Background and Objectives: Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids. Methods: and Results: In this study, vascularized spheroids were generated from non-adherent microwell culture system of human umbilical vein endothelial cells, human dermal fibroblasts and human umbilical cord blood derived mesenchymal stem cells. These vascular spheroids were used for fusion with iPSCs induced cerebral organoids. Immunostaining studies of vascularized organoids demonstrated well organized vascular structures and reduced apoptosis. We showed that the vascularization in cerebral organoids up-regulated the Wnt/β-catenin signaling. Conclusions We developed vascularized cerebral organoids through assembly of brain organoids with vascular spheroids. This method could not only provide a model to study human cortical development but also represent an opportunity to explore neurological disease.

Objectives: . This study aimed to investigate whether optical coherence tomography (OCT) provides useful information about the microstructures of the middle and inner ear via extratympanic approach and thereby could be utilized as an alternative diagnostic technology in ear imaging. Methods: . Five rats and mice were included, and the swept-source OCT system was applied to confirm the extent of visibility of the middle and inner ear and measure the length or thickness of the microstructures in the ear. The cochlea was subsequently dissected following OCT and histologically evaluated to compare with the OCT images. Results: . The middle ear microstructures such as ossicles, stapedial artery and oval window through the tympanic membrane with the OCT could be confirmed in both rats and mice. It was also possible to obtain the inner ear images such as each compartment of the cochlea in the mice, but the bone covering bulla needed to be removed to visualize the inner ear structures in the rats which had thicker bulla. The bony thickness covering the cochlea could be measured, which showed no significant differences between OCT and histologic image at all turns of cochlea. Conclusion . OCT has been shown a promising technology to assess real-time middle and inner ear microstructures noninvasively with a high-resolution in the animal model. Therefore, OCT could be utilized to provide additional diagnostic information about the diseases of the middle and inner ear.

PURPOSE: A dedifferentiated chondrosarcoma is a rare lethal tumor characterized by a low grade chondrosarcoma juxtaposed with a high grade dedifferentiated sarcoma, such as osteosarcoma, fibrosarcoma. The aim of our study was to document the clinical manifestation and oncologic outcomes of a dedifferentiated chondrosarcoma. MATERIALS AND METHODS: This study identified 11 patients who were diagnosed and treated for dedifferentiated chondrosarcoma between January 2007 and December 2016. The identified cohort was then reviewed regarding age, sex, symptom onset, tumor location, magnetic resonance imagings (MRIs), surgical margin, and pathologic diagnosis. The time to local recurrence and/or metastasis, follow-up duration, and the patients' final status were analyzed. RESULTS: The patients were comprised of 7 males and 4 females with a mean age of 54 years (range, 33–80 years). The location of the tumor was in the femur in 6 cases, pelvis in 4 cases, and metatarsal in 1 case. The average tumor diameter was 12.7 cm (range, 6.0–26.1 cm). At the time of diagnosis, 2 patients showed pathologic fracture; 1 patient was Enecking stage IIA, 9 patients were stage IIB, and 1 patient was stage III. Eight patients were classified as a primary dedifferentiated chondrosarcoma and 3 patients were secondary. One of the primary lesions was misinterpreted initially as a low grade chondroid lesion by MRI and underwent curettage. Local recurrence occurred in 8 cases and distant metastasis occurred in 10 cases with a mean duration of 8 months (range, 2–23 months) and 7 months (range, 1–32 months), respectively. The three-year overall survival of patients with dedifferentiated chondrosarcoma was 18%, and 10 patients died due to disease progression. CONCLUSION: Dedifferentiated chondrosarcoma developed lung metastases in the early period of the clinical courses and the prognosis was dismal.
Chondrosarcoma ; Cohort Studies ; Curettage ; Diagnosis ; Disease Progression ; Female ; Femur ; Fibrosarcoma ; Follow-Up Studies ; Fractures, Spontaneous ; Humans ; Lung ; Magnetic Resonance Imaging ; Male ; Metatarsal Bones ; Neoplasm Metastasis ; Osteosarcoma ; Pathology ; Pelvis ; Prognosis ; Recurrence ; Sarcoma

