Osteosclerotic myeloma with polyneuropathy and hypocalcemia

A case is presented of a 46-year-old man with multifocal osteosclerotic bone lesions, peripheral polyneuropathy and hypocalcemia. Histologic examination of a bone marrow biopsy disclosed a multiple myeloma. Immunoelectrophoresis revealed a small M-component identified as IgG-lambda. Osteosclerotic myeloma lacking any osteolytic lesions seems to be very rare and shows several different features as compared with classical myeloma. A review of the current literature suggests that multiple myeloma is not a uniform disease but rather a group of clinical syndromes characterized by the special properties of their proliferating plasma cell clones.     

Clues potentially distinguishing lytic lesions of multiple myeloma from those of metastatic carcinoma

This study was conducted to determine whether individual bony lesions are specific for recognizing multiple myeloma and thereby distinguish it from metastatic cancer and leukemia. The lytic skeletal lesions of multiple myeloma are characterized by sharply defined, spheroid lesions. They have smooth borders and effaced/erased trabeculae. Unique spheroid myeloma lesions appear to be responsible for the “punched out” appearance of affected bone. The total absence of remodeling in myeloma forms a contrast to irregular preservation of trabeculae and buttressing, isolated “fronts of” cortical bone “resorption” coalescing to confluence, and the “golf-ball surface” phenomenon observed in metastatic cancer. The uniform effacement of both cortical and trabecular bone in multiple myeloma also contrasts with some cortical preservation in metastatic cancer. Leukemic lesions are more numerous than those of myeloma, but they lack the latter's “space-occupied” appearance. The relatively small holes and “fronts of resorption” of leukemia are quite different from the “space-occupied” lesions of multiple myeloma. Uniform size is a characteristic traditionally attributed to the bone lesions of multiple myeloma. The occurrence of isolated examples of uniform size lesions in metastatic cancer and of variable size lesions in some individuals with multiple myeloma precludes unequivocal use of size in differential diagnosis. Fortunately, the newly recognized macroscopic characteristics appear to separate multiple myeloma from metastatic cancer, and also distinguish myeloma from leukemia. Am J Phys Anthropol 105:241–250, 1998. © 1998 Wiley-Liss, Inc.     

An unusual clinical and pathological variant of malignant catarrhal fever in a white-tailed deer

A captive male white-tailed deer (Odocoileus virginianus) developed an acute illness over a 3-day period characterized predominantly by neurological, ocular and respiratory signs which were accompanied by prominent gross lesions of multiple organ systems. Histologically, a proliferative vasculitis consisting primarily of lymphocytic-lymphoblastic cellular infiltration was found in ocular, oral, respiratory, cardiac and neural tissues. The extensive nature of these infiltrations resulted in grossly apparent nodular foci in the lung, lymphoid tissue and myocardium which were suggestive of a lymphoproliferative disorder. This is contrasted to the more necrotizing nature of the vasculitis observed in other reported cases of malignant catarrhal fever in white-tailed deer. Although virus isolation was not attempted, serologic findings of antibodies to malignant catarrhal fever virus detected by indirect immunofluorescence and virus neutralization supported a diagnosis of malignant catarrhal fever in this deer.     

Whole body MR in patients with multiple myeloma

BackgroundMultiple myeloma is a cancer of plasma cells which leads to bone marrow infiltration.AimWhole-body MR is the most sensitive imaging method available to detect multiple myeloma lesions.Material and MethodsMR scans were performed in 100 patients with multiple myeloma who were receiving treatment in the Haematology Clinic in Poznań in the years 2005–2006. Whole-body MR scans were performed with general coil 1.0 T in STIR sequences and T1 sequences, in coronal and sagittal planes with scanning area covering the head, neck, trunk and the limbs (FOV for specific regions was 36–48 cm). The bone lesions were classified as focal (monofocal/multifocal lesions), in-filtrative, mixed and “salt and pepper” type. Depending on the size of the lesions the patients were included in one of three groups according to Salmon-Durie Plus classification.ResultsFour main types of multiple myeloma were distinguished based on MR scans: focal (48 patients; monofocal in 10 patients), infiltrative (17 patients), mixed type (19 patients) and “salt and pepper” type (4 patients). The remaining 12 patients had no multiple myeloma lesions in the bone marrow. Additionally, in 18% of patients a soft tissue mass could be observed. According to Salmon-Durie Plus categorisation 27 subjects were classified as having stage I, 16 patients stage and 57 patients stage III disease. In 12% of patients MR data changed the disease staging.ConclusionsWB MR is a sensitive and effective diagnostic method with an important impact on staging and further treatment of multiple myeloma.     

