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Fibrous dysplasia, including McCune-Albright syndrome, is a genetic, non-inheritable benign bone disorder that may involve a single or multiple bone, typically occurring in the diaphysis or the metaphysis of long bones. In very rare instances polyostotic fibrous dysplasia present involvement of the epiphysis in long bones. Aneurysmal bone cysts are benign, expansile, lytic bone lesions formed by cystic cavities containing blood, that may occur de novo or secondary to other lesions of bone, including fibrous dysplasia. We report a case of an 18-year-old female with polyostotic fibrous dysplasia (McCune-Albright syndrome) with diaphyseal and unusual multiple foci of epiphyseal involvement of long bones as well as in the patella, and a simultaneous aneurysmal bone cyst of the left femoral neck with pathologic fracture. This is the first report of a simultaneous aneurysmal bone cyst in a patient with polyostotic fibrous dysplasia (McCune-Albright syndrome) with involvement of diaphysis and epiphysis of long bones, highlighting that fibrous dysplasia should be included in the differential diagnosis of polyostotic tumors involving the diaphysis as well as the epiphysis. In patients with polyostotic fibrous dysplasia there should be an active search for lesions in the epiphysis.

BACKGROUND Polyostotic fibrous dysplasia (PFD) is an uncommon developmental bone disease in which normal bone and marrow are replaced by pseudotumoral tissue. The etiology of PFD is unclear, but it is generally thought to be caused by sporadic, post-zygotic mutations in the GNAS gene. Herein, we report the case of a young female with bone pain and lesions consistent with PFD, unique physical findings, and gene mutations. CASE SUMMARY A 27-year-old female presented with unbearable bone pain in her left foot for 4 years. Multiple bone lesions were detected by radiographic examinations, and a diagnosis of PFD was made after a biopsy of her left calcaneus with symptoms including pre-axial polydactyly on her left hand and severe ophthalmological problems such as high myopia, vitreous opacity, and choroidal atrophy. Her serum cortisol level was high, consistent with Cushing syndrome. Due to consanguineous marriage of her grandparents, boosted whole exome screening was performed to identify gene mutations. The results revealed mutations in HSPG2 and RIMS1, which may be contributing factors to her unique findings. CONCLUSION The unique findings in this patient with PFD may be related to mutations in the HSPG2 and RIMS1 genes.

Background Dysplastic gangliocytoma is a sporadic cerebellar benign tumor with the characteristics of hamartoma and true tumor, also known as Lhermitte-Duclos disease (LDD). Bone fibrous dysplasia (FD) is a slowly progressive self-limited benign bone tissue disease. Cowden syndrome, an autosomal dominant genetic disorder caused by germline mutations in the PTEN gene, is considered to be closely related to dysplastic gangliocytoma. McCune-Albright syndrome is a disease characterized by cafe-au-lait skin macules, polyostotic FD, and precocious puberty. The etiologic mechanism of both conditions is not yet clear. We report a rare case of bilateral dysplastic gangliocytoma with concurrent polyostotic FD. Case Description We describe a 16-year-old boy with both LDD and FD. He presented for medical examination with headache and poor eyesight. Magnetic resonance imaging revealed proliferation of the skull and abnormal signals in the cerebellum, and supratentorial hydrocephalus. Subtotal resection of the cerebellar tumor was performed, and the diagnosis of LDD and FD was confirmed by histopathology. No other abnormal changes were found in systemic medical examination and no PTEN gene mutation was found in the genetic analysis; therefore, the diagnoses of Cowden syndrome and McCune-Albright syndrome were excluded. Conclusions LDD and FD are 2 rare diseases, and the simultaneous occurrence of the 2 conditions has not been reported before, to our knowledge. Our report challenges the etiology of the 2 diseases and the relationship between them, hoping to provide a reference for the study of the 2 diseases.

Introduction GNAS mutations have been reported in both McCune-Albright syndrome (MAS) and juvenile granulosa cell tumors (JGCT) but have never been reported simultaneously in the same patient. Case Presentation A 15-year-old girl developed secondary oligomenorrhea. Laboratory studies revealed suppressed gonadotropin levels with markedly elevated estradiol and inhibin B levels. Pelvic ultrasound showed a 12-cm heterogeneous right adnexal mass; pelvic magnetic resonance imaging to further characterize the mass displayed heterogeneous bilateral femoral bone lesions initially concerning for metastatic disease. Positron emission tomography/computed tomography showed minimal 18F-fluorodeoxyglucose (FDG) uptake in the pelvic mass but unexpectedly revealed FDG uptake throughout the skeleton, concerning for polyostotic fibrous dysplasia in the context of MAS. The adnexal mass was excised and pathology confirmed a JGCT. The patient’s affected bone and JGCT tissue revealed the same pathogenic GNAS p.R201C mutation, while her peripheral blood contained wild-type arginine at codon 201. Conclusion This mutation has been previously reported in cases of MAS and JGCT but never simultaneously in the same patient. This demonstration of a GNAS mutation underlying both JGCT and MAS in the same patient raises questions about appropriate surveillance for patients with these conditions.

