DNA Mutational and Copy Number Variation Profiling of Primary Craniofacial Osteosarcomas by Next-Generation Sequencing.

BACKGROUND: Craniofacial osteosarcomas (CFOS) are uncommon malignant neoplasms of the head and neck with different clinical presentation, biological behavior and prognosis from conventional osteosarcomas of long bones. Very limited genetic data have been published on CFOS. METHODS: In the current study, we performed comprehensive genomic studies in 15 cases of high-grade CFOS by SNP array and targeted next generation sequencing. RESULT: Our study shows high-grade CFOS demonstrate highly complex and heterogenous genomic alterations and harbor frequently mutated tumor suppressor genes TP53, CDKN2A/B, and PTEN, similar to conventional osteosarcomas. Potentially actionable gene amplifications involving CCNE1, AKT2, MET, NTRK1, PDGFRA, KDR, KIT, MAP3K14, FGFR1, and AURKA were seen in 43% of cases. GNAS hotspot activating mutations were also identified in a subset of CFOS cases, with one case representing malignant transformation from fibrous dysplasia, suggesting a role for GNAS mutation in the development of CFOS. CONCLUSION: High-grade CFOS demonstrate highly complex and heterogenous genomic alterations, with amplification involving receptor tyrosine kinase genes, and frequent mutations involving tumor suppressor genes.

Melanotic neuroectodermal tumor of infancy arising in the skull: a case report.

Melanotic neuroectodermal tumor of infancy is a rare and usually benign neoplasm occurring in children of young age. This pigmented tumor typically presents in the head and neck region, but other locations may be involved. We report in this article a rare case of a 3-month-old girl presenting with a slowly growing mass localized in the anterior fontanelle. The patient's magnetic resonance imaging (MRI) showed a mass extending both extracranial and intracranial, and compressing the adjacent structures. The patient underwent subtotal resection of the mass and a histological study confirmed the diagnosis of melanotic neuroectodermal tumor of infancy. The patient presented later on with a recurrence. An early diagnosis and surgical management for these tumors remain the only guarantees to limit the progression and prevent their recurrence and metastasis.

Rare Presentation of Rapidly Involuting Congenital Hemangioma of the Skull: A Case Report.

BACKGROUND Rapidly involuting congenital hemangioma (RICH) of the fetal skull is an extremely rare vascular disease which undergoes proliferation only in utero and progresses with maximal size at birth. RICH can be detected by prenatal imaging but is easily misdiagnosed. CASE REPORT A 28-year-old nulliparous woman was referred at 38 weeks of gestation for routine screening with obstetric ultrasonography. The ultrasonography revealed a female fetus with a previously undetected head tumor (32×22 mm). Certain unusual sonographic features were observed: the lesion was fusiform, with a wide base adjacent to the frontal bone. Tumor growth appeared to be toward the brain parenchyma rather than outwards (ie, toward the skull), which suggested that the mass may have been derived from the skull. The mass may have remained undiagnosed due to its small size or due to the superimposition of the skull in poor quality ultrasound images. On the basis of ultrasound findings, the lesion was diagnosed as an intracranial tumor, but fetal MRI findings led to the suspicion of RICH of the fetal skull. Finally, the patient was followed up until 1 year after birth, by which time the lesion had completely disappeared. CONCLUSIONS Careful evaluation of prenatal ultrasound is necessary to ensure detection of any mass adjacent to the skull, and the ultrasonography technician should carefully examine the features of any suspected mass to diagnose it correctly to avoid affecting the treatment strategy.

Desmoplastic fibroma of the pediatric cranium with CTNNB1 mutation: case report and literature review.

PURPOSE: Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature. CASE PRESENTATION: A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22 months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg). CONCLUSION: Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF.

Misdiagnosed long-standing unilateral nasal obstruction: ossifying fibroma of the inferior turbinate.

A man in his 20s presented with complaints of unilateral nasal obstruction for the past 6 years that progressively worsened leading to irrational use of over-the-counter nasal decongestants. With the worsening of symptoms, a non-contrast CT was done. It showed a dense expansile sclerotic lesion of the right inferior turbinate, which was excised endoscopically. Cemento-ossifying fibromas of the inferior turbinate are rare and require assessment and surgical excision to relieve the symptom of nasal obstruction. It derives its name from the variable proportions of fibrous and mineralised tissue present in it and exclusively develops in the craniofacial region. It can be surgically managed by an endoscopic, an endonasal non-endoscopic (with a speculum) or an open approach (lateral rhinotomy, sublabial approach or mid-facial degloving). Here, we present how such a case was detected and managed surgically by the endoscopic approach, which is a minimally invasive option with shorter hospital stay and early recovery.

