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Cureus Mar 2024Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hematological disorder of immune dysregulation associated with significant challenges in diagnosis...
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.
PubMed: 38650799
DOI: 10.7759/cureus.56738 -
Cureus Mar 2024Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition that results from excessive immune activation and inflammation. This condition may be...
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition that results from excessive immune activation and inflammation. This condition may be triggered by various factors, including infections, malignancies, or autoimmune diseases. Here, we report the case of a 39-year-old male who developed HLH secondary to T-cell lymphoma and had a history of multiple autoimmune disorders. Our patient presented with shortness of breath and weakness which led to an admission for methicillin-resistant bacteremia. His hospital course deteriorated rapidly due to his worsening condition. He was confirmed to have HLH based on the HLH-2004 criteria with the presence of fever, splenomegaly, hypertriglyceridemia, hypofibrinogenemia, low natural killer cell function, high ferritin, and soluble interleukin 2 receptor levels. Peripheral blood smear and bone marrow biopsy showed atypical lymphocytes consistent with a T-cell lymphoma, but no hemophagocytosis. He was treated with dexamethasone and etoposide. Despite treatment, the patient passed away. This case aims to contribute further to the understanding of secondary HLH in the setting of T-cell lymphoma. It also illuminates how vital early recognition and treatment are in patients with secondary HLH.
PubMed: 38646290
DOI: 10.7759/cureus.56558 -
JCEM Case Reports Apr 2024Parathyroid carcinoma (PC) is a rare endocrine neoplasm that typically presents with osteopenia/osteoporosis, nephrolithiasis, asthenia, and neuropsychiatric symptoms....
Parathyroid carcinoma (PC) is a rare endocrine neoplasm that typically presents with osteopenia/osteoporosis, nephrolithiasis, asthenia, and neuropsychiatric symptoms. We describe the case of a 48-year-old woman, presenting with a large painful hematoma in the cervicomediastinal area. The neck ultrasound (US) demonstrated a solid lesion measuring 40 × 80 × 55 mm, markedly hypoechoic, which extended from the right thyroid lobe to the mediastinum. The blood tests showed elevated serum calcium and parathyroid hormone (PTH) concentrations, consistent with hypercalcemic primary hyperparathyroidism. The patient was rehydrated and treated with furosemide, cholecalciferol, and bisphosphonate, and underwent right lower parathyroidectomy, right hemithyroidectomy, and lymphadenectomy of the right VI cervical level. Histological examination was diagnostic for nonangioinvasive or neuroinvasive PC, and the thyroid lobe was the site of lymphocytic thyroiditis; all removed lymph nodes were benign. The postoperative course was regular. Postoperative neck US showed a hypoechoic left thyroid lobe without evidence of residual neoplasm in the right thyroid bed. Levothyroxine therapy of 50 mcg/day was started because of serum thyrotropin concentrations elevated at 18 mcIU/mL (normal reference range, 0.35-4.0 mIU/mL). Eight years after diagnosis, the patient is in good general condition, with no clinical, biochemical, or imaging evidence of disease persistence/recurrence.
PubMed: 38638336
DOI: 10.1210/jcemcr/luae063 -
Clinical Case Reports Apr 2024When seeing patients who present with atypical lymphocytes and abdominal pain without accompanying symptoms of pharyngitis or lymphadenopathy, acalculous cholecystitis...
KEY CLINICAL MESSAGE
When seeing patients who present with atypical lymphocytes and abdominal pain without accompanying symptoms of pharyngitis or lymphadenopathy, acalculous cholecystitis caused by CMV infection should be considered as a differential diagnosis.
ABSTRACT
A teenage man presented with a fever and epigastric pain. The patient tested positive for cytomegalovirus IgG and IgM. Abdominal ultrasonography and contrast-enhanced CT revealed hepatosplenomegaly and gallbladder wall thickening. MRI did not identify gallstones or tumorous lesions. He was diagnosed with infectious mononucleosis and acalculous cholecystitis caused by cytomegalovirus.
