Are There Any Differences in the Healing Capacity between the Medial Collateral Ligament's (MCL) Proximal and Distal Parts in the Human Knee? Quantitative and Immunohistochemical Analysis of CD34, α-Smooth Muscle Actin (α-SMA), and Vascular Endothelial Growth Factor (VEGF) Expression Regarding the Epiligament (EL) Theory.

The human knee is a complex joint that comprises several ligaments, including the medial collateral ligament (MCL). The MCL provides stability to the knee and helps prevent its excessive inward movement. The MCL also has a thin layer of connective tissue known as the epiligament (EL), which adheres to the ligament. This unique feature has drawn attention in the field of ligament healing research, as it may have implications for the recovery process of MCL injuries. According to the EL theory, ligament regeneration relies heavily on the provision of cells, blood vessels, and molecules. The present study sought to compare the expression of vascular endothelial growth factor (VEGF), CD34, and α-smooth muscle actin (α-SMA) in healthy knees' proximal and distal MCL segments to better understand how these proteins affect ligament healing. By improving the EL theory, the current results could lead to more effective treatments for ligament injury. To conduct the present analysis, monoclonal antibodies were used against CD34, α-SMA, and VEGF to examine samples from 12 fresh knee joints' midsubstance MCLs. We identified a higher cell density in the EL than in the ligament connective tissue, with higher cell counts in the distal than in the proximal EL part. CD34 immunostaining was weak or absent in blood vessels and the EL, while α-SMA immunostaining was strongest in smooth muscle cells and the EL superficial layer. VEGF expression was mainly in the blood vessels' tunica media. The distal part showed more SMA-positive microscopy fields and higher cell density than the proximal part (4735 vs. 2680 cells/mm2). Our study identified CD34, α-SMA, and VEGF expression in the MCL EL, highlighting their critical role in ligament healing. Differences in α-SMA expression and cell numbers between the ligament's proximal and distal parts may explain different healing capacities, supporting the validity of the EL theory in ligament recovery.

Do the Differences in the Epiligament of the Proximal and Distal Parts of the Anterior Cruciate Ligament Explain Their Different Healing Capacities? Quantitative and Immunohistochemical Analysis of CD34 and α-SMA Expression in Relation to the Epiligament Theory.

The aim of this study was to assess the epiligament theory by determining the normal epiligament morphology of the proximal and distal parts of the anterior cruciate ligament in humans and analyzing the differences between them and the midportion of the ligament in terms of cell numbers and expression of CD34 and α-SMA. Samples were obtained from the anterior cruciate ligaments of 12 fresh knee joints. Monoclonal antibodies against CD34 and α-SMA were used for immunohistochemistry. Photomicrographs were analyzed using ImageJ software, version 1.53f. The cell density was higher in the epiligament than in the ligament connective tissue. Cell counts were higher in the proximal and distal thirds than in the midsubstance of the epiligament. CD34 was expressed similarly in the proximal and distal thirds, although it seemed slightly more pronounced in the distal third. α-SMA expression was more robust in the proximal than the distal part. The results revealed that CD34 and α-SMA are expressed in the human epiligament. The differences between the numbers of cells in the proximal and distal parts of the epiligament and the expression of CD34 and α-SMA enhance epiligament theory. Future investigations into improving the quality of ligament healing should not overlook the epiligament theory.

Chondroblastoma Affecting the Apophysis of the Greater Trochanter in a Child.

Chondroblastomas are rare primary bone tumours typically affecting the epiphyses and less frequently the apophyses of the growing skeleton. Most cases are treated by intralesional curettage with or without local adjuvants and this technique can produce good long-term outcomes. Herein, we describe a case of chondroblastoma of the greater trochanter in a 12-year-old male child that was treated by intralesional curettage and grafting with calcium phosphate bone cement (Neocement Inject® P, Bioceramed, Loures, Portugal). A brief review of the literature is also presented.

A comparative study of the epiligament of the medial collateral and anterior cruciate ligaments in the human knee: Immunohistochemical analysis of CD 34, α-smooth muscle actin and vascular endothelial growth factor in relation to epiligament theory.

