Extensive Sclerosis Research Articles

Nonneoplastic and neoplastic sclerosing lesions of the breast.

Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplasticentities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed.

Thoracic solitary fibrous tumors with small cell features: A clinicopathological and immunohistochemical analysis of 5 cases

Five cases of thoracic solitary fibrous tumor (SFT) with small cell features are presented mimicking a neuroendocrine neoplasm. The patients were four men and one woman aged 43 to 74 years who presented with symptoms of chest pain, cough, dyspnea or hemoptysis. Two tumors were intrapulmonary neoplasms, while three were pleural-based. Grossly, the tumors ranged in size from 4 to 6 cm and were white and solid; in two tumors necrosis was apparent. Histologically, they were characterized by a cellular proliferation composed of small cells with round nuclei and inconspicuous nucleoli. The cellular proliferation in some areas had a subtle nested pattern, while in other areas the tumor showed extensive sclerosis and small vessel proliferation. Cellular pleomorphism was not marked and the mitotic activity varied from 1 to 5 mitotic figures per 10 high power fields. Microscopically, necrosis was observed in two cases and focally present in one. Immunohistochemical stains showed tumors cells universally negative for pancytokeratin; in the two pulmonary cases, focal staining for synaptophysin, CD56, and INSM1 was observed. The unexpected lack of expression of pancytokeratin led to additional analysis revealing positive staining with CD34 and STAT6 confirming a diagnosis of SFT. Clinical follow-up showed tumor recurrence in one patient while three patients remained alive and well after a period of 12 to 20 months. The current cases highlight an unusual variant of SFT that may be confused with other small cell tumor entities, such as neuroendocrine or neuroectodermal tumors, especially when originating in the thoracic cavity.

Sclerosing Central Mucoepidermoid Carcinoma: Rare Case Series and Review

Introduction:
 The most frequent malignant tumour of the salivary glands is mucoepidermoid carcinoma which accounts for 30% of all malignancies of the salivary glands. There are numerous histologic variations with various levels of differentiation. Sclerosing MEC (SMEC) is a rare subtype of MEC that has the potential to be misdiagnosed as a low-grade non-SMEC malignancy or a benign reactive condition. There have been no cases of the extremely rare sclerosing variant of central or intraosseous MEC reported as of yet.
 Case reports:
 We present two cases of Sclerosing Central MEC, in which histologic analysis revealed relatively well-circumscribed, nonencapsulated tumours made up of dispersed epithelial islands of low-grade MEC and extensive central sclerosis. Similar sclerotic stroma was present in the tumor in the second case, but the epithelial component was of intermediate grade. Both cases showed abundant intracytoplasmic mucin and positive Mayer mucicarmine and PAS stains.
 Conclusions:
 Sclerosing central mucoepidermoid carcinoma was identified as the cause. Both cases underwent a complete resection of the tumor and have since been free of the disease.

Case report: Tuberculosis as a cause unilateral of sacroiliitis in lupus patients

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease, with variable manifestations, which is frequently exacerbated, requiring differential diagnosis with infectious conditions. In the case report, the patient satisfied the following criteria as per ACR/EULAR (2019): FAN 1:640 homogeneous nuclear, fever, alopecia, hypocomplementemia, antidsDNA 1:80 and lymphopenia. She was on: prednisone 20mg/day, hydroxychloroquine 400mg/day and calcium+vitamin D3. She was pale (3/4+), dehydrated and tachycardic. Osteoarticular examination: Patrick-Fabere positive for left sacroiliac; pain in external and internal rotation in left hip and painful palpation in the metacarpal, proximal interphalangeal, wrists, knees, ankles, hip and thigh joints, especially in the left and right. Radiography showed extensive sclerosis (grades 3 and 4) in left sacroiliac and rectified lumbar lordosis. Later, magnetic resonance imaging revealed extensive subcortical bone marrow edema at the left sacroiliac associated with capsulitis. In addition to positive BAAR TRM-TB, Lupus patients present a high incidence of TB, which is an important hypothesis in febrile cases with inflammatory lombalgy, since its osteoarticular form mainly affects the spine. Therefore, the importance of differential diagnosis for effective management is evident.

