immunofluorescence in situ hybridisation in four resected cases with >10% desmin-positive tumour cells. The results suggested that the CD163-positive cells differed from desmin-positive cells with AHRR::NCOA2 fusion in all four cases. CONCLUSION: Our findings suggested that AHRR::NCOA3 could be the second most frequent fusion gene, and histiocytic marker-positive cells are not genuine neoplastic cells in AFST.

High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis.

Myxoid liposarcoma (MLPS) is genetically characterized by FUS-DDIT3 or EWSR1-DDIT3 gene fusion and the high frequency of hotspot mutations (C228T or C250T) in the promoter region of telomerase reverse transcriptase (TERT) that encodes the TERT protein. The latter leads to telomerase reactivation, a mechanism of telomere maintenance. Although the TERT promoter hotspot mutation is a poor prognostic factor in various tumors, its effect on MLPS has not been reported in detail. In the present study, we examined the clinicopathological characteristics, prognosis, and telomere maintenance mechanisms in 83 primary tumor samples of MLPS, which were resected surgically at the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, from 2008 to 2020. TERT promoter hotspot mutations were observed in 77% (63/82) cases, and alternative lengthening of telomeres (ALT) was absent in all cases. Among the cases without TERT promoter hotspot mutations, TERT rearrangements, and minor point mutations in the TERT promoter region were found in 3 and 2 cases, respectively. TERT mRNA expression was observed consistently even in patients for whom no genomic TERT aberrations were detected, and the presence of TERT promoter hotspot mutation did not correlate significantly with either overall and metastasis-free survival (P = .56, P = .83, respectively) or clinicopathological features. Therefore, patients with MLPS characteristically shows TERT expression and a high prevalence of TERT aberrations. Our findings suggest that TERT aberration is not prognostic factor, but might occur at an early stage and play a key role in tumorigenesis.

Post-Systemic Chemotherapy Prognoses of Recurrent/Metastatic Soft Tissue Sarcoma Patients with Retroperitoneal/Intra-Abdominal Origin versus Those with Extremities/Trunk Origin.

BACKGROUND: The clinical benefit of systemic chemotherapy for recurrent/metastatic retroperitoneal/intra-abdominal soft tissue sarcoma (STS) compared to its benefits for other primary lesions has not been known or sufficiently evaluated. METHODS AND PATIENTS: We retrospectively reviewed the cases of the STS patients who consulted a department of medical oncology in Tokyo between June 2011 and March 2018, and we extracted the cases of patients with primary sites at the retroperitoneum/intra-abdomen (cohort R) or extremities/trunk (cohort E) who received systemic chemotherapy in a recurrent/metastatic setting, comparing the cohorts' characteristics, chemotherapy details, and prognoses. RESULTS: Of all 337 STS patients, we enrolled 49 patients in cohort R and 75 patients in cohort E. Liposarcoma was more frequently observed in cohort R (51.0%) than cohort E (22.7%). The median chemotherapy treatment line was two lines (range: 1-6) in cohort R and three lines (range: 1-9) in cohort E. The doxorubicin usage rates differed in recurrent/metastatic settings (90.0% in cohort R and 55.0% in cohort E), due mainly to the higher rate of a perioperative chemotherapy treatment history in cohort E (52.0% vs. 6.1% in cohort R). The median overall survival from the start of salvage chemotherapy was 31.9 months (cohort R; 95% CI: 20.9-42.8) and 27.1 months (cohort E; 95% CI: 21.6-32.5) (p = 0.549). CONCLUSION: There were differences in the distributions of pathology and antitumor drugs used in a salvage setting between retroperitoneal/intra-abdominal and extremities/trunk STS patients in recurrent/metastatic settings, but the prognoses with salvage chemotherapy were similar in the two cohorts.

Osteosarcoma in patients over 50 years of age: Multi-institutional retrospective analysis of 104 patients.

