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Long-term study of gammopathies. Clinically benign cases showing transition to malignant plasmacytomas after long periods of observation.

Since 1968, our Clinical Chemistry laboratory has been performing protein electrophoresis on sera of patients with total protein levels of over 85.0 g/L and under 55.0 g/L. Monoclonal gammopathies were found in 534 cases. Immunoelectrophoresis was carried out using antisera to the heavy chains gamma, alpha, mu, delta, and epsilon, and to the light chains kappa and lambda. Urine from these patients was tested for Bence-Jones protein. Records and smears, when available, were examined for clinical or hematologic evidence of multiple myeloma and other lymphoid malignancies. Sixty-five percent of these 534 cases were referred to the laboratory with a provisional diagnosis of plasmacytoma but 35% were not clinically suspected. Twenty-two cases with gammopathy, but no clinical or hematologic symptoms of plasma cell dyscrasia, were selected and followed up. Eight of these patients (36%) had converted to malignancy by the end of ten years. These results show the value of screening for abnormal proteins and the need for a long-term follow-up in such patients, prior to diagnosis of plasma cell dyscrasia.

Adult↗

Radiotherapy of extramedullary plasmacytoma of the head and neck.

The purpose of this study is to report the results of megavoltage irradiation in 23 previously unreported cases of extramedullary plasmacytoma of the head and neck. It has been found that 3500 cGy (rad) in three weeks provides good local control of disease with minimal morbidity and a significant proportion do not go on to multiple myeloma. Prognostic factors of significance with respect to subsequent development of multiple myeloma include site and presence or absence of bone destruction. The presence or absence of an M protein peak appears to be of no significance.

Adult↗

Plasmacytoma of the head and neck.

Fourteen cases of plasmacytoma arising in the head and neck are described. Good local tumour control was achieved with minimal surgery and moderate doses of radiation. Subsequent myelomatosis did occur but this was unusual and no more frequent with tumours arising in the maxilla and mandible than at extramedullary sites. It is recommended that all apparently solitary plasma cell tumours of the head and neck are treated by radiotherapy with curative intent and then followed up carefully for life.

Adult↗

Sodium butyrate suppresses apoptosis in human Burkitt lymphomas and murine plasmacytomas bearing c-myc translocations.

We report that sodium butyrate, a natural product of fiber degradation by colonic bacteria, markedly suppresses c-Myc-mediated apoptosis induced in murine plasmacytomas and human Burkitt lymphomas by growth factor deprivation, but not in cell lines devoid of c-myc translocations. Attenuation of cell death is associated with downregulation of the rearranged c-myc and activation of pRb via its dephosphorylation. We suggest that in vivo sodium butyrate may play an important role in plasmacytomagenesis by supporting the survival of cells with c-myc translocations, which otherwise would be eliminated by the lack of growth factors.

Animals↗

Intestinal multinodular A lambda-amyloid deposition associated with extramedullary plasmacytoma in three dogs: clinicopathological and immunohistochemical studies.

Intestinal extramedullary plasmacytomas (EMPs) are rare tumours in dogs. Three cases of canine intestinal EMP with amyloid deposits are described in this report. These tumours, which were located in the rectal submucosa, had variable numbers of well-differentiated plasma cells and fewer multinucleated giant cells of plasmacytoid and histiocytic morphology, admixed with abundant amyloid. Two cases had metaplastic cartilage and bone within the amyloid deposits. Immunohistochemically, the plasma cells of all three tumours reacted for lambda-light chains of immunoglobulins but not for kappa-chains, indicating monoclonality. Plasma cells of two tumours were also positive to CD79a antiserum. Amyloid deposits were labelled with an A lambda (amyloid of immunoglobulin lambda-light chain origin) antiserum but not with antisera against its precursor protein, the immunoglobulin lambda-light chains, indicating possible conformational changes of amyloidogenic proteins during their transformation into amyloid.

Amyloid↗

Plasmacytoma of the testis.

We report a case of plasmacytoma of the testis without evidence of bone or immunoglobulin abnormalities. The presentation, evaluation and management of this extremely unusual tumor are reviewed.

Humans↗

Composite mantle-cell lymphoma and plasmacytoma.

We report a case of a composite lymphoma comprising both mande cell lymphoma and a plasmacytoma. The two components were morphologically and immunohistochemically quite distinct. These properties, coupled with both direct and indirect molecular genetic evidence, suggest that these were two separate tumours occurring together by chance or by unknown oncogenic mechanisms, rather than clonally linked lymphomas.

Biomarkers↗

Foster-Kennedy syndrome caused by solitary intracranial plasmacytoma.