Cemento-ossifying fibroma transforming to osteosarcoma.

Ossifying fibroma is a type of fibro-osseous lesion categorised into cemento-ossifying fibroma and juvenile ossifying fibroma. Malignant transformation of fibro-osseous lesions is documented especially for fibrous dysplasia, but scarcity is seen when we search for malignant transformation of ossifying fibroma. Thus, we are presenting an extremely rare case of cemento-ossifying fibroma transforming into osteosarcoma with long sequential radiographic details.

Long-Term Survival after Primary Ewing's Sarcoma of the Skull with Intracranial Extension.

BACKGROUND AND OBJECTIVE: Primary Ewing's sarcoma of the skull is a very rare malignant neoplasm, predominantly occurring in children and adolescents. We describe here the clinical, neuroradiologic, and histopathologic features of a patient with primary Ewing's sarcoma of the skull and discuss the standards of therapy for this type of tumor. CLINICAL PRESENTATION: This 18-year-old male patient presented with a primary Ewing's sarcoma of the skull, involving the dura of the frontal and parietal lobes of the left cerebral hemisphere. He was treated with gross total surgical excision of tumor, skull reconstruction, chemotherapy, and irradiation. Twelve years after the surgery, the patient has no evidence of local recurrence or distant metastases. Radical surgical excision of the primary tumor with safety margins is thought to play a role in the favorable clinical course. CONCLUSION: The presented case is the longest surviving patient after treatment of primary Ewing's sarcoma of the skull bone. This rare type of tumor may allow better survival rates under adequate management than sarcoma elsewhere in the body.

Single-port Endoscopic Removal of Forehead Osteoma: An Otolaryngologist's Procedure.

For otolaryngologists, single-port endoscopic removal of forehead osteoma draws upon a familiar skill set and is a robust technique for complete tumor removal with excellent cosmesis. Laryngoscope, 134:2194-2197, 2024.

[Primary intraosseous cavernous hemangioma of the cranium: a case report]. / Pervichnaya vnutrikostnaya kavernoznaya gemangioma kostei cherepa: obzor literatury i opisanie klinicheskogo nablyudeniya khirurgicheskogo lecheniya.

Primary intraosseous cavernous hemangioma (PICH) is a rare benign vascular tumor. This neoplasm is common in the spine and less common in skull. Toynbee J. first described this tumor in 1845. PICH of the cranium does not always have typical X-ray features and should be always differentiated with other more common skull lesions. Surgical resection is preferable since total resection is followed by favorable prognosis. We present a 65-year-old patient with asymptomatic tumor of the right parietal bone. CT revealed osteolytic lesion that required total resection and skull repair. Histopathological analysis revealed intraosseous cavernous hemangioma.

Lesiones de cráneo en el mieloma múltiple / Skull Lesions in Multiple Myeloma

Fig A) Radiografía de cráneo en proyección lateral: se observan múltiples lesiones radiolúcidas distribuidas en todo el cráneo. B) Acercamiento donde se evidencian múltiples lesiones en sacabocado, compatibles con mieloma múltiple(AU)

Spontaneous Regression of Ossifying Fibroma in the Oral and Maxillofacial Region: A Rare Case With 4-Year Follow-Up.

The case presented in this study is a rare instance of an ossifying fibroma (OF), a type of benign fibro-osseous lesions, spontaneously regressed without surgical intervention. A 9-year-old boy with an intraosseous lesion in the left maxilla was diagnosed as OF. The surgeon suggested surgical excision, but due to personal reasons, the patient and his parents deferred the surgery and opted for regular follow-up. During a 4-year follow-up, the surgeon found that the lesion had significantly decreased in size and the facial deformity had remitted. At the latest follow-up, the deformity of his left face became almost unnoticeable, and the lesion seemed to be subtle on cone-beam computed tomography images. This case highlights the possibility of spontaneous regression of OF. This phenomenon may occur due to the teeth eruption, which can lead to the formation of periodontal ligaments and engage the regression of OF.

Kaposiform hemangioendothelioma of skull base with dura invasion in a pediatric patient: a case report.

