[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.

Utility of immunologic testing in suspected rheumatologic disease.

The use of diagnostic testing in the clinical practice of medicine has been a shifting landscape from the time that the first blood test was utilized. This is no different in the field of immunology and in particular rheumatology. As the field of immunology is relatively young, the clinical tests are not well established and therefore guidelines for use are still under debate. In this review, we seek to look at some of the key autoantibodies, as well as other tests that are available to diagnose suspected rheumatologic disease, and examine how to best use these tests in the clinic. In particular, we will focus on the anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, complement, cryoglobulins, rheumatoid factor, and anti-citrullinated protein antibodies.

Screening panels for detection of monoclonal gammopathies.

BACKGROUND: The repertoire of serologic tests for identifying a monoclonal gammopathy includes serum and urine protein electrophoresis (PEL), serum and urine immunofixation electrophoresis (IFE), and quantitative serum free light chain (FLC). Although there are several reports on the relative diagnostic contribution of these assays, none has looked at the tests singly and in combination for the various plasma cell proliferative disorders (PCPDs). METHODS: Patients with a PCPD and all 5 assays performed within 30 days of diagnosis were included (n = 1877). The diagnoses were multiple myeloma (MM) (n = 467), smoldering multiple myeloma (SMM) (n = 191), monoclonal gammopathy of undetermined significance (MGUS) (n = 524), plasmacytoma (n = 29), extramedullary plasmacytoma (n = 10), Waldenström macroglobulinemia (WM) (n = 26), primary amyloidosis (AL) (n = 581), light chain deposition disease (LCDD) (n = 18), and POEMS syndrome (n = 31). RESULTS: Of the 1877 patients, 26 were negative in all assays. Omitting urine from the panel lost an additional 23 patients (15 MGUS, 6 AL, 1 plasmacytoma, 1 LCDD), whereas the omission of FLC lost 30 patients (6 MM, 23 AL, and 1 LCDD). The omission of serum IFE as well as urine lost an additional 58 patients (44 MGUS, 7 POEMS, 5 AL, 1 SMM, and 1 plasmacytoma). CONCLUSIONS: The major impact of using a simplified screening panel of serum PEL plus FLC rather than PEL, IFE, and FLC is an 8% reduction in sensitivity for MGUS, 23% for POEMS (7 patients), 4% for plasmacytoma (1 patient), 1% for AL, and 0.5% for SMM. There is no diminution in sensitivity for detecting MM, macroglobulinemia, and LCDD.

Polymorphic reticulosis and conventional lymphomas of the nose and upper aerodigestive tract: a clinicopathologic study of 70 cases, and immunophenotypic studies of 16 cases.

Seventy patients with malignant lymphomas, including the entity known as polymorphic reticulosis (PR), involving the nose, nasal sinuses, nasopharynx, oropharynx (excluding tonsil), and larynx were studied. There were 26 cases of PR, 19 cases of lymphoma with features of PR (ML[PR]) and 25 cases of conventional lymphomas. Fourteen of the 25 conventional lymphomas were due to dissemination from distant sites. For all histologic types of primary lymphoma, the presenting symptoms were similar, and the nasal cavity was more commonly involved than the nasopharynx. Patients with PR were younger, had a higher male:female ratio, and had a better overall survival rate than patients with conventional lymphomas. Cryostat section immunohistochemistry performed on 17 samples from 16 patients showed only one B lymphoma out of 11 primary lesions; the other 10 cases and three recurrent tumors at distant sites showed phenotypic markers of T lymphocytes and natural killer cells. All three secondary tumors were of B-cell type. Of eight patients with sequential biopsies, progression to a more malignant histopathologic type was found in six. In the PR and ML[PR] biopsies, angiocentricity was detected in 11%, and angioinvasion in 22%. We could not confirm identity of PR with other angiocentric immunoproliferative lesions.

Detection of immunoglobulin heavy chain genes rearrangements in B-cell leukemias, lymphomas, multiple myelomas, monoclonal and polyclonal gammopathies.