Maxillofacial Radiology 199

Both patients presented with extensive sclerosis limited to the tooth-bearing regions of the jaws. The areas affected by secondary osteomyelitis show radiolucent zones surrounding the radiopaque lesions (Figure 1). The first patient presented with a jaw fracture following a failed extraction attempt (Figure 1- arrow). Due to the extensive bony sclerosis, associated impacted teeth are common (Figure 2).

Incidence, demographic, biochemical, and clinicopathological profile of primary IgAN in a tertiary care center from Northern India

BackgroundPrimary IgA nephropathy (IgAN) has variable distribution and clinicopathological spectrum throughout the world. We report the incidence, demographic, and clinicopathological profile of primary IgAN from a tertiary care center in Northern India.MethodsThis is a single-center, prospective, observational study conducted at Sheri- Kashmir Institute of Medical Sciences, J&K, India, from January 2015 to December 2018. The study was approved by the hospital ethical committee.ResultsA total of 106 patients were included in this study, accounting for 19% (106/558) of all native kidney biopsies done during the period from January 2015 till December 2018. Males and females accounted for 60.4% (64/106) and 39.6% (42/106), respectively, with a ratio of 1.5:1. The mean age was 31.37±11.60 years. Edema and hypertension were the most common presenting symptoms and signs, seen in 69 (65.1%) and 72 (67.9%) patients, respectively. The baseline 24-h urine protein excretion was 2.32 ±1.34 g, Nephrotic range proteinuria (≥3.5g/day) was seen in 23/106 (21.7%). Average serum creatinine was 1.6±0.80 mg/dl and estimated glomerular filtration rate using CKD-EPI was <60 ml/min/1.73 m2 in 48.1% of patients (51/106). In patients with < 1 g proteinuria, 36.8% had E1, 78.9% had S1, 36.8% had T1, and 42.1% had T2 lesions.ConclusionsIgAN is common in North India and has a more severe histopathological presentation, characterized by extensive sclerosis and tubulointerstitial fibrosis. Renal dysfunction and nephrotic range proteinuria are common. Hypertension, low eGFR, and proteinuria correlate with the presence of segmental scarring, endocapillary hypercellularity, and IFTA. Screening of asymptomatic individuals might help in early diagnosis and long-term preservation of renal function.

Extensive Sclerosis ("mummification") in Lacrimal Gland Pleomorphic Adenoma May Indicate Neighboring Malignant Transformation.

Salivary gland pleomorphic adenomas not uncommonly show extensive sclerosis ("dense hyalinization," "coagulative necrosis," or "mummification"), which arise spontaneously or after prior surgery, and this change is considered a high-risk factor for malignant transformation of benign salivary adenomas. While minor hyalinization is common in lacrimal gland adenomas, massive sclerosis-where almost all (90% or more) of the tumor is replaced by an amorphous hyaline material-is extremely rare. Four patients (2 males) are described in whom, despite not having an acute inflammatory episode, their lacrimal gland tumor showed marked sclerotic necrosis within the majority of either the benign or malignant parts of the tumor. Three tumors had evidence of malignant change, 2 to adenocarcinoma, and 1 to mucoepidermoid carcinoma, but none of the malignant areas showed perineural or endovascular invasion. Extensive sclerosis in association with a lacrimal gland pleomorphic adenoma (LGPA) is rare (4/110 of the cases) and-as with salivary adenomas-appears to be associated with a high chance of associated malignant change. Both the surgeon and the histopathologist should regard extensive sclerotic necrosis as a harbinger for malignant change in association with benign pleomorphic adenomas of the lacrimal gland.

