Humoral and Cellular Immunology in Human Prostate Cancer: Plasma Cells and T and B Lymphocytes / Inmunología Humoral y Celular en el Cáncer de Próstata Humano: Células Plasmáticas y Linfocitos T y B

SUMMARY: In solid and malignant tumors, innate and adaptive immunity are combined in antitumor responses. This study aimed to analyze the activation of plasma cells and the correlation between the infiltration of B and T lymphocytes with the degree of malignancy or Gleason grade in human prostate biopsies diagnosed with cancer. Prostate cancer biopsies were obtained from the Clinical Hospital of Universidad de Chile (n=70), according to the bioethical norms of the institution. Histological sections of 5µm thickness were processed for immunohistochemistry with primary antibodies against BL and total TL (HRP/DAB). Recognition and quantification were performed under a Leica DM750 optical microscope. Microsoft Excel and GraphPad software were used for the statistical study. Correlation coefficient (Pearson) and mean comparison tests (Kruskal-Wallis and Dunn) and p≤ 0.05 were developed. B and T lymphocyte populations were inversely interregulated in prostate cancer (Gleason) (r= -0.46). Their relationship with Gleason grade is variable according to lymphocyte type (LB vs. Gleason r= -0.0.47 and LT vs. Gleason r= -0.21). Histological diagnosis of prostate cancer correlates with a predominance of LT. The malignancy of the pathology correlates with a predominance of LTs, according to the Gleason grade. The increased knowledge of B and T lymphocyte infiltration and plasma cell activation could be used to better target clinical trials on treatments based on immune system responses. Immunotherapy could be a new paradigm to apply better antitumor therapy strategies.

En tumores sólidos y malignos, la inmunidad innata y adaptativa se combinan en respuestas antitumorales. Este estudio tuvo como objetivo analizar la activación de células plasmáticas y la correlación entre la infiltración de linfocitos B y T con el grado de malignidad o grado de Gleason en biopsias de próstata humana diagnosticadas con cáncer. Las biopsias de cáncer de próstata se obtuvieron del Hospital Clínico de la Universidad de Chile (n=70), de acuerdo con las normas bioéticas de la institución. Secciones histológicas de 5 µm de espesor fueron procesadas para inmunohistoquímica con anticuerpos primarios contra LB y LT total (HRP/DAB). El reconocimiento y las cuantificaciones se realizaron bajo un microscopio óptico Leica DM750. Para el estudio estadístico se utilizaron los programas Microsoft Excel y GraphPad. Se desarrollaron pruebas de coeficiente de correlación (Pearson) y comparación de medias (Kruskal-Wallis y Dunn) y p≤ 0.05. Los resultados muestran que las poblaciones de linfocitos B y T están inversamente interreguladas en el cáncer de próstata (r= -0,4578). Su relación con el grado de Gleason es variable según el tipo de linfocito (LB vs Gleason r= -0,47* y LT vs Gleason r= -0,21). Se concluye que la malignidad del cáncer de próstata se correlaciona con un predominio de LT, versus el grado de Gleason. El mayor conocimiento de la infiltración de linfocitos B y T y la activación de células plasmáticas podría aprovecharse para una mejor orientación de ensayos clínicos en tratamientos basados en las respuestas del sistema inmunitario. La inmunoterapia podría ser un nuevo paradigma para aplicar mejores estrategias de terapias antitumorales.

