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.

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.

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.

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.