Recurrent Lymphadenopathy Research Articles

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome and Syndrome of Unexplained Recurrent Fevers in Children and Adults.

Children and adults with autoinflammatory disorders, who often experience recurrent fevers, rashes, cold-induced symptoms, conjunctivitis, lymphadenopathy, recurrent infections, aphthous stomatitis, and abnormal blood cell counts, may present to the allergist/immunologist because the symptoms mimic allergies and disorders of immunity. In recent years, there has been increased recognition of non-monogenic autoinflammatory disorders, including periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome and syndrome of undifferentiated recurrent fevers. For many clinical practitioners, the natural history, diagnostic criteria, differential diagnoses, and preferred therapies remain challenging because of the presumed rarity of patients and the evolving field of autoinflammation. Here, we aim to provide a practical framework for the clinical allergist/immunologist to evaluate and treat this patient population.

A Unique Association of Recurrent Swollen Lymph Nodes and Sweet Products in Pediatrics: A Cross Sectional Analysis in Rural Population of KPK

Introduction: The current study was aimed to investigate the association of dental caries with sweet products (especially sweetened milk at night) with lympha- denopathy in pediatrics. There is a well established mechanism of sweets with dental caries, and such caries can be the cause of recurrent lymphadenopathy. Methodology: A total 201 patients were assessed at pediatric and dental clinic, patients of ages 1 to 5 years having recurrent lymphadenopathy and dental caries were included while the rest were excluded. They were evaluated for a number of parameters including dental caries grading, raised TLC, body temperature, pain, addiction towards sweets, hunger status, difficulty in chewing, sleep habits, social behavior, while their parents were interviewed regarding awareness about dental caries. Results: It was observed that 90% of the patients were addicted to sweets, and 79% were having grade 4 dental caries, 82% were having aggressive behavior, 91% were having pyrexia, 94% were having raised TLC, 75% were in severe pain, 88% were facing difficulty in chewing solid food, 61% were underweight, 58% were anorexic, while 98% of the parent were not having any proper knowledge about caries development. The practical implication of the study is to develop new strategies to minimize the consumption of sugary products that are the ultimate cause of dental caries. Such caries are then responsible for a number of issues including swollen lymph nodes. Conclusion: All these issues may have a worst impact on the social, physical and mental growth of children. As all the patients were having recurrent lymphadenitis, yet it can be claimed that dental caries are among the primary causes. Keywords: Dental caries; Lymphadenopathy; Pediatrics; Street sweets; Sweetened Milk

FIVE INTERFERON RECEPTOR TRIPLICATES: A UNIQUE CASE OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN A DOWN SYNDROME PATIENT

<h3>Introduction</h3> Down Syndrome (DS) is recognized as a mild interferonopathy with features of autoimmunity, developmental delays and brain calcifications explained by triplicates of four of the six interferon receptors (IFNAR1, IFNAR2, IFNGR2, and IL10RB) found on chromosome 21. We describe hemophagocytic lymphohistiocytosis (HLH) in a DS patient who was found to have a second copy number gain encompassing IFNGR1. <h3>Case Description</h3> An ex 35-week male with a history of DS and transient abnormal myelopoiesis in the newborn period presented at 10 months of age with recurrent fever, lymphadenopathy and splenomegaly. He met criteria for HLH with anemia, hyperferritinemia, elevated soluble CD25, elevated fibrinogen and a cervical lymph node biopsy showing evidence of hemophagocytosis. Evaluation for underlying triggers was unremarkable. Given a disproportionately elevated interleukin-18 (148,566pg/mL) and S100A12 (26,911ng/mL) compared to CXCL9 (161pg/mL), targeted treatment with anakinra was initiated. The patient defervesced and laboratory findings improved. A primary immunodeficiency gene panel revealed copy number variants consistent with chromosome 21, along with a duplication of <i>IFNGR1</i> gene located on chromosome 6. A post-natal microarray confirmed trisomy 21 and revealed a duplication on chromosome 6p23.3 involving the <i>IFNGR1</i> gene. His type I interferon gene signature (IGS) was only slightly elevated while on therapy. <h3>Discussion</h3> DS has been established to have both elevated Type I and II IGS in the setting of 4/6 interferon receptor gene triplicates. Our patient has the unique overexpression of the IFNGR1 gene as well, likely contributing to his HLH-like presentation.