Amiloidose nodular - relato de rara apresentação da amiloidose localizada cutânea / Nodular amyloidosis - report of a rare presentation of cutaneous localized amyloidosis

Contexto: Amiloidose é um grupo de doenças caracterizadas pelo depósito de proteínas fibrilares, denominadas substância amiloide. Podem ser divididas em formas localizadas ou sistêmicas, sendo que dentre as localizadas, a forma nodular é a mais rara. Descrição do caso: Relatamos o caso de amiloidose primária localizada cutânea nodular que se apresentou com nódulos violáceos no dorso, e placas acastanhadas na região cervical há 8 anos sem evidências de envolvimento sistêmico. Discussão: Como cerca de 1% a 7% dos casos de amiloidose nodular localizada cutânea podem evoluir com envolvimento sistêmico, o seguimento dos pacientes faz-se necessário. O tratamento não é obrigatório, a retirada das lesões pode ser feita se o paciente o desejar, contudo as recidivas são frequentes. Conclusões: Mesmo possuindo baixa prevalência, a amiloidose nodular deve ser reconhecida pelo risco de progredir para acometimento sistêmico e associação com discrasias plasmocitárias, como mieloma múltiplo.

Dermatosis con infiltrados plasmocitarios, ¿secundaria a queratosis actínica? / Dermatosis with plasma cell infiltration, secondary to actinic keratosis? / Dermatose com infiltrados plasmocíticos, secundária a queratose actínica?

Las dermatosis plasmocitarias son un conjunto de enfermedades inflamatorias poco frecuentes, cuyo diagnóstico definitivo se realiza mediante el hallazgo histopatológico de un infiltrado dérmico de células plasmáticas policlonales sin una causa subyacente demostrable. Presentamos el caso de una mujer de 89 años que desarrolló en la evolución de una queratosis actínica un infiltrado plasmocitario denso. Hasta esta publicación no se han encontrado reportes de casos de dermatosis plasmocitaria secundaria a queratosis actínica.

Cutaneous plasmacytosis is an uncommon cutaneous disorder, the final diagnosis of which is done when cutaneous polyclonal plasma cell skin infiltrations without underlying proven causes are found. The study presents the case of an 89-year-old patient with actinic keratosis who developed dense plasma cell infiltration. There were no case reports of cutaneous plasmacytosis secondary to actinic keratosis in literature until this study was published.

As dermatoses plasmocitárias constituem um grupo de doenças inflamatórias raras, cujo diagnóstico definitivo é feito pelo achado histopatológico de um infiltrado dérmico de plasmócitos policlonais sem causa subjacente demonstrável. Apresentamos o caso de uma mulher de 89 anos que desenvolveu um infiltrado plasmocítico denso durante o curso de queratose actínica. Até esta publicação, não havia relato de caso de dermatose plasmocitária secundária a queratose actínica.

Plasma cell cheilitis in an elderly female: A case report

Introduction@#Plasma cell cheilitis (PCC) is a rare, chronic inflammatory dermatitis of unknown etiology. Due to the limited number of cases reported, no guidelines have been established for its treatment. We present a case of PCC clinically similar to actinic cheilitis or mucosal lichen planus, and squamous cell carcinoma but showed response to topical tacrolimus 0.1% ointment. @*Case Report@#A 62-year-old female with extreme fondness to piping hot food presented with a solitary painful ulceration with some pustules and bleeding on the lower lip with three (3) months duration. Skin punch biopsy revealed a dense band-like infiltrate of plasma cells which is consistent with Plasma cell cheilitis. The patient was given tacrolimus 0.1% ointment and showed significant improvement after a month of treatment.@*Conclusion@#PCC is a rare condition that should still be considered in patients presenting with persistent cheilitis. Clinical and histological correlation is advised for proper management and prognostication.

Pathological significance of plasma cell infiltration in diagnosing lymph node diseases / 中华病理学杂志

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.

Research Progress of Regulatory T Cells in the Pathogenesis of Multiple Myeloma --Review / 中国实验血液学杂志

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.

Plasmocitoma extramedular de canal auditivo externo: caso clínico / Extramedullary plasmacytoma of external auditory canal: a case report

Resumen El plasmocitoma extramedular es una neoplasia de células plasmáticas poco frecuente, que se ubica en 80% a 90% de los casos en la cabeza o cuello. Esta neoplasia representa menos del 1% de toda la patología maligna de cabeza y cuello. Dada la poca frecuencia de la patología y la escasez de casos publicados, esta entidad presenta una gran dificultad clínica y terapéutica. El diagnóstico se basa en el análisis histológico con inmunohistoquímica de la muestra obtenida, y el tratamiento varía según la ubicación, donde se puede realizar radioterapia o cirugía. En este artículo presentamos el caso de una paciente de 56 años, con antecedentes de otorrea de larga data en oído derecho, al examen físico presentaba un tumor que obstruía todo el conducto auditivo externo. Se realizó exéresis tumoral y la biopsia evidenció un plasmocitoma.