BACKGROUND: Primary osteosarcoma in elderly patients are rare malignant tumors. Its optimal treatment has not yet been determined. METHODS: This retrospective study included 104 patients aged >50 years with resectable, non-metastatic osteosarcoma treated by the members of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group. The effects of adjuvant chemotherapy were estimated by comparing outcomes in patients who received surgery plus chemotherapy with those who underwent surgery alone. RESULTS: Median age at presentation was 59 years. Neoadjuvant and adjuvant chemotherapy was administered to 83 (79.8%) patients. Patients who underwent surgery plus chemotherapy and those who underwent surgery alone had 5-year overall survival (OS) rates of 68.6% and 71.7%, respectively (p = 0.780), and 5-year relapse free survival (RFS) rates of 48.2% and 43.6%, respectively (p = 0.64). Univariate analysis showed that resection with wide margins was significantly correlated with better prognosis. CONCLUSIONS: The addition of chemotherapy to surgery did not improve OS or RFS in patients aged >50 years with resectable, non-metastatic osteosarcoma. Surgery with wide margins was only significantly prognostic of improved survival. The effect of chemotherapy in elderly osteosarcoma patients was unclear.

Definitive surgery of primary lesion should be prioritized over preoperative chemotherapy to treat high-grade osteosarcoma in patients aged 41-65 years.

BACKGROUND: Recently, the number of osteosarcomas in middle-aged and older patients has demonstrated an increasing trend; moreover, their results are comparatively worse than those of young patients. In Europe and the USA, the prognosis for osteosarcoma in middle-aged and older patients has improved with adjuvant chemotherapy. In Japan, however, the prognosis has remained poor. MATERIALS AND METHODS: We retrospectively analyzed the outcomes of osteosarcoma, especially in regards to preoperative chemotherapy, from January 1980 to July 2014. A total of 29 patients with high-grade osteosarcoma between the age of 40 and 65 years were included. We included patients without distant metastasis and with primary lesions that were deemed resectable. The mean age was 52.8 years (range 41-65 years), and the mean follow-up period was 103.2 months (range 5-314 months). RESULTS: Adjuvant chemotherapy was administered to 27 of 29 patients (93%), and 8 of 15 cases (53%) were able to undergo preoperative chemotherapy as planned, including CDDP. A major complication of chemotherapy was acute kidney injury due to CDDP (26%). The 5-year OS and 5-year EFS were 64.9% and 57.1%, respectively. After 2006, a policy to prioritize the resection of the primary lesion was implemented, and if the primary lesion was deemed resectable, preoperative chemotherapy was either not administered or administered for only a short duration. The 5-year OS after 2006 improved to 78.8%. CONCLUSIONS: This study shows that administration of high-dose intensity preoperative chemotherapy was difficult in middle-aged and older patients due to their high rate of acute kidney injury by CDDP. For cases of osteosarcoma in middle-aged and older patients, if the primary lesion is resectable, preoperative chemotherapy should be minimized to prioritize the resection of the primary lesion. It was considered that, with appropriate measures to prevent complications, adjuvant chemotherapy may lead to improved prognosis. LEVEL OF EVIDENCE: V.

Case of mesenchymal tumor with the PPP6R3-USP6 fusion, possible nodular fasciitis with malignant transformation.

Nodular fasciitis (NF) is a self-limiting benign disease that is characterized by rapid proliferation of fibroblastic and myofibroblastic cells. The characteristic gene fusion containing the USP6 gene is a genetic hallmark of NF and MYH9-USP6 is the most frequent fusion, suggesting that NF is not a reactive condition but a neoplastic disease. Malignant transformation of NF has been reported rarely as a single case associated with the PPP6R3-USP6 fusion. Here we report a case of soft part tumor of which the histological feature was a typical NF but showed aggressive and non-regressing growth with local invasion. Targeted RNA sequencing and fluorescence in situ hybridization analysis identified PPP6R3-USP6 with gene amplification. These findings indicate that the present case is the second case of malignant NF, and we suggest potential malignant transformation in certain NF cases.

Retrospective analysis of treatment patterns among recurrent/metastatic soft tissue sarcoma patients who consulted medical oncologists in Japan.

