Extraskeletal Soft Tissues Research Articles

Innovations in the classification of soft tissue tumors

Soft tissue tumors are avery heterogeneous group of tumors. Their classification is regularly updated by the World Health Organization (WHO), most recently in 2020. The current classification of soft tissue tumors emphasizes molecular biological tumor characteristics, which enable tumor-specific treatment. In addition to Ewing's sarcoma, which occurs as bone as well as extra-skeletal soft tissue tumors as asmall round cell sarcoma, three other subtypes of undifferentiated, small and round cell sarcomas have been introduced. Some names of the new sarcomas can be derived from the gene mutations. The groups of adipocytic and (myo)fibroblastic tumors have been extended by three further entities. There were further additions to vascular soft tissue tumors, smooth muscle cell tumors, peripheral nerve sheath tumors and tumors of uncertain differentiation. Adistinction is made between benign, intermediate locally aggressive, intermediate rarely metastatic and malignant soft tissue tumors.

Heterotopic Ossification at Uncommon Sites: A Case Series of 4 Rare Cases

Heterotopic ossification (HO) is a condition of formation of mature lamellar bone in the extra skeletal soft tissue where bone does not usually exist. It is most commonly seen in muscle tissue and central nervous system following trauma. In this case series, we have reported 4 rare cases of heterotopic bone formations at uncommon sites. One case of HO in clear cell renal cell carcinoma, one case of HO in tendoachilles, one case of HO in intramuscular vascular malformation and one case HO in abdominal incision scar. HO is a rare entity. In most of the cases exact etiology is unknown. Further studies needed for more conclusive information regarding the clinical significance of heterotopic ossification.

Calcified apoptotic vesicles from PROCR+ fibroblasts initiate heterotopic ossification.

Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single-cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV-releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification.

Uncovering a Novel Site of Ewing's Sarcoma: the Hypopharynx.

Ewing's sarcoma is usually seen in bones but 20-30% are found in extra skeletal soft tissues like in head and neck region. We present the case of Ewing sarcoma of hypopharynx in a 1year old child who presented to us with acute respiratory distress. Child was intubated using videolaryngoscope and mass was removed using microdebrider. Final histopathological examination revealed Ewing sarcoma. EWSR1 gene rearrangement studies were advised, which the patient refused. Post-operative patient was started on adjuvant chemotherapy. PET CT after 2months showed no FDG avid lesions within or elsewhere in the region of the body surveyed.There is no case of Ewing's sarcoma in hypopharynx reported to date.The clinical presentation, management and outcome has been discussed with a review of the literature.

Atraumatic myositis ossificans of mentalis muscle

Rationale: Atraumatic myositis ossificans circumscripta is a benign condition characterized by the aberrant formation of bone in extraskeletal soft tissues without a usual connection to trauma. Patient Concern: A female patient of around 17 years of age reported with the main complaint of pain and swelling over the chin area for 6 months with no history of trauma. Diagnosis: Clinical, radiographic, and histopathological examinations were performed and all signs and symptoms pointed to a diagnosis of Atraumatic Myositis Ossificans in the Mentalis muscle. Intervention: Surgical exploration of the area concerned was done under (L.A) local anesthesia with adrenaline (1:1,00,000), where the nodes were extracted from the lower surface of the Mentalis muscle. The wound was sutured back to its normal physiologic anatomy, and the patient then was advised of postoperative instructions. Results: The patient recovered with a good prognosis and returned to a normal routine with good functional capacity. Lessons Learned: The practitioner must consider Atraumatic Myositis ossificans as a viable diagnosis for painful soft tissue calcification when a history of trauma is not present.

Extraosseous Ewing Sarcoma in a Pelvic Region: A Case Report

Ewing sarcoma; neoadjuvant chemotherapy; radiation therapy.

