Alveolar bone response distal to applied orthodontic forces in ovariectomized rats.

OBJECTIVES: The aim of this study was to investigate the effect of the application of orthodontic tooth forces on the alveolar bone distal to the loaded teeth, in ovariectomized female rats. METHODS: Twenty-four eight-month-old Wistar rats were divided into one group ovariectomized at the age of six months and one control. An orthodontic appliance delivering a mesial traction force of 60 gr* was placed on the right maxillary 1st molar of all animals for 14 days. Histology of the alveolar bone, of the adjacent and distal teeth to the loaded molar and the contralateral side, was performed following euthanasia. RESULTS: In the non-ovariectomized rats, extensive resorption was noticed in the direction of the orthodontic movement in the 2nd and 3rd molar interdental space, whereas the respective contralateral interdental space did not show any remodeling activity. Ovariectomized rats displayed reduced osseous tissue in the interdental space of both sides. The alveolar bone in the interradicular area of the 2nd loaded molar revealed frontal resorption, whereas, the alveolar interradicular bone of the contralateral 2nd molar showed internal resorption. CONCLUSIONS: In conclusion, orthodontic forces applied to the dentoalveolar complex of ovariectomized rats affect bone remodeling, even in areas distal to the site of force application. This finding should be taken into account during orthodontic treatment of women during menopause.

The effect of osteopenia on tooth movement in ovariectomized rats. An experimental study.

OBJECTIVE: The purpose of this experimental study was to investigate in depth the effects of osteopenia related to the rate, as well as to the quality of orthodontic tooth movement, by combining experimental ovariectomy and molar movement in rats. METHODS: Twenty-four six-month-old female Wistar rats were used in this study. The animals were divided into two groups consisting of twelve animals each: Group A (control group) was subjected to orthodontic movement of the upper right first molars. Group B was subjected to orthodontic movement of the upper right first molar following bilateral ovariectomy. Ovariectomy was performed on the first experimental day and the upper right first molars were subjected to orthodontic forces 60 days post-ovariectomy, lasting for 14 days. RESULTS AND CONCLUSION: Direct inspections of the upper jaws, measurements of orthodontic movement of the upper right first molars of Group A and B, as well as histologic examinations of the alveolar bone in the upper right and left first molar regions, showed that osteopenia affects the rate of orthodontic tooth movement, as well as the quality of alveolar bone remodeling, in ovariectomized rats. Specifically, in the ovariectomized animals the alveolar bone of the non-loaded side showed extensive internal resorption, with large marrow cavities, whereas the alveolar bone of the loaded side was dense with almost no marrow cavity and frontal resorption on the surface. It appears that alveolar remodeling after the exertion of orthodontic forces follows the general paradigm of osteoporotic bone remodeling after loading.

Lymphoepithelioma-like breast carcinoma.

Nasopharyngeal lymphoepithelioma is an undifferentiated carcinoma in a dominated lymphoplasma-histiocyte stroma. Lymphoepithelioma-like carcinoma of the breast is the mammary counterpart of the lymphoepithelioma of the nasopharynx and is characterised by proliferation of poorly differentiated malignant cells within a prominent lymphoid infiltrate. It is a very rare primary carcinoma of the breast first reported in 1994 by Kumar and Kumar. Fewer than 40 cases have been reported in the English literature. In this manuscript a case of lymphoepithelioma-like carcinoma of the breast in a 57-year-old patient is reported along with a literature review on this rare entity.

Effects of mechanical loading on the expression of pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta in a rat spinal deformity model.

Mechanical loading of the spine is a major causative factor of degenerative changes and causes molecular and structural changes in the intervertebral disc (IVD) and the vertebrae end plate (EP). Pleiotrophin (PTN) is a growth factor with a putative role in bone remodeling through its receptor protein tyrosine phosphatase beta/zeta (RPTPß/ζ). The present study investigates the effects of strain on PTN and RPTPß/ζ protein expression in vivo. Tails of eight weeks old Sprague-Dawley rats were subjected to mechanical loading using a mini Ilizarov external apparatus. Rat tails untreated (control) or after 0 degrees of compression and 10°, 30° and 50° of angulation (groups 0, I, II and III respectively) were studied. PTN and RPTPß/ζ expression were evaluated using immunohistochemistry and Western blot analysis. In the control group, PTN was mostly expressed by the EP hypertrophic chondrocytes. In groups 0 to II, PTN expression was increased in the chondrocytes of hypertrophic and proliferating zones, as well as in osteocytes and osteoblast-like cells of the ossification zone. In group III, only limited PTN expression was observed in osteocytes. RPTPß/ζ expression was increased mainly in group 0, but also in group I, in all types of cells. Low intensity RPTPß/ζ immunostaining was observed in groups II and III. Collectively, PTN and RPTPß/ζ are expressed in spinal deformities caused by mechanical loading, and their expression depends on the type and severity of the applied strain.