BACKGROUND: Many new antitumor drugs to treat soft tissue sarcoma (STS) were approved in the 2010's, and the need for the management of STS patients by medical oncologists has been increasing. Clinical data about the patterns of treatment of STS patients by medical oncologists in Japan are lacking. METHODS: We retrospectively reviewed the clinical records of STS patients who consulted the Department of Medical Oncology at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research between August 2012 and March 2017. The STS patients who received any systemic chemotherapy at the Department of Medical Oncology were enrolled in the analyses. We evaluated the details of the systemic chemotherapies used: treatment regimens, drugs, and treatment settings. We focused on the treatment lines and the prognoses of salvage chemotherapy administered for recurrent and/or metastatic STS patients. RESULTS: Among the 273 patients who consulted the Department of Medical Oncology, 185 patients (68%) received some systemic chemotherapy; 20 patients received chemotherapy as definitive and/or in a perioperative setting, and 171 patients in a salvage setting. The median overall survival of the 171 recurrent and/or metastatic STS patients who received salvage chemotherapy was 14.1 months (95%CI: 10.4-17.8), and the median number of salvage chemotherapy treatment lines throughout their follow-up periods was two lines (range 1-9). CONCLUSION: About two-thirds of the STS patients who consulted a medical oncologist underwent chemotherapy. In the recurrent and/or metastatic settings, newly approved drugs such as pazopanib were frequently used, and the prognoses of the STS patients treated by medical oncologists were similar to those reported in recent global clinical trials. For the better management of patients with STS, medical oncologists should contribute to the management as multidisciplinary team members.

Current state of therapeutic development for rare cancers in Japan, and proposals for improvement.

This article discusses current obstacles to the rapid development of safe and effective treatments for rare cancers, and considers measures required to overcome these challenges. In order to develop novel clinical options for rare cancers, which tend to remain left out of novel therapeutic development because of their paucity, efficient recruitment of eligible patients, who tend to be widely dispersed across the country and treated at different centers, is necessary. For this purpose, it is important to establish rare cancer registries that are linked with clinical studies, to organize a central pathological diagnosis system and biobanks for rare cancers, and to consolidate patients with rare cancers to facilities that can conduct clinical studies meeting international standards. Establishing an all-Japan cooperative network is essential. Clinical studies of rare cancers have considerable limitations in study design and sample size as a result of paucity of eligible patients and, as a result, the level of confirmation of the efficacy and safety shown by the studies is relatively low. Therefore, measures to alleviate these weaknesses inherent to external conditions need to be explored. It is also important to reform the current research environment in order to develop world-leading treatment for rare cancers, including promotion of basic research, collaboration between industry and academia, and improvement of the infrastructure for clinical studies. Collaboration among a wide range of stakeholders is required to promote the clinical development of treatment for rare cancers under a nationwide consensus.

Analysis of the Infiltrative Features of Chordoma: The Relationship Between Micro-Skip Metastasis and Postoperative Outcomes.

BACKGROUND: Chordomas are very rare primary malignant bone tumors that arise commonly from the sacrum (50-60%) and clivus (25-35%). Chordomas have a high rate of recurrence. The authors confirmed a unique histologic infiltration pattern of chordomas that resembles a skip-metastatic lesion in normal tissue around tumor, which they named "micro-skip metastasis." This study aimed to examine the correlations between the clinicopathologic features of chordomas, including micro-skip metastasis, and the clinical outcomes, including overall survival, local recurrence-free survival, and distant metastasis-free survival. METHODS: The study analyzed histopathologic and clinical data from patients with sacral chordomas who underwent en bloc resection from July 1991 through July 2014. Cases with a minimum follow-up period shorter than 20 months after resection were excluded. Kaplan-Meier survival analyses with log-rank tests were performed for overall survival, metastasis-free survival, and recurrence-free survival. RESULTS: The study retrospectively reviewed 40 patients. The mean follow-up period was 98.2 months (range 22-297 months). The local recurrence rate was 41.3%. Micro-skip metastases, observed in 17 patients (42.5%), were associated with a significantly increased risk of local recurrence (p = 0.023) but not with overall survival or distant metastasis-free survival. Poorer overall survival was associated with histologic vascular invasion (p = 0.030) and a greater maximum tumor diameter (p = 0.050). CONCLUSIONS: The presence of micro-skip metastasis was associated with a higher rate of local recurrence. The maximum tumor diameter and the presence of histologic vascular invasion were associated with poorer overall survival.

Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304.

BACKGROUND: Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS. METHODS: We compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities. RESULTS: Seventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival. CONCLUSION: In the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study.

BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. METHODS: We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. RESULTS: Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2-41) and 6 (1-14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p < 0.001). CONCLUSION: The recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB.

Changes in the diagnosis and treatment of soft tissue sarcoma in Japan, 1977-2016.

The treatment of soft tissue tumors has maderemarkable progress through advancements in diagnostic imaging and analysis ofsurgical materials. Changes in the treatment of soft tissue tumors are describedfrom my experience since 1977. Prior to the introduction of CT scans, radiography and angiography were the only methods for tumor localization. Wholebody CT, echography, and soft tissue radiography were introduced around 1980,and significant progress was seen in the localization of soft tissue tumors.Although the localization and diagnostic characteristics of tumors becameeasier with the introduction of MRI, radiography and ultrasound still remainedthe primary diagnostic method for soft tissue tumors. Since 1980, preoperative needle biopsy hasbecome a powerful diagnostic procedure by combining rapid cytological andpathological diagnosis at the Cancer Institute Hospital.The curative wide resection method, based on barrier theory, was an index forpreoperative planning. In addition, with the advent of evaluation methods forsurgical margins, the curability of wide resections can be discussed on acommon platform to open new possibilities in limited resection. However,because current evaluation methods for surgical margins were based onmacroscopic findings, diagnostic measures for invasive sarcomas are stillneeded in future investigations. The development of In Situ Preparation (ISP) isuseful for acquiring information that cannot be obtained with preoperativeimages as it allows for intraoperative evaluation of margins without the riskof tumor contamination, and the surgical technique could be consideredessential for limited resection. In most areas, the preservation of affectedlimbs was made possible by combining ISP with vascular reconstruction, flaptransplantation, joint arthroplasty, bone grafting, among other techniques. Inorder to improve the outcome for the treatment of sarcoma, which is a rarecancer, it is essential to consolidate facilities.

Giant cell tumor of the distal femur: Outcome beyond 20 years of follow-up after curettage with polymethylmethacrylate.

BACKGROUND: Polymethymethacrylate (PMMA) is often used to reconstruct defects after curettage of Giant Cell Tumors (GCT). While GCTs usually originate in the epiphysis, the use of PMMA in distal femoral lesions may induce the risk of degenerative osteoarthritis (OA). We investigated the limb function of patients after curettage with PMMA beyond 20 years of follow-up. METHODS: Patients with more than 20 years of follow-up who underwent curettage with PMMA for distal femoral GCTs were observed. We retrospectively investigated the radiographic assessment of OA and functional assessment of the limb. The Kellgren and Lawrence (KL) grading system was used for radiographic evaluation. RESULTS: Five patients were included in this study. The mean age was 33 years, and the mean period from application of PMMA to final follow-up observation was 28.1 years. Four lesions were primary, and one lesion was recurrent. There were no patients with postoperative recurrence. There were no OA changes in preoperative radiographs. The shortest mean distance from PMMA to the articular cartilage was 4.6 mm on radiographs immediately after surgery. On radiographs at final follow-up observation, the KL grading were as follows: grade 1, 2 patients; grade 2, 1 patient; grade 3, 2 patients. All patients were able to independently ambulate without a crutch, and there was not enough pain to require nonsteroidal anti-inflammatory drugs. The mean flexion of the knee joint was 116°. CONCLUSIONS: Although PMMA used for distal femoral GCTs exhibited OA changes beyond a 20 year follow-up period, there were no cases requiring artificial joints, and the affected limbs demonstrated good function.

Haploidentical hematopoietic cell transplantation for disseminated Ewing sarcoma.

We describe the case of a 13-year-old girl with multifocal disseminated Ewing sarcoma family of tumor (ESFT) who received a 5/8 human leukocyte antigen-matched haploidentical hematopoietic cell transplantation to generate a graft-versus-tumor effect. The patient had grade 2 acute graft-versus-host disease (GVHD) of the skin and chronic GVHD nausea and abdominal pain that required prednisolone for 17 months, but has been free from ESFT for 3 years 10 months after therapy. The present case suggests a beneficial effect of haploidentical hematopoietic cell transplantation in disseminated ESFT.

Multicentric giant cell tumor of bone: Case series of 4 patients.