Abstract Extramedullary plasmacytoma is a rare plasma cell neoplasm, affecting 80% to 90% of the head or neck. This neoplasm represents less than 1% of all malignant head and neck pathology. Given the infrequency of the pathology and the scarcity of published cases, this entity presents great clinical and therapeutic difficulty. Diagnosis is based on histology and immunohistochemistry and treatment varies depending on the location, where radiation therapy or surgery can be performed. In this article, we present the case of a 56-year-old patient with a history of long-standing otorrhea in the right ear. Physical examination presented a tumor that obstructed the entire external auditory canal. Tumor excision was performed, and the biopsy revealed a plasmacytoma.

Detección y cuantificación de células plasmáticas (plasmocitos) en granulomas periapicales inducidos experimentalmente en ratas / Detection and quantification of plasma cells in experimentally induced rat periapical granulomas

Objetivo: En los granulomas periapicales, los plasmocitos (PL) participan activamente mediante la liberación de inmunoglobulinas. El propósito de este ensayo fue identificar y contar el número de PL en diferentes períodos de tiempo en lesiones periapicales experimentales en ratas. Materiales y métodos: Mediante la exposición al medio oral de la pulpa de los primeros molares inferiores izquierdos, se indujeron granulomas periapicales en ratas a las que previamente se les suministró anestesia. La pulpa de los primeros molares inferiores derechos no fue expuesta, y estos dientes se utilizaron como control. Los animales fueron eutanasiados a los 10, 30 y 60 días de la exposición. Los maxilares inferiores fueron removidos, y los primeros molares, junto con los tejidos circundantes, se procesaron para su estudio histológico. Se obtuvieron secciones semiseriadas, posteriormente coloreadas con verde de metilo-pironina (VMP). Cada tres secciones, las tres siguientes fueron coloreadas con hematoxilina y eosina (H-E). Los controles también fueron coloreados con H-E. Resultados: Todos los especímenes experimentales coloreados con H-E revelaron la presencia de granulomas periapicales. Luego de la exposición pulpar, el número de PL que reaccionó positivamente al VMP se incrementó de manera progresiva desde el día 10 hasta los días 30 y 60. A pesar de que a los 60 días el número de PL fue ligeramente menor que a los 30 días, no hubo diferencias estadísticamente significativas entre estos dos períodos. Los especímenes del grupo control coloreados con H-E mostraron que los tejidos periapicales se encontraban dentro de los parámetros normales en todos los períodos de observación. Conclusiones: Los resultados de este estudio revelaron que el número de plasmocitos VMP positivos se incrementa progresivamente en función del tiempo transcurrido pero se estabiliza al finalizar el experimento. También sugieren que el empleo de la coloración de VMP es un procedimiento adecuado para la identificación y la cuantificación de plasmocitos en los granulomas periapicales inducidos experimentalmente en ratas (AU)

