Ex vivo model of pathological calcification of human aortic valve.

The development of drug therapy for the pathological calcification of the aortic valve is still an open issue due to the lack of effective treatment strategies. Currently, the only option for treating this condition is surgical correction and symptom management. The search for models to study the safety and efficacy of anti-calcifying drugs requires them to not only be as close as possible to in vivo conditions, but also to be flexible with regard to the molecular studies that can be applied to them. The ex vivo model has several advantages, including the ability to study the effect of a drug on human cells while preserving the original structure of the valve. This allows for a better understanding of how different cell types interact within the valve, including non-dividing cells. The aim of this study was to develop a reproducible ex vivo calcification model based on valves from patients with calcific aortic stenosis. We aimed to induce spontaneous calcification in valve tissue fragments under osteogenic conditions, and to demonstrate the possibility of significantly suppressing it using a calcification inhibitor. To validate the model, we tested a Notch inhibitor Crenigacestat (LY3039478), which has been previously shown to have an anti-calcifying effect on interstitial cell of the aortic valve. We demonstrate here an approach to testing calcification inhibitors using an ex vivo model of cultured human aortic valve tissue fragments. Thus, we propose that ex vivo models may warrant further investigation for their utility in studying aortic valve disease and performing pre-clinical assessment of drug efficacy.

Calcifying Odontogenic Cyst Associated with Complex Odontoma: Report of a Rare Case.

Calcifying odontogenic cyst, also known as Gorlin cyst is a rare benign cystic lesion primarily found in the jawbones, accounting less than 1% of odontogenic cysts. It can be associated with odontogenic tumors such as odontomas. We report a rare case of COC associated with complex odontoma in a young patient and discuss its clinical features, diagnosis, and treatment options. An 18-year-old female patient presented with a painless radiopaque lesion of the right mandibular bone at Oral Medicine and Oral Surgery department. Radiographs revealed irregular tooth-like structures in the canine-premolar area. The lesion was surgically removed, and histopathology confirmed COC with a complex odontoma. As of the World Health Organization's 2022 definition, COC is a developmental odontogenic cyst characterized by calcified ghost cells. It typically affects individuals during their second and third decades of life, with no gender preference, almost equally in the maxilla and the mandible. The main treatment is total enucleation, with a generally favorable prognosis. Histopathology is essential for diagnosis due to its mimicry of other jaw conditions. Long-term follow-up is needed to prevent recurrences.

An unusual presentation of calcifying odontogenic cyst with literature review.

The calcifying odontogenic cyst (COC) is an uncommon developmental odontogenic cyst, the oral counterpart of Malherbe's cutaneous calcifying epithelioma (pilomatricoma). This article presents two unique cases of calcifying odontogenic cysts each exhibiting distinctive histopathological features and its literature review. One case with an unexpected finding of cholesterol granuloma (CG), a rare occurrence in non-inflammatory cysts within an unusual location between two maxillary central incisors. One more instance involves the presence of a compound odontome in conjunction with COC. The cases underscore the clinical and histopathological diversity of COC and highlight the importance of radiological and histopathological assessments for accurate diagnosis. The unexpected association of COC with cholesterol granuloma challenges traditional diagnostic expectations. Additionally, the second case suggests that COCs may warrant sub-categorization to better understand their varied presentations and biological behavior. This article contributes to the expanding knowledge of COC, emphasizing the significance of documenting rare cases to enhance comprehension of its nature, pathogenesis, and oral cavity origin.

Comparative Morphology of Skeletal Development in Homo sapiens and Raja asterias: Divergent Stiffening Patterns Due to Different Matrix Calcification Processes.

