Recurrent and metastatic cellular cutaneous fibrous histiocytoma: A case report and literature review.

Cutaneous fibrous histiocytoma (FH) is considered a benign dermal tumor. The cellular variant is rare and poorly documented. Besides presenting a high risk of local recurrence, it has a low but serious metastatic potential. We present a case of metastatic cellular FH and also review the literature on this tumor, given its unusual metastatic development. A 47-year-old male patient presented with a lesion in the anterior surface of the right thigh, which has been present since adolescence but had grown during last year. Anatomopathological evaluation revealed a cellular FH, and the lesion was completely removed. Six months later, tumor recurrence with multiple compartment muscle involvement and pulmonary metastasis were detected. Both lesions were completely resected and after 3 years of follow-up, the patient is asymptomatic and free of the disease. We conclude that FH should be carefully sampled to detect variants with high local recurrence rates or with some metastatic risk such as the cellular one. We recommend wide surgical resection and a close follow-up including chest x-rays or thorax computed tomography (CT) in all cellular FH cases with local recurrence.

Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma.

BACKGROUND: Survival in patients who have Ewing sarcoma is correlated with postchemotherapy response (tumor necrosis). This treatment response has been categorized as the response rate, similar to what has been used in osteosarcoma. There is controversy regarding whether this is appropriate or whether it should be a dichotomy of complete versus incomplete response, given how important a complete response is for in overall survival of patients with Ewing sarcoma. The purpose of this study was to evaluate the impact that the amount of chemotherapy-induced necrosis has on (1) overall survival, (2) local recurrence-free survival, (3) metastasis-free survival, and (4) event-free survival in patients with Ewing sarcoma. METHODS: In total, 427 patients who had Ewing sarcoma or tumors in the Ewing sarcoma family and received treatment with preoperative chemotherapy and surgery at 10 international institutions were included. Multivariate Cox proportional-hazards analyses were used to assess the associations between tumor necrosis and all four outcomes while controlling for clinical factors identified in bivariate analysis, including age, tumor volume, location, surgical margins, metastatic disease at presentation, and preoperative radiotherapy. RESULTS: Patients who had a complete (100%) tumor response to chemotherapy had increased overall survival (hazard ratio [HR], 0.26; 95% CI, 0.14-0.48; p < .01), recurrence-free survival (HR, 0.40; 95% CI, 0.20-0.82; p = .01), metastasis-free survival (HR, 0.27; 95% CI, 0.15-0.46; p ≤ .01), and event-free survival (HR, 0.26; 95% CI, 0.16-0.41; p ≤ .01) compared with patients who had a partial (0%-99%) response. CONCLUSIONS: Complete tumor necrosis should be the index parameter to grade response to treatment as satisfactory in patients with Ewing sarcoma. Any viable tumor in these patients after neoadjuvant treatment should be of oncologic concern. These findings can affect the design of new clinical trials and the risk-stratified application of conventional or novel treatments.

Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: could the combination with other drugs improve its antitumoral effect?

BACKGROUND: Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS). METHODS: In this study, we evaluated the effect of eribulin on proliferation, migration and invasion capabilities in LPS, leiomyosarcoma (LMS) and fibrosarcoma (FS) models, using both monolayer (2D) and three-dimensional (3D) spheroid cell cultures. Additionally, we explored combinations of eribulin with other drugs commonly used in the treatment of STS with the aim of increasing its antitumour activity. RESULTS: Eribulin showed activity inhibiting proliferation, 2D and 3D migration and invasion in most of the cell line models. Furthermore, we provide data that suggest, for the first time, a synergistic effect with ifosfamide in all models, and with pazopanib in LMS as well as in myxoid and pleomorphic LPS. CONCLUSIONS: Our results support the effect of eribulin on LPS, LMS and FS cell line models. The combination of eribulin with ifosfamide or pazopanib has shown in vitro synergy, which warrants further clinical research.

Treatment of infantile fibrosarcoma associated to an abdominal aortic aneurysm with larotrectinib: a case report.

