Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

The Diagnostic Performance of Magnetic Resonance Imaging in the Categorization of Pediatric Neck Lymph Nodes: Radiologic and Pathologic Correlations.

BACKGROUND/AIM: To present MRI features of neck lymph nodes in benign and malignant conditions in the pediatric population. MATERIALS AND METHODS: MRIs of the neck of 51 patients 1 to 18 years old (40 boys, 11 girls [10.08±4.73]) with lymph node biopsy were retrospectively analyzed. Those were grouped as benign including reactive (27 [52.9%]) and lymphadenitis (11 [21.6%]), and malignant (13 [25.5%]). The groups were evaluated multiparametrically in terms of quantitative and qualitative variables. RESULTS: The long axis, short axis, area, and apparent diffusion coefficient (ADC) values of the largest lymph node were 21 (17 to 24) mm, 14 (12 to 18) mm, 228.60 (144.79 to 351.82) mm 2 , 2531 (2457 to 2714) mm 2 /s for reactive, 24 (19 to 27) mm, 15 (11 to 20) mm, 271.80 (231.43 to 412.20) mm 2 , 2534 (2425 to 2594) mm 2 /s for lymphadenitis, 27 (23.50 to 31.50) mm, 20 (15 to 22) mm, 377.08 (260.47 to 530.94) mm 2 , 2337 (2254 to 2466) mm 2 /s for malignant, respectively. Statistical analysis of our data suggests that the following parameters are associated with a higher likelihood of malignancy: long axis >22 mm, short axis >16 mm, area >319 cm 2 , ADC value <2367 mm 2 /s, and supraclavicular location. Perinodal and nodal heterogeneity, posterior cervical triangle location are common in lymphadenitis ( P <0.001). Reactive lymph nodes are distributed symmetrically in both neck halves ( P <0.001). CONCLUSION: In the MRI-based approach to lymph nodes, not only long axis, short axis, surface area, and ADC, but also location, distribution, perinodal, and nodal heterogeneity should be used.

Severe BCG immune reconstitution inflammatory syndrome lymphadenitis successfully managed with pre-antiretroviral counseling and a non-surgical approach: a case report.

BACKGROUND: Bacillus Calmette-Guérin (BCG) reactions are the most common cause of immune reconstitution inflammatory syndrome (IRIS) in HIV-positive infants who initiate antiretroviral therapy (ART). There is limited evidence regarding the incidence of BCG-IRIS; however, reports from outpatient cohorts have estimated that 6-9% of infants who initiated ART developed some form of BCG-IRIS within the first 6 months. Various treatment approaches for infants with BCG-IRIS have been reported, but there is currently no widely accepted standard-of-care. CASE PRESENTATION: A 5-month-old male HIV-exposed infant BCG vaccinated at birth was admitted for refractory oral candidiasis, moderate anemia, and moderate acute malnutrition. He had a HIV DNA-PCR collected at one month of age, but the family never received the results. He was diagnosed with HIV during hospitalization with a point-of-care nucleic acid test and had severe immune suppression with a CD4 of 955 cells/µL (15%) with clinical stage III disease. During pre-ART counseling, the mother was educated on the signs and symptoms of BCG-IRIS and the importance of seeking follow-up care and remaining adherent to ART if symptoms arose. Three weeks after ART initiation, he was readmitted with intermittent subjective fevers, right axillary lymphadenopathy, and an ulcerated papule over the right deltoid region. He was subsequently discharged home with a diagnosis of local BCG-IRIS lymphadenitis. At six weeks post-ART initiation, he returned with suppurative lymphadenitis of the right axillary region that had completely eviscerated through the skin without signs of disseminated BCG disease. He was then started on an outpatient regimen of topical isoniazid, silver nitrate, and oral prednisolone. Throughout this time, the mother maintained good ART adherence despite this complication. After 2.5 months of ART and one month of specific treatment for the lymphadenitis, he had marked mass reduction, improved adenopathy, increased CD4 count, correction of anemia, and resolution of his acute malnutrition. He completely recovered and was symptom free two months after initial treatment without surgical intervention. CONCLUSIONS: This case details the successful management of severe suppurative BCG-IRIS with a non-surgical approach and underlines the importance of pre-ART counseling on BCG-IRIS for caregivers, particularly for infants who initiate ART with advanced HIV.

