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H syndrome is a rare autosomal recessive genodermatosis that falls under the histiocytosis-lymphadenopathy plus syndrome. The term "H syndrome" includes manifestations such as hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height, and occasionally hyperglycemia. The syndrome is associated with mutations in the SLC29A3 gene, which encodes the human equilibrative transporter 3 present in endosomes, lysosomes, and mitochondria. The generalized and ubiquitous presence of affected lysosomes and mitochondria contributes to the systemic and phenotypically heterogeneous manifestations of the syndrome. H syndrome manifestations are cutaneous, systemic, and organ-specific. The pathognomonic signs are hypertrichosis and hyperpigmentation in the inner thighs and shins. However, not all patients present with these symptoms. H syndrome management involves a multidisciplinary approach to address specific symptoms and complications. The prognosis of H syndrome depends on several factors, including the extent and severity of clinical manifestations, the presence of complications, and timely diagnosis and management. Further studies are needed to explore the association between prognosis and the different mutations encountered in H syndrome., (Copyright © 2024 Hematology/Oncology and Stem Cell Therapy.)

Non-Hodkin's lymphoma (NHL) is the most frequent hematologic malignancy in humans and dogs. NKG2D is one of the most critical receptors on NK cells, recognizing their natural ligands on malignant cells such as A and B major histocompatibility complex-related proteins (MIC-A and MIC-B). Soluble molecules (sMIC-A and sMIC-B) can interfere with immune synapsis between NK cells and tumor cells, impeding NK cytotoxicity. The main objectives of this study were to analyze, in dogs with diffuse large B cell lymphoma, NK cell lymphoma, and reactive lymphadenopathies, the role of NK cells, their activating receptors NKG2D and NKp46, and their ligands MIC-A and MIC-B, as well as soluble molecules sMIC-A and sMIC-B. Thirty-six dogs with a possible diagnosis of NHL and eight healthy dogs were studied. NHL was diagnosed in 28 (78 %) dogs; in the other 8 (22 %), reactive lymphadenopathies were present. Most of the lymphomas corresponded to B cell NHL (82 %). The most predominant subtype was diffuse large B cell lymphoma (21, 71.5 %), followed by five cases (18 %) that were Non-B Non-T lymphomas (presumably NK cell lymphomas) and other B cell lymphomas (3, 10.5%). There were no cases of T cell NHL. MIC-A was positive in 7 of 27 (26 %) cases of NHL, and MIC-B in 20 of 27 (74 %) NHL. In non-malignant lymphadenopathies, three (37.5 %) dogs were positive for MIC-A, and five (62.5 %) expressed MIC-B. Dogs with lymphoma had higher numbers of NK cells than eight healthy dogs. In 15 dogs (12 cases with NHL and three cases with reactive adenopathies) and eight controls, there were no differences in the number of NK cells expressing NKP46 and NKG2D. NHL dogs had higher values of sMIC-A and sMIC-B. B-cell and NK cell lymphomas correspond to 86 % and 14 % of all canine lymphomas. MIC-A, MIC-B, and sMIC-A and sMIC-B were increased in canine lymphomas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

