A single-day polychemotherapy regimen with proteasome inhibitor combinations for relapsed/refractory myeloma in the era of novel therapies.

PCAB (prednisone, cyclophosphamide, doxorubicin, carmustine) is a single-day regimen previously used for induction and now in relapsed/refractory multiple myeloma (RRMM). We retrospectively analysed the outcomes of 85 patients from five Australian centres. These included 30 patients (35.3%) who received PCAB with one additional agent (bortezomib most frequently). Median age of the patients was 65 years (37-80), with a median of four (1-8) prior lines of therapy. ORR was 37% (CR 4.9%). Median progression free survival and overall survival were 4.4 months (95% CI 3.5-6.7) and 7.4 months (95% CI 6.4-10.2), respectively. Extramedullary disease (EMD) was associated with shorter survival. Grade 3 or 4 cytopenia and febrile neutropenia occurred in 76.2% and 39.1%, respectively, with six (7.1%) treatment-related mortalities. Median inpatient stay was 3.3 days/28-day cycle (IQR 0.6-13), and for patients who died, a median of 20.2% of days alive were spent inpatient (IQR 6.4-39.1%). Three patients were successfully bridged to CAR T-cell therapy using PCAB, despite being penta-exposed and having EMD. PCAB may be considered as a useful salvage therapy amongst other polychemotherapy regimens in late relapse. Further studies is warranted to investigate and define its role as a bridging therapy to novel therapeutics.

Differences in survival of patients with multiple myeloma in rural versus metropolitan regions: Analysis of population data of an Australian local health district.

OBJECTIVE: The objective of this study is to determine if there are differences in outcome for patients diagnosed with multiple myeloma in a rural setting compared to a metropolitan setting and which factors influence these outcomes. DESIGN: Retrospective cohort study. SETTING: Illawarra Shoalhaven Local Health District. PARTICIPANTS: A total of 391 patients diagnosed with multiple myeloma between 2000 and 2022. MAIN OUTCOME MEASURES: Treatment and survival outcomes of these patients. RESULTS: Patients being treated in a rural cancer care centre had lower overall survival compared to those treated at a metropolitan cancer care centre (median OS = 44.4 months vs. 80.2 months, p = 0.002), despite access to similar treatments by the same group of haematologists. There was a significantly higher rate of upfront autologous transplantation (38% vs. 20%, p = 0.001) and higher rate of inclusion in clinical trials (16% vs. 7%, p = 0.021) in patients treated at a metropolitan cancer care centre compared to the rural cancer care centre. CONCLUSIONS: Multiple myeloma patients treated at a rural centre had shorter survival compared to patients treated at a metropolitan centre, and this may be related to lower rates of autologous transplantation and inclusion in clinical trials.

A Representation of Metastatic Plasma Cell Myeloma as an Uncommonly Shaped Liver Tumor-A Case Report.

The presence of an oval-shaped lesion in the liver is mainly associated with either primary liver cancer or metastatic disease from another malignancy. However, we present the case of a 62-year-old patient diagnosed with plasma cell myeloma, which reveals that these kinds of lesions can also be found during the course of this disease. Rarity and non-specificity make this a very challenging diagnosis for radiologists. It involves a special alert from the doctors taking care of the patient. Biopsy may sometimes be necessary to make a correct diagnosis. It is significant to ensure that the correct treatment is implemented and that the patient is not exposed to the unnecessary diagnosis of another neoplastic disease.

A Challenging Diagnosis Of Rare Co-Existent Multiple Myeloma And Prostate Adenocarcinoma: A Systematic Review Of Case Reports.

