EMP is relatively rare, in our hospital, the total number of EMP diagnosed in period of 1990 and 2007 was 39, accounting for 13.97% (39/279) of all plasma cell neoplasms and 0.46% (39/8481) of all lymphoid neoplasms diagnosed during this period. Recently, Dores GM et al  reviewed plasma cell neoplasms reported in the literature in period of 1992-2004, and analyzed the incidence and survival for plasmacytoma of bone, EMP and multiple myeloma (MM) reported in the United States in this period. There were 1543 cases of plasmacytomas, and EMP occupied 30.7% (474/1543). In all 474 cases of EMP, most patients were white males with advanced age, only 41 of them were Asians. To date, the largest number of EMP (68 cases) was reported from Canada by Bachar et al  in 2008. The clinical features in current group of the cases are summarized as follows: (1) the patients were old, with a mean age of 60 years and male predominant; (2) in about 72% of the patients, the tumors were located in the midfacial region, and a high percentage of skin involvement was noticed; (3) most patients received no treatment, and the prognosis was relatively poor; (4) no development of MM was found. As a result, the general clinical manifestations of the patients are almost same as that reported in the literatures, including the age, gender, anatomic sites of the tumor and so on [2–4, 6, 9, 10]. Talking about the treatment of the tumor, because the upper respiratory tract is most commonly involved, it is almost impossible to remove the tumor completely by operation, so that radiotherapy is often the first choices. No does-response relationship was observed now. The optimal radiation dose ranges from 40 to 50 Gy. If the tumor is greater than 5 cm in diameter, a higher does of radiation may be necessary for an effective treatment . In the patients received radiotherapy, local recurrence rate of the tumor is usually less than 5%. Secondly, for the EMP of other anatomic sites, complete surgical removal should be considered if feasible. In addition, no recommendation for adjuvant radiotherapy can be made for patients who have undergone complete surgical excision with negative margins . Bachar et al  reported 68 cases of solitary EMP of head and neck, the 5-year local recurrence-free rate (LRFR) was 81%, regional recurrence at 5 year was 5%, MM developed in 23% of the patients, and the 5-year survival rate was 76%. In current study, because most of our patients did not receive further treatment, after the diagnosis of EMP was established, their prognosis were not as good as that reported in the literature at all [5, 6, 11].
The histologic features of the cases in the current study are summarized as follows: (1) the neoplastic cells were moderately or poorly differentiated (grade II and III) in 40% of cases; (2) Variety degree of coagulative necrosis was observed in one third of the cases; (3) Amyloid deposition with granulomatous reaction and Dutcher's bodies were seen in 18.8% and 12.5% of the cases, respectively. Based on the report in literature, Most of EMP are well differentiated, the neoplastic cells are similar to normal plasma cells, especially the lesion of the upper aerodigestive tracts, there are often intermingled with variety of inflammatory cells, distinction between non-specific inflammation and plasma cell neoplasm is always problematic, Ig light chain restriction and Ig gene rearrangement analysis are useful in distinguishing non-neoplastic polyclonal proliferation from neoplastic clonal proliferation of plasma cells. In addition, because the morphologic changes of EMP are almost similar to those of extramedullary invasion of well differentiated MM, the diagnosis of EMP must be established on absolutely rule out the possibility of MM. The major clinical features of MM include hypercalcemia, renal insufficiency, anemia, multiple osteolytic lesions and so on. A constellation of clinical, laboratory, radiological and pathologic findings play an important role in diagnosis of MM as well. Sometimes, distinction from a marginal zone lymphoma with marked plasma cell differentiation is also a problem, particularly in skin and gastrointestinal tract, and may not be possible in some instance . In contrast to the reports in literatures, higher percentage of grade II and III cases was noticed in current study, The differential diagnosis include the following neoplasms, such as large B-cell lymphoma (LBCL), poorly differentiated carcinoma, melanoma, as well as other types of sarcomas with features of epithelial differentiation. Immunohistochemistry will help a lot in distinction among those tumors. For LBCL, the neoplastic cells usually give a positive reaction to B-cell differentiation antigens, such as CD19, CD20, CD79a, PAX5 and so on, and usually negative for plasma cell markers of CD138 and CD38. Cytokeratins of different molecular weights are the useful markers for identification of various kinds of epitheliums. Sometimes, the neoplastic cells of poorly differentiated squamous cell carcinoma or adenocarcinoma, may also express CD138 or PC, it is necessary to choose a penal of antibodies in differentiation between carcinoma and EMP. The neoplastic cells of melanoma usually express HMB-45, MART-1 and S-100 protein, and it is easy to distinguish melanoma from EMP.