Before calcification begins, the early embryonic and fetal skeletal development of both mammalian Homo sapiens and the chondrichthyan fish Raja asterias consists exclusively of cartilage. This cartilage is formed and shaped through processes involving tissue segmentation and the frequency, distribution, and orientation of chondrocyte mitoses. In the subsequent developmental phase, mineral deposition in the cartilage matrix conditions the development further. The stiffness and structural layout of the mineralized cartilage have a significant impact on the shape of the anlagen (early formative structure of a tissue, a scaffold on which the new bone is formed) and the mechanical properties of the skeletal segments. The fundamental difference between the two studied species lies in how calcified cartilage serves as a scaffold for osteoblasts to deposit bone matrix, which is then remodeled. In contrast, chondrichthyans retain the calcified cartilage as the definitive skeletal structure. This study documents the distinct mineral deposition pattern in the cartilage of the chondrichthyan R. asterias, in which calcification progresses with the formation of focal calcification nuclei or "tesserae". These are arranged on the flat surface of the endo-skeleton (crustal pattern) or aligned in columns (catenated pattern) in the radials of the appendicular skeleton. This anatomical structure is well adapted to meet the mechanical requirements of locomotion in the water column. Conversely, in terrestrial mammals, endochondral ossification (associated with the remodeling of the calcified matrix) provides limb bones with the necessary stiffness to withstand the strong bending and twisting stresses of terrestrial locomotion. In this study, radiographs of marine mammals (reproduced from previously published studies) document how the endochondral ossification in dolphin flippers adapts to the mechanical demands of aquatic locomotion. This adaptation includes the reduction in the length of the stylopodium and zeugopodium and an increase in the number of elements in the autopodium's central rays.

Rare calcifying fibrous pseudotumor of the peritoneum in an adult woman as a random finding during laparoscopic surgery.

Calcifying fibrous pseudotumors (CFT) are rare benign lesions diagnosed by histological and immunohistochemical studies. Our case presents a rare detection of a CFT in the parietal peritoneum. These lesions can be falsely interpreted as myomas or adnexal masses and thus gynecologists should be aware of the existence of CFTs.

Calcifying Odontogenic Cyst Presenting Odontogenic Keratocyst-Like Areas: A Rare Case Report.

An 81-year-old male patient presented with a well-demarcated, unilocular radiolucent lesion in the right mandibular body, identified during a routine radiographic examination. Based on the clinical hypothesis of a residual cyst, enucleation with curettage was performed, and the specimen was submitted for histopathological analysis. Microscopically, the cystic lesion was predominantly lined by ameloblastomatous epithelium with numerous ghost cells and dentinoid. Additionally, other cystic cavities lined by stratified squamous epithelium with corrugated parakeratin were observed in the fibrous capsule. Based on these features, a final diagnosis of a calcifying odontogenic cyst with odontogenic keratocyst-like areas was established. No recurrence was observed over a 9-year follow-up period. The association of a calcifying odontogenic cyst with odontogenic keratocyst or odontogenic keratocyst-like areas is very rare. To date, this is the second case report in the literature presenting these findings.

Peripheral calcifying odontogenic cyst in maxillary anterior gingiva: A case report.

BACKGROUND: Calcifying odontogenic cysts (Gorlin cysts) most commonly present centrally and have only rarely been reported in peripheral locations. The purpose of this report is to describe a new case of peripheral calcifying odontogenic cyst (PCOC) occurring in the anterior maxillary gingiva and to review the management and differential diagnosis of such a lesion. METHODS: A 37-year-old female presented with a long-standing submucosal nodule on the gingiva between the maxillary central incisors, with asymptomatic growth over the last three years. Following an initial incisional biopsy, a diagnosis of PCOC was established. To exclude the possibility of a central process, a corresponding small field of view cone beam CT scan was obtained and the patient returned for a 6 mm excisional biopsy to the depth of the periosteum. RESULTS: Results of these additional assessments supported the original diagnosis of PCOC. Following uneventful healing of the second biopsy, no recurrence or other clinical findings were noted at 1-year follow-up. CONCLUSION: While rare, the peripheral variant of calcifying odontogenic cyst, and other peripheral counterparts to recognized central cysts and tumors, should be considered in a differential diagnosis for a benign gingival nodule. Gingival tissue should be submitted for histologic evaluation to ensure a neoplastic process is not present. KEY POINTS: Various lesions may present on the gingiva as a "bump"; these can represent common clinical entities, such as pyogenic granuloma, peripheral ossifying fibroma, peripheral giant cell granuloma, and fibroma, or more rare conditions that may not be adequately considered in the differential diagnosis. A rarely documented case of peripheral calcifying odontogenic cyst (PCOC; Gorlin cyst) on the maxillary anterior gingiva of an adult female is reported here and compared with the few other similar PCOC cases in the literature. A biopsy of gingival lesions is always necessary to establish the correct diagnosis and provide the appropriate treatment. PLAIN LANGUAGE SUMMARY: Several different lesions can appear on the gingiva (gums). Some are quite common, and some are rare. This report documents the occurrence of a new case of calcifying odontogenic cyst (Gorlin cyst), a type of cyst that has been rarely found outside the jawbone, presenting as a "bump" on the gingiva between the maxillary central incisor teeth of an adult female. Because of the patient history, a peripheral calcifying odontogenic cyst (PCOC) was not initially suspected. Following a biopsy, a PCOC diagnosis was given. The possibility of a lesion within the bone was then excluded by an X-ray (cone beam CT) scan examination. A second, more extensive biopsy confirmed the diagnosis and the removal of the lesion. The patient had no complications or recurrence for the following 12 months. This case highlights the need to always biopsy lesions presenting on the gums to obtain a proper diagnosis and provide the correct treatment.

