A case of gaucher disease with a rare complication of gaucheroma and protein-losing enteropathy.

This case report describes a patient initially diagnosed with Gaucher disease (GD) with type I with homozygous mutation c.1448T > C p. (Leu483Pro) at age of 2, presenting with hepatosplenomegaly and cytopenia. Imiglucerase replacement therapy was initiated. At age 17, bilateral hearing loss developed, with subsequent Cranial MRI revealing thalamic damage, leading to a reclassification as type 3 GD. By age of 20, the patient presented with a range of symptoms, including abdominal pain, diarrhea, hypoproteinemia, multiple lymphadenopathy, edema, and Gaucher cell infiltration in the lymph nodes. Comprehensive diagnosis identifies Gaucher tumor and protein-losing enteropathy. Imiglucerase therapy at 90-120 U/kg every 2 weeks significantly improved clinical symptoms, emphasizing the importance of tailored interventions for managing GD manifestations.

Extranodal Rosai-Dorfman disease manifesting as Sjögren's syndrome combined with panuveitis and hypertrophic pachymeningitis: a case report and review of literature.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by massive lymphadenopathy and systemic extranodal lesions. We present the case of a 28-year-old woman who presented with recurrent blurred vision in her right eye for 3 months. She developed blindness and atrophy in her left eye a decade prior to presentation. She subsequently developed headache, fever, and impaired mental status. Cranial magnetic resonance imaging indicated hypertrophic pachymeningitis (HP), and 18F-fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography revealed significant FDG uptake in the left dura mater. Autoimmune testing revealed elevated anti-nuclear, anti-SS-A, and anti-SS-B antibody levels. Incisional biopsy of the atrophic eyeball revealed RDD with marked polyclonal plasmacytosis. The patient was diagnosed with RDD accompanied by multisystem involvement, including Sjögren's syndrome (SS), panuveitis, and HP. Treatment with methylprednisolone for several weeks resulted in significant improvement. This is the first reported case of RDD presenting with SS in combination with panuveitis and HP. Although RDD is rarely diagnosed in young patients, interdisciplinary collaboration is essential to prevent a delayed diagnosis.

Mediastinal Rosai-Dorfman Disease with KRAS mutation case report and literature review.

BACKGROUND: Rosai-Dorfman Disease (RDD) is a rare self-limiting histiocytosis, more prevalent in children and young adults. It typically manifests as painless bilateral massive cervical lymphadenopathy but may also extend to extra-nodal sites, with intrathoracic RDD noted in 2% of cases. Distinguishing mediastinal RDD from thymoma on imaging poses challenges, underscoring the reliance on pathological features and immunohistochemical staining for diagnosis. CASE PRESENTATION: Patient, male, 33 years old, underwent lung a CT revealing an enlarged round soft tissue shadow in the anterior superior mediastinum, compared to a year ago. Surgical resection removed the entire mass, thymus, and part of the pericardium, confirming RDD on pathology. Genetic testing using second-generation testing technology identified a KRAS gene point mutation. CONCLUSIONS: No established treatment protocol currently exists for this disease. However, as genetic mutation research progresses, a novel therapeutic avenue is emerging: targeted therapy integrated with surgical interventions.

Management of Persistent Low-Suspicion Cervical Lymphadenopathy in Pediatric Patients.

INTRODUCTION: Cervical lymphadenopathy in children is typically self-limited; however, the management of persistent lymphadenopathy remains unclear. This study aimed to evaluate the management and outcomes of patients with persistent cervical lymphadenopathy. METHODS: Single-institution, retrospective review of children <18 years undergoing ultrasound (US) for cervical lymphadenopathy from 2013 to 2021 was performed. Patients were stratified into initial biopsy, delayed biopsy, or no biopsy groups. Clinical characteristics and workup were compared, and multivariate analyses were performed to assess predictors of delayed biopsy. RESULTS: 568 patients were identified, with 493 patients having no biopsy, 41 patients undergoing initial biopsy, and 34 patients undergoing delayed biopsy. Presenting symptoms differed: no biopsy patients were younger, were more likely to present to the emergency department, and had clinical findings often associated with acute illness. Patients with USs revealing abnormal vascularity or atypical architecture were more likely to be biopsied. History of malignancy, symptoms >1 week but <3 months, and atypical or change in architecture on US was associated with delayed biopsy. Patients with long-term follow-up (LTF) were followed for a median of 99.0 days. Malignancies were identified in 12 patients (2.1%). All malignancies were diagnosed within 14 days of presentation, and no malignancies were identified in LTF. CONCLUSIONS: Patients with persistent low suspicion lymphadenopathy are often followed for long durations; however, in this cohort, no malignancies were diagnosed during LTF. We propose an algorithm of forgoing a biopsy and employing primary care surveillance and education, which may be appropriate for these patients in the proper setting.