A RARE CASE OF KIKUCHI-FUJIMOTO DISEASE IN THE SETTING OF ASPLENIA

A RARE CASE OF KIKUCHI-FUJIMOTO DISEASE IN THE SETTING OF ASPLENIA

P147 Fungal osteomyelitis in patients with chronic granulomatous disease: a case series from a tertiary care medical centre.

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectivesTo present details of a case series of fungal osteomyelitis initially misdiagnosed as disseminated tuberculosis, in pediatric patients with chronic granulomatous disease.MethodInformed consent was obtained from the parents of three children (known cases of chronic granulomatous disease) with clinical features suggestive of chronic osteomyelitis. Clinical history was collected by interview and chart review. Samples were sent to the mycology laboratory for direct microscopy and fungal culture. Following a diagnosis of fungal osteomyelitis, antifungal therapy was administered and patients were monitored till discharge.ResultsFirst case:The first patient presented with fever, cough and progressive painful swelling over the left lower chest, and a past history of recurrent pneumonia and cervical lymphadenopathy, which were previously empirically treated with anti-tubercular therapy (ATT) and broad-spectrum antibiotics. Imaging revealed a soft tissue abscess with underlying rib osteomyelitis and pulmonary consolidation. Pus samples showed hyaline septate hyphae in direct microscopy and growth of Aspergillus nidulans in culture. The patient was successfully treated with intravenous voriconazole, which was switched to oral formulation on discharge.Second case:The second patient presented with fever and post-auricular swelling with multiple discharging sinuses, and a past history of fever and hilar lymphadenopathy, which were previously empirically treated with ATT and broad-spectrum antibiotics. Imaging revealed osteomyelitis involving mandible, temporal bone and skull base, with underlying sigmoid sinus thrombosis. Pus and tissue samples showed hyaline septate hyphae in direct microscopy and growth of Aspergillus fumigatus in culture. The patient was successfully treated with a combination of intravenous voriconazole and liposomal amphotericin B, and discharged on oral posaconazole.Third case:The third patient presented with progressive painful swelling over the right upper chest, and a past history of pneumonia, hemoptysis, and mediastinal lymphadenopathy, which were previously empirically treated with ATT and broad-spectrum antibiotics. During a previous hospitalization, imaging showed features suggestive of fungal pneumonia; BAL showed hyaline septate hyphae in direct microscopy and growth of Aspergillus fumigatus and Aspergillus flavus in culture, providing a diagnosis of fungal pneumonia which was treated with voriconazole and liposomal amphotericin B. During the present admission, imaging of the chest lesion revealed pus collection with underlying rib osteomyelitis, communicating with a cavity in the middle lobe of the right lung. FNAC from the lesion showed hyaline septate hyphae in direct microscopy but no growth in culture (probably due to previous antifungal therapy). The patient was successfully treated with a combination of intravenous voriconazole and liposomal amphotericin B, and discharged on oral posaconazole.ConclusionsFungal pneumonia and fungal osteomyelitis are often misdiagnosed as tuberculosis or bacterial infections, leading to unnecessary and ineffective ATT or broad-spectrum antibiotics. A high index of suspicion for fungal osteomyelitis is required in pediatric patients with a history of recurrent/chronic soft tissue infections, preceded by febrile episodes and/or pneumonia, especially if a diagnosis of chronic granulomatous disease (CGD) has already been established; if not, this characteristic clinical picture should in fact warrant evaluation for CGD.

Rapid diagnosis of Talaromyces marneffei infection by metagenomic next-generation sequencing technology in a Chinese cohort of inborn errors of immunity.

Talaromyces marneffei (T. marneffei) is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with T. marneffei in recent years. The disseminated infection of T. marneffei can be life-threatening without timely and effective antifungal therapy. Rapid and accurate pathogenic microbiological diagnosis is particularly critical for these patients. A total of 505 patients with IEI were admitted to our hospital between January 2019 and June 2022, among whom T. marneffei was detected in 6 patients by metagenomic next-generation sequencing (mNGS), and their clinical and immunological characteristics were summarized. We performed a systematic literature review on T. marneffei infections with published immunodeficiency-related gene mutations. All patients in our cohort were confirmed to have genetic mutations in IL12RB1, IFNGR1, STAT1, STAT3, and CD40LG. T. marneffei was detected in both the blood and lymph nodes of P1 with IL12RB1 mutations, and the clinical manifestations were serious and included recurrent fever, weight loss, severe anemia, splenomegaly and lymphadenopathy, all requiring long-term antifungal therapy. These six patients received antifungal treatment, which relieved symptoms and improved imaging findings. Five patients survived, while one patient died of sepsis after hematopoietic stem cell transplantation. The application of mNGS methods for pathogen detection in IEI patients and comparison with traditional diagnosis methods were investigated. Traditional diagnostic methods and mNGS tests were performed simultaneously in 232 patients with IEI. Compared to the traditional methods, the sensitivity and specificity of mNGS in diagnosing T. marneffei infection were 100% and 98.7%, respectively. The reporting time for T. marneffei detection was approximately 26 hours by mNGS, 3-14 days by culture, and 6-11 days by histopathology. T. marneffei infection was first reported in IEI patients with IL12RB1 gene mutation, which expanded the IEI lineage susceptible to T. marneffei. For IEI patients with T. marneffei infection, we highlight the application of mNGS in pathogenic detection. mNGS is recommended as a front-line diagnostic test for rapidly identifying pathogens in complex and severe infections.

Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review.

Background: Variants in the phospholipase C gamma 2 (PLCG2) gene can cause PLCG2-associated antibody deficiency and immune dysregulation (PLAID)/autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) syndrome. Linking the clinical phenotype with the genotype is relevant in making the final diagnosis. Methods: This is a single center case series of five related patients (4–44 years), with a history of autoinflammation and immune dysregulation. Clinical and laboratory characteristics were recorded and a literature review of APLAID/PLAID was performed. Results: All patients had recurrent fevers, conjunctivitis, lymphadenopathy, headaches, myalgia, abdominal pain, cold-induced urticaria and recurrent airway infections. Hearing loss was detected in two patients. Inflammatory parameters were slightly elevated during flares. Unswitched B-cells were decreased. Naïve IgD+CD27− B-cells and unswitched IgD+CD27+ B-cells were decreased; switched IgD-CD27+ B-cells were slightly increased. T-cell function was normal. Genetic testing revealed a heterozygous missense variant (c.77C>T, p.Thr26Met) in the PLCG2 gene in all patients. Genotype and phenotype characteristics were similar to previously published PLAID (cold-induced urticaria) and APLAID (eye inflammation, musculoskeletal complaints, no circulating antibodies) patients. Furthermore, they displayed characteristics for both PLAID and APLAID (recurrent infections, abdominal pain/diarrhea) with normal T-cell function. Conclusion: The heterozygous missense PLCG2 gene variant (c.77C>T, p.Thr26Met) might cause phenotypical overlap of PLAID and APLAID patterns.

Общая вариабельная иммунная недостаточность: сложности своевременной диагностики (клинический случай)

Common variable immunodeficiency (CVID) belongs to the group of primary immunodeficiencies with a predominant deficiency in antibody synthesis and the most common diagnosis among clinically significant cases of primary immunodeficiency in adults. The main laboratory criterion for this disease is considered to be hypogammaglobulinemia (a decrease in the level of IgG less than 4.5 g/l with a decrease in the level of IgA, with/without a decrease in the level of IgM). Clinical manifestations of CVID are diverse: infectious syndrome (chronic infections of the lower respiratory tract, sinusitis, otitis, infectious diarrhea, septic arthritis), autoimmune syndrome (cytopenias, systemic rheumatic diseases), non-infectious pathology of the gastrointestinal tract (celiac-like or IBD-like syndromes , nodular hyperplasia of the mucosa), interstitial lung diseases, pathological non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly), oncological diseases, the formation of non-caseating granulomas in the internal organs). Due to the lack of a typical clinical picture, the diagnosis of CVID in adults is often made many years late, especially if the clinical picture is dominated by non-infectious manifestations. The article presents a clinical case when the patient had recurrent lymphadenopathy as the main symptom for several years. After examination by various specialists, she was referred to an immunologist because hypoproteinemia and a sharp decrease in the gamma fraction of globulins have been revealed. An immunological study revealed agammaglobulinemia and a pronounced imbalance of T-lymphocyte subpopulations (a significant decrease in the number of CD4+ cells and an increase in CD8+ cells). The clinical significance of T-lymphocyte disorders in CVID, the need for treatment with adequate doses of intravenous immunoglobulins are discussed.

M155 AUTOINFLAMMATORY DISORDER, IMMUNODEFICIENCY, OR BOTH?