Aim: Plasma cells (PL) release immunoglobulin in periapical lesions. The purpose of this assay was to identify and count the number of plasmocytes observed in periapical lesions in rats. Materials and methods: By exposing the pulp of the lower left first molars to the oral environment, periapical granulomas were induced in rats previously anesthetized. The pulp of right mandibular first molars was not exposed and these teeth were used as negative controls. The animals were euthanized at 10, 30 and 60 days after pup exposure. The mandibles were removed and specimens of the molar teeth along with the surrounding tissues were prepared for histology. Semi serial sections of the left first molar were stained with methyl green pyronine (MGP). Every three sections, the following three sections were stained with hematoxilyn and eosin (H-E). Negative control samples were stained with H-E. Results: All the H-E stained experimental samples revealed the presence of periapical granulomas. After pulp exposure, the number of PL increased from day 10 to 30 and 60. In the 60-day samples the number of PL was slightly less than that of the 30-day samples, with no statistically significant difference. The H-E stained control samples showed normal periapical tissues in all observation periods. Conclusions: The results of this study revealed that the number of VMP positive PL, increased progressively with time but it was stabilized at the end of the experiment. In addition, the results suggest that the use of VMP stain is a suitable procedure for the identification and counting of PL in experimentally induced periapical granulomas in rats (AU)

Inflammatory infiltrates in melanocytic lesions / Infiltrados inflamatorios en lesiones melanocíticas

SUMMARY: Inflammatory infiltrates are frequently present in melanocytic lesions, with different distribution and composition. Much attention has been devoted to tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment, establishing their prognostic and predictive value in many malignancies, including melanoma. However, lymphocytes, albeit the most numerous and consistent presence, constitute only part of the immune microenvironment. Other inflammatory cells, including neutrophils, plasma cells, eosinophils and mast cells, are found in melanoma and other melanocytic lesions.Few studies offer a detailed count of these inflammatory infiltrates across the spectrum of melanocytic lesions. By using whole slide image analysis and open source software, in the present study we report the enumeration of different inflammatory infiltrates in benign melanocytic nevi, dysplastic nevi, melanoma in situ and invasive malignant melanomas. Significant higher numbers of plasma cells and neutrophils were observed in melanoma. These results indicate that composition of the inflammatory infiltrate may contribute to the diagnostic algorithm of melanocytic lesions.

RESUMEN: Los infiltrados inflamatorios están presentes con frecuencia en las lesiones melanocíticas, con diferente distribución y composición. Se ha prestado mucha atención a los linfocitos infiltrantes de tumores (TIL) en el microambiente tumoral, estableciendo su valor pronóstico y predictivo en muchas neoplasias malignas, incluido el melanoma. Sin embargo, los linfocitos de presencia más numerosa y constante, constituyen solo una parte del microambiente inmunológico. Otras células inflamatorias, incluidos neutrófilos, células plasmáticas, eosinófilos y mastocitos, se encuentran en el melanoma y otras lesiones melanocíticas. Pocos estudios ofrecen un recuento detallado de estos infiltrados inflamatorios en todo el espectro de lesiones melanocíticas. Mediante el uso de análisis de imágenes de diapositivas completas y software de código abierto, en el presente estudio informamos la enumeración de diferentes infiltrados inflamatorios en nevos melanocíticos benignos, nevos displásicos, melanoma in situ y melanomas malignos invasivos. Se observaron números significativamente más altos de células plasmáticas y neutrófilos en el melanoma. Estos resultados indican que la composición del infiltrado inflamatorio puede contribuir al algoritmo diagnóstico de las lesiones melanocíticas.

Solitary plasmacytoma of mandible: an unusual bilateral presentation

Plasmacytoma is a neoplastic proliferation of monoclonal plasma cells, which can present clinically as solitary bone neoplasm, extramedullary plasmacytoma, and multiple myeloma. The biological behavior of these tumors is variable from periods of clinical latency to rapid growth and progression from localized forms to more disseminated multiple myeloma. We present the case of solitary plasmacytoma of the mandible with rare bilateral involvement in a 65-year-old female patient. This paper highlights the importance of understanding the maxillofacial manifestations of the disease by the dentist for early diagnosis and thus better prognosis.