IL‑17A, the effector cytokine of T helper (Th) 17 cells, plays a crucial role in the pathogenesis of psoriasis. The Notch1 and PI3K/AKT signaling pathways are implicated in Th17 cell differentiation and IL‑17A production. The present study aimed to evaluate the regulatory effect of the Notch1/hairy and enhancer of split 1 (Hes1)‑PTEN/AKT/IL‑17A feedback loop on Th17 cell differentiation via the PI3K/AKT inhibitor LY294002 in a mouse model of psoriasis. Mice were randomly divided into 3 groups: a control group, a model group [5% imiquimod (IMQ)‑induced group] and an intervention group (5% IMQ‑induced plus LY294002‑treated group). Skin structural characteristics were recorded and evaluated by hematoxylin and eosin staining. The weights of the spleens and inguinal lymph nodes were measured. Th17 cell percentage, as well as the mRNA and protein expression levels of Notch1, Notch1 intracellular domain (NICD1), Hes1, PTEN, AKT, phosphorylated (p)‑AKT, mTOR complex 1 (mTORC1), p‑mTORC1, S6 kinase (S6K)1, S6K2 and IL‑17A were detected in skin samples of the three experimental groups. Additionally, splenic mononuclear cells from model mice were treated by 10 and 50 µM LY294002 to further evaluate its regulatory effect on Notch1/Hes1‑PTEN/AKT/IL‑17A feedback loop. Increased Th17 cell percentage, increased expression of Notch1, NICD1, Hes1, AKT, p‑AKT, mTORC1, p‑mTORC1, S6K1, S6K2 and IL‑17A, and decreased PTEN levels were observed in model mice alongside marked psoriasis‑like skin inflammation, splenomegaly and lymphadenopathy. LY294002 treatment significantly alleviated the severity of psoriasis‑like skin inflammation in the intervention mice, attenuated the degree of epidermal hyperplasia and dermal inflammatory cell infiltration, and mitigated splenomegaly and lymphadenopathy. In addition, LY294002 treatment reversed the increased Th17 cell percentage, as well as the increased expression of Notch1, NICD1, Hes1, AKT, p‑AKT, mTORC1, p‑mTORC1, S6K1, S6K2 and IL‑17A, and the decreased expression of PTEN. In vitro study from 5% IMQ‑induced mouse splenic mononuclear cells presented that high dose of LY294002 exerted more obviously regulatory effect on Notch1/Hes1‑PTEN/AKT/IL‑17A feedback loop. The current findings suggested that the Notch1/Hes1‑PTEN/AKT/IL‑17A feedback loop regulates Th17 cell differentiation within the disease environment of psoriasis. Blocking the Notch1/Hes1‑PTEN/AKT/IL‑17A feedback loop may thus be a potential therapeutic method for management of psoriatic inflammation.

Context.—: Both salivary lymphadenomas (LADs) and Warthin-like mucoepidermoid carcinoma (MEC) contain components of epithelium and lymphoid stroma and their differential diagnosis can be difficult on the basis of morphology alone., Objective.—: To clarify whether Warthin-like MEC was diagnosed as a LAD, and to compare their clinicopathologic features., Design.—: A total of 16 LAD cases were analyzed for MAML2 rearrangement by using fluorescence in situ hybridization, and the clinical, histologic, immunohistochemical, and prognostic features were compared between MAML2 rearrangement-positive and MAML2 rearrangement-negative groups., Results.—: Among the 16 cases investigated, 9 harbored a MAML2 rearrangement and were reclassified as Warthin-like MEC. The remaining 7 cases were classified as LADs with 1 nonsebaceous and 6 sebaceous cases. The patients with Warthin-like MEC had a wider age range (10-75 years) than the patients with LADs (36-68 years). Histologically, 2 of the 9 Warthin-like MECs (22.2%) showed focal invasion, whereas all the LADs had complete capsules. Warthin-like MECs exhibited a diverse epithelial cell morphology, including basaloid, glandular, cuboidal, epidermoid, with mucinous cells, although these cytologic features were seen only focally in some cases. Nonsebaceous LAD was composed of basaloid and glandular epithelial cells predominantly. In sebaceous LAD, the epithelial cells were composed of basaloid and large foamy sebaceous cells. In all cases, the stroma was composed mainly of lymphocytes accompanied by lymphoid follicles, although plasma cell infiltration could be much heavier in Warthin-like MEC. All the patients had a good outcome after a longer follow-up (3-166 months)., Conclusions.—: Warthin-like MEC can be misdiagnosed as a LAD owing to overlap in clinicopathologic features of the 2 entities. Careful histologic evaluation and detection of MAML2 rearrangement can facilitate their differential diagnosis.