PubMed: 38634095
DOI: 10.1002/ccr3.8771 -
Frontiers in Immunology 2024The clinical evolution of steroid-sensitive forms of pediatric idiopathic nephrotic syndrome (INS) is highly heterogeneous following the standard treatment with...
INTRODUCTION
The clinical evolution of steroid-sensitive forms of pediatric idiopathic nephrotic syndrome (INS) is highly heterogeneous following the standard treatment with prednisone. To date, no prognostic marker has been identified to predict the severity of the disease course starting from the first episode.
METHODS
In this monocentric prospective cohort study we set up a reproducible and standardized flow cytometry panel using two sample tubes (one for B-cell and one for T-cell subsets) to extensively characterized the lymphocyte repertoire of INS pediatric patients. A total of 44 children with INS at disease onset were enrolled, sampled before and 3 months after standard induction therapy with prednisone and followed for 12 months to correctly classify their disease based on relapses. Age-matched controls with non immune-mediated renal diseases or with urological disorders were also enrolled. Demographical, clinical, laboratory and immunosuppressive treatment data were registered.
RESULTS
We found that children with INS at disease onset had significantly higher circulating levels of total CD19 and specific B-cell subsets (transitional, mature-naïve, plasmablasts/plasmacells, CD19CD27, unswitched, switched and atypical memory B cells) and reduced circulating levels of Tregs, when compared to age-matched controls. Prednisone therapy restored most B- and T-cell alterations. When patients were subdivided based on disease relapse, relapsing patients had significantly more transitional, CD19CD27 memory and in particular unswitched memory B cells at disease onset, which were predictive of a higher risk of relapse in steroid-sensitive patients by logistic regression analysis, irrespective of age. In accordance, B-cell dysregulations resulted mainly associated with steroid-dependence when patients were stratified in different disease severity forms. Of note, Treg levels were reduced independently from the disease subgroup and were not completely normalized by prednisone treatment.
CONCLUSION
We have set up a novel, reproducible, disease-specific flow cytometry panel that allows a comprehensive characterization of circulating lymphocytes. We found that, at disease onset, relapsing patients had significantly more transitional, CD19CD27 memory and unswitched memory B cells and those who are at higher risk of relapse had increased circulating levels of unswitched memory B cells, independently of age. This approach can allow prediction of clinical evolution, monitoring of immunosuppression and tailored treatment in different forms of INS.
Topics: Humans; Child; Nephrotic Syndrome; Prednisone; Flow Cytometry; Prospective Studies; Prognosis; Antigens, CD19; Recurrence
PubMed: 38629076
DOI: 10.3389/fimmu.2024.1379924 -
Science Signaling Apr 2024An unexpected integrin pairing enhances T cell receptor signaling and cytotoxicity in antitumor T cells.
An unexpected integrin pairing enhances T cell receptor signaling and cytotoxicity in antitumor T cells.
Topics: Humans; Integrins; Signal Transduction; Neoplasms; T-Lymphocytes
PubMed: 38626008
DOI: 10.1126/scisignal.adp7684 -
Parasitology International Aug 2024Various opportunistic infections develop during immunodeficiency due to human immunodeficiency virus (HIV) infection. The treatment options for malignant lymphoma (ML)...
Various opportunistic infections develop during immunodeficiency due to human immunodeficiency virus (HIV) infection. The treatment options for malignant lymphoma (ML) and toxoplasmic encephalitis (TE) are completely different; therefore, their discrimination is critical. A 25-year-old female of foreign nationality had been experiencing headaches for several weeks and suddenly developed convulsions. Brain computed tomography revealed multiple intracranial lesions; therefore, the patient was referred to the neurosurgery department. Brain magnetic resonance imaging (MRI) revealed multiple masses with surrounding edema, accompanied by enhanced contrast. The largest mass (2 cm) in the left occipital lobe exhibited ringed contrast enhancement. Her blood test results showed a CD4 count of 40/μL, positive HIV Ag/Ab, HIV-RNA level of 56 × 10 copies/mL, positive anti-Toxoplasma IgG (63 IU/mL), and negative anti-Toxoplasma IgM. Tl- single photon emission computed tomography (Tl-SPECT) revealed abnormal accumulation only in the tumor in the left occipital lobe (early T/N ratio, 3.034; delayed T/N ratio, 2.738; retention index, 0.9), which was suspected to be a ML. Both tumors, with or without high accumulation of Tl, were subjected to craniotomy biopsy. Pathological examination revealed infiltration of small lymphocytes with a necrotic background. The patient was diagnosed with TE based on a positive result of a tissue polymerase chain reaction test for Toxoplasma gondii. Two weeks after sulfamethoxazole and trimethoprim combination therapy, MRI imaging showed dramatic improvement in multiple brain tumors. This case is atypical because ML was ruled out despite high Tl-SPECT uptake and retention. Careful diagnosis through pathological examination and DNA testing is important.
