Detection of serum M-protein in acetonitrile precipitates by MALDI-TOF mass spectrometry: A novel, low-cost methodology.

BACKGROUND: Several studies have demonstrated the analytical sensitivity of MALDI-TOF mass spectrometry (MALDI-TOF MS) by immunoenrichment for M-protein analysis. We report the results of a novel, low-cost, reagent-based extraction process using acetonitrile (ACN) precipitation to enrich for κ and λ light chains which can be analysed by MALDI-TOF MS. METHODS: Institutional Ethics committee approval was obtained. Serum samples from patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), plasmacytoma, AL amyloidosis and Waldenström macroglobulinemia (WM) underwent ACN precipitation. The images obtained were overlaid on apparently healthy donor serum samples to confirm the presence of M-protein. A sample was considered positive for M-protein if there was a sharp or broad peak within the κ or λ mass/charge (m/z) range: m/z- [M + 2H]2+: 11,550-12,300 Da and λ m/z- [M + 2H]2+: 11,100-11,500 Da. Images were acquired at a m/z range of 10,000-29,000 Da. Corresponding serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (IFE) and serum free light chain (sFLC) assay by nephelometry were performed for all the samples. RESULTS: Two-hundred-and-two serum samples were included in the study: MM- 184 (91%); AL amyloidosis- 2 (1%); plasmacytoma- 8 (4%); MGUS- 6 (3%) and WM- 2 (1%). All the SPEP positive samples were identified by MALDI-TOF MS. Out of 179 samples positive for M-protein by IFE, MALDI-TOF MS was positive in 176 samples (98%). Compared to IFE, the sensitivity and specificity of M-protein identification by MALDI-TOF MS were 98.3% and 52.2%, respectively. CONCLUSIONS: This study demonstrates the feasibility of qualitatively identifying M-protein without the need for antibody-based immunoenrichment, making the technique cost-effective.

Expert review on soft-tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations.

In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.

[Prevalence investigation of solitary plasmacytoma in China: A calculation based on national urban medical insurance in 2016].

Objective: The aim of this study is to analyze the distribution features of patients with solitary plasmacytoma and calculate the prevalence of solitary plasmacytoma in China in the year 2016. Methods: This study was based on China's urban employees' basic medical insurance and the urban residences' basic medical insurance from 21 provinces from January 1, 2016 to December 31, 2016. Patients with solitary plasmacytoma were identified by disease names and codes. Subgroup analyses were carried out by sex, region, and age. Furthermore, sensitivity analyses were performed to test the robustness of the results. Age-adjusted prevalence was calculated based on the 2010 Chinese census data, the 2013 Revised European Standard Population, the 2010 US population, and the 2011 Australian population. Results: In 2016, the prevalence of solitary plasmacytoma in China was 1.18 per 100 000 population (95%CI, 1.06-1.31) , with 1.26 per 100 000 population (95% CI, 1.10-1.43) and 1.10 per 100 000 population (95% CI, 0.93-1.29) for males and females, respectively. The age-adjusted prevalence based on the 2010 Chinese census data was 0.85 per 100 000 population (95% CI, 0.82-0.88) . Conclusion: This study estimated the prevalence of solitary plasmacytoma in China on the basis of the national urban medical insurance, which can provide clues for the enactment of solitary plasmacytoma-related medical policies and basic studies about solitary plasmacytoma.

Overall Survival Trends and Clinical Characteristics of Plasmacytoma in the United States: A National Cancer Database Analysis.