Typical and Atypical Radiographic Features of Symptomatic Osteoblastoma in the Spine

Spine osteoblastomas (OBs) are relatively rare. In contrast to osteoid osteoma, radiologic and clinical manifestations of OB can be varied and atypical. Typical radiographic features in spinal OB include peritumoral bone sclerosis, bone marrow edema, and soft tissue edema. Atypical radiographic features include lesions involving ≥3 segments, lesions with extensive (≥3 segments) bone sclerosis, excessive edema (≥3 segments) of soft tissue and bone marrow, no intralesional calcification, and location in the vertebral body only. The aim of this study was to identify typical and atypical features of OB. Pretreatment computed tomography scans and magnetic resonance imaging were reviewed retrospectively. Percutaneous biopsies were performed to confirm pathology in atypical cases. A total of 50 images from patients with diagnosed OB were reviewed. Atypical radiographic features were found in 18 cases (36%). Pathologic diagnosis was confirmed as OB in 86.2% (25/29) cases after percutaneous computed tomography-guided biopsy. Our results show that >30% of spinal OB cases might have atypical radiographic features. In cases with atypical radiographic features, computed tomography-guided biopsies are recommended.

Pancytopenia Secondary to Adult Osteopetrosis

Osteopetrosis (OP) is a rare genetically metabolic bone disorder caused by severe impairment of osteoclast-mediated bone resorption. It is characterised by extensive sclerosis of the skeleton, fragility fracture, haematopoietic insufficiency, nerve entrapment syndromes, and growth impairment. It is clinically classified into two major types: infantile (autosomal recessive, malignant) and adult (autosomal dominant, benign) OP. The infantile type is usually diagnosed early in life, while adult type is diagnosed in late adolescence or adulthood. Approximately one-half of patients are asymptomatic and the diagnosis is made incidentally. However, some patients might present with one or more complications of OP, and the diagnosis is made during the work-up and evaluation. Here, the authors describe an unusual case of adult type OP presented with pancytopenia.

MON-363 Massive Bony Exostoses and Diffuse Osteosclerosis Secondary to Hepatitis C: Case Report

Introduction:Acquired osteosclerosis due to hepatitis C is a rare complication. While there are previously published case reports of this condition, to our knowledge this is the first case reported with diffusely increased osteosclerosis and prominent bony exostoses.Clinical Case:A 52-year old woman was evaluated in the Metabolic Bone Clinic for non-radiating left hip pain and visibly prominent hard, non-tender masses at the lateral aspect of her bilateral hips and proximal humerus. She denied history of fragility fractures, radiation exposure, risk factors for sexually transmitted diseases or substance abuse. Laboratory evaluation showed vitamin D deficiency with a value of 18 ng/mL (reference range: 25-100 ng/mL), elevated alkaline phosphate of 426 IU/L (reference range: 30-116 IU/L) and markedly increased serum C-telopeptide with a value of 1901 pg/mL (reference range: <1008 pg/mL). Plain radiographs showed multiple exostoses at the pelvis, hip, and shoulders. MRI showed extensive thoracic spine endplate sclerosis and increased sclerosis throughout the pelvis and proximal femurs. Massive calcifications adjacent to the greater trochanters were also identified. A total body bone scan revealed intensely increased uptake in multiple bones consistent with a “super scan.” Bone biopsy showed sclerotic bone with extensive remodeling. Computed tomography of the chest, abdomen, and pelvis was negative for malignancy. Given the symmetric nature of these lesions and diffusely increased uptake, the diagnosis of metabolic bone disease was considered. Further testing revealed hepatitis C Ab positivity confirmed with HCV Quant PCR 1553475 IU/mL (reference range: undetected). Pathologic findings were attributed to hepatitis C and treatment for hepatitis c was initiated with subsequent improvement in alkaline phosphate to 273 IU/L.Clinical Lessons:Osteosclerosis represents a little-known complication of hepatitis C. It is postulated that hepatitis C itself or other unknown agents may stimulate hepatic growth factors that increase osteoblast action. The radiographic and bone scan findings are classic for acquired osteosclerosis seen as increased cortical thickening with an intensely increased uptake in multiple bones. It frequently affects the lower extremity and this condition may take years to develop. Bone formation markers such as alkaline phosphate are typically elevated and bone biopsies show increased rates of remodeling as seen in our patient. While bisphosphonates may improve the serum markers for bone formation, they have not been shown to reverse or halt the progression of skeletal changes. Thus far, there has been a single case report showing improvement in sclerosis following treatment for hepatitis C with ribavirin and interferon. Natural history, progression and treatment of this condition have not been well established.