BACKGROUND: This study evaluated and compared the expression of VEGF, CD34, and α-SMA in the anterior cruciate ligaments and medial collateral ligaments in healthy human knees in order to enrich the epiligament theory regarding ligament healing after injury. METHODS: Samples from the mid-substance of the anterior cruciate ligament and the medial collateral ligament of 12 fresh knee joints were used. Monoclonal antibodies against CD34, α-SMA, and VEGF were used for immunohistochemical analysis. Photomicrographs were analyzed using the ImageJ software. RESULTS: The epiligament of the anterior cruciate ligament showed slightly higher expression of CD34, α-SMA, and VEGF than the epiligament of the medial collateral ligament. Overall, among the tested markers, α-SMA expression was most pronounced in anterior cruciate ligament epiligament images and CD34 dominated in medial collateral ligament epiligament images. The intensity of DAB staining for CD34, α-SMA, and VEGF was higher in vascular areas of the epiligament than in epiligament connective tissue. CONCLUSIONS: The results illustrate that CD34, α-SMA, and VEGF are expressed in the human epiligament. The differences between the epiligament of the investigated ligaments and the fact that CD34, α-SMA, and VEGF, which are known to have a definite role in ligament healing, are predominantly expressed in the main vascular part of the ligament-epiligament complex enlarge the existing epiligament theory. Future investigations regarding better ligament healing should not overlook the epiligament tissue.

The novel epiligament theory: differences in healing failure between the medial collateral and anterior cruciate ligaments.

According to current literature, 90% of knee ligament injuries involve the medial collateral ligament or the anterior cruciate ligament. In contrast to the medial collateral ligament, which regenerates relatively well, the anterior cruciate ligament demonstrates compromised healing. In the past, there were numerous studies in animal models that examined the healing process of these ligaments, and different explanations were established. Although the healing of these ligaments has been largely investigated and different theories exist, unanswered questions persist.Therefore, the aim of this article is 1) to review the different historical aspects of healing of the medial collateral ligament and present the theories for healing failure of the anterior cruciate ligament; 2) to examine the novel epiligament theory explaining the medial collateral ligament healing process and failure of anterior cruciate ligament healing; and 3) to discuss why the enveloping tissue microstructure of the aforementioned ligaments needs to be examined in future studies.We believe that knowledge of the novel epiligament theory will lead to a better understanding of the normal healing process for implementing optimal treatments, as well as a more holistic explanation for anterior cruciate ligament healing failure.

Giant Cell Tumor of Bone in the Talus Treated by Extended Curettage and Synthetic Bone SubstituteReport of a Rare Case.

Giant cell tumor of bone is extremely rare in the talus and is usually observed in the third decade of life. Herein, we report a case of a 19-year-old male with a giant cell tumor of bone in the talus mimicking a simple bone cyst that was treated by intralesional curettage and, for the first time, bone grafting with a synthetic bone substitute. The patient had no evidence of recurrence at 7-year follow-up but did have non-progressing mild degenerative joint disease and slightly limited range of movement at the ankle joint.

Translation and Validation of the Bulgarian Version of the Boston Carpal Tunnel Questionnaire.

