Human follicular helper T lymphocytes critical players in antibody responses / Linfócitos T auxiliares foliculares humanos: células essenciais para a resposta de anticorpos

ABSTRACT Follicular helper T lymphocytes are a subpopulation of CD4+ T lymphocytes initially identified in germinal centers of follicles found in secondary lymphoid organs. The primary function of follicular helper T lymphocytes is to help B lymphocytes' antibody production. Changing of antibody class and affinity, B cell differentiation and memory generation depend on cooperation between follicular helper T lymphocytes and B cells. In blood, follicular helper T lymphocytes are called circulating follicular helper T lymphocytes. They are considered to have specificities similar to those developed in the secondary lymphoid organs. The phenotype of human follicular helper T lymphocytes is given by simultaneous expression of the markers CXCR5, Bcl-6, CD40L, PD-1, and ICOS. In germinal centers, follicular helper T lymphocytes synthesize interleukin 21 as predominant cytokine. In blood, subpopulations of circulating follicular helper T lymphocytes can be recognized, with different expressions of the classical follicular helper T lymphocytes markers and, in addition, can express other markers such as CXCR3 and CCR6. Presently, there is great interest in follicular helper T lymphocytes and circulating follicular helper T lymphocytes in vaccination studies as indicators of immunization efficacy. In addition, follicular helper T lymphocytes are investigated as possible markers of activity in many diseases and potential therapeutic intervention. This short review describes aspects of immunobiology and quantification of follicular helper T lymphocytes and circulating follicular helper T lymphocytes, and presents a few examples of related findings in systemic lupus erythematosus, rheumatoid arthritis, HIV infection and vaccination.

RESUMO Linfócitos T auxiliares foliculares são uma subpopulação de linfócitos T CD4+ identificada inicialmente nos centros germinativos dos folículos dos órgãos linfoides secundários. Sua função primordial é auxiliar os linfócitos B na produção de anticorpos. A mudança de classe e de afinidade dos anticorpos, a diferenciação das células B e a geração de memória dependem da cooperação entre os linfócitos T auxiliares foliculares e as células B. No sangue, recebem o nome de linfócitos T auxiliares circulantes. Considera-se que possuem especificidades semelhantes às desenvolvidas nos órgãos linfoides secundários. O fenótipo dos linfócitos T auxiliares humanos é dado pela expressão conjunta dos marcadores CXCR5, Bcl-6, CD40L, PD-1 e ICOS. Nos folículos, linfócitos T auxiliares sintetizam a interleucina 21 como citocina predominante. No sangue, são descritas várias subpopulações de linfócitos T auxiliares circulantes com expressões variadas dos marcadores clássicos de linfócitos T auxiliares, além de poderem agregar outros, como CXCR3 e CCR6. Existe um enorme interesse no estudo de linfócitos T auxiliares e linfócitos T auxiliares circulantes, para a avaliação de eficácia de vacinação. São também investigados como possíveis marcadores de atividade em muitas doenças e potenciais intervenções terapêuticas. Esta breve revisão descreve aspectos da imunobiologia e da quantificação de linfócitos T auxiliares humanos e linfócitos T auxiliares circulantes, além de apresentar alguns achados relacionados em lúpus eritematoso sistêmico, artrite reumatoide, infecção por HIV e vacinação.

Methionyl-tRNA Synthetase is a Useful Diagnostic Marker for Lymph Node Metastasis in Non-Small Cell Lung Cancer

