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The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

The serum free light chain (FLC) assay is an important tool in the management of patients with monoclonal gammopathies. MEDLINE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from January 2000 through July 2013, were used as data sources. The available evidence is rather weak. For screening of multiple myeloma and related conditions, the association of the FLC assay with the traditional serum tests avoids urine study. Screening for immunoglobulin light-chain (AL) amyloidosis or other rare syndromes requires the urine examination. FLC measurement is used in the assessment of the risk of progression of precursor diseases to overt myeloma, and for risk stratification in solitary plasmacytoma, multiple myeloma and AL amyloidosis. In patients with oligosecretory myeloma and AL amyloidosis, the quantification of FLC is essential for monitoring and categorization of response to therapy. Further studies with improved design are warranted to strengthen the available evidence.

A Syrian hamster developed marked swelling of the ventral neck. The radiological features were homogeneous mass and relatively nonspecific. Fine needle aspiration cytology of the mass showed numerous polymorphic plasma cells. Necropsy examination revealed a 2 × 3 × 2 cm encapsulated oval mass within the area of the right and the left submandibular salivary glands and the adjacent cervical lymph node. Histopathological examination of the mass confirmed that the submandibular salivary glands were effaced by large numbers of neoplastic plasma cells. A complete multiple myeloma work-up, including bone marrow biopsy, total body skeletal survey, immunoelectrophoresis, quantitative immunoglobulins, and urinary Bence Jones proteins remained negative. Salivary gland plasmacytomas are extremely rare in people and, to the best our knowledge, only one case has been previously reported in nonhuman species. The occurrence of such neoplasms in a hamster suggests that this species may be predisposed to developing tumors of this type.

Permanent proteinuria is an early marker of the kidney dysfunction. Tracking by urinary strip, imposes a precise quantification by the laboratory. In front of the difficulties of urine collection during 24 hours, protein determination can be carried out on the urine of a miction and can be expressed as g per g of creatinine (uPCR). We analysed the impact of the expression of the proteinuria in g/L (uP) as compared to uPCR on the urinary electrophoretic profiles. A revision and a simplification of this in practice clinical interpretation is proposed. The proteinuria of 696 in-patients was quantified on an Olympus AU2700. The urinary electophoretic profiles (SDS-AGE) were interpreted by two biologists. uP and uPCR are well correlated (r=0.847, p0.0001). Data agreed for proteinuria1 g/L but concordance was obtained only in 74% of the subjects and 55% of the pathological patients. A repetition of the analyses is suggested. The interpretative diagram suggested with simplified comments improved interpretation. We advise an interpretation by two biologists. In conclusion, interpretation of the urinary electrophoretic profile rests on the rate of total proteinuria. Expression of the proteinuria as g/g of creatinine must be associated with the expression in g/L because of the analytical conditions. The SDS-AGE Technique does not allow the identification of the monoclonal compound but allows a quantitative follow-up under treatment and especially an early tracking of the type of renal dysfunction.