[Comparison of the efficacy of phlebotomy under touch pain point and ultrasound-guided puncture decompression in the treatment of acute calcific supraspinatus tendinitis].

OBJECTIVE: To compare the efficacy of blood letting under pain point touch and ultrasound-guided puncture decompression in the treatment of acute supraspinatus muscle calcifying tendinitis. METHODS: From January 2020 to January 2023, 45 patients with acute supraspinatus muscle calcifying tendinitis were selected and divided into treatment group and control group. In the treatment group, a total of 22 patients were treated with ultrasound-guided puncture decompression, including 16 females and 6 males, aged from 20 to 64 years old(39.31±5.80) years old, 11 on the left shoulder and 11 on the right shoulder. In the control group, there were 23 cases, including 15 females and 8 males, aged from 19 to 66 years old (40.67±6.13) years old, 12 on the left shoulder and 13 on the right shoulder. The treatment was treated with pain point touch bloodletting therapy. The visual analog scale (VAS) pain score, University of California, Los Angeles(UCLA) shoulder system score and shoulder Constant-Murley score were used to evaluate the therapeutic effect before treatment, 1 weeks, 1 month and 3 months after treatment, respectively. RESULTS: One patient in the control group gave up follow-up for personal reasons after 1 week of treatment, and the other 44 patients completed all follow-up. Six months after treatment, there were no recurrence cases in both groups. After statistical analysis, VAS pain score, UCLA score and Constant-Murley score of the treatment group and the control group were significantly different from those before treatment (P<0.05), and the improvement was more obvious in the treatment group. There was no statistical significance between the two groups (P>0.05). CONCLUSION: Bloodletting under pain point touch and ultrasound-guided puncture decompression are effective in the treatment of acute calcific supraspinatus tendinitis, with simple operation and low cost, which can effectively reduce local pain and effectively improve shoulder joint function. Primary hospitals can selectively operate treatment according to their own conditions.

Successful thoracoscopic enucleation of a calcifying fibrous tumor of the lower mediastinum in a young woman.

BACKGROUND: Calcifying fibrous tumor (CFT) arising from the pleura is a relatively rare benign lesion in young and middle-aged adults. We report a 31-year-old woman with pleural CFT who underwent successful complete thoracoscopic enucleation. CASE PRESENTATION: An asymptomatic woman presented with a mass in the right lower lung field that was incidentally detected on a chest X-ray during a routine medical checkup. Chest computed tomography showed a well-defined mass in the lower mediastinum, with a maximum diameter of approximately 5.5 cm. Esophagogastroduodenoscopy showed no abnormal findings in the esophagus. An endoscopic ultrasonography (EUS) revealed a well-defined tumor with no internal blood flow. EUS-fine needle aspiration failed to establish a definitive diagnosis. Therefore, thoracoscopic tumor enucleation was performed for diagnostic and therapeutic purposes. Based on the histopathological findings of the resected specimen, the presence of a tumor with a high fibrous component in a young woman, and the identification of granulomatous calcifications, a diagnosis of CFT was established. CONCLUSIONS: Complete thoracoscopic tumor enucleation was successfully performed for CFT arising from the pleura in a young adult woman.

