Keeping it real: Merging traditional and contemporary practices in musculoskeletal pathology: A special issue of neoplastic and non-neoplastic bone and soft tissue pathology.

There is no shortage of comprehensive review articles on bone and soft tissue pathology, almost always representing a regurgitation of the literature with little to no guidance on personal "best practices," recommended applications of ancillary testing, and alternative points of view. This special issue of Human Pathology uniquely unites evidence-based medicine, where appropriate, with the collective personal experiences of a wide range of accomplished pathologists from varying institutions and backgrounds, addressing problematic areas, updated and sometimes imperfect classification systems, and their personal preferences for cost-effectively incorporating ancillary testing. For the preponderance of general pathologists (and specialists), whether academic or non-academic, non-neoplastic musculoskeletal diseases represent a far higher percentage of their practice than bone and soft tissue neoplasia. One of the most common frozen sections performed at many hospitals throughout the USA is revision arthroplasty, relying on the pathologist to help determine the presence (or absence) of periprosthetic joint infection, largely based on the hematoxylin & eosin (H&E) slide. Not every institution has access to the latest molecular techniques; fortunately, many of the current immunohistochemical antibodies serve as reliable surrogate markers of genetic mutations, allowing for cheaper but accurate diagnoses, when deemed necessary. Furthermore, molecular testing is often not necessary to establish a specific diagnosis, even among neoplasms with known underlying genetic abnormalities. It must be remembered that most bone and soft tissue tumors were recognized and classified correctly, before we uncovered and understood, among a subset, their underlying and unique molecular aberrations. Perhaps not surprisingly, in some cases, more than one molecular pathway may lead to the same histologic tumor subtype. Less commonly, an identical genetic driver/fusion may result in immunophenotypically and biologically distinct neoplasms, sometimes with entirely different clinical behaviors. "Dedifferentiation," a concept recognized among a variety of bone and soft tissue neoplasms, including but not limited to chondrosarcoma, parosteal osteosarcoma, and liposarcoma, needs to be objectively reassessed, particularly for liposarcoma. The following reviews attempt to address the above concepts, re-emphasizing the important role the practicing pathologist continues to (and must) play in the differential diagnoses of neoplastic and non-neoplastic musculoskeletal diseases.

Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases.

Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, and impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is a key regulator in the expression of genes in a multitude of biological processes. m6A is composed of 0.1-0.4% adenylate residues, especially at the beginning of 3'-UTR near the translation stop codon. The m6A regulator can be classified into three types, namely the "writer", "reader", and "eraser". Studies have shown that the epigenetic modulation of m6A influences mRNA processing, nuclear export, translation, and splicing. Regulated cell death (RCD) is the autonomous and orderly death of cells under genetic control to maintain the stability of the internal environment. Moreover, distorted RCDs are widely used to influence the course of various diseases and receiving increasing attention from researchers. In the past few years, increasing evidence has indicated that m6A can regulate gene expression and thus influence different RCD processes, which has a central role in the etiology and evolution of MSDs. The RCDs currently confirmed to be associated with m6A are autophagy-dependent cell death, apoptosis, necroptosis, pyroptosis, ferroptosis, immunogenic cell death, NETotic cell death and oxeiptosis. The m6A-RCD axis can regulate the inflammatory response in chondrocytes and the invasive and migratory of MM cells to bone remodeling capacity, thereby influencing the development of MSDs. This review gives a complete overview of the regulatory functions on the m6A-RCD axis across muscle, bone, and cartilage. In addition, we also discuss recent advances in the control of RCD by m6A-targeted factors and explore the clinical application prospects of therapies targeting the m6A-RCD in MSD prevention and treatment. These may provide new ideas and directions for understanding the pathophysiological mechanism of MSDs and the clinical prevention and treatment of these diseases.

Fatty infiltration in the musculoskeletal system: pathological mechanisms and clinical implications.

Fatty infiltration denotes the anomalous accrual of adipocytes in non-adipose tissue, thereby generating toxic substances with the capacity to impede the ordinary physiological functions of various organs. With aging, the musculoskeletal system undergoes pronounced degenerative alterations, prompting heightened scrutiny regarding the contributory role of fatty infiltration in its pathophysiology. Several studies have demonstrated that fatty infiltration affects the normal metabolism of the musculoskeletal system, leading to substantial tissue damage. Nevertheless, a definitive and universally accepted generalization concerning the comprehensive effects of fatty infiltration on the musculoskeletal system remains elusive. As a result, this review summarizes the characteristics of different types of adipose tissue, the pathological mechanisms associated with fatty infiltration in bone, muscle, and the entirety of the musculoskeletal system, examines relevant clinical diseases, and explores potential therapeutic modalities. This review is intended to give researchers a better understanding of fatty infiltration and to contribute new ideas to the prevention and treatment of clinical musculoskeletal diseases.

