[Light-chain deposition disease is a hematologic problem]. / Bolezn' depozitov legkikh tsepei ­ gematologicheskaia problema.

AIM: To analyze clinical and laboratory data and treatment results in patients with light-chain deposition disease (LCDD). SUBJECTS AND METHODS: Nine patients with LCDD and kidney injury were examined. The diagnosis was based on the results of light and immunofluorescence microscopy of renal biopsy specimens. All the patients received bortezomib, cyclophosphamide, and dexamethasone (VCD) induction therapy. RESULTS: Six patients were diagnosed with multiple myeloma; in 3 patients LCDD was considered within monoclonal gammopathy manly involving the kidney. By the initiation of therapy, all the patients were diagnosed as having chronic kidney disease (Stage III (n=2), Stage IV (n=2), and dialysis-related renal failure (n=5)). After the VCD treatment, 7 of 9 patients achieved a hematologic response. Second-line therapy with lenalidomide proved to be effective in the other 2 cases. Five patients achieved complete remission; 3 had a very good partial remission. Thereafter, 2 patients received high-dose melphalan chemotherapy and autologous hematopoietic stem cell transplantation. Better renal function was noted in only 2 cases. CONCLUSION: Despite the high efficiency of therapy aimed to reduce monoclonal light chains; improved renal function was observed in only 2 (22%) patients. Such low rates of a renal response were due to the late initiation of therapy.

Intravenous Immunoglobulin G Improves Pregnancy Outcome in Women with Recurrent Pregnancy Losses with Cellular Immune Abnormalities.

PROBLEM: We investigated the therapeutic effect of intravenous immunoglobulin (IVIG) in women with recurrent pregnancy loss (RPL). METHOD OF STUDY: This was a retrospective observational study. Total 189 RPL women who experienced ≥2 miscarriages were enrolled and investigated conventional etiologies, thrombophilia, and cellular immunity. Patients were divided into four groups; known etiology with (Gr1) and without cellular immune abnormality (Gr2), unknown etiology with (Gr3) and without cellular immune abnormality (Gr4). IVIG was administrated from early pregnancy to 30 weeks of gestation to women with cellular immune abnormality (Gr1 + Gr3). RESULTS: Cellular immune abnormalities (increased level or cytotoxicity of NK cells and Th1/Th2 ratio) were present in 111 of 189 RPL women (58.7%). Live birth rates of women with and without cellular immune abnormality were not different (Gr1 + Gr3, 84.8% versus Gr2 + Gr4, 89.7%). Furthermore, IVIG success rates were the same between Gr1 and Gr3, those who had cellular immune abnormality. Nevertheless lack of an appropriate control in this study, our IVIG outcome demonstrated better live birth rate compared with those of other investigators. CONCLUSION: Treatment modalities stratified by underlying etiologies of RPL may improve pregnancy outcome. Administration of IVIG is likely to have clinical efficacy in RPL women with cellular immune abnormality.

Lesión destructiva de linea media inducida por cocaína / Destructive lesion of the median line induced by cocaine

Presentamos el caso de un paciente que sufre una complicación por el uso continuado de cocaína inhalada, raramente descrita, como es la necrosis centrofacial, asociando perforación septal y palatal. Revisamos los posibles diagnósticos diferenciales a los que debe someterse cualquier caso de destrucción de línea media facial, y la actitud a seguir cuando la etiología es la cocaína (AU)

A case of lymphomatoid granulomatosis/angiocentric immunoproliferative lesion with long clinical course and diffuse brain involvement.

Lymphomatoid granulomatosis (LYG)/angiocentric immunoproliferative lesions (AIL) consist of angiocentric and angiodestructive lymphoreticular proliferation predominantly involving the lungs and other extranodal sites, such as the central nervous system (CNS). This clinical entity is considered as a B cell process related to Epstein-Barr virus (EBV) infection and EBV positive diffuse large B-cell lymphoma. The CNS is involved in 20% of cases of LYG, but initial involvement is rare. In cases without pulmonary symptoms, diagnosis may be difficult. We report a rare case involving initial progression of CNS symptoms followed by a pulmonary abnormality.A 14-year-old girl suffered from high fever, ataxic gait and paraparesis. MRI revealed diffuse T2 high signals with multiple gadolinium enhancements in the cerebellum, brain stem and cerebral white matter. Her symptoms briefly improved after steroid therapy, but ataxia gradually progressed. Dyspnea due to pulmonary interstitial involvement appeared when she was 18 years old. Steroid therapy proved effective for respiratory symptoms. At 20 years old she suffered from disseminated intravascular coagulopathy (DIC) and hemophagocytic syndrome (HPS) with respiratory symptoms and repeated seizures. Her symptoms improved after the administration of cyclophosphamide. Mild hemiparesis and gait disturbance appeared when she was 22 years old. MRI revealed new lesions at the basal ganglia and subcortical white matter, brain atrophy and diffuse T2 high intensity of cerebral white matter. Cyclophosphamide was effective and there has been no recurrence of symptoms in the last 5 years. We reviewed the non-tumorous LYG/AIL involving the CNS, and discussed the clinical features, MRI imaging and diagnosis of the LYG/AIL.