Epidemiology of odontogenic tumours and selected cysts diagnosed at a single New Zealand oral pathology centre- A 15-year retrospective study.

PURPOSE: This research aimed to investigate the relative frequency of odontogenic tumours (OT) and selected odontogenic cysts in a single oral pathology center in New Zealand from 2008 to 2023. METHODS: Histopathological records from the Oral Pathology Centre, University of Otago (2008-2023) were examined to identify OT. Odontogenic keratocyst (OKC) and calcifying odontogenic cyst (COC), previously classified as OT were also included. Patient demographics, clinical details and histopathologic diagnoses were recorded. Data were analyzed using SPSS. RESULTS: Of the 34,225 biopsies over the 15-year period, 1.8% were identified as OTs, COC and OKCs and accounted for 47%, 1.5% and 51.5% respectively. The most prevalent OT types were odontoma (43.7%), ameloblastoma (27%) and cemento-ossifying fibroma (7.5%). Malignant OT, ameloblastic carcinoma, constituted 1.4% of OT. The average age at diagnosis for OKC, COC and OT patients were 48.2 ± 20.9, 33.7 ± 23.3 and 28.9 ± 19.3 years. Overall, male and mandibular site predilections were observed. Recurrence of OKC and ameloblastoma occurred in 15.2% and 13.7% of patients. The time for recurrence for OKC and Ameloblastoma were 61.7 ± 56.5 months and 122 ± 152 months respectively. CONCLUSION: The demographic features and range of OT, COC and OKC in New Zealand align with those of other western countries. The study also confirms need for long term follow up for patient with OKC and ameloblastoma.

Pilomatrixoma of the Ankle: A Case Report.

Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a rare benign skin tumor originating from hair follicle matrix cells. It typically presents as a firm, painless subcutaneous nodule, most commonly found in the head, neck, and upper extremities. Pilomatrixoma can occasionally appear in atypical locations, posing a diagnostic challenge due to its nonspecific clinical presentation. A 43-year-old female presented with a painless, slowly enlarging mass on the lateral side of her left ankle, which had been present for approximately one year. Physical examination revealed a firm, well-circumscribed subcutaneous nodule measuring about 2 cm in diameter with normal overlying skin. An MRI of the left ankle demonstrated a well-circumscribed, subcutaneous mass with heterogeneous signal intensity, consistent with calcifications, suggesting pilomatrixoma. A fine-needle aspiration biopsy confirmed the presence of basaloid cells, shadow cells, and areas of calcification. The lesion was surgically excised, and histopathological examination validated the diagnosis of pilomatrixoma. The patient had an uneventful postoperative course, with no recurrence at the six-month follow-up. This case underscores the importance of considering pilomatrixoma in the differential diagnosis of subcutaneous nodules, even in unusual locations. A comprehensive diagnostic approach, including clinical evaluation, imaging, and histopathological examination, is essential for an accurate diagnosis. Surgical excision with clear margins is the treatment of choice, ensuring low recurrence rates and excellent patient outcomes. This report enhances the understanding of pilomatrixoma and highlights the necessity for a multimodal diagnostic strategy in managing this rare condition effectively.

Unravelling the mystery of the central dentinogenic ghost cell tumor- a rare case report and recurrent insights.

Dentinogenic ghost cell tumor (DGCT) is a rare benign neoplasm form of calcifying odontogenic cyst (COC) characterized by ghost cells. Although benign, it presents an aggressive behavior. DGCT accounts for 2% to 14% of all COCs and less than 0.5% of all odontogenic tumors. It is a benign odontogenic tumor despite its local invasion and the likelihood of recurrence. To detect recurrence, central DGCT patients must be monitored long-term. We present the case of a 51-year-old male who reported pain in the right upper back tooth region. On examination, a soft to firm, bright red swelling was present in the buccal vestibule and gingival margin of the maxillary right first and second molar, which extended up to the palate. Histopathological analysis confirmed the diagnosis of a DGCT, which occurred in a previously treated calcifying odontogenic cyst. The case is reported here, along with a review of the literature update of such recurred instances in the past.

Case report: A large gastric calcifying fibrous tumor treated with endoscopic submucosal excavation.