Infantile fibrosarcoma (IFS) is a rare pediatric tumor which often presents the ETV6-NTRK3 gene fusion. NTRK3 encodes the neurotrophin-3 growth factor receptor tyrosine kinase, a druggable therapeutic target. Selective tropomyosin receptor kinase (TRK) inhibitors, such as larotrectinib, have shown efficacy and safety in the treatment of IFS. We report a case of an abdominal IFS diagnosed in a newborn associated with an aortic aneurysm that was successfully treated with larotrectinib without relevant adverse effects.

Genetic variation analysis in a follow-up study of gastric cancer precursor lesions confirms the association of MUC2 variants with the evolution of the lesions and identifies a significant association with NFKB1 and CD14.

Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes. After follow-up, 45.5% of the lesions remained stable, 37% regressed and 17.5% progressed to a more severe lesion. Genetic association with the evolution of the lesions (progression or regression) was analyzed by multinomial and binomial logistic regression. After correction for multiple comparisons, the results obtained confirmed the inverse association between MUC2 variants and the regression of the lesions. A significant association was also observed between NFKB1 and CD14 variants and the evolution of the lesions; interestingly, this association was with both progression and regression in the same direction, which could reflect the dual role of inflammation in cancer. Stratified analyses according to H. pylori virulence factors indicated some significant and differential effects but none of them passed the FDR test. These results confirm that genetic variability in MUC2, NFKB1 and CD14 may have a role in the evolution of the GCPLs along time and in gastric carcinogenesis.

Are Biopsy Tracts a Concern for Seeding and Local Recurrence in Sarcomas?

BACKGROUND: A biopsy is the final step in the diagnosis of sarcomas. Complete resection of the biopsy tract traditionally has been recommended in musculoskeletal oncology guidelines, as that tract is considered potentially seeded with tumor cells. However, to our knowledge, the frequency and implications of contamination of the biopsy tract-specifically with respect to the likelihood of local recurrence-and the factors that affect cell seeding are not well described. QUESTIONS/PURPOSES: We asked: (1) How often are biopsy tracts contaminated with pathologically detectable tumor cells at the time of tumor resection? (2) What factors, in particular biopsy type (open versus percutaneous), are associated with tumoral seeding? (3) Is biopsy tract contamination associated with local recurrence? METHODS: This is a retrospective study of a database with patient data collected from a single center between 2000 and 2013. We treated 221 patients with sarcomas. A total of 27 patients (12%) were excluded and 14 (6%) were lost to followup. One hundred eighty patients finally were included in the analysis who either had biopsies at our center (112) or biopsies at outside institutions (68). Of those performed at our center, 15 (13%) were open and 97 (87%) were percutaneous; of those at outside centers, those numbers were 47 (69%) and 21 (31%) respectively. Median followup was 40 months (range, 24-152 months). During the study period, we generally performed percutaneous biopsies as a standard practice for the diagnosis of bone and soft tissue sarcomas and open biopsies were done when the percutaneous procedure failed to provide a histologic characterization. The mean age of the population was 48 years (range, 7-87 years); 60% were male; 42% had bone sarcomas. Nineteen patients had preoperative radiotherapy and 56 had postoperative radiotherapy. Fifty-seven patients received neoadjuvant chemotherapy and 73 had adjuvant chemotherapy. We determined what proportion of biopsy tracts were contaminated by pathologic analysis of the biopsy tract specimen; during the period in question, our routine practice was to excise the biopsy tract whenever possible at the time of the definitive resection. Using the logistic regression test and Mantel-Haenszel test, we compared open with percutaneous biopsies in terms of the proportion of those that were contaminated at our site and for outside referral biopsies separately, because we do not assume the level of expertise was the same (our site is a referral tumor center). We compared the local recurrence-free survival between patients with and without contamination and between open and percutaneous biopsies using the Kaplan Meier test, again separating those performed at our site from those referred for purposes of this analysis. RESULTS: Twenty-one of 180 biopsy tracts were contaminated (12%). Twenty of 62 (32%) of the open biopsies and one of 118 (0.8%) of the percutaneous core needle biopsies had cell seeding (odds ratio [OR], 56; 95% CI, 7-428; p < 0.001. One of 97 (1%) percutaneous biopsies performed in our center, and none of the 21 (0%) percutaneous biopsies performed in other centers had contaminated biopsy tracts (p = 0.047). Two of 15 (13%) open biopsies performed at our center and 18 of 41(38%) open biopsies performed at other centers had contaminated biopsy tracts (OR, 4; 95% CI, 1-7; p = 0.001). Four of 74 (5%) bone sarcomas and 18 of 106 (17%) soft tissue sarcomas had biopsy tract contamination (OR, 3; 95% CI, 1-10; p = 0.023). The local recurrence-free survival was longer for patients without contaminated tracts (mean, 107 months; 95% CI, 74-141 months) than for those with biopsy tract seeding (mean, 11 months; 95% CI, 1-20 months; p < 0.001). CONCLUSIONS: Open biopsies were associated with an increased risk of tumoral seeding of the biopsy site, and tumoral seeding was associated with an increased risk of local recurrence. However, it is possible that other factors, such as increased complexity of the tumor or a difficult location, influenced the decision to obtain an open biopsy. Even so, based on these results, we believe that higher risk of local recurrence may be caused by an incomplete biopsy tract resection. In our opinion, the percutaneous biopsy with neoadjuvant or adjuvant therapy is the preferred method of biopsy at our center. LEVEL OF EVIDENCE: Level III, therapeutic study.

