The Current and Future Impact of Lymph Node Fine-Needle Aspiration Cytology on Patient Care.

Lymph node (LN) fine-needle aspiration cytology (FNAC) is a common diagnostic procedure for lymphadenopathies. Despite the qualities and potentialities of LN-FNAC, the number of possible pathologies and the variety of clinical contexts represent a challenge and require a continuous upgrading of the procedure according to the emerging clinical requests and new technologies. This study presents an overview of the current and future impact of LN-FNAC on the care of patients with lymphadenopathy.

Mediastinal lymphadenopathy due to VEXAS syndrome.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a rare disease first reported in 2020, most commonly seen in men aged 56-75 years old. Common clinical features include skin lesions (83.5%), fever (63.6%), relapsing chondritis (36.4%), venous thrombosis (34.7%) and lymph node enlargement (33.9%). The patient is a man in his 40s who presented with testicular and lower extremity pain, followed by a rash and bicytopenia. He was initiated on corticosteroids and sulfasalazine. He was found to have mediastinal lymphadenopathy and underwent an endobronchial ultrasound and transbronchial needle aspiration followed by a video-assisted thoracic surgery biopsy which were unrevealing. Eventually, an ubiquitin-like modifier activating enzyme (UBA-1) gene analysis was performed that was consistent with VEXAS syndrome. Patients with VEXAS syndrome usually present with a red or violaceous rash and dyspnoea. Laboratory abnormalities include anaemia, elevated mean corpuscular volume, thrombocytopenia and elevated inflammatory markers. Diagnosis is based on the genetic mutation and associated symptoms. The treatment includes steroids and Janus kinase (JAK) inhibitors, specifically ruxolitinib.

Clinical prediction model for pediatric lymphadenopathy: enhancing diagnostic precision and treatment decision making.

INTRODUCTION: Lymph node enlargement is common in children, with 90% of physiologically palpable lymph nodes. This study aimed to develop a predictive model based on clinical characteristics to enhance the diagnosis of pediatric lymphadenopathy and provide insights into biopsy outcomes. MATERIALS AND METHODS: A clinical prediction rule was developed using a retrospective, cross-sectional design for patients under 15 years who underwent lymph node biopsy from 2012 to 2022. Multivariable risk regression was used to analyze benign and malignant lesions, presenting results through risk difference and AUROC for each group. Predicted probabilities were applied in a logistic regression equation to classify patients' lymphadenopathy as reactive hyperplasia, benign, or malignant. RESULTS: Of 188 children, 70 (37.2%) had benign lymphadenopathy beyond reactive hyperplasia, and 27 (14.4%) had malignant lymphadenopathy. The predictive model included 12 characteristics such as size, location, duration, associated symptoms, and lymph node examination. Predictive accuracy was 92.2% for benign cases (AUROC = 0.92; 95% CI 0.87-0.96) and 98.6% for malignancy (AUROC = 0.98; 95% CI 0.94-0.99). Overall accuracy for predicting both benign and malignant tumors was 68.3%. CONCLUSION: The model demonstrated reasonably accurate predictions for the clinical characteristics of pediatric lymphadenopathy. It tended to overestimate malignancy but did not miss diagnoses, aiding in reducing unnecessary lymph node biopsies in benign cases.

Lymphadenopathy: Differential Diagnosis and Indications for Evaluation.

Lymphadenopathy is a common finding on physical examination in the pediatric population. Although it is often physiologic, lymphadenopathy can also be associated with more serious illnesses and has many possible etiologies. A broad differential diagnosis can be narrowed with a thorough clinical history, physical examination, laboratory studies, and imaging. The goal of this review is to provide a framework for understanding normal physiology, identify when enlarged lymph nodes may be associated with pathology, develop differential diagnoses associated with lymphadenopathy, and apply a systematic approach for diagnostics and appropriate management, with a focus on findings concerning for malignancy and the initial evaluation.

A 53-Year-Old Woman with Axillary Lymphadenopathy.

AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 53-year-old woman with a history of breast cancer who presented with abnormal axillary lymph nodes detected on surveillance imaging. Using history, physical examination, and diagnostic workup, an illness script for her presentation emerges. A differential diagnosis is developed and refined until a final diagnosis is confirmed.

Reevaluating Diagnosis of Sarcoidosis: Biopsy with Necrosis in Mycobacterial Endemic Areas.

