Distinct Roles of Glutamine Metabolism in Benign and Malignant Cartilage Tumors With IDH Mutations.

Enchondromas and chondrosarcomas are common cartilage neoplasms that are either benign or malignant, respectively. The majority of these tumors harbor mutations in either IDH1 or IDH2. Glutamine metabolism has been implicated as a critical regulator of tumors with IDH mutations. Using genetic and pharmacological approaches, we demonstrated that glutaminase-mediated glutamine metabolism played distinct roles in enchondromas and chondrosarcomas with IDH1 or IDH2 mutations. Glutamine affected cell differentiation and viability in these tumors differently through different downstream metabolites. During murine enchondroma-like lesion development, glutamine-derived α-ketoglutarate promoted hypertrophic chondrocyte differentiation and regulated chondrocyte proliferation. Deletion of glutaminase in chondrocytes with Idh1 mutation increased the number and size of enchondroma-like lesions. In contrast, pharmacological inhibition of glutaminase in chondrosarcoma xenografts reduced overall tumor burden partially because glutamine-derived non-essential amino acids played an important role in preventing cell apoptosis. This study demonstrates that glutamine metabolism plays different roles in tumor initiation and cancer maintenance. Supplementation of α-ketoglutarate and inhibiting GLS may provide a therapeutic approach to suppress enchondroma and chondrosarcoma tumor growth, respectively. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

[Carney triad]. / Carneyho trias.

Carney triad is a synchronous or metachronous association of gastric gastrointestinal stromal tumors (GIST), pulmonary chondroma and extra-adrenal paraganglioma. The majority of patients have only one or two components of the triad, all three tumors being found in only about 2% of the patients at the time of the first diagnosis. The most common combination is gastric and pulmonary tumors. We report a case of Carney triad which was diagnosed at Masaryk Memorial Cancer Institute. A 57-year-old female patient with a history of gastric resection for leiomyosarcoma at the age of 14 and with an unclear pulmonary lesion evident on chest X-ray since as early as 2003. She was referred to our Clinic of Comprehensive Cancer Care after being diagnosed with unspecified tumors of the stomach, the left retroperitoneum and two liver metastases. Biopsy of the retroperitoneal mass was performed and histological examination showed pheochromocytoma. The patient underwent resection of the retroperitoneal tumor and wedge resection of the gastric tumor, left hemihepatectomy and left adrenalectomy (in two separate operations). The excised gastric tumor was a gastrointestinal stromal tumor (GIST) with a low risk of malignancy. Analysis of a liver specimen, however, showed two GIST metastases. No pathology was found in the left adrenal gland and the retroperitoneal tumor was positive for chromogranin A. Paraganglioma was thus diagnosed. Subsequently, mutational analysis of genes coding for succinate dehydrogenase subunits B, C and D (SDHB, SDHC, SDHD) and analysis of DNA methylation at the gene locus of SDHC was made. Carney triad was thus confirmed and the unclear pulmonary lesion could be described as benign chondroma. This report demonstrates the difficulty in distinguishing between Carney triad and Carney-Stratakis syndrome. Molecular information should improve the diagnosis of Carney triad.Key words: Carney triad - GIST pulmonary chondroma extraadrenal paragangliomaCarney-Stratakis syndrome.

Synchronous adrenocortical neoplasms, paragangliomas, and pheochromocytomas: syndromic considerations regarding an unusual constellation of endocrine tumors.

The most common clinical syndromes presenting with paragangliomas and/or pheochromocytomas as their endocrine components are multiple endocrine neoplasia type 2, neurofibromatosis, Von Hippel-Lindau syndrome, Carney-Stratakis syndrome, Carney triad, and the recently described hereditary paraganglioma syndrome. Only Carney triad is known to also present with adrenocortical adenomas, currently representing the only described syndrome in which all 3 of the aforementioned tumors are found together. In most cases, prototypical lesions of the triad such as gastrointestinal stromal tumor and pulmonary chondromas are also seen. We present a case of a young woman with synchronous paragangliomas, adrenal/extra-adrenal cortical neoplasms, and pheochromocytoma without genetic mutations for multiple endocrine neoplasia 2, Von Hippel-Lindau syndrome, neurofibromatosis, and succinate dehydrogenase. We speculate that this represents a previously undescribed presentation of Carney triad and, at the very least, indicates the need for monitoring for the development of other tumors of the triad.