PURPOSE: Identification of lymph node (LN) metastasis in non-small cell lung cancer (NSCLC) is critical for disease staging and selection of therapeutic modalities. Sometimes it is not possible to obtain LN core tissue by endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA), resulting in low diagnostic yield. MATERIALS AND METHODS: In this study, 138 specimens were collected from 108 patients who underwent EBUS-TBNA under the suspicion of LN metastasis of NSCLC. Diagnostic yields of anti-CD45 and anti-methionyl-tRNA synthetase (MRS), immunofluorescent (IF) staining on cytology specimens were compared with those of conventional cytology and positron emission tomography-computed tomography (PET-CT). RESULTS: MRS was strongly expressed in NSCLC cells metastasized to LNs, but weakly expressed in cells at the periphery of the LN germinal center. The majority of cells were CD20 positive, although a few cells were either CD3 or CD14 positive, indicating that CD45 staining is required for discrimination of non-malignant LN constituent cells from NSCLC cells. When the diagnostic efficacy of MRS/CD45 IF staining was evaluated using 138 LN cellular aspirates from 108 patients through EBUS-TBNA, the sensitivity was 76.7% and specificity was 90.8%, whereas those of conventional cytology test were 71.8% and 100.0%, respectively. Combining the results of conventional cytology testing and those of PET-CT showed a sensitivity and specificity of 71.6% and 100%, and the addition of MRS/CD45 dual IF data to this combination increased sensitivity and specificity to 85.1% and 97.8%, respectively. CONCLUSION: MRS/CD45 dual IF staining showed good diagnostic performance and may be a good tool complementing conventional cytology test for determining LN metastasis of NSCLC.

Role of immunoreactive patterns of lymph nodes in neck dissection cases of oral squamous cell carcinoma: a clinical and histopathological study

OBJECTIVES: Metastasis in oral squamous cell carcinoma (OSCC) can occur in a variety of ways, and draining lymphatics and lymph nodes serve as a common route. Prior to metastasis, lymph nodes elicit an immune response to either wall off or create a favorable environment for homing of tumor cells. This immune response to tumor stimuli is visualized by recognizing various immunoreactive patterns exhibited by the lymph node. The present study aims to evaluate the role of immuno-morphologic patterns of the lymph node in neck dissection for cases of OSCC. MATERIALS AND METHODS: Our retrospective study included 50 neck dissection cases of OSCC and a total of 1,078 lymph nodes. The grades of primary tumors with eight different immunoreactive patterns were compared. Vascularity and metastasis in lymph nodes were also evaluated. RESULTS: The lymphocyte predominant pattern was the most common immunoreactive pattern found in 396 of 1,078 lymph nodes. Patterns of lymphocyte predominant (P=0.0005), sinus histiocytosis (P=0.0500), paracortical hyperplasia (P=0.0001), cortical hyperplasia (P=0.0001), and increased vascularity (P=0.0190) were significantly associated with tumor grade. CONCLUSION: The present study adds to the understanding of lymph node immunoreactivity patterns and their correlation with tumor grade. We recommend further study of lymph node patterns for all sentinel lymph node biopsies and routine neck dissections for OSCCs.

Follicular Bronchiolitis Mimicking Lung Cancer in a Patient with Primary Sjögren's Syndrome

Follicular bronchiolitis (FB) is an uncommon pulmonary lymphoproliferative disorder that is characterized by the presence of peribronchiolar hyperplastic lymphoid follicles with reactive germinal centers. FB could be associated with systemic illnesses including immunodeficiency, infection, and autoimmune diseases. In Korea, a single case of FB with rheumatoid arthritis was recently described but there has been no report on FB associated with other rheumatic diseases. Herein, we describe the first case of FB presenting nodular ground-glass opacities (GGO), which mimicked lung cancer, in patients with primary Sjögren's syndrome (SS). The differential diagnosis of nodular GGO lesions should include FB although it is a rare manifestation in SS patients.