Capripoxvirus disease in an Arabian oryx (Oryx leucoryx) from Saudi Arabia.

Lumpy skin disease caused by a capripoxvirus was observed in a captive-bred female Arabian oryx (Oryx leucoryx) at the National Wildlife Research Center, Taif, Saudi Arabia. Clinical signs included severe general depression with fever, anorexia, greater than 1,000 nodular cutaneous lesions and gradual recovery over 2 mo. The virus was found by electron microscopy and paired sera showed an increasing virus neutralization antibody titer against capripoxvirus. A serologic survey of the herd of 90 oryx showed a low prevalence (2%) of this infection. This report describes the first case of lumpy skin disease in an Arabian oryx.     

Tartrate-resistant acid phosphatase (TRAP) activity in serum: potential use in assessing bone resorption in patients with multiple myeloma

We measured serum tartrate-resistant acid phosphatase (TRAP) activity in 120 healthy subjects and 35 patients with multiple myeloma as well as urinary hydroxyproline excretion in the myeloma patients. Young subjects (0-18 years) showed higher TRAP levels (ANOVA p less than 0.01) compared with the other age classes due to the more active bone remodelling processes associated with growth. Myeloma patients with bone lytic lesions (MM+) showed higher serum TRAP values than controls (p less than 0.01). Hydroxyproline excretion was higher in MM+ patients but the difference between patients with and without bone lesions was not statistically significant. Our data suggest that serum TRAP activity may be a suitable, simple biochemical test to assess bone turnover in patients with multiple myeloma but that its clinical usefulness as a marker of bone resorption needs further evaluation.     

Role of osteoblast suppression in multiple myeloma

Multiple myeloma is the most common form of plasma cell dyscrasia and virtually all cases of myeloma exhibit osteolytic lesions, which result in bone pain, pathological fractures, spinal cord compression, and hypercalcaemia. Malignant plasma cells disrupt the delicate balance between bone formation and bone resorption, which ultimately leads to the debilitating osteolytic lesions. This review focuses principally on mechanisms of osteoblast inhibition by malignant plasma cells with emphasis placed on our experimental findings, which support a model for abnormal Wnt signaling in osteoblast suppression. We describe how excessive amounts of soluble Wnt inhibitors secreted by malignant plasma cells in multiple myeloma could promote osteolytic lesions, tumor growth, suppress hematopoiesis, prevent proper engraftment, and expansion of transplanted stem cells. Finally, we detail current therapies shown to disrupt the interaction between the myeloma cell and the microenvironment, leading to activation of osteoblasts.     

Pulmonary langerhans cell histiocytosis (histiocytosis X) on bronchoalveolar lavage: a report of 2 cases