Multiple lymphadenopathies in eosinophilic granulomatosis with polyangiitis: differentiating from IgG4-related lymphadenopathy.

We report a case of eosinophilic granulomatosis with polyangiitis (EGPA) in a 75-year-old man who developed mononeuritis multiplex and purpura in the lower legs concomitantly presenting with lymphadenopathies. Biopsied lymph node tissue pathologically demonstrated fibrinoid necrotizing vasculitis with perivascular eosinophil infiltration, resulting in EGPA diagnosis. Additionally, abundant IgG4-positive plasma cell infiltration exhibiting >70% IgG4/IgG ratio, without storiform pattern fibrosis and obliterative phlebitis, was observed in the biopsied lymph node. Clinical improvement was observed after corticosteroid therapy. IgG4-related lymphadenopathy (IgG4-LAD) has been defined as a distinct clinical category regardless of fulfilling IgG4-related disease classification criteria. However, some autoimmune diseases, including EGPA, can develop lymphadenopathy pathologically similar to IgG4-LAD.

Recurrence of sarcoidosis accompanied by lung cancer after drug-induced pulmonary sarcoidosis with lung injury.

Sarcoidosis is a multisystemic granulomatous disease that is frequently localized in the lungs and lymph nodes. We herein report a case of pulmonary sarcoidosis secondary to shin'iseihaito administration. During remission with 5 mg prednisolone/day of maintenance treatment, chest computed tomography revealed a mass in the left lower lobe with re-enlarged bilateral hilar/mediastinal lymph nodes. Transbronchial lung biopsy of the mass and endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes revealed adenocarcinoma and noncaseating granulomas, respectively. Based on these findings, the patient was diagnosed with sarcoidosis recurrence associated with lung cancer without cancer metastasis. We present the case of sarcoidosis recurrence associated with lung cancer after drug-induced pulmonary sarcoidosis with lung injury. To our knowledge, this is the first report of sarcoidosis triggered by drug administration and lung cancer. Histological diagnosis of mediastinal lymphadenopathy with lung cancer is essential for differentiating metastasis from sarcoidosis.

Kaposi's Sarcoma with Primary Lymph Node Involvement in a Retroviral Infected (RVI) Patient.

One kind of angioproliferative disorder is Kaposi's sarcoma (KS). Growth of spindle-shaped cells, edema, inflammation, and neoangiogenesis are its defining features. Because it lacks the typical indicators of malignancy, it is classified as an intermediate neoplasm. People who are immunocompromised, receiving organ transplants, or receiving antiretroviral therapy are linked to KS. Although lymph node involvement by KS is extremely uncommon, when it does occur, it usually manifests as either the epidemic form in (Human Immuno-deficiency) HIV-positive patients or the endemic form in Africans. There are four primary clinical manifestations of KS that have been documented: endemic, epidemic, iatrogenic, and classic. The diagnosis of KS is made by history, physical examination, and tissue biopsy. When treating localized disease, highly active antiretroviral therapy (HAART) may be sufficient to either improve or completely eradicate the illness. Nonetheless, chemotherapy and HAART would be necessary in the case of widespread illness. Here, we present the case of a 28-year-old female patient who is HIV positive and has a viral load that is not detected. She presented with generalized lymphadenopathy of 8 months duration. She had no cutaneous manifestations. The lymphadenopathy involved the tonsils, axilla, inguinal, and an unusual site, intraparotid on both sides. After a pathologic examination of the lymph nodes, she was found to have epidemic-type KS and was treated with HAART and chemotherapy. In our nation, we are not aware of any published case reports pertaining to a case like this. The purpose of this case report is to raise physicians' awareness of this uncommon ailment and to encourage them to suspect KS when HIV patients exhibit generalized lymphadenopathy. The early initiation of systemic treatment is lifesaving for these patients.

Kikuchi-Fujimoto Disease: A Case Report of Prolonged Fever and Lymphadenopathy in a Young Girl.

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disorder that usually presents with regional cervical lymphadenopathy and fever. We report a case of a 12-year-old female who complained of fever, night sweating, significant weight loss, and tender right cervical lymph node enlargement for 2 months. A full workup including laboratory tests and imaging studies, an excisional biopsy, and histopathological analysis were done, and the diagnosis of KFD was confirmed. The patient was treated with analgesia and oral prednisolone, resulting in good improvement. A high degree of clinical suspicion is imperative for physicians, given the rarity of the disease and the associated diagnostic challenges.

