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).

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.

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

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.

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.