PURPOSE: Clear cell chondrosarcoma may have a benign appearance even on a magnetic resonance imaging (MRI). Hence, it can be confused with benign bone tumors, such as a giant cell tumor or chondroblastoma. The aim of our study was to document the doctorassociated diagnostic errors in patients with clear cell chondrosarcoma and oncologic outcomes of these lesions, which were misdiagnosed as benign bone tumors. MATERIALS AND METHODS: We identified 10 patients who were diagnosed with and treated for clear cell chondrosarcoma between January 1996 and December 2014. One patient was excluded due to insufficient clinical data. We then reviewed their data regarding age, gender, symptom onset, tumor location, initial imaging diagnosis, and associated previous treatment. We examined the errors of surgeons and pathologists with respect to patient and tumor characteristics. We also analyzed treatment delay, time to local recurrence, metastasis, follow-up duration, and the oncologic outcome. RESULTS: The initial presumptive diagnosis based on MRIs for all 9 patients was benign bone tumor. Among 8 patients who underwent inappropriate procedure, half of them were diagnosed as clear cell chondrosarcoma immediately after the curettage. As for the remaining 4 patients, the surgeon did not send any tissue samples to a pathologist for a definite diagnosis in three patients and a pathologist made an incorrect diagnosis in one patient. We performed an appropriate surgery on all patients with a wide surgical margin. The average treatment delay was 27 months (range, 0–127 months), and the average follow-up duration was 65 months (range, 13–164 months). One patient had local recurrence after 12 months. Metastatic disease developed in 2 patients with a median time to definitive treatment of 24 months (12–37 months). Ten-year overall survival of patients with clear cell chondrosarcoma was 78%, and two patients died due to disease progression. CONCLUSION: Misdiagnosis of clear cell chondrosacroma as a benign bone tumor is not uncommon, even for experienced orthopaedic oncologists, resulting in definite curative surgery without biopsy. An inappropriate primary treatment may increase the risk of local recurrence and metastasis. Therefore, a proper subsequent surgery is mandatory for patients with clear cell chondrosarcoma who received inadvertent curettage.
Biopsy ; Chondroblastoma ; Chondrosarcoma ; Curettage ; Diagnosis ; Diagnostic Errors ; Disease Progression ; Follow-Up Studies ; Giant Cell Tumors ; Humans ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Recurrence ; Surgeons

PURPOSE: Solitary fibrous tumors (SFT) represent a rare entity of soft tissue tumors which are exclusively located in the thoracic cavity as pleural fibrous tumors. Extrathoracic SFT in the soft tissues are very rare. We analyzed the oncologic outcome of the soft tissue SFT. MATERIALS AND METHODS: Between January 2009 and December 2014, we treated 6 soft tissue SFT cases. Patients' clinical data, magnetic resonance imagings and pathologic findings were reviewed. RESULTS: The patients included two women and four men. The average age of the patients was 45 years (range, 32-56 years). The mean tumor size is 7.2 cm (range, 3.5-13.0 cm). One patient received wide excision of the tumor and remaining 5 patients marginal excision. After the excision, pathologic report confirmed that 4 patients showed margin positive. However, no patient received further surgery or adjuvant treatments. After the immunohistochemistry, 2 out of 6 patients identified as malignant soft tissue SFT. The mean follow-up period was 25.8 months (range, 6-66 months). Although 4 patients revealed margin positivity, no subsequent local recurrence or distant metastasis was observed. CONCLUSION: Since the SFT are categorized as intermediated biological potential with a low risk of metastasis and recurrence, marginal excision can be a one of the surgical options for these tumors which are located adjacent to vital structures. However, close observation is needed because local recurrence can be significantly higher the patients with positive resection margins.
Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Male ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Soft Tissue Neoplasms ; Solitary Fibrous Tumors* ; Thoracic Cavity

PURPOSE: Giantcell-rich osteosarcoma (GCRO) is a rare subtype of osteosarcoma. We reviewed; 1) radiological finding of GCRO and clinical impression-related diagnostic workup at referral center, 2) diagnostic delay until a proper diagnosis is made, 3) impact of diagnostic delay on the oncologic outcome. MATERIALS AND METHODS: We reviewed 17 patients with GCRO. We investigated the plain radiographic finding, tumor size and location, presence of pathologic fracture, clinical impression and pathological diagnosis at referral center, diagnostic delay, definitive treatment, local recurrence, metastasis, and survival rate. RESULTS: Eleven cases (64.7%) showed a plain radiographically, purely osteolytic pattern while 6 cases (35.3%) showed mixed osteolytic and sclerotic lesion. Diagnosis at primary center was osteosarcoma in 7 (41.2%), giant cell tumor in 7 (41.2%), and benign bone tumor in 3 (17.6%). Six patients (35.3%) experienced diagnostic delay. Mean diagnostic delay was 3.1 months (1 to 8). At final follow-up 5-year actuarial survival rate of 17 patients was 65%+/-25%. Although 11 patients without diagnostic delay showed a tendency of high survival over 6 patients with diagnostic problem, there was no statistical significance (p=0.14). CONCLUSION: GCRO is a rare subtype of osteosarcoma simulating giant cell tumor both pathologically and radiologically. Careful diagnostic approach is required in order not to misdiagnose this malignant tumor.
Diagnosis ; Diagnostic Errors ; Follow-Up Studies ; Fractures, Spontaneous ; Giant Cell Tumors ; Humans ; Neoplasm Metastasis ; Osteosarcoma* ; Recurrence ; Referral and Consultation ; Survival Rate

Rosai-Dorfman disease (RDD) is an idiopathic histioproliferative disorder of lymph node and extranodal site. Bone involvement is very rare. We report a case of extranodal RDD of the tibia in 32-year old male. The patient presented with pain with no evidence of lymphadenopathy. Clinico-radiologic diagnosis was metastatic carcinoma or Langerhans cell histiocytosis, but, histopathologic examination confirmed the diagnosis with RDD. We performed curettage on the osteolytic lesion of tibia. In South Korea, there was no report about RDD of the extremity and we want to report this case with review of the literature.
Curettage ; Diagnosis ; Extremities ; Histiocytosis, Langerhans-Cell ; Histiocytosis, Sinus* ; Humans ; Korea ; Lymph Nodes ; Lymphatic Diseases ; Male ; Tibia*

