Severe Diffuse Infiltration Research Articles

The role of CT in PET/CT for assessing diffuse infiltration of bone marrow in multiple myeloma using the Durie-Salmon PLUS staging system.

PET/CT has been identified as one of the routine methods for the assessment of multiple myeloma (MM) bone marrow infiltration. In the routine method of performing PET/CT, the 18F-Fludeoxyglucose (18F-FDG) uptake in this disease is often used in the assessment of this condition, however CT diagnosis is not currently commonly used. The aim of the present study was to investigate the importance of CT in PET/CT for assessing diffuse infiltration (DI) of bone marrow in MM. MRI was used as a control in the present study, which is the gold standard for assessing DI of bone marrow and is divided into 3 levels: Mild, moderate and severe DI. Subsequently, a total of four combinations of PET and CT results were listed using the enumeration method for the evaluation of DI in the bone marrow. These combinations were respectively compared with the three levels of MR imaging to screen the most consistent method. The concordances of the new method and routine 18F-FDG PET/CT for the assessment of DI with MR imaging were compared using the McNemar test, respectively. The results of the DI assessment from the two methods were verified by performing Durie-Salmon (D-S) PLUS staging. Compared with MR imaging, the results were as follows: PET and CT exhibited negative results, suggesting mild DI; one of them was positive, suggesting moderate DI; and two were positive, suggesting severe DI. The results of concordance between two methods (new and routine) and MR imaging are indicated as follows: For the new method, McNemar test, P=0.513 and Kappa=0.745; for the routine 18F-FDG PET/CT method, McNemar test, P=0.03 and Kappa=0.547. Re-performance of D-S PLUS staging presented the following results: New method, McNemar test, P=0.317 and Kappa=0.93; for the routine method, McNemar test, P=0.223 and Kappa=0.811. These findings indicated that the CT component of PET/CT could improve the concordance with MRI results in the assessment of DI, and the same results were obtained when D-S PLUS staging was performed. The CT in PET/CT can enhance diagnostic accuracy in the assessment of DI by reducing the false negatives when compared with the routine 18F-FDG method.

Association between magnetic resonance imaging patterns and baseline disease features in multiple myeloma: analyzing surrogates of tumour mass and biology.

To assess associations between bone marrow infiltration patterns and localization in magnetic resonance imaging (MRI) and baseline clinical/prognostic parameters in multiple myeloma (MM). We compared baseline MM parameters, MRI patterns and localization of focal lesions to the mineralized bone in 206 newly diagnosed MM patients. A high tumour mass (represented by International Staging System stage III) was significantly associated with severe diffuse infiltration (p = 0.015) and a higher number of focal lesions (p = 0.006). Elevated creatinine (p = 0.003), anaemia (p < 0.001) and high LDH (p = 0.001) correlated with severe diffuse infiltration. A salt and pepper diffuse pattern had a favourable prognosis. A higher degree of destruction of mineralized bone (assessed by X-ray or computed tomography) was associated with an increasing number of focal lesions on MRI (p < 0.001). Adverse cytogenetics (del17p/gain1q21/t(4;14)) were associated with diffuse infiltration (p = 0.008). The presence of intraosseous focal lesions exceeding the mineralized bone had a borderline significant impact on prognosis. Diffuse bone marrow infiltration on MRI correlates with adverse cytogenetics, lowered haemoglobin values and high tumour burden in newly diagnosed MM whereas an increasing number of focal lesions correlates with a higher degree of bone destruction. Focal lesions exceeding the cortical bone did not adversely affect the prognosis. • Diffuse MRI correlates with adverse cytogenetics, lowered haemoglobin and high tumour burden. • Higher numbers of MRI focal lesions correlate with increasing degree of bone destruction. • Focal lesions exceeding the cortical bone borderline significantly influence survival. • Moderate/severe diffuse infiltration and more than 23 focal lesions adversely affect survival.

Over 30% of Smoldering Myeloma Patients Have Tumor Cell Bone Marrow Infiltration Patterns Similar to Multiple Myeloma: A Large (n=544) Clinical Study Using Whole-Body MRI.

