Extensive Ossification Research Articles

Fibrodysplasia Ossificans Progressiva-related Activated Activin-like Kinase Signaling Enhances Osteoclast Formation during Heterotopic Ossification in Muscle Tissues

Fibrodysplasia ossificans progressiva is characterized by extensive ossification within muscle tissues, and its molecular pathogenesis is responsible for the constitutively activating mutation (R206H) of the bone morphogenetic protein type 1 receptor, activin-like kinase 2 (ALK2). In this study, we investigated the effects of implanting ALK2 (R206H)-transfected myoblastic C2C12 cells into nude mice on osteoclast formation during heterotopic ossification in muscle and subcutaneous tissues. The implantation of ALK2 (R206H)-transfected C2C12 cells with BMP-2 in nude mice induced robust heterotopic ossification with an increase in the formation of osteoclasts in muscle tissues but not in subcutaneous tissues. The implantation of ALK2 (R206H)-transfected C2C12 cells in muscle induced heterotopic ossification more effectively than that of empty vector-transfected cells. A co-culture of ALK2 (R206H)-transfected C2C12 cells as well as the conditioned medium from ALK2 (R206H)-transfected C2C12 cells enhanced osteoclast formation in Raw264.7 cells more effectively than those with empty vector-transfected cells. The transfection of ALK2 (R206H) into C2C12 cells elevated the expression of transforming growth factor (TGF)-β, whereas the inhibition of TGF-β signaling suppressed the enhanced formation of osteoclasts in the co-culture with ALK2 (R206H)-transfected C2C12 cells and their conditioned medium. In conclusion, this study demonstrated that the causal mutation transfection of fibrodysplasia ossificans progressiva in myoblasts enhanced the formation of osteoclasts from its precursor through TGF-β in muscle tissues.

Case of the Season: Usual Interstitial Pneumonia With Dendriform Pulmonary Ossification

Dendriform pulmonary ossification (DPO) is a rare disease characterized by the presence of mature bone in the lung parenchyma with typical radiologic findings of diffuse and numerous calcified nodules. We present two cases of primary DPO complicated by recurrent spontaneous pneumothorax.Case 1 is a 53-year-old male with recurrent pneumothorax unresponsive to chest tube drainage or subtotal pleurectomy via video assisted thoracoscopy (VATS) who was finally treated with talc pleurodesis. Chest computed tomography (CT) revealed bilateral partially calcified reticulonodular opacities with a basal predominance. VATS biopsy revealed patchy foci of fibrous organizing pneumonia with multifocal ossifications confirming DPO histopathology. Pneumothorax recurred on the same side eight months later managed with talc pleurodesis. Case 2 is a 45-year-old Caucasian male who presented for evaluation of three prior spontaneous left-sided pneumothoraces occurring over eight years, treated with chest tube drainage and eventual talc pleurodesis. Chest CT demonstrated multiple high attenuation peripheral branching opacities greatest in the left lower lobe with several nonspecific, non-calcified pulmonary nodules. VATS biopsy revealed cicatrical organizing pneumonia with associated extensive intraalveolar ossification consistent with DPO.We describe two cases of DPO complicated by recurrent pneumothorax and reviewed the world literature. Summarized findings included a propensity for middle-aged males with a generally indolent course though pneumothorax was often refractory to initial chest tube drainage requiring more definitive mechanical management. There was also a predominance of primary disease without associated causes other than several reports of obstructive lung disease (asthma).

Micro-computed tomography study of the abnormal osseous extensions of sella turcica

The paper presents anatomical considerations on the abnormal ossification, which occurred around the dorsum of the sella turcica in the human skull of the female individual. Probably the morphological alterations of the sellar region were associated with extensive heterotopic ossification of the dura mater attached to the dorsum of the sella turcica and the posterior clinoid processes. The analysis of gray values of the voxels representing the areas of abnormal ossification indicated on variation in bone density in the entire sample. We have established that the highest mineralisation of bony tissue occurred in the marginal parts of the osseous extensions deriving from the posterior clinoid processes. The ossified parts of dura mater attached to the posterior clinoid processes showed significantly higher content of the hydroxyapatite (1.9 g/cm3) than the dorsum of the sella turcica (1.0 g/cm3).