Objective: To review biochemical parameters, clinical characteristics, demographics, radiological and histopathological findings, treatment modalities and outcomes used to examine patients with coexisting multiple myeloma and prostate adencocarcinoma. METHODS: The systematic review comprised search on PubMed, Google Scholar, Science Direct and the Directory of Open Access Journal databases for case reports published till June 1, 2022. The search was done in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using appropriate key words. Case reports included were those dealing exclusively with human subjects, were published in the English language and had free, full-text, public access. Quality assessment was done using Joanna Briggs Institute's Critical Appraisal Checklist for Case Reports. Data was extracted and the case reports were evaluated for demographic, diagnostic and treatment parameters. RESULTS: Of the 515 studies initially identified, 5(0.97%) were analysed; all males with mean age 68.6±10.78 years. The most common symptom reported at presentation was low back pain 3(60%), Osteolytic lesions were seen in 4(80%) patients on imaging with elevated prostate surface antigen levels. Anaemia was found in 3(60%) patients and 2(40%) had thrombocytopenia. Conclusion: Multiple myeloma and prostate adenocarcinoma can coexist although it is rare. Awareness regarding the possible coexistence of the two prominent cancer types may further help clinicians during their practice in considering multiple myeloma as a differential diagnosis when encountered with patients having osteolytic bony lesions along with elevated levels of prostate-specific antigen. PROSPERO Registration Number: CRD42022334906.

Limitations of VS38c labeling in the detection of plasma cell myeloma by flow cytometry.

Plasma cell myeloma (multiple myeloma [MM]) is a malignant neoplasm originating from the plasma cells. Besides other methods, flow cytometric analysis of the patient's bone marrow aspirate has an important role in the diagnosis and also in the response assessment. Since the cell surface markers, used for identifying abnormal plasma cells, are expressed diversely and the treatment can also alter the phenotype of the plasma cells, there is an increasing demand for new plasma cell markers. VS38c is a monoclonal antibody that recognizes the CLIMP-63 protein in the membrane of the endoplasmic reticulum. CLIMP-63 is known to be expressed at high levels in normal and pathologic plasma cells in the bone marrow, thus VS38c antibody can be used to identify them. Although VS38c staining of plasma cells is reported to be constant and strong even in myeloma, we were wondering whether sample preparation can affect the staining. We have investigated the effect of different permeabilization agents and washing of the cells on the quality of the VS38c staining and found that in many cases the staining is inadequate to identify the plasma cells. We measured the VS38c staining of the bone marrow aspirates of 196 MM patients and observed that almost all cases showed bright staining with VS38c. However, permeabilization with mild detergent resulted in the appearance of a significant VS38cdim subpopulation, which showed increased sensitivity to mechanical stress (centrifugation). Our results indicate that VS38cdim MM cells can appear due to the improper permeabilization of the endoplasmic reticulum and this finding raises the possibility of the existence of a plasma cell subpopulation with different membrane properties. The significance of this population is unclear yet, but these cells can be easily missed with VS38c staining and can be lost due to centrifugation-induced lysis during sample preparation.

Gastrointestinal, hepatic, and pancreatobiliary involvement by plasma cell neoplasms: clinicopathologic correlations in a retrospective cohort of 116 cases.

AIMS: Plasma cell neoplasms (PCNs) may involve the gastrointestinal (GI) tract in two forms: plasmacytoma (PC), an isolated lesion that lacks marrow involvement, and extramedullary myeloma (EMM). However, previous literature on PCNs involving the GI tract, liver, and pancreas is limited. We evaluated the clinicopathologic features of the largest series of GI PCNs to date. METHODS AND RESULTS: Six institutional archives were searched for GI, liver, and pancreas cases involved with PCNs. Medical records were reviewed for clinical and imaging features. Histopathologic features evaluated included involved organ, tumor grade, and marrow involvement. Overall, 116 cases from 102 patients were identified. The tumors most presented as incidental findings (29%). The liver was most involved (47%), and masses/polyps (29%) or ulcers (21%) were the most common findings. Most cases had high-grade morphology (55%). The majority (74%) of GI PCNs were classified as EMM due to the presence of marrow involvement at some point during the disease course, occurring within a year of marrow diagnosis in 46% of patients. PC was classified in 26% of patients due to the lack of marrow involvement. Most (70%) patients died from disease within 10 years (median 14.1) of diagnosis and more than half (58%) died within 6 months. CONCLUSION: PC and EMM involving the GI tract, liver, and pancreas have a wide range of clinicopathologic presentations. Tumors may occur virtually anywhere in the GI tract or abdomen and may precede the diagnosis of marrow involvement. Both GI PC and EMM are associated with a poor prognosis.