BACKGROUND: Given the rarity of plasmacytoma, large-scale database analysis can provide useful information regarding the clinical presentation and patient-related factors impacting overall survival (OS). MATERIALS AND METHODS: The National Cancer Data Base was queried for patients with plasmacytoma between 2004 and 2013, excluding patients with systemic disease. Plasmacytomas were classified as originating in bone (P-bone), in extramedullary tissue (P-EM), or unspecified. Survival was estimated using the Kaplan-Meier and log-rank test method. We used Cox regression to determine specific outcomes adjusting for demographic, socioeconomic, geographic, facility type, year of diagnosis, and comorbid factors. RESULTS: In total, 6225 patients were identified, of which 61.5% were men. The median age at diagnosis was 64 years (range, 18-90 years), and the median follow-up was 58 months. The primary site of disease was P-bone in 4056 (65.1%) patients and P-EM in 1468 (23.6%), and the remaining 701 patients were P-unspecified. The unadjusted median survival for solitary P-bone was 89 months (95% confidence interval, 82.9-95.0 months), and for solitary P-EM was 117.3 months (95% confidence interval, 108.8 months to not reached). Factors associated with improved OS include younger age, private insurance, higher income, solitary lesion, and lower comorbidity score. Patients with P-bone disease treated at academic facilities had improved OS. Only 65% of patients with solitary plasmacytoma lesions received radiation treatment. Age greater than 75 years and increased distance to treatment facility was associated with a decreased likelihood of receiving radiation. CONCLUSIONS: This is the largest study examining outcomes of patients with plasmacytoma using a large database analysis, revealing unique aspects of P-EM versus P-bone and underutilization of radiation treatment.

Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel.

Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on high-dose radiation, but studies exploring the potential benefit of systemic therapies for high-risk patients are urgently needed. In this review, a panel of expert European hematologists updates the recommendations on the diagnosis and management of patients with solitary plasmacytoma.

18F-FDG PET/CT for Early Postradiotherapy Assessment in Solitary Bone Plasmacytomas.

PURPOSE: The purpose of this study was to evaluate the performance and possible prognostic value of early (18)F-FDG PET/CT (FDG PET/CT) assessment after radiotherapy (RT) in patients with solitary bone plasmacytoma (SBP). METHODS: Twenty-one patients affected by SBP who underwent FDG PET/CT scan for early restaging (≤6 months) postradiotherapy assessment were selected from the PET databases of University College London Hospital of London and San Raffaele Hospital of Milan. Patients with no abnormal uptake were classified as having no pathologic uptake (NPU). A SUV(max) cutoff value of 4 was chosen to discriminate minimal residual uptake (MRU; SUV(max) ≤ 4) from pathologic uptake (PU, SUV(max) >4). Progression-free survival (PFS) rate was estimated using Kaplan-Meier curves and Cox regression analysis. RESULTS: In 10 of 21 patients restaged by FDG PET/CT, further previous baseline scan was available also at staging, and results showed positive findings at the level of all biopsy-proven disease areas.Considering MRU as PU, FDG PET/CT showed a sensitivity and specificity of 86% and 29%, respectively. Using SUV(max) >4 as the cutoff, sensitivity and specificity were 86% and 93%, respectively. Kaplan-Meier curves revealed a significant difference in PFS probability between patients classified as positive on FDG PET/CT using a cutoff of SUV(max) >4 (PU) and those classified as negative (NPU + MRU) (log-rank, Mantel-Cox, P = 0.009; χ(2) = 6.85). Cox regression analysis of PFS using SUV(max) >4 as cutoff revealed an interesting relation in prediction of progression (HR, 9.458). CONCLUSION: (18)F-FDG PET/CT for early restaging after RT in patients with SBP should be considered carefully in view of the lack of specificity of a low SUV(max) value. The good correlation between a high SUV(max) value and follow-up suggests a possible prognostic role for FDG PET/CT in disease progression at early restaging after RT.

PET y PET/TC en el manejo de desórdenes de células plasmáticas (mieloma múltiple, plasmocitoma solitario y gamapatía monoclonal de significado incierto) / PET and PET-CT for the management of plasma cell disorders (multiple myeloma, solitary plasmocytoma and monoclonal gammopathy of undetermined significance) / PET e PET/TC no manejo de desordens de células plasmáticas (mieloma múltiplo, plasmocitoma solitário e gamapatia monoclonal de significado incerto)