Brucellosis Presenting as Isolated Abdominal Lymphadenopathy Masquerading as Lymphoma: A Case Report.

Mesenteric lymphadenopathy associated with high-grade fever can be frequently associated with hematologic malignancies, especially if accompanied by joint pain, weight loss, and anorexia. However, this constellation of symptoms, also known as "B Symptoms," can be the uncommon presenting manifestation of brucellosis, still a common zoonotic disease in the Middle Eastern basin. In this article, we report the case of a Lebanese man who presented with "B symptoms" of three weeks duration, who was thought to have lymphoma but was later found to have systemic brucellosis.

Pyrexia of Unknown Origin Caused by Non-Hodgkin's Lymphoma: A Diagnostic Challenge for Clinicians.

Non-Hodgkin's lymphomas (NHLs) are a group of lymphoproliferative diseases that originate from different cell types, namely B cells, T cells, or natural killer cells. Herein, we report the case of a 69-year-old male patient who presented with a gradual-onset, intermittent, low-grade fever for four months and a right-sided neck lump for two months. On examination, a right-sided enlarged lymph node sized 1 × 1 cm2 was noted, which was mobile, hard in consistency, and non-tender. No other lymphadenopathy was noted in other parts of the body. Imaging and biochemical studies done at the initial stages did not reveal features in favor of any lymphoproliferative disorders, and the two lymph node biopsies done two weeks apart were inconclusive as well. An extended panel of investigations was done in view of excluding other infective and inflammatory pathologies, which was negative, making the patient undiagnosed of any disease state despite being symptomatic for four months. Finally, the third lymph node biopsy tested positive, which paved the way for the diagnosis of NHL. This diagnosis underlines the importance of this case. Following the diagnosis, the patient was initiated on a few chemotherapeutic agents, after which a mild symptomatic improvement was achieved.

Malignancy-Associated Secondary Hemophagocytic Lymphohistiocytosis Mimicking an Infection: A Case Report and Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hematological disorder of immune dysregulation associated with significant challenges in diagnosis and management. Described as primary HLH secondary to genetic defects or more commonly secondary to infections, it can also occur secondary to malignancy, i.e., malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH). A five-year-old male child presented with left cervical adenopathy and a high-spiking fever for two weeks. He had pallor, anasarca, multiple enlarged and matted cervical lymph nodes, respiratory distress, and hepatomegaly. He had continuous high-grade fever spikes (maximum 105 °F), not touching baseline despite broad-spectrum antibiotics. The CBC revealed anemia with thrombocytopenia. Liver function tests showed mild transaminitis and hypoalbuminemia. The HLH workup showed elevated ferritin, low fibrinogen, and elevated triglycerides. Lymph node biopsy showed intermediate to large atypical monomorphic lymphocyte cells with ALK, CD30, CD5, CD3, CD45, and BCL-2 (weak positive) positivity and Ki-67-95%, suggestive of anaplastic large cell lymphoma (ALCL). The bone marrow aspiration showed reactive marrow with hemophagocytosis. The patient was started on dexamethasone and chemotherapy per the Children's Oncology Group's (COG) ALCL protocol. He showed remarkable clinical improvement and went into remission after the induction phase. Malignancy associated with HLH can mimic infection, as in our patient with high-spiking fever, consolidation, and mediastinal adenopathy. A high index of suspicion is necessary to arrive at an appropriate, early diagnosis, and workup for malignancy is to be considered when an infectious etiology is not identified after thorough evaluation.

Clinical Management of Mantle Cell Lymphoma With Concurrent Vascular Complications: A Case Report.

This is a case of a 70-year-old patient with no past medical history but a significant family history of cancer, who was admitted with acute pulmonary embolism and left lower extremity deep vein thrombosis concerning malignancy. Further investigations revealed mantle cell lymphoma. This case highlights the complex clinical management of patients presenting with concurrent hematological malignancy and vascular complications.

Kikuchi-Fujimoto Disease: A Rare Presentation in a Young Male.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare benign condition characterized by cervical lymphadenopathy and constitutional symptoms mimicking tuberculosis. We present the case of a 22-year-old male who presented with fever, dry cough, loss of appetite, multiple joint pains for 15 days, and loss of weight for one month. Physical examination revealed palpable cervical, occipital, axillary, and inguinal lymphadenopathy, and laboratory investigations were within normal limits except for raised erythrocyte sedimentation rate (ESR). Contrast-enhanced computed tomography (CECT) showed mediastinal lymphadenopathy with no pleuroparenchymal abnormality of the lung. Excision biopsy of a cervical lymph node confirmed necrotizing lymphadenitis consistent with KFD. The patient was treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, resulting in the resolution of symptoms and regression of lymphadenopathy. This case signifies the importance of considering KFD in the differential diagnosis of lymphadenopathy and highlights the significance of histopathological evaluation for accurate diagnosis and management guidance.