Innate immune cellular effectors are actively consumed during systemic inflammation, but the systemic traffic and the mechanisms that support their replenishment remain unknown. Here, we demonstrate that acute systemic inflammation induces the emergent activation of a previously unrecognized system of rapid migration of granulocyte-macrophage progenitors and committed macrophage-dendritic progenitors, but not other progenitors or stem cells, from bone marrow (BM) to regional lymphatic capillaries. The progenitor traffic to the systemic lymphatic circulation is mediated by Ccl19/Ccr7 and is NF-κB independent, Traf6/IκB-kinase/SNAP23 activation dependent, and is responsible for the secretion of pre-stored Ccl19 by a subpopulation of CD205 + /CD172a + conventional dendritic cells type 2 and upregulation of BM myeloid progenitor Ccr7 signaling. Mature myeloid Traf6 signaling is anti-inflammatory and necessary for lymph node myeloid cell development. This report unveils the existence and the mechanistic basis of a very early direct traffic of myeloid progenitors from BM to lymphatics during inflammation., Competing Interests: JS, SH, SK, JS, JF, AW, PR, YR, LC, HG, HG, SL, IM, JS, DS, JC No competing interests declared

Dermatopathic lymphadenopathy is a distinctive form of paracortical lymph node hyperplasia that usually occurs in the setting of chronic dermatologic disorders. The aim of this study is to update our understanding of the clinicopathologic and immunophenotypic features of dermatopathic lymphadenopathy. The study cohort was 50 lymph node samples from 42 patients diagnosed with dermatopathic lymphadenopathy. The patients included 29 women and 13 men with a median age of 49 years (range, 12-79). Twenty-two (52%) patients had a dermatologic disorder, including mycosis fungoides (n = 6), chronic inflammatory dermatoses (n = 13), melanoma (n = 1), squamous cell carcinoma (n = 1), and Kaposi sarcoma in the context of human immunodeficiency virus infection (n = 1). Twenty (48%) patients did not have dermatologic manifestations. Lymph node biopsy specimens were axillary (n = 22), inguinal (n = 21), cervical (n = 4), and intramammary (n = 3). All lymph nodes showed paracortical areas expanded by lymphocytes; dendritic cells, including interdigitating dendritic cells and Langerhans cells; and macrophages. Melanophages were detected in 48 (98%) lymph nodes. Immunohistochemical analysis provided results that are somewhat different from those previously reported in the literature. In the paracortical areas of lymph node, S100 protein was expressed in virtually all dendritic cells, and CD1a was expressed in a significantly greater percentage of cells than langerin (80 vs. 35%, p < 0.0001). These results suggest that the paracortical regions of dermatopathic lymphadenopathy harbor at least three immunophenotypic subsets of dendritic cells: Langerhans cells (S100 + , CD1a +(high) , langerin + ), interdigitating dendritic cells (S100 + , CD1a +(low) , langerin - ), and a third (S100 + , CD1a - , langerin - ) minor population of dendritic cells. Furthermore, in more than 60% of dermatopathic lymph nodes, langerin highlighted trabecular and medullary sinuses and cords, showing a linear and reticular staining pattern, which could be a pitfall in the differential diagnosis with Langerhans cell histiocytosis involving lymph nodes.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive, reliable technique for sampling mediastinal lymph nodes (LNs). Liquid-based cytology (LBC) is widely used for cervical cancer screening because it provides reliable and feasible results. The present study aimed to evaluate effectiveness of the combination of EBUS-TBNA and LBC in the diagnosis of mediastinal lymphadenopathy., Methods: A total of 602 LNs that were retrospectively analyzed were sampled in 442 patients who underwent EBUS-TBNA between January 2014 and December 2016. The histopathological result of TBNA tissue or cell blocks was considered as the gold standard to evaluate diagnostic utility of LBC and conventional smears (CS) for the diagnosis of mediastinal lymphadenopathy., Results: Of the 602 LNs, 265 were mediastinal LN metastases from lung cancer, four were lymphoma, and 333 were benign. The sensitivity of LBC and CS in the diagnosis of mediastinal LN metastases from lung cancer was 72.8% and 63%, respectively, and the specificity was 98.5% and 97%, respectively. The positive predictive values for LBC and CS were 97.5% and 94.4%, respectively, whereas the negative predictive values were 82.2% and 76.9%, respectively. The accuracy of LBC and CS was 88% and 83.7%, respectively. The diagnostic value of LBC was significantly higher than that of CS (P = .001)., Conclusions: The combination of EBUS-TBNA and LBC is a highly reliable and feasible procedure that optimizes diagnostic utility for the diagnosis of lung cancer and mediastinal LN staging., (© 2019 The Authors. Diagnostic Cytopathology published by Wiley Periodicals, Inc.)