The Significance of CD319 and CD269 in the Detection of Immunophenotyping and Minimal Residual Disease in Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CD319 and CD269 in plasma cells of patients with multiple myeloma (MM) and the feasibility of using CD319 instead of CD38 as a gating antigen in immunophenotyping and minimal residual disease (MRD) monitoring.@*METHODS@#The expression levels of CD319 and CD269 antigens in clonal bone marrow plasma cells of 387 patients were detected by CD38/CD138 gating strategy with 8-color flow cytometry, and the stability of antigens was also analyzed, and the sensitivity and correlation of two different gating strategies employing CD319/CD138 and CD38/CD138 were compared as well. The control group consisted of 53 cases with non-malignant blood disease matched by age and sex.@*RESULTS@#Monoclonal plasma cells were detected in 303 of 387 MM patients, among which 277 cases (91.42%) were positive for CD269, and all cases were positive for CD319 (100%). In newly diagnosed MM (NDMM) and recurrent refractory MM (RRMM) patients, the expression levels of CD269 were 97.53% (0-99.92%) and 94.96% (0.22%-99.99%), respectively, while levels of CD319 were 99.90% (87.77%-100%) and 99.78% (63.12%-100%), respectively. The expression levels of CD269 and CD319 in the control group were 97.00% (77.00%-100%) and 100% (89.00%-100%), respectively. There were no significant differences in the expression levels of CD269 and CD319 among NDMM, RRMM and the control group. Patients acquiring therapeutic effects were divided into complete remission (CR) group, very good partial response (VGPR) group and partial response (PR) group. Gating with CD38/CD138, median MRD values were 0.76% (0-1.88%), 0.77% (0-4.96%) and 1.75% (0.09%-10.90%) in the three groups, respectively, while gating with CD319/CD138, median MRD values were 0.57% (0.18%-1.96%), 1.07% (0.12%-4.85%) and 1.77% (0.08%-8.22%), respectively. There was no significant difference in MRD level by the two gating strategies, but a good correlation between the two (r=0.808, P<0.05). In addition, in 4 patients treated by CD38 monoclonal antibody (DARA), the expression level of CD38 was observed to be down-regulated or even negative after treatment. When the MRD level was very low, CD38/CD138 gating resulted in false MRD@*CONCLUSION@#CD319 and CD269 express stably and continuously in plasma cells of MM patients at different disease stages. CD319 can be used as an alternative of CD38 for immunophenotyping and MRD detection, especially for MRD detection after DARA treatment, while CD269 is suitable for detection before BCMA-CAR-T treatment.

Plasmocitosis cutánea: a propósito de un caso / Cutaneous Plasmacytosis: about a case

RESUMEN La plasmocitosis cutánea es una enfermedad poco frecuente, de curso crónico y benigno, que predomina en hombres entre los 20 y 62 años, particularmente en poblaciones asiáticas. Presentamos un caso de un hombre colombianoquien presentabamáculas y placas pardo-violáceas de bordes definidos, ligeramente infiltradas en tórax posterior y dorso de pies, sin otroshallazgos. Debido a que es una enfermedad que puede tener manifestaciones extracutáneaso transformación maligna por infiltración de células plasmáticas en otros órganos, se realizaron estudios de extensión que determinaron en este paciente que el compromiso era exclusivamente cutáneo. No existe un tratamiento estándar para esta enfermedad, se han usado antibióticos, corticosteroides tópicos y sistémicos, tacrolimus tópico, quimioterapia, talidomida, fototerapia UVB de banda estrecha y azatioprina, con resultados variables.

SUMMARY Cutaneous plasmacytosis is a rare disease of chronic and benign course, which occurs more frequently in men between 20 and 62 years, particularly in Asian populations. We present the case of a Colombian man who presents macules and violet-brown patches with defined edges, slightly infiltrated in the posterior thorax and feet, without any other manifestation. Because it is a disease that can have extracutaneous manifestations or malignant transformation due to the infiltration of plasma cells in other organs, extension studies were carried out, which determinedwhich determined exclusive cutaneous involvement. There is no standard treatment for this disease, antibiotics, topical and systemic corticosteroids, topical tacrolimus, chemotherapy, thalidomide, narrow-band UVB treatment and azathioprine have been used with variable results.

Review of a novel disease entity, immunoglobulin G4-related disease

Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.