Topics: Humans; Female; Adult; Toxoplasmosis, Cerebral; Lymphoma; HIV Infections; Magnetic Resonance Imaging; Diagnosis, Differential; Tomography, Emission-Computed, Single-Photon; Toxoplasma
PubMed: 38614255
DOI: 10.1016/j.parint.2024.102895 -
Internal Medicine (Tokyo, Japan) Apr 2024Sialadenitis has rarely been reported in patients with infectious mononucleosis (IM). Our patient was a 22-year-old man who presented with bilateral swelling of the...
Sialadenitis has rarely been reported in patients with infectious mononucleosis (IM). Our patient was a 22-year-old man who presented with bilateral swelling of the parotid and submandibular glands, a fever, malaise, and splenomegaly. Laboratory tests revealed an increased percentage of atypical lymphocytes in the leukocyte fraction. Serological testing for antibodies against Epstein-Barr virus (EBV) revealed an acute infection pattern. The patient was diagnosed with sialadenitis associated with IM caused by EBV infection. With symptomatic treatment, the salivary gland swelling completely resolved within a week. This case suggests that EBV-induced IM should be included in the differential diagnosis of diffuse sialadenitis with elevated atypical lymphocyte counts.
PubMed: 38599874
DOI: 10.2169/internalmedicine.2922-23 -
Immunity May 2024Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How...
Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11cCD80 cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.
Topics: Animals; Interferon Type I; Lymphocytic Choriomeningitis; Mice; Lymphocytic choriomeningitis virus; Memory B Cells; Epigenesis, Genetic; Mice, Inbred C57BL; Receptor, Interferon alpha-beta; Immunologic Memory; Chronic Disease; B-Lymphocyte Subsets; Single-Cell Analysis
PubMed: 38593796
DOI: 10.1016/j.immuni.2024.03.016 -
Clinical Case Reports Apr 2024F-MF is a rare non-classic variant of MF. In the case of hair loss, this should be a diagnostic consideration. The essence of the diagnosis of F-MF is a careful medical...
KEY CLINICAL MESSAGE
F-MF is a rare non-classic variant of MF. In the case of hair loss, this should be a diagnostic consideration. The essence of the diagnosis of F-MF is a careful medical history, physical examination, and a combination of immunohistological and molecular analyses (. 2022; 14:e21231, . 2012; 32:283, . 2012; 27:134, . 2016; 55:1396, . 2018; 39:994 and . 2018; 11:436).
ABSTRACT
Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma with multiple subtypes. Follicular MF (F-MF) is a non-classic variant of MF. Histological features entail folliculotropism and damage of the epithelium lining of the hair follicles with or without mucin deposition. A 52-year-old male patient complained of recurrent skin lesions on the scalp over 8 months. The lesions appeared suddenly, enlarged over time, and became itchy. A skin punch biopsy was performed. Histological features included mucin deposits in the epithelium of the hair follicles and dense, predominantly perifollicular atypical lymphocytes infiltrating the follicular epithelium. The lymphoid cells were composed of CD3-positive T cells (CD4/CD8-positive T cells) with a shift in favor of the former. The case was diagnosed as F-MF on an immunohistological basis. The diagnosis of F-MF is often difficult for dermatologists and dermatopathologists alike. Not only clinicopathological correlations but also immunohistochemical and molecular analysis are required.
PubMed: 38585584
DOI: 10.1002/ccr3.8731