Autoinflammatory disorders result from inborn errors causing innate immune system dysregulation. Clinical features include recurrent fever, rash, arthritis, and lymphadenopathy in the absence of infection. This can be contrasted with primary immunodeficiency, wherein a lack of functional immune response leads to recurrent infections. Nuclear factor-κ B essential modulator (NEMO) deficiency causes a spectrum of disease which can manifest with features of both autoinflammation and immunodeficiency. We report a challenging case with a working diagnosis of NEMO deficiency.

Flow Cytometry Analysis of Recurrent or Persistent Lymphadenopathy in Patients with Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Objectives: We recently examined the utility of flow cytometric analysis in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) by examining reactive T-cell features. This study aims to compare these features in sequential biopsies of persistent or recurrent lymphadenopathy in patients with NLPHL. Methods: We reanalysed the histopathology and flow cytometry findings of 9 patients with multiple biopsies for persistent or recurrent lymphadenopathy and either initial or recurrent NLPHL. A flow cytometry signature was considered suggestive of NLPHL if ≥12% of T-cells expressed CD57 or ≥3% of T-cells co-expressed CD4 and CD8. Results: A flow cytometry signature considered suggestive of NLPHL was seen in 18 of 20 specimens. Based on histopathology, 11 were diagnosed as NLPHL, 3 were initially underdiagnosed as atypical lymphoid proliferation, and 4 were initially incorrectly diagnosed as negative or progressive transformation of germinal centers. Flow cytometry showed similar expression patterns of CD57 and CD4/CD8 in T-cells between initial and subsequent biopsies. The remaining 2 specimens lacked the flow cytometry signature suggestive of NLPHL and were histopathologically diagnosed as reactive hyperplasia. Conclusion: Flow cytometry analysis based on our criteria is highly sensitive in detecting NLPHL. Correlation with the cytospin cytology may increase the diagnostic specificity. A negative flow essentially ruled out the possibility of NHLPHL.

Oropharyngeal squamous cell carcinoma diagnoses following resolution of isolated cervical lymphadenitis, a case series

IntroductionIsolated acute cervical lymphadenitis, without obvious initial source of infection is not common. This case series reviews patients who subsequently went on to be diagnosed with oropharyngeal Human Papilloma Virus related Squamous Cell Carcinoma (HPV-SCC), despite clinical resolution of initial lymphadenopathy. Study designA retrospective review of adult patients admitted with isolated acute lymphadenitis for the period 01/01/2008 to 31/12/2018. Presenting signs and symptoms, investigations, and outcomes were recorded for these patients. ResultsTwenty-one adults were admitted with isolated lymphadenitis during study time period. 6/21 resolved within 2 weeks, three were lost to follow up, the remainder underwent further investigation. Three males in their 5th decade experienced complete resolution of cervical lymphadenopathy, however, presented 13–17 months later with further cervical lymphadenopathy and were subsequently diagnosed with oropharyngeal HPV-SCC. Patients who went on to be diagnosed with HPV-SCC had a stronger inflammatory response (leucocytosis and raised CRP) and larger lymph nodes. ConclusionAs the natural history and characteristics of HPV-SCC, especially in the setting of acute inflammation, are not completely understood it is difficult to make recommendations with regards to further investigations to enable earlier detection. Patients and clinicians need to be aware of this possibility and investigate recurrent cervical lymphadenopathy promptly.

Infections in activated PI3K delta syndrome (APDS).

Activated PI3K-delta Syndrome (APDS), also called PI3K-delta activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI), is an autosomal dominant disorder caused by inherited or de novo gain-of-function mutations in one of two genes encoding subunits of the phosphoinositide-3-kinase delta (PI3Kδ) complex. This largely leukocyte-restricted protein complex regulates cell growth, activation, proliferation, and survival. Patients who harbor these mutations have early onset immunodeficiency with recurrent infections, lymphadenopathy, and autoimmunity. The most common infection susceptibilities are sinopulmonary (encapsulated bacteria) and herpesviruses. Multiple defects in both innate and adaptive immune function are responsible for this phenotype. Apart from anti-microbial prophylaxis and immunoglobulin replacement, patients are treated with a variety of immunomodulatory agents and some have needed hematopoietic stem cell transplants. Here, we highlight the spectrum of infections, immune defects, and therapy options in this inborn error of immunity.