Fibrous dysplasia (FD) is a fibro-osseous anomaly, where in normal bone is substituted with fibrous stroma. It is of unknown etiology but recently reported to be associated with mutation in GNAS1 gene (20q13.2) and consists of three subtypes monostotic, polyostotic and craniofacial. Craniofacial FD (CFD) mainly affects the bones of the craniofacial skeletal frame. This article reports a case of a 10 year old boy diagnosed with polyostotic fibrous dysplasia with clinical, radiographical and tissue pathological features.

Infantile Cushing’s syndrome is potentially found as part of McCune-Albright syndrome (MAS) which is caused by postzygotic somatic mutations of the GNAS gene. MAS is typically characterized by a triad of polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and precocious puberty or other endocrine hyperfunction. Here, we describe a 2-month-old female infant with features of Cushing’s syndrome without café au lait spots, polyostotic fibrous dysplasia, and clinical evidence of other endocrine hyperfunction. Investigations demonstrated adrenocorticotropic hormone-independent Cushing’s syndrome with bilateral adrenal gland enlargement. Whole-exome sequencing of leukocytes identified a de novo heterozygous novel missense mutation (c.521G>A, p.Cys174Tyr) in the GNAS gene. The patient experienced clinical improvement of Cushing’s syndrome during ketoconazole treatment. Her clinical course was complicated by Pneumocystis jiroveci pneumonia. She also had shortened activated partial thromboplastin time indicating a hypercoagulable state and resulting in pulmonary embolism. She eventually manifested gonadotropin-independent precocious puberty at the age of 13 months after ketoco­nazole was discontinued. This patient demonstrated that Cushing syndrome can be the presenting sign of MAS in infancy. A high index of suspicion followed by genetic analysis is essential in order to establish a diagnosis.

McCune Albright Syndrome (MAS) is caused by a mutation in the GNAS gene that results in multiple endocrinopathies such as Cushing syndrome, acromegaly, hyperthyroidism, and precocious puberty. Despite the presence of pleiotropy coupled with a GNAS gene mutation, malignancy is a rare occurrence in MAS. There is minimal literature showcasing squamous cell carcinoma (SCC) of the lung in patients with MAS. Here, we report a case of altered mental status and hypercalcemia in a 72-year-old female with a past medical history of fibrous dysplasia. On examination there was an expansive lesion of the left hemipelvis that had been present since birth; it was determined to be a characteristic of polyostotic fibrous dysplasia seen in MAS. Lab results revealed an elevated parathyroid hormone-related protein (PTHrP) and a chest X-ray (CXR) displayed masses in the right upper lobe. Computed tomography (CT)-guided lung biopsy confirmed the masses to be SCC of the lung. This case primarily highlights the importance of investigating other malignancies found in patients with MAS. Current literature shows that the GNAS mutation is an oncogenic driver in many tumor types such as pancreatic adenocarcinoma, adrenocortical carcinoma, and thyroid carcinoma; however, current data are limited on the role of GNAS mutations in SCC of the lung. In addition, it is important to investigate malignant causes of hypercalcemia in patients with MAS. The clinical features and treatments of MAS can lead to hypercalcemia and hypophosphatemia and thus mask a malignancy. Clinicians must be wary of a masked malignancy, as it could delay treatment and negatively impact overall outcomes for patients with MAS.

Bone involvement in Hodgkin lymphoma (HL) is rare. The differential diagnosis between HL bone localization and other malignant or benign skeletal diseases is challenging. We report the case of a girl affected by classic HL, initially staged IVA because of supradiaphragmatic lymph nodes and skeletal involvement. After 6 ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) cycles, positron emission tomography (PET) showed a complete metabolic response of the nodal localizations and a persistent, high metabolic activity of bone lesions. Salvage treatment followed by autologous stem cell transplant was carried out. After the transplant, the bone lesions maintained a high metabolic activity at PET. A targeted bone biopsy led to the diagnosis of a fibrous dysplasia excluding the presence of HL. To our knowledge, the concomitant presence of HL and fibrous dysplasia has not been previously reported. An in-depth evaluation of disease response to frontline treatment with a biopsy of the PET-hypercaptant bone lesions could have avoided overtreatment in this patient.

68Ga-labeled quinoline-based fibroblast activation protein inhibitors (68Ga-FAPIs) are promising agents for tumor imaging. However, some nonneoplastic lesions can also cause increased FAPI uptake. We report a case of a patient with polyostotic fibrous dysplasia who showed widespread and intense metabolic activity on 68Ga-FAPI PET/CT. Physicians should be aware that fibrous dysplasia can also cause elevated FAPI activity.