Kaposiform hemangioendothelioma is an extremely rare vascular tumor which shows aggressive local growth. We present a case of rapid growing vascular skull tumor with dura invasion in a pediatric patient with neurofibromatosis type 1. A 14-year-old male complained of headache and dizziness for 1 month after minor head trauma. Brain magnetic resonance imaging (MRI) revealed a 5-cm-sized tumor in the left frontotemporal bone with internal hemorrhage and cystic changes. The gross total resection of tumor was done. At the 7-month follow-up, brain MRI revealed a recurrent skull tumor with intracranial dura mass. He underwent second surgery, and the pathologic diagnosis was suggestive of Kaposiform hemangioendothelioma. For this vascular proliferative tumor, mTOR inhibitor was treated for 6 months, and there was the recurred nodular-enhancing mass along the sphenoid ridge. After additional 2 months of medication, the following MRI revealed a decreased nodular-enhancing mass.

Endoscopic Approach for Resection of Frontal Forehead Osteoma: Technical Case Report Instruction.

Forehead osteomas are benign bone tumors. They are frequently associated with exophytic growth in the outer table of the skull, causing cosmetic disfigurement of the face.1-9 The objective of this study was to present the efficacy and feasibility of the endoscopic treatment of forehead osteomas by presenting a case report with details of the surgical technique. A 40-year-old female patient presented with aesthetic complains of a progressing bulge in the forehead. A computed tomography scan with 3-dimensional reconstruction showed bone lesions on the right side of the forehead. The patient underwent surgery under general anesthesia with no noticeable incision, which was planned 2 cm behind the hairline in the midline because the osteoma was close to the midline plane on the forehead (Video 1). A retractor coupled with a 4-mm channel for endoscopy and a 30-degree optic was used to dissect, elevate the pericranium, and locate the 2 bone lesions in the forehead. The lesions were removed using a chisel, endoscopic facelifting raspatory, and a 3-mm burr drill. The tumors were resected completely, resulting in good cosmetic outcomes. The endoscopic approach for treating forehead osteomas is less invasive and facilitates complete removal of tumors, which results in good cosmetic outcomes. Neurosurgeons should consider and add this feasible approach to enhance their surgical armamentarium.

Combined endoscopic endonasal & transoral approach to transpatial lesion involving the infratemporal fossa and masticator space: A case study and literature review / Abordaje endoscópico combinado endonasal y transoral a una lesión transespacial involucrando la fosa infratemporal y el espacio masticador: Reporte de caso y revisión de la literatura

Transpatial skull base lesions involving the infratemporal fossa (ITF) are challenging due to the complex neurovascular structures of the region. Open approaches have traditionally been utilized to access these spaces. We present a 55-year-old woman presented with a mesenchymal mass involving the left ITF and masticator space. A combined endoscopic endonasal transpterygoid approach was performed followed by an endoscopic transoral-transmandibular corridor to access and resect the tumor. The post-operative course was unremarkable with no recurrence during her follow-up. Combined endoscopic approaches for transpatial tumor resection offered sufficient exposure to access safely each space (AU)

Las lesiones de la base craneal con una distribución transespacial e involucrando la fosa infratemporal (ITF) representan un desafío debido a las complejas estructuras neurovasculares de dicha región. Los abordajes abiertos han sido empleados tradicionalmente para acceder a estas regiones. Presentamos el caso de una mujer de 55 años que consultó por una lesión mesenquimal localizada en la ITF izquierda y en el espacio masticatorio. Se realizó un abordaje combinado endoscópico transpterigoideo endonasal seguido de un abordaje endoscópico transoral-transmandibular para acceder y resecar el tumor. El curso postoperatorio fue anodino, y no ha presentado recidiva con 21 meses de seguimiento. Los abordajes endoscópicos combinados para la resección de lesiones tumorales, con una distribución transespacial involucrando la ITF, ofrecen una exposición suficiente para acceder de forma segura a cada espacio (AU)

Transillumination of an Anterior Fontanelle Dermoid Cyst.

Dermoid cysts are slowly growing benign lesions of ectodermal tissue that often occur in the anterior fontanelle. Clinicians often rely on a negative transillumination test to begin the process of correctly diagnosing a dermoid cyst. However, here the authors present a case of a 7-month-old girl who presents with a transilluminating dermoid cyst.

