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Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare, cutaneous lymphoma involving subcutaneous adipose tissue. SPTL is associated in less than 20% with hemophagocytic syndrome (HPS). A 5-year overall survival rate is inferior in patients with SPTL and HPS (46%) as compared with 91% in patients without HPS. No standardized therapy for SPTCL has yet been established. This is a case of 35-year-old Caucasian man with a one-month history of B symptoms with the suspicion of Still's disease, at admission with leucopenia, high LDH, ferritin, sIl-R2, and triglycerides levels, hepatosplenomegaly, small right supraclavicular nodule, and irregular thickening of trunk subcutaneous tissue. The abdomen MRI showed generalized thickening of mesentery and colonic mucosa. In the patient, diagnosis of SPTCL was established with secondary HPS. CHOEP chemotherapy and modified HLH 2014 protocol were applied with subsequent high dose chemotherapy (BEAM) supported by autologous stem cells transplantation. Treatment was complicated by pancytopenia and pneumonia. The outcome of the disease treated by intensive protocol seems to be good.

Mastocytosis is a clonal hematopoietic disorder characterized by proliferation of abnormal mast cells in various organs including the skin, digestive system, lymph nodes, and bone marrow. We report on a 75-year-old woman presenting with abdominal pain, vomiting, diarrhoea, myalgia, and weight loss. Abdominal CT showed hepatosplenomegaly with heterogeneous splenic parenchyma, lymphadenopathy, and osteopenia with areas of osteosclerosis but no primary tumour. AnDie Mastozytose ist eine klonale hämatopoetische Erkrankung, welche durch eine Proliferation von abnormalen Mastzellen in verschiedenen Organen wie Haut, Verdauungstrakt, Lymphknoten und Knochenmark gekennzeichnet ist. Wir berichten über eine 75-jährige Frau mit Bauchschmerzen, Erbrechen, Diarrhö, Myalgie und Gewichtsverlust. Ein CT des Abdomens zeigte eine Hepatosplenomegalie mit heterogenem Milzparenchym, Lymphadenopathie und Osteopenie mit osteosklerotischen Herden, aber keinen Primärtumor. Im PET/CT fand sich eine insgesamt niedrige metabolische Aktivität der Läsionen, mit einer diffusen Knochenmarkbeteiligung die verdächtig auf eine hämatologische Neoplasie war. Eine Untersuchung des Knochenmarks und des peripheren Blutes bestätigte anschließend die Diagnose einer aggressiven systemischen Mastozytose.

Wolman disease is a lethal rare autosomal recessive disorder defined by the deficiency of acid lipase enzyme. The disease is a lysosomal storage disease. Multiple organs such as adrenal glands, liver, spleen, bone marrow, small bowel loops, and abdominal lymph nodes are infiltrated by the deposition of lipids. Infants generally present with failure to thrive, abdominal distention, vomiting, steatorrhea, and hepatosplenomegaly. Authors’ present a 1 month-old male infant with abdominal distention and failure to thrive who was referred for abdomen CT scan. The CT scan revealed stippled calcifications of both enlarged adrenal glands, without the distortion of the adreniform shape, fatty liver, splenomegaly and thickened small bowel loops; characteristic imaging findings of Wolman disease. CT scan is the imaging modality of choice for the recognition of the disease. There is no definite cure explained yet. Further studies are required to find the definite treatment of the disease.

To explore the clinical and pathological features, therapy and prognosis of Castleman’s disease (CD) in the head and neck. We retrospectively analyzed the clinical and pathological data of 44 patients with head and neck CD who were diagnosed in the Fujian Medical University Union hospital (Fujian, China) between May 2008 and June 2021. According to the clinical classification, they were divided into two groups, the unicentric CD (UCD, n = 20) and the multicentric CD (MCD, n = 24). Their clinical features, imaging findings, laboratory examination, and treatment results were, respectively, analyzed. The age of UCD patients was younger than that of MCD patients. Most of the UCD patients (80%) were female, with asymptomatic single lymphadenectasis, and the prognosis was favorable; while 70.8% of the MCD patients were male, with multiple lymph nodes throughout the body, and more prone to hepatosplenomegaly, pneumonia, serous effusion, anemia, hypoalbuminemia, elevated globulin, coagulation disorders, etc., the prognosis was bleak. Two cases of MCD patients were with systemic lupus erythematosus (SLE). UCD usually manifests as asymptomatic single lymph node enlargement, complete surgical resection was the mainstay of treatment modality. MCD has relatively complicated clinical symptoms and poor prognosis, and anti-IL-6 therapy may be effective.

Introduction The myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement (MLN-Eos) are a rare group of hematopoietic neoplasms with diverse and often perplexing presentations that can cause challenges, and even potential pitfalls, for the diagnostic pathologist.1 The MLN-Eos demonstrate a male predominance, often strikingly so. While these MLN-Eos occur across a range of ages, the median age of onset is typically in the 40s, younger than in many other types of cancer, indicating that this is not a typical age-related cancer. Clinically these patients may show fatigue, pruritis, hepatosplenomegaly, and other protean symptomatology associated with eosinophilia, including restrictive pulmonary fibrosis, restrictive cardiomyopathy due to endomyocardial fibrosis, and eosinophilic gastritis or dermatitis as well as direct mass-forming symptoms. Often there is elevated tryptase and vitamin B12 associated with the granulocytic hyperplasia.

Hemophagocytic lymphohistiocytosis is rare life-threatening syndrome, hereditary or acquired, mainly affecting children. Hemophagocytic lymphohistiocytosis is an immune deficiency characterized by severe inflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages. The usual biological and clinical data may associate polyadenopathy, hepatosplenomegaly, fever, multivisceral damages, and cytopenias with potential multiorgan dysfunction and death. We report the case of a 4-year-old girl, hospitalized for recurrent cerebellar symptoms (ataxia) associated later with fever and pancytopenia. 18F-FDG PET/CT revealed a node pathological uptake, which was biopsied and confirmed a diagnosis of hemophagocytic lymphohistiocytosis.

T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive neoplasm derived from post-thymic T-cells. Patients are typically middle aged with a slight male predominance who present with a high white blood cell count, hepatosplenomegaly, lymphadenopathy, and other symptoms typically associated with leukemia. Although cutaneous involvement has been reported in up to 30% of cases of T-PLL, to our knowledge, none have presented with a presentation resembling livedoid vasculopathy. In the correct clinical context, an underlying hematolymphoid neoplasm should be included in the differential diagnosis of a patient presenting with livedoid vasculopathy.