Fine Needle Aspiration Cytology of Lymph Nodes in Metastatic Cancer and Lymphoma: Our Single-institution Experience.

Background: Lymphadenopathy is a common finding in clinical practice. The cause of enlarged nodes on clinical examination alone is challenging and there may be multiple reasons for this enlargement. It may become enlarged due to stimulation by infectious agents or the involvement of metastasis or malignant diseases, such as lymphoma. Objective: The aim of the study was to investigate the diagnostic role of fine needle aspiration cytology of lymph nodes in metastatic cancer and lymphoma. Methods: A total of 48 FNAC lymph nodes suspicious for malignancy were sampled with follow-up biopsy in Clinical Center of University of Sarajevo from 2017 to 2023. Lymph nodes were aspirated using 20-22 G needle with minimally 2 passes, spread on slides, air-dried, stained with May-Grünwald-Giemsa or Papanikolaou and residual material sent for cytoblock. Results: Out of 48 cytological samples, 30 (62.5%) revealed metastatic epithelial cells and 12 (25%) lymphoproliferative neoplasm. Three samples were suspected for malignancies, one sample was unrepresentative, one inconclusive and one falsely negative. Histopathological confirmation had 35 patients, while others were confirmed based on clinical presentation and radiological techniques. Compared to histopathological diagnosis, cytology had a sensitivity of 89.47%, specificity of 93.33%, positive predictive value (PPV) 95.04% and negative predictive values (NPV) 86.13% for epithelial metastatic cancer. The overall diagnostic test accuracy was 91.06%. For lymphoproliferative neoplasms cytology in comparison to histopathology had sensitivity 85.71%, specificity 91.18%, PPV 76.4% and NPV 95.04%. The overall diagnostic test accuracy was 89.81%. In both ways cytology is showing significant possibility to be used as a primary tool in detecting cancers. Conclusion: FNAC is a fast, reliable, and efficient method for diagnosing malignant lymphadenopathy. The cytological diagnosis can sometimes be accepted as the definitive diagnosis without further correlation with histopathology, especially in advanced malignancies and known primary malignancies.

Clinical values of different specimen preparation methods for the diagnosis of lung cancer by EBUS-TBNA.

BACKGROUND AND OBJECTIVE: EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer. METHODS: 181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies. RESULTS: EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods. CONCLUSION: When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.

Development of a Novel Contrast-Enhanced Ultrasound-Based Nomogram for Superficial Lymphadenopathy Differentiation: Postvascular Phase Value.

OBJECTIVE: The aim of this study was to develop and prospectively validate a prediction model for superficial lymphadenopathy differentiation using Sonazoid contrast-enhanced ultrasound (CEUS) combined with ultrasound (US) and clinical data. METHODS: The training cohort comprised 260 retrospectively enrolled patients with 260 pathological lymph nodes imaged between January and December 2020. Two clinical US-CEUS models were created using multivariable logistic regression analysis and compared using receiver operating characteristic curve analysis: Model 1 included clinical and US characteristics; Model 2 included all confirmed predictors, including CEUS characteristics. Feature contributions were evaluated using the SHapley Additive exPlanations (SHAP) algorithm. Data from 172 patients were prospectively collected between January and May 2021 for model validation. RESULTS: Age, tumor history, long-axis diameter of lymph node, blood flow distribution, echogenic hilus, and the mean postvascular phase intensity (MPI) were identified as independent predictors for malignant lymphadenopathy. The area under the curve (AUC), sensitivity, specificity, and accuracy of MPI alone was 0.858 (95% confidence interval [CI], 0.817-0.891), 86.47%, 74.55%, and 81.2%, respectively. Model 2 had an AUC of 0.919 (95% CI, 0.879-0.949) and good calibration in training and validation cohorts. The incorporation of MPI significantly enhanced diagnostic capability (p < 0.0001 and p = 0.002 for training and validation cohorts, respectively). Decision curve analysis indicated Model 2 as the superior diagnostic tool. SHAP analysis highlighted MPI as the most pivotal feature in the diagnostic process. CONCLUSION: The employment of our straightforward prediction model has the potential to enhance clinical decision-making and mitigate the need for unwarranted biopsies.