PURPOSE: We report the diagnosis, treatment outcomes and prognosis of the patients with soft tissue malignant myoepithelioma in the extremities. MATERIALS AND METHODS: We retrospectively reviewed 6 patients with soft tissue malignant myoepithelioma in the extremities who were treated at our institution between 2008 and 2014. Two patients received unplanned excision at another hospital and remaining 4 patients underwent the biopsy procedures and received wide excision at our hospital. RESULTS: There were 3 men and 3 women with mean age of 41 (33-54) years. The average follow up was 28 (9-45) months. Among the 6 patients, only 4 patients underwent biopsy procedures under the impression of malignant soft tissue sarcoma. Surgical margins for these 4 patients were negative. Two patients who had unplanned excision received another re-excision and one of them showed no residual tumor in the resected specimen. Local recurrences were developed in all patients and distant metastasis in 4 patients. All 4 patients who developed distant metastasis died due to disease progression. Among the 2 patients who developed local recurrence only, one patient has another local recurrence after re-operation and remaining one patient is no evidence of disease for 2 years after resection of locally recurred mass. CONCLUSION: Soft tissue malignant myoepithelioma in the extremities is a rare disease and shows an aggressive behavior. Appropriate biopsy under the impression of soft tissue malignancy is necessary and complete surgical resection with wide margins is the recommended treatment of choice.
Biopsy ; Diagnosis ; Disease Progression ; Extremities* ; Female ; Follow-Up Studies ; Humans ; Male ; Myoepithelioma* ; Neoplasm Metastasis ; Neoplasm, Residual ; Prognosis ; Rare Diseases ; Recurrence ; Retrospective Studies ; Sarcoma

PURPOSE: We analyzed the diagnosis and the treatment outcomes of patients with central low grade osteosarcoma. MATERIALS AND METHODS: We retrospectively reviewed 16 patients with central low grade osteosarcoma were treated at out institution between 1994 and 2011. RESULTS: There were 4 men and 12 women with mean age of 26 years. Eleven patients were correctly diagnosed but 5 patients were misdiagnosed as osteoid osteoma, non ossifying fibroma, aneurysmal bone cyst, desmoplastic fibroma. 15 patients finally received wide margin en bloc excision and one of them treated under neoadjuvant chemotherapy. Final survival status was continuous disease free in 14 and 1 patient died of renal cell cancer. Remaining 1 with multifocal lesions is alive with disease for 7 years only treated radiation therapy on residual tumors. Nine (56%) of 16 tumors showed extra-osseous extension of tumor (56%) and 1 of them showed extra-compartmental tumors. CONCLUSION: The diagnosis of central low grade osteosarcoma is challenging, however, considering of the clinical suspicion, the typical findings of radiologic and pathologic features, proper diagnosis is needed. This tumor should be treated with wide excision, even after an intralesional excision, to avoid local recurrence or transformation to higher histologic grade.
Aneurysm ; Bone Cysts ; Carcinoma, Renal Cell ; Diagnosis* ; Drug Therapy ; Female ; Fibroma, Desmoplastic ; Fibroma, Ossifying ; Humans ; Male ; Neoplasm, Residual ; Osteoma, Osteoid ; Osteosarcoma* ; Prognosis* ; Recurrence ; Retrospective Studies

BACKGROUND: We assessed the plain radiographic characteristics of 10 cases of osteosarcomas during the initial painful period that had been overlooked by a primary physician. In addition, we evaluated chronologic changes in radiographic findings from initial symptomatic period to the time of accurate diagnosis. METHODS: The clinical records were reviewed for clinical parameters including age, sex, location, presenting symptoms, initial diagnosis, duration from initial symptoms to definite diagnosis, and initial and follow-up plain radiographic findings of the lesion. RESULTS: Initial clinical diagnoses included a sprain in 6, growing pain in 2, stress fracture in 1, and infection in 1 patient. Initial plain radiographic findings were trabecular destruction (100%), cortical disruption (60%), periosteal reaction (60%), and soft tissue mass (10%). Intramedullary matrix changes were osteosclerosis in 6 and osteolysis in 4 patients. On progression, 4 cases with minimal sclerosis changed to osteoblastic lesion in 3 patients and osteolytic lesion in 1. Four cases with faint osteolytic foci transformed into osteolytic lesion in 3 and mixed pattern in 1. CONCLUSIONS: Notable plain radiologic findings of incipient-stage osteosarcoma include trabecular disruption along with faint osteosclerosis or osteolysis. In symptomatic patients with trabecular destruction, additional imaging study including magnetic resonance imaging should be performed to exclude osteosarcoma in the incipient phase, even without radiologic findings suggesting malignant tumor, such as cortical destruction or periosteal reaction.
Adolescent ; Adult ; Age Factors ; Bone Neoplasms/diagnosis/*radiography ; *Diagnostic Errors ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Osteosarcoma/diagnosis/*radiography ; Retrospective Studies ; Young Adult