An alternative technique for the management of phalangeal enchondromas with pathologic fractures.

PURPOSE: Enchondroma of the hand with a pathologic fracture is generally treated by tumor curettage and bone grafting after the fracture has healed. However, delayed surgery postpones definitive diagnosis and prolongs the period of disability. We have treated pathologic fractures in a single stage through a modified lateral surgical approach with curettage of the tumor and stabilization using injectable calcium sulfate cement. The aim of this study was to report the outcomes of treatment with this material and the modified approach. METHODS: Between 2006 and 2010, we enrolled 8 patients with solitary hand enchondromas and pathologic fractures. The surgical procedure involved a lateral approach, an extended lateral cortical window, thorough tumor evacuation, and reconstruction of the bone defects using commercially available injectable calcium sulfate cement. We performed evaluations before surgery and in the postoperative follow-up series by radiographs and clinical assessments, including measurement of joint motion by goniometry and a visual analog pain scale. RESULTS: The average time of follow-up was 19 months (range, 12-36 mo). The pathologic fractures of all patients healed clinically and radiographically within 8 weeks after surgery, and the mean active motion arcs of the metacarpophalangeal joints and proximal interphalangeal joints of the involved digit were 90° and 94°, respectively at 3-month follow-up. All patients returned to ordinary daily activities without obvious pain by 3 months postoperatively. We found no major complications, such as unacceptable alignment, nonunion, infection, or tumor recurrence, during follow-up. CONCLUSIONS: This study demonstrated the outcomes of early management of phalangeal enchondromas with pathologic fractures using a lateral approach and injectable calcium sulfate cement for reconstruction. This combined approach avoided the need for supplemental internal fixation, allowed early mobilization, and resulted in minimal joint stiffness. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Seguimiento radiológico en paciente con fibroma condromixoide del seno frontal. Diagnóstico diferencial, alternativas terapéuticas y revisión de la literatura / Radiological follow-up of a patient with chondromyxoid fibroma of the frontal sinus. Differential diagnosis, therapeutic alternatives and a revision of theliterature

Introducción. El fibroma condromixoide es un tumor benigno de crecimiento lento y poco frecuente. Su incidencia en la región craneofacial es rara, especialmente en el seno frontal. Objetivos. Presentamos el seguimiento a largo plazo de un paciente intervenido en relación a un fibromacondromixoide del seno frontal. Se discuten los distintos diagnósticos diferenciales y las alternativas terapéuticas. Discusión. Desde el punto de vista de anatomía patológica es necesario hacer el diagnóstico diferencialcon condrosarcoma, mixosarcoma, mixoma y cordoma. Desde el punto de vista radiológico, el diagnóstico de fibroma condromixoide ha de ser considerado en toda lesión ósea aislada con expansión u osteolisis, márgenes lobulados y septos intralesionales. El tratamiento del fibromacondromixoide incluye principalmente curetaje o resección en bloque, mientras que la radioterapia aislada no se considera de primera elección.Conclusiones. La naturaleza benigna del fibroma condromixoide implica la importancia de evitar tratamientos radicales. El abordaje subcraneal se presenta como una alternativa válida para el tratamiento de lesiones localizadas en el seno frontal. Es fundamental un seguimiento clínico-radiológicoadecuado para identificar precozmente posibles recidivas

Introduction. Chondromyxoid fibroma is a slow growingand rare benign bone tumor. Its location in the craniofacial skeleton is not common, especially in the frontal sinus. Objectives. We present a long-term follow-up of a patient with a frontal chondromyxoidfibroma who was operated four years ago. We discussthe various differential diagnoses and possible treatments. Discussion. The differential diagnosis includes chondrosarcoma, myxosarcoma, myxoma and chordoma. From the radiological point of view, chondromyxoid fibroma must be always considered as a diagnosticpossibility when a solitary bone lesion appears with expansion or cortical osteolysis, lobulated margins and intralesional septi. Treatment includes curettage or monoblock resection with immediate bone graft reconstruction. Radiation therapy alone mustnot be considered as the first therapeutic possibility. Conclusions. the benign nature of the tumor does not justify radical, unnecessary treatment. The subcranial approach is appropriate for lesions located in the frontal sinus. A clinical and radiological follow-up isneeded to identify tumor relapse

No local recurrence of enchondroma after curettage and plaster filling.