Detecting Proteomic Indicators to Distinguish Diabetic Nephropathy from Hypertensive Nephrosclerosis by Integrating Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging with High-Mass Accuracy Mass Spectrometry

Introduction: Diabetic nephropathy (DN) and hypertensive nephrosclerosis (HN) represent the most common causes of chronic kidney disease (CKD) and many patients progress to ­end-stage renal disease. Patients are treated primarily through the management of cardiovas­cular risk factors and hypertension; however patients with HN have a more favorable outcome. A noninvasive clinical approach to separate these two entities, especially in hypertensive patients who also have diabetes, would allow for targeted treatment and more appropriate resource allocation to those patients at the highest risk of CKD progression. Meth­ods: In this preliminary study, high-spatial-resolution matrix-assisted laser desorption/ion­ization (MALDI) mass spectrometry imaging (MSI) was integrated with high-mass accuracy MALDI-FTICR-MS and nLC-ESI-MS/MS analysis in order to detect tissue proteins within kidney biopsies to discriminate cases of DN (n = 9) from cases of HN (n = 9). Results: Differences in the tryptic peptide profiles of the 2 groups could clearly be detected, with these becoming even more evident in the more severe histological classes, even if this was not evident with routine histology. In particular, 4 putative proteins were detected and had a higher signal intensity within regions of DN tissue with extensive sclerosis or fibrosis. Among these, 2 proteins (PGRMC1 and CO3) had a signal intensity that increased at the latter stages of the disease and may be associated with progression. Discussion/Conclusion: This preliminary study represents a valuable starting point for a future study employing a larger cohort of patients to develop sensitive and specific protein biomarkers that could reliably differentiate between diabetic and hypertensive causes of CKD to allow for improved diagnosis, fewer biopsy procedures, and refined treatment approaches for clinicians.

Total Hip Arthroplasty in Patient with Melorheostosis (Case Report)

Melorheostosis is a rare mesenchymal dysplasia of bone manifesting as regions of sclerosing and thickening of bone tissue. This disease may involve the adjacent soft tissues and lead to joint pain, limitation of joint motion, stiffness resulting from abnormal ossification and soft-tissue contractures due to periarticular fibrosis. The paper describes a clinical case of a patient who presented with pain and stiffness in the proximal part of the left hip which patient suffered for the last 10 years. At first the patient had intermittent pain in the lower back and left hip during and after walking. Radiographs revealed dense sclerotic and wavy cortex and hyperostosis involving the left iliac crest, the acetabulum, and the femur. CT angiography with contrast was performed for preoperative planning. During the procedure the authors performed total hip arthroplasty of the left hip with excision of fibro-ossifications in the left ilioinguinal area. Severe periarticular fibrosis of the soft tissue was observed intraoperatively and cartilage-like formation was visible around the joint. A sample of the ossification bone was resected for histologic confirmation of the diagnosis; extensive cortical sclerosis with varying thickness typical of melorheostosis was found. Early postoperative period went without complications following routine post-THR protocol. Postoperative X-rays at 6, 12, 24 months did not reveal any complications or new ossifications. Full ROM and pain-free function were achieved in the left hip and lower back of the patient. The present clinical case of total hip arthroplasty with excision of fibroossifications provided good clinical outcome for melorheostosis of the left hip.

Anatomical hemispherectomy revisited-outcome, blood loss, hydrocephalus, and absence of chronic hemosiderosis.