Pleomorphic adenoma of parotid gland with extensive bone formation – A rare case report

Pleomorphic adenoma is the most common type of all salivary gland tumors, involving more frequently the parotid gland. In most series, it represents 45–75% of all salivary gland neoplasms. We report an unusual case of a huge tumor that measured 9×8cm & 400g by weight with extensive bone formation, occurring in the parotid gland of a 22year old man. Thorough clinical examination was done. FNAC was done which showed Myxochondroid matrix with glandular epithelial cells suggesting pleomorphic adenoma. CT scan head & neck revealed a large mass with nodular areas of calcification within soft tissue with marked narrowing of orophayngeal lumen. Total parotidectomy with preservation of facial nerve was done by the Transcervical Transparotid approach. The histopathological findings suggested the possibility of extensive endochondral ossification in pleomorphic adenoma. Preservation of facial nerve functions is a key to successful parotid surgery.

Extensively Ossifying Oral Leiomyoma: A Rare Histologic Finding

Oral leiomyoma are rare neoplasms of the oral cavity. Ossification within leiomyoma is not unusual but is mostly reported in leiomyoma of the deep soft tissue. Ossifying leiomyoma is extremely rare in the head and neck. We identified a total of three cases of extensively ossified leiomyoma in the head and neck in the literature including lesions in the lateral pterygoid muscle and orbit. To the best of our knowledge, only one case of extensively calcified leiomyoma has been reported in the oral cavity. We present two such rare cases of oral leiomyoma with extensive intratumoral calcifications and ossification. Ossified leiomyoma should be considered in the differential diagnosis of calcified or hard/firm soft tissue masses in the oral cavity.

A Novel Factor, Tmem176b, Induced by Activin-like Kinase 2 Signal Promotes the Differentiation of Myoblasts into Osteoblasts

Previous studies have suggested some interactions between muscle tissues and bone metabolism. The constitutively activating mutation (R206H) of the BMP type I receptor, activin-like-kinase 2 (ALK2), causes fibrodysplasia ossificans progressiva (FOP), which is characterized by extensive ossifications within muscle tissues. In the present study, we revealed that Tmem176b mRNA levels were upregulated by stable transfection of ALK2 (R206H) in mouse myoblastic C2C12 cells. Transient Tmem176b overexpression elevated levels of osteoblast differentiation markers, such as Osterix and alkaline phosphatase, as well as mineralization in C2C12 cells. In addition, Tmem176b overexpression elevated the levels of these markers in mouse osteoblastic MC3T3-E1 cells. On the other hand, Tmem176b overexpression suppressed the levels of myogenic markers, such as MyoD and myogenin in C2C12 cells, although it did not affect the levels of chondrogenic markers, such as type II and X collagens. In conclusion, the present study is the first to demonstrate that Tmem176b induces the differentiation of myoblasts into an osteoblast lineage.

Extensive ossification of an intramuscular venous malformation in the submental region

We describe a 62-year-old male patient with an extensively ossified venous malformation within the mylohyoid muscle. Phleboliths and calcifications are characteristic of venous malformations, while massive ossification is rare. To our knowledge, no extensive ossified venous malformation within the mylohyoid muscle has been reported. Intramuscular vascular lesions occur with an incidence of 0.8 in 10, occurring in the head and neck region in 15% of cases. Most are venous malformations. The diagnosis is rarely made before surgery and requires a definitive histological analysis, as there are no pathognomonic clinical or radiographic findings, especially with extensive ossification. Spontaneous regression does not occur, and treatment must be based on aesthetic and functional disturbances. We reviewed the classification of vascular anomalies, focusing on differentiating between venous malformations and haemangiomas, which are frequently confused in the literature.