TAFRO Syndrome: A Syndrome or a Subtype of Multicentric Castleman Disease?

TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis of bone marrow/renal dysfunction, organomegaly) syndrome is a systemic inflammatory disorder of unknown etiology. It has been recognized as a subtype of idiopathic multicentric Castleman disease (iMCD), and the international diagnostic criteria for iMCD-TAFRO require a lymph node histopathology consistent with iMCD. Furthermore, TAFRO syndrome is defined as a heterogeneous clinical entity caused by underlying diseases such as malignancy, autoimmune diseases, or infections. However, the cases that led to the proposal of TAFRO syndrome lacked recognizable lymphadenopathy and were inconsistent with any other diseases, despite vigorous efforts in differential diagnosis. Irrespective of the presence or absence of Castleman disease (CD)-like histology, TAFRO syndrome exhibits homogeneous clinical, laboratory, and prognostic features, setting it apart from iMCD without TAFRO syndrome. Defining iMCD-TAFRO apart from TAFRO syndrome is deemed meaningless and confusing. MCD is a heterogeneous lymphoproliferative disorder consisting of several subtypes with different pathogenesis, clinical manifestations, and histological features. Typical MCD in Japan, characterized by the histology of plasma cell type and marked polyclonal hypergammaglobulinemia, is identical to idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL). Although IPL is classified into iMCD-NOS (not otherwise specified), it should be recognized as a distinct clinicopathological entity. Furthermore, we propose to separate TAFRO syndrome from the MCD category as a defined disorder.

Incidence, Timing, and Long-Term Outcomes of COVID-19 Vaccine-Related Lymphadenopathy on Screening Mammography.

OBJECTIVE: To determine the incidence, timing, and long-term outcomes of unilateral axillary lymphadenopathy ipsilateral to vaccine site (UIAL) on screening mammography after COVID-19 vaccination. METHODS: This retrospective, multisite study included consecutive patients undergoing screening mammography February 8, 2021, to January 31, 2022, with at least 1 year of follow-up. UIAL was typically considered benign (BI-RADS 1 or 2) in the setting of recent (≤6 weeks) vaccination or BI-RADS 0 (ultrasound recommended) when accompanied by a breast finding or identified >6 weeks postvaccination. Vaccination status and manufacturer were obtained from regional registries. Lymphadenopathy rates in vaccinated patients with and without UIAL were compared using Pearson's χ2 test. RESULTS: There were 44,473 female patients (mean age 60.4 ± 11.4 years) who underwent screening mammography at five sites, and 40,029 (90.0%) received at least one vaccine dose. Ninety-four (0.2%) presented with UIAL, 1 to 191 days postvaccination (median 13.5 [interquartile range: 5.0-31.0]). Incidence declined from 2.1% to 0.9% to ≤0.5% after 1, 2, and 3 weeks and persisted up to 36 weeks (P < .001). UIAL did not vary across manufacturer (P = .15). Of 94, 77 (81.9%) were BI-RADS 1 or 2 at screening. None were diagnosed with malignancy at 1-year follow-up. Seventeen (18.1%) were BI-RADS 0 at screening. At diagnostic workup, 13 (76.5%) were BI-RADS 1 or 2, 2 (11.8%) were BI-RADS 3, and 2 (11.8%) were BI-RADS 4. Both BI-RADS 4 patients had malignant status and ipsilateral breast malignancies. Of BI-RADS 3 patients, at follow-up, one was biopsied yielding benign etiology, and one was downgraded to BI-RADS 2. DISCUSSION: Isolated UIAL on screening mammography performed within 6 months of COVID-19 vaccination can be safely assessed as benign.

Rosai-Dorfman disease as chronic bilateral granulomatous anterior uveitis: A case report.

Rosai-Dorfman disease is a rare non-Langerhans cell histiocytosis disorder, also known as sinus histiocytosis, with massive lymphadenopathy. Rosai-Dorfman disease is classified into nodal and extranodal diseases. Ocular involvement is one of the common extranodal manifestations; however, uveitis manifestation is infrequent. We reported an interesting Rosai-Dorfman disease patient who presented with chronic bilateral granulomatous anterior uveitis with disc hyperemia and cystoid macular edema. She was a 60-year-old Thai female who had abnormal skin nodules on her back after multiple recurrent chronic anterior uveitis. The diagnosis has been made based on a constellation of the patient's information, physical examination, and histopathological results. We successfully treated the patient with topical steroids, posterior subtenon triamcinolone 20-mg injection, and methotrexate.