Amyloidosis is characterized by extracellular deposition of insoluble protein fibrils in a beta-pleated sheet configuration. Breast amyloidosis is a rare entity which has previously been reported to present with localized involvement, or as a late manifestation of systemic amyloidosis. However, descriptions of the clinicopathologic features of localized breast amyloidosis remain limited. A retrospective search for breast amyloidosis diagnosed at our institution yielded 10 cases of breast amyloidosis. All patients were female, with a mean age of 69. Median follow-up for survival or progression was 13 months. Indications for breast or axilla biopsy included mammographic calcifications, mass, and axillary lymphadenopathy. Amyloid showed positive staining with Congo red in all cases, and amyloid typing revealed light chain lambda in 3 cases, amyloid transthyretin in 2 cases, light chain kappa in 1 case, and iatrogenic insulin-derived amyloidosis in 1 case. Amyloid occurred within axillary lymph nodes and alongside both benign and neoplastic breast tissue, including atypical ductal hyperplasia, lobular carcinoma in situ and ductal carcinoma in situ. Most cases were associated with predisposing clinical conditions, including autoimmune disease in 4 cases, B cell lymphomas in 2 cases, and diabetes mellitus treated with insulin in 1 case. In contrast to previously published case series, no patient had clinical evidence of systemic amyloidosis. Amyloidosis of the breast should be considered in the differential diagnosis of all mammographic calcifications and masses of the breast or axilla. When recognized correctly on biopsy, the diagnosis of amyloidosis can not only prevent further unnecessary surgical interventions due to radiology-pathology discordance, but initiate the necessary amyloidosis work-up. Although rare, an awareness of the clinicopathologic characteristics of this easily overlooked entity is of great importance for every practicing pathologist reviewing breast biopsies., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