Genomic Profiling of the Craniofacial Ossifying Fibroma by Next-Generation Sequencing.

BACKGROUND: Ossifying fibroma (OF) of the craniofacial skeleton is a fibro-osseous lesion characterized by various patterns of bone formation in a cellular fibroblastic stroma. The molecular landscape of OF remains mostly unknown. There are a few known pathogenic abnormalities in OF, including HRPT2 mutations in conventional OF and SATB2 translocations in juvenile psammomatoid OF. On the other hand, conflicting reports exist regarding MDM2 gene amplification and chromosomal copy number alterations (CNA) in OF. METHODS: Surgically removed biopsies and curettage specimens from OF patients were obtained. Clinical, radiographic, and pathologic features of tumors were reviewed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded blocks of tumor tissue. Capture-based DNA next-generation sequencing targeting the coding regions 529 cancer genes and select introns was performed. RESULTS: We identified 17 OF cases from 8 male and 8 female patients with mean age of 22 years (range 1-58 years). Nine case occurred in the gnathic bones and 8 in the extragnathic craniofacial bones. These cases included 3 juvenile psammomatoid OF, 6 conventional OF and 8 juvenile trabecular OF. Large-scale CNAs were present in 6 of 17 cases. Seven cases (41%) had focal amplifications including FOSB (n = 2, 11%), FOS (n = 4, 23%), COL1A1 (n = 4, 23%) and TBX3 (n = 5, 29%). Three cases (17%) had pathogenic CDC73 mutations. No cases showed focal MDM2 amplification. CONCLUSIONS: Here, we provided a comprehensive molecular characterization of OF that reveals a heterogeneous genetic profile with occasional large-scale CNAs (n = 6, 35%). FOS, FOSB, and TBX3 genes that regulate AP-1 transcriptional complex are frequently altered in OF (n = 7, 41%), chiefly in juvenile trabecular OF. These genes encode transcription factors that act as downstream effectors of the MAP kinase signaling pathway. MDM2 amplification is an exceedingly rare event in OF, if present at all, so identification of this event should continue to raise concern for low-grade gnathic osteosarcoma. In summary, our findings suggest that OF represents a heterogeneous group of tumors at the genetic level but dysregulation of the AP-1 pathway may play a role in pathogenesis of juvenile trabecular OF.

A Clinical, Radiological and Histopathological Review of 74 Ossifying Fibromas.

BACKGROUND: Ossifying fibroma (OF) is a fibro-osseous lesion of the jaws and craniofacial bones. Accurate diagnosis can be challenging due to significant overlap of clinicopathological features. This study aimed to evaluate the clinical, radiological and histological features that can aid in diagnosis and identify characteristics that allow categorisation into the three subtypes: juvenile trabecular, psammomatoid and cemento-ossifying OF. METHODS: A total of 74 cases of OF were systematically reviewed for their principle features. Of these, 46 cases were evaluated for their radiographic features including size, location and relationship to the teeth. Histological assessment and stereological point counting were performed in 69 cases to assess the pattern, type and proportion of calcification, the nature of the stroma, the border of the lesion and the presence of secondary changes. Fisher's exact test and Chi-squared tests were used to determine associations between clinicopathological parameters and maxillary, mandibular, odontogenic, non-odontogenic and psammomatoid or trabecular lesions. RESULTS: OF showed a female predilection (F: M; 2:1) and a slight bimodal age distribution with peaks in the second (23%) and fourth decades (27%) (Mean age: 32.4 years). 83% of cases presented as an intra-oral swelling, with the mandible being the most common site (73%). Histologically, a range of morphological patterns were seen, with 50% of cases showing mixed trabecular and psammomatoid features. However, there were no significant differences between the variants of OF in terms of age, gender or histological features. CONCLUSION: Histological features of OF cannot be used to differentiate between the subtypes.

Multiple primary intraosseous meningioma mimicking fibrous dysplasia: a case report.

Primary intraosseous meningioma (PIM) is a rare subtype of primary extradural meningiomas. These rare ectopic meningiomas have been usually reported in the frontotemporal regions of the calvarium, orbits, and anterior cranial fossa. We report a case with bilateral tumors located in frontoparietal regions of calvarium. Our initial diagnosis was fibrous dysplasia but the lesions were seen to expand under follow-up. One was resected and the histopathological diagnosis was PIM. This is the second reported case of multiple PIM.