Engineered osteoclasts as living treatment materials for heterotopic ossification therapy

Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically. Naive OCs have limitations for the removal of ectopic calcification, such as in heterotopic ossification (HO), due to their restricted activity, migration and poor adhesion to sites of ectopic calcification. HO is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these unexpected calcified plaques. In the present study, we develop a chemical approach to modify OCs with tetracycline (TC) to produce engineered OCs (TC-OCs) with an enhanced capacity for targeting and adhering to ectopic calcified tissue due to a broad affinity for calcium minerals. Unlike naive OCs, TC-OCs are able to effectively remove HO both in vitro and in vivo. This achievement indicates that HO can be reversed using modified OCs and holds promise for engineering cells as “living treatment agents” for cell therapy.

Peripheral Osteoma of the Mandible-A Case Report

Osteomas are benign osteogenic tumour characterised by proliferation of compact or cancellous bone. Thethree varieties of osteoma are central variant arising from endosteum, the peripheral variant arising fromperiosteum and the extra skeletal soft tissue osteomas arising within a muscle. Osteoma arising in facialbone is a rare entity. Peripheral osteoma has been known to occur in frontal, ethmoid and maxillary sinusesbut not common in jaw bones. We describe here a case report of peripheral osteoma of mandible in a middleagedfemale patient.

Primary pulmonary Ewing\u2019s sarcoma: rare cause of massive hemothorax in a young girl-case report

BackgroundEwing’s sarcoma is a common malignant bone tumor in children and young adults. Rarely, extra-skeletal soft tissues and visceral organs can also be the site of origin of Ewing’s sarcoma. Primary pulmonary Ewing’s sarcoma is an extremely rare malignancy.Case presentationWe report an unusual case of primary pulmonary Ewing’s sarcoma in a 15-year-old girl who initially presented with massive hemothorax. By histopathology evaluation of surgical biopsy specimens, the diagnosis of extraosseous Ewing’s sarcoma was confirmed by both light microscopy and immunohistochemistry. Emergency, open surgery was performed by thoracic surgery at an early stage. After 3 cycles of chemotherapy, the patient was found to be stable at follow-up examination. No more hydrothorax or other symptoms.ConclusionsWe have described an extremely rare case of primary pulmonary Ewing’s sarcoma with massive hemothorax. The patient underwent surgical resection and postoperative chemotherapy, no sign of recurrence to date as an outcome.

A nontraumatic myositis ossificans case of the forearm: Case report and literature review.

Myositis ossificans (MO) is a rare, benign ossifying lesion characterized by focal formation of heterotopic bone and cartilage in extraskeletal soft-tissue that most commonly occurs in young adults. In most cases, no causative factor can be identified. The diagnosis of MO is usually based on the patient's history of trauma, clinical signs, on imaging appearance and histological examination. We present a non-traumatic MO case of the forearm in a 40-year-old man with weakness in left finger motion, a decrease in prehension for more than three weeks, without any weight loss, malaise, anorexia or fever. The clinical symptoms and radiological findings can be easily confused with malignant lesions. Treatment is usually conservative but, due to the limited strength and range of motion of the left hand, the tumor was extirpated and the diagnosis of MO was made by biopsy. The patient had no neurological deficits after surgical treatment and was discharged on the fifth day after the surgery in good condition with the recommendation to begin a rehabilitation program.

Myositis ossificans revisited – The largest reported case series

IntroductionMyositis ossificans (MO) is a condition characterised by the formation of non-neoplastic heterotropic ossification in extraskeletal soft tissues. Material and methodsWe performed a retrospective study of our radiology databases within our tertiary orthopaedic centre to identify all cases of MO, reported on X ray, Magnetic resonance imaging (MRI) and Computed tomography (CT) over the past 13 years (2007–2020). ResultsWe identified 68 cases of MO, which were included into our cohort. The average age of our patients was 36 years (range 4–84 years). 73% of cases (n = 50) were found to affect the lower limb muscles with the majority in the quadriceps. ConclusionWe report the largest case series of MO and discuss the demographics, diagnoses and management.