Cervical lymphadenitis from Mycobacterium avium complex.

We present an instructive case of cervical lymphadenitis in a young man without a history of HIV infection. The patient developed spontaneous left-sided neck swelling that progressed over 4 months. CT imaging demonstrated a necrotic left-sided neck mass within the cervical lymph node chain. He was initially prescribed azithromycin and rifampin for presumed cat scratch disease with improvement but incomplete resolution of symptoms. Blood cultures ordered 2 months later grew Mycobacterium avium complex (MAC) and the patient had an excellent clinical response to MAC therapy. Here, we review the case, including presentation and management, and describe the implications for the immune status of the host and long-term considerations for treatment.

Susceptibility of Mediterranean Buffalo (Bubalus bubalis) following Experimental Infection with Lumpy Skin Disease Virus.

Lumpy skin disease (LSD) is a viral disease of cattle and water buffalo characterized by cutaneous nodules, biphasic fever, and lymphadenitis. LSD is endemic in Africa and the Middle East but has spread to different Asian countries in recent years. The disease is well characterized in cattle while little is known about the disease in buffaloes in which no experimental studies have been conducted. Six buffaloes and two cattle were inoculated with an Albanian LSD virus (LSDV) field strain and clinically monitored for 42 days. Only two buffaloes showed fever, skin nodules, and lymphadenitis. All samples collected (blood, swabs, biopsies, and organs) were tested in real-time PCR and were negative. Between day 39 and day 42 after inoculation, anti-LSDV antibodies were detected in three buffaloes by ELISA, but all sera were negative by virus neutralization test (VNT). Cattle showed severe clinical signs, viremia, virus shedding proven by positive real-time PCR results, and seroconversion confirmed by both ELISA and VNT. Clinical findings suggest that susceptibility in buffaloes is limited compared to in cattle once experimentally infected with LSDV. Virological results support the hypothesis of buffalo resistance to LSD and its role as an accidental non-adapted host. This study highlights that the sensitivity of ELISA and VNT may differ between animal species and further studies are needed to investigate the epidemiological role of water buffalo.

An assessment of radiology resident competency in identifying suppurative retropharyngeal lymphadenitis: an examination using the WIDI SIM platform.

BACKGROUND AND PURPOSE: Suppurative retropharyngeal lymphadenitis is a retropharyngeal space infection almost exclusively seen in the young (4-8 years old) pediatric population. It can be misdiagnosed as a retropharyngeal abscess, leading to unnecessary invasive treatment procedures. This retrospective study aims to assess radiology residents' ability to independently identify CT imaging findings and make a definitive diagnosis of suppurative retropharyngeal lymphadenitis in a simulated call environment. MATERIALS AND METHODS: The Wisdom in Diagnostic Imaging Emergent/Critical Care Radiology Simulation (WIDI SIM) is a computer-aided emergency imaging simulation proven to be a reliable method for assessing resident preparedness for independent radiology call. The simulation included 65 cases across various imaging modalities of varying complexity, including normal studies, with one case specifically targeting suppurative retropharyngeal adenitis identification. Residents' free text responses were manually scored by faculty members using a standardized grading rubric, with errors subsequently classified by type. RESULTS: A total of 543 radiology residents were tested in three separate years on the imaging findings of suppurative retropharyngeal lymphadenitis using the Wisdom in Diagnostic Imaging simulation web-based testing platform. Suppurative retropharyngeal lymphadenitis was consistently underdiagnosed by radiology residents being tested for call readiness irrespective of the numbers of years in training. On average, only 3.5% of radiology residents were able to correctly identify suppurative retropharyngeal lymphadenitis on a contrast-enhanced computed tomography (CT). CONCLUSIONS: Our findings underscore a potential gap in radiology residency training related to the accurate identification of suppurative retropharyngeal lymphadenitis, highlighting the potential need for enhanced educational efforts in this area.