BACKGROUND: Sarcoidosis is a multisystem inflammatory disease with a variable presentation. The most characteristic feature of sarcoidosis is nonnecrotizing granulomas. However, when sarcoidosis presents with rare organ involvement, and biopsy shows necrosis, the diagnosis becomes challenging. CASE PRESENTATION: Here, we present three cases of sarcoidosis with unusual organ involvement and biopsy findings of necrosis, leading to a delay in diagnosis and treatment. Case 1 was presented with lymphoreticular involvement within the intraparotid lymph node and genitourinary area. Biopsy from the epididymis showed necrosis, initially leading to treatment for tuberculosis (TB). Case 2 describes lymphoreticular involvement and cardiac symptoms. His cervical and bone marrow biopsies showed necrosis. Case 3's presentation was disseminated lymphadenopathy with hepatosplenomegaly, initially suspected as malignancy or TB. CONCLUSION: While biopsy plays a significant role in diagnosing sarcoidosis, the presence of necrosis alone should not lead to its exclusion.

[A Case of Xanthogranulomatous Pyelonephritis with Multiple Lymphadenopathy that was Difficult to Differentiate from Renal Tumor].

A 74-year-old woman presented to our hospital with the main complaint of anorexia and weight loss for several months. Computed tomography (CT) revealed right urinary stone, hydronephrosis, multiple lymphadenopathy, and a mass in the right kidney. Considering these findings, she was suspected to have renal malignancy (kidney or renal pelvis cancer) with multiple lymph node metastases; therefore, nephrectomy was performed. Her pathological diagnosis was xanthogranulomatous pyelonephritis (XGPN). There was no postoperative renal function decline, and multiple lymphadenopathy also disappeared on CT 3 months after surgery. It was judged to be reactive swelling due to inflammation. XGPN is a pathological condition characterized by accumulation of mast cells and activated macrophages in the renal tissue; and, the renal tissue recognizes yellowish granulation growth because of repeating pyelonephritis due to urinary tract passing impairment. In some cases, it is difficult to differentiate XGPN from renal malignancy. Moreover, lymphadenopathy may be lymph node metastasis but may also present reactive enlargement due to the effect of inflammation, making it even more difficult to differentiate when accompanied by lymphadenopathy. We report this case in which it was difficult to differentiate XGPN from renal malignancy considering the scarcity of reports of XGPN accompanied by multiple lymphadenopathy.

An atypical presentation of human monkeypox infection with clinicopathologic correlation.

There is growing evidence to support new modes of transmission for human monkeypox infection. As these methods are being explored, this report delineates the day-to-day clinical sequelae following the initial exposure in an HIV-positive man who had sexual intercourse with another man days preceding his infection. We describe atypical cutaneous manifestations involving widespread erythematous pustules with preceding anogenital ulcerations and concomitant bilateral inguinal lymphadenopathy. Clinicopathologic correlation is used to assist in the workup and establishing the diagnosis. Our case supports others reported in the literature that suggest sexual contact as a means of transmission. More research is needed that investigates the presence of infection in both men and women, including those who could act as carriers, to elucidate other pathways in this evolving yet evasive viral disease.

Endobronchial ultrasound-guided transbronchial fine needle aspiration of mediastinal lymphadenopathy: Diagnostic performance and clinical implications of the World Health Organization reporting system.

INTRODUCTION: Lymph node fine-needle aspiration cytology (LN-FNAC) is a common, rapid, minimally invasive and cost-effective diagnostic method. For mediastinal lymph nodes, endobronchial ultrasound (EBUS) guided LN-FNAC is a first-line investigation and has an indispensable role in the diagnosis and staging of patients with suspected lung cancer. Recently, a new WHO system has been proposed for classification of LN-FNAC heralding five different diagnostic categories; insufficient, benign, atypical, suspicious for malignancy and malignant. The aim of this study was to evaluate the diagnostic accuracy and risk of malignancy (ROM) of these categories in EBUS-guided LN-FNAC from mediastinal lymph nodes. METHOD: We evaluated 2110 consecutive mediastinal lymph nodes during this one-year retrospective study. Corresponding radiological images and histologic material were used as ground truth to calculate accuracy, sensitivity, specificity and ROM. RESULTS: The WHO system showed an overall accuracy of 93.7% with a sensitivity of 83.0% and a specificity of 97.5%. The positive predictive value was 92.3% and the negative predictive value 94.2%. The overall ROM for each category in the WHO classification system was 12.8% for the inadequate, 2.4% for the benign, 47.4% for the atypical, 81.0% for the suspicious for malignancy and 93.6% for the malignant category. CONCLUSION: The results of the present study indicate that the new WHO system entails a high diagnostic accuracy regarding EBUS-guided LN-FNAC assessment of mediastinal lymph nodes and supports its integration into clinical practice. Application of the WHO system standardizes risk assessment thus facilitating communication between cytopathologists and clinicians and minimizes the need for histopathological analysis.