Introduction: Fibrous dysplasia is a benign fibro-osseous lesion of unknown etiology, characterized by the development of fibrous tissue that gradually replaces normal bone. The pathology can appear in two ways: monostotic, when it involves only one bone; and polyostotic, affecting multiple bones. Malignant transformation of fibrous dysplasia is rare, occurring in less than 1% of cases of the disease and has already been described in both forms of the injury. Objective: The present study aims to present a rare clinical case of craniofacial poliostotic fibrous dysplasia that evolved with malignancy in a 53-year-old woman. Case report: The patient presented with a fast and progressive hemifacial tumor, painful symptoms and imaging findings with a "ground-glass" characteristic, aspects suggestive of malignancy. A biopsy was performed using the Core Biopsy method, which confirmed, through the immunohistochemistry test, the differentiation in intermediate grade fusocellular sarcoma. The patient died after three months from the start of treatment due to gastrostomy complications. Final considerations: Although rare, malignant changes associated with fibrous dysplasia have a poor prognosis. Therefore, the maxillofacial surgeon must be attentive to the signs of malignancy to initiate the appropriate treatment. Introducción: La displasia fibrosa es una lesión fibroósea benigna de etiología desconocida, caracterizada por el desarrollo de tejido fibroso que reemplaza gradualmente al hueso normal. La patología puede presentarse de dos maneras: monostótica, cuando involucra solo un hueso; y poliostótico, que afecta a múltiples huesos. La transformación maligna de la displasia fibrosa es rara, ocurre en menos del 1% de los casos de la enfermedad y ya se ha descrito en ambas formas de la lesión. Objetivo: El presente estudio tiene como objetivo presentar un caso clínico poco frecuente de displasia fibrosa poliostótica craneofacial que evolucionó con malignidad en una mujer de 53 años. Informe del caso: El paciente tenía un tumor hemifacial progresivo y de rápido crecimiento, síntomas dolorosos y hallazgos de imágenes con una característica de "vidrio esmerilado", aspectos que sugieren malignidad. Se realizó una biopsia utilizando el método Core Biopsy, que confirmó, a través de la prueba de inmunohistoquímica, la diferenciación en el sarcoma fusocelular de grado intermedio. El paciente falleció después de tres meses de comenzar el tratamiento debido a complicaciones de gastrostomía. Consideraciones finales: Aunque es raro, los cambios malignos asociados con la displasia fibrosa tienen un pronóstico desfavorable. Por lo tanto, el cirujano maxilofacial debe estar atento a los signos de malignidad para iniciar el tratamiento adecuado. Introdução: A displasia fibrosa é uma lesão fibro-óssea benigna de etiologia ainda desconhecida, caracterizada pelo desenvolvimento de tecido fibroso que substitui gradualmente o osso normal. A patologia pode se apresentar de duas formas: monostótica, quando envolve apenas um osso; e poliostótica, afetando múltiplos ossos. A transformação maligna da displasia fibrosa é rara, ocorrendo em menos de 1% dos casos da doença e já foi descrita nas duas formas da lesão. Objetivo: O presente trabalho tem como objetivo apresentar caso clínico raro de displasia fibrosa poliostótica craniofacial que evoluiu com malignização em uma mulher de 53 anos de idade. Relato de caso: A paciente apresentava tumoração hemifacial de crescimento rápido e progressivo, sintomatologia dolorosa e achados de imagem com característica de “vidro-fosco”, aspectos sugestivos de malignidade. Realizou-se biópsia por meio do método core biopsy, o qual confirmou, através do teste de imuno-histoquímica, a diferenciação em sarcoma fusocelular de grau intermediário. Paciente evoluiu com óbito após três meses do início do tratamento por complicações da gastrostomia. Considerações finais: Embora raras, alterações malignas associadas a displasia fibrosa têm prognóstico ruim. Por isso, o cirurgião bucomaxilofacial deve estar atento aos indícios de malignidade para iniciar o tratamento adequado.

Fibrous dysplasia may show locally aggressive behaviour reflecting secondary intralesional changes, extension to soft tissue, or malignant transformation. We report the case of a patient with polyostotic fibrous dysplasia who had a giant mandibular lesion consisting of histologically typical, genotypically-confirmed, fibrous dysplasia merged with a fibrotic and hypocellular desmoplastic fibroma-like tissue in which the same Gsα-R201H mutation was detected. The occurrence of the same mutation in both the fibrous dysplasia and areas of desmoplastic fibroma suggests that the fibroma-like tissue reflects an unusual secondary tissue change within an otherwise typical fibrous dysplasia. To the best of our knowledge, only four cases of fibrous dysplasia with desmoplastic fibroma-like tissue changes have been reported.

McCune-Albright syndrome is a rare condition consisting of triad of fibrous dysplasia, hyperfunctioning endocrinopathy, and café au lait macules of skin. A 31-year-old man was diagnosed with fibrous dysplasia 18 years before presenting with pathologic fracture. No workup for polyostotic fibrous dysplasia was performed at that time. He now presented with left facial swelling and skeletal features of acromegaly. MRI revealed a 15-cm enhancing tumor diagnosed histopathologically as high-grade osteosarcoma. Tc-methylene diphosphonate bone scintigraphy revealed decreased uptake at the tumor site contrary to the usual finding of avid uptake by the neoplastic bone forming tumor.