INTRODUCTION: The most common treatment of enchondromas is curettage (with or without adjuvant therapy) followed by cancellous bone grafting. To avoid donor-site morbidity of the iliac crest, we applied plaster of Paris as a bone defect filler after curettage of enchondromas. MATERIALS AND METHODS: We treated 19 enchondromas of the hand and foot in 19 patients (mean age 40 years, range 21-79 years) with curettage and filling of the cavity with sterile plaster of Paris (calcium sulphate/phosphate) tablets. RESULTS: The diagnosis was histologically confirmed in all cases. After a mean follow-up of 53 months (range 15-139 months), the mean functional Muskuloskeletal Tumor Society Score was 29.1 points (97%; range 28-30). There were no local recurrences although adjuvant therapy was not utilized. CONCLUSION: Plaster of Paris appears safe and effective as a bone-filling substance after curettage of enchondroma.

Interventional radiology in Carney triad.

Interventional therapeutic methods are presented in Carney triad, which is a syndrome defined as the simultaneous presence of gastric leiomyosarcoma, extra-adrenal paraganglioma, and pulmonary chondroma. The paragangliomas in the carotid bifurcation and the mediastinum were successfully treated via transarterial embolization with particles. Three intrapulmonary chondromas were ablated using MRI-guided laser-induced thermotherapy (LITT) after previous devascularization via transvenous pulmonary particle embolization. In summary, interventional techniques could be a therapeutic option in patients suffering from Carney triad.

Pathologic fracture of metacarpal enchondroma: case study and differential diagnosis.

OBJECTIVE: To discuss a case of enchondroma initially appearing as a pathologic fracture in a metacarpal bone. The recommended treatment for a pathologic fracture of an enchondroma in the hand is reviewed. Additionally, a reasonable list of differential considerations is presented with accompanying radiographic and advanced imaging characteristics. CLINICAL FEATURES: A 25-year-old male chiropractic student had a painful, bruised, and swollen thumb following athletic trauma. Radiographs showed a pathologic comminuted fracture of the first metacarpal, with a resultant anterior angulation of the distal fragment. Fracture occurred through a well-defined, geographic, lucent lesion in the proximal metaphysis consistent with enchondroma. INTERVENTION AND OUTCOME: Closed reduction of the fracture and casting were used. No treatment was administered for the enchondroma. Adequate healing of the fracture took place with residual angulation at the fracture site. Size and extent of the enchondroma were unchanged after fracture healing. CONCLUSIONS: Recommended treatment for a pathologic fracture through an enchondroma in the hand is casting, which allows fracture healing. Curettage of the lesion without packing of the resultant cavity is then recommended. In this case, casting and fracture healing took place without any treatment directed at the enchondroma. The patient was advised of the rationale for undergoing the removal of the enchondroma. Removal was recommended to prevent fracture recurrence from structural weakening, which would be likely due to the unusually high level of mechanical stress from the professional demands of manual treatment.

Condromalacia patelar. Correlación clínico-artroscópica de un nuevo signo clínico / Patellar chondromalatia. Clinical-arthroscopical correlation of a new sign

Se elaboro el presente trabajo, prospectivo longitudinal, tomando 200 artroscopias efectuadas en el servicio, con el diagnóstico clínico preoperatorio de condromalacia patelar. A todos los pacientes se les realizó anamnesis dirigida así como exploración física que incluyó la búsqueda de los signos clásicos: palpación de facetas rotulianas, cepillo rotuliano y escape rotuliano, además, se realizó la maniobra de Carriedo, variante del escape rotuliano. Al establecer la correlación clínico-artroscópica se encontró que los signos clásicos sólo son confiables en cuanto al diagnóstico y no así en cuanto a la clasificación del grado de lesión. El signo de Carreido, en forma opuesta, mostró una alta confiabilidad para fines diagnósticos y sobre todo, para determinar el grado de lesión particularmente en las condromalacias grados III y IV. Lo anterior es de relevante importancia debido al elevado número de pacientes sin condromalacia o con ella en grados I y II a quienes se les efectúa una intervención artroscópica cuando, preferentemente, deberían ser manejados en forma conservadora. Se propone que en los servicios de ortopedia sea investigado este nuevo signo en forma sistemática en los pacientes en quienes se sospecha condromalacia patelar

[Response of cartilaginous neoplasms of the larynx to surgery and alternative therapies]. / Comportamiento de las neoplasias cartilaginosas de la laringe frente al tratamiento quirúrgico y las terapéuticas alternativas.