INTRODUCCIÓN: El mieloma múltiple (MM) es un tumor maligno hematológico caracterizado por la proliferación clonal de células plasmáticas. La sobrevida global a 5 años es del 44% según estadísticas oficiales estadounidenses recientes. La Tomografía por Emisión de Positrones (PET) y la misma con Tomografía Computada asociada (PET/TC) se postulan dentro del esquema de diagnóstico en aquellos pacientes con sospecha clínica de MM puesto que al detectar más tempranamente las lesiones óseas líticas podría adelantar el diagnóstico y tratamiento, o bien para identificar lesiones óseas en otras discracias de células plasmáticas. Se lo propone también para la estadificación y pronóstico en pacientes con diagnóstico establecido de MM. TECNOLOGÍA: La PET y PET/TC son técnicas de imagen funcional y anatómica que utilizan radiofármacos marcados que se inyectan al paciente, como el 18-FDG (fluorina-18 fluorodesoxiglucosa) para lograr detectar áreas de hipercaptación metabólica. La tomografía computada (TC) combinada permite una alta resolución espacial, con ventajas en la sensibilidad y precisión anatómica en comparación con la PET solo. OBJETIVO: Evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura para el uso de la PET y PET/TC en el manejo de desórdenes de células plasmáticas (mieloma múltiple, plasmocitoma solitario y gamapatía monoclonal de significado incierto). MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas (MEDLINE, Cochrane, CRD, DARE, NHS EED), en buscadores genéricos de Internet, agencias de evaluación de tecnologías sanitarias y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas, meta-análisis, estudios clínicos aleatorizados y controlados, guías de práctica clínica, evaluaciones de tecnologías sanitarias, evaluaciones económicas y políticas de cobertura de otros sistemas de salud. RESULTADOS: Se utilizaron para este trabajo cuatro revisiones sistemáticas (RS), nueve estudios observacionales comparativos, dos políticas de cobertura, y seis recomendaciones o guías de práctica clínica. CONCLUSIONES: Existe evidencia de moderada calidad metodológica que señala que la 18-FDG-PET y PET/TC podrían desempeñar un papel complementario al de otros métodos como RNM y TAC en el proceso diagnóstico. Adicionalmente, por su capacidad de distinguir lesiones metabólicamente activas podría ser de ayuda en monitorear la respuesta luego del tratamiento, incluyendo pacientes trasplantados. Las políticas de cobertura identificadas coinciden en brindar cobertura en las indicaciones mencionadas. En relación a los demás desórdenes de células plasmáticas (plasmocitoma y MGUS) no se identificaron recomendaciones claras.

INTRODUCTION; Multiple myeloma (MM) is a hematological malignant tumor characterized by clonal proliferation of plasma cells. Overall survival at 5 years is 44% based on recent official US statistics. PET-CT is considered as part of the diagnostic scheme for those patients with clinically suspected MM because, as lytic bone lesions are detected earlier, it could advance its diagnosis and treatment, or it could be used to identify bone lesions in other plasma cell dyscrasias. It is also proposed for staging and prognosis in patients with known MM diagnosis. TECHNOLOGY: PET and PET-CT are anatomical and functional imaging techniques that use radiolabeled drugs, injected to the patient, such as 18-FDG (fluorine 18-fluorodeoxyglucose) to detect areas of metabolic uptake. Combined computed tomography (CT) provides a high spatial resolution, with advantages in sensitivity and anatomical precision compared with PET alone. PURPOSE: To assess the available evidence on efficacy, safety and issues related to coverage policies on the use of PET and PET/CT for the management of plasma cell disorders (multiple myeloma, solitary plasmocytoma and monoclonal gammopathy of undetermined significance). METHODS: A bibliographic search was carried out on the main databases (MEDLINE, Cochrane, CRD, DARE, NHS EED), on Internet general search engines, in health technology assessment agencies and health sponsors. Priority was given to including systematic reviews, meta-analysis, randomized controlled clinical trials, clinical practice guidelines, health technology assessments, financial assessments, and coverage policies from other health systems. RESULTS: For this work, four systematic reviews (SRs), nine observational comparative studies, two coverage policies, and six recommendations or clinical practice guidelines were used. CONCLUSIONS: There is evidence of moderate methodological quality stating that 18-FDG-PET and PET-CT may supplement other methods such as MRI and CT scan in the diagnostic process. Furthermore, since it can distinguish active metabolic lesions it could help monitor response after treatment, including transplanted patients. The coverage policies identified agree to cover it for the above-mentioned indications. In relation to the other plasma cell conditions (plasmocytoma and monoclonal gammopathy of undetermined significance), no clear recommendations were found.