1. Karen Ferreira, MS, MLS (ASCP)CM[⇑][1] 1. Department of Pathology, Hematology, Rhode Island Hospital, Providence, RI 1. Address for Correspondence: Karen Ferreira MS, MLS (ASCP)CM, Department of Pathology, Hematology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 401-444-4215, KAFerreira{at}Lifespan.org 1. Explain the pathophysiology of multiple myeloma. 2. Outline the different subsets of presentation. 3. Correlate the immunophenotype with the clinical and genetic aspects of myeloma. 4. List the results of the laboratory tests routinely evaluated in multiple myeloma. Introduction Plasma cell myeloma (multiple myeloma, myelomatosis, medullary plasmacytosis, Kahler's disease) is a B-cell neoplasm resulting from the expansion of a single clone of plasma cells (PC). The PCs synthesize a monoclonal immunoglobulin (paraprotein), a monoclonal immunoglobulin light chain (Bence-Jones protein) or both.1 The Bence-Jones proteins may lead to renal failure and the paraproteins can lead to peripheral blood (PB) hyperviscosity.2 Plasma cell myeloma (PCM) is clinically heterogeneous and may present with no symptoms or as an extremely aggressive disease.3 PCM is usually confined to the bone marrow (BM), with extramedullary involvement seen only in end stage cases.4,5 Epidemiology and Etiologies PCM constitutes 10-15% of all hematologic malignancies and 1% of all malignancies.6,7,8 PCM incidence increases with age with 40% of patients presenting under 60 years and only 2% occurring under the age of 40. The median age at diagnosis is 70. Incidence is greater in men than women (1.4:1), and occurs twice as frequently in African Americans than in Caucasians. The risk of PCM increases by 3.7 fold for individuals with a first degree relative with the disease.9,10 In 2007 approximately 20,000 new cases were diagnosed and 11,000 patients died from the disease.11,12 Clinical Features/Diagnostic Criteria The patients usually present with bone pain and pathologic fractures (due to lytic bone lesions). Anemia (due to bone marrow replacement of clonal PCs), recurrent infections (decreased normal immunoglobulin levels), and renal failure (Bence Jones deposition in kidneys) are common findings. Other clinical findings include hyperviscosity syndrome, hypercalcemia (increased osteoclastic activity), and epidural… ABBREVIATIONS: PCM – plasma cell myeloma, PC – plasma cell, PB – peripheral blood, BM – bone marrow, NCAM - neural cell adhesion mutation, VDC – cyclophosphamide, dexamethazone, bortezimib 1. Explain the pathophysiology of multiple myeloma. 2. Outline the different subsets of presentation. 3. Correlate the immunophenotype with the clinical and genetic aspects of myeloma. 4. List the results of the laboratory tests routinely evaluated in multiple myeloma. [1]: #corresp-1

Remarkable advances in understanding human biology in health and disease, propelled by technological innovations, have contributed to an increase in the number and quality of diagnostic tests. This evolving scenario has been accompanied by the proliferation of false myths and legends in laboratory diagnostics, consuming valuable human and economic resources and jeopardizing the clinical reasoning. The aim of this article is to provide a synthetic overview about some paradigmatic examples of false beliefs in laboratory diagnostics involving activated partial thromboplastin time (APTT), cardiospecific troponins, ischemia modified albumin (IMA), D-dimer, prostate specific antigen (PSA), dibucaine number, Bence Jones protein (BJP), lipoprotein(a), neutrophil gelatinase-associated lipocalin (NGAL), potassium and reference ranges. Although the suggestive cases described in this article are not intended to be comprehensive, we hope that their description may help remove some mysticisms in laboratory diagnostics.

Introduction: Multiple myeloma is a plasma cell cancer causing infiltration of bone marrow and presence of monoclonal proteins in plasma and/or the Urine causing mortality and morbidity. Multiple myeloma with Biclonal Gammopathy is rare and accounting about 1-2%.Clinical case description: In this report, we encountered a patient presented with backache and weakness since a month, the lab investigation revealed reversal A/G ratio suspected towards para-protein and electrophoresis showed 2 distinct band in the gamma region, peripheral smear, bone marrow and X-ray reports supported findings, urine positive for Bence Jones Protein, Immunofixation showed 2 distinct bands in IgA and Kappa region. It is a rare Immunofixation pattern which is seen in any multiple myeloma cases. Conclusion: Hence with the clinical feature and the investigation the multiple myeloma was found to be positive, and 2 bands in IgA and kappa region pointing it to be a Biclonal Gammopathy.

Multiple myeloma is a malignant plasma cell proliferation characterized by infiltration of the bone marrow plasma cells synthesizing a complete or incomplete monoclonal immunoglobulin. To describe the different clinical, radiological and biological aspects of myeloma with chest localization, we achieved a retrospective study over a period of 5 years (2010-2015) including 18 multiple myeloma patients with chest location hospitalized in service of pneumology. There were twelve men and six women. The average age was 60 years. Diffuse bone pain was noted in 80% of cases with chest pain (50%), hemoptysis (50%), parietal mass (40%), fever (30%) and altered general condition (100%). Chest imaging showed a peripheral opacity (15 cases) and a rib lysis (7 cases). The triad: spinal lesions, elevated ESR and positive Bence Jones proteinuria was found in 80% of cases. The histological diagnosis of multiple myeloma was posed by myelogram (5 cases), the bone marrow biopsy (3 cases), biopsy of the parietal mass (5 cases). All patients have already a bad prognosis. Sixteen patients had received chemotherapy. Radiotherapy has been indicated to three patients with persistent bone pain and two patients had died before starting treatment. The evolution is marked by the aggravation. Chest locations myeloma are rare and their management should be multidisciplinary.