We describe 7 human immunodeficiency virus-infected Malawian children with Kaposi sarcoma who met criteria for Kaposi sarcoma herpesvirus (KSHV) inflammatory cytokine syndrome. Each presented with persistent fevers, bulky lymphadenopathy, massive hepatosplenomegaly, and severe cytopenias. Plasma analyses were performed in 2 patients, both demonstrating extreme elevations of KSHV viral load and interleukin 6., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Case Presentation: A 3-year-old girl was referred to a pediatric pulmonologist for dyspnea and recurrent upper respiratory tract infections (RTIs). The patient was born full term to unrelated Dutch parents after an uneventful pregnancy and birth. The year before presentation, she had suffered from pneumonia and > 10 upper RTIs. Apart from the recurrent RTIs, which started in infancy, her medical history was not significant and did not include allergies or eczema. An adenotonsillectomy was performed at the age of 2 years, and she was treated with multiple antibiotic regimens and inhalation therapy with salbutamol and corticosteroids, with no relief of symptoms., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Lymphocyte profiles in mediastinal lymph nodes may reflect the immune status of patients with sarcoidosis. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is useful for the diagnosis of diseases with mediastinal lymphadenopathy including sarcoidosis. The purpose of this study was to determine lymphocyte profiles of lymph nodes in sarcoidosis by analyzing EBUS-TBNA samples. We prepared single cell suspensions from EBUS-TBNA samples of mediastinal lymph nodes from patients with sarcoidosis or lung cancer and analyzed surface markers (CD3, CD4, CD8, CD19, CD25) and FoxP3 expression in the resultant lymphocytes using flow cytometry. We studied 26 patients with sarcoidosis and 16 with lung cancer with mediastinal lymph node metastases. In sarcoidosis, the CD4/CD8 ratio was significantly more elevated in lymph nodes than in bronchoalveolar lavage fluid (P<0.001), although both were strongly correlated. The CD4/CD8 ratio was significantly higher in stage I than in stage II both in the BAL fluid and lymph nodes. When compared with lung cancer lymph node metastasis, the CD4/CD8 ratio was significantly higher in sarcoidosis, whereas the CD3/CD19 ratio was significantly higher in lung cancer. The proportion of regulatory T cells (CD4+, CD25+, FoxP3 high) did not differ between sarcoidosis and lung cancer samples. Lymphocyte profiles in mediastinal lymphadenopathy can be analyzed by flow cytometry of EBUS-TBNA samples. These findings might help elucidate the immunopathology of sarcoidosis., Competing Interests: The authors have declared that no competing interests exist.

Necroptosis is a form of cell death associated with inflammation; however, the biological consequences of chronic necroptosis are unknown. Necroptosis is mediated by RIPK1, RIPK3, and MLKL kinases but in hematopoietic cells RIPK1 has anti-inflammatory roles and functions to prevent necroptosis. Here we interrogate the consequences of chronic necroptosis on immune homeostasis by deleting Ripk1 in mouse dendritic cells. We demonstrate that deregulated necroptosis results in systemic inflammation, tissue fibrosis, and autoimmunity. We show that inflammation and autoimmunity are prevented upon expression of kinase inactive RIPK1 or deletion of RIPK3 or MLKL. We provide evidence that the inflammation is not driven by microbial ligands, but depends on the release of danger-associated molecular patterns and MyD88-dependent signaling. Importantly, although the inflammation is independent of type I IFN and the nucleic acid sensing TLRs, blocking these pathways rescues the autoimmunity. These mouse genetic studies reveal that chronic necroptosis may underlie human fibrotic and autoimmune disorders., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Purpose: The higher sensitivity of new diagnostic tools makes it easier to detect relapse in asymptomatic stages when classic procedures of lymph node biopsies are difficult to perform. The aim of this article is to describe the combination of gamma probe and 18F-FDG positron emission tomography-computed tomography (PET-CT) images in combination with sentinel lymph node biopsy technique for detection of nonpalpable lymph nodes., Methods: After a dose of 18F-FDG was administered and PET-CT images that showed the location of suspected pathologic lymph nodes were obtained, transcutaneous localization of the lymph nodes with the highest captation of the tracer was done. The gamma probe was programmed to detect the radioactive signal from the F18, instead of the Tc99m that is usual in the sentinel node biopsy technique. Once the hottest point was detected, a short incision was made on this area, and suspicious nodes with the highest uptake registered by the gamma probe were localized and removed. After the surgical removal from the operating field, the surgical pieces stood positive to the gamma probe. Lymph node involvement, and subsequent relapse, was diagnosed before their clinical manifestation., Conclusions: This methodology confirms new horizons for the surgical approach of lymph node biopsies in patients with previous tumors with 18F-FDG avidity and suspicion of relapse.