[Recurrent lymphadenitis was Kikuchi-Fujimoto disease]. / Lymfadenit som mystiskt återkom var Kikuchi­Fujimotos sjukdom.

Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is in most cases a benign disease which affects lymph nodes in the cervical region. Cervical adenopathy and fever are the most common symptoms, and young adults are mostly affected. Lymph node biopsy is the mode of diagnosis with demonstration of paracortical areas of apoptotic necrosis with abundant karyorrhectic debris and a proliferation of histiocytes, plasmacytoid dendritic cells, and CD8+ T cells in the absence of neutrophils. In most cases, the disease is self-limiting but it can be recurrent or evolve to SLE. Treatment varies from symptomatic to more systemic with cortisone and intravenous immunoglobulin.

Activity of biogenic silver nanoparticles in planktonic and biofilm-associated Corynebacterium pseudotuberculosis.

Corynebacterium pseudotuberculosis is a gram-positive bacterium and is the etiologic agent of caseous lymphadenitis (CL) in small ruminants. This disease is characterized by the development of encapsulated granulomas in visceral and superficial lymph nodes, and its clinical treatment is refractory to antibiotic therapy. An important virulence factor of the Corynebacterium genus is the ability to produce biofilm; however, little is known about the characteristics of the biofilm produced by C. pseudotuberculosis and its resistance to antimicrobials. Silver nanoparticles (AgNPs) are considered as promising antimicrobial agents, and are known to have several advantages, such as a broad-spectrum activity, low resistance induction potential, and antibiofilm activity. Therefore, we evaluate herein the activity of AgNPs in C. pseudotuberculosis, through the determination of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), antibiofilm activity, and visualization of AgNP-treated and AgNP-untreated biofilm through scanning electron microscopy. The AgNPs were able to completely inhibit bacterial growth and inactivate C. pseudotuberculosis at concentrations ranging from 0.08 to 0.312 mg/mL. The AgNPs reduced the formation of biofilm in reference strains and clinical isolates of C. pseudotuberculosis, with interference values greater than 80% at a concentration of 4 mg/mL, controlling the change between the planktonic and biofilm-associated forms, and preventing fixation and colonization. Scanning electron microscopy images showed a significant disruptive activity of AgNP on the consolidated biofilms. The results of this study demonstrate the potential of AgNPs as an effective therapeutic agent against CL.

Extensive Bilateral Cervicofacial Lymphadenitis Caused by Atypical Mycobacterium.

Non-tuberculous mycobacterial (NTM) lymphadenitis typically presents as a unilateral, non-tender, slowly enlarging cervical, submandibular, or pre-auricular lymph node in children. Disseminated NTM infection is most often seen in immunocompromised children. Here, we present an unusual case of extensive bilateral cervical and retropharyngeal lymphadenitis caused by Mycobacterium Avium Complex (MAC) in an ostensibly immunocompetent pediatric patient.

Kawasaki disease in neonates: a case report and literature review.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that affects infants and young children but is extremely rare in neonates, especially afebrile KD. We present a case of KD without fever in a neonate and review the literature on KD in neonates. CASE PRESENTATION: A newborn female was hospitalized because her peripheral blood leukocytes increased for half a day. The admission diagnosis was considered neonatal sepsis and bacterial meningitis. She had no fever since the admission, but a rash appeared on her face by the 7th day. On day 11 after admission, there was a desquamation on the distal extremities. On day 15 after admission, ultrasound showed non-suppurative cervical lymphadenopathy. Echocardiogram revealed coronary artery aneurysms in both sides. Finally, the patient was diagnosed with incomplete KD (IKD). The follow-up echocardiogram showed that the internal diameter of both coronary arteries returned to normal three months after birth. CONCLUSIONS: Fever, rash, and distal extremity desquamation during the recovery phase are the most common symptoms of IKD. When newborns present with clinical manifestations such as rash, distal extremity desquamation and cervical lymph adenitis and with an increased peripheral blood leukocyte count and progressive increase in platelets simultaneously, the medical staff should be highly alert to the possibility of KD even without fever. The echocardiogram needs to be performed promptly. The incidence of coronary artery lesions is significantly higher if neonatal KD patients miss timely diagnosis and treatment.