To evaluate microsurgical trans-sylvian trans-ventricular anatomical hemispherectomy with regard to seizure outcome, risk of hydrocephalus, blood loss, and risk of chronic hemosiderosis in patients with intractable seizures selected for surgery using current preoperative assessment techniques. Out of 86 patients who underwent hemispherectomy between February 2000 and April 2019, by a single surgeon, at a tertiary care referral center, 77 patients (ages 0.2-20years; 40 females) who had an anatomical hemispherectomy were analyzed. Five of these were 'palliative' surgeries. One-stage anatomical hemispherectomy was performed in 55 children, two-stage anatomical hemispherectomy after extraoperative intracranial monitoring in 16, and six hemispherectomies were done following failed previous resection. Mean follow-up duration was 5.7years (range 1-16.84years). Forty-six patients had postoperative MRI scans. Ninety percent of children with non-palliative hemispherectomy achieved ILAE Class-1 outcome. Twenty-seven patients were no longer taking anticonvulsant medications. Surgical failures (n = 4) included one patient with previous meningoencephalitis, one with anti-GAD antibody encephalitis, one with idiopathic neonatal thalamic hemorrhage, and one with extensive tuberous sclerosis. There were no failures among patients with malformations of cortical development. Estimated average blood loss during surgery was 387ml. Ten (21%) children developed hydrocephalus and required a shunt following one-stage hemispherectomy, whereas 10 (50%) patients developed hydrocephalus among those who had extraoperative intracranial monitoring. Only 20% of the shunts malfunctioned in the first year. Early malfunctions were related to the valve and later to fracture disconnection of the shunt. One patent had a traumatic subdural hematoma. None of the patients developed clinical signs of chronic 'superficial cerebral hemosiderosis' nor was there evidence of radiologically persistent chronic hemosiderosis in patients who had postoperative MRI imaging. Surgical results of anatomical hemispherectomy are excellent in carefully selected cases. Post-operative complications of hydrocephalus and intraoperative blood loss are comparable to those reported for hemispheric disconnective surgery (hemispherotomy). The rate of shunt malfunction was less than that reported for patients with hydrocephalus of other etiologies Absence of chronic 'superficial hemosiderosis', even on long-term follow-up, suggests that anatomical hemispherectomy should be revisited as a viable option in patients with intractable seizures and altered anatomy such as in malformations of cortical development, a group that has a reported high rate of seizure recurrence related to incomplete disconnection following hemispheric disconnective surgery.

Combination treatment for giant cell tumors of the bone.

e22504 Background: Positive effect of the monoclonal antibody denosumab in cancer treatment has been reported in recent years. Since surgical treatment is considered the main method of treatment for giant-cell tumors of the bone (GCTB), the purpose of our study was to improve treatment outcomes using denosumab. Methods: The study included 10 patients with verified GCTB (5 men, 5 women, mean age 36±3.14 years). Tumors were located in the upper third of the tibia (3 patients), the lower third of the tibia (3), iliac bone (1), heel bone - 1, the lower third of the femur - 1, the lower third of the humerus - 1.Patients received 2 cycles of neoadjuvant denosumab treatment (120 mg subcutaneously once every 4 weeks) with further tumor resection. The bone defect was reconstructed with bone grafting in marginal resections and endoprosthetics in segmental resections. The effect of neoadjuvant therapy was assessed morphologically by optical light microscopy; histological and histochemical methods were used. Results: Neoadjuvant treatment reduced pain syndrome and restored the support ability. X-ray and spiral X-ray CT showed sclerotic sites in the lytic foci. Consolidation of pathological fractures in the tumor area was registered, as well as fibrosis of the tumor focus. The tissue on the sections of removed material appeared dryish and whitish, it replaced the medullary canal. Microscopic examination of tumors revealed areas of extensive sclerosis foci, and a slight lymphohistiocytic infiltration in some cases. Osteoclasts and osteoblasts were absent in the histological preparations. Conclusions: Neoadjuvant denosumab in GCTB with the following surgery has a pronounced positive effect. This was confirmed by the morphological picture of the operative material demonstrating the development of extensive foci of loose and dense fibrous connective tissue with a small amount of lymphohistiocytic elements.

Incidence of Chronic Radiodermatitis after Fluoroscopically Guided Interventions: A Retrospective Study

PurposeTo assess the incidence and risk factors for chronic radiodermatitis after fluoroscopically guided interventions (FGIs) in high-risk patients. Materials and MethodsBetween 2010 and 2016, of 55,782 patients who underwent FGIs, 359 had a risk procedure for skin injury (maximal skin dose > 3 Gy, air kerma > 5 Gy, dose area product [DAP] > 500 Gy.cm2, or fluoroscopy time > 60 minutes). Ninety-one of these patients were examined by a dermatologist for radiodermatitis (median time after procedure, 31.2 months [95% confidence interval, 14.2–50.7]). In each case, the clinical features and topography of the skin lesions were recorded and their incidence calculated. The characteristics of the patients and of the FGIs were tested as risk factors. ResultsEight patients (8.8%) had chronic radiodermatitis; 19 (20.9%) had acute radiodermatitis. Body mass index, DAP value, and air kerma were the only risk factors identified. ConclusionsThis study shows that chronic radiodermatitis may be considered a frequent side effect in an at-risk population. The lesions are commonly benign, but extensive sclerosis can occur. Patients should be better informed about the side effects and offered a skin exam periodically.