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is an interstitial lung disease characterized by bilateral nodular and cystic lesions. Clinically it seems to be a reactive process related to cigarette smoking. CASES: In 2 cases of PLCH, cytologic and immunocytochemical evaluation of bronchoalveolar lavage (BAL) fluid was successfully used for the diagnosis of PLCH. Two heavy smokers complained of fever, cough and debilitation. Serologic and hematologic values were normal. In both cases radiography and computed tomography (CT) were similar, showing multiple bilateral nodular or cystic lesions in the middle and upper lung zones. Cytospins obtained from BAL were Papanicolaou and May-Grünwald-Giemsa stained; others were immunostained with cytokeratin cocktail, CD1a and S-100. Cytospins showed a monomorphous and dispersed cell population consisting ofmononucleated or binucleated and occasionally multinucleated histiocytes. Single cells showed wide, well-defined, acidophilic cytoplasm and oval or kidney-shaped, vesicular nuclei with irregular shapes, evident nucleoli and frequent grooves and indentations. Immunocytochemical staining showed diffuse cytoplasmic positivity for S-100 and CD1a and negativity for cytokeratin; only the few cylindrical cells present in the cytospins were positive for cytokeratin. In both cases the cytologic diagnosis of PLCH was confirmed by subsequent CT and clinical follow-up. CONCLUSION: Cytologic and immunocytochemical evaluation of BAL fluid permits a definitive diagnosis of PLCH. This cytologic diagnosis is clinically relevant because it permits surgical biopsy to be bypassed and allows waiting for a possible spontaneous or pharmacologic resolution.     

Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics

Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.     

Clinical manifestations of multiple myeloma: relation to class and type M component.

From analysis of serum samples and clinical data from 632 patients with multiple myeloma it was determined that IgG was the commonest class of myeloma and that this type seemed to be the most benign. IgD myeloma and lambda light-chain disease were the most aggressive types; patients with these types were usually younger at diagnosis and more commonly had azotemia, osteolytic lesions and Bence Jones proteinemia. The sexes were equally represented in all but IgD myeloma, in which males predominated. Prognosis was more favourable when the M component had kappa light chains.     

Correlation of residual leukocyte subsets with neutropenic fever during severe leukopenia after high-dose chemotherapy and autologous stem cell transplantation

BACKGROUND: High-dose chemotherapy with autologous stem cell transplantation is the standard treatment of eligible patients with multiple myeloma. However, this treatment is associated with a substantial risk of infectious complications during leukopenia. The aim of our pilot study was to determine the residual leukocyte subsets during severe cytopenia after high-dose melphalan and to correlate this with the occurrence of neutropenic fever. METHODS: Residual leukocyte subsets in the peripheral blood on days 4-7 following autologous stem cell transplantation were analyzed by three-color flow cytometry in 20 patients with multiple myeloma. In addition, we determined the number of T cells that were transfused with the autografts. RESULTS: Absolute numbers of lymphocytes (mean 25/microL) and monocytes (mean 4/microL) were strongly reduced but rather constant during the period of severe neutropenia. Neutrophil engraftment and duration of neutropenia were very similar in patients with and without neutropenic fever. Low absolute lymphocyte counts and absolute CD4+ T-cell counts on days 4-7 after stem cell transplantation correlated with neutropenic fever. Furthermore, T-cell numbers in the autologous stem cell grafts that the patients received were significantly lower in patients with neutropenic fever. DISCUSSION: These observations suggest that the number of T cells, and in particular CD4+ T cells, in the blood during severe cytopenia is playing a role in defense of infection. T-cell numbers in the graft could provide a predictive factor for the risk of infection in the post-transplant period. However, this needs to be confirmed in a larger study.     

Establishment of a new model of human multiple myeloma using NOD/SCID/gammac(null) (NOG) mice

We developed a new experimental animal model of human multiple myeloma using immunodeficient NOD/SCID/gammac(null) (NOG) mice. A human myeloma cell line, U266, was intravenously inoculated into 20 NOG mice, all of which developed hind leg paralysis and distress around 6 weeks after transplantation. Pathological studies showed that only the bone marrow was infiltrated with U266 cells, and no cells were present in other organs. Osteolytic lesions in cortical bones and loss of trabecular bones were prominent in U266-transplanted NOG mice. In contrast, U266 cells were not detected in CB17scid or NOD/SCID mice 6 weeks after intravenous inoculation. Human IgE, produced by U266 cells, was detected in the serum of U266-transplanted NOG mice by ELISA. The results indicated that this hu-myeloma NOG model might be useful for studying the pathogenesis of myeloma and related osteolytic lesions, and are suggestive of its applicability to the future development of new drugs.     

Plasmacytoid transitional cell carcinoma. Report of a case with initial presentation mimicking multiple myeloma.

