The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.
Humans ; Multiple Myeloma/pathology* ; T-Lymphocytes, Regulatory/pathology* ; Immune Tolerance ; Plasma Cells/pathology* ; Immunosuppression Therapy ; Tumor Microenvironment

Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.
Humans ; Castleman Disease/pathology* ; Plasma Cells/pathology* ; Immunoglobulin G4-Related Disease ; China ; Lymphadenopathy/pathology* ; Inflammation/pathology* ; Lymph Nodes/pathology* ; Diagnosis, Differential ; Lymphadenitis/pathology* ; Immunoglobulin G/metabolism*

Multiple myeloma (MM) is a common plasma cell malignancy, accounting for the second largest hematological malignancy. Proteasome inhibitors represented by bortezomib (BTZ) have been the main treatment for patients with newly diagnosed and relapsed or refractory myeloma in nearly two decades. Although BTZ has improved the prognosis of MM patients, MM remains incurable in most patients, mainly because MM cells become resistant to BTZ. This review is to better understand the mechanism of MM resistance to BTZ and explore possible new therapeutic strategies.
Humans ; Bortezomib/therapeutic use* ; Multiple Myeloma/pathology* ; Proteasome Inhibitors/pharmacology* ; Prognosis ; Plasma Cells/pathology* ; Drug Resistance, Neoplasm ; Antineoplastic Agents/pharmacology* ; Cell Line, Tumor

OBJECTIVE: to analyze the effect of circulating plasma cells(CPC) on the prognosis of patients with multiple myeloma(MM) in the era of new drugs, and to explore the new definition standard of primary plasma cell leukemia(pPCL). METHODS: The clinical data of 321 patients with newly diagnosed MM and 21 patients with pPCL admitted to our hospital from January 2014 to May 2022 were retrospectively analyzed. According to the proportion of CPC in peripheral blood smears, all patients were divided into 4 groups: CPC 0% group(211 cases), CPC 1%-4% group(69 cases), CPC 5%-19% group(41 cases) and CPC≥20% group(21 cases). The clinical features of patients in each group were compared and the prognosis fators was analyzed. RESULTS: The median OS of the four groups were 44.5,21.3,24.6 and 12.8 months, respectively. Among them, 295 patients(86.3%) were treated with new drugs, and the median OS of the four groups were not reached, 26.7, 24.6 and 14.9 months, respectively. As the survival curves of CPC 5%-19% group and CPC≥20% group were similar, the patients were divided into CPC<5% group and CPC≥5% group, the median OS of CPC<5% group was better than that in CPC≥5% (43.5 vs 22.3 months, P<0.001). In addition, the median OS of patients in the CPC 1%-4% group was also significantly lower than that in the CPC 0% group and similar to that in the CPC≥5% group. Multivariate analysis showed that 1%-4% CPC was an independent risk factor for the OS of patients with CPC<5%. The patients with CPC<5% were stratified by R-ISS staging, and the OS of R-ISS stage Ⅰ or stage Ⅱ with 1%-4% CPC was similar to that of R-ISS stage Ⅲ. The newly defined pPCL patients showed increased tumor load and obvious invasive characteristics. Multivariate analysis showed no independent prognostic factors for pPCL, and high-risk cytogenetic abnormalities(HRCA) had no significant effect on the prognosis. CONCLUSION The validity of IMWG's new pPCL definition standard was verified, and it was found that the survival of MM with 1%-4% CPC also is poor and the prognosis is very close to pPCL. In addition, the newly defined pPCL has unique clinical and biological characteristics.
Humans ; Multiple Myeloma/pathology* ; Plasma Cells/pathology* ; Retrospective Studies ; Prognosis ; Leukemia, Plasma Cell/diagnosis*

Humans ; Plasma Cells/pathology* ; Hyperplasia/pathology* ; Immunoblastic Lymphadenopathy ; B-Lymphocytes/pathology* ; Lymphoma, T-Cell