Lymphadenopathy continues to be a common problem to radiologists and treating physicians because of the difficulty in confidently categorizing a node as being benign or malignant using standard diagnostic techniques. The goal of our research was to assess whether magnetic resonance (MR) spectroscopy contains the necessary information to allow differentiation of benign from malignant lymph nodes in an in-vitro approach using a modern pattern recognition method. Tissue samples from a tissue bank were analyzed on a nuclear magnetic resonance (NMR) spectrometer. A total of 69 samples were studied. The samples included a wide variety of malignant and benign etiologies. Using 45 samples, we initially created a model which was able to predict if a certain spectrum originates from benign or malignant lymph nodes using a pattern-recognition technique which takes into account the entire magnetic spectrum rather than single peaks alone. The remaining 24 samples were blindly loaded in the model to assess its performance. We obtained an excellent accuracy in differentiating benign and malignant lymphadenopathy using the model. It correctly differentiated as malignant or benign, in a blinded fashion, all of the malignant samples (13 of 13) and 10 out of the 11 benign samples. We thus showed that magnetic spectroscopy is able to differentiate benign from malignant causes of lymphadenopathy. Additional experiments were performed to verify that the differentiating abilities of our model were not due to differential tissue decay in between benign and malignant tissues. If future experiments demonstrate that a similar approach could be executed with standard MR imaging, this technique could be useful as a problem-solving tool when assessing lymphadenopathy in general. Alternatively, our in-vitro technique could also be useful to pathologists faced with indeterminate pathologies of the lymph nodes after validating our results with a larger sample size.

BACKGROUND Chronic lymphocytic leukemia (CLL) usually expresses CD5 antigen. However, 7-20% of patients are CD5 negative. We report here a series of 19 CD5-negative B-CLL cases. MATERIAL AND METHODS We reviewed 19 consecutive CD5-negative B-CLL cases seen in our medical center from 2009 to 2015 and compared them with 105 CD5-positive B-CLL cases. The two groups were compared in terms of clinical parameters, laboratory parameters, and survival characteristics. RESULTS Lymphadenopathy was present in 31.5% of the CD5-negative group and 51.4% of the CD5-positive group (p=0.029). Splenomegaly was present in 42.1% of the CD5-negative group and 16.1% of the CD5-positive group (p=0.029). There was no difference between the groups in terms of Binet A, B, and C stages (p=0.118, p=0.051, and p=0.882, respectively). The median thrombocyte count was 144×109/L and 160×109/L in the CD5-negative and CD5-positive groups, respectively (p=0.044). There was no difference between the two groups in terms of median neutrophil count (p=0.169). The mean lymphocyte count was 43.2±4.0×10^9/L and 36.7±3.2×10^9/L in the CD5-negative and CD5-positive groups, respectively (p=0.001). There was no difference between the groups in terms of autoimmune hemolytic anemia and autoimmune thrombocytopenia. In five-year follow-up, 84.2% of CD5-negative patients and 90.5% of CD5-positive patients were alive (p=0.393). CONCLUSIONS We found more isolated splenomegaly, less lymphadenopathy, a higher lymphocyte count, and a lower thrombocyte count in the CD5-negative group. There was no difference between the groups in terms of clinical stage, autoimmune phenomena, hemoglobin and neutrophil count, and survival.

Rosai-Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare benign disorder usually characterized by massive painless cervical lymphadenopathy and systemic manifestations. Extranodal involvement, especially spinal involvement, is extremely rare. We report a 41-year-old man who presented with only intermittent dorsodynia. His condition was diagnosed as non-specific inflammatory disease on the basis of preoperative puncture biopsy results. We performed total surgical resection. Histopathological findings showed distinctive emperipolesis and immunohistochemistry results were positive for cluster of differentiation CD68 and S100 and negative for CD1a. A good prognosis was confirmed at the 3-month follow-up visit. This is the first case of RDD of the subdural spine with such a long segment lesion. There is still no consensus regarding appropriate therapy for this type of RDD and the preoperative diagnosis remains challenging. The unusual presentation of our case serves as a reference when diagnosing and treating RDD.