Plasmacytoma and plasma cell myeloma affecting the jaws: A multi-institutional collaborative study.

BACKGROUND: Plasma cell neoplasms are characterized by the proliferation of a single clone of plasma cells with production of a monoclonal immunoglobulin. They can manifest as a single lesion (plasmacytoma) or as multiple lesions (multiple myeloma). METHODS: Paraffin-embedded tissue blocks of patients microscopically diagnosed with plasma cell neoplasms in the jaws were retrieved from five pathology files. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed and follow-up status were retrieved from the pathology reports. RESULTS: Fifty-two cases were retrieved (mean age: 59.4 years) without sex predilection. The mandible was the most affected site (67.3%), usually associated with pain and/or paresthesia (53.8%). Lesions in other bones besides the jaws were reported for 24 patients (46.2%). Radiographically, tumours usually presented as poorly defined osteolytic lesions with unilocular or multilocular images, while microscopy revealed diffuse proliferation of neoplastic plasma cells with nuclear displacement and abundant eosinophilic cytoplasm. Two cases were classified as anaplastic, and amyloid deposits were found in two other cases. Immunohistochemistry was positive for plasma cell markers and negative for CD20 and CD3, and monoclonality for kappa light chain predominated. The overall survival rate after 5 years of follow-up was 26.6%. CONCLUSION: Plasma cell neoplasms are aggressive tumours with a poor prognosis and involvement of the jaws may be the first complaint of the patient. Thus, oral pathologists, head and neck surgeons and dentists should be aware of their clinical, radiographic and microscopic manifestations.

Extraoral plasmablastic lymphomas in a high human immunodeficiency virus endemic area.

AIMS: Plasmablastic lymphoma (PBL) occurs mainly in immunocompromised individuals, usually secondary to human immunodeficiency virus (HIV) infection. It classically occurs intraorally, but has been described in extraoral locations. The aim of this study was to define the immunophenotype and Epstein-Barr virus (EBV) status in a large single-centre cohort of extraoral PBL (EPBL) in South Africa, a high-prevalence HIV setting. METHODS AND RESULTS: This retrospective study of 45 EPBLs included patients' age, gender, race, HIV status, and site. Cases were reviewed histologically, and classified morphologically as pure plasmablastic or plasmablastic with plasmacytic differentiation, and assessed immunohistochemically with antibodies against CD45, CD20, CD79a, PAX5, CD138, MUM1/IRF4, BLIMP1, VS38c, Ki67, bcl-6, CD10, cyclin D1, and human herpesvirus-8, by the use of standard automated procedures. EBV was assessed by the use of chromogenic in-situ hybridisation. Tumours were assessed with a fluorescence in-situ hybridisation (FISH) MYC break-apart probe. Twenty-seven PBLs showed pure plasmablastic morphology, and 18 showed plasmacytic differentiation. The male/female ratio was 1.5:1. The anus was the favoured extraoral site (31.1%), followed by lymph nodes (15.6%). All 29 patients with known HIV status were HIV-positive. The immunohistochemical profile recapitulated that reported for oral PBLs and EPBLs in HIV-positive and HIV-negative patients. EBV was positive in 92.5% of PBLs. FISH analysis showed MYC rearrangement in 48% of cases. CONCLUSION: This study showed a strong association of EPBLs with HIV and EBV infection, similarly to the previously described oral PBL. The strong EBV association together with other clinicopathological parameters and an immunohistochemical profile that includes CD45, CD20, MUM1/IRF4, CD138 and Ki67 may be used in distinguishing PBL from diffuse large B-cell lymphoma and plasma cell myeloma.