Background and Objective: Carpal tunnel syndrome (CTS) is the most common mononeuropathy in humans. Despite the continuous improvement of diagnostic and treatment methods, difficulties remain in the evaluation and quantification of such symptoms as pain, paresthesias, hypesthesia, and hyperesthesia. Numerous tests and questionnaires have been developed for patients with upper limb disease, but the most specific for CTS and the most commonly used is the Boston Carpal Tunnel Questionnaire (BCTQ). BCTQ has been translated and validated for use in many languages, but there is no valid version in Bulgarian yet. The purpose of this work is to create and validate a Bulgarian version of BCTQ, with a recommendation for its use in Bulgarian patients. METHODS: The process was divided into two parts. The first part included a translation and a cultural-linguistic adaptation of the Bulgarian version of BCTQ. In the second part, verification of the psychometric properties of the Bulgarian BCTQ, we investigated the reliability, validity and responsiveness of the Bulgarian version of BCTQ. We evaluated BCTQ's construct validity by comparing its results with the score of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. The study was performed on a group of 64 patients with a confirmed diagnosis of CTS. All patients were evaluated using the BCTQ and DASH questionnaires. A subgroup of 26 patients underwent open surgical decompression of the carpal canal using a mini-incision technique. The subgroup was evaluated through BCTQ and DASH questionnaires preoperatively and through BCTQ postoperatively at the third month after the intervention. RESULTS: In the first part of the study, the final version of the questionnaire was presented. Cronbach's alpha coefficient was 0.88 for the Symptom Severity Scale (SSS) and 0.87 for the Functional Status Scale (FSS). The reproducibility of scores showed an extremely high degree of correlation between the two consecutive BCTQ scores at one-week interval (SSS r=0.99, p<0.0001; FSS r=1, p<0.0001). The criterion validity of the Bulgarian version of BCTQ revealed a strong correlation between the results of the BCTQ and the DASH questionnaires. (SSS r(62)=0.569, p<0.00001; FSS r(62)=0.605, p<0.00001). There was a statistically significant decrease in BCTQ results after surgery for both the SSS (t=-9.43, p<0.00001) and the FSS (t=-9.82, p<0.00001). CONCLUSION: Our study created a translated and culturally adapted version of BCTQ. The Bulgarian version of BCTQ is reliable, valid, and responsive for measuring symptoms and functional deficits in patients with CTS.

A Non-ossifying Fibroma and a Stress Fracture of the Femur Mimicking Bone Malignancy in a Child.

Herein, we report a rare case of a stress fracture through a pre-existing non-ossifying fibroma (NOF) of the femur of a 12-year-old child that raised suspicion of a malignancy. Although NOFs are very frequent, in the vast majority of cases, they are completely asymptomatic. When encountered in a painful area, especially if combined with atypical radiographic features, they may mimic a malignancy. We discuss the radiographic findings, the differential diagnosis, and the relevant points of the patient's history that helped to establish the diagnosis.

A comparative study of the epiligament of the medial collateral and the anterior cruciate ligament in the human knee. Immunohistochemical analysis of collagen type I and V and procollagen type III.

BACKGROUND: Recent reports in rat models have shown that fibroblasts in the epiligament, an enveloping tissue of the ligament, are not static cells and play an important role during the early ligament healing of isolated grade III injury of the collateral ligaments of the knee. Fibroblasts produce collagen types I, III and V and infiltrate within the ligament body via the endoligament. In addition, similarities have been reported between the structure of the epiligament of the medial collateral ligament and anterior cruciate ligament of the knee in rat and in human. In line with the ascribed role of the epiligament tissue and the synthesis of these collagens and their role in ligament healing, the aim of this study was to determine their presence in the normal epiligament of the aforementioned ligaments in humans, to compare their differential expression and to present a novel hypothesis about the failure of healing of the anterior cruciate ligament in contrast to the medial collateral ligament. MATERIALS AND METHODS: We used samples from the mid-substance of the medial collateral and the anterior cruciate ligament of the knee joint, acquired from 12 fresh knee joints. Routine histological analysis was performed through hematoxylin and eosin stain, Mallory's trichrome stain and Van Gieson's stain. The immunohistochemical analysis was conducted using monoclonal antibodies against collagen type I and V and procollagen type III. The number of cells in the epiligament, endoligament and the ligament tissue was assessed quantitatively through a computerized system for image analysis NIS-Elements Advanced Research and Statistica software. RESULTS: Our observations revealed certain differences in the morphology of the epiligament, as well as variations in the expression of the investigated molecules. Expression of collagen type I was mostly low-positive (1+) in the epiligament and positive (2+) in the ligament tissue of both ligaments. Expression of procollagen type III was mostly positive (2+) in the epiligament and ligament tissue of the medial collateral ligament, low-positive (1+) in the epiligament and negative (0) in ligament tissue of the anterior cruciate ligament. Expression of collagen type V was predominantly low-positive (1+) in the epiligament and negative (0) in the ligament tissue of both ligaments. The immunoreactivity for all three molecules was always higher in the epiligament of the medial collateral ligament than that of the anterior cruciate ligament. CONCLUSIONS: The results of our study illustrate for the first time that fibroblasts in the human epiligament are indeed responsible for the synthesis of the main types of collagen participating in the early ligament healing, thus corresponding to previous data of the medial collateral ligament healing in animal models. The differences between the epiligament of the investigated ligaments could add a novel explanation for the failed anterior cruciate ligament healing.