Clinical and Pathological Features of Osteosarcomas of the Jaws: A Retrospective Study.

INTRODUCTION: Osteosarcomas of the jaw (OSJs) are rare tumors with distinct characteristics from osteosarcomas affecting other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of OSJs. METHODS: A retrospective, descriptive cross-sectional study including patients diagnosed with OSJ registered at the "La Paz" University Hospital, Madrid, was performed. RESULTS: Data of eight patients with a diagnosis of OSJ were obtained during the study period of 22 years (2002-2024). The mean age of the patients was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most predominant histological type. Survival rate at 5 years was 50%, which decreased to 25% at 10 years. CONCLUSIONS: OSJs differ from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment. However, more studies are needed through which more standardized protocols can be proposed for adjuvant therapeutic management.

Characterisation of new in vitro models and identification of potentially active drugs in angiosarcoma.

Angiosarcoma is a rare soft tissue sarcoma originating from endothelial cells. Given that current treatments for advanced disease have shown limited efficacy, alternative therapies need to be identified. In rare diseases, patient-derived cell models are crucial for screening anti-tumour activity. In this study, cell line models were characterised in 2D and 3D cultures. The cell lines' growth, migration and invasion capabilities were explored, confirming them as useful tools for preclinical angiosarcoma studies. By screening a drug library, we identified potentially effective compounds: 8-amino adenosine impacted cell growth and inhibited migration and invasion at considerably low concentrations as a single agent. No synergistic effect was detected when combining with paclitaxel, gemcitabine or doxorubicin. These results suggest that this compound could be a potentially useful drug in the treatment of AGS.

Cytopathological findings of intranodal palisaded myofibroblastoma: Case report and review of the literature.

INTRODUCTION: Intranodal palisaded myofibroblastoma (IPM) is an exceedingly rare benign mesenchymal tumor of the lymph nodes. Magnetic resonance imaging (MRI) findings are unspecific, which may present diagnostic challenges to fine-needle aspiration cytology (FNAC). The histological and immunohistochemical features of IPM are unique. CASE REPORT: A previously healthy 40-year-old male patient presented a slow-growing solitary left inguinal mass. FNAC revealed clustered cells within a metachromatic stroma, single spindle cells without atypia, hemosiderin pigment, and siderophages. An MRI showed a central hyperintense septum in fat-suppressed, T2-weighted sequences. The excised lymph node contained central haphazard fascicles of spindle cells with focal nuclear palisading, hemosiderin pigment, extravasated erythrocytes, and hemorrhagic areas. Vimentin and smooth muscle actin were diffusely positive. Amianthoid collagen fibers were not clearly observed. CONCLUSION: IPM is an extremely rare mesenchymal benign intranodal tumor that should be included in the differential diagnosis of spindle cell lesions in the inguinal region.