Visceral leishmaniasis is an important yet neglected parasitic disease caused by infection with Leishmania donovani or L infantum. Disease manifestations include fever, weight loss, hepatosplenomegaly, immune dysregulation, and extensive hematological complications. Thrombocytopenia is a dominant hematological feature seen in both humans and experimental models, but the mechanisms behind this infection-driven thrombocytopenia remain poorly understood. Using a murine model of experimental visceral leishmaniasis (EVL), we demonstrated a progressive decrease in platelets from day 14 after infection, culminating in severe thrombocytopenia by day 28. Plasma thrombopoietin (TPO) levels were reduced in infected mice, at least in part because of the alterations in the liver microenvironment associated with granulomatous inflammation. Bone marrow (BM) megakaryocyte cytoplasmic maturation was significantly reduced. In addition to a production deficit, we identified significant increases in platelet clearance. L donovani–infected splenectomized mice were protected from thrombocytopenia compared with sham operated infected mice and had a greater response to exogenous TPO. Furthermore, infection led to higher levels of platelet opsonization and desialylation, both associated with platelet clearance in spleen and liver, respectively. Critically, these changes could be reversed rapidly by drug treatment to reduce parasite load or by administration of TPO agonists. In summary, our findings demonstrate that the mechanisms underpinning thrombocytopenia in EVL are multifactorial and reversible, with no obvious residual damage to the BM microenvironment.

Background Hemophagocytic lymphohistiocytosis (HLH) is characterized by hyperinflammation and life-threatening cytopenias. Survival is poor, and management is pivotal on rapid identification of the disease. HLH is associated with hematologic malignancies, however correlation with myelodysplastic syndromes (MDS) is exceedingly unusual. Although minimizing overwhelming hyperinflammation by treating hemophagocytosis are central for HLH outcome, there is urgent necessity to identify potential initiating mechanisms that could assist in therapy design. Case description Here, we describe an elderly African American patient who developed rapid onset of cytopenias and coagulopathy associated with hepatic and bone marrow hemophagocytosis. We analyze four additional similar cases to isolate clinical, laboratory and cytogenetic findings expected in patients exhibiting concurrent HLH and MDS. HLH linked with MDS retains common HLH features associated with systemic hyperinflammation such as fever, hypotension, hepatosplenomegaly, hyperferritinemia, coagulopathy and rapidly evolving cytopenias. Typical MDS chromosomic abnormality such as trisomy 8 was frequently observed in our studied cases. Conclusion Our case describes difficulties while managing HLH in MDS patients. Diagnosis should be based on identifying HLH appropriate criteria and if possible karyotypic abnormalities normally observed in MDS.

Mastocytosis is a heterogeneous group of disorders characterized by the accumulation of clonal mast cells in organs such as the skin and bone marrow. In contrast to adults, most affected children have only cutaneous involvement. This article reviews the molecular pathogenesis, skin findings, mast cell mediator-related symptoms, evaluation, and management of childhood-onset mastocytosis, noting differences from adult-onset disease. Current classification of cutaneous mastocytosis and the natural histories of different variants in pediatric patients are highlighted, with a focus on clinical manifestations with prognostic implications. A practical algorithm is provided to guide clinical assessment, laboratory and other investigations, and longitudinal monitoring, including recognition of hepatosplenomegaly as a marker of systemic disease and utilization of allele-specific quantitative PCR (ASqPCR) to detect KIT mutations in the peripheral blood. Updated information and consensus-based recommendations regarding possible triggers of mast-cell degranulation (e.g., physical, medications) are discussed, with an emphasis on patient-specific factors and avoiding excessive parental concern. Lastly, an individualized, stepwise approach to treatment of symptoms, skin-directed therapy, and potential use of kinase inhibitors for severe systemic disease is outlined.

Juvenile myelomonocytic leukemia (JMML) is a rare childhood hematopoietic disorder typically presenting with hepatosplenomegaly, lymphadenopathy, pallor, fever, and cutaneous findings. The authors report the first case, to our knowledge, of JMML presenting in a pediatric patient with a subdural hematoma. A 7-month old male with recurrent respiratory infections and a low-grade fever presented with a full fontanelle and an increasing head circumference and was found to have chronic bilateral subdural collections. Abusive head trauma, infectious, and coagulopathy workups were unremarkable, and the patient underwent bilateral burr holes for evacuation of the subdural collections. The postoperative course was complicated by the development of thrombocytopenia, anemia, and an acute subdural hemorrhage which required evacuation. Cytologic analysis of the subdural fluid demonstrated atypical cells, which prompted flow cytometric analysis, a bone marrow biopsy, and ultimately a diagnosis of JMML. Following chemotherapy, the patient’s counts improved, and he subsequently underwent a hematopoietic stem cell transplant. Subdural collections may rarely represent the first presenting sign of hematologic malignancies. In patients with a history of recurrent infections and a negative workup for abusive head trauma, clinicians should include neoplastic etiologies in the differential for chronic subdural collections and have a low threshold for fluid analysis.

The article describes a rare clinical case of Gaucher disease in a 5 month old girl, confirmed by molecular genetic analysis. In the presentedclinical case, there is a onset of lysosomal accumulation disease, which is accompanied by changes in the clinical analysis of blood (anemia,thrombocytopenia), hepatosplenomegaly, congenital malformations (open arterial duct, open oval window) and severe neurologic deficit.

Background: Schistosomiasis is a contagion caused by intestinal and urinary blood trematodes affecting around 200 million people worldwide. Adult worms colonize human blood vessels for years, successfully escaping the immune system while excreting hundreds to thousands of eggs daily. The chronic infection can cause anemia, retarded growth, hepatosplenomegaly, neurological sequlae and even death. For Diagnosis of schistosomiasis, microscopic examination of human wastes as well as tissues remains the gold standard owing to the characteristic shape and size of the eggs. Objective: to present a case of bilharzial polyps presented to endoscopy unit of the department of Tropical Medicine, Faculty of Medicine, Alexandria University, Egypt for colonoscopy and mistaken for IBD with suspicious polypoidal transfromation versus malignant process. Methodolgy: Snare polypectomy was done and tissues were sent for histopathological evaluation which revealed multiple fresh and calcified bilharzial ova seen in mucosa and submucosa. Conclusion: This unusual long standing case will give us the chance to recall schistosomiasis, its occurrence as colon polyps, clinical presentation and means of management.