Osteoid Osteoma of the Middle Phalanx of the Third Finger in a Child Mimicking a Malignancy.

Osteoid osteoma is a rare occurrence in the hand, especially in children. We report here a rare case of a 12-year-old boy complaining of growing painful swelling of the middle phalanx of the third finger that had started 3 months earlier and had not responded to anti-inflammatory medication. Based on the clinical findings and plain radiographs, osteomyelitis or Ewing's sarcoma was suspected. However, MRI revealed the typical characteristics of osteoid osteoma. The lesion was excised, and the histological examination confirmed the diagnosis. We make a brief review of the literature concerning this uncommon localization and discuss the differential diagnosis and treatment modalities.

A Rare Case of Dermatofibrosarcoma Protuberans of the Thumb in an 80-year-old Woman.

Dermatofibrosarcoma protuberans (DFSP) has been described as a rare, locally invasive, malignant fibroblastic tumor with a high rate of recurrence that usually affects middle-aged patients. Herein, we describe a rare case of a pedunculated dermatofibrosarcoma protuberans of the right thumb in an 80-year-old woman treated with excision through the base of the pedicle. We also make a brief literature review concerning this tumor.

Neoadjuvant and Adjuvant Treatment with Denosumab in Aggressive Giant-cell Tumor of Bone in the Proximal Fibula: a Case Report.

Giant cell tumor of bone is a histologically benign but locally aggressive osteolytic lesion, capable of spreading 'benign' metastases mainly to the lungs. Since its description as a separate entity, surgery has been the mainstay of treatment. Recently, target therapy has been introduced using denosumab - an inhibitor antibody for the receptor activator of nuclear factor kappa B ligand with dramatic eff ect on the natural course of the tumor. Herein, we report a rare case of an aggressive stage 3 giant cell tumor of bone of the proximal fibula that was successfully downstaged using neoadjuvant denosumab treatment and then treated by surgical excision followed by adjuvant target therapy. The clinical characteristics and treatment modalities of giant cell tumor of bone, the indications for target therapy, therapy response, and histological changes are also briefly discussed.

Matrix Metalloproteinase-2 and -9 Expression in the Epiligament of the Medial Collateral and Anterior Cruciate Ligament in Human Knees: A Comparative Study.

Aim Ninety percent of knee ligament injuries involve the medial collateral ligament (MCL) and the anterior cruciate ligament (ACL) of the knee joint. Matrix metalloproteinases (MMPs) are a large group of calcium- and zinc-dependent endopeptidases responsible for cleaving and rebuilding various connective tissue components. Previous studies showed that MMP-2 and 9 have a significant effect on the healing process of injured ligaments. Therefore, the aim of this study was to evaluate for the first time in literature the expression and localization of MMP-2 and 9 in the epiligament (EL) and the ligament tissue of the MCL and the ACL of the human knee joint in order to assess their role in ligament healing. Materials and methods For the present study, we used histological material from the mid-portion of the MCL and the ACL of 14 knee joints from fresh cadavers. For the purpose of the immunohistochemical analysis, we used primary polyclonal antibodies against MMP-2 and 9. The obtained results were evaluated semi-quantitatively through ImageJ. Results Immunoreactivity for MMP-2 was predominantly positive (2+) in the EL of the MCL and remained mostly negative (0) in the ligament tissue. The expression of MMP-9 was mostly low-positive (1+) in the EL of the MCL and almost entirely negative (0) in the ligament tissue. In the EL of the ACL, the immunohistochemical expression of MMP-2 was predominantly low-positive (1+) and that of the MMP-9 was read as mostly low-positive (1+). Expression of the two enzymes in the ligament tissue was similar to the MCL. Conclusion The present study is the first comparison of the expression of the aforementioned MMPs in the EL tissue of the MCL and the ACL in human knees, which may play a key role in physiological and pathophysiological processes such as tissue healing and repair and basement membrane degradation.