The case of a 63-year-old man with a previously undescribed morphologic variant of transitional cell carcinoma of the urinary bladder is reported. The patient initially presented with multiple lytic bony metastases of the ribs and skull. Aspiration biopsy of one of the lytic lesions of the skull showed tumor cells with a striking plasmacytoid appearance, similar to the plasma cells seen in myeloma, leading to an initial observer's diagnosis of multiple myeloma. Subsequently, a bladder tumor with the same cytomorphology was found; immunohistochemical and ultra structural studies performed on the aspirated material and on the bladder biopsy specimen clearly established the epithelial nature of this neoplasm.     

Oral desmoplastic melanoma mimicking inflammatory hyperplasia

doi: 10.1111/j.1741‐2358.2011.00482.x Oral desmoplastic melanoma mimicking inflammatory hyperplasia Introduction: Desmoplastic melanoma (DM) arising in the oral cavity is a rare neoplasm that may be confused with a variety of non‐melanocytic benign or malignant lesions. Objectives: To present a case of DM in the oral mucosa mimicking fibrous inflammatory hyperplasia, discusses the difficulties involved in the diagnosis and offers a literature review on the clinicopathologic and immunohistochemincal aspects of this neoplasm. Case report: A 62‐year‐old white male, smoker, was referred with a chief complaint of pain and swelling in the palate. The oral examination revealed multiple brown‐to‐black patches and a non‐pigmented sessile nodule located on the mucosa of the hard palate. The clinical diagnosis of the pigmented lesions was either oral melanosis or melanoma. The nodular lesion was clinically diagnosed as fibrous inflammatory hyperplasia. Incisional biopsy was performed on the pigmented lesion and the microscopic sections revealed a melanotic macule. The nodular lesions histologically revealed an amelanotic desmoplastic melanoma. Conclusions: Reactive lesions close to a pigmented area should be investigated with great care.     

Multiple myeloma superimposed on chronic myelocytic leukemia

A 65-year-old woman with chronic myelocytic leukemia and multiple myeloma is described. Cases of acute leukemia complicating multiple myeloma have been reported in recent years, but to our knowledge this is the first case where multiple myeloma developed in a patient who had pre-existing chronic myelocytic leukemia.     

Glucocorticoids in cancer therapy

Glucocorticoids are often included with other agents in cancer treatment although the mode of action is not clear. They are useful in the primary combination chemotherapy of both acute and chronic lymphocytic leukaemias, Hodgkins' and non-Hodgkin's lymphomas, multiple myeloma and breast cancer. Other uses for glucocorticoids in cancer patients include an anti-inflammatory action for the oedema of cranial and spinal metastases, a weak antihypercalcaemic effect and the ability to suppress tumour-related fever.     

血源性兔VX2肿瘤脑及脑膜转移瘤动物模型的建立及MRI检测

目的：研究MRI对血源性脑及脑膜转移瘤动物模型转移灶的检出效果。方法：18只新西兰大白兔随机分为3组,分别从左颈总动脉内接种VX2瘤细胞,A组：20％甘露醇注入5min后接种VX2瘤细胞：B组：20％甘露醇注入5min后,加入肝素再接种VX2瘤细胞;C组,对照组,单纯注入等量生理盐水。术后2周后行MRI检查。病理取材HE染色光镜下观察。结果：平扫：A组,1只（1／6）发现脑内结节并脑膜结节样增厚,T1WI为等信号,T2WI为稍高信号。B组,2只（2／6）为脑内多发结节,T1WI为等信号,TM为稍高信号。2只（2／6）脑膜结节样增厚。增强扫描：A组,2只（2／6）脑内见强化结节灶;直径在1．5mm-7．0mm之间。4K（4／6）脑膜线样增厚或结节样增厚强化。B组,6只（6／6）脑内见直径在1．5mm-5．0mm的高信号结节,其中5只为脑内多发结节灶;4只（4／6）脑膜线样或结节样增厚强化,左侧为主,其中2只（2／6）为双侧脑膜增厚。增强扫描A、B组问脑内病灶差异有统计学意义（Fisher’s确切概率值为0．04）。C组平扫及增强扫描均未见异常信号。结论：上述方法制成的动物模型可为医学影像学研究提供可靠的动物模型,加入肝素可提高瘤灶的形成几率,并证实血脑屏障对脑转移瘤的形成起重要作用。MRI增强检查是检出脑内及脑膜转移瘤的首选方法。     