Polymerase chain reaction (PCR) based assays were found to be a realistic alternative to Southern blot hybridization for the assessment of clonal immunoglobulin heavy chain gene rearrangements. However, a comparison of the different PCR based studies reveals considerable variation in experimental design and marked differences in the reported results. This study compared different single- and double-step PCR assays relying on various FR3, FR2, FR1 and JH based primers for the detection of B cell clonality in acute lymphoblastic leukemias (ALL), non-Hodgkin's-lymphoma (NHL), multiple myeloma (MM), monoclonal gammopathies of unknown significance (MGUS) and three polyclonal gammopathies (PG). The highest monoclonality rate was observed using seminested CDR-III region amplification. This method achieved a monoclonal product in 6 of 13 pro-B ALL 21 of 29 c-ALL, 7 of 8 pre-B-ALL, 18 of 21 B-ALL, 14 of 17 B-NHL (intermediate or high grade) with bone marrow involvement, 0 of 9 B-NHL without bone marrow involvement, 9 of 9 low grade B-NHL (immunocytoma and including chronic lymphocytic leucemia), 13 of 19 MM, 2 of 9 MGUS, and 0 of 3 PG. Additional monoclonality was detected with nested CDR I PCR in 1 pro-B-ALL, 1 c-ALL, and 2 MM. CDR III IgH PCR has been confirmed as an efficient method for determining clonality in B-cell neoplasias. Some additional monoclonal products can be seen with CDR I-based PCR. Detection of monoclonality depends on the maturation grade of the neoplastic B-cell population.

Polyclonal systemic immunoblast proliferation: an unusual hematologic entity presenting as a medical examiner case.

A 43-year-old woman who was receiving oral antibiotics for several days for a superficial foot infection developed a persistent rash, fever, and lymphadenopathy, despite discontinuation of the antibiotic and administration of steroids for a presumed drug reaction. Hours after a subsequent visit to the emergency room for worsening symptoms, she died at home. At autopsy, there was a florid, systemic proliferation of polyclonal plasma cells and immunoblasts infiltrating nearly every organ and tissue of the body, most notably the lymph nodes and spleen. The polyclonal nature of the process was confirmed by immunofixation electrophoresis and immunohistochemistry. Cases of fatal polyclonal systemic immunoblast proliferations are extremely rare, and the trigger for such proliferations is not always known. We review the literature on this unusual entity and discuss the clinical and pathologic findings.

A triclonal gammopathy in a relapsing multiple myeloma patient, detected by immunosubtraction method.

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the malignant proliferation of a plasma cell clone that produces a monoclonal immunoglobulin. Diagnosis and management of patients with monoclonal gammopathies depend on accurate identification and characterization of monoclonal proteins. We present a 67-year-old male patient with anaemia, weakness and weight loss for six months. His physical examination was normal with no fever, and no bone lesions were present in the imaging studies. Laboratory investigations revealed low haemoglobin and albumin concentrations with high total protein and beta 2-microglobulin concentrations. Capillary zone electrophoresis with immunosubtraction method revealed a triclonal pattern of M-protein (IgG κ + IgG λ + IgA κ) which was not prominent with immunofixation electrophoresis. After bone marrow biopsy, MM with triclonal gammopathy was diagnosed and autologous stem cell transplantation was performed. Six months later, again a triclonal M-protein was detected by immunosubtraction method, and a relapse was confirmed with a second bone marrow biopsy. The occurrence of monoclonal and biclonal gammopathies can often be seen upon diagnosis in plasma cell dyscrasias and lymphoproliferative disorders, but triclonal paraproteins are very rare and their clinical significance is unknown. In this particular patient, triclonality was detected by an alternative method called immunosubtraction by capillary electrophoresis. The patient was resistant to therapy suggesting that more than one monoclonal M protein may be a negative prognostic factor, and with new technologies and methods, the number of patients with different monoclonal patterns may increase.

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.

Systemic polyclonal immunoblastic proliferations.

This report describes the clinical and pathologic features of four patients with a florid, systemic immunoblastic proliferation. The blood of these patients exhibited a mild to marked leukocytosis with a high percentage of immunoblasts and plasma cells. The bone marrow also was infiltrated extensively by immunoblasts. Lymph node biopsy specimens from two patients showed near total effacement of the nodal architecture by a diffuse infiltration of immunoblasts and plasma cells. The proliferative process was determined to be polyclonal with immunohistochemical techniques. Cytogenetic studies of bone marrow from two patients showed a pseudodiploid abnormal clone, with a translocation involving a break in band 14q32 in each case. The pathogenesis of these proliferative disorders in unclear, although three patients had some evidence of an acute immune disorder. One of these patients was treated with steroids, vincristine, and cyclophosphamide. Another patient was treated with steroids only, and one patient was treated with steroids and cyclophosphamide. All had rapid regression of the disease process. Two patients are alive and apparently free of disease 31 and 48 months after diagnosis. One died of sepsis. The fourth patient had acquired immune deficiency syndrome (AIDS) and died without therapy. The biology of the immunoblastic proliferation of these patients is uncertain. The immunohistochemical results suggest a reactive, polyclonal proliferation, but the cytogenetic abnormalities in two patients indicate the possibility of a cryptic neoplastic clone.