Osteopetrosis is a severe and frequently fatal condition characterized by the formation of thick, dense bone, with a concomitant loss of bone marrow spaces secondary to defective osteoclast function or development. Clinical symptoms include pancytopenia, hepatosplenomegaly, fractures, cranial nerve impingement, and increased cranial pressure, among others. The condition requires rapid diagnosis and clinical intervention, as hematopoietic stem cell transplantation performed early in life can be curative in the majority of cases and can prevent the irreversible neurological impairment associated with the disease. We report a six-month-old male with osteopetrosis where bone marrow examination and molecular studies allowed a definitive diagnosis. Microscopic examination of a bone marrow biopsy demonstrated increased bone formation at various stages of ossification, decreased marrow spaces, and increased osteoclasts rimming the bone. Next-generation sequencing (NGS) demonstrated that the patient was homozygous for mutations in the TCIRG1 gene, which encodes an osteoclast vacuolar proton pump and is the most common mutation associated with the autosomal recessive or infantile malignant form of osteopetrosis. The patient underwent a cord blood stem cell transplant, but unfortunately expired four months after diagnosis. This case highlights the importance of bone marrow biopsy evaluation as part of the integrated approach to diagnosing osteopetrosis.

IntroductionSystemic mastocytosis (SM) with an associated hematological neoplasm (SM-AHN) constitutes about 40% of all patients with SM. AHN commonly includes myeloid neoplasms and chronic myelomonocytic leukemia (CMML) is seen in about 30% of these patients.Case reportA 67-year-old male presented to hematologist with fatigue and significant weight loss. Abdominal ultrasound and computed tomography (CT) detected hepatosplenomegaly, abdominal lymphadenopathy, and ascites. He was anemic with leukocytosis and eosinophilia. Trephine biopsy showed > 30% of spindle-shaped mast cells. The KITD816V mutation was present. Serum tryptase level was elevated to 62 ng/mL. The patient was diagnosed with aggressive SM and received six cycles of cladribine with partial response. Three years later, he developed severe anemia. Eosinophilia and monocytosis (5.6 × 109/L) were demonstrated in blood film. Hepatosplenomegaly and abdominal lymphadenopathy were also present. Trephine biopsy did not demonstrate the presence of spindle-shaped mast cells, but dysplasia in erythroid and myeloid lineages was evident. The histological result of lymph node biopsy as well as blood and bone marrow findings were in line with CMML. He received hydroxyurea, but he transformed soon into fatal acute monocytic leukemia.ConclusionsThe prognosis of SM-AHN depends on AHN component. Leukemic transformation of AHN component may occur in a proportion of patients.

Mucopolysaccharidosis are lysosomal storage diseases, secondary to the accumulation of mucopolysaccharides. Type 1 mucopolysaccharidosis is the most common form and affects between 0.69 and 1.66 newborns per 100,000. The severity of mucopolysaccharidosis is variable with lethal forms in utero and attenuated forms diagnosed in adults. The most common symptoms are short stature, facial dysmorphism, chronic articular pains that can mimic chronic inflammatory rheumatism, axial and peripheral bone involvement, hepatosplenomegaly and an early carpal tunnel. Depending on the type of mucopolysaccharidosis, corneal, cerebral or cardiac involvements are possible. Screening is based on the analysis of urinary glycosaminoglycans. The deficient enzyme assay and the gene analysis confirm the diagnosis. Mucopolysaccharidosis recognition is important for patient management and family screening. In addition, specific enzyme replacement therapy exists for certain types of mucopolysaccharidosis. Role of clinician is important to evoke and diagnose mucopolysaccharidosis.

Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania protozoa. Since sporadic cases of this disease are noted in non-endemic areas and are associated with a limited outbreak, the disease is easily overlooked. In addition, other illnesses exhibit similar symptoms. It is difficult for clinicians to establish an accurate diagnosis and develop effective treatments for this disease. The present study reported a case of a 25-year-old young man admitted to the hospital due to oblique hernia. The case was diagnosed as VL. The patient presented with persistent night sweats and fatigue as described in his admission history. However, the body temperature was normal. Routine examination revealed that the patient exhibited chronic hepatitis B infection, pancytopenia, hepatosplenomegaly, increased erythrocyte sedimentation rate, significant plasma cell infiltration in bone marrow aspirate and hypergammaglobulinemia. The retrospective analysis of the present case can improve the diagnostic accuracy and treatment rate of VL in non-epidemic areas.

Gaucher disease (GD), code E75.2, is the most common form of hereditary enzymopathies united in the group of lysosomal diseases with autosomal recessive type of inheritance. The occurrence of GD is caused by a mutation of the gene responsible for the synthesis of the enzyme в-glucocerebrosidase (acid в-glucosidase), which is involved in the hydrolytic cleavage of glucosylceramide (a component of cell membranes) into glucose and ceramide. Insufficient activity (or insufficient amount) of в-glucocerebrosidase leads to the accumulation of glucosylceramide inside the cells of the reticuloendothelial system, which are thus converted into Gaucher cells. Clinically, this is expressed by a polysystemic disease with progressive hepatosplenomegaly, hematological disorders and lesions of the bones of the skeleton, which leads to severe pain syndrome, increased bone fragility and as a consequence — to severe disability. The “gold standard” of GD treatment is currently enzyme replacement therapy. To increase the availability of drug therapy and optimize approaches to the treatment of children with GD the search and development of new drugs is carried out.

Introduction: Leukemia is the most common childhood malignancy accounting for 30%–40% of cases. Acute lymphoblastic leukemia is the most common leukemia in children with peak incidence in 2–6 years of age. The present study aims to assess the incidence of acute leukemia in patients presenting with musculoskeletal manifestations. Materials and Methods: This is a retrospective study conducted in a tertiary center from January 2014 to December 2018. A total of 63 children presented with musculoskeletal manifestations and underwent bone marrow examination. Based on final marrow diagnosis, the study group was divided into leukemic and nonleukemic groups. Results: Fever was the most common presenting complaint and was present in all the patients of both the groups. The occurrence of hepatosplenomegaly was comparatively higher in the leukemic group than in patients with juvenile idiopathic arthritis (JIA). The predominant type of arthritis was oligoarticular (68.15%) in the leukemic group and polyarticular (77.27%) in the nonleukemic group. Rheumatoid rash was noted in 20% of JIA patients, and none of the patients in the leukemic group had rash. The percentages of anemia, leukopenia, and thrombocytopenia were statistically higher in leukemia patients than in JIA patients. Conclusion: Bone marrow studies are a prerequisite in diagnosing leukemias. However, based on the presence of few atypical clinical and laboratory features, leukemia can be excluded in JIA patients.