Expression and Significance of LncRNA RP11-513G11.1 in Peripheral Blood of Patients with Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and significance of LncRNA RP11-513G11.1 in peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL), and to analyze its correlation with clinicopathological features and prognosis of patients.@*METHODS@#The serum samples of 93 patients with DLBCL(DLBCL group) and 62 normal persons (control group) were collected from the Department of Hematology, Southwest Medical University. The expression of RP11-513G11.1 in serum samples was detected by real-time fluorescence quantitative PCR, the relationship between the RP11-513G11.1 expression with clinicopathological characteristics and prognosis was analyzed.@*RESULTS@#Compared with normal control group, the expression of RP11-513G11.1 significantly increased in DLBCL patients (P<0.001). The expression of RP11-513G11.1 not related with the age, sex, course of treatment and germinal center B-cell-like lymphoma(GCB) subtypes of the patients, but it related with the diameter of tumor,Ann Arbor stage,B symptoms,chemosensitivity and the international prognostic index(IPI) (P<0.05). The progression-free survival time and overall survival time of patients, whom with high expression of RP11-513G11.1 were significantly shorter than those of RP11-513G11.1 low expression（P<0.001）. The median progression-free survival time and overall survival time of chemotherapy-sensitive patients were significantly longer than those of chemotherapy-resistant patients (P<0.001). Univariate analysis and multivariate Cox regression analysis showed that Ann Arbor stage, RP11-513G11.1 expression, IPI and chemosensitivity were also the independent factors affecting the prognosis of DLBCL patients（P<0.05）.@*CONCLUSION@#RP11-513G11.1 is highly expressed in patients with DLBCL, which is related with the prognosis of DLBCL patients.

Curcumin Elevates T(FH) Cells and Germinal Center B Cell Response for Antibody Production in Mice

Curcumin is a natural product extracted from Curcuma longa. It has been reported as a potent antioxidant and anti-inflammatory compound. Previous studies have demonstrated that curcumin suppresses pro-inflammatory cytokine production via inhibition of NF-κB in macrophages. However, its role in adaptive immune cells such as T cells, in vivo, has not clearly been elucidated. Here, we examined the effects of curcumin in T follicular helper (T(FH)) cells and on Ab production during NP-ovalbumin immunization in mice. The results revealed that curcumin administered daily significantly increased CXCR5⁺B-cell lymphoma 6⁺ T(FH) cells and CD95⁺GL-7⁺ germinal center (GC) B cells in draining lymph nodes. In addition, curcumin treatment in mice induced total Ab production as well as high affinity IgG1 and IgG2b Ab production. Collectively, these results suggest that curcumin has positive regulatory roles in T(FH) cell functions and GC responses. Thus, this could be an advantageous supplement to enhance humoral immunity against infectious diseases and cancer.

Respiratory Syncytial Virus Fusion Protein-encoding DNA Vaccine Is Less Effective in Conferring Protection against Inflammatory Disease than a Virus-like Particle Platform

Formalin-inactivated respiratory syncytial virus (RSV) vaccination causes vaccine-enhanced disease (VED) after RSV infection. It is considered that vaccine platforms enabling endogenous synthesis of RSV immunogens would induce favorable immune responses than non-replicating subunit vaccines in avoiding VED. Here, we investigated the immunogenicity, protection, and disease in mice after vaccination with RSV fusion protein (F) encoding plasmid DNA (F-DNA) or virus-like particles presenting RSV F (F-VLP). F-DNA vaccination induced CD8 T cells and RSV neutralizing Abs, whereas F-VLP elicited higher levels of IgG2a isotype and neutralizing Abs, and germinal center B cells, contributing to protection by controlling lung viral loads after RSV challenge. However, mice that were immunized with F-DNA displayed weight loss and pulmonary histopathology, and induced F specific CD8 T cell responses and recruitment of monocytes and plasmacytoid dendritic cells into the lungs. These innate immune parameters, RSV disease, and pulmonary histopathology were lower in mice that were immunized with F-VLP after challenge. This study provides important insight into developing effective and safe RSV vaccines.

Clinical features and treatment outcomes of Hodgkin lymphoma: A retrospective review in a Malaysian tertiary hospital