Soft Tissue Aneurysmal Bone Cyst in the Sartorius Muscle of a 13-Year-Old Boy Mimicking Myositis Ossificans: Case Report.

INTRODUCTION: A soft tissue aneurysmal bone cyst is an extremely rare tumor. The objective of the article is to present the clinical, radiological, and histopathological features of a very unusual neoplasm of soft tissues. CASE REPORT: A 13-year-old male patient presented a painful, mobile, and rapidly growing mass on the posteromedial aspect of his left knee. Imaging studies revealed a mass that arose from the medial surface of the distal sartorius muscle, with extension to the subcutaneous fat tissue. It was a well-circumscribed solid tumor with a peripheral rim calcification on plain film, computerized tomography, and ultrasound (zonal phenomenon). On magnetic resonance imaging, a heterogenous mass on T1-weighted images (WI) and T2-WI was seen, with a peripheral hypointense rim in both sequences. An outstanding edema on T2-WI extending to the soft tissue and muscles of the medial compartment of the knee was detected. The mass was resected, and the "tumoral mimickers" histopathological and molecular (next-generation sequencing) diagnoses confirmed a soft tissue aneurysmal bone cyst. A follow-up showed that the patient was free of disease 12 months after surgery. CONCLUSION: Soft tissue aneurysmal bone cyst is a rare tumor. Appropriate clinical and radiological correlation should be performed to differentiate it from other tumor mimickers.

HPV infection in oral cancer, our experience: prevalence, clinical implications, and current vaccination program in Spain.

Background: Oral cancer is the 11th most common type of cancer in the world, with established major risk factors as tobacco and alcohol, and recently included high-risk human papillomavirus types 16 and 18. HPV types 16 and 18 are the etiologic agents of cervical cancers and a proportion of oropharyngeal cancers. However, the picture of HPV and the clinical implications of oral cancers are not clear with most reports combining oral cancer data with head and neck cancers. It has been confirmed as a favorable prognostic factor in oropharyngeal cancer. However, the prognostic value of HPV in oral squamous cell carcinoma is still unclear. Material and Methods: The main objective of this article is to present the evidence encountered following a bibliographical review of recent publications specifically related to oral cancer and its differences from oropharyngeal cancer. The secondary goals are to present the findings of a five-year retrospective observational study of the prevalence of HPV infection in oral cancer patients treated by the Oral and Maxillofacial Surgery Department at La Paz University Hospital (Madrid, Spain), and finally, we to evaluate and compare our country's HPV prevention program in comparison to other European countries. Results: According to the review of the literature, HPV positive oral squamous cell carcinoma is associated with significantly decreased overall survival and distant control. Bibliographic review suggest HPV infection can be used as a negative prognostic factor in oral squamous cell carcinoma. Conclusions: As regards diagnostic testing for HPV, it should be extended to as many cases of oral cavity squamous cell carcinoma as possible, especially in those with risk factors. The current vaccination program in Spain does not have adequate coverage and is significantly under the level of other European Union countries; it should be expanded and catch-up strategies should be included. Key words:HPV, OSSC, Papillomavirus, oral carcinoma, prevention.

Therapeutic strategies and clinical evolution of patients with infantile fibrosarcoma: a unique paediatric case series.

BACKGROUND: Infantile fibrosarcoma is the most frequent soft tissue sarcoma in newborns or children under one year of age. This tumour often implies high local aggressiveness and surgical morbidity. The large majority of these patients carry the ETV6-NTRK3 oncogenic fusion. Hence, the TRK inhibitor larotrectinib emerged as an efficacious and safe alternative to chemotherapy for NTRK fusion-positive and metastatic or unresectable tumours. However, real-world evidence is still required for updating soft-tissue sarcoma practice guidelines. OBJECTIVE: To report our experience with the use of larotrectinib in pediatric patients. METHODS: Our case series shows the clinical evolution of 8 patients with infantile fibrosarcoma under different treatments. All patients enrolled in this study received informed consent for any treatment. RESULTS: Three patients received larotrectinib in first line. No surgery was needed with larotrectinib, which led to the rapid and safe remission of tumours, even in unusual anatomical locations. No significant adverse effects were observed with larotrectinib. CONCLUSION: Our case series supports that larotrectinib may be a therapeutic option for newborn and infant patients with infantile fibrosarcoma, especially in uncommon locations.