Diagnostic approach of tuberculous lymphadenitis in a multicenter study.

INTRODUCTION: Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the demographic, clinical, and laboratory variables that differentiate TBLN from non-tuberculous lymphadenitis (NTBLN), as well as the etiology of lymphadenopathy in adults. METHODOLOGY: Patients who were over 18 years old and were referred to the infectious disease outpatient clinics with complaints of swollen peripheral lymph nodes, and who underwent lymph node biopsy between 1 January 2010 and 1 March 2021, were included in this multicenter, nested case-control study. RESULTS: A total of 812 patients at 17 tertiary teaching and research hospitals in Turkiye were included in the study. TBLN was the most frequent diagnosis (53.69%). The proportion of patients diagnosed with TBLN was higher among females; and among those who had a higher erythrocyte sedimentation rate, positive purified protein derivative test, and positive interferon-gamma release test result (p < 0.05). However, TBLN was less frequent among patients with generalized lymphadenopathy, bilateral lymphadenopathy, axillary lymphadenopathy, inguinal lymphadenopathy, hepatomegaly, splenomegaly, leukocytosis, and moderately increased C reactive protein levels (p < 0.05). CONCLUSIONS: Identifying the variables that predict TBLN or discriminate TBLN from NTBLN will help clinicians establish optimal clinical strategies for the diagnosis of adult lymphadenopathy.

Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review.

Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "atypical lymphoplasmacytic and immunoblastic lymphadenopathy" from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial.

Significance of Various Diagnostic Modalities in Detection of Tuberculosis in Cervical Lymphadenopathy: A Study of 200 Cases.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) makes for 25% of all instances of tuberculosis (TB) patients. The enigmatic clinical presentation of EPTB makes identification difficult since it simulates other chronic conditions such as neoplastic and inflammatory disorders and could culminate in treatment that is either insufficient or not required. For an affirmative and confirmed diagnosis, a substantial level of suspicion is imperative. The paucibacillary feature of EPTB makes diagnosis extremely difficult and necessitates the use of many diagnostic methods to arrive at a precise diagnosis. In December 2010, the World Health Organization recommended using GeneXpert/cartridge-based nucleic acid amplification test (CBNAAT) for the initial assessment of suspected cases of EPTB. Furthermore, fine-needle aspiration cytology (FNAC), Ziehl-Neelsen (ZN) stain, and the CBNAAT have to be utilized to exclude other possible origins of granulomatous inflammation. The goal of the current investigation is to comprehend how FNAC and ZN stains relate to CBNAAT and their diagnostic value. METHODS: The evaluation included all suspected instances of tubercular lymphadenopathy, and adequate aspirates were obtained from the site of the enlarged cervical lymph nodes. Smears were made following FNAC and stained with ZN stain as well as hematoxylin and eosin stain. Simultaneously, CBNAAT and culture evaluations were conducted on the same aspirates. This cross-sectional study took place at a tertiary care center and encompassed 200 individuals with clinical manifestations of EPTB. RESULTS: There were 200 cases of suspected tubercular lymphadenitis (TBLN). According to the FNAC results, TBLN was detected in 71 (47.6%) of these 200 cases, followed by necrotizing lymphadenitis in 56 (37.5%), chronic caseating granulomatous lymphadenitis in 47 (31.5%), and reactive lymphadenitis in 26 (17.4%). They were correlated with CBNAAT results, which showed that all instances of tuberculous lymphadenitis, 85.71% of cases of necrotizing lymphadenitis, 55.32% of cases of chronic caseating granulomatous lymphadenitis, and 2 (7.69%) cases of reactive lymphadenitis were CBNAAT positive. CONCLUSION: CBNAAT should be utilized with FNAC and ZN staining to diagnose EPTB. The CBNAAT assay demonstrated a significant advantage in the identification of previously unidentified FNAC patients. Despite being a simple diagnostic tool, FNAC has a lower specificity and significantly lower precision than CBNAAT in correctly identifying cases of EPTB because it exhibits similar cytomorphological characteristics with lesions that are not associated with TB.

Using T2-weighted magnetic resonance imaging-derived radiomics to classify cervical lymphadenopathy in children.