Gastric calcifying fibrous tumor (CFT) is a rare benign mesenchymal tumor. Several previous studies have reported surgical resection for gastric CFT larger than 20mm for the difficulty in preoperative diagnosis. Here, we report a rare case of large gastric CFT treated with endoscopic submucosal excavation (ESE). A 70-year-old woman presented with recurrent epigastric pain and underwent endoscopy, which revealed a 35mm-sized submucosal tumor in the gastric body. ESE was performed after imaging examination and endoscopic ultrasonography. En bloc resection was achieved, but due to the specimen's substantial size and difficulty in mincing, it posed challenges for removal through the mouth. Finally, the specimen was temporarily placed in the stomach and was completely removed two days later. The diagnosis was confirmed based on pathological and immunohistochemical findings. There was no recurrence during the patient's 11-month follow-up. We provided a case report related to the diagnosis and endoscopic treatment for large gastric CFT. In addition, our experience of temporarily leaving a large postoperative specimen, considered a benign lesion, in the stomach for later removal was successful but requires appropriate timing to avoid blockage of the gastrointestinal tract.

Calcifying odontogenic cysts: A novel outlook on classification, diagnosis and management.

BACKGROUND: The Calcifying Odontogenic Cysts (COC) displays a wide range of clinical and histopathological variations as well as diverse biological behaviors. This diversity has led to confusion and disagreement regarding the terminology and classification of this lesion. The previous classification attempts to categorize COC into two concepts. The first concept, termed "monistic," suggests that all COCs are neoplastic despite the majority being cystic in structure and seemingly non-neoplastic. The second concept, known as "dualistic," posits that COC comprises two distinct entities: a cyst and a neoplasm. This research discusses various previous classifications of COC found in the literature and proposes a new, straightforward universal classification based solely on histopathology, aiming to facilitate understanding for surgeons. MATERIAL AND METHODS: Fifteen cases of COC have been collected with clinicopathological parameters including detailed information regarding patient demographics, symptoms, anatomical site, radiological characteristics, duration of evolution, recurrence, and types of histopathology according to the proposed classification. RESULT: A total of fifteen cases of COC were analyzed. According to the histological analysis of the proposed classification Type 1: 5 (33.3), Type II: 4 (26.6), Type III: 3(20), and Type IV:3(20) and recurrence in 3 (20 %) of cases. CONCLUSION: It simplifies the complexities arising from variations in the cystic linings of type IV of COC, which can be overlooked and have caused recurrence in the current research. Therefore, the key requirement for arriving at a validated and practical conclusion lies in the accurate histological classification of calcifying odontogenic cysts and their impact on treatment.

Calcifying Epithelial Odontogenic Cysts of the Anterior Maxilla: Report of Two Cases.

This article is a discussion of two cases of young adults with lesions in similar locations in the anterior maxilla, i.e., the canine-to-canine region, similar history, and comparable radiology. Both cases were histologically diagnosed as calcifying odontogenic cysts. Case 1 was a male aged 28 years with diffuse, firm left malar area facial swelling with pain in associated teeth for a month. Intraorally, he had a gingivo-vestibular swelling also extending palatally in the anterior left maxillary region extending from the distal surface of the left maxillary central incisor to the mesial surface of the left maxillary canine. The overlying mucosa was normal in appearance. The radiograph showed a large unilocular radiolucency in the affected region. The lesion was excised followed by curettage and primary closure. Case 2 was a female aged 25 years with a lumpy mass and pain in associated teeth since one year in the left canine-premolar region with an external swelling in the left ala of the nose region that extended superiorly to the zygomatic arch. The color of the skin as well as the intraoral mucosa was normal, and an orthopantomogram (OPG)revealed a unilocular radiolucency in the left maxillary canine-premolar region with resorption of premolar roots. Treatment included surgical enucleation and bone curettage. Both cases have been in follow-up for about a year and have shown non-incidental healing.

Multiple calcifying fibrous tumors from gastric and retroperitoneal tissue: A case report.