Prognosis Value of Immunoregulatory Molecules in Oral Cancer Microenvironment: An Immunohistochemical Study.

OBJECTIVES: To evaluate the relationship of the immune-checkpoint PD-1/PD-L1 with the clinical evolution of OSCC; to assess survival in OSCC based on the characteristics of TME and histologic risk score; to evaluate the clinical and histopathological relationship of OSCC with immunological TME. MATERIAL AND METHODS: A retrospective study was carried out on 65 samples from patients with OSCC on the floor of the mouth or tongue. Clinicopathological variables and the expression of the biomarkers PD-1, PD-L1, FoxP3, CD4, CD8, CSF1R, and p16 were recorded. The relationship of the clinical and histological variables with the expression of the biomarkers and survival was studied. RESULTS: The univariate and multivariate analysis indicated that positive PD-1 expression was an independent protective factor for survival (overall, disease-free, disease-specific survival) and that high PD-L1 also improved survival. Poorly differentiated histological grades and metastasis were associated with a worse prognosis. CONCLUSIONS: PD-1 is a protective survival factor that is maintained independently of PD-L1 expression. High values of PD-L1 expression also improve survival. Higher expression of PD-1 is observed in smaller tumors, and higher expression of PD-L1 is more likely in women. No relationship between the tumor microenvironment and histologic risk score was found to influence the survival patterns studied in the OSCC. There is no evidence of a relationship between the histopathological features and the studied markers, although the positive PD-1 and PD-L1 cases have a lower risk of a high WPOI score, and positive PD-1 expression was associated with a lower DOI.

Oligometastases in oncological orthopedic surgery. Our experience. / Oligometástasis en la cirugía ortopédica oncológica. Nuestra experiencia.

OBJECTIVE: To analyze the incidence and survival of patients with oligometastases (solitary and normal) when they are treated in centers that are experts in multidisciplinary approach to patients with sarcoma. MATERIAL AND METHOD: Retrospective analysis of 414 patients with bone metastases secondary to carcinomas at Hospital Universitario La Paz and Hospital MD Anderson Cancer Center (Madrid) between May 2006 and May 2019. Metastases located in the pelvis and axial skeleton were excluded, analyzing a total of 28 patients who met the criterion for solitary metastases or oligometastases with normal criteria. The study survival estimate was carried out following the Kaplan-Meier statistical method. RESULTS: The survival of the patients following the oligometastases criteria (solitary and normal) was 53%. Breast cancer was the most prevalent and had a survival rate of more than 70%. The average age of the patients was 58 years old. DISCUSSION: Systemic treatments in cancer treatment have managed to improve disease-free survival curves and lead us to redirect on the paradigm for the treatment of oligometastases, stating that treatment should be carried out in the centers that are experts in the treatment of sarcomas. CONCLUSIONS: The choice of surgical treatment for patients with oligometastases in the strict sense (solitary) and normal should be evaluated by multidisciplinary teams according to the prognoses of the patient, anatomical location and histiotype of the neoplasm.

Jaw in a day: Osseointegration of the implants in the patient's leg before reconstructive surgery of a maxilla with ameloblastoma. A 4-year follow-up case report.

BACKGROUND: To describe a clinical case of a cancer patient who underwent ablative tumor surgery, including treatment planning, surgical resection and subsequent implant rehabilitation. CASE REPORT: A 61-year-old patient with a diagnosis of multicystic follicular ameloblastoma in the maxilla, in which it was necessary a multidisciplinary approach and two surgical steps. In the first surgical intervention osseointegrated implants (OII) were placed in the fibula, until their osseointegration period of 8 weeks was complete. Afterwards, in the second surgery, the micro-vascularized free fibular flap bearing the implants was transplanted into the oral cavity, in order to perform simultaneous reconstruction and early rehabilitation. The final prosthetic rehabilitation consisted in a hybrid prosthesis fabricated using CAD CAM technology. RESULTS: The latest advances in medical research have improved our understanding of the oral cavity's regenerative capacity after oncological treatment. This, aided by the advances in digital 3D technologies, has allowed meticulous treatment planning prior surgery. CONCLUSIONS: The functional and esthetic reconstructions described in these two case reports were made possible by coordinating multidisciplinary approaches involving dentists and oral and maxillofacial surgeons. Advances in medicine have improved understanding of the regenerative capacity of the oral region following oncologic treatment, facilitating meticulous advance planning, while advances in digital 3D technologies for planning make it possible to reduce the number of surgical sessions and the time taken for the patient to recover both the esthetics and function of the stomatognathic system. Key words:Oral rehabilitation, oral cancer, oral surgery.