BACKGROUND: Cervical lymphadenopathy is common in children and has diverse causes varying from benign to malignant, their similar manifestations making differential diagnosis difficult. OBJECTIVE: This study aimed to investigate whether radiomic models using conventional magnetic resonance imaging (MRI) could classify pediatric cervical lymphadenopathy. METHODS: A total of 419 cervical lymph nodes from 146 patients, and encompassing four common etiologies (Kikuchi disease, reactive hyperplasia, suppurative lymphadenitis and malignancy), were randomly divided into training and testing sets in a ratio of 7:3. For each lymph node, 1,218 features were extracted from T2-weighted images. Then, the least absolute shrinkage and selection operator (LASSO) models were used to select the most relevant ones. Two models were built using a support vector machine classifier, one was to classify benign and malignant lymph nodes and the other further distinguished four different diseases. The performance was assessed by receiver operating characteristic curves and decision curve analysis. RESULTS: By LASSO, 20 features were selected to construct a model to distinguish benign and malignant lymph nodes, which achieved an area under the curve (AUC) of 0.89 and 0.80 in the training and testing sets, respectively. Sixteen features were selected to construct a model to distinguish four different cervical lymphadenopathies. For each etiology, Kikuchi disease, reactive hyperplasia, suppurative lymphadenitis, and malignancy, an AUC of 0.97, 0.91, 0.88, and 0.87 was achieved in the training set, and an AUC of 0.96, 0.80, 0.82, and 0.82 was achieved in the testing set, respectively. CONCLUSION: MRI-derived radiomic analysis provides a promising non-invasive approach for distinguishing causes of cervical lymphadenopathy in children.

Presentation of B-cell lymphoma in childhood and adolescence: a systematic review and meta-analysis.

BACKGROUND: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. AIMS: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence. METHODS: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis. RESULTS: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin's lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin's lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%]). CONCLUSION: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease.

Clinical features and recurrence predictors of histiocytic necrotizing lymphadenitis in Chinese children.

OBJECTIVES: To characterize the clinical features and to identify the predictors of recurrence of histiocytic necrotizing lymphadenitis (HNL) in Chinese children. STUDY DESIGN: This study retrospectively analyzed the clinical characteristics, laboratory and pathological findings, and recurrence status of children diagnosed with HNL at a single center in China from January 2018 to May 2023. Logistic regression analysis was employed to identify predictors of HNL recurrence. RESULTS: 181 Chinese children with histopathologically confirmed HNL were enrolled (121 males and 60 females). The mean age was 9.3 ± 2.9 years. The most prominent clinical features were fever (98.9%) and cervical lymphadenopathy (98.3%). Aseptic meningitis was the most frequent complication (38.5%), while hemophagocytic lymphohistiocytosis and autoimmune disease were rare (1.7% and 1.2%, respectively). Recurrence occurred in 12.7% of patients. Erythrocyte sedimentation rate (> 30 mm/h) was the significant predictors of HNL recurrence, with odds ratios of 6.107, respectively. CONCLUSION: Our study demonstrates that fever and cervical lymphadenopathy are the most frequent clinical manifestations of HNL in Chinese children, which often coexist with aseptic meningitis. HNL patients with risk factors require follow-up for recurrence.

Francisella tularensis Infection Causing Parinaud Oculoglandular Syndrome.

BACKGROUND Parinaud oculoglandular syndrome is a unilateral granulomatous palpebral conjunctivitis associated with preauricular, submandibular, and cervical lymphadenopathies. Several infectious diseases can cause Parinaud oculoglandular syndrome, usually with a conjunctival entry. The most common underlying pathology is cat scratch disease, followed by the oculoglandular form of tularemia. Diagnosis is usually a serious challenge as these infections are themselves rare. On the other hand, Parinaud oculoglandular syndrome may be a rare manifestation of more common disorders (eg, tuberculosis, syphilis, mumps, herpes simplex and Epstein-Barr virus, adenovirus, Rickettsia, Sporothrix, Chlamydia infections). CASE REPORT We present the case of a 66-year-old man with granulomatous conjunctivitis and ipsilateral preauricular, submandibular, and upper cervical lymphadenopathies following a superficial corneal injury. Although the systematic amoxicillin/clavulanic acid and metronidazole antibiotic therapy started immediately at admission, the suppuration of the lymph nodes required surgical drainage. Based on his anamnesis (sheep breeding; a twig scratching his eye 2 days before the initial attendance) and symptoms, a zoonosis, namely the oculoglandular form of tularemia, was suspected, empiric ciprofloxacin therapy was administered, and the patient recovered without sequelae. The Francisella tularensis infection was eventually confirmed by microagglutination serologic assay. CONCLUSIONS If Parinaud oculoglandular syndrome is diagnosed and cat scratch fever as the most common etiology is not likely, other zoonoses, especially the oculoglandular form of tularemia, should be suspected. Serology is the most common laboratory method of diagnosing tularemia. Empiric fluoroquinolone (ciprofloxacin) or aminoglycoside (gentamicin or streptomycin) antibiotic therapy should be started immediately at the slightest suspicion of oculoglandular tularemia.