Giant Cranionasal and Cystic-Solid Craniopharyngioma Associated With Extensive Bone Erosion and Ossification

Craniopharyngioma (CP), a rare benign and slow-growing epithelial tumor, is mainly located within the sellar/parasellar region. Primary CP involving the nasal cavity and the sellar region with extensive erosion of the skull base and ossification simultaneity has not been described previously. The authors report a 23-year-old man who presented to our institute with complaints of repeated nasal cavity bloodshed, liquid flow, and progressive visual loss. A neuroimaging examination showed a giant cranionasal and cystic-solid CP extending from the suprasellar region to the nasopharynx with inhomogeneous enhancement, which is associated with extensive erosion of the skull base and ossification. The patient underwent a transsphenoidal surgery to resect the nasopharyngeal component of CP and a subfrontal craniotomy with a total removal of intracranial component by grinding 3 months later. A histopathologic examination revealed characteristic features of adamantinomatous CP associated with ossification. The current study demonstrates that CP can exhibit cranionasal growth pattern and arise from residue of craniopharyngeal duct. Extensive erosion of the skull base, calcification, and ossification can present in tumor simultaneity. A 2-stage stratagem is important for its total removal because of the peculiar hardness. Postsurgical course is unevenly and should be dealt with carefully.

Extensive Ossification of Thymoma in a Child

A case of thymoma with extensive ossification in an 8-year-old female child is presented. The presence of extensive ossification in the stroma of the thymoma is an extremely rare feature. To date, there is a single report of ossifying thymoma in children. This report represents the second known case in a child in the worldwide literature.

Extensive Diffuse Pulmonary Ossification after Acute Respiratory Distress Syndrome

Extensive Diffuse Pulmonary Ossification after Acute Respiratory Distress Syndrome

Heterotopic ossification in the reaming tract of a percutaneous antegrade femoral nail: a case report

IntroductionHeterotopic ossification is a rare complication of musculoskeletal injuries, characterized by bone growth in soft tissues. Percutaneous antegrade intramedullary nailing represents the ‘gold standard’ for the treatment of femur shaft fractures. Minor bone growth is frequently seen around the proximal end of reamed femoral nails (so-called ‘callus caps’), which are asymptomatic and lack a therapeutic implication. The occurrence of excessive, symptomatic heterotopic ossification around the entry site of an antegrade femoral nail is rarely described in the literature.Case presentationWe present the case of a 28-year-old Caucasian woman who developed extensive heterotopic ossification around the reaming seeds of a reamed femoral nail. She developed severe pain and significantly impaired range of motion of the hip joint, requiring revision surgery for heterotopic ossification resection and adjunctive local irradiation. She recovered full function of the hip and remained asymptomatic at her two-year follow-up appointment.ConclusionsSevere heterotopic ossification represents a rare but potentially detrimental complication after percutaneous femoral nailing of femur shaft fractures. Diligent care during the reaming procedure, including placement of a trocar to protect from osteogenic seeding of the soft tissues, may help decrease the risk of developing heterotopic ossification after reamed antegrade femoral nailing.

Lumbar Disc Herniation with End-Plate Fracture and Secondary Ossification Mimicking an Epidural Tumor: A Case Report

We report a unique case of lumbar disc herniation, in particular, with end-plate and surrounded by extensive ossification, mimicking a tumor with calcification. A 69-year-old female suffered from right buttock and leg pain. Computed tomography (CT) showed an intracanalar mass with calcification or ossification, which most likely originated from the vertebral body at the L1/2 level epidural space. On a T1-weighted gadolinium magnetic resonance image, the capsule of the mass was enhanced and not only the content of the mass but also that of the L2 vertebral body were partially and slightly enhanced. The final pathological diagnosis was disc herniation with end-plate fracture and secondary ossification. A combination of these pathological conditions as accompanied by both end-plate fractures and extensive secondary ossifications has not been previously reported. This rare pathological condition needs to be recognized as a differential diagnosis.

Squamous cell carcinoma of lung with osteo-cartilaginous metaplasia – a case report and review of the literature

Calcification and ossification are very rare in primary squamous cell carcinoma of the lung. We report a 55-year-old male with primary squamous cell carcinoma of the lung who on histopathological examination was seen to have extensive calcification and ossification. Squamous carcinoma of the lung rarely presents with osteocartilaginous metaplasia. The case is presented here for its unique presentation.