The first case of typical Foster-Kennedy syndrome, including decreased olfaction of the side of the optic atrophy due to a primary solitary intracranial extraskeletal plasmacytoma, is reported. Its appearance on a computed tomography scan was compatible with a meningioma or subdural hematoma. The patient demonstrated a chronic, corticosteroid-sensitive, relapsing optic neuropathy associated with an elevated sedimentation rate and a monoclonal gammopathy. The diagnosis, treatment, and prognosis of such tumors are reviewed.

Brain Neoplasms↗

MUC1 expression in plasmacytoma.

Plasmacytoma (Pm) is a plasma cell (PC) neoplasia consisting of PCs and some of them show progression to multiple myeloma. But there is no clear indicators predicting this progression. In this study, MUC1 expression was evaluated in Pm cases to determine the predictive value and was compared with histopathologic grade which is known to be a prognostic indicator in Pm. Nine of 31 cases with Pm showed MUC1 expression. Only two of the 18 cases with mature morphology showed MUC1 expression while seven of 13 cases with immature morphology showed MUC1 expression and this was statistically significant (P<0.006). Additionally, four of 11 cases with BM involvement showed MUC1 expression while five of 20 cases without BM involvement showed MUC1 expression. There was a trend MUC1 expression with BM involvement but there was not statistically significant association between MUC1 expression and BM involvement. We found that MUC1 expression is associated with immature morphology which is an important prognostic indicator in Pm and by analogy MUC1 expression may be an additional prognostic indicator in patients with Pm.

Adult↗

Similar effects of electroporational stress and treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate on vimentin expression in mouse plasmacytoma cells.

In mouse plasmacytoma cells (MPC-11), an activation of the normally repressed vimentin gene was observed as a response to transfectional stress. Effects of electroporation on vimentin gene expression were compared at the cellular and chromatin level to those caused by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). At the cellular level, similar changes in vimentin gene activity and cell-cycle distribution were observed by flow cytometry, whereas at the chromatin level similar changes in patterns of hypersensitive regions were detected by DNase I mapping. Additionally, a region located 700 bp upstream of the transcriptional start became hypersensitive to DNase I digestion upon electroporation and TPA treatment. This region overlaps two adjacent AP-1-like binding elements and generates specific DNA/AP-1 complexes in bandshift experiments. Therefore, the transcription factor AP-1 seems to play a central role in the activation of vimentin gene expression induced by these 2 different forms of stress.

Animals↗

CD8+ tumor-specific Tc cells primed in vivo or in vitro against the BALB/c plasmacytoma ADJ-PC-5 use the same TcR V beta families but display distinct TC1 or TC2 characteristics.

The involvement of counteractive CD8+ T cell subsets in tumor-specific unresponsiveness was analyzed in a syngeneic murine tumor model. CD8+ cytotoxic T cells against the IL-10 producing BALB/c plasmacytoma ADJ-PC-5 can be easily induced in vitro, in a primary syngeneic mixed lymphocyte tumor cell culture (MLTC), or in vivo, by repeated immunization of syngeneic BALB/c mice with high doses of X-irradiated ADJ-PC-5 tumor cells. Long term cultivated CD8+ ADJ-PC-5-specific Tc lines use either TcR of the V beta 6 or V beta 8.1/8.2 type, irrespective if the lines were derived from a primary MLTC or from immunized mice. While most of the Tc lines produce type-1 cytokines (IFN-gamma, no IL-4) upon stimulation, at least two of them, which were derived from a primary MLTC, display a type-2 cytokine spectrum (IL-4, no IFN-gamma). The primary in vitro Tc response against ADJ-PC-5 cells shows characteristics of a TC2 response: CD8+ Tc cells which are induced in a primary MLTC do not produce IFN-gamma, and the tumor-specific Tc response is enhanced by IL-4 but suppressed by IFN-gamma or IL-12. In contrast, ADJ-PC-5-specific CD8+ Tc cells from immunized mice are IFN-gamma producing TC1 cells. Since the primary in vitro Tc response against the tumor is suppressed even by lowest numbers of irradiated ADJ-PC-5-specific TC1 cells via IFN-gamma, these TC1 cells behave similar to a previously described regulatory subset of IFN-gamma producing CD8+ T cells, which are induced during early stages of ADJ-PC-5 tumorigenesis and inhibit the induction of a tumor-specific Tc response from naive BALB/c spleen cells in vitro.

Adjuvants, Immunologic↗

Cutaneous involvement of multiple myeloma and extramedullary plasmacytoma.