Differences of B cells, plasma cells, and related cytokines expression in gingival tissues between periodontitis and periodontal healthy subjects / 华西口腔医学杂志

OBJECTIVE@#This study aimed to compare the differences of B cells, plasma cells, and related cytokines expression in gingival tissues between periodontitis and periodontal healthy subjects.@*METHODS@#Gingival tissues were collected from periodontal healthy subjects (periodontal healthy group, n=12) and periodontitis patients (periodontitis group, n=15). Hematoxylin-eosin (HE) staining was used for histopathological examination. Immunohistochemical staining (CD19, CD38, and CD138) was applied to detect the expression of B cells and plasma cells. B cell-activating factor (BAFF) and soluble receptor activator of nuclear factor-κB ligand (sRANKL) were detected by enzyme-linked immunosorbent assay.@*RESULTS@#Extensive inflam-matory cell infiltration was found in the gingival tissues of the periodontitis group. The number of CD19(+), CD38(+), and CD138(+) cells of the periodontitis group was significantly higher than that of the periodontal healthy group (P<0.000 1). BAFF and sRANKL levels of the periodontitis group were higher than those of the periodontal healthy group (P<0.01, P<
0.001, respectively).@*CONCLUSIONS@#The expression of B cells, plasma cells, and their related BAFF and sRANKL cytokines were significantly higher in periodon-titis patients than those in the periodontal healthy subjects, sug-gesting that B cells and plasma cells may be involved in the development of periodontitis.

Clinical, Laboratory, and Bone Marrow Findings of 31 Patients With Waldenström Macroglobulinemia

BACKGROUND: Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma (LPL) with bone marrow (BM) involvement and an IgM monoclonal gammopathy of any level. We aimed to identify the clinical, laboratory, and BM findings of patients with WM and to evaluate the usefulness of CD154 for the diagnosis and prognosis of WM.METHODS: We reviewed the medical records and BM studies and/or flow cytometric immunotyping of 31 patients with untreated WM. Semiquantitative immunohistochemistry (CD20, CD138, tryptase, and CD154) of BM was performed.RESULTS: Only six patients presented with symptoms of hyperviscosity syndrome. Eleven patients had solid cancer and/or another hematologic malignancy. Mast cells (MC) increased in all samples, with some in close contact with tumor cells. Tryptase-positive MC (17.1/ high-power fields [HPF], 1.2–72.0/HPF) and CD154-positive MC (8.6/HPF, 0.1–31.1/HPF) were observed. The high CD154-positive MC (≥8.6/HPF) group showed a lower overall five-year survival rate than the low CD154-positive MC (<8.6/HPF) group (71.9% vs. 100.0%; P=0.012). Flow cytometric immunophenotyping of BM aspirates showed increased B lymphocytes and plasma cells with a normal phenotype (CD138⁺/CD38⁺/CD19⁺/CD45⁺/CD56⁻).CONCLUSIONS: Approximately one third of WM patients showed other malignancies and all patients had increased MC. Immunohistochemistry and flow cytometric immunophenotyping are useful for diagnosing WM, and increased CD154-positive MC can indicate poor prognosis.

Impact of the Long-Lived Plasma Cells in Patients With Chronic Rhinosinusitis With Nasal Polyps

No abstract available.