Macrophage-specific metalloelastase (MMP-12) immunoexpression in the osteochondral unit in osteoarthritis correlates with BMI and disease severity.

BACKGROUND: Metalloproteinase 12 (MMP-12) is induced in chondrocytes during fetal development and malignant transformation. OBJECTIVES: The aim of our study is to examine the expression of MMP-12 in the cartilage and the subchondral bone of patients with osteoarthritis (OA) and to correlate its expression with disease severity and anthropometric characteristics. METHODS: Overall, 60 sections from 20 patients with idiopathic OA, were examined for the immunolocalization of MMP-12. As controls, we used the femoral heads of 4 patients treated with seniarthroplasty after fracture. Demographic characteristics and Body Mass Index (BMI) were calculated for all subjects. RESULTS: Specimens were divided into four groups based on the Mankin histological severity score. The immunohistochemical study showed MMP-12 expression in the cartilage and subchonral bone of OA patients, while there was no expression in normal controls. At the moderate OA changes (Mankin score: 6-7), MMP-12 was detected mainly at the matrix of fibrocartilage tissue. During disease progression, MMP-12 was expressed at the sides of the cartilage and bone erosion and in the bone cysts. Furthermore, it was traced in the osteocytes of the subchondral bone. Osteoblast-like cells and bone lining cells express MMP-12 during the stage of severe OA (Mankin: ≥8). Osteoclasts expressing MMP-12 were also detected in the group of severe OA. Interestingly, MMP-12 expression was positively correlated with the age and the BMI of OA patients. CONCLUSION: The increased expression of MMP-12 in the bone-cartilage unit of OA patients suggests a possible role in OA pathogenesis and progression. LEVEL OF EVIDENCE: III, prospective comparative study.

Encapsulating peritoneal sclerosis with favorable outcome in hemodialysis: an unusual case with a literature review.

Encapsulating peritoneal sclerosis is a rare condition of a poorly understood pathogenesis with recognized risk factors, such as medications, surgical interventions, systemic diseases, and malignancies. In endstage renal disease it has been associated with chronic peritoneal dialysis. We hereby report the case of a 59-year-old male hemodialysis patient, who was never treated with peritoneal dialysis and developed an unexplained massive ascites 4 months post laparoscopic cholecystectomy for gallstones. A second laparoscopy and histological evaluation revealed encapsulating peritoneal sclerosis-like findings with parietal peritoneum and spleen involvement. The patient was successfully treated for 12 months with prednisone and tamoxifen. Possible pathogenetic mechanisms of the disease in this case are discussed including peritoneal irritation by chronic cholecystitis, low-grade inflammation of hemodialysis, intraoperative complications and the hypothetical role of oxidized regenerated cellulose used for hemostasis. In conclusion, the suspicion of peritoneal sclerosis should be encountered in cases of unexplained ascites in patients undergoing hemodialysis. The early diagnosis includes laparoscopy and histological evaluation and can result in a good outcome under medical treatment; otherwise, there is a high possibility of bowel obstruction with fatal outcome.

Biological response to ß-tricalcium phosphate/calcium sulfate synthetic graft material: an experimental study.

PURPOSE: The aim of this study was to evaluate the effect of a biphasic synthetic bone graft material composed of ß-tricalcium phosphate (ß-TCP) and calcium sulfate (CS) in 12 New Zealand rabbits. MATERIALS AND METHODS: A circular bicortical critical-size cranial defect was created in each of 12 rabbits. The defects were grafted with ß-TCP/CS. Animals were euthanized at 3 and 6 weeks. Harvested tissue specimens were evaluated histologically and histomorphometrically. Parameters associated with new bone formation and graft resorption were measured and calculated. The results were statistically analyzed using the Mann-Whitney test. RESULTS: Our data demonstrated the biocompatibility of synthetic ß-TCP/CS, as no inflammatory response was observed, and no fibrosis was developed between the graft particles and the newly formed bone. Moreover, ß-TCP/CS acted as an osteoconductive scaffold that allowed a significant bone regeneration and graft biodegradation with time. CONCLUSION: In this animal model, synthetic ß-TCP/CS proved to be a biocompatible, osteoconductive, and bioresorbable bone graft substitute.

