Presence Of Bone Destruction Research Articles

Proto-oncogene mutations in middle ear cholesteatoma contribute to its pathogenesis

BackgroundChronic inflammation causes bone destruction in middle ear cholesteatomas (MECs). However, the causes of their neoplastic features remain unknown. The present study demonstrated for the first time that neoplastic features of MEC are based on proto-oncogene mutations.ResultsDNA was extracted from MEC and blood samples of five patients to detect somatic mutations using depth-depth exome sequencing. Exons with somatic variants were analyzed using an additional 17 MEC/blood test pairs. Variants detected in MECs but not in blood were considered pathogenic variant candidates. We analyzed the correlation between proto-oncogene (NOTCH1 and MYC) variants and the presence of bone destruction and granulation tissue formation. MYC and NOTCH1 variants were detected in two and five of the 22 samples, respectively. Two of the NOTCH1 variants were located in its specific functional domain, one was truncating and the other was a splice donor site variant. Mutations of the two genes in attic cholesteatomas (n = 14) were significantly related with bone destruction (p = 0.0148) but not with granulation tissue formation (p = 0.399).ConclusionsThis is the first study to demonstrate a relationship between neoplastic features of MEC and proto-oncogene mutations.

Orbital Lymphoma; A search for MRI predictors of disease extent and treatment response

Background/aims: Lymphoma is the most common orbital malignancy in adults. We aimed to investigate pretreatment MRI predictors of systemic involvement and early therapy response.
 Material and Method: Histopathologically confirmed orbital lymphoma patients with MRI scans at the time of diagnosis and after treatment constituted the study group. Involvement of lacrimal gland, intraconal and extraconal fat, eyelid, optic nerve and/or optic nerve sheath, extraocular muscles, intraocular involvement and presence of bone destruction were evaluated from pretreatment MR scans by two radiologists. Measurements of ADC values of the mass and pons were collected and the ratio (rADC= lymphoma ADC/ pontine ADC) was calculated. Response to treatment was evaluated from the follow-up MR images. 
 Results: Twenty patients (F/M= 10/10, mean age 57.3 ± 19.7) constituted the study group and histopathologic diagnosis was predominantly B cell lymphoma, extranodal marginal zone lymphoma being the most common (n=12, 60%). The most commonly involved structures were extraconal fat tissue (70%), lacrimal gland (50%) extraocular muscles (40%). Intraconal fat involvement was significantly higher (p=0.017) in patients with systemic disease compared to localized disease. rADC values showed no difference between patients with systemic and localized disease or patients with complete or partial response (p>0.05).
 Conclusion: Intraconal fat involvement of orbital lymphoma could predict a systemic disease. The predictive value of pretreatment ADC levels should be searched in larger future cohorts.

The assessment of imaging diagnosis of brucellar spondylitis

Objective To explore the imaging features of brucellar spondylitis (BS). Methods The imaging data of 49 cases who were diagnosed as brucellar spondylitis by a positive standard tube agglutination titer test (≥1∶100) and (or) the isolation of brucella species from blood or other tissue at our institution between September 2012 and October 2016 were retrospectively reviewed. X-ray, CT scan and MRI examination was performed in 49, 28 and 42 cases, respectively, of which 19 cases underwent both CT scan and MRI examination. The imaging manifestations of the spine were analyzed. The χ2 test or Fisher's exact test were applied to compare the imaging manifestations of the patients who underwent both CT scan and MRI examination. Results Of the 49 patients, 34 patients (69.4%) had involvement of the lumbar vertebra. Forty-five patients (91.8%) had contiguous involvement at adjacent 2 vertebral bodies. There were 10 cases (20.4%) with bony spur or bone bridge, 3 cases (6.1%) with spondylolisthesis and 3 cases (6.1%) with slightly kyphosis deformity. There were 8 cases (28. 6%) showing bone destruction of more than half of the vertebral body and 6 cases (21.4%) with sequestra on CT. There were 14 cases (33.3%) with psoas abscesses, of which 2 (4.8%) had migrating abscess. Epidural abscesses with dural sac compression were found in 17 cases (40.5%) and 3 cases (7.1%) showed nerve roots compression. There were statistically significant differences in the detection of vertebral bone destruction, bone marrow edema, hyperosteogeny, intervertebral disc changes, abscess formation and sequestrum between CT and MRI (P<0.05). Conclusion BS has characteristic imaging features. The presence of bone destruction, sequestrum, and migrating abscess should warrant the possibility of BS. Key words: Brucellosis; Spondylitis; Tomography, X-ray computed; Magnetic resonance imaging; Diagnosis