Evidence for the Presence of Long-Lived Plasma Cells in Nasal Polyps

PURPOSE: Plasma cells and immunoglobulins (Igs) play a pivotal role in the induction and maintenance of chronic inflammation in nasal polyps. During secondary immune responses, plasma cell survival and Ig production are regulated by the local environment. The purpose of the present study was to investigate the presence of long-lived plasma cells (LLPCs) and specific survival niches for LLPCs in human nasal polyps.METHODS: Nasal mucosal samples were cultured with an air-liquid interface system and the Ig levels in culture supernatants were analyzed by enzyme-linked immunosorbent assay. The characteristics of LLPCs in nasal polyps were determined by immunohistochemistry and immunofluorescence. The expression of neurotrophins as well as their receptors was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blotting.RESULTS: The numbers of CD138⁺ total plasma cells and BCL2⁺ plasma cells were increased in both eosinophilic and non-eosinophilic nasal polyps compared with those in normal tissues. The production of IgG, IgA, and IgE was detected in culture supernatants even after a 32-day culture of nasal polyps. Although the total numbers of plasma cells were decreased in nasal polyps after culture, the numbers of BCL2⁺ plasma cells remained stable. The expression of nerve growth factor (NGF) as well as tropomyosin receptor kinase (Trk) A, a high-affinity receptor for NGF, was upregulated in both eosinophilic and non-eosinophilic nasal polyps. In addition, BCL2⁺ plasma cell numbers were positively correlated with NGF and TrkA mRNA expression in nasal mucosal tissues. Polyp plasma cells had the expression of TrkA.CONCLUSIONS: Human nasal polyps harbor a population of LLPCs and NGF may be involved in their prolonged survival. LLPCs may be a novel therapeutic target for suppressing the local Ig production in nasal polyps.

Plasma cell cheilitis: the diagnosis of a disorder mimicking lip cancer

Plasma cell cheilitis (PCC) is an inflammatory disorder of unknown etiology that affects the lip. It is characterized histologically by a dense infiltrate of plasma cells with a variety of clinical features. The response to different therapeutic modalities is controversial, especially regarding the effectiveness of corticosteroids. We present a case of a 56-year-old Caucasian man with a painful ulcerated and crusted area in the lower lip, resembling a squamous cell carcinoma or actinic cheilitis. Topical corticosteroid was used for one week, which resulted in partial regression and motivated a biopsy. The histological examination provided the diagnosis of PCC. The patient has been disease-free for six months. We also provide a discussion on the criteria of differential diagnosis and management of this rare condition.

A Case of Hepatic Inflammatory Pseudotumor Occurred in a Patient with Lupus Nephritis

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affecting various organs. Among its manifestations, inflammatory pseudotumor (IPT) is an extremely rare disease about which no case has been reported of it occurring in the liver. We present a case of a SLE patient with hepatic IPT (hIPT) successfully treated with immunosuppressants. A 16-year-old male with elevated liver enzymes visited our clinic and was diagnosed as SLE. Although no lesion was observed in the initial abdomen ultrasonography, the abdominal CT on hospital day 7 revealed a new hepatic mass resembling an abscess. Despite 5 weeks of antibiotics treatment, the hepatic mass remained, and was re-diagnosed as hIPT secondary to SLE with an abdominal MRI. After high dose prednisolone and mycophenolate mofetil treatment, lupus activity subsided and hIPT disappeared in the follow-up CT. This case suggests that hIPT should be considered as a differential diagnosis among hepatic mass in SLE patients.

Primary Necrobiotic Xanthogranulomatous Sialadenitis with Submandibular Gland Localization without Skin Involvement

Necrobiotic xanthogranulomatous reaction is a multiorgan, non-Langerhans cell histiocytosis with an unknown etiology. Occurrence in the salivary gland is extremely rare. We recently identified a case of necrobiotic xanthogranulomatous sialadenitis in a 73-year-old Korean woman who presented with a painless palpable lesion in the chin. There was no accompanying cutaneous lesion. Partial resection and subsequent wide excision with neck dissection were performed. Pathological examination showed a severe inflammatory lesion that included foamy macrophages centrally admixed with neutrophils, eosinophils, lymphocytes, plasma cells, and scattered giant cells, as well as necrobiosis. During the 12-month postoperative period, no grossly remarkable change in size was noted. Necrobiotic xanthogranulomatous inflammation may be preceded by or combined with hematologic malignancy. Although rare, clinicians and radiologists should be aware that an adhesive necrobiotic xanthogranuloma in the salivary gland may present with a mass-like lesion. Further evaluation for hematologic disease and close follow-up are needed when a pathologic diagnosis is made.