Angiocentric immunoproliferative lesions of the lung associated with diffuse renal involvement.

A 62-year-old Japanese man presented with high fever, cough, and sputa. Computed tomography (CT) scan of the chest revealed lung infiltrates with air bronchogram of the right middle lobe and mediastinal lymphadenopathy. Bronchoscopic examination was performed, and Mycobacterium avium complex was detected from bronchoalveolar lavage fluid. Although the administration of clarithromycin and levofloxacin improved the patient's symptoms, the lung infiltrates on chest CT scan gradually worsened. Lung biopsy of segments 4 and 8 by video-assisted thorachoscopy revealed angiocentric and angiodestructive massive lymphoplasmocytic infiltrations with multinucleated giant cells, which were compatible with grade II angiocentric immunoproliferative lesions. The patient was found to have deterioration of renal function, and glomerular filtration rate was 32.6 mL/min. His kidneys were enlarged and showed prominent and diffuse uptake of gallium-67 citrate. Percutaneous renal biopsy revealed massive infiltration of CD4+ mononuclear cells, plasma cells, and eosinophils in the interstitium and destruction of normal structure of tubules. Blood vessels were destroyed and replaced by inflammatory cells. The combination chemotherapy achieved a remission, and the patient has remained free of disease at 2 years after onset of the illness. We recommend the imaging of kidneys for diagnosis and following renal biopsy to evaluate the renal involvement of angiocentric immunoproliferative lesions.

[Cancer and primary humoral immunodeficiency]. / Cancer et déficit primitif de l'immunité humorale.

The occurrence of cancers in patients with primary humoral immunodeficiency syndrome (X-linked agammaglobulinemia, common variable immunodeficiency, IgA deficiency) is more than mere coincidence. An increased risk of non Hodgkin's lymphoma and gastric adenocarcinoma, particularly for patients with common variable immunodeficiency, is well established. A literature review is presented on this subject with analysis of case reports, prospective and retrospective studies, and data from the Minnesota Immunodeficiency Cancer Registry.

[Triclonal gammopathy and malignant immunoproliferative syndrome]. / Gammapathie triclonale et syndrome immunoprolifératif malin.

Three distinct monoclonal gammopathies were identified in the serum of a 79 year-old man. In 1972 he presented with Waldenström's macroglobulinemia IgM Kappa. Twenty years later multiple myeloma was diagnoses. Serum protein electrophoresis performed at this time showed three monoclonal bands. Immunofixation identified these bands as monoclonal IgM kappa, IgG kappa and IgA kappa. Twenty-six cases of triclonal gammopathies were previously reported. Sixteen cases were associated with malignant immuno-proliferative diseases (non-hodgkin lymphoma, Waldenström's macroglobulinemia, multiple myeloma); five cases with non-hematologic diseases; three cases were of undetermined significance. The origin of three distinct monoclonal proteins may derive from three unrelated clones or alternatively from a single clone in which an isotype switch has occurred.

Co-existence of Dubowitz and hyper-IgE syndromes: a case report.

UNLABELLED: A case of a 5-year-old girl is described whose clinical features included postnatal growth retardation, microcephaly and characteristic facial appearance. These are recognized as the main features of the Dubowitz syndrome. Apart from these features, our patient had recurrent infections of the sinopulmonary tract, high serum IgE levels, defective chemotaxis of polymorphonuclear cells and defective antibody response, findings characterizing the hyper-IgE syndrome. The co-existence of these two syndromes is rare and we suggest that this is the first such case in the literature. CONCLUSION: Patients with the Dubowitz syndrome will Dubowitz syndrome will require long-term follow up because there is a considerable risk for the syndrome to co-exist with primary immunodeficiency or for malignancies to develop.

Angiocentric immunoproliferative lesion associated with chronic active Epstein-Barr virus infection in an 11-year-old boy. Clonotopic proliferation of Epstein-Barr virus-bearing CD4+ T lymphocytes.

We report a pulmonary angiocentric immunoproliferative lesion (AIL) in an 11-year-old boy with chronic active Epstein-Barr virus (EBV) infection. The phenotypes of the proliferating lymphoid cells in the biopsied pulmonary lesion were CD2+, CD3+, CD4+, CD5+, CD7+, and HLA-DR+. EBV DNA was detected in the tumorous and the nontumorous tissue by Southern-blotting studies. Dual immunostains and combined immunohistochemistry/in situ hybridization showed the simultaneous presence of EBV-determined nuclear antigen or EBV-encoded small RNAs and T-cell markers in the lymphoid cells. Molecular genetic analysis of the tumorous lesion diagnosed as AIL grade III showed no clonal rearrangement of the T-cell receptor beta gene but a single type of fused terminal band of EBV. No such evidence of monoclonality was identified in the surrounding nontumorous tissue diagnosed as AIL grade I or II. The present case was a rare example of AIL in childhood and provides further histopathologic and molecular biological evidence supporting the concept of AIL as a continuous spectrum from premalignant lymphoproliferative disorders to monoclonal, overt malignant lymphoma.

Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis.

Monoclonal immunoglobulin deposition occurs in tissues as Congo Red binding fibrils in light chain amyloidosis, as less structured deposits in light chain deposition disease, and as similar but distinct deposits in light and heavy chain deposition disease. The nonamyloid forms were found in 13 patients who had evidence of plasmacytic dyscrasia by the immunohistochemical detection of immunoglobulin light chains of kappa or lambda class (with or without staining for a single heavy chain isotype) and by the absence of amyloid P component in tissue sections that did not show the birefringence characteristic of amyloid after Congo Red staining. All but two of the patients presented with proteinuria with or without azotemia. Clinical syndromes involving other organ systems were less common but occasionally severe. Four patients had overt multiple myeloma. Three others had hypercalcemia and mild bone marrow plasmacytosis but no lytic lesions. Analyses of immunoglobulin synthesis in bone marrow cells from seven patients showed excess light chains in all and incomplete light chains or heavy chain fragments in six, regardless of whether an intact monoclonal protein or related subunit was in the serum or urine. The fibrillar (amyloidotic) and nonfibrillar forms of monoclonal immunoglobulin deposition occur either in overt multiple myeloma or in the course of less neoplastically aggressive plasmacytic dyscrasias. Bone marrow cells from patients with either type produce immunoglobulin fragments that are related to those deposited in the affected tissues.

The clinical significance of pure Bence Jones proteinuria at low concentration.

The clinical significance of Bence Jones (BJ) proteinuria at low concentration (less than 0.2 g/24 hours) was investigated in 33 unselected patients who had no intact monoclonal immunoglobulin in their serum. The great majority (79%) of the patients were recognized as having malignant lymphoproliferative diseases, such as chronic lymphocytic leukemia (46%), hairy cell leukemia (6%), and non-Hodgkin's lymphoma (27%), whereas only two patients (6%) had multiple myeloma or systemic amyloidosis. Five patients (15%) had no evidence of definite malignant immunoproliferative disorders at the time of recognition of BJ proteinuria. Three of them, who were excreting steadily low amounts of BJ protein in their urine for 47, 61, and 73 months, respectively, without development of any B-lymphocytic malignancy, were classified as having a monoclonal gammopathy of undetermined significance. In the remaining two patients, BJ protein disappeared spontaneously 14 and 18 months, respectively, after its recognition. The study indicates that pure BJ proteinuria, even when occurring at low concentration, is most consistently associated with malignant proliferations of B-lymphocytic origin. However, the possibility should be considered that the clinical spectrum of the monoclonal gammopathy of the light chain type also includes benign and transient forms.

Fatal legionellosis in patients with malignant hematologic diseases.

Pneumonia was present in 70/157 (44.6%) autopsied patients with malignant hematologic diseases. In 16/70 patients (22.9%), legionellae were found to be the causative agents by screening lung tissue specimens with the direct fluorescent antibody method. In 5/16 patients with Legionella pneumonia, in whom legionellosis had been suspected clinically, the diagnosis had already been established by serology, urinary Legionella antigen detection, and culture. These results provide evidence that legionellosis is an important pneumonia etiology in patients with malignant hematological diseases. Thus, Legionella diagnostics should be applied routinely, and antibiotics effective in the treatment of legionellosis should be added to the usual therapy in patients with etiologically unexplained pneumonias. In view of the common occurrence of relapses of Legionella pneumonia, antibiotic therapy should be continued for an extended period.

Virus-associated hemophagocytic syndrome: identification of an immunoproliferative precursor lesion.

Virus-associated hemophagocytic syndrome (VAHS) is a nonneoplastic, generalized histiocytic proliferation with marked hemophagocytosis associated with a systemic viral infection. Histologic studies of lymph nodes usually show lymphoid depletion and histiocytic proliferation. In this report we describe the case of a patient with Epstein-Barr virus-associated VAHS in which initial lymph node biopsy samples showed an immunoproliferative lesion that preceded the usual generalized histiocytic proliferation. This finding suggests that some cases of VAHS may have an immunoproliferative precursor lesion.

Plasma fibronectin in hemoblastosis.

Fibronectin (FN) is a glycoprotein whose plasma concentrations are reduced in many pathological conditions. In patients with hemoblastosis plasma FN was correlated with some clinical and biological parameters (stage of the disease, hepatosplenomegaly, infections and DIC), in order to assess its value as a tumor marker. The results suggest a poor relationship between FN levels and the course of the disease. However, the behaviour of the protein in relation with treatment was dynamic.

Immunoproliferative small-intestinal disease with lymphoma--diagnostic difficulties and pitfalls. Case reports.

Immunoproliferative small-intestinal disease and related diffuse intestinal lymphoma is a debilitating illness prevalent in South Africa. Case reports are presented to illustrate that the early course may be deceptively prolonged and 'benign'; diarrhoea is not invariable, and an initial clinical response to antibiotics may occur. The combination of villous atrophy and a predominantly plasma cell infiltration of the lamina propria in jejunal biopsy specimens may indicate lymphoma in adjacent bowel or regional lymph nodes.