tecnica - P***



Discrasie plasmacellulari e Mieloma

(scheda a cura di Marco Chilosi e Maria Grazia Zorzi)

In una percentuale di casi di mieloma è dimostrabile iper-espressione di CD56, mentre le plasmacellule midollari delle MGUS (gammapatie di incerto significato) non mostrano elevati livelli di questo marcatore. E' suggerito da alcuni autori l'utilizzo di CD56 in questo contesto di diagnosi differenziale utilizzando metodo immunoistochimico su BOM. Il dato non è però suffragato da evidenze significative utilizzando la citometria a flusso.

Dubbio inoltre il significato prognostico dell'eterogeneità di espressione nell'ambito del mieloma.

Intensa espressione di CD56/N-CAM in due casi di mieloma

Non tutti i casi di MM esprimono CD56
per cui sono da valorizzare solamente i risultati positivi

Controllo interno: osteoblasti ed endostio paratrabecolare


Am J Pathol 2002 Apr;160(4):1293-9 
Expression of CD56/neural cell adhesion molecule correlates with the presence of lytic bone lesions in multiple myeloma and distinguishes myeloma from monoclonal gammopathy of undetermined significance and lymphomas with plasmacytoid differentiation. 
Ely SA, Knowles DM. 

Department of Pathology, Weill Medical College of Cornell University, New York

Unlike monoclonal gammopathy of undetermined significance (MGUS) or non-Hodgkin's lymphomas (NHLs) with plasmacytoid differentiation, multiple myeloma (MM) is commonly associated with lytic bone lesions. Although the mechanisms of increased osteoclast activity are partially understood, comparatively little is known about the mechanisms that lead to the observed decrease in osteoblast function. Studies have shown neural cell adhesion molecule (NCAM) homophilic binding between MM cell lines and osteosarcoma cell lines, and that binding results in decreased osteoid production in vitro. Thus, we postulated that the expression of NCAM by MM cells contributes to lytic lesion formation by causing decreased osteoid production in vivo. We used immunohistochemistry in bone marrow core biopsies to assess NCAM expression in osteoblasts and plasma cells (PCs) in vitro. We found consistent, strong, uniform NCAM expression by the osteoblasts in all bone marrow core biopsies (352 of 352, 100%). Strong expression of NCAM by PCs correlated with the presence of lytic bone lesions (chi-square, 33.39: P <0.000; odds ratio, 16.9). There was also a strong correlation between NCAM expression and the diagnosis of MM in comparison to reactive PCs, MGUS, or NHLs with plasmacytoid differentiation (all P values <0.000). In conclusion, using immunohistochemistry, we found strong expression of NCAM by osteoblasts and that when equal to the intensity of osteoblast expression, NCAM expression by PCs correlates with the presence of lytic bone lesions and distinguishes MM from reactive plasmacytosis, NHLs with plasmacytoid differentiation, and most cases of MGUS.

Br J Haematol. 2002 Jun;117(4):882-5.
Clinicopathological and prognostic characteristics of CD56-negative multiple myeloma.
Sahara N, Takeshita A, Shigeno K, Fujisawa S, Takeshita K, Naito K, Ihara M, Ono T, Tamashima S, Nara K, Ohnishi K, Ohno R.
Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, 431-3192 Japan.

We analysed CD56 expression in 70 patients with multiple myeloma (MM) to determine its clinicopathological and prognostic significance. Fifty-five (79%) patients were CD56+. CD56- patients (n = 15) had higher beta2 microglobulin levels and a higher incidence of extramedullary disease, Bence Jones protein, renal insufficiency and thrombocytopenia than CD56+ patients. Their myelomas more frequently had a plasmablastic morphology. Overall survival was significantly lower in CD56- than CD56+ patients (22 vs 63 months, P = 0.0002). We conclude that CD56- MM is a discrete entity associated with more aggressive disease. The higher incidence of plasmablastic cases suggested that CD56- MM may develop from a less mature plasma cell than CD56+ MM.

Leuk Lymphoma. 2004 Jan;45(1):61-5.
Prognostic significance of surface markers expressed in multiple myeloma: CD56 and other antigens.
Sahara N, Takeshita A.
Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, 431-3192, Japan.

Multiple myeloma (MM) is characterized by increased numbers of malignant plasma cells. Plasma cells, that represent the terminal differentiation of B lymphocytes, have considerable heterogeneity of surface markers expressed on them. Some studies showed the prognostic significance of several immunophenotypic molecules on MM cells. Here, we review several surface markers related to their prognostic significance in MM patients. We also report that CD56-negative MM is the unique entity characterized by poor prognosis with high incidence of extramedullary disease, Bence Jones protein, renal insufficiency, thrombocytopenia and plasmablastic morphology.

Leuk Lymphoma. 2006 Jan;47(1):43-7.
Prognostic relevance of CD56 expression in multiple myeloma: a study including 107 cases treated with high-dose melphalan-based chemotherapy and autologous system cell transplant.
Chang H, Samiee S, Yi QL.
Department of Laboratory Hematology, Princess Margaret Hospital/University Health Network, University of Toronto, ON, Canada.

CD56 is a neural adhesion molecule and expressed in 70-80% cases of multiple myeloma (MM). Lack of CD56 expression has shown to be a poor prognosis in MM patients treated with conventional chemotherapy, but its prognostic relevance in MM treated with high dose chemotherapy and autologous stem cell transplant (ASCT) is not known. CD56 expression was evaluated by immunohistochemistry on bone marrow paraffin embed specimens from 107 MM cases undergoing Melphalan-based high dose therapy and ASCT. CD56 was expressed by the myeloma cells in 71% of the patients. CD56 negative myeloma was associated with bone lesions (p = 0.032), but there was no association with any other biological or genetic risk factors including deletions 13q, p53 and IgH translocations, as evaluated by fluorescence in situ hybridization (FISH). There was no significant difference between CD56 positive and CD56 negative myeloma for progression free or overall survival (p = 0.28 and p = 0.67, respectively). In contrast to reports of CD56 in myeloma treated with conventional chemotherapy, CD56 negativity was not found to confer a poor prognosis in these patients, suggesting Melphalan-based high-dose chemotherapy and ASCT may overcome the adverse influence of CD56 negative myeloma.