High-grade transformation of a polymorphous adenocarcinoma of the salivary gland: a case report and review of the literature.

Background: Polymorphous adenocarcinoma (PAC) represents the second most widespread neoplasm of the minor salivary glands. These tumors rarely develop a histological progression from low-grade to high-grade malignancy, named "high-grade transformation" (HGT). Only nine cases are described in literature. Case description: Here, we describe the case of a 76-year-old male patient with a PAC recurrence of the oral floor displaying HGT, and we explore the tumor cytomorphological features, genomic profiling, and the patient's clinical management. The tumor mass was characterized by poorly atypical cellular elements with vesicular nuclei and comedonecrosis foci. The growth pattern was predominantly solid, tubular, and cribriform. The lesion did not show microsatellite instability or targeted molecular alterations. The case was successfully treated with radical surgery followed by radiotherapy. Conclusion: We report for the first time the recurrence of a PAC with HGT arising in the oral floor after 20 years from the primary lesion. These preliminary data and the literature analysis enhance the knowledge of this extremely rare disease.

Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas.

Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed. Furthermore, NGS, microsatellite instability, and in silico analyses were carried out. RT-PCR identified the upregulation of CDH1, SLUG, MMP9, RAB22a, S100P, and LAPTM4b, representing promising biomarkers for this disease. Pharmacological profiling showed the highest sensitivity with anthracycline-based regimen in both 2D and 3D culture systems. NGS analysis detected RAB3IP-HMGA2 in frame gene rearrangement and FGFR4 mutation; microsatellite instability analysis did not detect any alteration. In silico analysis confirmed the mutation of FGFR4 as a promising marker for poor prognosis and a potential therapeutic target. We report for the first time the molecular and pharmacological characterization of rare entities of adult head and neck and posterior trunk RMS. These preliminary data could shed light on this poorly understood disease.

Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas.

OBJECTIVE: Squamous cell carcinoma (SCC) represents the most common histotype of all head and neck malignancies and includes oropharyngeal squamous cell carcinoma (OSCC), a tumor associated with different clinical outcomes and linked to human papilloma virus (HPV) status. Translational research has few available in vitro models with which to study the different pathophysiological behavior of OSCCs. The present study proposes a 3-dimensional (3D) biomimetic collagen-based scaffold to mimic the tumor microenvironment and the crosstalk between the extracellular matrix (ECM) and cancer cells. METHODS: We compared the phenotypic and genetic features of HPV-positive and HPV-negative OSCC cell lines cultured on common monolayer supports and on scaffolds. We also explored cancer cell adaptation to the 3D microenvironment and its impact on the efficacy of drugs tested on cell lines and primary cultures. RESULTS: HPV-positive and HPV-negative cell lines were successfully grown in the 3D model and displayed different collagen fiber organization. The 3D cultures induced an increased expression of markers related to epithelial-mesenchymal transition (EMT) and to matrix interactions and showed different migration behavior, as confirmed by zebrafish embryo xenografts. The expression of hypoxia-inducible factor 1α (1α) and glycolysis markers were indicative of the development of a hypoxic microenvironment inside the scaffold area. Furthermore, the 3D cultures activated drug-resistance signaling pathways in both cell lines and primary cultures. CONCLUSIONS: Our results suggest that collagen-based scaffolds could be a suitable model for the reproduction of the pathophysiological features of OSCCs. Moreover, 3D architecture appears capable of inducing drug-resistance processes that can be studied to better our understanding of the different clinical outcomes of HPV-positive and HPV-negative patients with OSCCs.

Synchronized "One-Step" Resection and Cranio-Orbital Reconstruction for Spheno-Orbital Lesions With Custom Made Implant.

BACKGROUND: In the last few years, skull base tumors involving the fronto-orbital region have been approached with complex, invasive, and time-consuming cranial reconstruction techniques. On the other hand, recent custom-made implants allow easier and faster procedures, with excellent aesthetic results. The authors propose an easy surgical-planned protocol with a synchronized "one-step" resection and reconstruction of these complex lesions, with a preformed poly-methyilmethacrylate (PMMA) cranioplasty. METHODS: Our technique consists of a 2-phases procedure. In the first one, the so-called "virtual" phase, the authors get a tailored 3D-PMMA model based on high-resolution (HR) CT-scans of the patient's skull. Afterward, the authors perform the planned craniotomy on the 3D-PMMA model with the assistance of intraoperative navigation system. Therefore, a further CT-scan of the resected model is performed to develop the final implant. In the second phase, the "surgical phase," a single procedure consisting in a cranial resection and custom reconstruction is performed with the assistance of stealth-navigation. The authors describe 6 cases of complex fronto-orbital-sphenoidal benign tumors that required skull reconstruction. All patients were examined 3 months after surgery through cosmetic (facial and eyes symmetry and globe position) and ophthalmology tests (visual field, visual impairment, and diplopia). Postsurgical HR CT-scans of the head and MRI-scans of the brain documented a total resection of the tumor and an optimal accuracy of skull reconstruction. RESULTS: In all cases, the authors obtained a highly accurate skull reconstruction following cranio-orbital tumor resection, with a less aggressive and faster procedure compared to autologous bone graft. Final cosmetic and functional results were excellent, with good results in cases of presurgical exophthalmos and orbital asymmetry. None of the patients developed implant-related complications. CONCLUSIONS: The "one-step" resection and reconstruction of benign tumors involving the spheno-orbital region with neuronavigation assistance is a technique that allows an accurate tumor removal and a cranial-bone reconstruction within a single surgical procedure, with fewer complications and excellent cosmetic and functional results.

Osteosarcoma of the Jaws: A Literature Review.