Extrapulmonary tuberculosis with recurrent multiple lymphadenopathy in a pediatric patient

Although tuberculosis is a disease that can be prevented and treated, it remains a significant health problem in developing countries, such as our country. Tuberculosis is an important public health problem in children as well as in adults in our country. Both pulmonary and extrapulmonary tuberculosis can be seen in children. In children, the most common form of extrapulmonary tuberculosis is tuberculous lymphadenitis. Although viral factors are more common in pediatric patients presenting with lymphadenopathy, tuberculosis is also an important disease to be considered in the etiology of lymphadenopathy in children. In this case report, we aimed to emphasize the importance of tuberculosis in terms of etiologic approach in a patient who presented to the pediatrics outpatient clinic with multiple lymphadenopathies.

Hyper IgE syndrome associated with novel DOCK8 heterozygous mutation: а case report

Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive combined immunodeficiency within the spectrum of hyper-IgE syndromes.Here we report a patient with a novel heterozygous mutation in DOCK8 gene associated with a clinical presentation of hyper-IgE syndrome (HIES).A case report. The patient presented with severe congenital atopic dermatitis, allergic rhinitis and bronchial asthma which was developed during the 3rd year of life. Also, the patient suffered from recurrent otitis and lymphadenopathy of the inguinal lymph nodes. The immune evaluation showed normal lymphocytes subpopulation and increased serum IgE — 32.131 ІU/L. Genetic sequencing revealed a heterozygous defect c.5266A>T (p.Ile1756Phe) in the DOCK8 gene. Therapy with omalizumab was started and a significant improvement of skin syndrome was achieved.Conclusions. Our data and therapeutic approach may be clinically useful as the diagnostic and treatment approach for severe atopic dermatitis that does not fit the full criteria for previously reported hyper-IgE syndromes.The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institution. The informed consent of the child's parents was obtained from the studies.No conflict of interest was declared by the authors.

A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1.

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways1. Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development2,3. However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomal-dominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients' peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts.

Utility of Flow Cytometry in the Diagnostic Evaluation of Recurrent or Persistent Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Abstract Objectives We previously reported that lymph nodes involved by nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) had unique flow cytometric features. To further validate their diagnostic utility, we have examined the flow cytometry features in cases of persistent lymphadenopathy (LAD) prior to the diagnosis of NLPHL or recurrent LAD following diagnosis and treatment for NLPHL. Methods We retrospectively identified nine patients (2-3 specimens per patient for a total of 20 specimens) with persistent or recurrent lymphadenopathy before or after they were diagnosed with NLPHL between the ages of 13 and 76 years. Their histopathology diagnoses were reviewed and flow cytometry data were reanalyzed. Results Based on our published criteria (Am J Clin Pathol 2016;145:107-115), positive flow cytometry findings (at least 12% of T cells expressing CD57 or at least 3% of T cells coexpressing CD4 and CD8) were seen in 18 specimens. Based on histopathology, 11 of them were correctly diagnosed as NLPHL, 3 of them initially underdiagnosed as atypical lymphoid proliferation, and 4 of them initially incorrectly diagnosed as negative or progressive transformation of germinal centers (PTGCs). The flow cytometry studies showed similar expression patterns of CD57, CD4, and CD8 in T cells and very similar high percentages of CD57+ T cells and CD4+CD8+ T cells between initial biopsies and subsequent biopsies in these patients. Negative flow cytometry findings were seen in two specimens pathologically confirmed as negative for NLPHL in two patients after treatment. Their initial diagnostic specimens showed positive flow cytometry findings, different from that seen in the subsequent specimens posttreatment. Conclusion Flow cytometry appears to be a useful adjunct in detecting early or relapsed NLPHL, especially in atypical lesions. The presence of positive flow cytometry features is very sensitive in detecting recurrent or persistent NLPHL, while absence of positive flow cytometry features helps rule out NLPHL.

Omenn syndrome- A rare immunodeficiency disorder: A case report

Introduction: Omenn syndrome, a variant of severe combined immunodeficiency disorder, is a rare condition, with few cases reported in literature. Case Characteristics: A three month old female infant presented with recurrent severe infections, chronic diarrhea, severe erythroderma and lymphadenopathy. Immunological work-up revealed agammaglobulinemia, with both B cell and T cell deficiency. Genetic studies were compatible with Omenn syndrome. Outcome: Bone marrow transplantation was planned, but the infant succumbed to complications. Message: In a young infant with recurrent severe infections, characteristic skin lesions and combined immunodeficiency, Omenn syndrome should be suspected. Keywords: Immunodeficiency, Omenn syndrome, Early diagnosis.