To investigate the magnetic resonance imaging (MRI) features for ductal carcinoma in situ (DCIS) and plasma cell mastitis (PCM) , and to improve diagnostic accuracy for DCIS and PCM. 
 Methods: The MRI morphology confirmed by surgical pathology and dynamic enhancement for 35 patients with DCIS and 45 patients with PCM were retrospectively analyzed, which included T1 pre-scan high signal, enhanced distribution characteristics, internal strengthening mode, whether centrifugation or centripetal diffusion, dynamic enhancement curve morphology, diffusion-weighted imaging (DWI) signal characteristics, and apparent diffusion coefficient (ADC) values. 
 Results: The segmental distribution, clustered ring, T1 pre-catheters diffusion and the dynamic delayed concentric diffusion were more common in DCIS than those in PCM (P<0.05). Regional distribution, internal heterogeneity enhancement, and enhanced delay period eccentric diffusion were more common in PCM than those in DCIS (P<0.05). In the PCM group, nipple repertoire, DWI center high signal, adjacent skin thickening, and sinus formation were significantly higher than those in the DCIS group (P<0.05).
 Conclusion: Both DCIS and PCM show a non-mass like enhancement on MRI. Images in DCIS mostly show duct-like, branch-like and segment-like distribution. The internal enhancement mode is centripetal diffusion. Images in PCM mostly show regional distribution, and the inside displays heterogeneity enhancement with the adjacent skin thickening and nipple subsided.
Breast Neoplasms ; diagnostic imaging ; Carcinoma, Ductal, Breast ; diagnostic imaging ; Contrast Media ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging ; Mastitis ; diagnostic imaging ; Plasma Cells ; pathology ; Retrospective Studies

PURPOSE: To report a case of immunoglobulin G4 (IgG4)-related ophthalmic disease associated with adult xanthogranulomatous disease. CASE SUMMARY: A 38-year-old male with a history of cholecystectomy visited our clinic for bilateral periorbital swelling. Histopathology of the orbital biopsy showed diffuse infiltration of foamy histiocytes with Touton giant cells and lymphoid follicles, with a diagnosis of adult-onset xanthogranuloma. After excisional biopsy, he was treated with azathioprine and prednisolone. Four years after treatment, he again visited the clinic due to bilateral, yellowish eyelid masses. Serological examinations were all nonspecific findings, except for elevation of IgG and IgG4 levels. Magnetic resonance imaging showed bilateral symmetric soft tissue enlargement with slightly heterogeneous T1/T2 isosignal intensity, with contrast enhancement at the superolateral aspect of extraconal spaces. Excisional biopsy and blepharoplasty were performed. Immunohistochemical sections showed that the IgG4+/IgG plasma cell ratio was 10–20% and the IgG4 plasma cell count was 22/high power field (HPF). His past sections of 2013 from the pathology department were again stained and showed that the IgG4+/IgG plasma cell ratio was 40–50% and the IgG4 plasma cell count was 59/HPF. Thus, he was definitely diagnosed with IgG4-related ophthalmic disease. CONCLUSIONS: If there is recurrent eyelid swelling, IgG4-related ophthalmic disease should be considered as a differential diagnosis. And the patient with adult xanthogranulomatous disease can be diagnosed with IgG4-related ophthalmic disease.
Adult ; Azathioprine ; Biopsy ; Blepharoplasty ; Cholecystectomy ; Diagnosis ; Diagnosis, Differential ; Eyelids ; Giant Cells ; Histiocytes ; Humans ; Immunoglobulin G ; Immunoglobulins ; Magnetic Resonance Imaging ; Male ; Orbit ; Pathology ; Plasma Cells ; Prednisolone