Time Trend of Multiple Myeloma and Associated Secondary Primary Malignancies in Asian Patients: A Taiwan Population–Based Study

Studies involving second malignancies in patients with multiple myeloma are limited for the Asian population. Using data from population-based insurance claims, we assessed the risk of developing secondary malignancies after multiple myeloma, in particular hematologic malignancies. A retrospective cohort study was conducted in 3970 patients with newly diagnosed multiple myeloma from the registry of catastrophic illnesses between 1997 and 2009. A total of 15880 subjects without multiple myeloma were randomly selected as comparisons from the insured population, frequency-matched based on gender, age, and the date of diagnosis. The incidence of secondary malignancies was ascertained through cross-referencing with the National Cancer Registry System. The Cox proportional hazards model was used for analyses. The incidence of multiple myeloma in the insured population increased annually. The overall incidence of secondary malignancy was lower in the multiple myeloma cohort than in the comparison cohort (93.6 vs. 104.5 per 10,000 person-years, IRR = 0.90, 95% CI = 0.78–1.04). The incidence of hematologic malignancies was 11-fold greater for multiple myeloma patients (47.2 vs. 4.09 per 10,000 person-years) with an adjusted HR of 13.0 (95% CI = 7.79–21.6) compared with the comparison cohort. The relative risk of secondary malignancy was also strong for myeloid leukemia (21.2 vs. 1.36 per 10,000 person-years). Gender- and age-specific analysis for secondary hematologic malignancies showed that males and patients with multiple myeloma <60 years of age had a higher risk of secondary malignancy than females and patients with multiple myeloma >60 years of age. In conclusion, patients with multiple myeloma, especially younger patients, are at a high risk of hematologic malignancies.     

Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-Squares Estimation (IDEAL) Magnetic Resonance Imaging as a Biomarker for Symptomatic Multiple Myeloma

IntroductionTo evaluate the effectiveness of iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) magnetic resonance imaging (MRI) to discriminate between symptomatic and asymptomatic myeloma in lumbar bone marrow without visible focal lesions.ResultsUnivariate analysis showed that β2-microglobulin and bone marrow plasma cell percent (BMPC%) were significantly higher and fat-signal fraction was significantly lower with symptomatic myeloma than with asymptomatic myeloma. Areas under the curve were 0.847 for β₂;-microglobulin, 0.834 for fat-signal fraction, and 0.759 for BMPC%.ConclusionThe fat-signal fraction as a biomarker for multiple myeloma enables discrimination of symptomatic myeloma from asymptomatic myeloma. The fat-signal fraction offers superior sensitivity and specificity to BMPC% of biopsy specimens.     

Cutaneous relapse in Hodgkin's disease: a case report

BACKGROUND: Skin involvement in Hodgkin's disease is rare, can be seen in advanced stages of the disease and indicates a poor prognosis. CASE: A young male presented with multiple nodular lesions on the chest wall and matted cervical lymph nodes. Aspiration smears from skin lesions showed atypical mononuclear cells with a prominent nucleolus, many lymphocytes and plasma cells. Smears from the lymph nodes showed classical Reed-Sternberg cells in a polymorphous background. The cytologic diagnosis of Hodgkin's lymphoma was entertained and later confirmed on skin biopsy. Past history revealed that the patient had been diagnosed with Hodgkin's disease and treated for it 2 years earlier, but had been lost to follow-up during treatment. CONCLUSION: Cutaneous Hodgkin's disease should always be considered in smears from skin lesions showing atypical mononuclear cells in a polymorphous background, even in the absence of a definitive clinical diagnosis at the time of presentation.