An Active Giant Cell Tumor of the Patella: A Case Report.

Primary neoplasms of the patella account for less than 1% of all primary bone tumors of the lower extremity, the most frequent of them being the giant cell tumor of bone, the chondroblastoma, and the aneurysmal bone cyst. Herein, we report the case of a 29-year-old woman with an active giant cell tumor of the patella (GCTP) with its clinical and radiological features and a brief review of the literature.

Extraskeletal osteochondroma within the iliopsoas muscle: case report.

Osteochondromas, occurring usually in the metaphyses of long bones, are among the most frequent benign musculoskeletal neoplasms and both their sporadic and hereditary variants have been studied extensively. Extraskeletal osteochondromas, however, are much less common. They have been shown to arise near joints or synovial spaces of feet, hands, or bursae. Herein, we present a very rare case of an extraskeletal osteochondroma within the iliopsoas muscle.

Light and electron microscopic study of the medial collateral ligament epiligament tissue in human knees.

AIM: To examine the normal morphology of the epiligament tissue of the knee medial collateral ligament (MCL) in humans. METHODS: Several samples of the mid-substance of the MCL of the knee joint from 7 fresh human cadavers (3 females and 4 males) were taken. Examination of the epiligament tissue was conducted by light microscopy and photomicrography on semi-thin sections of formalin fixed paraffin-embedded blocks that were routinely stained with haematoxylin and eosin, Mallory stain and Van Gieson's stain. Electron microscopy of the epiligament tissue was performed on ultra-thin sections incubated in 1% osmium tetroxide and contrasted with 2.5% uranyl acetate, lead nitrate, and sodium citrate. RESULTS: The current light microscopic study demonstrated that the epiligament of the MCL consisted of fibroblasts, fibrocytes, adipocytes, neuro-vascular bundles and numerous multidirectional collagen fibers. In contrast, the ligament body was poorly vascularised, composed of hypo-cellular fascicles which were formed of longitudinal groups of collagen fibers. Moreover, most of the vessels of the epiligament-ligament complex were situated in the epiligament tissue. The electron microscopic study revealed fibroblasts with various shapes in the epiligament substance. All of them had the ultrastructural characteristics of active cells with large nuclei, well developed rough endoplasmic reticulum, multiple ribosomes, poorly developed Golgi apparatus, elliptical mitochondria and oval lysosomes. The electron microscopy also confirmed the presence of adipocytes, mast cells, myelinated and unmyelinated nerve fibers and chaotically oriented collagen fibers. CONCLUSION: Significant differences exist between the normal structure of the ligament and the epiligament whose morphology and function is to be studied further.

A Giant Deep-seated Lipoma in a Child's Forearm.

Deep-seated giant lipomas are rare relative to the overall incidence of the tumor and their occurrence grows more frequent with age. A case of an unusual deep-seated giant lipoma in the forearm of a four-year-old child is reported.

Symptomatic Os Subtibiale Associated with Chronic Pain Around the Medial Malleolus in a Young Athlete.

An os subtibiale is a rare accessory bone located below or behind the medial malleolus. Herein we present a rare case of a painful os subtibiale in a young triathlete who presented with pain, redness and swelling below his left medial malleolus. Plain radiographs and three-dimensional computed tomography revealed a well-defined oval bone distal to the left medial malleolus. After conservative treatment failed, the ossicle was excised in an open surgery with complete resolution of symptoms. This case report emphasizes the need for clinical awareness of different anatomical variations of the bones of the foot.