Giant anterior cervical osteophyte leading to Dysphagia.

Large anterior cervical osteophytes can occur in degeneration of the cervical spine or in diffuse idiopathic skeletal hyperostosis(DISH). Large osteophytes can produce otolaryngological symptoms such as dysphagia, dysphonia, and foreign body sensation. We describe a DISH patient with giant anterior cervical osteophyte causing chronic dysphagia and dysphonia. A 56-year-old man presented with increasing dysphagia, dysphonia, neck pain and neck stiffness. Physical examination of the neck showed a non-tender and hard mass on the left side at the level of C4-5. Radiography showed extensive ossification of anterior longitudinal ligament along the left anterolateral aspect of vertebral bodies from C2 to T1. The ossification was espe cially prominent at the level of C4-5 and linear breakage was noted at same level. Esophagogram revealed a filling defect along the pharynx and lateral displacement of the esophagus. Giant anterior cervical osteophyte was removed through the leftsided anterolateral cervical approach to the spine. Anterior cervical interbody fusion at C4-5 was followed by posterior cervical fixation using lateral mass screws from C3 to C6. After surgery, dysphagia and dysphonia improved immediately. One year later, cervical CT showed bone fusion at C4-5 bodies and no recurrence of osteophyte. DISH is a common cause of anterior cervical osteophyte leading to progressive dysphagia. Keeping this clinical entity in the differential diagnosis is important in patients with progressive neck stiffness, dysphagia or dysphonia. And surgical treatment of symptomatic anterior cervical osteophyte due to DISH should be considered with a solid fusion procedure preventing postoperative instability or osteophyte progress.

Heterotopic ossificans in chronic venous insufficiency: a new consideration for clinical, aetiology, anatomy and pathophysiology staging

Heterotopic ossification is defined as the abnormal formation of true bone within extra-skeletal soft tissues. It may be associated with a variety of clinical conditions, but is most frequently seen with musculoskeletal trauma, neurologic injury or genetic abnormalities. It has also been described in patients with chronic venous insufficiency; however, it often goes underdiagnosed due to chronic ulceration that masks exam findings. To date, few reports of heterotopic ossification due to chronic venous disease exist within the literature with the most recent dating back to the 1970s. We present a case study of a man presenting with extensive leg ulceration and a history of chronic venous insufficency. He had a large non-healing venous stasis ulcer of the left lower extremity with extensive heterotopic ossification discovered intraoperatively. The patient was managed with serial wound debridement, innovative woundcare and eventual split thickness skin grafting that achieved limb salvage despite the complexity of his wound. Our discussion focuses on the epidemiology, pathophysiology, diagnostic work-up and management of heterotopic ossification in the setting of chronic venous insufficiency. We propose that heterotopic ossification be included in any future modifications of the clinical, aetiology, anatomy and pathophysiology system classification as a complication of chronic venous disease.

Low-power laser therapy for repairing acute and chronic-phase bone lesions

To evaluate the therapeutic activity of low-power laser (InGaAlP: 670nm/30mW), at doses of 90J/cm2, on the process of acute and chronic-phase repair of bone lesions of Wistar rats. Sixty-three adult males were divided into nine groups subjected to bone injury, in order to form the following treatments: T1 (control); T2 (acute-phase); T3 (chronic-phase) which were subdivided into three subgroups (n=7), analyzed on the 9th, 17th and 28th days post-surgery, after a period of daily treatment with laser. The animals with acute-phase treatment presented a more extensive endochondral ossification process. Laser-treated animals showed significant increases in serum alkaline phosphatase levels and had an effect on biomechanical property, resulting in a gradual increase in bone stiffness. Laser therapy aided the bone consolidation process and favored the physiopathologic mechanisms involved in bone tissue repair, and its effects were more prominent when treatment started during the acute phase of the injury.