BACKGROUND: Classical Hodgkin lymphoma (cHL) is a clinicopathologically unique, aggressive lymphoma arising from germinal center B-cells and is one of the most curable hematological malignancies. This study aimed to determine the clinical course, treatment regimens, response rates, and survival data of patients diagnosed with cHL in a tertiary center. METHODS: A retrospective review was conducted to include patients with a diagnosis of cHL from 2013 to 2017. Data of demographic and clinical characteristics, treatment regimens, and outcomes were collected and analyzed. RESULTS: We recruited 94 patients with a median age of 27.0 [interquartile range (IQR), 12] years. Most of the patients were male (61.7%) and 73.4% were ethnic Malay. Nodular sclerosis was the most common histology (77.6%), followed by mixed cellularity (6.4%) and others (16%). The median follow-up time was 28.0 (IQR, 32) months. All patients received chemotherapy but only 13.8% received radiotherapy as consolidation. The doxorubicin-bleomycin-vinblastine-dacarbazine regimen was the most common (85.1%), followed by the escalated bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristineprednisolone-procarbazine regimen (14.9%). Following treatment, 76.1% of patients achieved complete response. The 2-year overall survival (OS) and progression-free survival (PFS) of the entire cohort were 96.5% and 71.1%, respectively. The 2-year OS and PFS for advanced-stage disease were 93.9% and 62.8%, compared to 100% and 82.7% for early-stage disease, respectively (P=0.252 and P=0.052, respectively). CONCLUSION: This study provides insight into the clinical presentation and treatment outcomes among patients with cHL in Malaysia. A longer study duration is required to identify OS and PFS benefits and treatment-related complications for different chemotherapeutic regimens.

Histopathological and microbiological findings in buffalo chronic mastitis: evidence of tertiary lymphoid structures

Buffalo mastitis is an important economic problem in southern Italy, causing qualitative/quantitative alterations in milk and resulting in economic losses due to the sub-clinical course and chronic evolution. We investigated 50 udders of slaughtered buffaloes and subjected them to effectual microbiological screening to evaluate macro and microscopic mammary gland changes, immune-characterize the cell infiltrates, and compare the degree of tissue inflammation with somatic cell counts. Numerous Gram-positive and Gram-negative bacteria were isolated from all samples, majority of which were environmental mastitis pathogens. Histological features referable to chronic mastitis were observed in 92% udders. Lymphocytes, plasma cells and macrophages were found to evolve into aggregates in 48% udders, which often organized to form tertiary lymphoid structures (TLSs). A predominance of interstitial CD8+ over CD4+ lymphocytes and, in TLSs, scattered CD8+ lymphocytes in the mantle cells and CD79+ lymphocytes in germinal centers, were evidenced. Environmental pathogens are known to persist and cause chronic inflammatory changes in buffaloes, where CD8+ lymphocytes play an important role by controlling the local immune response. Moreover, the TLSs evidenced here for the first time in buffalo mastitis, could play a role in maintaining immune responses against persistent antigens, thereby contributing in determining the chronic course of mastitis.

Virus-like Particle Vaccine Containing Toxoplasma gondii Rhoptry Protein 13 Induces Protection against T. gondii ME49 Infection in Mice

Toxoplasma gondii can infect humans worldwide, causing serious diseases in pregnant women and immunocompromised individuals. T. gondii rhoptry protein 13 (ROP13) is known as one of the key proteins involved in host cell invasion. In this study, we generated virus-like particles (VLPs) vaccine expressing T. gondii rhoptry ROP13 and investigated VLPs vaccine efficacy in mice. Mice immunized with ROP13 VLPs vaccine elicited significantly higher levels of T. gondii-specific IgG, IgG1, IgG2a, and IgA antibody responses following boost immunization and challenge infection, whereas antibody inductions were insignificant upon prime immunization. Differing immunization routes resulted in differing antibody induction, as intranasal immunization (IN) induced greater antibody responses than intramuscular immunization (IM) after boost and challenge infection. IN immunization induced significantly higher levels of IgG and IgA antibody responses from feces, antibody-secreting cells (ASCs), CD4⁺ T, CD8⁺ T cells and germinal center B cell responses in the spleen compared to IM immunization. Compared to IM immunization, IN immunization resulted in significantly reduced cyst counts in the brain as well as lesser body weight loss, which contributed to better protection. All of the mice immunized through either route survived, whereas all naïve control mice perished. These results indicate that the ROP13 VLPs vaccine could be a potential vaccine candidate against T. gondii infection.