A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review.

Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.

Effect of autologous platelet-rich plasma in combination with a biphasic synthetic graft material on bone healing in critical-size cranial defects.

PURPOSE: The aim of the study was to investigate the effect of autologous platelet-rich plasma (PRP) on the osteogenic potential of a biphasic synthetic graft material composed of hydroxyapatite and beta-tricalcium phosphate (HA/ß-TCP) in critical-size cranial defects in rabbits. MATERIALS AND METHODS: Three circular bicortical critical-size cranial defects were created in each of 18 rabbits. The first of the defects was grafted with autologous PRP and HA/ß-TCP, the second was grafted with HA/ß-TCP without PRP, and the third was left unfilled as a negative control. Animals were euthanized at 2, 4, and 6 weeks after surgery. Harvested tissue specimens were evaluated histologically and histomorphometrically. Several parameters associated with osteoclastic and osteoblastic activities were measured and calculated. The results were statistically analyzed using the 1-way analysis of variance statistical method. RESULTS: Histologic analysis of the samples showed bone tissue formation at all experimental sites including untreated control defects. A statistically significant difference in new bone formation between the defects treated with HA/ß-TCP + PRP and defects treated with HA/ß-TCP alone was not observed. Control untreated defects showed the greatest bone regeneration. CONCLUSIONS: In this animal model, autologous PRP had no effect on bone healing in addition to a biphasic HA/ß-TCP synthetic graft material after 2, 4, and 6 weeks of implantation.

Experimental study of the effect of autologous platelet-rich plasma on the early phases of osteoinduction by allogenic demineralized bone matrix.

PURPOSE: To evaluate the effect of autologous platelet-rich plasma (PRP) on the early phases of osteoinduction by allogenic demineralized bone matrix (DBM) in rabbit intramuscular positions. MATERIALS AND METHODS: Allogenic DBM was produced from bones of 3 healthy rabbits. In each of 6 experimental animals, 0.3 mL autologous PRP was prepared and 2 muscle pouches were created, where 250 mg DBM + PRP (experimental sites) and 250 mg DBM without PRP (control sites) were randomly implanted. Animals were euthanized 3 weeks postoperatively. RESULTS: Histologic examination revealed uneventful healing in all cases, whereas remineralization of the periphery of the bone graft particles was a constant finding. In both control and experimental sites, fibroblasts and other mesenchymal cells (probably osteoprogenitor cells and preosteoblasts) were observed. The main histological difference was the recolonization of the empty lacunae of the bone graft particles by osteocytes at the control sites. The degradation of the graft at the control sites was statistically significantly quicker, although a statistically significant difference regarding the amount of the newly formed fibrous connective tissue was not observed. CONCLUSION: The present study demonstrated that in this experimental model, the addition of PRP to DBM had a negative effect on the early phases of osteoinduction at 3 weeks of observation.

Sex, but not age and bone mass index positively impact on the development of osteochondral micro-defects and the accompanying cellular alterations during osteoarthritis progression.

Background: Osteoarthritis (ΟΑ) is characterized by cartilage breakdown and subchondral sclerosis. Micro-fractures of the calcified tissues have been, also, detected, but their exact role has not been elucidated yet. This study was to examine the frequency of cracks during OA progression and to correlate them with the underlying cellular modifications and matrix metalloproteinase-2 (MMP-2) expression using histological/immunohistological methods. Methods: Overall, 20 patients and 3 controls (9 specimens per patient), aged 60-89 years, diagnosed with hip/knee OA were included. The development of cracks was examined in 138 sections, whereas the expression of MMP-2 was examined in 69 additional sections. Results: Based on Mankin score, three groups of OA severity were analyzed: Group I (mild) was constituted of sections with score 1-5 while Groups II (moderate) and III (severe) with score 6-7 and greater or equal to 8, respectively. Demographic characteristics did not reveal any association between the number of microdefects and age or body mass index (BMI). Cartilage micro-cracks were increased during moderate and severe OA, while bone cracks were increased during mild and severe OA. In knee OA, cartilage cracks were not correlated with Mankin score, whereas in hip OA they appeared association with severity score. Bone cracks were positively correlated with matrix apoptotic osteocytes and osteoblastic cells, but not with osteoclasts. MMP-2 immunostaining was increasing by OA severity in the osteochondral unit. Similarly, MMP-2 was expressed on the microcracks' wall mainly in Group III. Conclusion: Our data displayed that bone cracks during primary OA stages, represent an early adaptative mechanism aiming to maintain cartilage integrity. Accumulation of bone defects and concomitant increase of apoptotic osteocytes activated an abnormal remodeling due to osteoblastic activity, in which MMP-2 played a pivotal role, leading to subchondral sclerosis promoting further osteochondral deformities.