Disseminated histoplasmosis can occur in immunocompromised patients such as in HIV disease and patients with medication-induced immunosuppression. Most of these patients present with fever, weight loss, hepatosplenomegaly, lymphadenopathy, and pancytopenia. There are increasing reports of coronavirus disease 2019 (COVID-19) pneumonia associated with fungal infections including aspergillus and mucormycosis. It is not typical for immunocompetent patients to present with disseminated fungal disease. We herein report a case of a 50-year-old immunocompetent male with a recent recovery from COVID-19 pneumonia who presented with fever and pancytopenia. Chest computed tomography (CT) demonstrated new-onset right upper lobe lung mass, subcarinal lymphadenopathy, and splenomegaly. Mediastinal lymph nodes and bone marrow biopsies were performed, and the patient was diagnosed with disseminated histoplasmosis. The association between COVID-19 pneumonia and fungal infections is increasingly reported. Diagnosis requires a high index of suspicion, especially in immunocompetent patients.

Objective(s) To describe the spectrum of neurological presentations of chloromas. Method Two case reports. Results A 72 year-old female presented with a right-sided cavernous sinus syndrome on a background of a myeloproliferative disorder. MRI brain demonstrated a FLAIR hyperintense lesion centred on the right cavernous sinus. Cerebrospinal fluid (CSF) was acellular with negative cytology and flow cytometry. FDG PET/CT demonstrated diffuse marrow hypermetabolism, hepatosplenomegaly and focal FDG uptake in the cavernous sinus and a remote paraspinal region, suspicious for chloromas. The patient developed pancytopaenia with blasts, and tumour lysis syndrome (TLS) consistent with transformation to acute myeloid leukaemia (AML). The patient was given pulse methylprednisolone, hydroxyurea and external beam radiotherapy to the cavernous sinus lesion with symptomatic improvement. The second case is of a 76 year-old male who presented with progressive lower limb weakness with acute faecal incontinence. This was on a background of AML treated with induction STIMULus (cytarabine and thioguanine) followed by remission confirmed on a recent bone marrow biopsy. CSF showed a marked lymphocytosis with many undifferentiated cells, and flow cytometry was consistent with AML. An MRI whole spine demonstrated a solitary avidly enhancing intramedullary T11 cord lesion with associated oedema. In the context of AML and CSF pathology this was thought to reflect an intramedullary chloroma. The patient was treated with external beam radiotherapy, pulse intravenous methylprednisolone and intrathecal chemotherapy with symptomatic improvement. Conclusion These two cases demonstrate the diversity of neurological clinical presentations of chloromas, an unusual collection of leukaemic cells exerting mass-like effect.

It is often a challenge and a dilemma for clinicians encountering patients with pyrexia of unknown origin. Numerous tests performed to determine the underlying cause often give inconclusive results. We present a 52-year-old man with undulating fever for more than ten months consistent with diagnosis of pyrexia of unknown origin (PUO). It was associated with persistent hyperferritinaemia, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), leukocytosis, thrombocytopaenia, hepatosplenomegaly, hypertrigyceridaemia, raised fibrinogen index and arthritis of the ankle joints. Serological markers, repeated septic workout, cerebrospinal fluid and bone marrow and trephine biopsy (BMT) studies were all negative otherwise. The imaging studies (computed tomography scan of whole body) apart from findings of mild hepatosplenomegaly, was otherwise normal. The positron-emission tomography (PET) scan shows evidence of polyarthritis. Based on these findings, diagnosis of refractory adult-onset Still’s disease complicated by haemophagocytic lymphohistiocytosis was made although the BMT findings was inconclusive. Despite corticosteroids, disease modifying anti-rheumatic agents (DMARD) and immune-modulator therapy, he succumbed to the illness. This case history illustrates the diagnostic complexity of adult-onset Still’s disease with protean manifestation.

Reactive intralymphovascular immunoblastic proliferations (ILVIPs) may mimic aggressive lymphomas and are rarely reported. Herein, we characterize the clinicopathologic features of 8 patients with ILVIPs. No patients had lymphadenopathy, hepatosplenomegaly, or other findings suggestive of lymphoma. The ILVIPs involved the small or large intestine (n=5) and appendix (n=3). Patients were evaluated for abdominal pain, suspected appendicitis, intestinal obstruction, diverticulitis, volvulus, or tumor resection. Histologic sections showed expanded lymphovascular spaces filled by intermediate to large immunoblasts, positive for CD38, CD43, CD45, CD79a, and MUM1/IRF4 in all cases tested. Five of 6 (83%) cases were positive for CD30. CD20 was weakly positive in a subset of cells in 2 (25%) cases, and PAX5 was weakly positive in 4 (50%) cases. The immunoblasts expressed polytypic light chains in all cases tested. In 1 case, a subset of immunoblasts expressed T-cell markers indicating the presence of a T-cell component. The immunoblasts were negative for ALK, BCL-2, BCL-6, CD10, CD56, CD138, and Epstein-Barr virus-encoded small RNA in all cases assessed. The proliferation index shown by Ki-67 was high with a median of 80%. In all 6 cases tested, the immunoblasts were shown within lymphatic channels highlighted by D2-40. In conclusion, ILVIPs can be rarely observed in patients with inflammatory or infectious conditions, especially in gastrointestinal tract surgical specimens. The immunoblasts are predominantly of B-lineage with a postgerminal center immunophenotype and are located within lymphatic channels. It is essential to distinguish reactive ILVIPs from aggressive lymphomas to avoid unnecessary therapy.

Lymphopenia is associated with poor outcome in Hodgkin lymphoma (HL), but the impact of specific cytopenias is unexplored. We report a case of isolated B-cell lymphopenia with HL, EBV infection, and autoimmune hemolytic anemia (AIHA). Our patient is a 19-year-old male without any significant past medical history who presented with two weeks of epigastric abdominal pain, subjective fevers, night sweats, fatigue and a five-pound weight loss. At presentation, he had a white blood cell count of 10.3 k/uL and positive Coombs with a panagglutinin. Infectious testing was negative for HIV but positive for EBV. Peripheral lymphocyte flow cytometry identified 2% CD19+ cells with an absolute count of 43 cells/uL. This profound B-cell lymphopenia persisted despite the EBV viral load diminishing to barely detectable levels of less than 28 copies/mL. Computed tomography (CT) scan of the chest, abdomen and pelvis identified diffuse mediastinal and abdominal lymphadenopathy, as well as hepatosplenomegaly with focal lesions in the liver and spleen. A periaortic lymph node biopsy was morphologically consistent with Classical Hodgkin Lymphoma, Mixed Cellularity subtype (CHL, MC). Diagnosed with CHL, stage IVB, he was treated with the standard combination therapy of cyclophosphamide, doxorubicin, vincristine, bleomycin, prednisone, and etoposide, and he achieved a complete remission. This case highlights the unique presentation of isolated B cell lymphopenia and autoimmune hemolytic anemia in a young patient with HL.