MicroRNA-mediated Regulation of the Development and Functions of Follicular Helper T cells

The germinal center reaction is a key event of humoral immunity, providing long-lived immunological memory. Follicular helper T (T(FH)) cells are a specialized subset of CD4⁺ T cells located in the follicles, which help B cells and thus control the germinal center reaction. T(FH) cell development is achieved by multi-step processes of interactions with dendritic cells and B cells along with the coordination of various transcription factors. Since the T helper cell fate decision program is determined by subtle changes in regulatory molecules, fine tuning of these dynamic interactions is crucial for the generation functional T(FH) cells. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulatory molecules for gene expression, which consequently modulate diverse biological functions. In the last decade, the miRNA-mediated regulation network for the germinal center reaction has been extensively explored in T cells and B cells, resulting in the identification of several key miRNA species and their target genes. Here, we review the current knowledge of the miRNA-mediated control of the germinal center reaction, focusing on the aspect of T cell regulation in particular. In addition, we highlight the most important issues related to defining the functional target genes of the relevant miRNAs. We believe that the studies that uncover the miRNA-mediated regulatory axis of T(FH) cell generation and functions by defining their functional target genes might provide additional opportunities to understand germinal center reactions.

Pulmonary Nodular Lymphoid Hyperplasia with Mass-Formation: Clinicopathologic Characteristics of Nine Cases and Review of the Literature

BACKGROUND: Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features. METHODS: We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients. RESULTS: Two of the nine patients had experienced tuberculosis 40 and 30 years prior, respectively. Interestingly, none were current smokers, although two were ex-smokers. Three patients complaining of persistent cough underwent computed tomography of the chest. PNLH was incidentally discovered in five patients during examination for other reasons. The remaining patient was diagnosed with the disease following treatment for pneumonia. Imaging studies revealed consolidation or a mass-like lesion in eight patients. First impressions included invasive adenocarcinoma and mucosal-associated lymphoid tissue‒type lymphoma. Aspergillosis was suspected in the remaining patient based on radiological images. Resection was performed in all patients. Microscopically, the lesions consisted of nodular proliferation of reactive germinal centers accompanied by infiltration of neutrophils and macrophages in various degrees and surrounding fibrosis. Ultimately, all nine patients were diagnosed with PNLH and showed no evidence of recurrence on follow-up. CONCLUSIONS: PNLH is an uncommon but distinct entity with a benign nature, and understanding the radiological and clinicopathological characteristics of PNLH is important.

Tuberculosis of the thyroid

@#<p style="text-align: justify;"><strong>OBJECTIVE:</strong> To present a case of thyroid tuberculosis and to discuss its clinical presentation, differential diagnoses and management.<br /><strong>METHODS:</strong><br /><strong>Design:</strong> Case Report<br /><strong>Setting:</strong> Tertiary Government Hospital<br /><strong>Patient:</strong> One<br /><strong>RESULTS:</strong> A 55-year-old farmer presented with an 8-month progressively enlarging anterior neck mass, and fine needle aspiration biopsy yielded grossly turbid straw-colored aspirate admixed with blood with microscopy showing scattered inflammatory cells and macrophages set against a colloid background. After total thyroidectomy, hispathology revealed parenchymal infiltration by multiple aggregates of plump spindled to epitheloid cells forming granulomas with interspersed multinucleated giant cells, central caseation necrosis and surrounding fibrosis with chronic inflammatory infiltrates. The nodal masses also showed prominent germinal centers with interspersed epitheloid cells and foamy macrophages. Final diagnosis was chronic granulomatous inflammation consistent with tuberculosis.<br /><strong>CONCLUSION:</strong> Tuberculosis (TB) of the thyroid is a rare occurrence that can present as inflammation, infection or tumor formation of the thyroid gland. Diagnosis depends on identification of the tubercle from tissues and aspirates by acid fast staining and TB culture. Treatment consists of multiple drug therapy for tuberculosis but thyroidectomy may be an option if the thyroid gland is severely diseased.</p>

Enforced Expression of CXCR5 Drives T Follicular Regulatory-Like Features in Foxp3⁺ T Cells