INTRODUÇÃO: O mieloma múltiplo (MM) é um tumor maligno hematológico caracterizado pela proliferação clonal de células plasmáticas. A sobrevida global a anos é de 44 segundo estatísticas oficiais estadunidenses recentes. Postula-se o PET/TC dentro do esquema diagnóstico naqueles pacientes com suspeita clínica de MM visto que ao detectar mais precocemente as lesões ósseas líticas poderia adiantar o diagnóstico e tratamento, ou bem para identificar lesões ósseas em outras alterações de células plasmáticas. Propõe-se também para a estadificação e prognostico em pacientes com diagnóstico estabelecido de MM. TECNOLOGIA: A PET e PET/TC são técnicas de imagem funcional e anatômica que utilizam radio-fármacos marcados que que se injetam ao paciente, como o 18-FDG (fluor-18- fluordesoxiglicose) para conseguir detectar áreas de hipercaptação metabólica. A tomografia computadorizada (TC) combinada permite uma alta resolução espacial, com vantagens na sensibilidade e precisão anatômica em comparação com somente a PET. OBJETIVO: Avaliar a evidencia disponível sobre a eficácia, segurança e aspectos relacionados às políticas de cobertura para o uso da PET e PET/TC no manejo de desordens de células plasmáticas (mieloma múltipla, plasmocitoma solitário e gamapatia monoclonal de significado incerto). MÉTODOS: Realizou-se uma busca nas principais bases de dados bibliográficas (como Medline, Cochrane y CRD), em buscadores genéricos de Internet, agências de avaliação de tecnologias em saúde e financiadores de saúde. Priorizou-se a inclusão de revisões sistemáticas, ensaios clínicos controlados aleatorizados (ECAs), avaliações de tecnologias em saúde e econômicas, guias de prática clínica (GPC) e políticas de cobertura de outros sistemas de saúde quando disponíveis. RESULTADOS: Utilizaram-se para este trabalho quatro revisões sistemáticas (RS), nove estudos observacionais comparativos, duas políticas de cobertura e seis recomendações ou guias de prática clínica. CONCLUSÕES: Existe evidencia de moderada qualidade metodológica que aponta que a 18-FGD-PET e PET/TC poderiam desempenhar um papel complementar aos outros métodos como RNM e TAC no processo diagnóstico. Adicionalmente, por sua capacidade de distinguir lesões metabolicamente ativas poderia ser de ajuda para monitorizar a resposta após tratamento, incluindo pacientes transplantados. As políticas de cobertura identificadas coincidem em brindar cobertura para as indicações mencionadas. Em relação as demais desordens de células plasmáticas (plasmocitoma e MGUS) não se identificaram recomendações claras.

Comparison of whole-body diffusion MRI and conventional radiological assessment in the staging of myeloma.

PURPOSE: In multiple myeloma, skeletal radiographs are still regarded as the reference imaging examination because they help to establish the stage of the disease according to the Durie-Salmon Staging System. Whole-body MRI using T1 and STIR sequences increases the detection of myeloma lesions. MRI-measured diffusion has demonstrated high sensitivity in terms of detection in oncology. The main objective of this study is to compare conventional radiographic staging with an MRI whole-body diffusion technique (called DWIBS) in detecting bone lesion monoclonal plasma cell pathologies (multiple myeloma, plasma cell leukaemia, plasmacytoma and MGUS). MATERIALS AND METHODS: Twenty-seven patients were included (multiple myeloma: 24; plasma cell leukaemia, MGUS and plasmacytoma: 1 each). All of them had a whole-body MRI diffusion examination (using a DWIBS sequence). Diffusion MRI and conventional radiographs were compared according to the Durie-Salmon Staging System. In case of doubtful lesions, 12 months of monitoring was used as the reference method for the definitive diagnosis. RESULTS: The overall concordance rate between the two techniques was 63%. The DWIBS sequence detected a higher number of lesions leading to a higher Durie-Salmon stage in 37% of the patients: one stage I to II, seven stage I to III, and two stage II to III. In 18.5% of the patients, the MRI was positive while the radiographs were normal and these discrepancies were most often located in sites poorly explored by X-ray (spine, pelvis and ribs). In one patient (4%), the MRI provided a stage lower than that of the X-rays (stage II vs. III). In this case, the X-rays were positive at the humerus and femur, unlike the DWIBS sequence. Our per site analysis confirmed the clear superiority of the DWIBS sequence when compared with X-rays in the exploration of the cervical spine (56 vs. 0%, P<0.001), dorsal spine (81vs. 31%,P<0.0002), lumbar spine (70 vs. 35%, P<0.0124), pelvis (81 vs. 33%, P<0.0005) and ribs (74 vs. 36%, P<0.0009). CONCLUSION: The DWIBS MRI leads to an increase in the final Durie-Salmon stage. Although its place in the preoperative treatment of multiple myeloma still has to be assessed, this study suggests its potential interest.