Somatic gain‐of‐function mutations of GNAS cause a spectrum of clinical phenotypes, ranging from McCune‐Albright syndrome (MAS) to isolated disease of bone, endocrine glands, and more rarely, other organs. In MAS, a syndrome classically characterized by polyostotic fibrous dysplasia (FD), café‐au‐lait (CAL) skin spots, and precocious puberty, the heterogenity of organ involvement, age of onset, and clinical severity of the disease are thought to reflect the variable size and the random distribution of the mutated cell clone arising from the postzygotic mutation. We report a case of neonatal MAS with hypercortisolism and cholestatic hepatobiliary dysfunction in which bone changes indirectly emanating from the disease genotype, and distinct from FD, led to a fatal outcome. Pulmonary embolism of marrow and bone fragments secondary to rib fractures was the immediate cause of death. Ribs, and all other skeletal segments, were free of changes of typical FD and fractures appeared to be the result of a mild‐to‐moderate degree of osteopenia. The mutated allele was abundant in the adrenal glands and liver, but not in skin, muscle, and fractured ribs, where it could only be demonstrated using a much more sensitive PNA hybridization probe‐based FRET (Förster resonance energy transfer) technique. Histologically, bilateral adrenal hyperplasia and cholestatic disease matched the abundant disease genotype in the adrenals and liver. Based on this case and other sporadic reports, it appears that gain‐of‐function mutations of GNAS underlie a unique syndromic profile in neonates characterized by CAL skin spots, hypercortisolism, hyperthyroidism, hepatic and cardiac dysfunction, and an absence (or latency) of FD, often with a lethal outcome. Taken together, our and previous cases highlight the phenotypic severity and the diagnostic and therapeutic challenges of MAS in neonates. Furthermore, our case specifically points out how secondary bone changes, unrelated to the direct impact of the mutation, may contribute to the unfavorable outcome of very early‐onset MAS. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Fibrous dysplasia (FD) is a benign bone disorder, in which normal bone structure is replaced by fibrous connective tissue. Polyostotic FD is also related to McCune-Albright syndrome with possible endocrine disorder and Cafe-au-lait macules. Although FD commonly presents as craniofacial bone abnormality, atypical presentation can be misleading and pose a difficulty in clinical diagnosis. Here we report a case of polyostotic FD, who presented as an accidental finding of multiple spinal osseous lesions, leading to clinic workup for metastatic cancer.

A 33-year-old woman with McCune-Albright syndrome was referred for a Ga-DOTATATE PET/CT study for evaluation and staging of a biopsy-proven pancreatic tail neuroendocrine tumor. The scan demonstrated intense focal octreopeptide uptake corresponding to the known neuroendocrine tumor at the pancreatic tail/splenic hilum. There was no evidence of octreopeptide-avid metastases. Diffuse octreopeptide uptake was demonstrated in multiple bones involving the right side of the skeleton. The concurrent CT demonstrated corresponding expansile lucent changes consistent with the known fibrous dysplasia.

Multiple non-ossifying fibromas (MNOFs) occur either isolated or in association with other anomalies, are usually localized in the long bones of the lower limbs, may be radiographically confused with other skeletal lesions, and tend to heal spontaneously with the completion of the skeletal growth. Segmental distribution, either monomelic or polymelic and ipsilateral, is rare and commonly observed in the context of developmental diseases known as "RASopathies", which are caused by mutations in genes that encode components or regulators within the Ras/mitogen-activated protein kinase signaling pathway. We describe here the radiographic and pathologic features of an 18-year-old Caucasian boy, whose clinical history started at the age of 3 when the diagnosis of aneurysmal bone cyst was made on a lytic lesion of his left clavicle. Over the following 2 years, the patient developed polyostotic and monomelic lesions within the left humerus, radius, and ulna. No other skeletal and extra-skeletal anomalies were clinically detected. The lesions were interpreted as consistent with polyostotic fibrous dysplasia and MNOFs and showed an unusually aggressive clinical course with progressive increase in size and coalescence. The definitive diagnosis of MNOFs was made after the exclusion of fibrous dysplasia by molecular analysis. The polyostotic and monomelic distribution of the lesions and the unusually aggressive clinical course contribute to make this case of MNOFs unique.

Polyostotic fibrous dysplasia is a skeletal disease that results from somatic activating mutations in the gene GNAS in skeletal stem cells, leading to proliferation of immature osteogenic cells with replacement of normal marrow and bone with fibro-osseous tissue. Lesions may cause bone deformity or fracture. In the surgical care of polyostotic fibrous dysplasia, the role of grafting and the optimal grafting material are not clear. The purpose of this study was to evaluate the long-term survival of bone-grafting procedures in subjects with polyostotic fibrous dysplasia over time.The operative reports and radiographs of a cohort of subjects with polyostotic fibrous dysplasia followed in a natural history study were reviewed. Twenty-three subjects (mean age at the time of enrollment, thirteen years [range, two to forty years]) with fifty-two bone-grafting procedures had a mean follow-up time of 19.6 years (range, twenty-nine months to forty-seven years). Kaplan-Meier life table estimates, Cox proportional hazard models, and t tests comparing means were performed to assess various aspects of graft survival.Kaplan-Meier curves showed a 50% estimate of survival of 14.5 years. Cox proportional hazards models showed no advantage comparing allograft with autograft or structural with nonstructural graft materials. The mean age of the patients was significantly greater (p0.001) in the subgroup of subjects in whom grafts were maintained over time (20.9 years) compared with the subgroup of patients whose grafts were resorbed over time (9.8 years).Bone-grafting, including both allograft and autograft, is of limited value in ablating the lesions of fibrous dysplasia. The expectations of patients and surgeons should include the high probability of graft resorption over time with return of bone characteristics of fibrous dysplasia, particularly in younger patients. This suggests the maintenance of normal bone mechanics with implant support should be the priority of any surgical intervention.