Investigation of perfusion impairment in degenerative cervical myelopathy beyond the site of cord compression.

The aim of this study was to determine tissue-specific blood perfusion impairment of the cervical cord above the compression site in patients with degenerative cervical myelopathy (DCM) using intravoxel incoherent motion (IVIM) imaging. A quantitative MRI protocol, including structural and IVIM imaging, was conducted in healthy controls and patients. In patients, T2-weighted scans were acquired to quantify intramedullary signal changes, the maximal canal compromise, and the maximal cord compression. T2*-weighted MRI and IVIM were applied in all participants in the cervical cord (covering C1-C3 levels) to determine white matter (WM) and grey matter (GM) cross-sectional areas (as a marker of atrophy), and tissue-specific perfusion indices, respectively. IVIM imaging resulted in microvascular volume fraction ([Formula: see text]), blood velocity ([Formula: see text]), and blood flow ([Formula: see text]) indices. DCM patients additionally underwent a standard neurological clinical assessment. Regression analysis assessed associations between perfusion parameters, clinical outcome measures, and remote spinal cord atrophy. Twenty-nine DCM patients and 30 healthy controls were enrolled in the study. At the level of stenosis, 11 patients showed focal radiological evidence of cervical myelopathy. Above the stenosis level, cord atrophy was observed in the WM (- 9.3%; p = 0.005) and GM (- 6.3%; p = 0.008) in patients compared to healthy controls. Blood velocity (BV) and blood flow (BF) indices were decreased in the ventral horns of the GM (BV: - 20.1%, p = 0.0009; BF: - 28.2%, p = 0.0008), in the ventral funiculi (BV: - 18.2%, p = 0.01; BF: - 21.5%, p = 0.04) and lateral funiculi (BV: - 8.5%, p = 0.03; BF: - 16.5%, p = 0.03) of the WM, across C1-C3 levels. A decrease in microvascular volume fraction was associated with GM atrophy (R = 0.46, p = 0.02). This study demonstrates tissue-specific cervical perfusion impairment rostral to the compression site in DCM patients. IVIM indices are sensitive to remote perfusion changes in the cervical cord in DCM and may serve as neuroimaging biomarkers of hemodynamic impairment in future studies. The association between perfusion impairment and cervical cord atrophy indicates that changes in hemodynamics caused by compression may contribute to the neurodegenerative processes in DCM.

Morphometric and fractal analysis of injured skeletal muscle tissue subjected to a combination of treatments; cryotherapy and therapeutic ultrasound / Análisis de la morfometría y de la dimensión fractal en la lesión del tejido muscular esquelético expuesto en la combinación de los tratamientos de crioterapia y ultrasonido

The aim of this study was to analyze the effects of an association of cryotherapy and therapeutic ultrasound on the treatment of muscle injured by impact. Fifty-five Wistar rats were divided into five groups (n = 11), Acute Injury (AI), Injury (I), Cryotherapy (CR), Therapeutic Ultrasound (TU) and Association of Cryotherapy and Therapeutic Ultrasound (CRTU). The CR and CRTU groups received applications of Cryotherapy three times (immediately, 24 and 48 h after injury) of 20 minutes duration. The TU and CRTU groups received applications of Therapeutic Ultrasound for seven days, for five minutes, in pulsed mode, 0.5 w/cm intensity, frequency 1 MHz. Body mass and gastrocnemius mass were analyzed. In addition to histological slides stained with hematoxylin and eosin used for morphometric analysis, picrosirius dye was used for quantification of collagen by Fractal Dimension (FD). The results of the intra-group analysis showed lower body mass and gastrocnemius in the CRTU group in relation to the AI (p = 0.001), I (p = 0.001), CR (p = 0.001) and TU groups (p = 0.001), and lower values of FD to quantify collagen in the CRTU group in relation to the AI (p = 0.007) and CR groups (p = 0.014). In summary, the present study showed that the association of Cryotherapy with Therapeutic Ultrasound promoted better results in the aspects analyzed compared to application of the therapies in isolation.