The paper describes a case of a perinatal lethal Gaucher disease in a 29-week-old fetus with non-immune hydrops, facial dysmorphia, hepatosplenomegaly, and hypoplasia of cerebellum and pons. Gaucher cells were found in the lymph nodes, spleen, lungs, thymus, cerebellum, and bone marrow. No storage cells have been detected in the placenta. There was a significant placental weight increase due to swelling. The diagnosis of Gaucher disease was confirmed by biochemical analysis (deficiency of glucocerebrosidase activity and sharply increased hexanoylsphingosine concentration) and molecular genetic techniques (the presence of two mutations of theОписано наблюдение перинатального летального варианта болезни Гоше у 29-недельного плода с неиммунной водянкой, признаками лицевой дизморфии, гепатоспленомегалией, гипоплазией мозжечка и моста. Клетки Гоше обнаружены в лимфатических узлах, селезенке, легких, тимусе, мозжечке и костном мозге. В плаценте клеток накопления не выявлено, отмечено значительное повышение ее массы за счет отека. Диагноз болезни Гоше подтвержден биохимическими (снижением активности глюкоцереброзидазы и резким повышением концентрации гексаноилсфингозина) и молекулярно-генетическими (наличие двух мутаций гена

Gaucher disease (GD) is an autosomal recessive disease characterized by the buildup of glucocerebrosides in macrophages, resulting in the formation of “Gaucher cells.” These cells predominantly infiltrate the liver, spleen, and bone marrow leading to hepatosplenomegaly, cytopenia, and bone pain. Anemia in GD is typically considered to result from non-hemolytic processes. Although rare, a higher rate of hemolytic anemia of the autoimmune type has been reported in GD than in the general population. The literature on non-immune hemolytic anemia in GD is scarce. We review the literature on hemolytic anemia in GD and report on a case of non-immune hemolytic anemia secondary to GD. We believe this is the first description of a patient with confirmed GD and symptomatic non-immune hemolytic anemia that responded to GD-specific treatment.

The article analyzes clinical data, blood test results, tonsil mucus bacteriological testing, and salivary lactate dehydrogenase activity in children with acute infectious mononucleosis caused by an Epstein-Barr viral infection. Research involves 280 children aged from 7 months to 19 years 8 months with infectious mononucleosis, who were hospitalized in the Lviv Infectious Cli­nical Hospital. Group 1 included 234 children infectious mononucleosis caused by Epstein-Barr virus, group 2 — 46 patients with infectious mononucleosis caused by the combination of Epstein-Barr virus and cytomegalovirus. Severe hepatosplenomegaly, lymphadenitis, nasal speech and snoring, hyperthermic syndrome, acute tonsillitis were found in patients with infectious mononucleo­sis. A bacteriological study identified a number of pathogens that can be classified as pathogenic or opportunistic flora. Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Candida fungi were identified in 43.8 % of children with an isolated form of mononucleosis and in 51.7 % of children with mixed infection. In children with infectious mononucleosis caused by mixed infection, we observed the more severe course of the disease and a significantly higher lactate dehydrogenase activity. A significantly increased activity of lactate dehydrogenase in the saliva of patients with infectious mononucleosis in the presence of pathogenic microflora on the mucous membranes indicates destructive processes in the tissues of the tonsils., У статті проаналізовані клінічні дані, показники крові, результати бактеріологічного дослідження слизу з мигдаликів, активність ферменту лактатдегідрогенази (ЛДГ) у слині дітей із гострим інфекційним мононуклеозом (ІМ), зумовленим Епштейна — Барр-вірусною (ЕБВ) інфекцією. Обстежені 280 дітей віком від 7 місяців до 19 років 8 місяців з ІМ, які перебували на стаціонарному лікуванні у Львівській інфекційній клінічній лікарні. До групи 1 увійшли 234 дитини з ІМ ЕБВ-етіології, до групи 2 були включені 46 дітей з ІМ, зумовленим вірусом Епштейна — Барр і цитомегаловірусом. У пацієнтів з інфекційним мононуклеозом були виявлені виражена гепатоспленомегалія, лімфаденіт, гугнявість та хропіння, гіпертермічний синдром та гострий тонзиліт. При бактеріологічному дослідженні була виділена низка збудників, яких можна класифікувати як патогенну чи умовно-патогенну флору. У 43,8 % дітей з ізольованою формою мононуклеозу та в 51,7 % дітей із коінфекцією були ідентифіковані збудники роду Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeroginosa та грибки роду Candida. З’ясовано, що тяжчий перебіг захворювання та вірогідно вища активність ЛДГ спостерігаються в дітей з інфекційним мононуклеозом, зумовленим коінфекцією. Різко підвищена активність ЛДГ у слині пацієнтів з ІМ за наявності патогенної мікрофлори на слизових вказує на наявність деструктивних процесів у тканинах мигдаликів.

We report a preterm newborn diagnosed as having congenital cyto-megalovirus infection who developed lung cysts during her clinical follow-up. The lung cysts were shown in chest X-ray, and confirmed by thoracic computed tomography. A few weeks after starting ganciclovir therapy, we observed that the cystic lung changes of the patient were completely improved. No adverse effects of antiviral therapy were ob-served. Based on this presented patient, it should be kept in mind that congenital cytomegalovirus infection may cause lung cysts. © 2020 by Turkish Pediatric Association.

Haemoglobinopathies (thalassaemia and haemoglobin (Hb) variants) are the most common of all inherited monogenic disorders. More than 1800 mutations in alpha or beta globin genes are known to be responsible for haemoglobinopathies.1 The clinical spectrum of haemoglobinopathies is quite heterogeneous and depends on the underlying mutations. Here, we report, a de novo emergence of rare alpha chain variant Hb G-Waimanalo in a sickle cell disease patient. An 8-year-old Gond tribal girl born from a non-consanguineous marriage was referred to Division of Genetic Disorders at Indian Council of Medical Research-National Institute of Research in Tribal Health (ICMR-NIRTH) for differential diagnosis for haemolytic anaemia. She had a history of severe anaemia (Hb 47 g/L) and frequent bone and joint pain. She also had a history of multiple blood transfusions since the age of 3 years. Her weight was below 3 SD (17 kg). She exhibited pallor, icterus and typical thalassemic facial features with hepatosplenomegaly (spleen 9 cm and liver 5 cm below respective costal margins). Serum bilirubin count was 87.72 µmol/L (direct bilirubin=6.6 µmol/L and indirect bilirubin=81.57 µmol/L). Serum aspartate aminotransferase was 47.3 mg/dL, alanine aminotransferase was 19.6 mg/dL. Serum lactate dehydrogenase levels were also elevated (540 IU/L) suggesting haemolytic anaemia. Direct Coombs test was negative and glucose six phosphate dehydrogenase levels were within normal limits. Cellulose acetate Hb electrophoresis at alkaline pH (8.4) showed the presence of three Hb variants (figure 1A). One faint band was seen just below the HbA band, and other two bands were seen at position corresponding …