A 43 year old black male patient presented with progressive respiratory symptoms, fever and malaise of short duration accompanied by mild epistaxis. Physical examination revealed generalised lymphadenopathy and hepatosplenomegaly. Peripheral blood examination showed a striking plasmacytosis. Further investigation revealed Bence Jones proteinuria consisting of both kappa and lambda light chains. There was no monoclonal peak on serum electrophoresis and cytoplasmic immunoglobulin and gene rearrangement studies on the peripheral blood plasma cells demonstrated polyclonality. The possible role of Epstein-Barr virus in stimulating B cell proliferation in this case is discussed.

We describe a patient with polycythaemia vera, who in the course of investigations for polycythaemia was also found to have multiple myeloma. A 75 year old Caucasian male was refered for investigations of a raised haemoglobin from a dermatology clinic. He was attending dermatology clinic for intractable, generalised pruritus for 6 months. Initial investigations confirmed the diagnosis of primary proliferative polycythaemia. Further examination of the bone marrow and trephine bone biopsy revealed an increase in plasma cells with morphological atypia. Serum protein electrophoresis confirmed a monoclonal band and urinary examination revealed excretion of Bence Jones proteins. Immunoperoxidase stains of the trephine biopsy confirmed monoclonal light chain restriction. Coexistence of polycythaemia vera and multiple myeloma is an extremely rare situation.

Multiple myeloma is a disorder of plasma cells which can involve kidneys in the form of cast nephropathy. Neoplastic plasma cells produce either complete immunoglobulins or fragments of immunoglobulins leading to a monoclonal spike in the serum and/or Bence Jones proteinuria. Very few patients present as non-secretory myeloma when no immunoglobulins (M spike) are produced or only light chains are secreted which can only be detected in urine. Acute renal failure due to cast nephropathy can rarely be the first presentation of multiple myeloma. We here in report a case in which primary diagnosis of multiple myeloma was made on renal biopsy due to its characteristic histomorphology. The diagnosis was later on supported by presence of neoplastic plasma cells in the aspirate and biopsy of bone marrow.

A nine-year-old spayed female labrador retriever presented with marked paraparesis. Radiographic imaging revealed regions of osteolysis within the spinous process of the L1 vertebra and the lamina and pedicles of the T13 vertebra. Cytological examination of the bone marrow exhibited a marked increase in plasma cells; histopathology of a core needle biopsy from the L1 spinous process revealed normal bone marrow findings with only scattered plasma cells. The serum biochemical profile demonstrated multiple abnormalities, some of which are frequently observed in cases of multiple myeloma such as hypercalcaemia and hyperglobulinemia. Initial serum protein electrophoresis (SPE) exhibited a tall, narrow peak of the β-1 region superimposed onto a broad total β globulin base. The SPE also demonstrated a second α-2 spike and low γ fraction. Although a urinalysis revealed a significant proteinuria, the patient lacked a Bence Jones proteinuria. The combined diagnostic workup was consistent with multiple myeloma.

The effectiveness of bortezomib treatment for multiple myeloma (MM) is well established. However, the protocol by which maintenance therapy using bortezomib should be continued for myeloma patients requiring regular hemodialysis remains to be established. We herein report a case of MM with severe renal insufficiency requiring hemodialysis for nearly 30 months which was finally withdrawn from renal replacement therapy during monthly maintenance treatment with bortezomib and dexamethasone for two years. The details of this case are essential for establishing clinical guidelines for applying intermittent low-frequency bortezomib therapy in dialysis-dependent myeloma patients.

Solitary plasmacytoma of the skull is rare and few cases have been reported in the English literature. Plasmacytoma of the skull has a wide spectrum of pathology, including a quite benign, solitary plasmacytoma (SPC), and an extremely malignant, multiple myeloma (MM) at the two ends of the spectrum. The prognosis for solitary plasmacytoma of the skull appears to be good when it can be diagnosed on strict criteria. The clinical features of solitary plasmacytoma of the skull are complex and not easily identified, resulting in a high misdiagnosis rate. A comprehensive examination and analysis which includes radiological examination, immunoglobulin, biochemistry, test for Bence Jones protein in the urine and bone marrow is needed for correct diagnosis. If the skull lesion is isolated, with accompanying marked swelling in the area and tenderness, plasmacytoma must be considered as a possibility for the cause of solitary skull masses. Two cases of solitary plasmacytoma of the skull lesions were retrospectively reviewed, in which a comprehensive examination was used in order to predict the clinical course of solitary plasmacytoma of the skull. The patients received postoperative radiation and/or chemotherapy. Survival following surgery was longer than 2 years for patient 1, and patient 2 is alive at the 18-month follow-up.