BACKGROUND: We aimed to retrospectively investigate patients with multicentric giant cell tumor (MCGCT) who were treated at our hospital and to clarify their clinical features, treatment policy, and follow-up method. METHODS: Four patients with two or more giant cell tumor (GCT) that occurred in the same patient were treated at our institution between 1978 and 2015. These patients were evaluated for the following: frequency, age of onset, number and site of occurrence, time to occurrence of the next lesion, treatment, recurrence, malignant transformation, metastasis, and oncological outcome. RESULTS: The rate of occurrence was 1.7%. The average age was 25.2 (17-44). The total number of lesions was three in two cases and two in two cases. All four cases had only one lesion during the initial visit. The most frequent site of occurrence was the proximal femur, followed by two lesions that occurred in the metaphysis. The interval between confirmation of the initial lesion and occurrence of the second lesion was in average 12.1 years (0.8-27.0). Initial presentations of lesions were treated by en bloc resection in one case and curettage in three cases. Local recurrences occurred in two cases that underwent curettage. The six lesions that occurred after the initial lesion were treated as follows: en bloc resection in four lesions, curettage and radiation therapy in one, and embolization and radiation therapy in one. Pathologically, no lesions presented malignancy. Pulmonary metastasis occurred in one case. The oncological outcome was NED in three cases and AWD in one case. CONCLUSIONS: No lesions were malignant, and by providing the same treatment as solitary GCT, the oncological outcome was good. It is unnecessary to be concerned of its risks and postoperatively conduct long-term searches for focal lesions across the body.

Risk factors for pneumothorax in advanced and/or metastatic soft tissue sarcoma patients during pazopanib treatment: a single-institute analysis.

BACKGROUND: After the approval of pazopanib for the treatment of soft tissue sarcoma (STS), pneumothorax was reported as an unexpected adverse event during pazopanib treatment. The incidence and risk factors of pneumothorax during pazopanib treatment for STSs have not been established yet. METHODS: We retrospectively reviewed the cases of all of the STS patients treated with pazopanib between November 2012 and December 2014 at our institute and evaluated the prevalence, incidence, treatment details and risk factors for pneumothorax in the STS patients during pazopanib treatment. RESULTS: A total of 58 patients were enrolled; 45 of them had lung and/or pleural lesions at the start of pazopanib treatment. During the median follow-up time of 219 days (range 23-659), 13 pneumothorax events occurred in six patients; the prevalence and incidence of pneumothorax were 10.3 % and 0.56 per treatment-year, respectively. The median onset of pneumothorax was day 115 (range 6-311). No patients died of pneumothorax, but pazopanib was interrupted in 10 events and chest drainage was performed in eight events. Pazopanib continuation or restart after the recovery from pneumothorax was conducted after 9 of the 13 events. The median progression-free survival of patients with and without pneumothorax events were 144 and 128 days (p = 0.89) and the median overall survival periods were 293 and 285 days (p = 0.69), respectively. By logistic regression analyses, the maximum diameter of the lung metastases ≥ 30 mm (OR 13.3, 95 % CI 1.1-155.4, p = 0.039) and a history of pneumothorax before the pazopanib induction (OR 16.6, 95 % CI 1.1-256.1, p = 0.045) were significantly predictive of pneumothorax. CONCLUSIONS: In our retrospective analysis, pneumothorax was observed in 10.3 % of 58 STS patients during pazopanib treatment. The diameter of the lung metastases and a history of pneumothorax could be useful for evaluating the risk of pneumothorax in pazopanib treatment.

Rapidly growing giant cell tumor of bone in a skeletally immature girl.