Cervicofacial tissue infarction in patients with acute invasive fungal sinusitis: prevalence and characteristic MR imaging findings

Tissue infarction is known as one of the characteristic features of invasive fungal sinusitis (IFS). The purpose of this study was to investigate the prevalence and characteristic MR imaging findings of cervicofacial tissue infarction (CFTI) associated with acute IFS. We retrospectively reviewed MR images in 23 patients with histologically or microbiologically proven acute IFS. CFTI was defined as an area of lack of enhancement in and around the sinonasal tract on contrast-enhanced T1-weighted images. We divided CFTI into two groups, i.e., intrasinonasal and extrasinonasal. Particular attention was paid to the location of extrasinonasal CFTI and the signal intensity of CFTI on T1- and T2-weighted images. The presence of bone destruction on CT scans was also recorded. CFTI was found in 17 (74%) of 23 patients. All of these 17 patients had intrasinonasal CFTI, and 13 patients also had extrasinonasal CFTI. All 13 patients with extrasinonasal CFTI died of disease directly related to IFS. Various locations were involved in the 13 patients with extrasinonasal CFTI, including the orbit (n = 8), infratemporal fossa (n = 7), intracranial cavity (n = 3), and oral cavity and/or facial soft tissue (n = 4). Various signal intensities were noted at the area of CFTI on T1- and T2-weighted images. Bone destruction was found on CT scans in only 3 of 17 patients with CFTI. CFTI with preservation of the bony wall of the involved sinonasal tract may be a characteristic MR imaging finding of acute IFS. The mortality is very high once the lesion extends beyond the sinonasal tract.

Increased expression of proto-oncogene survivin predicts joint destruction and persistent disease activity in early rheumatoid arthritis

Background. Rheumatoid arthritis (RA) is characterized by an uncontrolled spread of destructive joint inflammation resembling malignancy. Epidemiological studies have established strong correlation between inflammation and predisposition for cancer. Here we assess the predictive role of the circulating proto-oncogene survivin for clinical and radiological outcome of early RA.Patients and methods. Serum survivin was measured by sandwich ELISA in 651 patients with early RA (mean duration 6 months). X-rays of hands and feet were prospectively obtained at base-line and after 1, 2, and 5 years and evaluated for the presence of bone destruction by a modified Sharp method. The predictive value of survivin for radiological destruction was calculated using multivariate regression models including antibodies against cyclic citrullinated peptides (aCCP) and rheumatoid factor (RF). Remission was assessed by the EULAR (European League Against Rheumatism) criteria and by criteria proposed by Mäkinen.Results. At base-line, 391 patients (60%) had high levels of survivin. Radiological progression at 5 years was significantly more frequent (P= 0.001) among survivin-positive patients than among survivin-negative. Survivin positivity predicted radiological progression independently of aCCP and RF. The positive predictive value of survivin was proved both in the group of patients with and in the group without erosions at base-line. The combination of positive tests for both survivin and aCCP had the highest prediction for radiological progression (positive predictive value 0.75). Additionally, a positive test for survivin was an independent predictor of not being in remission.Conclusion. Detection of survivin in early RA predicted joint destruction and failure of achieving remission after 5 years in patients with early RA.

Tumoral calcinosis causing bone erosion in a renal dialysis patient

Tumoral calcinosis is a rare disorder manifest by large calcific periarticular masses. Associated bone destruction has been described previously only once. The radiographic and computed tomographic (CT) findings of bone erosion in a case of tumoral calcinosis in a renal dialysis patient are presented. Although the presence of bone destruction may suggest a neoplasm, it does not exclude the diagnosis of tumoral calcinosis