INTRODUCTION AND IMPORTANCE: Calcifying fibrous tumor (CFT) is a rare benign mesenchymal lesion that has been occurred in the gastrointestinal tract, especially occurs most commonly in the stomach and the small and large intestines. CASE PRESENTATION: 74-year-old woman was admitted to our hospital with complaints of epigastric discomfort. Whole-body computed tomography (CT) revealed a 2.2-cm mass with a 1.2-cm low-density area at the anterior wall in the gastric cardia and lesser omentum; however, no abnormal uptake at the same site was noted on positron emission tomography (PET). We performed laparoscopic tumor resection of the two sites. The postoperative course was good without complications. Histopathological findings revealed collagen fibrous granulation connective tissue and psammomatous calcification. Subsequently, the patient has been relapse-free for 6 months. CLINICAL DISCUSSION: CFT is a rare benign tumor that commonly occurs in soft tissues, such as the subcutaneous extremities and neck. In particular, development from the stomach and lesser omentum has never been reported. Our case was incidentally found on a general examination. In our case, CT showed a low-density area, MRI showed a low-intensity area, and PET examination showed no uptake; it was difficult to establish a preoperative diagnosis. Therefore, in our case, laparoscopic tumor resection was performed, with GIST as the differential diagnosis. CONCLUSIONS: We herein reported a rare gastric and lesser omentum CFT that was successfully treated by laparoscopic surgery. For curative treatment of CFT, complete surgical resection is necessary.

Conservative management of gynecomastia in Peutz-Jeghers syndrome: Case series and review of the literature.

Peutz-Jeghers syndrome (PJS) is a childhood-onset cancer predisposition syndrome that is associated with oral freckling and gastrointestinal polyposis. Male patients with PJS are at risk for large-cell calcifying Sertoli cell tumors in childhood. These tumors are estrogen-producing and can cause symptoms of precocious puberty, gynecomastia, and growth acceleration. Here we discuss our experience with spontaneous resolution or stabilization of breast enlargement without medical intervention in three patients with PJS and gynecomastia. These cases indicate that a watchful waiting approach can be considered in the management of gynecomastia in male children with PJS.

Pulmonary Calcifying Fibrous Tumor in a Pediatric Patient: A Case Report.

A calcifying fibrous tumor (CFT), also known as calcifying fibrous pseudotumor, is an uncommon non-cancerous neoplasm usually located in the gastrointestinal tract. Its location in the lung is extremely rare, and only a few case reports have been published. This case report describes our diagnostic approach in a 9-year-old male patient with an incidental pulmonary mass. The mass was initially misdiagnosed, requiring multiple imaging tests and interventions to obtain the definitive diagnosis of pulmonary CFT. This paper aims to contribute to the limited information available on pulmonary CFT by presenting detailed findings from computed tomography and magnetic resonance imaging.

Tumor fibroso calcificante intestinal: reporte de caso / Intestinal calcifying fibrous tumor: case report

El tumor fibroso calcificante (TFC) es una inusual lesión benigna de origen mesenquimal que puede presentar características similares a otros tumores más comunes. El caso involucra a una mujer de 36 años con un tumor en el yeyuno proximal, inicialmente sospechoso de ser un tumor del estroma gastrointestinal (GIST). Se realiza una resección quirúrgica, revelando un nódulo bien delimitado en el borde antimesentérico con características microscópicas típicas de TFC. Las células tumorales presentaban positividad para CD34 y negatividad para demás marcadores, diferenciándolo de otras neoplasias. El TFC puede confundirse con tumores más comunes debido a su apariencia, pero un diagnóstico preciso respaldado por inmunohistoquímica es esencial. La extirpación quirúrgica completa suele ser curativa. (AU)

Calcifying fibrous tumor (CFT) is a rare benign lesion of mesenchymal origin that may present similar characteristics to other more common tumors. We present the case of a 36-year-old woman with a tumor in the proximal jejunum, initially suspected to be a gastrointestinal stromal tumor (GIST). Surgical resection was performed, revealing a well-demarcated nodule at the anti-mesenteric border with microscopic features typical of a calcifying fibrous tumor. The tumor cells were positive for CD34 and negative for other markers, differentiating it from other neoplasms. Calcifying fibrous tumors can be confused with more common tumors because of its appearance, but an accurate diagnosis supported by immunohistochemistry is essential. Complete surgical excision is usually curative. (AU)