Serum concentrations of κ- and λ-free light chains and their ratios were compared in 126 patients with monoclonal gammapathies (age 23-80 years) and 60 normal subjects (25-82 years). The main group included patients with intact immunoglobulin multiple myeloma, Bence Jones multiple myeloma, nonsecreting multiple myeloma, plasmocytoma, and monoclonal gammapathy of unknown origin. The accuracy of the method was evaluated by the analysis of 3 serum specimens with different concentrations of κ- and λ-free light chains. The variability of the method did not surpass the coefficient of variations permissible for this kind of analysis (10%). The new immunochemical method is characterized by high analytical sensitivity 100-fold surpassing that of electrophoretic methods. High concentrations of free light chains were most often found in the sera of patients with multiple myeloma with intact immunoglobulin secretion, Bence Jones multiple myeloma, and plasmocytoma. The diagnostic sensitivity of measurements of serum free light chains by the immunoturbidimetric method attained 90.5%. Combination of this method with serum protein electrophoresis and immunofixation resulted in detection of monoclonal gammapathy in 98.8% cases. These data indicate high specificity and analytical and diagnostic sensitivity of the immunoturbidimetric method for measurement of serum free light chains.

In order to analyze the cai]ses of delayed diagnosis and raise the level of early diagnosis of atypical multiple myeloma (MM), the differences of presenting features between the patients presented to nephrologists and those presented to hematologists were compared. MM patients in our hospital were studied retrospectively. Those who referred renal impairment were divided into two groups: group I presented to nephrologists prior to MM diagnosis (n=29) and group II presented to hematologists directly (n=62). The age, sex, initial symptoms, haematological and biochemical parameters, the phenotype of paraprotein, bone marrow biopsy and cytology were undertaken and analyzed. The results showed that the median time between the initial symptoms and diagnosis in the patients of group I was longer than that in group II (P

Non-excretory myeloma is a rare variety of multiple myeloma in which classical techniques of research of the stigmata of chronic secretion fail to highlight the monoclonal peak or proteinuria of Bence Jones. Lytic bone lesions are rare in this type of myeloma. We report the case of a patient in whom we confirmed multiple myeloma by bone marrow aspiration and we have classified stage III of Durie and Salmon in view of hypercalcemia, anemia, and lytic lesions observed. However, we could not isolate a secretion of monoclonal immunoglobulin in blood but urinary secretion was evident by proteinuria and urinary light chains. The radiographs of our patient were highly suggestive of osteolysis seen diffuse the practice of sternal puncture has emerged even in the absence of criteria such as blood secretion highlighting the monoclonal peak in serum protein electrophoresis or the quantitation of immunoglobulins. Our case original seen that the diffuse osteolytic lesions were often observed within the secretory disease and rarely in the form of non-secreting.

Solitary plasmacytoma (SPC) of the skull (SPS) is rare, and only a few cases have been reported in the literature so far. Plasmacytoma of the skull has a wide spectrum of pathology, including a quite benign, SPC, and an extremely malignant, multiple myeloma at the two ends of the spectrum. SPC of bone including SPS is characterized by a radiologically solitary bone lesion, neoplastic plasma cells in the biopsy specimen, fewer than 5% plasma cells in bone marrow

Isolated constant domains of two Bence Jones proteins, VAD and BIR, are able to form amyloid fibrils, but only the first one retains this feature within the intact protein. The conformation and stability of these proteins were studied using scanning microcalorimetry, circular dichroism, fluorescence spectroscopy, and analytical centrifugation at physiological conditions (10 mM phosphate buffer, pH 7.0, 100 mM NaCl), and it was shown that isolated pairs of constant domains (CL-CL) of VAD and BIR had reduced stability in comparison to ordinary (nonamyloidogenic) Bence Jones proteins. However, in the intact BIR protein, the stability of the constant domain block increased dramatically, in agreement with the loss of ability to form amyloid fibrils.