Three primary cartilaginous tumors of the larynx are reported: two chondrosarcomas (including an undifferentiated chondrosarcoma with prolonged survival) and one chondroma. The need for accurate histological staging, only possible after surgery, is emphasized. Surgery is teh preferred initial treatment.

Immunohistochemical study on collagenous proteins and biophysical analysis of crystals in extraskeletal chondroma.

The immunohistological distribution of collagen types I, II, III, and VI in five cases of extraskeletal chondroma was examined and compared with that in six cases of enchondroma. In addition, the composition of crystals deposited in three cases of extraskeletal chondroma were biophysically analyzed with special attention to the relationship between the collagen types of the matrix and the crystal deposition. In extraskeletal chondroma, immunoreactivity of type II collagen in the extracellular matrix and type VI collagen in the pericellular area, which were strongly and diffusely recognized in the normal hyaline cartilage and enchondroma, was diminished. Instead, additional types of collagen, types I and III, were demonstrated in the matrix. Electron roentgenographic microanalysis and infrared light spectroscopic analysis revealed that calcium pyrophosphate dihydrate (CPPD) was included in the crystals of extraskeletal chondroma. CPPD crystals were observed in/around collagen types I and III. The possible relationship between the difference of collagen composition in the matrix and the CPPD crystal deposition is discussed.

On the treatment of enchondroma.

We recommend simply removing an enchondroma without filling the cavity with cancellous bone or plaster-of-Paris. This method can also be applied to other benign bone conditions, such as aseptic necrosis.

[Therapy of enchondroma with a plaster implant--renaissance of a treatment principle]. / Enchondromtherapie mit Gipsplombe--Renaissance eines Behandlungsprinzips.

The treatment of tuberculous osteitis, osteomyelitis or bone tumors by filling the cavity with plaster of Paris implants after complete removal of the focus or tumor tissue by curettage is a method, nearly 100 years old, practised successfully again and again but little noted. Finally Richter et al. gave an account of 25 cases of tuberculous osteitis, osteomyelitis and bone tumors treated by this method. We have practised this method since 1984 in the treatment of enchondroma. Careful scraping-out with a sharp curette, milling the sclerosed wall and rinsing the cavity with dehydrated alcohol is followed by immediate reconstruction, filling the cavity with a gamma-ray-sterilized CaSO4-paste mixed with the local antibiotic Nebacetin siccum. As observed by other authors, this implant clearly stimulates osteogenesis. It is not necessary to take spongiosa fragments out of the iliac crest and we need no general anaesthesia. There were no complications and no tumor recurrences thus far.

Hereditary multiple exostosis: another etiology of short leg and scoliosis.

A case study is presented demonstrating a patient with a scoliosis as a result of a short leg. The etiology of the short leg was a large sessile osteochondrom in a patient with Hereditary Multiple Exostoses (HME). A review of the condition is presented.

Malignant degeneration of hereditary multiple exostosis: a case history.

Hereditary multiple exostosis is not an uncommon condition; and must be watched for malignant degeneration. A case is reported which has both typical and atypical characteristics. A young male presented with painless metaphyseal lumps, but in addition had a suspicious ischial mass which, when further evaluated, was found to be malignant.

[Bone tumor macroelements]. / Makroélementy opukholei kostei.

Neutron-activation method was employed to determine the concentration of magnium, sodium, chlorine, phosphorus and calcium in different bone tumors. In relation to normal skeletal tissue in tumor tissues higher concentrations of chlorine and sodium but lower concentrations of calcium and phosphorus were found. The greatest changes in the macromolecular content were noted in sarcoma tissues. Bone tumors differ reliably one from the other by concentrations or ratios of macroelements concentrations, this fact may be used for the differential diagnosis.