The McCune-Albright syndrome (MAS) is a sporadic rare disease characterized by a triad of physical signs: Cafe-au lait spots, polyostotic fibrous dysplasia, and autonomous endocrine hyperfunction. Based on the studies, it can be concluded that this syndrome is caused by mutations that happen in the gene: GNAS1. A small number, but not all, of the patient’s cells contain this faulty gene (mosaicism). MAS is predominantly observed in girls and is rarely reported in males. We report a 5-year-old boy with cafe-au-lait spots, polyostotic fibrous dysplasia, and without any endocrine dysfunction.

A 53-year-old female patient presented with complaint of volume increase in the face with 5 months’ of evolution. Physical examination showed a right hemifacial tumor, spontaneous pain, dystopia, amaurosis, right nasal obstruction, and multinodular hardened lesions on the right upper alveolar ridge. The tomographic examination revealed hyperdense lesions in frontal bone enveloping the ethmoid bilaterally, maxillary sinus, and nasal cavity, in addition to the other long bones, which led to the diagnosis of polyostotic fibrous dysplasia. No other endocrinologic finding suggested a syndromic variant, and the rapid and progressive growth led the team to investigate the malignancy. After an angiotomographic study, intense periosteum activity and central vascularization by the external carotid artery were observed. Biopsy was chosen through the core biopsy method, in which the immunohistochemistry confirmed the differentiation in intermediate-grade spindle cell sarcoma. The proposed treatment was chemotherapy and radiotherapy, evolving to death within 3 months’ of the disease.

Fibrous dysplasias are developmental bone disorders in which the medullary cavity is replaced by fibrous tissue. It can be monostotic involving a single bone or polyostotic involving multiple bones. Unlike the monostotic type, the polyostotic type of fibrous dysplasia is associated with non skeletal manifestations like café au lait macule and/or endocrine hyperfunction. The presence of endocrine involvement differentiates McCune Albright syndrome from Jaffe Lichtenstein syndrome. We hereby report a case of an 11-yearold male child presenting with polyostotic type of fibrous dysplasia involving bilateral femurs with café au lait macule having no endocrine disease consistent with the diagnosis of Jaffe Lichtenstein disease. He also had unilateral absent testis which is rarely reported in this syndrome.

Fibrous dysplasia is a rare disorder of bone that is uncommon in the head and neck region. Herein, we present a rare case of polyostotic fibrous dysplasia involving the right temporal bone and thyroid cartilage in a 19-year-old male. This unique location necessitates close surveillance due to the proximity to the airway and the potential for malignant degeneration.

Guanine nucleotide-binding protein/α-subunit (GNAS) mutations are involved in fibrous dysplasia (FD) pathogenesis. Here, we analyzed GNAS mutations in FD which were performed by pyrosequencing DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue. The mutation detection rate was determined in FD specimens with and without decalcification. GNAS mutation was identified in 28 cases out of 87 FDs (32.18%) [p.R201C (N = 14) and p.R201H (N = 14)]. GNAS mutation was more likely to occur in polyostotic FD (7/28, 25.0%); FD without GNAS mutation was mostly monostotic form (56/59, 94.9%, P = 0.011). The G > A (R201H) mutation was more frequent in polyostotic FD (6/14 patients, 42.9%) than the C > T (R201C) mutation (1/14, 7.1%) (P = 0.077). We divided the FD cases into two subgroups: tissue specimens that were not decalcified (N = 35, 40.2%), and tissue specimens that were decalcified (N = 52, 59.8%). GNAS mutation was more frequently identified in FD specimens that were not subjected to decalcification (23/35, 65.7%) than in FD specimens that were decalcified (5/52, 9.6%) (P = 0.001). In conclusion, mutation analysis of GNAS by pyrosequencing has diagnostic value in FFPE tissue of patients with FD, especially in specimens that were not decalcified. The R201H substitution mutation of GNAS may be involved in the pathogenesis of polyostotic FD.

Background: McCune-Albright syndrome (MAS), which includes polycystic fibrous dysplasia, precocious puberty, and café au lait spots, is a rare disorder caused by somatic activating mutations of the GNAS gene. GNAS mutations have also been implicated in various sporadic tumors, including hepatobiliary and pancreatic neoplasms. Aim: The aim of this study was to assess the prevalence of hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome. Patients and Methods: Nineteen patients diagnosed between 1995 and 2012 with MAS in a tertiary referral center for rare growth disorders were screened with dedicated gadolinium-enhanced magnetic resonance imaging for hepatobiliary and pancreatic neoplasms between June 2011 and December 2012. Results: Six (32%) of the 19 screened patients were found to have hepatic, pancreatic, or biliary lesions, excluding liver hemangiomas, liver cysts, and focal nodular hyperplasia. This includes pancreatic ductal lesions observed in 4 patients, including numerous branch-duct intraductal papillary mucinous neoplasms in 3 patients. Biliary lesions were observed in 1 patient, with a large choledochal cyst also involving the left biliary branch. Finally, multiple inflammatory/telangiectatic hepatic adenomas were observed in 2 patients, including 1 with proven somatic GNAS mutation. Conclusion: We describe the first observation of syndromic intraductal papillary mucinous neoplasms and the new association between MAS and pancreatic neoplasms, namely intraductal papillary mucinous neoplasms of the pancreas but also rare hepatobiliary neoplasms including liver adenomas and choledochal cysts. These findings strongly suggest that somatic activating GNAS mutations, possibly through cAMP pathway disorders, are involved in the tumorigenesis of hepatobiliary and pancreatic tissues originating from the foregut endoderm and have led us to use a routine screening by dedicated magnetic resonance imaging including both pancreatobiliary and liver sequences in patients with MAS.