SAT-LB101 Sclerosing Mucoepidermoid Carcinoma with Eosinophilia (SMECE) of the Thyroid: Benign Long Term Course with Conservative Treatment in a High Risk Thyroid Cancer

SMECE is a rare thyroid carcinoma (<1%), on the background of Hashimoto's thyroiditis, with a female predominance. SMECE is characterized by inflammatory infiltrate of eosinophils, extensive sclerosis and squamous and glandular differentiation. It is mostly regarded as an aggressive tumor. Most SMECE stain negative with thyroglobulin and positive with p63, but to date lack a pathgnomonic molecular/genetic/epigenetic diagnostic marker. SMECE should be differentiated from salivary mucoepidermoid carcinoma, papillary carcinoma with squamous metaplasia and Hodgkin lymphoma. Here we describe a 42-year-old female that presented with a right-sided thyroid swelling. A total-thyroidectomy was preformed and the pathological report described a tumor of 2.2cm which reached the inked surgical margins at several foci. Staining showed typical features of SMECE. Calcitonin, thyroglobulin stains were negative but cytokeratin staining was positive. No extra-thyroidal extension was seen. Post-operative PET scan and US showed no evidence of residual/recurrence disease during the next 9 years of follow -up. There are about 55 cases of SMECE described in the literature. SMECE was categorized as low-grade tumor but recent reports suggested a more aggressive behavior both locally and occasionally by distant metastasis. In the largest published series nearly half of the cases presented with an extrathyroidal extension and over 1/3 had lymph node metastases. After an average of 4 years follow up, 24% were deceased and 15% were alive with disease. In the present case, despite some involvement of the surgical margins no other aggressive feature was noted. This case then may indicate that a localized tumor, at diagnosis, without extrathyroidal and lymph node involvement may be regarded as a low-grade tumor with a favorable prognosis. Shah A et al - Modern Pathology 2017; 30: 329-339 Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Locally Invasive Pheochromocytoma Combined with Primary Malignant Adrenal Lymphoma

Pheochromocytoma (PHEO) combined with primary adrenal lymphoma is extremely rare. We describe a case of locally invasive PHEO combined with primary malignant lymphoma. We provide a case description with biochemical analyses, imaging, and pathologic findings. A 79-year-old male presented with a 17-cm, complex mass in the left adrenal gland with non-contrast Hounsfield units of 100 and left para-aortic enlarged lymph nodes imaged by computed tomography. Biochemical evaluation showed plasma and 24-hour urinary normetanephrine significantly elevated about 22 times (about 13.5 times above the normal upper limit) while metanephrine levels were normal. With adequate perioperative preparation, en bloc resection of the left adrenal gland was performed. The pathology revealed a tumor consisting of B-cell lymphoma, a PHEO forming a large adrenal mass with soft tissue invasion with extensive sclerosis and a separate nodule with PHEO without sclerosis. Immunohistochemistry and in situ hybridization of the lymphoma were consistent with Epstein-Barr virus-positive, diffuse large B-cell lymphoma. Immunohistochemistry of the PHEO was positive for chromogranin, synaptophysin, and S100. The Ki67 index was 8.7% and PHEO of the adrenal gland scaled score was 8 (≥4 is considered potentially malignant). To the best of our knowledge this is the first case demonstrating locally invasive and potentially malignant PHEO combined with primary malignant lymphoma in the same adrenal gland.