IgG4 plasma cell myeloma: Clinicopathological characteristics and diagnosis.

Plasma cell myeloma (PCM) is usually associated with the presence of M-protein in the serum and urine of patients, and about half of the PCM cases exhibit the IgG M-protein and increased gamma-globulin fraction on membrane electrophoresis. The IgG4 subclass is located in the beta-2 fraction on membrane electrophoresis. The aim of this study was to develop a method to evaluate IgG4-producing PCM (IgG4-PCM) and its clinicopathological characteristics. We found three cases of IgG4-PCM among 80 cases of IgG-producing PCM by membrane electrophoresis, which were confirmed by IgG4 immunostaining. None of the cases had a clinical history of IgG4-related disease, although they exhibited high levels of serum IgG4. A bone marrow aspiration specimen had an increased number of plasma cells with a relatively mature morphology. No cases exhibited lymphoplasmacytic inflammation, obliterative phlebitis or fibrosis. Immunohistochemistry revealed that tumor cells expressed CD138 and IgG4 and showed monoclonal expression of kappa. We revealed that IgG4-PCM might not be associated with IgG4-related disease and that the detection of M-protein with beta-globulin fraction by electrophoresis may be useful for screening IgG4-PCM.

Prevalence of Cytoplasmic Actin Mutations in Diffuse Large B-Cell Lymphoma and Multiple Myeloma: A Functional Assessment Based on Actin Three-Dimensional Structures.

Mutations in actins have been linked to several developmental diseases. Their occurrence across different cancers has, however, not been investigated. Using the cBioPortal database we show that human actins are infrequently mutated in patient samples of various cancers types. Nevertheless, ranking these studies by mutational frequency suggest that some have a higher percentage of patients with ACTB and ACTG1 mutations. Within studies on hematological cancers, mutations in ACTB and ACTG1 are associated with lymphoid cancers since none have currently been reported in myeloid cancers. Within the different types of lymphoid cancers ACTB mutations are most frequent in diffuse large B-cell lymphoma (DLBCL) and ACTG1 mutations in multiple myeloma. We mapped the ACTB and ACTG1 mutations found in these two cancer types on the 3D-structure of actin showing they are in regions important for actin polymer formation or binding to myosin. The potential effects of the mutations on actin properties imply that mutations in cytoplasmic actins deserve dedicated research in DLBCL and multiple myeloma.

What difficulties can we encounter in the diagnosis of plasma cell myeloma?

Plasma cell myeloma is a cancer originating from plasmocytes. This disease is characterized by a bone marrow infiltration by plasmocytes, which produce monoclonal immunoglobulin or light chains of immunoglobulins (so-called M-protein) and release cytokines stimulating bone destruction. It represents 1% of all neoplasms and 10-15% of haematological neoplasms. The median age of the disease is 70 years. In imaging, PCM lesions are described as osteolytic, osteoporotic or mixed. This radiological appearance can occur in many diseases' categories. A CASE REPORT: A 60-year-old patient was admitted to the Department of Maxillofacial Surgery in Lublin in 2018 in order to diagnose and treat a pathological lesion of the right maxilla. Patient has been treated due to generalised PCM since 2016. CT examination of the bones indicated the presence of osteolytic lesion of the right maxilla, radiologically corresponded to the odontogenic cyst. However, because of the coexisting disease, it was impossible to make a final diagnosis at this stage of diagnostics. After additional examinations, the patient was qualified for enucleation of the lesion. The result of histopathological examination confirmed the presence of a follicular cyst. CONCLUSIONS: In the described case, particular attention has been paid to the differentiation of cysts with bone osteolytic defects occurring in PCM. The final diagnosis is the result of histopathological examination of the tissue material obtained during an enucleation procedure of the pathological lesion of the maxilla.