The immunophenotypic features of the cases in this study are summarized as follows: (1) the neoplastic cells of all cases expressed one or more plasma cell associated antigens; and CD138 and CD38 were better than PC in both sensitivity and specificity as well; (2) some difference of immunophenotypic expression in EMP, SPB and inflammation of sinonasal regions with numerous PC infiltrations were observed; (3) 87.5% of the cases displayed Ig light chain restriction, with Igλ type predominant; (4) Ki-67 index was elevated with the advanced histologic grading. In contrast to MM, there are limited reports giving a special observation for the immunophenotypic feature of plasmacytomas and their significance in literatures.
CD45, a key regulator of antigen mediated signaling and activation in lymphocytes, is present in early stages of PCs development. Kumar S et al  reported a total of 75 patients with untreated MM (29), relapsed MM (17), smoldering MM (12), and monoclonal gammopathy of undetermined significance (MGUS) (17), the proportion of PCs expressing CD45 was higher among those with early disease (MGUS or smoldering MM) compared to those with advanced disease (new or relapsed MM) (43 vs 22%; P¼0.005). Moreau P  reported that patients with CD45 negative MM receiving high-dose therapy have a shorter survival than those with CD45 positive MM. In this series of cases, 34.4% of EMP gave a positive reaction to CD45, whereas in 12 cases of inflammation of aerodigestive tracts, the infiltrated plasma cells were all positive for CD45.
Aberrant expression of CD56 is almost always observed in MM and more than 70% cases of MM express CD56 [14–16]. Few reports revealed that CD56 expressed in solitary plasmacytoma of bone (SPB) and in 10% EMP cases [4, 17] Kermer M et al  compared the difference of Immunophenotype between EMP and MM. the results showed that EMP was infrequent expression of CD56, in contrast to both intra- and extra-medullary MM. In this series of cases, the percentage of CD56 expression was slightly higher than that reported in literature. We also observed CD56 expression in a group of inflammatory lesions of sinonasal regions with numerous plasma cell infiltrations; no PC gave a positive reaction to CD56 (the data did not show in this paper). The results suggested that CD56 may be used as a marker in differentiation between EMP and MM.
CD27 is a member of the still growing TNF receptor family [18, 19] and is a marker of memory B cells, and its interaction with its ligand, CD70, is very important for differentiation into plasma cells [20–24]. Although CD27 is detected on normal plasma cells, its expression is significantly reduced with the progression of multiple myeloma (MM) [25–29]. MM patients in complete clinical remission displayed a higher percentage of CD27+ PC compared with patients at diagnosis, relapse or in partial remission . No report has been found for CD27 expression in EMP yet. In current study, 43.8% of cases were positive for CD27.
CD44v6 is an isoform of the type 1 transmembrane glycoprotein CD44 generated by alternative splicing and has been implicated in cell adhesion and signaling, growth factor and cytokine presentation, as well as tumor dissemination [31–35]. Data on the incidence of CD44v6 in clonal plasma cell disorders are scarce. Liebisch et al  had observed CD44v6 expression in a group of plasma cell disorders, the results showed that CD44v6 was expressed in 13/32 in stage II/III MM correlated with chromosome 13q deletion, 1/6 in stage IA MM as well as 1/16 in MGUS. Therefore, the authors believed that CD44v6 is frequently expressed in advanced, high-risk MM. CD44v6 expression correlates with chromosomal band 13q14 deletions, a well known risk factor in MM. Eisterer et al  reported that CD44s was expressed strongly in all plasma cell populations included normal individuals, MGUS, MM, eMM and EMP. Although in 49 MMs, CD44v3 and CD44v6 expressed in 7 cases and 6 cases respectively, in 5 eMMs they were expressed in 3 cases and 4 cases respectively and in 2 EMPs they were expressed in all. In current series of cases, 56.3% of the cases expressed CD44v6, slightly higher than that reported in the literature. No difference of CD56, CD27 and CD44v6 expression was found in both low and high grade of EMP in current study at all.
The neoplastic cells of EMP and MM are positive for Bcl-2, whereas the reactive plasma cells usually do not express Bcl-2. Several authors also observed the relationship among CD45, Bcl-2 and Ki-67. No critical result was found now, in this study, nothing new was found as well.