Abstract 2911 Background:Traditionally, anti-myeloma therapy is initiated by presence of end-organ damage defined by CRAB criteria (hypercalcemia, renal failure, anemia, and/or lytic bone lesions). Recently, several clinical trials have been initiated to evaluate the role of treatment in smoldering myeloma (SMM) patients, which by diagnostic criteria lack end-organ damage. Several studies have indicated the prognostic significance of magnetic resonance imaging (MRI) for patients with smoldering (SMM) and multiple myeloma (MM). Given that the risk of transformation from SMM to MM varies greatly, we have conducted a large retrospective clinical study, using whole-body MRI, to characterize patterns of tumor infiltration in the bone marrow among patients diagnosed with SMM. These patients were then followed longitudinally for progression to MM. Furthermore, we have expanded MRI studies to patients with monoclonal gammopathy of undetermined significance (MGUS), and have analyzed the imaging findings within established prognostic parameters of this group of patients. Methods:A total of 157 patients with SMM, 138 with monoclonal gammopathy of undetermined significance (MGUS), and 249 with MM were assessed by whole body MRI. Patients with second malignancies, amyloidosis, solitary plasmocytoma or preceding systemic treatment were excluded from the study. In patients with MGUS and SMM initiation of systemic treatment and in patients with MM, relapse after systemic therapy was defined as end point for progression free survival. For all patients we collected extensive clinical and diagnostic data. Using logistic regression, we evaluated the presence/absence of focal or diffuse signal abnormalities. Using log-rank test we defined treatment-free survival for SMM in relation to imaging results. Median follow-up was 4.0, 4.5 and 3.7 years for MGUS, SMM and MM patients, respectively. Results:In MGUS patients, focal lesions were detectable in 23.9% and a diffuse infiltration in 53%. Diffuse and focal infiltration patterns appeared independently from each other. The presence and number of focal lesions as well as a severe diffuse infiltration were statistically significant adverse prognostic factors for progression free survival. In multivariate analysis, only the number of focal lesions remained statistically significant (p=0.0005). In SMM patients, focal lesions were present in 34.4% and a diffuse infiltration pattern in 45.9%. Plasma cell percentage, a moderate diffuse infiltration (but not focal lesions) and beta2-microglobulin were statistically significant prognostic parameters.Whole-body MRI indicated that for 65.6% of the patients with SMM, patterns of tumor cell infiltration in the bone marrow were similar to MGUS patients; whereas 34.4% showed patterns similar to MM patients. Sensitivity and specificity of prediction performance of the classification model was 0.8 and 0.76, respectively. Using a log-rank test for prediction of treatment-free survival of SMM patients in relation to whole-body MRI patterns of tumor cell infiltration in the bone marrow, we found a borderline difference between MGUS-like SMM (n=124) and MM-like SMM patients (n=33) (p=0.08); whereas the difference between MM-like SMM patients and the 138 MGUS patients was significant (p=0.02). Conclusions:In summary, in this first large clinical study including 544 patients, whole-body MRI was able to discern over 30% of patients with SMM presenting with patterns of tumor cell infiltration in the bone marrow similar to those of MM. Given that many patients with SMM develop symptomatic disease within 1–2 years, in the future, advanced imaging may play a major role in defining patients with SMM who should be candidates for early treatment. Disclosures:No relevant conflicts of interest to declare.

Tubulointerstitial nephritis and uveitis syndrome with transient hyperthyroidism in an elderly patient

A 69-year-old Japanese woman without any specific medical or family history was admitted to our hospital for renal insufficiency with proteinuria. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 34.9 mg/dL and creatinine level was 1.78 mg/dL) and elevated urinary levels of N-acetyl-β-D-glucosaminidase (23.4 U/L) and β2-microgloblin (20200 μg/L) were observed. We performed a renal biopsy. The biopsied specimen showed severe diffuse infiltration of mononuclear cells into the interstitium, with normal glomeruli, and these findings were compatible with acute tubulointerstitial nephritis (ATIN). At that time, ATIN seemed to be idiopathic. We performed gallium scintigraphy, and the results revealed uptake by the bilateral kidneys, thyroid gland, and right parotid gland. Serum thyroid stimulating hormone (TSH) was undetectable, free triiodothyronine was normal (3.11 pg/mL), and free thyroxine was elevated to 2.4 ng/dL. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Two months later, burning pain and conjunctival congestion developed in both eyes. She had uveitis, as diagnosed by slit-lamp examination. Topical corticosteroid was used for the uveitis with success. We could not detect any cause of the uveitis, so a diagnosis of tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) with associated hyperthyroidism was made. Treatment was started with 15 mg/day of prednisolone. Now her renal function is slowly recovering. There are few reports of TINU syndrome with transient hyperthyroidism. This case suggests the possibility of thyroid dysfunction in patients with TINU syndrome. A laboratory evaluation of thyroid function should be considered in the diagnostic evaluation of TINU syndrome.

Ectima contagioso em ovinos e caprinos no semi-árido da Paraíba

Descrevem-se dez surtos de ectima contagioso em caprinos e dois em ovinos no semi-árido da Paraíba. Os animais jovens foram os mais afetados, mas em oito surtos animais adultos também foram afetados, principalmente cabras lactantes que apresentavam lesões no úbere. Em nenhum dos rebanhos afetados havia antecedentes de vacinação contra ectima contagioso. Histologicamente a epiderme apresentava acantose com hiperplasia pseudoepiteliomatosa e com múltiplos focos de degeneração hidrópica formando vesículas ou pústulas. Inclusões intracitoplasmáticas eosinofílicas foram observadas em queratinócitos. Havia restos celulares necróticos formando crostas, hiperqueratose e microabscessos intracorneais ou extensas áreas ulceradas. Na derme observou-se infiltrado inflamatório mononuclear difuso. Também foi registrado um caso humano em um pesquisador que tinha administrado planta por via oral a um caprino que, posteriormente, apresentou lesões de ectima contagioso. Neste caso, também foram observadas lesões características em uma biopsia e o vírus foi identificado por microscopia eletrônica. Conclui-se que a doença é endêmica no semi-árido e que é necessária a vacinação sistemática dos rebanhos para diminuir os prejuízos econômicos causados pela mesma. A utilização de luvas para o manuseio de animais afetados é necessária para evitar casos humanos da enfermidade.

Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism

We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.