A man aged 53 years presented to a general practitioner (GP) with a 1–2-month history of a rapidly increasing skin growth on his right medial ankle. It had become tender and bled readily on contact. He had a history of right leg venous insufficiency, with three previous venous ulcers in the same location as the new skin lesion. The venous insufficiency was being managed with a class 2 compression stocking. He had no history of skin cancer. On examination there was a 3.5 cm × 3.5 cm exophytic, friable skin growth with a crusted rim over his right medial malleolus (Figure 1). His leg showed chronic changes of venous insufficiency. There was no palpable lymphadenopathy of the affected leg and groin, and no palpable hepatosplenomegaly.

Background Histoplasmosis is one of the invasive fungal infections and presents with symptoms mainly in the lungs. Disseminated histoplasmosis (DH) is rare and its lesions in the gastrointestinal tract are even uncommon. The concomitant involvement of the upper and lower gastrointestinal tract has never been described in the immunocompetent individuals. Case presentation A 44-year-old immunocompetent Chinese man presented with fever, hepatosplenomegaly, fungal esophagitis and protuberant lesions with central depression and erosion along the mucous membrane of the colon. The patient was diagnosed as disseminated histoplasmosis by gastrointestinal endoscopy. Conclusions Histoplasmosis should be taken caution in patients with fever and hepatosplenomegaly. Actions should be taken to avoid its disseminated infection associated high mortality.

Background: Chronic myelomonocytic leukemia (CMML) is a clonal hematological neoplasm with features of both myeloproliferation and myelodysplasia with an incidence 0.4 per lakh population. A number of prognostic risks scoring systems have attempted to predict survival and risk of CMML patients, like International Prognostic Scoring System (IPSS), the Spanish Score, the modified Bournemouth Score, the Dusseldorf Score and the MDAP Score. But no prognostic system has been widely accepted. More data from different regions are required to create a widely accepted working prognostic system for CMML. No case series on CMML has been published in literature from India in our knowledge. This article attempts to put to light the various clinicopathological parameters of CMML cases from India and the impact of these parameters on final outcome. Methods: All admitted patients in a tertiary center in western India, with a diagnosis of either a chronic myeloproliferative disease or a myelodysplastic disease over a period of 3 years (2015-2018) were evaluated, out of which nine(n=9) cases fulfilled the diagnostic criteria of CMML. All patients underwent peripheral blood examination, bone marrow aspirate, bone marrow biopsy and cytogenetic studies. Result: All patients (n=9) were between 50 and 80 years and most were males (n=8). Five patients presented with hepatosplenomegaly. Renal and liver function of one patient was deranged who had pleural effusion, ascites. Most patients (n=8) had total leukocyte count above 13000/cumm, while three had low platelet counts. Two out of three patients classified as CMML-II with increased blasts in peripheral blood and bone marrow had fatal outcomes. Patients whose karyotypes were available had normal karyotypes without any additional cytogenetic abnormalities. All were negative for JAK2 and BCR-ABL1. Conclusion: The study concluded that altered biochemical tests (LDH, LFT), blast percentage, CMML II, relative lymphocytosis and transformation to AML were associated with poor outcome.

We examined a 22-year-old woman who was admitted to our hospital with abdominal distention. At 19 years of age, the patient presented with hepatosplenomegaly. She was examined several times in another hospital; however, the cause was unidentified. Our evaluation showed severe pancytopenia and a spleen 13×24 cm in size. The serum levels of angiotensin-converting enzyme and lysozyme were elevated. She was diagnosed with liver sarcoidosis based on non-caseating epithelioid granuloma in liver biopsy tissue. To improve the symptoms, splenectomy was performed, and her pancytopenia and symptoms improved. Sarcoidosis should be considered in cases of massive splenomegaly.

Farber disease (FD) is a rare lysosomal storage disorder (LSD) characterized by systemic ceramide accumulation caused by a deficiency in acid ceramidase (ACDase). In its classic form, FD manifests with painful lipogranulomatous nodules in extremities and joints, respiratory complications, and neurological involvement. Hepatosplenomegaly is commonly reported, and severe cases of FD cite liver failure as a cause of early death. Mice homozygous for an orthologous patient mutation in the ACDase gene (Asah1P361R/P361R) recapitulate the classical form of human FD. In this study, we demonstrate impaired liver function and elevation of various liver injury markers in Asah1P361R/P361R mice as early as 5 weeks of age. Histopathology analyses demonstrated significant formation and recruitment of foamy macrophages, invasion of neutrophils, progressive tissue fibrosis, increased cell proliferation and death, and significant storage pathology within various liver cell types. Lipidomic analyses revealed alterations to various lipid concentrations in both serum and liver tissue. A significant accumulation of ceramide and other sphingolipids in both liver and hepatocytes was noted. Sphingolipid acyl chains were also altered, with an increase in long acyl chain sphingolipids coinciding with a decrease in ultra-long acyl chains. Hepatocyte transcriptome analyses revealed significantly altered gene transcription. Molecular pathways related to inflammation were found activated, and molecular pathways involved in lipid metabolism were found deactivated. Altered gene transcription within the sphingolipid pathway itself was also observed. The data presented herein demonstrates that deficiency in ACDase results in liver pathology as well as sphingolipid and gene transcription profile changes that lead to impaired liver function.

A case of chronic enteropathy associated with SLCO2A1 gene (CEAS) is presented. The female patient was readmitted four times during a three-year follow-up period for intractable dropsy and anemia. Multiple ulcers of small bowel wall were revealed by endoscopic examination. Computed tomography enterography (CTE) and magnetic resonance enterography (MRE) showed the segmental wall thickening of the small bowel. Hepatosplenomegaly and increased bone density of spine and pelvis suggested the diagnosis of myelofibrosis. X-ray films showed the cortical thickening of tibiofibula. The mutations of SLCO2A1 gene were revealed by gene test and the diagnosis of CEAS was confirmed. According to our case report, imaging examinations, including CTE, MRE and X-ray films provide additional valuable information during the diagnostic procedure of CEAS.