Genetic and Acquired Heterotopic Ossification: A Translational Tale of Mice and Men.

Heterotopic ossification is defined as an aberrant formation of bone in extraskeletal soft tissue, for which both genetic and acquired conditions are known. This pathologic process may occur in many different sites such as the skin, subcutaneous tissue, skeletal muscle and fibrous tissue adjacent to joints, ligaments, walls of blood vessels, mesentery and other. The clinical spectrum of this disorder is wide: lesions may range from small foci of ossification to massive deposits of bone throughout the body, typical of the progressive genetically determined conditions such as fibrodysplasia ossificans progressiva, to mention one of the most severe and disabling forms. The ectopic bone formation may be regarded as a failed tissue repair process in response to a variety of triggers and evolving towards bone formation through a multistage differentiation program, with several steps common to different clinical presentations and distinctive features. In this review, we aim at providing a comprehensive view of the genetic and acquired heterotopic ossification disorders by detailing the clinical and molecular features underlying the different human conditions in comparison with the corresponding, currently available mouse models.

Diclofenac for prophylaxis of heterotopic ossification after hip arthroplasty: a systematic review.

Heterotopic ossification (HO) is defined as the formation of lamellar bone in extraskeletal soft tissues. HO can be a severe complication after hip arthroplasty but can possibly be prevented by postoperative treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or radiotherapy. Diclofenac is 1 of the most used drugs in HO prophylaxis because it is effective and long established. However, there is still no uniform therapy regimen in terms of duration, dose and side effect profile regarding the application of diclofenac in HO prevention. We have, therefore, conducted the first systematic review investigating diclofenac for HO prophylaxis after hip arthroplasty. The aim of this study is to assess the efficacy, dose and duration of diclofenac therapy in preventing HO after total hip arthroplasty (THA). According to the PRISMA Guidelines we performed a systematic literature search in EMBASE via Ovid, in MEDLINE via PubMed and in the Cochrane Library addressing all studies in English and German regarding the prophylaxis of HO with diclofenac after THA. We identified 731 potential studies and included 6 randomised controlled trials with 957 patients. The studies were heterogeneous with regard to duration of therapy, dose, comparative group and follow-up period. The therapy duration ranged from 9 to 42 days, the applied diclofenac doses ranged from 75 mg to 150 mg daily. Patients treated with diclofenac showed a significant reduction in the total incidence of HO regarding to the Brooker Classification compared to placebo and no clinically relevant ossifications occured (Brooker III and IV). Diclofenac is efficacious in the prevention of HO and can be used routinely after THA. The existing data indicates that a minimum dose of 75 mg diclofenac per day started on the first postoperative day for a minimum of 9 days is needed to prevent HO with an acceptable incidence of side effects, such as gastrointestinal symptoms.

Ewing Sarcoma With Emphasis on Extra-skeletal Ewing Sarcoma: A Decade's Experience From a Single Centre in India.

Introduction:The diagnosis of Ewing sarcoma family of tumours (ESFT) is challenging, especially in adults and in extra-skeletal or visceral location. Several morphologic mimics with varied treatment options and prognosis confer diagnostic dilemmas. Application of ancillary diagnostic modalities in surgical pathology in clinical routine has enabled accurate diagnosis of ESFT in bone, soft tissues, and viscera.Aim:The study aims to assess the clinicopathological features including molecular test results of ESFT with emphasis on sex, age, and location, especially extra-skeletal soft tissue and visceral location.Material and Methods:Data of clinicopathological, molecular tests (wherever performed), diagnosis rendered in 302 ESFT over a decade from our centre were reviewed. Statistical comparison of skeletal and extra-skeletal tumours with reference to age and sex was done using SPSS package. The P value of <.05 was considered significant.Results:The cohort included 302 ESFTs with 49% skeletal and 51% extra-skeletal tumours. Thigh was most common site among skeletal tumours; chest wall, paraspinal location, and retroperitoneum among soft tissues (39.4%); and kidney, ovary, and cervix among visceral tumours (11.3%). Fluorescence in situ hybridisation for EWSR1 gene rearrangement was positive in 54 patients and reverse-transcriptase polymerase chain reaction in 19 patients. Predominance of male sex, younger age and location in extremities among skeletal tumours and lack of gender predilection, higher age and axial location in extra-skeletal tumours were noted, which were statistically significant. Molecular tests were performed more frequently in extra-skeletal tumours, especially in visceral tumours to establish the diagnosis.Conclusions:The study showed statistically significant differences in the age, sex, and location between skeletal and extra-skeletal ESFT. The increased percentage of extra-skeletal tumours especially in viscera was attributed to the increased awareness and availability of ancillary techniques.