Clinical features of adult-onset chronic active Epstein-Barr virus infection

Chronic active Epstein-Barr virus infection (CAEBV) presents with mononucleosis-like symptoms such as chronic persistent or recurrent pyrexia, lymphadenopathy, and hepatosplenomegaly because of the reactivation of Epstein-Barr virus (EBV) as demonstrated by the recurrence of EBV-infected cells. The mechanism of CAEBV remains obscure, and CAEBV can lead to fatal conditions such as hemophagocytic syndrome and malignant lymphoma by clonal expansion of EBV-infected T- or NK-cells. Without hematopoietic stem cell transplantation, CAEBV has a poor prognosis. CAEBV is listed in the revised 2016 World Health Organization classification as a chronic active EBV infection of T- and NK-cell types, systemic form, among EBV-positive T- and NK-cell lymphoproliferative diseases of childhood. However, similar clinical conditions have been reported in adult patients. Therefore, we investigated the clinical features of adult patients with CAEBV-like features (adult-onset CAEBV) in a relatively small number of cases. Additionally, genetic alterations related to CAEBV development have also been reported. Along with these results, we reviewed the clinical characteristics of adult-onset CAEBV.

Clinical and pathological features of 13 children with Epstein-Barr virus-positive lymphoproliferative disease

Objective: To summarize the clinical characteristics, virological and histopathological features, clinical outcome of Epstein-Barr virus-positive lymphoproliferative disease (EBV(+)LPD) in children. Methods: The clinical and follow-up data of 13 children histopathologically diagnosed as EBV(+)LPD in the Department of Infectious Disease of Beijing Children's Hospital between January 2011 and December 2016 were summarized. Results: Of the 13 patients, 5 were males and 8 females. The median age of disease onset was 6.0 years (range 1.3 to 15.0 years). The median duration between disease onset and diagnosis was 3 months (range 1 to 24 months). All the 13 patients had fever, 9 cases had hepatosplenomegaly and lymphoadenopathy, 4 cases had only lymphoadenopathy, 7 cases had reduced peripheral blood cells, 7 cases had lung involvement, 3 cases had central nervous system involvement, 3 cases had cardiac involvement, 3 cases had intestinal involvement, 2 cases had skin involvement and 1 case had abdominal mass. All the 13 patients underwent whole blood EBV-DNA PCR examination and the copies ranged from 1×10(8)/L to 1×10(11)/L. Pathology of lymph node confirmed 6 cases, skin pathology confirmed 2 cases, lung pathology, ileum mucosa pathology, liver pathology, abdominal mass pathology and bone marrow pathology confirmed 1 case each. Among 13 patients, 9 cases presented with EBV-positive T cell lymphoproliferative disease(EBV(+) T-LPD), 2 cases with hydroa vacciniforme (HV) and 2 cases with EBV-positive diffuse large B-cell lymphoma (EBV(+) DLBCL) . All the patients were followed up for 2 days to 65 months after discharge. Among 9 cases of EBV(+)T-LPD, 1 case died in a short time, 1 case died after evolved to T-cell lymphoma, 2 cases recovered after hematopoietic stem cell transplantation, 1 case recovered after the chemotherapy of hemophagocytic lymphohistiocytosis(HLH) 2004 protocol and 4 cases were stable now. Of 2 cases of HV patients, 1 case died after evolved to HV like lymphoma and the other still have symptoms. Among 2 cases of EBV(+) DLBCL, 1 case died shortly after discharge and the other was still stable after chemotherapy. Conclusions: Chronic recurrent fever, lymphadenopathy and hepatosplenomegaly are the most common clinical manifestations in children with EBV(+)LPD. Involvement of lung, central nervous system, intestinal tract, skin and other organs are also involved frequently. For children with chronic fever of unknown cause and accompanied by lymphadenopathy and (or) hepatosplenomegaly, EBV (+) LPD should be considered highly when the whole blood EBV-DNA load continues to increase significantly, early biopsy of the proliferative lesion should be performed to make a definite diagnosis. The prognosis of EBV (+) LPD is poor, and some evolve to lymphoma, hematopoietic stem cell transplantation is an effective way to treat this disease.

Removal of thyroid remnant for cancer in the previously operated central neck

Reoperative central neck dissection requires a concise set of steps to complete a comprehensive dissection of recurrent lymphadenopathy seen in thyroid cancer. The main considerations take into account the recurrent laryngeal nerve and the parathyroid glands. This chapter specifies those steps from a preoperative evaluation to the pearls during dissection to ensure a complete reoperative dissection that removes all residual thyroid tissue and lymphadenopathy while ensuring the best outcomes.