Dental implants rehabilitation in a patient with head and neck radiotherapy for osteosarcoma in the jaw. A clinical case report.

A 52-year-old female patient with a diagnostic of osteosarcoma in the mandible, in which it was necessary a reconstruction with a microvascularized osteomyocutaneous fibula bone. Coadjuvant chemotherapy was scheduled. Two years later, 4 osseointegrated implants (OII) were placed in the fibula a 2 OII in the right mandible, using a splint guided surgery. The final prosthodontic consisted in a metal ceramic restoration using CAD/ CAM technology. Key words:Oral rehabilitation, oral cancer, head and neck radiotherapy, oral oncology.

Primary malignant PEComa of the mandible. Report of an unusual case.

Malignant PEComa is a rare entity that usually origins at visceral, retroperitoneal and abdominopelvic sites. In the present paper, we describe an extremely unusual manifestation of malignant PEComa involving the mandible in a 48 years-old female patient focusing on the anatomopathological findings and differential diagnosis. The therapeutic management based on the head and neck tumor board indications is also discussed. Key words:Malignant PEComa, PEComa of the mandible, PEComa pathology, Oral cavity unusual neoplasm.

Anti-CXCR4 Antibody Combined With Activated and Expanded Natural Killer Cells for Sarcoma Immunotherapy.

Sarcoma is one of the most severe forms of pediatric cancer and current therapies -chemotherapy and surgery- fail to eradicate the disease in half of patients. Preclinical studies combining new therapeutic approaches can be useful to design better therapies. On one hand, it is known that CXCR4 expression is implicated in rhabdomyosarcoma progression, so we analyzed relapses and chemotherapy-resistant rhabdomyosarcoma tumors from pediatric patients and found that they had particularly high levels of CXCR4 expression. Moreover, in assays in vitro, anti-CXCR4 blocking antibody (MDX1338) efficiently reduced migration and invasion of alveolar rhabdomyosarcoma RH30 cells. On the other hand, activated and expanded natural killer (NKAE) cell therapy showed high cytotoxicity against sarcoma cells in vitro and completely inhibited RH30 tumor implantation in vivo. Only the combination of MDX1338 and NKAE treatments completely suppressed metastasis in mice. In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis. These results provide the first evidence for the efficacy of this combined immunotherapy for preventing sarcoma disease dissemination.

Head and neck manifestations of an undiagnosed McCune-Albright syndrome: clinicopathological description and literature review.

Craniofacial fibrous dysplasia, characteristic of McCune-Albright syndrome (MAS), is usually present in patients with MAS-related acromegaly. We report here the first case of a patient with an undiagnosed MAS presenting with an acute hydrocephalus. A 21-year-old male with gigantism and craniofacial fibrous dysplasia consulted for rapidly progressive headache. An acute obstructive hydrocephalus due to a 39 × 35-mm cystic lesion in the third ventricle was discovered and operated, obtaining hydrocephalus resolution. Pathology described a colloid cyst material and a growth hormone-secreting pituitary adenoma. Genetic study revealed the mosaic GNAS R201H mutation in the pituitary tissue, confirming a MAS diagnosis. Adequate hormonal control was achieved postoperatively. Our results suggest that long-term untreated growth hormone excess in patients with MAS-related craniofacial fibrous dysplasia might end compromising cerebrospinal fluid flow. A prompt diagnosis and coordinated multidisciplinary treatment may help to avoid long-term deleterious impact of hyperfunctioning endocrinopathies in these patients.