Gastric neuroendocrine tumor with extensive ossification

A 40-year-oldman underwent endoscopic ultrasound (EUS) because of suspected submucosal gastric tumor diagnosed after an episode of severe bleeding (● Fig.1). EUS revealed a well-delineated, 18-mm hypoechogenic lesion in the submucosa with a calcified area inside it (● Fig.2, ● Video1). Three lymph nodes near the celiac trunk showed the same characteristics of the gastric lesion: well-delineated and hypoechogenic, with central calcification (● Fig.3, ● Video1). A fine-needle aspiration (FNA) biopsy of the largest lymph node (14mm) was carried out using a 22-G needle, and histological examination revealed reactive lymphadenitis. The patient was referred for surgery, which showed an ulcerated submucosal tumor in the anterior gastric wall with pathological lymph nodes in the coronary gastric chain. The finding of the intraoperative study was a neuroendocrine gastric tumor (● Fig.4) with nodal neuroendocrine metastasis. All the regional lymph nodes were removed and a total gastrectomy was carried out. An intraoperative ultrasound examination was done to rule out any pancreatic or duodenal lesions. Microscopically, the tumor consisted of uniform, small cells with round or oval nuclei and moderate atypia, lying in nests and within the bone trabeculae. The number of mitoses was 4 per 10 high power field (HPF). Extensive stromal bone formation was seen within the tumor (● Fig.5). The tumor cells stained positive for cytokeratin, chromogranin A (● Fig.6), synaptophysin, enolase, and CD56, and the index of tumoral proliferation was 15%. Final histopathologic diagnosis was neuroendocrine tumor G2 (World Health Organization [WHO] classification, 2010). Most gastric neuroendocrine tumors are multiple and associated with hypergastrinemia. Solitary tumors have a poor prognosis [1]. To our knowledge, there are only four reports of gastric carcinoid tumors with ossification [2–5]. We report a case of a type 3 (G2) neuroendocrine gastric tumor with lymph node metastases with ossification diagnosed with EUS.

Extensive Heterotopic Ossification After Suspensory Cortical Fixation of Acute Distal Biceps Tendon Ruptures

Suspensory cortical fixation is commonly used for distal biceps tendon repair and reconstruction with one of several commercially available devices. The single-incision approach typically used with these devices is believed to have a lower incidence of heterotopic ossification than the dual-incision technique, but the true incidence of heterotopic ossification is unknown. The role of chemotherapeutic or radiation prophylaxis is undefined. We have identified 4 cases of extensive heterotopic ossification after biceps fixation with a suspensory button and single-incision approach. Surgeons should be aware of this potential complication when using suspensory cortical buttons for distal biceps fixation.

Early Presentation of Heterotopic Ossification Mimicking Pyomyositis - Two Case Reports -

Early diagnosis and treatment of heterotopic ossification (HO) is essential to the prevention of complications. It is difficult to diagnose HO in its initial phase because non-specific clinical manifestations, laboratory findings and imaging findings of immature HO may mimic other diseases such as cellulitis, osteomyelitis, thrombophlebitis, deep vein thrombosis and local infection with abscess. We experienced two cases of HO, which were misdiagnosed as pyomyositis at first by clinical signs and MRI findings indicating the deep infection; the extensive intramuscular ossification appeared later on. We observed an increase of C-reactive protein and creatine kinase followed by the elevation of alkaline phosphatase with abnormal triphasic bone scan. The trajectory of these biomarkers was analyzed to get more insight into the early stages of HO along with the imaging findings. Although our cases cannot be generalized as typical of immature HO, they clearly demonstrate that the change of specific biomarkers with a careful history taking and physical examination should be noted to detect HO as early as possible while avoiding confusion with other mimicking conditions.

Idiopathic diffuse pulmonary ossification, an incidental finding at autopsy: a case report and literature review

Idiopathic diffuse pulmonary ossification is a rare condition characterised by widespread osseous metaplasia within the lungs. It is usually asymptomatic and often diagnosed at autopsy. There have been a limited number of case reports in the literature. This report presents a case of idiopathic diffuse pulmonary ossification diagnosed at autopsy in a 76-year-old gentleman who died of a ruptured myocardial infarct. Macro-scopically the lungs appeared to show extensive parenchymal ossification. The presence of heterotopic bone was confirmed histologically. A review of published literature on this unusual entity is presented.