Fibrous dysplasia is a benign tumor-like lesion of bone believed to be developmental in origin. Polyostotic fibrous dysplasia (FD) is a rare condition. Our case was further complicated by the presence of secondary aneurysmal bone cyst (ABC). This is the second reported case of polyostotic FD with secondary ABC.

McCune-Albright syndrome (MAS) is characterized by polyostotic fibrous dysplasia, café-au-lait skin pigmentations, and gonadotropin-independent sexual precocious puberty, resulting from a somatic postzygotic activating mutation of the GNAS1 gene.We report a virilizing sclerosing-stromal tumor of the ovary in a young female with MAS.She presented polyostotic fibrous dysplasia of the left upper and lower limbs and a café-au-lait skin spot in the posterior area of the neck. She had a history of precocious puberty, diagnosed at the age of 6 years and treated with cyproterone acetate until the age of 10 years; then she developed central puberty with severe oligomenorrhea. At the age of 23 years, she was hospitalized for a virilization syndrome including hirsutism, acne, deepening of the voice, amenorrhea, and clitoromegaly. Serum levels of T were dramatically increased (1293 ng/dl; normal range, 10-80). The abdominal computed tomography scan revealed a solid mass located on the left ovary.An ovariectomy was performed, and histological examination revealed a sclerosing-stromal tumor with pseudolobular pattern.Immunohistochemical studies revealed that the tumor cells expressed all steroidogenic enzymes involved in androgen synthesis. Molecular analysis revealed that ovarian tumor cells harbored the Arg 201 activating mutation in the GNAS1 gene. After surgery, T levels returned to normal, the patient retrieved a normal gonadal function, and she was able to become pregnant.This observation extends the clinical spectrum of ovarian pathology of women with MAS. However, the mechanisms causing this ovarian tumor remain unclear, even if the gsp oncogene has been implicated in the pathogenesis of some gonadal tumors.

McCune- Albright Syndrome (MAS) is a rare fibrosseous lesion, characterized by a classic triad of polyostotic fibrous dysplasia (PFD), cafι -au-lait macules (CALM) and underlying endocrinopathies. We present the oral findings of an interesting case of MAS with relevant review of literature. A 30-year-old male presented to us with swelling of both jaws over a period of two years. Cutaneous examination revealed cafι - au - lait macule over the back, crossing the midline. Skeletal survey showed expansile, osteolytic, mixed radiolucent- radiopaque lesions in skull and jaw bones. Serum alkaline phosphatase was elevated (388 IU/L), with normal calcium, phosphorus, parathyroid hormone and 25 hydroxy vitamin D levels. Diagnosis of McCune- Albright syndrome was made and he was treated with parenteral bisphosphonates (intravenous Zoledronate 4 mg) and is under follow up for surgical recontouring of the jaws. Early recognition facilitates better treatment and improves prognosis by reducing the morbidity.

Malignant changes in polyostotic fibrous dysplasia are very rare. Most common malignancies reported are osteosarcoma and fibrosarcoma, chondrosarcoma and malignant fibrous histiocytoma. Here, we report a previously diagnosed case of fibrous dysplasia who has developed leiomyosarcoma; diagnosis of which was delayed for about one year despite repeated fine needle aspiration and open biopsy.

Results are presented of measurements of skeletal blood flow made in 80 patients with painful benign or malignant diseases of the skeleton, excluding patients with Paget's disease. In crush fracture osteoporosis, total bone blood flow was slightly lower than normal although skeletal perfusion was normal. High values of bone blood flow were seen in 14 20 patients with osteomalacia and 3 12 patients with primary hyperparathyroidism. Very high values, comparable to those seen in the most severely affected patients with Paget's disease, were seen in polyostotic fibrous dysplasia, 2 out of 4 cases of Engelmann's disease and 1 out of 3 cases of renal osteodystrophy. Results were less elevated in myositis ossificans, secondary skeletal involvement with breast and prostatic carcinomata, myelomatosis and sympathetic osteodystrophy.

Malignant transformation of fibrous dysplasia (FD) is exceedingly rare, occurring in less than 1% of all FD cases, and has been described in both monostotic and polyostotic forms of this entity. We report a case of a large proximal femur mass arising in a 45-year-old man. The biopsy revealed a high-grade pleomorphic malignancy that focally expressed multiple keratins. Based on the presence of keratin immunoreactivity, the morphologic differential diagnosis included metastatic sarcomatoid carcinoma. However, review of the clinical information revealed a history of polyostotic FD, and imaging findings were compatible with malignant transformation of FD. The resected neoplasm was biphasic and composed of areas of conventional FD admixed with a high-grade pleomorphic malignancy. Activating GNAS mutations were identified in both components. To the best of our knowledge, this is the first description of keratin expression in malignant transformation of FD.