Concomitant continuous infusion chemotherapy and radiation

Attempts to duplicate the cytotoxic effect of oxygen on radioresistant tissues spurred a search by radiation oncologists for other radiosensitizing techniques. This led to large-scale investigations using neutrons and other heavy particle radiations, hyperthermia, altered fractionation schedules, and the systemic use of the halogenated pyrimidines and the electron-affinic compounds. Unfortunately, the promise that the nitroimidazole compounds would selectively sensitize the radioresistant tumor cells and prove to be an effective systemic agent has not been borne out in clinical trials thus far. Existing pharmokinetic and cytokinetic studies have suggested that continuous infusion chemotherapy given concomitantly (CCIC) with irradiation (RT) acts synergistically, resulting in a significant increase in tumor cell killing. These observations have been supported by clinical research studies treating certain epithelial cancers that have resulted in considerably higher locoregional control rates and improved survival. Although initially used in treatment of only advanced or inoperable epithelial carcinomas, CCIC and RT are now being employed in the treatment of lower staged cancers as an organ-sparing procedure. Carcinoma of the anus treated by anteroposterior (AP) resection alone have reported 5-year survival rates of 30% to 60%. CCIC and RT using 5-fluorouracil (5-FU) and mitomycin C have achieved a local control rate of 90% to 100% and a 5-year survival rate of 80% to 86% with sphincter preservation in 90% of these cases. The 5-year survival rate in advanced urinary bladder carcinoma is 25% to 30% for either radiation or surgery and 42% when combined in a preoperative radiation schedule. Using 5-FU CCIC and RT, the local control rate of transitional cell carcinoma of the bladder has been 71% to 86% with a 5-year survival of 62%. 5-FU CCIC and cisplatin and RT used in the treatment of Stages III and IV carcinoma of the cervix yields a locoregional control of 74% compared with the radiation alone local control of 63% for Stage III and 30% for Stage IV disease. Advanced head and neck and paranasal sinus carcinomas treated by cisplatin CCIC and RT show improved tumor clearance even in the presence of bone destruction. A complete response rate of 87% has been reported with the use of cisplatin CCIC and hyperfractionated radiation. Hyperfractionated radiation also appears to improve the local control of advanced head and neck cancers over patients treated with single fractions of radiation with 66% surviving at 22 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Acropachy in lymphatic leukemia.

Bone lesions in adults with leukemia are not common, and the presence of bone destruction, clubbing, and edema of overlying soft tissues, termed leukemic acropachy (acros = extremity, pachus = thick), is rare indeed. Schittenhelm first described this entity in 1925 (12), and only one similar case (1) has been found in the literature since that time. The case of leukemic acropachy described below differs from the other two in that the patient has shown clinical and radiographic reversal of the abnormalities after drug therapy. Case Report A 41-year-old Negro male entered the Cincinnati Veterans Administration Hospital in March 1964. In November 1963 rhinorrhea and painful swelling of the fingertips of both hands developed. In February 1964, biopsy of an indurated area of the left palm was diagnosed as lymphoma cutis. Physical examination revealed a healthy-appearing male with normal vital signs. The tip of the spleen was palpable. There was no lymphadenopathy or hepatomegaly. All of the fingers were clubbed, red, and tender (Fig. 1, A). The toes showed erythema and tenderness, but they were not clubbed. Hemoglobin was 11.4 g per 100 ml, hematocrit 37 mm, and leukocyte count 108,000 per mm3 with 70 per cent lymphocytes. Many of these lymphocytes were abnormal with monocytoid nuclei and some binucleated forms. Platelet and reticulocyte counts were normal. Blood urea nitrogen was 27 mg per 100 ml, and uric acid was 6.9 mg per 100 ml. A variety of other blood chemistries were normal. A Coombs' test and tuberculin and histoplasmin skin tests were normal. A sternal bone marrow aspirate showed infiltration with mature abnormal lymphocytes. Similar cells were seen in the pleural fluid and in biopsy specimens of the left palm and skin of the dorsum of the distal left middle finger. A chest roentgenogram on the fifth hospital day showed small bilateral effusions and fluffy infiltrates in both upper lobes. Roentgenograms of the hands are described later. Chlorambucil, 6 mg/day, was prescribed. Over the next ten months the leukocyte count gradually decreased, and there was slow regression of the clubbing. By May 1965 the clubbing had completely disappeared and has not recurred (Fig. 1, B). Chlorambucil was discontinued after fourteen months, and for the past thirty-four months the patient has been in remission without further drug therapy. A sternal bone marrow aspiration in September 1967 was normal. The leukocyte count in April 1968 was 9,600 per mm3, with a normal differential (a few abnormal lymphocytes were still present). Roentgen Findings The striking feature of the admission roentgenogram of the hands was the symmetrical bilateral destruction of the terminal phalanges. The other phalanges and metacarpals appeared completely normal (Fig. 2, A). The destructive process involved primarily the midportions of the distal phalanges but also involved the terminal tufts and bases.