Cost-effectiveness analysis of a risk-adapted algorithm of plerixafor use for autologous peripheral blood stem cell mobilization.

Historically, up to 30% of patients were unable to collect adequate numbers of peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (ASCT). Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has shown superior results in mobilizing peripheral blood (PB) CD34+ cells in comparison to G-CSF alone, but its high cost limits general use. We developed and evaluated risk-adapted algorithms for optimal utilization of plerixafor. In plerixafor-1, PBSC mobilization was commenced with G-CSF alone, and if PB CD34 on day 4 or day 5 was <10/µL, plerixafor was administered in the evening, and apheresis commenced the next day. In addition, if on any day, the daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Subsequently, the algorithm was revised (plerixafor-2) with lower thresholds. If day-4 PB CD34 <10/µL for single or <20/µL for multiple transplantations, or day-1 yield was <1.5 × 10(6) CD34/kg, or any subsequent daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Three time periods were analyzed for results and associated costs: January to December 2008 (baseline cohort; 319 mobilization attempts in 278 patients); February to November 2009 (plerixafor-1; 221 mobilization attempts in 216 patients); and December 2009 to June 2010 (plerixafor-2; 100 mobilization attempts in 98 patients). Plerixafor-2 shows a significant improvement in PB CD34 collection, increased number of patients reaching minimum and optimal goals, fewer days of apheresis, and fewer days of mobilization/collection, albeit at increased costs. In conclusion, although the earlier identification of ineffective PBSC mobilization and initiation of plerixafor (plerixafor-2) increases the per-patient costs of PBSC mobilization, failure rates, days of apheresis, and total days of mobilization/collection are lower.

Efficacy assessment of interferon-alpha-engineered mesenchymal stromal cells in a mouse plasmacytoma model.

Bone marrow mesenchymal stromal cells (BM-MSCs) may survive and proliferate in the presence of cycling neoplastic cells. Exogenously administered MSCs are actively incorporated in the tumor as stromal fibroblasts, thus competing with the local mesenchymal cell precursors. For this reason, MSCs have been suggested as a suitable carrier for gene therapy strategies, as they can be genetically engineered with genes encoding for biologically active molecules that can inhibit tumor cell proliferation and enhance the antitumor immune response. We used BM-MSCs engineered with the murine interferon-alpha (IFN-α) gene (BM-MSCs/IFN-α) to assess in a mouse plasmacytoma model the efficacy of this approach toward neoplastic plasma cells. We found that IFN-α can be efficiently produced and delivered inside the tumor microenvironment. Subcutaneous multiple administration of BM-MSCs/IFN-α significantly hampered the tumor growth in vivo and prolonged the overall survival of mice. The antitumor effect was associated with enhanced apoptosis of tumor cells, reduction in microvessel density, and ischemic necrosis. By contrast, intravenous administration of BM-MSCs/IFN-α did not significantly modify the survival of mice, mainly as a consequence of an excessive entrapment of injected cells in the pulmonary vessels. In conclusion, BM-MSCs/IFN-α are effective in inhibiting neoplastic plasma cell growth; however, systemic administration of engineered MSCs needs to be improved to make this approach potentially suitable for the treatment of multiple myeloma.

Clinical and histological characteristics of nasopharyngeal cancer in Sokoto, north-western, Nigeria.