The spectrum of cytological findings in patients with BCG lymphadenitis: A series of 13 cases.

CONTEXT: Bacillus Calmette-Guérin (BCG) vaccine has been used to prevent tuberculosis and/or its severe complications for long. BCG lymphadenitis is a common complication of the vaccine, which is sometimes subjected to cytological examination. The aim of the study is to describe the cytological findings of BCG lymphadenitis. SETTINGS: The study was conducted in a tertiary care hospital in the western part of India from January 2021 to December 2022. DESIGN: The study was performed on archived material of all patients who were referred to the fine needle aspiration clinic for cytology examination. Clinical and pathological data of cases were retrieved, and cases of BCG lymphadenitis were selected in the study based on these data. Slides of cases were retrieved, and cytological findings were studied. MATERIALS AND METHODS: Papanicolaou, Giemsa, and Hematoxylin & eosin-stained smears, as well as Ziehl-Neelson stain (Z.N. stain) smears of all BCG lymphadenitis cases, were retrieved. Cases were reviewed for individual cytological features and overall cytological diagnostic categories. Z.N. stain smears were evaluated for acid-fast bacilli. RESULTS AND CONCLUSIONS: Diagnostic categories observed in BCG lymphadenitis include suppurative lymphadenitis/abscess (15 %), necrotizing lymphadenitis (23 %), necrotizing granulomatous lymphadenitis (46 %), suppurative granulomatous lymphadenitis (8 %), non-necrotizing granulomatous lymphadenitis (8 %). Acid-fast bacilli were detected by Z.N. stain in 8 cases (62 %). The cytological findings of BCG lymphadenitis closely overlap with those of tuberculous lymphadenitis. So, clinical context is very important while reporting isolated axillary lymphadenopathy, specifically in recently vaccinated infants, to avoid misdiagnosis as tuberculous lymphadenitis.

A comparison of ultrasound-guided aspiration with open surgical drainage in the management of pediatric acute suppurative cervical lymphadenitis.

OBJECTIVES: Image-guided aspiration has been proposed as an alternative to the traditional open drainage in acute suppurative cervical lymphadenitis, although little evidence comparing these approaches exists. The aim of this study was to compare ultrasound-guided aspiration and open surgical drainage in the management of pediatric acute suppurative cervical lymphadenitis. METHODS: Patients treated for acute suppurative cervical lymphadenitis at a tertiary referral pediatric hospital over a three-year period were retrospectively analyzed. RESULTS: Of eighteen patients included, 9 (50 %) underwent aspiration and 9 (50 %) underwent open surgical drainage. None required repeat intervention or readmission over a median follow up of 10.5 weeks. Those undergoing aspiration had a shorter post-operative length of stay (1.67 vs 4.33 days, p = 0.001) compared with open surgical drainage. CONCLUSION: Ultrasound-guided aspiration of pediatric acute suppurative cervical lymphadenitis is a safe and effective alternative to open drainage.

The Detection of Neoplastic Cells Using Objective Cytomorphologic Parameters in Malignant Lymphoma.

Pathologic evaluation is the most crucial method for diagnosing malignant lymphomas. However, there are no established diagnostic criteria for evaluating pathologic morphology. We manually circled cell nuclei in the lesions of 10 patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and reactive lymphadenitis. Seventeen parameters related to nuclear shape, color, and other characteristics were measured. We attempted to compare the statistical differences between these subtypes and extract distinctive disease-specific populations on the basis of these parameters. Statistically significant differences were observed between the different types of lymphoma for many of the 17 parameters. Through t-distributed stochastic neighbor embedding analysis, we extracted a cluster of cells that showed distinctive features of DLBCL and were not found in follicular lymphoma or reactive lymphadenitis. We created a decision tree to identify the characteristics of the cells within that cluster. Based on a 5-fold cross-validation study, the average sensitivity, specificity, and accuracy obtained were 84.1%, 98.4%, and 97.3%, respectively. A similar result was achieved using a validation experiment. Important parameters that indicate the features of DLBCL include Area, ConcaveCount, MaxGray, and ModeGray. By quantifying pathologic morphology, it was possible to objectively represent the cell morphology specific to each lymphoma subtype using quantitative indicators. The quantified morphologic information has the potential to serve as a reproducible and flexible diagnostic tool.