We recently performed a retrospective clinicopathologic study of five patients with cutaneous involvement of multiple myeloma or extramedullary plasmacytoma. Cutaneous nodules without extension from an underlying bony focus of disease developed in each case. In two cases skin lesions occurred in the more common setting of advanced disease, but in two others skin lesions provided early clues to the diagnosis. In three patients the appearance of skin lesions heralded a rapidly deteriorating clinical course, but two other patients had reasonably long survivals despite cutaneous disease (6 and 3 years, respectively). Two histopathologic configurations were identified in cutaneous lesions: nodular and infiltrative. Both patients with the latter form had multiple myeloma. In all cases tumor cells were pyroninophilic. Immunoperoxidase studies on fixed, paraffin-embedded tissues confirmed the electrophoretic findings in two cases, but findings were equivocal in three others. In one case, cells were positive for epithelial membrane antigen, and in another, alpha 1-antichymotrypsin-positive cells were observed in the centers of tumor islands. Cutaneous involvement with plasma cell neoplasms is recognized infrequently. Immunohistochemical techniques may prove to be valuable in evaluating these cases, but they are not without technical and interpretative difficulties.

Aged↗

Intramedullary plasmacytoma in an unusual location in a renal transplant patient.

Transplant patients have increased risk for developing neoplasia. This is due to the use of more potent and long-term immunosuppression. We report a case of a 46-year-old man with a cadaver renal transplant who developed an intramedullary plasmacytoma in an unusual location. The patient had a total right elbow replacement and received 4 weeks of local radiotherapy. The pain completely resolved and the low-dose immunosuppression was continued.

Bone Neoplasms↗

Extramedullary plasmacytoma of the breast simulating breast cancer.

A patient with a palpable mass in the breast suggestive of carcinoma underwent radical modified mastectomy. Surprisingly, histology of the tumor revealed an extramedullary plasmacytoma. Further diagnostic work up showed no evidence of underlying multiple myeloma. Among neoplastic lesions of the breast, although rare, malignancy of mesenchymal or lymphoproliferative origin should always be considered.

Aged↗

Microsomal cAMP-independent histone H1 kinase activity in plasmacytoma, Morris hepatoma and normal liver.

A protein kinase activity with high specificity for histone H1 was isolated from mouse plasmacytoma, Morris hepatoma and normal mouse liver and compared by ion exchange chromatography after DEAE-cellulose, hydroxylapatite and Sephadex G-200 chromatography. This cAMP-independent histone H1 kinase is not affected by the heat-stable cAMP-dependent protein kinase inhibitor. It has the following particular properties: it prefers GTP to ATP as substrate and was found to be present with a great activity only in neoplastic tissues. No phosphatase activity was detected in the partially purified histone H1 kinase fraction from normal and neoplastic cells. These results suggest either an increase amount of histone H1 kinase and/or of its activator in neoplastic cells, or the presence of a strong inhibitor in normal cells. This histone H1 kinase appears to be analogous to the chromatin bound kinase which phosphorylates histone H1 at the NH2 and COOH terminal regions. We might suggest an implication of this kinase in the regulation of cell division.

Adenosine Triphosphate↗

Solitary bone plasmacytoma: outcome and prognostic factors following radiotherapy.

PURPOSE: To clarify the natural history of solitary plasmacytoma of bone (SBP) after radiation treatment. METHODS AND MATERIALS: Between 1965-1996, we identified 57 previously untreated patients with a SBP. A serum myeloma protein was present in 33 patients (58%) and Bence Jones proteinuria was present in an additional eight patients (14%). The median radiotherapy dose was 50 Gy (range, 30-70 Gy). Overall survival, cause-specific survival, and freedom from progression to multiple myeloma were calculated actuarially. RESULTS: Local control was achieved in 55 of 57 patients (96%). For those 29 patients (51%) who subsequently developed multiple myeloma, the median time to progression was 1.8 years. There was a direct correlation between persistence of abnormal protein following radiotherapy and the likelihood of developing multiple myeloma. Among 11 patients with disappearance of myeloma protein, only two developed multiple myeloma after 4 and 12 years, in contrast to progression in 57% of patients with a persistent protein peak and 63 % of those with nonsecretory disease (p = 0.02). Among 23 patients with thoracolumbar spine disease, 7 of 8 patients staged with plain radiographs alone developed multiple myeloma in comparison with 1 of 7 patients who also had magnetic resonance imaging (MRI) (p = 0.08). For all patients, the median survival from radiotherapy was 11.0 years. The median cause-specific survival of patients with disappearance of myeloma protein was significantly longer than that of the remaining patients (p = 0.004). CONCLUSION: Results supported the importance of precise staging that includes MRI of the spine for optimum patient selection and the application of definitive radiotherapy. Those patients with myeloma protein that disappears following radiotherapy represent a category with a high likelihood of cure.

Adult↗

Plasmacytoma of the proximal humerus.

This is the case report of a 67-year-old man who developed a solitary lytic lesion of the proximal humerus. Through further studies that included MR imaging of the affected upper extremity and biopsy, a final diagnosis of plasmacytoma was given. We present the clinical, imaging, and histologic findings and review the general characteristics of this neoplastic condition.

Aged↗