CXCR5⁺ T follicular helper (Tfh) cells are associated with aberrant autoantibody production in patients with antibody-mediated autoimmune diseases including lupus. Follicular regulatory T (Tfr) cells expressing CXCR5 and Bcl6 have been recently identified as a specialized subset of Foxp3+ regulatory T (Treg) cells that control germinal center reactions. In this study, we show that retroviral transduction of CXCR5 gene in Foxp3⁺ Treg cells induced a stable expression of functional CXCR5 on their surface. The Cxcr5-transduced Treg cells maintained the expression of Treg cell signature genes and the suppressive activity. The expression of CXCR5 as well as Foxp3 in the transduced Treg cells appeared to be stable in vivo in an adoptive transfer experiment. Moreover, Cxcr5-transduced Treg cells preferentially migrated toward the CXCL13 gradient, leading to an effective suppression of antibody production from B cells stimulated with Tfh cells. Therefore, our results demonstrate that enforced expression of CXCR5 onto Treg cells efficiently induces Tfr cell-like properties, which might be a promising cellular therapeutic approach for the treatment of antibody-mediated autoimmune diseases.

Tuberculosis of the thyroid

OBJECTIVE: To present a case of thyroid tuberculosis and to discuss its clinical presentation, differential diagnoses and management.METHODS:Design: Case ReportSetting: Tertiary Government HospitalPatient: OneRESULTS: A 55-year-old farmer presented with an 8-month progressively enlarging anterior neck mass, and fine needle aspiration biopsy yielded grossly turbid straw-colored aspirate admixed with blood with microscopy showing scattered inflammatory cells and macrophages set against a colloid background. After total thyroidectomy, hispathology revealed parenchymal infiltration by multiple aggregates of plump spindled to epitheloid cells forming granulomas with interspersed multinucleated giant cells, central caseation necrosis and surrounding fibrosis with chronic inflammatory infiltrates. The nodal masses also showed prominent germinal centers with interspersed epitheloid cells and foamy macrophages. Final diagnosis was chronic granulomatous inflammation consistent with tuberculosis.CONCLUSION: Tuberculosis (TB) of the thyroid is a rare occurrence that can present as inflammation, infection or tumor formation of the thyroid gland. Diagnosis depends on identification of the tubercle from tissues and aspirates by acid fast staining and TB culture. Treatment consists of multiple drug therapy for tuberculosis but thyroidectomy may be an option if the thyroid gland is severely diseased.

Interleukin-17 Enhances Germinal Center Formation and Immunoglobulin G1 Production in Mice

OBJECTIVE: Interleukin (IL)-17 is a pro-inflammatory cytokine that has pleiotropic effects on multiple target cells and thereby contributes to the development of immune-mediated inflammatory disorders. However, the role of IL-17 in the humoral immune response has not been clearly elucidated. METHODS: Mice deficient in IL-17A (IL-17A knockout [KO] mice) and wild type (WT) C57BL/6 mice were compared. Distinct B cell (mature/precursor and marginal zone/follicular) and plasma cell populations were compared using fluorescence-activated cell sorting (FACS) and confocal immunostaining. Immunoglobulin production was assessed by enzyme-linked immunosorbent assay. RESULTS: There was no difference in B cell and plasma cell populations between IL-17A KO and WT mice. However, after T cell-dependent antigen challenge, IL-17A KO mice produced lower levels of immunoglobulin (Ig)G1 than wild-type animals. IL-17A KO mice also showed reduced germinal center (GC) formation and lower expression of activation-induced cytidine deaminase, the essential enzyme for class switch recombination (CSR). IL-17 had no effect on the proliferation or survival of naïve B cells in in vitro functional studies. However, IL-17 treatment promoted naïve B cell differentiation into plasma cells in synergy with IL-4, although IL-17 alone had no effect. CONCLUSION: Our findings suggest that IL-17 contributes to the humoral immune response by enhancing GC formation, CSR to IgG1, and plasma cell differentiation in synergy with IL-4.