Metaplastic Matrix-Producing Carcinoma and Apocrine Lobular Carcinoma In Situ Associated with Microglandular Adenosis: A Unique Case Report.

Microglandular adenosis is a non-lobulocentric haphazard proliferation of small round glands composed of a single layer of flat to cuboidal epithelial cells. The glandular structures lack a myoepithelial layer; however, they are surrounded by a basement membrane. Its clinical course is benign, when it is not associated with invasive carcinoma. In around 30% of cases, there is a gradual transition to atypical microglandular adenosis, carcinoma in situ, and invasive breast carcinoma of several different histologic subtypes, including an invasive carcinoma of no special type, metaplastic matrix-producing carcinoma, secretory carcinoma, metaplastic carcinoma with squamous differentiation, acinic cell carcinoma, spindle cell carcinoma, and adenoid cystic carcinoma. Recent molecular studies suggest that microglandular adenosis is a non-obligate precursor of triple-negative breast carcinomas. In this manuscript, we present a unique case of microglandular adenosis associated with metaplastic matrix-producing carcinoma and HER-2 neu oncoprotein positive pleomorphic lobular carcinoma in situ with apocrine differentiation in a 79-year-old patient.

Primary synovial chondrosarcoma of the hip joint in a 45-year-old male: case report and literature review.

Synovial chondrosarcoma is a rare tumor, seen most commonly arising from antecedent synovial chondromatosis, the more common benign entity. The distinction between the two can be difficult on the basis of clinical, imaging, and histologic criteria. The authors report a case of pathologically proven synovial chondrosarcoma of the hip in a 45-year-old male initially treated for presumed synovial chondromatosis. The case is made more unusual by the fact that no evidence of co-existent synovial chondromatosis was noted at histology. The literature as regards synovial chondrosarcoma, both de novo and secondary cases, is reviewed.

Tumor to Tumor Metastasis from Adenocarcinoma Not Otherwise Specified of the Parotid Gland to Uterine Leiomyoma: Presentation of a Unique Case.

Salivary gland adenocarcinoma not otherwise specified (NOS) is a malignant epithelial tumor composed of ductal/glandular structures with or without cystic formation. Histologically it is classified as high grade with relevant biological behavior. Although both minor and major glands may be involved, the majority (60%) implicate the parotid gland. Location, regional lymph node status, and histological grade are some of the factors that predict the progress of the disease and the development of metastases. Long follow-up is considered the standard option as distant metastases (DM) may occur despite regional control. Primary sites of DM, besides lymph nodes, include bone, lung, and liver. Herein we report a unique case of a 68-year-old female with a previous history of high-grade adenocarcinoma NOS of her right parotid gland. On her biannual follow-up examination, MRI revealed an abnormal increase in the size of a known uterine leiomyoma of the posterior uterine wall. Positron emission tomography-CT (PET-CT) showed increased uptake in the uterus and lungs. On frozen section, adenocarcinoma was found at the center of the leiomyoma. Histological and immunohistochemical findings were consistent with secondary involvement by the salivary gland adenocarcinoma NOS. Treatment consisted of cyclophosphamide, adriamycin, and cisplatin with poor outcome. The patient was lost to follow-up. Review of the literature indicates that no similar case has been reported in the English literature.

Invasive Lobular Carcinoma with Extracellular Mucin Production: Description of a Case and Review of the Literature.

Invasive lobular carcinoma of the breast is the second most common subtype of breast carcinoma. It accounts for 5-15% of the breast carcinoma cases reported. It shows a different metastatic pattern compared to invasive carcinoma of no special type. There are several variants of this cancer including the classic, solid, signet ring cell, tubulolobular, alveolar, trabecular, pleomorphic, and mixed subtypes each one with a distinctive morphology. Invasive lobular carcinoma has been associated with intracellular mucin production, in the form of intracytoplasmic lumina and signet ring cells whereas extracellular mucin production has been related to carcinomas of ductal origin. A new variant that displays extracellular mucin production was described recently. Only nineteen cases of this rare entity have been reported to date. In this manuscript, we report an additional case of invasive lobular carcinoma with extracellular mucin production, describing its clinico-pathological characteristics, and review the literature on the same.