Bone marrow aspiration & biopsy examination is often required for diagnosis & management of haematological disorders which have diverse modes of presentation. Mostly of the haematological disorders present as anaemia, which are diagnosed by bone marrow aspiration (BMA) and bone marrow biopsy (BMB). I n the department of pathology, the study was conducted to compare the role of bone marrow aspirate and trephine biopsy for diagnosing the haematological diseases and indications. Materials and Methods: To check the role of bone marrow aspiration and biopsy in the diagnosis of haematological disorders this is the aim of study. In the department of pathology at tertiary care teaching hospital this study was conducted over a period of 2 years from November 2016 to October 2018. A total of 572 cases were included in this study. Results: In the present study, both aspiration and biopsy cases were available are 572 were included. The age ranged from 6 months to 84 years. The 326(56.99%) were males and 246(43%) were females with M: F=1.32 :1. Clinical indications for bone-marrow examination, The most common indication was pancytopenia of 201 cases (35.13%) followed by anaemia 167 cases (29.19%), malignancy 79 cases (13.81%), Hepatosplenomegaly 48 cases (8.39%), thrombocytopenia 47 cases (8.21%) and fever 30 cases (5.24 %). Most of the cases had hypercellular bone marrow (53%) followed by normocellular marrow (32%) and hypocellular marrow (15%). Keywords: Bone marrow, Biopsy, Examination, Haematological disorders.

Gaucher disease (GD) is rare that is caused by an enzyme deficiency of lysosomal glucocerebrosidase and is one of the most frequent lysosomal storage diseases. We present here the case of an infant male with Type 2 GD (GD2). GD2 is clinically characterized by precocious and rapid neurological degeneration comprising brainstem involvement associated with hepatosplenomegaly, pulmonary and hematological involvements, and death will be in infancy or early childhood. We performed professional oral hygiene on a patient with GD2, and we contributed to the communication between the patient and his family. Here we report on the oral cavity features in GD2 and how our experience can contribute to the prevention of aspiration pneumonia.

We investigated the histologic findings and viral antigen distribution in 3 cases of natural coinfection of layer hens with subgroup J avian leukosis virus (ALV-J), Marek’s disease virus (MDV), and reticuloendotheliosis virus (REV) in hens. At autopsy, diseased hens were found to have hepatosplenomegaly and thickened proventriculi, with white tumor nodules in the liver, spleen, lung, kidney, and ovary. Microscopically, most tissues had been infiltrated by neoplastic lymphocytes; the spleen, lung, proventriculus, heart, and liver had been infiltrated by both neoplastic lymphocytes and myeloblastic cells and/or primitive reticular cells. Fluorescence multiplex immunohistochemistry staining revealed ALV-J, MDV, and REV antigens co-expressed in the same tissue, even the same cell.

Salmonellosis is a known cause of enteric disorders in calves. However, cases in the septicemic form may not present enteric lesions, which may lead the veterinary practitioner to not suspect salmonellosis, compromising the diagnosis. The current study describes the epidemiological, clinical, pathological and immunohistochemical aspects of septicemic salmonellosis in calves without enteric lesions. The protocols involving bovine material submitted to the Pathology Laboratory (LAP) of the “Faculdade de Medicina Veterinária e Zootecnia” (FAMEZ) of the “Universidade Federal do Mato Grosso do Sul” (UFMS) from January 1995 to July 2018 were studied. Cases confirmed or suggestive of septicemic salmonellosis in calves without enteric manifestations were selected. Fragments of the liver, lung, and spleen embedded in paraffin were submitted to immunohistochemistry (IHC). Only cases in which there was positive marking on the IHC or culture isolation of Salmonella were included in this study. Of a total of 5,550 cattle examined in the period, ten presented septicemic salmonellosis without enteric lesions. Clinical signs included mucosal pallor, apathy, hyperthermia, and dyspnea. Only three calves presented diarrhea, and two were found dead before clinical changes were observed. The most common necropsy findings were hepatosplenomegaly; yellow, orange or brown discolored livers; pale mucous membranes; inflated and sometimes red lungs; fibrin or fluid within body cavities; and gallbladder filled with inspissated bile. Jaundice was observed in three calves that had a concomitant infection with Anaplasma sp. Microscopically, paratyphoid hepatic nodules and interstitial pneumonia were the most frequent manifestations, followed by thrombosis and bacterial colonies in the spleen, lung, liver, and brain. A strong positive marking was observed in IHC, predominantly in the lung and to a lesser extent in the liver. Polymerase chain reaction (PCR) indicated the Dublin serotype as the causative agent in the samples of the four calves submitted to this procedure. In calves, the septicemic form was the major cause of death due to salmonellosis. Septicemic salmonellosis was usually not accompanied by diarrhea. The clinical signs of septicemia are nonspecific and of little assistance in the diagnosis. IHC has been shown to be efficient in the detection of the agent, mainly in the lung and especially in situations where it is not possible to perform bacterial culture.

A 62-year old British Caucasian woman normally resident in Spain presented with fever and pancytopaenia after returning to the UK. Her symptoms persisted despite broad-spectrum antibiotics, and she gradually became confused, hypotensive and progressively more pancytopaenic. Imaging demonstrated hepatosplenomegaly, and a bone marrow aspirate confirmed a diagnosis of haemophagocytic lymphohistiocytosis (HLH). Bone marrow polymerase chain reaction (PCR) and blood serology were both positive for Leishmania donovani, consistent with visceral leishmaniasis (VL). Following treatment with dexamethasone and amphotericin, she improved clinically and biochemically, and was able to return to Spain. Fever in the returning traveller is a common acute medical presentation. Although HLH and VL are rare diagnoses, both carry a very high mortality rate if undiagnosed and untreated.

Background Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive autoinflammatory condition. Recognised features include vasculitis predominantly affecting medium sized vessels, livedoid skin rash, central and peripheral nervous system involvement, variable degrees of immunodeficiency, and marrow failure, amongst other clinical presentations. We present the case of a six year old male with DADA2 who presented with acute testicular ischaemia secondary to vasculitis, the first such description in DADA2. Case presentation A six year old male presented acute right-sided testicular pain. His history included transient infantile neutropenia, resolved hepatosplenomegaly, and longstanding livedo racemosa, leading to screening and confirmation of DADA2 caused by homozygous c.139G > C (p.G47R) mutation of ADA2. As his only clinical feature was that of mild livedo racemosa with normal laboratory parameters at diagnosis, he was being actively monitored prior to starting any treatment. At a routine clinic follow-up a 24 h history of testicular pain was noted on systems review. He was afebrile, and his only physical signs were that of moderate livedo racemosa, and tenderness of the right testicle. Laboratory parameters revealed C-reactive protein (CRP) 8 mg/L (reference range [RR]

Hypersensitivity to mosquito bites (HMB) refers to skin reactions such as bullae and necrosis, which occurs after being bitten by mosquitoes and can present with multiple systemic reactions such as fever, lymphadenopathy, hepatosplenomegaly simultaneously or subsequently. A 48-year-old male patient presented with recurrent erythema, nodules, papules, vesicles and bullae over upper body and bilateral limbs with itching over the sites of mosquito bite for more than 1 year with low-grade fever and superficial lymph nodes enlargement. The patient's symptoms failed to improve from conventional anti allergic treatment although skin biopsy showed changes of HMB reaction. Subsequently, the lymph node was biopsied and was reported to be nodal marginal zone lymphoma (NMZL), and then the patient was eventually diagnosed with nodal marginal zone lymphoma with HMB. To date only one case of nodal marginal zone lymphoma with HMB has been reported from Korea, and this is the first case to be reported in China.