Giant cell tumor of bone (GCTB) in skeletally immature patients is rare, and little is known regarding how fast GCTB can grow. We report a case of a 10-year-old skeletally immature girl with pathologically proven GCTB with obvious growth plate invasion that showed surprisingly rapid growth over only 14 days. A radiograph of the left knee revealed well-circumscribed, geographic bone destruction at the distal metaphysis of the femur with a focal cortical defect, suggesting a pathologic fracture. No abnormal mineralization or periosteal reaction was seen. A CT without contrast and an MRI demonstrated a homogeneous lesion with cortical disruption posteriorly and laterally with a slight soft tissue extension. Biopsy showed numerous multinucleated giant cells and spindle-shaped mononuclear cells without any sign of malignancy, suggesting GCTB. However, rapid lesion enlargement and destruction of the surrounding cortex were noted 14 days after biopsy. Considering the amount of bone destruction, traditional treatment of curettage and bone cement would not suffice to sustain structural strength. In addition, considering the patient's age, the tumor location, and the aggressive course, a malignant tumor, especially a giant cell-rich osteosarcoma, could not be excluded. Therefore, en bloc resection, including the growth plate and prosthetic replacement, were performed. Confirmation of GCTB was made from a pathologic evaluation, and a breach to the growth plate was identified. Since very little inflammatory reaction, degenerative change, or aneurysmal, bone, cyst-like change was found, the growth plate invasion was confirmed as due to GCTB extension, not due to the preoperative biopsy.

Efficacy and safety of porous hydroxyapatite/type 1 collagen composite implantation for bone regeneration: A randomized controlled study.

BACKGROUND: Porous hydroxyapatite/collagen composite (HAp/Col) is a bioresorbable bone substitute composed of nano-scale HAp and porcine type 1 collagen. In this study, the efficacy and safety were assessed in comparison to commercially available porous ß-tricalcium phosphate (ß-TCP). METHODS: Patients with bone defects caused by benign bone tumors, fractures, or harvesting of autografts were randomly allocated for implantation of porous HAp/Col (n = 63) or porous ß-TCP (n = 63). X-ray images were scored and used to evaluate the efficacy of the implantation until 24 weeks after surgery. Blood tests and observation of the surgical site were also performed to evaluate the safety of the implants. In total, 59 and 60 cases were analyzed in the porous HAp/Col and ß-TCP groups, respectively. RESULTS: At 18 and 24 weeks after surgery, the highest grade of bone regeneration was more frequent in the porous HAp/Col group than in the porous ß-TCP group (p = 0.0004 and 0.0254 respectively). Wilcoxon's rank sum test confirmed the superiority of porous HAp/Col from early time points onward (p = 0.0084, 4 w; p = 0.0037, 8 w; p = 0.0030, 12 w; p < 0.0001, 18 w; and p = 0.0316, 24 w). The incidence of adverse effects was higher in the porous HAp/Col group than in the ß-TCP group. However, no serious adverse events were reported and no cases needed to drop out of the clinical trial. CONCLUSIONS: The superiority of porous HAp/Col for bone regeneration in comparison to an established porous ß-TCP was confirmed. Although the incidence of side effects associated with the porous HAp/Col implant was higher than that in the ß-TCP group, no serious adverse events occurred that resulted in rejection of the implants.

Risk factors for distant metastasis of dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) may recur locally but rarely metastasizes. Fibrosarcomatous transformation in dermatofibrosarcoma protuberans (FS-DFSP) is said to have worse prognosis compared with ordinary DFSP (O-DFSP). Since DFSP rarely metastasizes, there have been few reports summarizing data on distant metastasis cases at single institution. The aim of this retrospective study is to review DFSP cases in order to analyze risk factors for metastasis. PATIENTS AND METHODS: This retrospective study involved 67 patients. We analyzed O-DFSP and FS-DFSP metastasis rates, metastasis sites, time to metastasis, the relationship between frequency of local recurrence and metastasis, and the relationship between primary tumor size and metastasis. RESULTS: Distant metastasis was found in 5 (7.4 %) of 67 cases with DFSP. Of the five cases, the histopathological diagnosis was FS-DFSP in four cases and O-DFSP in one case. Out of five cases with metastasis, three had not recurred and two had recurred twice. No clear correlation was identified (Fisher's exact test: p = 0.216). The primary tumor diameters in the metastatic cases were 15.0, 12.6, 20.5, 13.0, and 5.0 cm, respectively. The tumor diameters in metastatic cases were significantly larger (Fisher's exact test: p < 0.0001). CONCLUSIONS: In this study, we identified a stronger correlation between DFSP metastasis and tumor size. There was a high possibility that the cases with large tumors might be FS-DFSP, having high rate of metastasis and poor prognosis. In treatment of DFSP, early diagnosis before primary tumor growth and wide resection is considered important.