The added value of SPECT-CT in the detection of heterotopic ossification on bone scintigraphy.

Heterotopic ossification (HO) is the abnormal osteogenesis in non-skeletal tissue. It can be difficult to detect, as it can mimic other conditions clinically and on imaging studies. The purpose of this study was to find the added value of SPECT-CT in accurate detection of HO. A total of 1780 reports on the PACS system of patients underwent bone scintigraphy at the Department of Nuclear Medicine and were filtered for the term "HO" or "heterotopic bone formation" and "SPECT-CT". Thirty-four patients fulfilled this criterion. All patients had bone scintigraphy and SPECT/CT in the same occasion. Images were reviewed by two nuclear medicine physicians blindly. The certainty of the presence of extra-skeletal soft tissue ossification on the planar with SPECT was graded as "definitely present", "maybe present", or "not present", and the same was determined on planar with SPECT-CT images. Based on SPECT/CT, 23 (67.6%) patients were found to have HO, and 11 (32.4%) did not have confirming findings. Of the 23 positive patients on SPECT/CT, eight (34.8%) showed "definitely present" and 12 (52.2%) patients were under "maybe present" on SPECT only. Three (13%) patients were negative on the SPECT and showed evidence of HO on CT. Of the 11 patients that did not demonstrate definite evidence of HO on SPECT/CT, seven (63.6%) were negative on SPECT alone and, four (36.4%) were under "maybe present" on SPECT. The definite detection of HO was statistically significant higher when CT is added to SPECT. Our findings suggest that adding the CT component to SPECT is valuable in the detection of HO.

Metachronous extraskeletal (soft tissue) epithelioid osteogenic sarcoma: a case report

BackgroundMetachronous osteosarcoma is a rare form of osteosarcoma. The occurrence of metachronous tumor in soft tissue is exceedingly rare. The pathogenesis of metachronous osteosarcoma, as to whether it represents multiple true primaries or metastatic disease, is still obscure.Case presentationA 49-year-old Indian man presented with progressively increasing swelling in his left hand of 2 months’ duration. An X-ray showed a soft tissue lesion. Contrast-enhanced computed tomography showed a soft tissue mass lesion, with peripheral enhancement and central necrotic areas in radial palmar soft tissue overlying second metacarpophalangeal region with no obvious bony osteolysis. Possibilities of acute abscess, resolving hematoma, or aggressive soft tissue mass lesion were suggested. An incision biopsy showed morphological features of epithelioid osteosarcoma, which was confirmed on immunohistochemistry. A detailed history revealed that our patient was diagnosed as having osteosarcoma of his right leg 3 years previously. Based on history, radiology, morphology, and immunohistochemistry, a final diagnosis of extraskeletal (soft tissue) epithelioid osteogenic sarcoma of the left hand occurring as a metachronous tumor 3 years after diagnosis of primary osteosarcoma in the right leg was given.ConclusionThis is probably the first reported case of extraskeletal (soft tissue) epithelioid osteosarcoma occurring as a metachronous tumor 3 years after diagnosis of primary osteosarcoma in the right leg. The prognosis of metachronous skeletal osteosarcoma is poor as compared to that of relapse limited to lungs. In late metachronous osteosarcoma, combined-modality therapy comprising surgery and aggressive chemotherapy may affect long-term survival. Lifelong follow-up of surviving patients with osteosarcoma is necessary and if metachronous osteosarcoma is discovered, it should be treated with curative intent.