Polyostotic fibrous dysplasia (PFD) is a sporadic benign skeletal condition that typically presents with bone pain, deformities and pathological fractures. It preferentially affects long bones. Sarcomatous transformation, most commonly osteosarcoma, occurs in 7% of patients with PFD.1 Diagnostic challenges exist as radiographic appearances range from cystic foci to pagetoid or sclerotic lesions. Differential diagnoses include juvenile bone cysts, aneurysmal bone cysts and giant cell tumours.2 We describe a case of a 27-year-old woman who had been diagnosed with PFD at the age of 12 years, and who had an extensive history of pathological …

Fibrous dysplasia is a benign and pseudoneoplasic osteopathy with slow progression, characterized by the replacement of normal bone by an excessive proliferation of fibrous connective tissue cell, interspersed with irregular bone trabeculae. In general, it affects 1 between 4,000 to 10,000 individuals living births. This is a not familiar, congenital disorder, which produces around 2.5% of all bone tumors and more than 7% of all non-malignant bone tumors. This article aims to report a clinical case of monostotic fibrous dysplasia in jaw, proceeding with its surgical correction and to make a review of literature, describing the most important features and the major controversies.

Objective Beyond the classic triad of peripheral precocious puberty, cafe-au-lait skin pigmentation and polyostotic fibrous dysplasia, partial presentation McCune–Albright syndrome (MAS) has been reported, including the association of isolated recurrent ovarian cysts in early infancy. The aims of this study were to determine whether isolated voluminous fetal unilateral ovarian cysts (diameter > 4 cm) may be associated with a Gsα activating mutation, suggestive of MAS. Design We followed five female fetuses presenting with voluminous unilateral ovarian cysts by ultrasonography until delivery. At birth, all patients underwent percutaneous cyst aspiration and two patients later underwent ovariectomy. A sensitive PCR-based method was used to analyze the Gsα activating mutation in DNA obtained from ovarian cystic fluids or tissue. Results Among the five cases, one Gsα mutation (R201C) was identified in the ovarian tissue. Conclusions We demonstrate for the first time that voluminous fetal unilateral ovarian cysts may be suggestive of MAS. Systematic search for the Gsα mutation should be performed in all newborns with voluminous fetal unilateral ovarian cysts requiring percutaneous cyst aspiration, because early diagnosis of MAS prevents unnecessary oophorectomy to eliminate questions of malignancy and imposes long-term clinical, biological, and imaging follow-up to detect other early manifestations of MAS. © 2012 John Wiley & Sons, Ltd.

McCune-Albright syndrome (polyostotic fibrous dysplasia, café-au-lait skin spots, and precocious puberty) is a genetically mosaic disorder with populations of mutant and normal cells in affected organs. Cushing syndrome, a rare feature of the condition, usually affects infants and is the result of corticotropin-independent primary bilateral adrenal disease, usually interpreted as nodular adrenocortical hyperplasia. In this study of 9 patients with Cushing syndrome and McCune-Albright syndrome, light microscopy revealed a characteristic bimorphic pattern of diffuse and nodular hyperplasia and a distinctive form of cortical atrophy with apparent zona glomerulosa hyperplasia in 8 patients, all very young. The pattern could be explained by the presence of a mosaic distribution of mutant and normal cells in the adrenal glands. The findings are different from those in inherited or other forms of genetically caused Cushing syndrome. The ninth patient, aged 17 years, had an adrenal adenoma and diffuse cortical hyperplasia in each adrenal gland.

McCune Albright syndrome (MAS) is a rare disease due to a sporadic mutation in Gs protein inducing polyostotic fibrous dysplasia, pigmented skin patches and hyper functioning endocrinopathies. We aimed to report its association with a hot thyroid nodule and gigantism. Case report. A man aged 37, with a history of pigmented skin lesions and lameness was referred for acromegaly. He was giant (height = 1.94 m/ target stature = 1.68 m), and had “cafe au lait” spots. Biological analyses argued for pituitary mixed secretion (random growth hormone = 22 ng/ mL, N

We report a rare case of polyostotic fibrous dysplasia on endocrine hyperfunction with elevated human growth hormone and normal serum level of prolactin. There were some differential points of gender, gigantism, endocrine function, and GNAS gene from McCune-Albright syndrome. Malignant transformation was suspected in the pelvic tumor from imaging because rapid growth of the tumor by imaging was observed; however, no malignant change occurred in this case.

McCune-Albright syndrome (MAS) is an extremely rare disorder that classically affects the bones, skin and endocrine system. Classical features are fibrous dysplasia of bone, skin pigmentation and dysfunction of certain endocrine glands. Diagnosis of MAS is usually established on clinical grounds. Different imaging modalities help to confirm the fibrous dysplasia, among those radio iso-tope bone scan is an excellent tool for early diagnosis and evaluation of bony extension.Bangladesh J. Nuclear Med. 19(1): 61-63, January 2016

Fibrous dysplasia, a benign fibro osseous condition involving one or more bones of the cranial and extra cranial skeleton, consists of non-encapsulated lesion which shows replacement of a normal bone by cellular fibrous tissue containing islands of metastatic bone (Edwards 1984). It has been classified by W.H.O. as developmental in origin. Fibrous dysplasia of bone is one of the most perplexing diseases of the osseous tissue. It is a lesion of unknown etiology, uncertain pathogenesis and diverse histopathology. A case report of fibrous dysplasia is presented here and discussed in detail.