Outcomes of secondary solid tumor malignancies among patients with myeloma: A population-based study.

BACKGROUND: Therapeutic advances have extended survival for patients with myeloma, who may develop secondary cancers. METHODS: Using the population-based Surveillance, Epidemiology, and End Results registry (2004-2015), the authors examined the characteristics, overall and cause-specific survival, and cumulative incidence function of cancer-related death among patients with myeloma with secondary cancers of the breast, prostate, lung, colon/rectum, or bladder or melanoma. Each patient was matched based on age, sex, race, and year of diagnosis to 50 controls from a general population who were diagnosed with the index cancer. RESULTS: Patients with myeloma with breast, prostate, or lung cancer were more commonly diagnosed at an early stage, whereas the stage distribution did not differ significantly among patients with melanoma, colorectal cancer, or bladder cancer. For all studied cancers except those of the lung, overall mortality was significantly higher among patients with myeloma compared with controls (hazard ratios, 1.84-2.81). However, the cumulative incidence function of cancer-related death did not differ (subhazard ratios, 0.84-0.99) and was surpassed by myeloma-related deaths (23% to 35% at 5 years). In patients with lung cancer, cancer-related mortality was uniquely lower among patients with myeloma (subhazard ratio, 0.59; 95% confidence interval, 0.52-0.68), even after adjustment for stage of disease. There was no significant difference noted with regard to noncancer deaths for any studied solid tumor. Use of surgery (evaluated in patients with nonmetastatic tumors, and in addition matched by disease stage) did not differ between cases and controls, except for fewer prostatectomies being noted among patients with myeloma (odds ratio, 0.56; 95% confidence interval, 0.42-0.74). CONCLUSIONS: The results of the current study support curative treatment approaches to secondary cancers among patients with myeloma while highlighting the need for ongoing active myeloma management.

Multiple myeloma epidemiology and patient geographic distribution in Canada: A population study.

BACKGROUND: Multiple myeloma (MM) is a malignancy of mature plasma cells. Environmental risk factors identified for this malignancy, among others, include farming and exposure to pesticides. METHODS: Using 3 independent population-based databases (the Canadian Cancer Registry, le Registre Québécois du Cancer, and Canadian Vital Statistics), this study analyzed patients' clinical characteristics and the incidence, mortality, and geographic distribution of MM cases in Canada during 1992-2015. RESULTS: In total, ~32,065 patients were identified, and 53.7% were male. The mean age at the time of diagnosis was 70 ± 12.1 years. The average incidence rate in Canada was 54.29 cases per million individuals per year, and linear regression modeling showed a steady rise in the annual rate of 0.96 cases per million individuals per year. At the provincial level, Quebec and Ontario had significantly higher incidence rates than the rest of Canada. An analysis of individual municipalities and postal codes showed lower incidence rates in large metropolitan areas and in high-latitude regions of the country, whereas high incidence rates were observed in smaller municipalities and rural areas. Land use analysis demonstrated increased density of crop farms and agricultural industries in high-incidence areas. A comparison with the available data from 2011-2015 showed several consistent trends at provincial, municipal, and regional levels. CONCLUSIONS: These results provide a comprehensive analysis of the MM burden in Canada. Large metropolitan cities as well as high-latitude regions were associated with lower MM incidence. Higher incidence rates were noted in smaller cities and rural areas and were associated with increased density of agricultural facilities.

Acquired von Willebrand syndrome associated with plasma cell myeloma - a rare histopathological bone marrow image.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that is associated with a variety of underlying diseases. We report a case of AVWS associated with plasma cell myeloma. The patient was a 57-year-old male with recurrent bleeding symptoms for a few months. Physical examination was normal. Laboratory studies revealed isolated prolongation of the activated partial thromboplastin time. His factor VIII activity, von Willebrand factor (VWF) Ag, and VWF activity were low. Bone marrow aspirate showed diffuse infiltration of atypical plasma cells and erythroid line hyperplasia.