BACKGROUND: Cancer of the nasopharynx poses diagnostic and therapeutic difficulties because of the hidden nature of the nasopharyngeal space, which allows for significant spread of the disease before diagnosis and hence poor prognosis. OBJECTIVE: To describe the clinical and histological characteristics of nasopharyngeal cancer in a tertiarty health institution in Northern Nigeria. METHODS: Clinical features of patients with nasopharyngeal cancer presenting at the Ear, Nose and Throat clinic of a University Teaching Hospital in North western Nigeria seen over a five-year period were analysed. RESULT: A total number of 30 cases, [22 (73.3%) males and 8 (27.7%) females] with a male to female ratio of 2.8:1 were seen. The mean age was 39.1 years with the fourth decade of life recording the highest number of 16 cases (53.3%) and the least in the thirth decade. The commonest clinical features were neck swelling caused by cervical lymphadenopathy 28 (93.3%), epistaxis 25 (83.3%), nasal obstruction 20 (66.7%),and deafness 11 (36.7%). Others were otalgia 9 (30%), palatal swelling 8 (26.7%),cranial nerve involvement 7 (23.3%) and visual impairment 6 (20%). According to the UICC 1997 staging for nasopharyngeal carcinoma, 23 (76.7%) and 7 (23.3%) were T3 and T4 or stages III and IV respectively. The histological diagnoses were squamous cell carcinoma 23 (76.7%) cases, non-Hodgkins lymphoma 3 (10%) cases, plasmacytoma 2 (6.7%) cases, rhabdomyosarcoma one (3.3%) case, karposis sarcoma one (3.3%) cases. Seventeen (56.7%) patients though accepted in principle never went for radiotherapy. Only 2 (6.7%) were still alive three and six years respectively from the time of diagnosis after chemoradiation while all others (93.3%) had died within one year of diagnosis. CONCLUSION: Nasopharyngeal cancer in Northern Nigeria is characterised by presentation with advanced disease, high mortality and low 5-year survival rates. Free or highly subsidized medical programme for early detection and treatment will reduce the high mortality rate associated with nasopharyngeal cancer in this region.

Extramedullary plasmacytoma of the nasal cavity: treatment perspective in a developing nation.

Extramedullary plasmacytomas are uncommon tumors, with a worldwide annual incidence of 3 per 100,000 population. They account for 1% of all tumors of the head and neck and 4% of all nonepithelial tumors of the nasal tract. A variety of treatment options has been suggested. These treatments vary according to the site of presentation, the presence of locoregional spread, and the histologic picture. Radiotherapy has been widely used as a treatment modality, but little has been written about surgery as a single management modality. However, such an option assumes importance in a developing nation, where patient follow-up is erratic and treatment costs must be kept low. We discuss the feasibility of surgery in such a circumstance, and we describe our surgical treatment of a case of extramedullary plasmacytoma in an elderly woman who presented to our hospital in India.

Assessment of all-trans retinoic acid (ATRA) efficacy as a single agent in primary lymphoid neoplasia.

All-trans retinoic acid (ATRA) is currently widely used in the therapy of acute promyelocytic leukemia and is being tested in vitro and in vivo on several other malignancies. Previously ATRA has been shown to inhibit the growth in vitro, of established human myeloma cell lines as well as cultured primary myeloma cells from patients. ATRA acts by down-regulating IL-6-receptor-alpha or gp130 on the surface of the myeloma cells. However, despite its in vitro effects on myeloma cells, ATRA therapy on advanced stage multiple myeloma (MM) patients has so far largely been ineffective. In current studies, we have assessed the efficacy of ATRA therapy against primary murine plasma cell tumors, which are an animal model for human MM. These tumors are induced at about 50% incidence in pristane-primed BALB/c mice by injection of v-raf/v-myc- containing retroviruses and are IL-6 dependent. Using this animal model, we assessed the effect of ATRA as a therapeutic agent against primary tumors at two early time points in disease development. ATRA was administered in liposomal vesicles (ATRAGEN), since liposomal-ATRA has been shown to circumvent clearance mechanisms by hepatic microsomes, which normally occur with free ATRA. In addition, ATRAGEN was previously shown to be less toxic in mice than free ATRA. ATRAGEN was administered beginning on day 25 or day 45 after virus injection and continued twice weekly for 8-11 weeks. ATRAGEN administration begun at either time point did not alter the incidence or the latency of plasma cell tumors compared with control animals. These results suggest that ATRA may not be an effective sole therapy against early MM.