A collection of plasma cells in the skin can represent a broad spectrum of disease entities. Secondary syphilis, primary cutaneous plasmacytoma, primary cutaneous plasmacytosis, cutaneous lymphoid hyperplasia and nodular amyloidosis are considered possible differential diagnoses. The primary cutaneous plasma cell disorders can range from malignant to benign plasma cell neoplasms. The malignant conditions are neoplastic diseases having monoclonal proliferations, rapid progression and fatal outcome while the benign plasma cell disorders usually show polyclonality, chronicity and benign process, including plasmacytosis. We present a case of cutaneous plasmacytosis. The patient was a 34-year-old man, presented with disseminated reddish-brown plaques and nodules on the right side of the hips, inguinal groove, and the thigh. Histopathologically, mature plasma cells perivascular infiltrates were observed mainly in the dermis. Polyclonality of infiltrating plasma cells with coexistence of both kappa and gamma chain-positive cells demonstrated with immunohistochemistry, as well as CD20+++, CD38++++, CD79a++++, CD138++, Ki67<30%. The diagnosis, cutaneous plasmacytosis, was established by the pertinent laboratory findings. Primary cutaneous plasmacytosis was an uncommon reactive lymphoplasmacytic disorder of uncertain etiology. Cutaneous plasmacytosis is a rare disease characterized by peculiar multiple eruptions and hyper gamma globulinemia. It has been mainly described in patients of Japanese descent, with only few reports in Caucasians and Chinese, although information concerning the disorder was limited to individual case reports. Cutaneous plasmacytosis is a rare disorder, which is characterized by multiple red to dark-brown nodules and plaques on the trunk and usually associated with polyclonal hyper gamma globulinaemia. Primary cutaneous plasmacytosis or cutaneous plasmacytosis was thought to be a reactive process with unknown etiology. Histologically, lesions contain dense perivascular infiltration of mature polyclonal plasma cells without any atypia, in the dermis and subcutaneous fat. The clinical course is chronic and benign without spontaneous remission. Available treatments for cutaneous plasmacytosis include psoralen ultraviolet A radiotherapy, systemic chemotherapy and intralesional steroid injection. The patient with cutaneous plasmacytosis in this report was treated with tacrolimus ointment and psoralen ultraviolet A.
Adult ; Humans ; Hyperplasia ; Immunosuppressive Agents/therapeutic use* ; Male ; Plasma Cells ; Plasmacytoma/immunology* ; Skin/pathology* ; Skin Diseases/immunology* ; Tacrolimus/therapeutic use*

OBJECTIVETo investigate whether plasma from patients with systemic lupus erythematosus (SLE) inhibits the suppressive effects of mesenchymal stem cells (MSCs) on lupus B lymphocytes.

METHODSMSCs isolated and expanded from the bone marrow of healthy donors were co-cultured with B cells purified from the peripheral blood of SLE patients in the presence of fetal bovine serum or pooled plasma from SLE patients, and the proliferation and maturation of the B lymphocytes were analyzed.

RESULTSs Co-culture with normal MSCs obviously inhibited the proliferation of lupus B cells and suppressed the maturation of B lymphocytes, which showed lowered expressions of CD27 and CD38. The pooled plasma from SLE patients significantly inhibited the suppressive effects of normal MSCs on B cell proliferation and maturation.

CONCLUSIONPlasma from SLE patients negatively modulates the effects of normal MSCs in suppressing lupus B cell proliferation and maturation to affect the therapeutic effect of MSC transplantation for treatment of SLE. Double filtration plasmapheresis may therefore prove beneficial to enhance the therapeutic effects of MSC transplantation for SLE.

B-Lymphocytes ; pathology ; Cell Proliferation ; Coculture Techniques ; Humans ; Lupus Erythematosus, Systemic ; blood ; Lymphocyte Activation ; Mesenchymal Stromal Cells ; cytology ; Plasma

Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration’s approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab. In concert with the technical advances in the cytogenetic and molecular diagnostics of MM, modifications of its diagnosis and staging system have been attempted for better risk stratification. The modified diagnostic criteria from the International Myeloma Working Group in 2014 enabled a strategy of more active treatment for some patients with smoldering MM, with an ultra-high risk of progression, and fine-tuned the definition of end-organ damage, known as CRAB (hypercalcemia, renal insufficiency, anemia, and bone lesions). Considering Korea’s trend of aging at an unprecedented rate, we can expect that the ASR of MM will maintain a gradual increase for many years to come; therefore, MM will be a cancer of critical importance from both medical and socioeconomic perspectives in Korea.
Aging ; Anemia ; Asian Continental Ancestry Group ; Cytogenetics ; Diagnosis ; Epidemiology ; Humans ; Incidence ; Korea ; Multiple Myeloma* ; Neoplasm Staging ; Pathology, Molecular ; Plasma Cells ; Renal Insufficiency