Primary peripheral neuroectodermal tumor (PNET) of the adrenal gland: a rare entity.

PURPOSE: Ewing Sarcoma/Primitive Neuroectodermal Tumor (ES/PNET) is a malignant small round cell tumor belonging to the Ewing Sarcoma Family of Tumors. It occurs more commonly in children and young adults. Its localization in the adrenal gland is extremely rare. We reviewed 35 cases of ES/PNET of the adrenal gland reported in the literature and presented our case. METHODS: Data were collected by searching for ES/PNET and adrenal gland key words on Google Scholar and PubMed in March 2018, including a case diagnosed in our department. We analyzed all reviewed cases for diagnosis, surgical and systemic therapy and outcome. RESULTS: To date 24 articles presenting cases of ES/PNET of the adrenal gland are reported in the literature. We included in our review 35 cases previously described and one new case. Histologically all cases consisted of sheets of small round cells. Immunohistochemistry was also performed in all cases. Most cases stained positive for CD99 and negative for lymphocytic markers. Markers of epithelial differentiation displayed variable results. In all cases tested, characteristic translocations were displayed supporting the diagnosis. All patients but four were treated surgically and the majority received adjuvant therapy. Only very few cases received neoadjuvant chemotherapy. CONCLUSIONS: Primary ES/PNET of the adrenal gland is a rare tumor, showing specific morphological, immunohistochemical and cytogenetic characteristics. Treatment consists of surgery, chemotherapy and radiotherapy. Further investigations paired with long term follow-up are necessary to define prognosis for this rare entity.

Primary squamous cell carcinoma of the ovary. Review of the literature.

PURPOSE: Primary squamous cell carcinoma (SCC) of the ovary is rare. Most cases arise from a cystic teratoma or less frequently from Brenner tumor or endometriosis. We reviewed 36 cases of primary ovarian SCC reported in the literature including a case diagnosed and treated in our institution. METHODS: Data was collected by using the key-words "primary squamous cell carcinoma" and "ovary" on Google Scholar and PubMed in April 2018. All reviewed cases were analyzed according to diagnosis, surgical approach, adjuvant therapy and outcome. RESULTS: To date 23 articles presenting 36 cases of primary ovarian SCC are reported. Nine patients had stage I, 8 stage II, 11 stage III and 5 stage IV disease, whereas 3 patients had in situ carcinoma. All patients underwent surgery (mainly hysterectomy with bilateral salpingo-oophorectomy). Adjuvant therapy was reported in 24 patients, 15 of which received chemotherapy, 6 radiotherapy and 3 a combination of both. Chemotherapy regimens were similar to the ones used in ovarian carcinoma (more often platinum plus paclitaxel). Follow-up period was in general short and survival varied between 9 days and 14 years, depending on the stage at diagnosis. CONCLUSIONS: Primary ovarian SCC is a rare entity with poor prognosis, compared to serous carcinoma. Treatment is usually extrapolated from classical ovarian carcinoma algorithms, including surgical management combined with adjuvant chemotherapy with or without radiotherapy. Further investigations are needed to define optimal treatment, such as chemotherapy regimens and the role of radiotherapy and lymph node dissection.

Vanishing bone disease: review and case reports.

Vanishing bone disease is a rare idiopathic disease, leading to extensive loss of bony matrix, replaced by proliferating thin-walled vascular channels and fibrous tissue. There are >191 cases reported in the English literature. Gorham and Stout made the first overview of the disease in 1955 and they first presented 24 cases known at that time. The etiology remains speculative, the prognosis unpredictable, and effective therapy still unknown. The disease can be monostotic or polyostotic although multicentric involvement is exceptional. We report 2 cases of a histologically studied vanishing bone disease involving the humerus and the femoral head. The patients' past history was noncontributory. The radiographic study revealed a destructive lesion of the left humerus in the first case, and complete disappearance of the femoral head in the second case. Laboratory findings including hormonological tests revealed no evidence of metabolic, immunologic, neoplastic, or infection etiology. Histopathological findings of the 2 cases revealed thickened bone of lamellar structure without marrow cavities next to fibrous tissue, with few fibroblasts and a small number of newly formed vascular channels. The prognosis varies from slight disability to death by involvement of vital skeletal structures. The treatment of vanishing bone disease is controversial. Several treatment modalities have been proposed. Surgical intervention has been suggested as a method of choice by many authors and concerns local resection of the affected bone, with or without replacement prosthesis or bone grafts.

Vascular endothelial growth factor for the treatment of femoral head osteonecrosis: An experimental study in canines.