Mycobacterium haemophilum infection in immunocompetent adults: a literature review and case report.

BACKGROUND: Mycobacterium haemophilum has been increasingly found in severely immunocompromised patients but is scarcely reported in immunocompetent adults. METHODS: We systematically reviewed previous literature to identify studies on infection in immunocompetent adults. Articles reporting at least one case of M. haemophilum infection were included. We excluded articles involving patients who had immunosuppression-related diseases and routinely used glucocorticoids or immunosuppressants. We also reported a case of a young immunocompetent woman infected by M. haemophilum along the eyebrows, which was probably due to the use of an eyebrow pencil retrieved from a sink drain. RESULTS: Twelve qualifying articles reporting M. haemophilum infection in immunocompetent adults were identified. Among them, most cases report skin lesions along the eyebrows, and the remaining had cervicofacial lymphadenitis, lesions on the arm or fingers, inflammation in the eyeballs, or ulceration in the perineal region. Most cases were caused by tattoos, make-up, injury, or surgical operation. For diagnosis, specialized tissue culture sensitivity was roughly 75%, and polymerase chain reaction (PCR) test sensitivity was approximately 89%. Triple antibiotic therapy for 3 to 24 months, or surgical excision was effective in controlling infection. CONCLUSION: M. haemophilum infection should be considered if routine antibacterial and glucocorticoid treatments are ineffective against the disease, even in healthy adults. To definitively diagnose this infection, conditioned tissue culture or PCR testing is required. Treatment usually involves a combination of multiple antibiotics and, if necessary, surgical removal of infected tissue.

Comparison of treatment modalities for non-tuberculous mycobacterial cervicofacial lymphadenitis in children.

PURPOSE: We aim to compare the different treatment modalities of non-tuberculous cervicofacial lymphadenitis in children, by means of a retrospective study conducted in the University Hospitals of Leuven of patients treated between 2012 and 2022. METHODS: For this retrospective cohort study, data were collected and pseudonimised from 52 patients with non-tuberculous cervicofacial lymphadenitis, who were treated in our hospital between January 2012 and December 2022, either conservatively, antibiotically, surgically, or with a combination of these options. We only included patients who were considered immunocompetent. All of the included patients were below 10 years at time of treatment. We collected data regarding time to resolution and adverse effects, i.e., skin discoloration, excessive scar formation, fistula formation, persistence of adenopathies after treatment, need for additional treatment, facial nerve paresis/paralysis, or systemic side-effects due to antibiotic treatment. RESULTS: The mean time to resolution (in days) when looking at primary treatments, was shortest in partial excisions (16), followed by complete excisions (19), antibiotic therapy (129), incision and drainage (153), curettage (240), and finally conservative management (280). Taking into account isolated treatments (i.e., both primary and adjuvant), we also observed consistently faster time to resolution in surgical and antibiotic treatments when compared to conservative treatment. Antibiotic therapy (p = 0.003), incision and drainage (p = 0,004) were associated with a significantly higher need for adjuvant treatment. Curettage was associated with a higher incidence of fistula formation (p = 0,006) and higher number of adjuvant treatments (p = 0,002). CONCLUSIONS: This study shows a faster resolution of nontuberculous mycobacterial cervicofacial lymphadenitis in children when treated surgically, more specifically when treated with partial or complete lymph node excision. Antibiotic treatment also leads to faster resolution than conservative management. There was a low rate of complications, and no permanent facial nerve damage was reported.

Tonsillotomy for Periodic Fever Syndrome: A Randomized and Controlled Trial.