The value of genotypic analysis in the assessment of cutaneous plasmacytomas.

We report a 79-year-old woman with primary cutaneous plasmacytoma in whom polymerase chain reaction (PCR) was used to demonstrate the monoclonality of the tumour. Four years after presentation, further skin lesions occurred and PCR again showed evidence of monoclonality despite the histology being non-specific. The reported frequency of multiple primary cutaneous plasmacytoma is increasing, and the mortality rate of patients with multiple lesions is three times that of those with a solitary lesion. PCR may be a useful technique for assessing such patients at presentation.

Optimal primer selection for clonality assessment by polymerase chain reaction analysis: I. Low grade B-cell lymphoproliferative disorders of nonfollicular center cell type.

Recent polymerase chain reaction (PCR)-based studies focused on the detection of immunoglobulin heavy chain gene (IgH) rearrangements have suggested that clonal populations may be amplified more easily from certain categories of B-cell neoplasia than others and that primer makeup can be a critical factor in successful amplification. However, these particular reports contained relatively few low grade B-cell lymphoproliferative disorders of nonfollicular center cell type (LG-BLPD) and used only a limited panel of available primer sets for PCR amplification of monoclonal B-cell populations. To address this issue more extensively we evaluated 156 samples of LG-BLPD by the PCR to determine optimal primer selection in this setting. All cases were classified according to standard morphological and immunophenotypic criteria, with monoclonality documented by Ig light chain restriction analysis. The LG-BLPD included 33 cases of chronic lymphocytic leukemia (CLL), 57 cases of small lymphocytic lymphoma (SLL), 10 cases of atypical CLL, 32 cases of mantle cell lymphoma (MCL), 17 plasma cell neoplasms (PCNs), and seven cases of hairy cell leukemia (HCL). All primer sets included a 3' IgH joining region consensus primer, whereas the 5' IgH variable region (VH) primer was different in each set. The first-line panel included the following: Set 1, VH-framework III consensus primer, and Set 2, seven separate VH-framework I family-specific primers. A reserve panel of alternate VH consensus primers directed at framework II or III regions was used only when Set 1 showed no evidence of B-cell monoclonality.(ABSTRACT TRUNCATED AT 250 WORDS)

[Aspects and role of spinal MRI in the assessment of solitary plasmacytoma and multiple myeloma. Apropos of 11 cases]. / Aspects et rôle de l'irm du rachis au cours de l'exploration du plasmocytome solitaire et du myélome multiple. A propos de 11 observations.

Spinal MRI was performed in 9 multiple myeloma and 2 solitary plasmacytoma, using sagittal, T 1-weighted (TR: 350-550 ms/TE: 15-26 ms) and T 2-weighted (TR: 2,000-2,500 ms/TE: 60-120 ms) sequences, with additional gadolinium injection in 3 cases. MRI features were the following: 1) round, patchy lesions with low T 1 signal highlighted by gadolinium and bright T 2 signal were present in 10 of the 11 patients: all osteolytic lesions seen on plain X-rays corresponded to such lesions and biopsy performed in 4 cases showed massive marrow replacement by plasma cells. 2) overall marrow signal was dramatically decreased in 3 patients (2 of whom had a high tumoral mass). 3) extra-dural compression was present in 4 cases. 4) 25 vertebral compression fractures (10 of whom with a "benign" appearance) and focal fat deposition were seen. 5) postradiation treatment examination seemed predictive of the outcome in the 2 solitary plasmacytomas. MRI proved to be more sensitive than plain X-rays or bone scintigraphy. Number and size of focal tumor-like lesions did not correlate with the low marrow signal appearance. Both correlated poorly with overall tumoral mass but diffuse abnormalities were associated with rapidly fatal outcome in three cases. These features might reflect qualitative rather than quantitative patterns of the disease (nodular or diffuse macroscopic marrow replacement). These findings are in agreement with those of the few previous studies. MRI is valuable for spinal cord damage assessment. It appears less accurate in benign versus malignant vertebral compression fracture determination than it does in bone metastasis. Its prognostic value is still questionable.