Progressive Transformation of Germinal Centers in Presacral Space: MRI Findings and Literature Review

Progressive transformation of germinal centers (PTGC) is an atypical feature seen in lymph nodes with unknown pathogenesis. PTGC most commonly presents in adolescent and young adult males as solitary painless lymphadenopathy with various durations. Cervical nodes are the most commonly involved ones while involvements of axillary and inguinal nodes are less frequent. PTGC develops extremely rarely in other locations. We report a rare case of solitary mass present in the presacral space. The mass as subsequently proven to be PTGC. To the best of our knowledge, PTGC in the presacral space has not been previously reported in the literature.

Twin Rectal Tonsils Mimicking Carcinoid or Mucosa-Associated Lymphoid Tissue Lymphoma

The rectal tonsil is a rare polypoid lesion exclusively found in the rectum and is considered a reactive proliferation of the lymphoid tissue. Although this lesion is benign, we recommend that it should be differentiated from carcinoid or polypoid type of mucosa-associated lymphoid tissue lymphomas, based on gross findings. In this case report, we describe a case of rectal lesions with a unique appearance in a 41-year-old man. Colonoscopy revealed two 5-mm-sized nodules located opposite from each other on the left and right sides of the lower rectum. Endoscopic mucosal resection was conducted. Histopathologically, both lesions were mainly located in the submucosa and consisted of prominent lymphoid follicles with germinal centers of various sizes. No immunoreactivity of Bcl-2 was seen in the germinal centers. Immunohistochemical staining for kappa and lambda light chains revealed a polyclonal pattern. Therefore, these lesions were diagnosed as rectal tonsils.

Secondary Cutaneous Follicular B-Cell Lymphoma Associated with Erythematous Swelling on the Leg: A Case Report / 대한피부과학회지

Cutaneous follicular B-cell lymphoma (CFBCL) is defined as the neoplastic proliferation of germinal center cells confined to the skin. Secondary CFBCL demonstrates a more aggressive clinical course compared to the primary form. We report the case of a 45-year-old man who presented with a 15-day history of lesions on his right leg. Clinical examination revealed multiple erythematous miliary/agminated papules on the right proximal thigh with erythematous swollen patches on the right lower leg. Biopsy of a thigh lesion revealed a massive dermal lymphocytic infiltrate with a follicular pattern. Immunohistochemical staining revealed atypical lymphocytes, which strongly expressed CD20, CD10, Bcl-2, Bcl-6 and Ki-67 proteins, but not CD3 and Cyclin D1. Additionally, further studies revealed that this cutaneous lesion had originated from a retroperitoneal lymph node. We treated the patient with systemic chemotherapy using a cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (CHOP) regimen and anti-CD20 monoclonal antibodies. This case illustrates a rarely reported example of secondary cutaneous follicular B-cell lymphoma showing peculiar clinical manifestations.

Secondary Cutaneous Follicular B-Cell Lymphoma Associated with Erythematous Swelling on the Leg: A Case Report / 대한피부과학회지

Cutaneous follicular B-cell lymphoma (CFBCL) is defined as the neoplastic proliferation of germinal center cells confined to the skin. Secondary CFBCL demonstrates a more aggressive clinical course compared to the primary form. We report the case of a 45-year-old man who presented with a 15-day history of lesions on his right leg. Clinical examination revealed multiple erythematous miliary/agminated papules on the right proximal thigh with erythematous swollen patches on the right lower leg. Biopsy of a thigh lesion revealed a massive dermal lymphocytic infiltrate with a follicular pattern. Immunohistochemical staining revealed atypical lymphocytes, which strongly expressed CD20, CD10, Bcl-2, Bcl-6 and Ki-67 proteins, but not CD3 and Cyclin D1. Additionally, further studies revealed that this cutaneous lesion had originated from a retroperitoneal lymph node. We treated the patient with systemic chemotherapy using a cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (CHOP) regimen and anti-CD20 monoclonal antibodies. This case illustrates a rarely reported example of secondary cutaneous follicular B-cell lymphoma showing peculiar clinical manifestations.