RADIOGRAPHIC PREDICTORS OF BONE EXPOSURE IN PATIENTS WITH STAGE 0 ONJ

Background Osteonecrosis of the jaws (ONJ) is a severe adverse effect of antiresorptive medications. Although the diagnosis of ONJ is based on the presence of necrotic bone in the oral cavity, patients at the initial phase of the disease (stage 0 ONJ) can present without bone exposure.1 Approximately 50% of stage 0 ONJ patients develop bone exposure within 6 to 12 months of initial presentation.2 However, diagnostic predictors of stage 0 ONJ progressing to clinical ONJ are absent. Objectives The aim of this study was to investigate stage 0 ONJ radiographic features associated with subsequent clinical exposure. Materials and Methods Files from 14 patients with stage 0 ONJ (history of antiresorptive medication and nonspecific clinical symptoms) were utilized. Imaging included panoramic radiographs and CBCT scans. Additionally, clinical photos were obtained. Cortical erosion, sclerosis, sequestration, periosteal reaction and crater-like defects were assessed as localized or extensive. Patients were followed up for 6 months to 2 years and absence or presence of clinical exposure was noted. Results Two patients reported a history of recent extraction, 3 were edentulous and 9 were dentate. Of the patients, 50% (7 of 14) presented with cortical erosion, 43% (6 of 14) showed bony sequestration or bony spicules, 50% (7 of 14) demonstrated crater-like defect, 50% (7 of 14) had extensive sclerosis, and 36% (5 of 14) presented with periosteal reaction. In follow-up, 50% (7 of 14) of patients with stage 0 ONJ developed clinical exposure during the observation period. Patients with subsequent exposure presented more frequently with abnormal radiographic findings. Interestingly, 6 of these patients presented with sequestration or bony spicules at the initial appointment. All patients with sequestrum advanced to clinical ONJ. Discussion Our data show an association of radiographic findings, in particular of sequestration, with development of bone exposure, and emphasize the importance of a thorough radiographic assessment in patients with suspected stage 0 ONJ. Currently, we are expanding our patient population to increase the statistical power of our studies.

Part II: Temporomandibular Joint (TMJ)-Regeneration, Degeneration, and Adaptation.

Elucidate temporomandibular joint (TMJ) development and pathophysiology relative to regeneration, degeneration, and adaption. The pharyngeal arch produces a highly conserved stomatognathic system that supports airway and masticatory function. An induced subperiosteal layer of fibrocartilage cushions TMJ functional and parafunctional loads. If the fibrocartilage disc is present, a fractured mandibular condyle (MC) regenerates near the eminence of the fossa via a blastema emanating from the medial periosteal surface of the ramus. TMJ degenerative joint disease (DJD) is a relatively painless osteoarthrosis, resulting in extensive sclerosis, disc destruction, and lytic lesions. Facial form and symmetry may be affected, but the residual bone is vital because distraction continues to lengthen the MC with anabolic bone modeling. Extensive TMJ adaptive, healing, and regenerative potential maintains optimal, life support functions over a lifetime. Unique aspects of TMJ development, function, and pathophysiology may be useful for innovative management of other joints.

Phenotypic expansion and progression of SPATA7-associated retinitis pigmentosa

To report an unusual phenotype of retinitis pigmentosa(RP) caused by compound heterozygous mutations in SPATA7, and describe the progression over a twoyear follow-up period. Retrospective case study. A 63-year-old man with a long history of nyctalopia, progressive visual field constriction, and a recent subacute decrease in visual acuity of the left eye presented for evaluation of a suspected retinal degeneration. Multimodal retinal imaging and functional assessment with full-field electroretinogram suggested a severe rod-cone dysfunction masquerading as a choroideremia-like phenotype. A vitreous opacity was found to explain recent changes in the left eye and a 25-guage vitrectomy and membrane peel was performed, yielding no change in visual acuity. Whole-exome sequencing revealed compound heterozygous variants in SPATA7 that were predicted to be pathogenic. Compound heterozygous c.1100A>G, p.(Y367C) and c.1102_1103delCT, p.(L368Efs*4) variants in SPATA7 manifest as an unusual RP phenotype in this case, showing extensive choroidal sclerosis and retinal pigment epithelium (RPE) atrophy with evidence of progression over twoyears on multimodal imaging.