In Chronic Lymphocytic Leukemia (CLL), infiltration of lymph nodes by leukemic cells is observed in patients with progressive disease and adverse outcome. We have previously demonstrated that B-cell receptor (BCR) engagement resulted in CXCR4 down-regulation in CLL cells, correlating with a shorter progression-free survival in patients. In this study, we show a simultaneous down-regulation of CXCR4, CXCR5 and CD62L upon BCR triggering. While concomitant CXCR4 and CXCR5 down-regulation involves PKDs, CD62L release relies on PKC activation. BCR engagement induces PI3K-δ-dependent phosphorylation of PKD2 and 3, which in turn phosphorylate CXCR4 Ser324/325. Moreover, upon BCR triggering, PKD phosphorylation levels correlate with the extent of membrane CXCR4 decrease. Inhibition of PKD activity restores membrane expression of CXCR4 and migration towards CXCL12 in BCR-responsive cells in vitro. In terms of pathophysiology, BCR-dependent CXCR4 down-regulation is observed in leukemic cells from patients with enlarged lymph nodes, irrespective of their IGHV mutational status. Taken together, our results demonstrate that PKD-mediated CXCR4 internalization induced by BCR engagement in B-CLL is associated with lymph node enlargement and suggest PKD as a potential druggable target for CLL therapeutics., Competing Interests: CONFLICTS OF INTERESTSSG, MQ, MB, SLC, VLa, LG, NVB, CLR and DL declare no conflict of interest concerning this article. VLé received honoraria from Roche, Jannsen and Gilead. FAC received honoraria from Roche, Jannsen, Gilead and Karyopharm.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized inflammatory condition with single- or multi-organ involvement. The disease is characterized by tumefactive lesions with dense IgG4 plasmacytic infiltration (an elevated IgG4(+)/IgG(+) cell ratio of > 40 %), storiform fibrosis, and obliterative phlebitis, with or without elevated serum IgG4 levels. The diagnostic criteria for IgG4-RD, proposed in 2011, were quite comprehensive and practical; however, it is important to remember that other diseases, such as hyper-interleukin (IL)-6 syndromes, may have common histopathological findings. Therefore, the histopathology of suspected IgG4-RD is occasionally not diagnostic. Here, we report a case of IgG4-related primary localized cervical lymphadenopathy without any other organ involvement. To our knowledge, there have been no previous reports of this. Additionally, the disease was associated with a 20-fold increase in IL-6 levels compared to that of the normal range., Case Presentation: We report the case of a 52-year-old Japanese man who presented with a painless, somewhat diffuse swelling in the left submandibular region. Although the case fulfilled diagnostic criteria for IgG4-RD, the diagnosis was not straightforward due to abnormally high levels of serum IL-6. After systematic evaluation of the patient, a final diagnosis of IgG4-RD was established. Since then, a specialist in connective tissue disorders has evaluated the patient on a regular basis. Two years after his initial visit, no disease progress or systemic involvement has been noted., Conclusion: We present a case of an IgG4-related primary localized cervical lymphadenopathy mimicking hyper-IL-6 syndrome. This case can serve as an excellent reminder that the definitive diagnosis of IgG4-RD should be established using a systematic approach, in particular when it appears as an atypical manifestation.

Signet ring cell lymphomas are a rare subtype of non Hodgkin lymphoma characterised by malignant lymphoid cells with cytoplasmic inclusions that displace the nucleus and imparts a “signet ring” appearance. This poses a diagnostic challenge as it can be mistaken for an adenocarcinoma or any other epithelial malignancy. A 54yr old male presented with a 6month history of generalised lymphadenopathy. Examination of excision biopsy of the lymph nodes show effacement of architecture by sheets neoplastic cells with abundant cytoplasm distended by eosinophilic amorphous substances. Immunohistochemistry with a panel of three monoclonal antibodies [LCA, CD20, and CD3] confirmed these cells to be of lymphoid origin.