Association of ABCB1 T-129C polymorphism and multiple myeloma risk in Polish population.

The possible interaction between gene polymorphism and cancer risk development is a very interesting issue. The genetic variants of the ATP-binding cassette superfamily B member 1 (ABCB1) are known to be involved in developing cancer risk and individual differences in chemotherapeutic response. Polymorphisms may affect the reduction of the activity and/or expression of important protective cellular proteins. The increased exposure to toxic compounds, including carcinogens is associated with an increased risk of developing cancers. The present study was aimed to evaluate the possible effect of ABCB1 T-129C single nucleotide polymorphism in risk of cancer development in Polish patients diagnosed with multiple myeloma. 91 multiple myeloma patients and 94 healthy controls were enrolled in this case-control study. The ABCB1 T-129C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). The distribution of particular genotypes between multiple myeloma patients and controls group was not significantly different for T-129C SNP (p = 0.4297). The studied polymorphism does not seem to affect the increased risk of multiple myeloma development.

Plasma Cell Myeloma - 20-Year Comparative Survival and Mortality of Three Plasma Cell Myeloma ICD-O-3 Oncologic Phenotypes by Age, Sex, Race, Stage, Cohort Entry Time-Period and Disease Duration: A Systematic Review of 111,041 Cases for Diagnosis Years 1973-2014: (SEER*Stat 8.3.4).

BACKGROUND: -The values of SEER site recode variables are based on the primary site and histology data fields submitted to SEER by the registries. The site recode variables define the major cancer site/histology groups that are commonly used in the reporting of cancer incidence data and are added to the SEER databases as a convenience for researchers. These codes and definitions are periodically updated and changed by the National Cancer Institute as newer and more applicable information becomes available. Because this myeloma analysis includes cases diagnosed 2010+, the ICD-O-3 recode-updates with adjustment for WHO 2008 hematopoietic histologies that account for changes in the obsolete classification of hematopoietic histology codes, and the assignment of new names (ie, multiple myeloma-MM - to - plasma cell myeloma-PCM) is adhered to and used here. Plasma cell myeloma (PCM) is a bone-marrow based multifocal plasma cell malignancy (primary site C421). PCM is characterized by a single clone of plasma cells, believed to be derived from lymphoid B cells, and spans a clinical spectrum from asymptomatic to aggressive forms, plus disorders caused by the deposition of abnormal immunoglobulin chains in tissue. The current myeloma group ICD-O-3 histologic morphology types consists of: ICD-O-3 9731: Plasmacytoma, NOS, occurring in bone (osseous plasmacytoma malignancy data reportable to SEER only beginning since 1986); ICD-O-3 9732: Plasma cell myeloma - composed of three clinical variants: a) asymptomatic, b) Non-secretory myeloma, and c) Plasma cell leukemia (all coded to 9732); ICD-O-3 9734: Extramedullary plasmacytoma; anatomic sites other than bone. OBJECTIVE: -Using the statistical database of SEER*Stat 8.3.4 (produced 4/14/2017 for diagnosis years 1973-2014), to assess, determine, compare, and summarize the occurrence, long-term survival and mortality indices of the three morphologic types of myeloma by age, sex, race and stage in two-cohort entry time-periods (1973-1994 and 1995-2014). All analyses are accomplished within the context of current SEER Site Recode ICD-O-3 (1/27/2003) definitions, terminologies and descriptions, and also in accordance with the rules of the consolidated Hematopoietic and Lymphoid Neoplasm Coding Manual data base (effective 1/1/2010 - release date January 2015). METHODS: -Population data including 111,041 cases collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Frequency Database (18 SEER Registries Research Data + Hurricane Katrina Impacted Louisiana Cases, November 2016 Submission, 1973-2014 varying) for diagnosis years 1973-2014: Relative Survival Statistics were analyzed in two cohorts: 1973-1994 and 1995-2014. Survival statistics were derived from: SEER*Stat Database: Incidence - SEER 9 Regs Research Data, November 2016 Submission (1973-2014) Released April 2017. RESULTS: -Tables 1-3 provide basic SEER comparative survival and mortality data of the three myeloma oncotypes by age, sex, stage and disease duration of patients in the 1973-2014 time-period. Epidemiologic, demographic, and case statistics data extracted from the most current NCI Cancer Statistics Review (CSR 2010-2014) are included. CONCLUSIONS: -Recent SEER age-adjusted incidence trends, 2011-2014, for all races has been downward, with an annual percentage change (APC) of -2.5% per year. Mean age in plasma cell myeloma (PCM) patients was about 1-year less in males (67.8 yrs) than in females (69.2 yrs). PCM is accompanied by a very high excess mortality and much reduced 5-year relative survival ratio especially in older age groups. Generally, first year excess death rates (EDRs) decreased with duration but increased with advancing entry age, and there was no sex difference. First year EDRs in blacks, all ages combined, was quite high but lower than EDRs in whites. Median survival, actual survival and 5-year relative survival ratios diminished precipitously to extremely low levels with increasing entry age attesting to the lethal character of this disease especially in older patients.