Propuesta de caracterización y tipificación de proteínas monoclonales aplicable al laboratorio clínico / Proposal of characterization and typification of monoclonal proteins applicable to clinical laboratory

En el presente trabajo se incorporan y ordenan procedimientos para obtener la mayor información posible a nivel laboratorio clínico en la indagación de proteínas "M" y la definición de su clase (cadenas pesadas) y tipo (cadenas livianas). Se propone una secuencia de las siguientes técnicas: electroforesis, inmunoelectroforesis, inmunofijación, inmunodifusión radial cuantitativa, tratamientos despolimerizantes e inmunosustracción. La inmunosustracción, descripta por W. A. White y col., consiste en la remoción de la inmunoglobulina en estudio mediante un antisuero específico en presencia de polietilenglicol, separación del inmunocomplejo precipitado y posterior evaluación del sobrenadante mediante inmunofijación; se identifica la cadena liviana que pertenece a la inmunoblobulina sustraída por su ausencia al fijar con el antisuero correspondiente. Es particularmente útil cuando se desea establecer la correspondencia liviana/pesada en presencia de bandas homogéneas múltiples, identificar bandas menores enmascaradas en un fondo policlonal y excluir la presencia coincidente de cadenas livianas libres. Se aconseja incorporar el tratamiento despolimerizante con 2-mercaptoetanol previamente a la cuantificación de IgM por inmunodifusión radial ya que la comparación previa entre controles tratados y no tratados reveló una diferencia muy significativa cuando se analizó mediante contraste de diferencias entre pares homólogos (n = 12, test t = 37,2 p <0,01)

Propuesta de caracterización y tipificación de proteínas monoclonales aplicable al laboratorio clínico / Proposal of characterization and typification of monoclonal proteins applicable to clinical laboratory

En el presente trabajo se incorporan y ordenan procedimientos para obtener la mayor información posible a nivel laboratorio clínico en la indagación de proteínas "M" y la definición de su clase (cadenas pesadas) y tipo (cadenas livianas). Se propone una secuencia de las siguientes técnicas: electroforesis, inmunoelectroforesis, inmunofijación, inmunodifusión radial cuantitativa, tratamientos despolimerizantes e inmunosustracción. La inmunosustracción, descripta por W. A. White y col., consiste en la remoción de la inmunoglobulina en estudio mediante un antisuero específico en presencia de polietilenglicol, separación del inmunocomplejo precipitado y posterior evaluación del sobrenadante mediante inmunofijación; se identifica la cadena liviana que pertenece a la inmunoblobulina sustraída por su ausencia al fijar con el antisuero correspondiente. Es particularmente útil cuando se desea establecer la correspondencia liviana/pesada en presencia de bandas homogéneas múltiples, identificar bandas menores enmascaradas en un fondo policlonal y excluir la presencia coincidente de cadenas livianas libres. Se aconseja incorporar el tratamiento despolimerizante con 2-mercaptoetanol previamente a la cuantificación de IgM por inmunodifusión radial ya que la comparación previa entre controles tratados y no tratados reveló una diferencia muy significativa cuando se analizó mediante contraste de diferencias entre pares homólogos (n = 12, test t = 37,2 p <0,01) (AU)

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)

[Sjogren's syndrome and lympho-proliferating syndrome-taking stock]

Sjogren's syndrome, the most frequent autoimmune connective tissue disorder, is associated with a risk of B lymphoid proliferation. The clinical risk factors are parotidomegaly, enlarged lymph nodes and splenomegaly. Fever, weight loss and a decline in the general health status as well as a rise in beta 2 micro globulin or the appearance of monoclonal immuno globulin in the plasma are the signs of malignant lymphoma complicating sjogren's syndrome. We discuss the therapeutic and physiopathologic implications of this ominous complication