Fibrous dysplasia is a nonspecific hamartomatous skeletal developmental anomaly, characterized by slow progressive replacement of a localized area of bone by an abnormal proliferation of isomorphic fibrous tissue. The exact etiology of it is in ambiguity. The recent concept with etiopathogenesis proposes that post-zygotic mutation in the guanine nucleotide binding protein a-stimulating activity polypeptide-1 gene. The Fibrous dysplasia can be of monostotic type which is common and affects maxilla, and polyostotic type, a rare variety. The incidence of cranial fibrous dysplasia is even rare amongst the primary bone lesions, representing less than one percent. There is no specifie treatment for fibrous dysplasia. Untreated fibrous dysplasias are associated with complications like hearing loss, trismus, and facial disfigurement for which cosmetic surgical treatment is rendered.

The authors sought to identify radiological criteria assisting in the diagnosis of craniofacial fibrous dysplasia and differential diagnosis of fibro-osseous lesions by comparing computed tomography (CT) and magnetic resonance imaging (MRI) findings and histological results in 23 patients with presumed fibrous dysplasia. From February 2000 to March 2005, 23 patients (17 women and six men, aged 9–66 years) with facial bone disease underwent CT and MRI studies. Imaging findings were compared with the results of histological examination performed within 1 month of the radiological diagnosis. The combination of CT and MRI led to a presumptive diagnosis of fibrous dysplasia in all cases, but histology confirmed the diagnosis in 18 cases only. In two cases that had initially been considered cyst-like variants of fibrous dysplasia and were associated with irregular enhancement at MRI, histology characterised the lesions as single locations of multiple myeloma. In one case, targeted biopsy of areas showing intense enhancement led to a diagnosis of low-grade fibrosarcoma; in the remaining two cases, the definitive diagnoses were ossifying fibroma and myeloproliferative disease. MRI proved useful in differentiating fibrous dysplasia from other bone diseases, defining clinical behaviour, identifying neoplastic foci within dysplastic tissue and distinguishing benign from malignant bone lesions. The authors suggest a broader use of contrast-enhanced MRI for the diagnosis and follow-up of dysplastic lesions of the facial bones and for planning appropriate surgical treatment.

Fibrous dysplasia of bone is a genetic, non-inheritable disease, characterized by bone pain, bone deformities and fracture, involving one or several bones. It is caused by mis-sense mutations occurring post-zygotically in the gene coding for the alpha-subunit of the stimulatory G-protein, Gs, in the guanine nucleotide binding, alpha stimulating (GNAS) complex locus in chromosome 20q13. This mutation results in osteoblastic differentiation defects, and bone resorption is often increased. The bone lesions may be associated with endocrine dysfunctions and café-au-lait spots; this is known as McCune-Albright syndrome. Patients with polyostotic fibrous dysplasia often have renal phosphate wasting. The disease, however, has a wide clinical spectrum, so many patients are asymptomatic. Diagnosis relies on radiographs and pathology. Bisphosphonates have been used in the treatment of fibrous dysplasia to relieve bone pain and improve lytic lesions, but they are still under clinical evaluation. Calcium, vitamin D and phosphorus supplements may be useful in some patients. Surgery is also helpful to prevent and treat fracture and deformities.

A 52-year-old man with long-standing craniofacial polyostotic fibrous dysplasia (FD) and no history of prior radiation therapy developed a spontaneous right temporal bone osteosarcoma. Such spontaneous sarcomatous degeneration of FD is rare, particularly in the calvarium/skull, where, to our knowledge, only six prior cases have been reported in the literature. We report this case because it is a rare entity with well-documented CT and MR images, and to emphasize the importance of depicting imaging features of sarcomatous degeneration among the complex imaging findings of FD.

Fibrous dysplasia of the spine is uncommon, especially in monostotic form. Isolated vertebral involvement in polyostotic form is very rare. We report a case of polyostotic fibrous dysplasia with lesions localized to dorso-lumbar spine in a 45-year-old rheumatoid arthritis patient. No associated appendicular lesions, cutaneous manifestations or endocrinopathies were seen. The extreme rarity of this type of lesion can pose a diagnostic dilemma, and biopsy is required for diagnosis. The association with rheumatoid arthritis in our case seems to be a chance occurrence.

McCune-Albright syndrome (MAS) is a rare disorder that develops from an activating mutation in the Gs gene. It is characterized by an association with Polyostotic fibrous dysplasia, and precocious puberty, Caf-au-lait pigmentation, and other endocrinopathies that result from the hyperactivity of a variety of endocrine glands. Recently we encountered a patient with MAS with fibrous dysplasia, skin pigmentation, acromegaly, hyperprolactinemia and a thyroid nodule. A 23-year-old male presented for an evaluation of a change in his facial structures. Fibrous dysplasia was diagnosed by a bone biopsy and radiographic studies. The GH level increased paradoxically after an oral glucose load. The plasma prolactin, IGF-1 and alkaline phosphatase were high. Thyroid ultrasonography revealed multiple nodules. The brain MRI demonstrated a mass in the left pituitary gland. Genetic analysis identified a change from Arg (CGT) at codon 201 to Cys (TGT).

Intramuscular myxomas are benign and rare tumors that affects predominantly the lower limbs. The association of myxomas and fibrous dysplasia, usually polyostotic, is rarer. This association is known as Mazabraud's syndrome, of which about 81 cases have been described in the literature. We present a new case of this uncommon association to emphasise the importance of recognizing this syndrome in the diagnosis and appropriate management of the patient.