A Sizeable Solitary Pedunculated Peripheral Osteoma of the Hard Palate: A Case Report.

Osteomas are benign, slow growing, usually sessile osteogenic tumors of unknown etiology. They arise from proliferation of either cancellous or compact bone. They can be central, peripheral or extra-skeletal based on their origin from endosteum, periosteum or extra-skeletal soft tissue respectively. They are commonly found in the skull and facial bones, the most common site in the maxillofacial region being paranasal sinuses. Among the jaw bones the most common site is the mandible. The hard palate is a rare site for such osteomas with a very few cases reported in literature. We report a case of large pedunculated peripheral osteoma of the hard palate in a 38year old male. The tumor was excised with no recurrence after 3years followup.

Challenges of heterotopic ossification-Molecular background and current treatment strategies.

Heterotopic ossification (HO) is an abnormal formation of mature lamellar bone within extraskeletal soft tissues, such as muscles, tendons, and ligaments. This process is thought to be induced by inflammation associated with tissue injuries. HO is classified using two subtypes: resulting from injury or genetically inherited. HO formation is associated with polytrauma patients with traumatic brain injuries and spinal cord injuries. Moreover, HO is also considered to be a post-operative risk factor in some orthopaedic procedures. In this review, we summarize our current understanding of the pathology of different types of HO and discuss its current and future therapies. Thus far, research has revealed cellular and molecular pathways leading to HO formation and proposed several possible mechanisms leading to HO and conserved signalling pathways common in the different HO subtypes. Non-steroidal anti-inflammatory drug treatment and localized low-dose irradiation are currently the only available prophylactic treatments for HO. However, they are not always effective and do not target the osteogenic processes directly. New therapeutic strategies targeting the pathological processes of HO, such as bone morphogenetic protein (BMP) inhibitors like noggin, BMP type 1 receptor inhibitor, and nuclear retinoid acid receptor-gamma (RARγ) agonists, are currently being investigated. In-depth understanding of the HO pathological process could help to develop effective therapeutic strategies.

Extra skeletal soft tissue chondroma (ESSC) of right thumb- a benign tumour diagnosed by FNAC – a rare case report

Extra skeletal soft tissue chondroma (ESSC) is very rare slowly growing benign tumours usually occur in hands and feet. Lesion must be differentiated from other benign and malignant lesions in these locations by clinical, radiological, cytological and histopathological examination for proper management of such benign entity. A case is presenting here in a thirty five years old lady suffering from similar type of lesion over right thumb diagnosed preoperatively by fine needle aspiration cytology because of rarity. Diagnosis was confirmed by surgical excision and histopathological examination.International Journal of Human and Health Sciences Vol. 02 No. 03 July’18. Page : 164-166

Current treatment landscape and emerging management options for extremity sarcoma

Malignant tumors of extremity are mostly of mesenchymal origin and arise from bone or extraskeletal soft tissue. Combination chemotherapy has greatly increased the survival of non-metastatic localized osteosarcoma and Ewing's sarcoma; however, there is conflicting evidence regarding the role of neoadjuvant and adjuvant chemotherapy in soft tissue sarcoma due to the rarity and heterogeneous population. Despite intensive multimodal therapy and valiant efforts, most of the patients with relapsed and metastatic sarcoma will succumb to their disease. Molecular studies like next-generation sequencing have revealed various targetable biomarkers which can be further explored in the therapeutic landscape with specific targeted therapies. We reviewed all ongoing and completed clinical trials involving chemotherapy, targeted therapy, and immunotherapy valid for patients with extremity sarcoma. We present the current viable therapeutic options for such a cohort of patients in routine clinical practice.