AIM: To evaluate the treatment of osteonecrosis of the femoral head (ONFH) with the use of vascular endothelial growth factor (VEGF). METHODS: In 30 mature beagles (6 groups of 5 beagles) ONFH was induced cryosurgically and one of the following solutions was administered locally in the femoral head (FH) in each group: Single injection of 500 µg VEGF (t-VEGFµ group); single injection of 500 ng VEGF (t-VEGFn group); continuous delivery of 500 µg VEGF through osmotic micropump (t-VEGFpump-µ group); continuous delivery of 500 ng VEGF through osmotic micropump (t-VEGFpump-n group); single injection of 0.9% sodium chloride (t-NS group), while one group that served as control group did not receive any local solution (No-t group). FHs were retrieved 12 wk postoperatively, underwent decalcification and hematoxylin/eosin and toluidine blue staining. In two canines per group, one half of FH was processed without decalcification and stained with modified Masson Trichrome. Histological sections were observed by light microscopy and measured with a semi-automatized bone histomorphometry system and Bone Volume/Total Volume (BV/TV), Marrow Volume/Total Volume (MaV/TV), and Trabecular Thickness (TbTh) were assessed. Standard and robust tests (Welch, Brown Forsythe) of analysis of variance along with multiple comparisons, were carried out among the categories. RESULTS: The untreated (No-t) group had signs of osteonecrosis, whereas the VEGF groups revealed reversal of the osteonecrosis. Statistical analysis of the decalcified specimens revealed a significantly better BV/TV ratio and a higher TbTh between the VEGF treatment groups (except the t-VEGFn group) and the No-t group or the control t-NS group. Single dose 500 µgVEGF group had significantly better BV/TV ratio and higher TbTh when compared to the No-t group (50.45 ± 6.18 vs 29.50 ± 12.27, P = 0.002 and 151.44 ± 19.07 vs 107.77 ± 35.15, P = 0.161 respectively) and the control t-NS group (50.45 ± 6.18 vs 30.9 ± 6.67, P = 0.004 and 151.44 ± 19.07 vs 107.14 ± 35.71, P = 0.151 respectively). Similar differences were found for the prolonged VEGF delivery/pump groups of 500 µg and 500 ng. Analysis of the totality of specimens (decalcified/non-decalcified) enhanced the aforementioned differences and additionally revealed significant differences in the comparison of the TbTh. CONCLUSION: In an experimental model of ONFH in canines it was found that local treatment with VEGF leads to bone tissue remodeling and new bone formation.

Dysplasia epiphysealis hemimelica (Trevor disease): a rare developmental disorder of bone mimicking osteochondroma of long bones.

Dysplasia epiphysealis hemimelica (DEH) is a rare developmental disorder of childhood and is characterized by asymmetric enlargement of the epiphyseal cartilage of the long bones. After 4 to 5 years of age, the lesions histologically resemble osteochondroma. To our knowledge, only one publication of this entity is available in an English pathology journal. The clinical, radiographic, and histologic features of 9 cases of DEH were retrospectively reviewed. The patients' age ranged from 3 to 15 years with single or multiple lesions of the femur, fibula, tibia, and talus. The etiology and pathogenesis of DEH are not known. Its origin and evolution has initially apparent similarities to the development and growth of epiphyseal secondary ossification centers. DEH can be differentiated from osteochondroma of long bones using clinical, radiologic, and pathologic parameters. DEH occurs in young children and adolescents manifesting as lesions that arise particularly from the epiphysis of the lower extremities and tarsus. Osteochondroma, in contrast, occurs most frequently between 10 and 30 years of age and originates from the metaphysis of long bones. Although the DEH cartilage resembles osteochondroma, there are several significant histologic differences. During infancy, lesions of DEH histologically reveal osteocartilaginous nodules that resemble secondary ossification centers. Usually after 4 to 5 years of age they develop into osteochondroma-like lesions. Although all cases of DEH contain small areas of calcified cartilage beneath the cartilage cap, a significant percentage of osteochondromas show large amounts. The nodules and cartilage cap of DEH contain bands of cartilage separating areas of cancellous bone; these bands are not present in osteochondroma. Among the other distinguishable features, recent molecular studies of DEH demonstrated normal expression levels of EXT1 and EXT2 genes, comparable to that of normal growth plate. Osteochondroma, in contrast, has low levels of EXT1 and EXT2 gene expression due to gene mutation. The histologic differences in combination with the distinct clinical and radiographic features should enable a pathologist to differentiate these entities.