CD117 (KIT) is a useful marker in the diagnosis of plasmablastic plasma cell myeloma.

AIMS: Plasmablastic plasma cell myeloma (PPCM) is a rare morphological presentation of multiple myeloma, and can resemble plasmablastic lymphoma (PBL), a human immunodeficiency virus (HIV)-related lymphoid neoplasm, morphologically and immunophenotypically. The aim of this study was to retrospectively search for factors that could help to differentiate these two entities. METHODS AND RESULTS: We used clinical looking glass, a data mining tool, to identify patients with a diagnosis of either PPCM or PBL with a CD117 test performed. We identified 27 cases from 16 patients in our institution with a diagnosis of either PPCM or PBL. There were 14 cases of PBL from eight patients and 13 cases of PPCM from eight patients. We found that six of eight patients with PPCM were positive for CD117, whereas no patients with PBL (0/8) showed positivity (P = 0.007 for patients). All (8/8) PPCM patients had a paraproteinaemia, whereas only two of eight PBL patients had a paraproteinaemia (P = 0.007). Lytic bone lesions were more indicative of a PPCM, with six of eight patients showing these lesions, and only one of eight PBL patients showing these lesions (P = 0.0406). HIV status was more likely to be positive in PBL patients, with six of seven patients showing positivity, and only one of five PPCM patients showing positivity (P = 0.072). Epstein-Barr virus-encoded RNA in-situ hybridization did not differentiate these two entities, with seven of eight PBL patients showing positivity, and two of five PPCM patients showing positivity (P = 0.2168). CONCLUSIONS: This study reveals that CD117 can be a useful marker to help differentiate PPCM from PBL and give the patient an appropriate prognosis and options for treatment.

Towards Stratified Medicine in Plasma Cell Myeloma.

Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies. Clinical staging, recurring acquired cytogenetic aberrations, and serum biomarkers such as ß-2 microglobulin, and free light chains are in widespread use but often fail to predict the disease progression or inform treatment decision making. Recent scientific advances have provided considerable insight into the biology of myeloma. For example, gene expression profiling is already making a contribution to enhanced understanding of the biology of the disease whilst Next Generation Sequencing has revealed great genomic complexity and heterogeneity. Pathways involved in the oncogenesis, proliferation of the tumour and its resistance to apoptosis are being unravelled. Furthermore, knowledge of the tumour cell surface and its interactions with bystander cells and the bone marrow stroma enhance this understanding and provide novel targets for cell and antibody-based therapies. This review will discuss the development in understanding of the biology of the tumour cell and its environment in the bone marrow, the implementation of new therapeutic options contributing to significantly improved outcomes, and the progression towards more personalised medicine in this disorder.