OBJECTIVE: Tonsillectomy is an effective treatment for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Tonsillotomy has a milder operative risk profile and postoperative morbidity in children than tonsillectomy. We aimed to compare the efficacy of tonsillotomy to observation-only in children with PFAPA syndrome at a 3-month follow-up. METHODS: This was a randomized multicenter trial with sequential design. Participants were randomized into a tonsillotomy group and a control group that was only observed. The trial started in 1/2017 and was accomplished in 12/2021 with 16 patients (10 boys, six girls, the mean age 4.2 years). The symptoms were monitored with daily symptom diaries. RESULTS: After the 3-month follow-up, 7/8 patients (87.5%) in the tonsillotomy group and 2/8 (25%) patients in the control group were free from PFAPA symptoms (95% CI 13% to 87%; p = 0.0021). The mean number of days with fever was 2.6 (SD 3.7) in the tonsillotomy group and 8.0 (SD 6.5) days in the control group (n = 8) (p = 0.06). Mean number of fever days compatible with PFAPA syndrome was 0.8 (SD 1.4) in the tonsillotomy group and 6.5 (SD 6.0) in the control group (95%CI -10% to -1%; p = 0.007). Rescue tonsillectomy was needed for all patients in the control group and none of the patients in the tonsillotomy group. CONCLUSIONS: Tonsillotomy might be an effective treatment option for children with PFAPA syndrome. Further studies are needed to clarify the long-term efficacy of tonsillotomy for treating PFAPA. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:968-972, 2024.

Management of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis with Intracapsular Tonsillectomy.

OBJECTIVE: This study aimed to present 2 children clinically diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and treated with intracapsular tonsillectomy with adenoidectomy (ITA). METHODS: We conducted a retrospective analysis of 2 children who were referred for an otolaryngology consultation between 2019 and 2022 for surgical treatment of PFAPA syndrome. Both patients had symptoms strongly suggestive of PFAPA and were at risk for total tonsillectomy (TT) complications. ITA was performed using a microdebrider. Both patients were followed up postoperatively to assess for symptomatic resolution and complications. RESULTS: Two children exhibited recurrent febrile episodes prior to ITA. The procedure was efficacious in both patients, with neither experiencing postoperative complications or recurring PFAPA symptoms for over 1 year after surgery. CONCLUSION: Our study reported on the use of ITA as a surgical treatment option for PFAPA. We showed that ITA eliminated febrile attacks and was safely performed without postoperative complications in 2 pediatric patients after 1-year follow-up. Future studies involving larger cohorts of PFAPA patients and lengthier follow-ups will need to be conducted to further evaluate ITA as a surgical option. Laryngoscope, 134:1967-1969, 2024.

The application of a multidisciplinary approach in the diagnosis of Castleman disease and Castleman-like lymphadenopathies: A 20-year retrospective analysis of clinical and pathological features.

BACKGROUND: Castleman disease (CD) comprises a group of rare and heterogeneous haematological disorders, including unicentric (UCD) and multicentric (MCD) forms, the latter further subdivided into HHV8-MCD, POEMS-MCD and idiopathic-MCD (iMCD). However, according to the Castleman Disease Collaborative Network guidelines, the diagnosis of CD can only be achieved through collaboration between clinicians and pathologists. METHODS: We applied these clinical and pathological criteria and implement with clonality testing to a retrospective cohort of 48 adult and paediatric Italian patients diagnosed with reactive lymphadenitis with CD-like histological features. RESULTS: We confirmed the diagnosis of CD in 60% (29/48) of the cases, including 12 (41%) UCD and 17 (59%; five HHV8-MCD, three POEMS-MCD and nine iMCD) MCD. Of the remaining 19 cases (40%) with multiple lymphadenopathy, 5 (26%) were classified as autoimmune diseases, 1 (5%) as autoimmune lymphoproliferative disorder, 1 (5%) as IgG4-related disease, 11 (83%) as reactive lymphadenitis and 1 (5%) as nodal marginal zone lymphoma. CONCLUSIONS: Our study emphasizes the importance of the multidisciplinary approach to reactive lymphadenitis with CD-like features in order to achieve a definitive diagnosis and choose the appropriate treatment.