Osteosarcoma of the jaws (OSJ) is a relatively rare disease, accounting for between 2% and 10% of all cases of osteosarcoma. It is morphologically and radiologically identical to the trunk and extremity variant, but distinct in several crucial aspects. The lesion is characterized by sarcomatous cells which produce a variable amount of osteoid bone. It arises centrally within the bone and can be subdivided into osteoblastic, chondroblastic and fibroblastic subtype, depending on the predominant cell type. Radiographically, these tumors display a spectrum of bone changes from well-demarcated borders to lytic bone destruction with indefinite margins and variable cortical bone erosion or, in some cases, images of sclerotic bone. Therapeutic options for OSJ include surgery, chemotherapy and radiotherapy, which are employed according to age of the patient, histological classification and localization of the tumor. Today, there is no general consensus in the treatment guidelines for the OSJ though surgery represents the key to the treatment. The main prognostic factor deeply influencing the patient's prognosis remains the complete tumor resection with negative surgical margins. The aim of the present review is to describe state of the art regarding diagnostic and surgical treatment aspects of the primary osteosarcoma of the jaws.

Congenital Ulcerated Lip Hemangioma Treated With a Cleft Lip Technique.

A neonate presented to our clinic for evaluation of unusual congenital cleft lip. The clinical follow-up showed at first an ulceration of the lesion and then a stable result after propanolol systemic therapy. After 18 months of clinical follow-up, surgical treatment was performed, which consisted of double unilimb Z-plasty according to Mulliken's microform cleft lip repair. Knowing the existence of these strange vascular anomalies of the lip will allow us to improve the differential diagnosis and treatment plan.

Does microvascular free flap reconstruction in oral squamous cell carcinoma improve patient survival?

OBJECTIVE: We analyzed our experiences with microvascular reconstruction after oncologic resections for oral squamous cell carcinoma. Has microvascular surgery changed the survival rate of these patients? DESIGN: Retrospective study. SUBJECTS AND METHODS: Forty-two consecutive patients enrolled from March 1999 to December 2004. Follow-up time ranged from 1 to 94 months. Survival rates were evaluated by the Kaplan-Meier method and compared among different groups with the use of Cox regression. RESULTS: The actuarial 5-year survival rate was 41.9% (SD = 9.6%). Survival rates were also analyzed according to T, N, and stage. The survival was significantly related only to N, which showed a 72.4% increase in the risk related to the increase of one N stage. CONCLUSIONS: A comparison between our study group and those of 3 previous similar studies would not provide definitive statistical evidence, but it could certainly suggest a trend. The comparison seems to support that microvascular free tissue transfer does not change the survival of these patients.

Oromandibular reconstruction using a fibula osteocutaneous free flap: four different "preplating" techniques.

BACKGROUND: The aim of oromandibular reconstruction following a partially or fully extended resection is to recreate the normal morphology with a mandibular profile as similar as possible to the original and to restore oral function. Oromandibular reconstruction can be performed with fibula osteocutaneous free flaps combined with the preplating technique. The authors report their experience using the preplating technique for oromandibular reconstruction. METHODS: Four different methods can be used to mold the titanium plate that will be used in reconstruction against the existing mandible before resection. The preplating technique was used in 18 patients between 1998 and 2003. In eight patients, the external cortical bone of the mandible was spared by the tumor and the vestibular preplating technique was used. In one patient, the internal cortical bone was unaffected and the lingual preplating technique was used. When the tumor affected both the internal and external cortical bones, the double preplating technique was adopted in eight cases and Luhr's approach was used in one case. RESULTS: A good cosmetic appearance was obtained through the accurate reconstruction of the inferior mandibular border. Mandible continuity was restored, and the masticatory and oral muscles were anchored to the titanium plate, resulting in good occlusal and functional rehabilitation. CONCLUSION: The preplating technique combined with a fibula microvascular free flap is a useful, predictable method for oromandibular reconstruction.

Traumatic encephalocele related to orbital roof fractures: report of six cases and literature review.

BACKGROUND: Orbital roof fractures after blunt injury are rare. Traumatic encephaloceles in the orbital cavity are even rarer, with only 15 cases published to date. METHODS: The clinical, radiological, and surgical findings of 6 cases of traumatic encephalocele treated at our institution from June 1998 to January 2000 are presented. They are also compared with previously published series. RESULTS: In contrast to other published cases, 5 out of 6 patients in our series were adults. The most common cause of trauma was road traffic accident. Ecchymosis and preoperative exophthalmos/proptosis were frequent. In all of our patients a coronal CT scan (3 mm increments with bone windows) was obtained. It demonstrated the extension of the orbital roof fractures and a possible encephalocele in 4 cases. Associated frontal brain contusions were seen in 5 cases. An MRI was performed in 3 patients (and only in 2 previously published cases); it showed the extension of the brain herniation into the orbital cavity. Surgical treatment via a fronto-basal approach with evacuation of the contused herniated brain tissue and orbital roof reconstruction was performed. The outcome at 6 months was good recovery in five patients with one patient still in a persistent vegetative state. Postoperatively the ocular disturbances improved in 5 cases. A review of the other published cases confirmed recovery of normal ocular function in the vast majority of the cases. CONCLUSIONS: Whenever orbital roof fractures associated with frontal contusions are identified in an acute brain injured patient, an orbital encephalocele should be suspected. In our opinion MRI is the investigation of choice in such patients. If the encephalocele is confirmed, a surgical approach via the subfrontal route is indicated with resection of herniated contused brain tissue, dural closure, and orbital roof reconstruction. Good results in regard to the orbital symptoms (mainly exophthalmos) can be expected.