El objetivo del estudio fue evaluar los efectos de la asociación de las técnicas de crioterapia y ultrasonido terapéutico en el tratamiento de la lesión muscular por impacto. Fueron utilizadas 55 ratas Wistar, expuestas a lesión y separadas en grupos (n = 11): Lesión aguda (LA), Lesión (L), Crioterapia (CR), Ultrasonido Terapéutico (UT) y Crioterapia + Ultrasonido Terapéutico (CRUT). Los grupos CR y CRUT recibieron la aplicación, durante 20 minutos, en tres momentos (inmediatamente, 24 y 48 horas, después de la lesión). Los grupos UT y CRUT, recibieron UT por siete días, con una duración de cinco minutos, en modo pulsado, con una intensidad de 0,5 W/cm2 y frecuencia de 1 MHz. Fueran medidos el peso corporal y el peso de los músculos gastrocnemios y se realizaron cortes histológicos del músculo gastrocnemio, los cuales fueron teñidos con hematoxilina-eosina (HE) para el análisis morfométrico y con picrosirius para el análisis del colágeno por dimensión fractal (DF). Los resultados de los análisis intragrupo demostraron una menor disminución de la masa coporal y muscular en el grupo CRUT. Además, fue observado un valor inferior en la morfometría en el grupo CRUT en comparación a los grupos LA (p = 0,001), L (p = 0,001), CR (p = 0,001) y UT (p = 0,001), y un menor valor de la DF con respecto al colágeno en el grupo CRUT en comparación a los grupos LA (p = 0,007) y CR (p = 0,014). En síntesis, el presente estudio demostró que el protocolo de asociación de las técnicas de CR y UT causaron mayores respuestas benéficas en los aspectos analizados en comparación a los protocolos con los tratamientos aplicados de forma aislada.

Musculoskeletal and cutaneous sarcoidosis: exuberant case report

Sarcoidosis is a multisystem granulomatous disease of unknown cause. The osteoarticular involvement in sarcoidosis is rare and is often associated with cutaneous and long-standing chronic multisystem disease. More common in black women, osseous sarcoidosis is difficult to diagnose, with an incidence of 3 to 13%. The most characteristic radiological clinical picture evidences rounded, well-defined cysts, with no periosteal reaction and without peripheral sclerosis. The small bones of hands and feet are the most frequently involved sites. This report aims to demonstrate a rare case of osteoarticular sarcoidosis with characteristic clinical presentation, and highlight the importance of detecting osteoarticular involvement in this pathology.

Rabdomiosarcoma embrionario hepatico: a propósito de un caso / Hepatic embrionary Rhabdomysarcoma: presentation of a case

El Rabdomiosarcoma es el sarcoma de tejidos blandos de origen musculoesqueléticos más frecuente en niños menores de 15 años y uno de los más comunes en adolescentes y adultos jóvenes. (1) Las áreas del cuerpo más comunes donde puede alojarse este tumor son la cabeza, el cuello, la vejiga, la vagina, los brazos, las piernas y el tronco. Aunque también puede encontrarse en la próstata, el oído medio y el sistema de conductos biliares. (2) En los niños con rabdomiosarcoma embrionario, esta anomalía se encuentra en el cromosoma 11, mientras el alveolar en los cromosomas 2 y 13. (1) Se reconocen tres subtipos: embrionario, alveolar y pleomórfico. El embrionario se observa en niños y adolescentes menores de 15 años y se localiza principalmente en la cabeza y en el cuello, tracto urogenital, retroperitoneo y extremidades. Los síntomas pueden incluir una masa visible o palpable que puede ser doloroso o no, parestesia, dolor. (2) El diagnóstico se establece a través del examen físico, historia médica completa, así como estudios imagenológicos, biopsia y punción de medula ósea. (3) El tratamiento específico será dado por la localización del tumor primario y el estadio del tumor, en algunos pacientes se administra quimioterapia preoperatorio en un intento de reducir la extensión de la intervención y de preservar órganos vitales. El pronóstico se relaciona con la edad del paciente, sitio de origen, resecabilidad. (4)

Lesión tumoral músculo-esquelética de evolución rápida: a propósito de un caso / Lesion skeletal tumoral muscle of quick evolution: a purpose of a case

El Fibrosarcoma es un tumor maligno de partes blandas primario o secundario a lesiones benignas pre-existentes, pueden ser endostal o parostal, comprende aproximadamente el 6.2 por ciento de los tumores primarios del hueso, predomimante en hombres, entre la 3era y 6ta década de vida, tiene predilección por el fémur, húmero, tibia y pelvis. Se describe paciente masculino de 25 años de edad quien inicia enfermedad en noviembre 2002 con aumento de volumen progresivo y dolor en rodilla derecha, acompañandose de limitación funcional; consulta en mayo 2003 con clínica exacerbada iniciándose su estudio.

Epidemiologia clinica da dor musculo-esqueletica / Clinical epidemiology of muscleskeletal pain

Varios estudos demonstram que as mulheres apresentam mais dor que os homens. Entretanto, os estudos sobre lombalgia e dor toracica nao sao conclusivos. Em casos de dores articulares e fibromialgia existe...