Gaucher disease is an autosomal recessive lysosomal storage disorder caused by mutations in the gene GBA1, which encodes the lysosomal protein glucocerebrosidase. Patients with Gaucher disease generally have a variety of clinical manifestations ranging from visceral to neurological involvement and some develop ocular involvement. The most commonly affected organs include the spleen, liver, and bone. Moreover, patients often have hepatosplenomegaly, thrombocytopenia, anemia, and bone involvement related to deficient glucocerebrosidase and the subsequent accumulation of glucosylceramide and glucosylsphingosine in cells. A subset of patients develops neurological manifestations, including seizures, myoclonic epilepsy, and progressive neurodegeneration. Eye involvement tends to be less common and presents with diverse clinical findings. These rare and variable ocular manifestations, involving the vitreous, retina, cornea, uvea, conjunctiva and eye movements, can pose a diagnostic challenge for clinicians, especially those not familiar with the disorder. In this review, we explore the different ophthalmologic findings reported in patients with Gaucher disease, aiming to facilitate diagnosis and expedite treatment for patients presenting with ocular manifestations of this rare disorder.

Our aim was to explore the relationship between liver cirrhosis (LC), portal hypertension (PH), and diabetes mellitus (DM). LC displayed hemodynamic alterations reflected by signs and symptoms of hypertension and hyperdynamic circulation. Portal hypertension also caused splenomegaly because of the blood flow into the spleen from the portal vessels and portal flow. The alcoholic cirrhosis displayed abnormal values (AST, ALT, AST/ALT, albumin, ammonia, bilirubin, blood platelet, erythrocytes, glucose, Hb, international normalized ratio (INR), PT, prothrombin index (PI), thymol test, white blood cell (WBC) count), which demonstrated the presence of portal hypertension, ascites, DM, infection, and coagulopathy. The evaluation of liver enzymes and other laboratories data helped to determine the severity of the condition and prognosis. Diabetes appeared to be less affecting the prognosis of patients with cirrhosis than LC itself, showing that hepatocellular failure was largely responsible for patients’ mortality rather than diabetes and its complications. Patients displayed a BMI correlating obesity, although affected by concomitant diseases that commonly cause a severe weight loss. The elevated BMI in this case was accentuated by the presence of ascitic fluid, which is responsible for the increase in weight and the inaccurate BMI evaluation. Ascites affect patients’ recovery from liver diseases. Obese patients with cirrhosis can be related to have a large amount of ascites and that physicians should be expecting to notice changes in their BMI pre- and postoperatively, subsequently making a prior classification as obese inappropriate. Disease severity could be assessed through the evaluation of PH stage, which was characterized by a significant depletion of WBC and as well as platelet counts.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and clinically aggressive type of T-cell lymphoma that characterized by proliferation in the liver, spleen and bone marrow. The article presents analytical review of literature and the clinical case of γδ HSTCL in 4 years old child. Patient's parents agreed to use personal dats and photos in research and publications.

Clinical polymorphism of non-Hodgkin's lymphoma causes difficulties in early diagnosis. Particular difficulties arise when a patient with lymphoma has specific organ lesions. The article presents a clinical case of non-Hodgkin's lymphoma in a 66-year-old woman hospitalized in the gastroenterology department with symptoms of hepatocellular insufficiency, cytolysis, cholestasis, and hepatosplenomegaly. Patient had a history of thrombocytopenia during 4 years. At the time of this hospitalization viral, toxic and autoimmune causes of liver damage were excluded. The presence of thrombocytopenia, lymphadenopathy of intrathoracic lymph nodes, hepatosplenomegaly allowed to suspect the presence of lymphoproliferative disease. Despite ongoing symptomatic therapy, the patient died. Autopsy confirmed the presence of non-Hodgkin's lymphoma with specific infiltration of multiple internal organs: liver, spleen, kidneys, adrenal glands, myocardium, and valvular apparatus of the heart. Affection of the heart, as a rare manifestation of non-Hodgkin's lymphoma, imitated in our clinical case the sonographic picture of myxoma.

Triple‐negative breast cancer (TNBC), an aggressive, metastatic and recurrent breast cancer (BC) subtype, currently suffers from a lack of adequately described spontaneously metastatic preclinical models that faithfully reproduce the clinical scenario. We describe two preclinical spontaneously metastatic TNBC orthotopic murine models for the development of advanced therapeutics: an immunodeficient human MDA‐MB‐231‐Luc model and an immunocompetent mouse 4T1 model. Furthermore, we provide a broad range of multifactorial analysis for both models that could provide relevant information for the development of new therapies and diagnostic tools. Our comparisons uncovered differential growth rates, stromal arrangements and metabolic profiles in primary tumors, and the presence of cancer‐associated adipocyte infiltration in the MDA‐MB‐231‐Luc model. Histopathological studies highlighted the more rapid metastatic spread to the lungs in the 4T1 model following a lymphatic route, while we observed both homogeneous (MDA‐MB‐231‐Luc) and heterogeneous (4T1) metastatic spread to axillary lymph nodes. We encountered unique metabolomic signatures in each model, including crucial amino acids and cell membrane components. Hematological analysis demonstrated severe leukemoid and lymphoid reactions in the 4T1 model with the partial reestablishment of immune responses in the immunocompromised MDA‐MB‐231‐Luc model. Additionally, we discovered β‐immunoglobulinemia and increased basal levels of G‐CSF correlating with a metastatic switch, with G‐CSF also promoting extramedullary hematopoiesis (both models) and causing hepatosplenomegaly (4T1 model). Overall, we believe that the characterization of these preclinical models will foster the development of advanced therapeutic strategies for TNBC treatment, especially for the treatment of patients presenting both, primary tumors and metastatic spread., What's new? Triple‐negative breast cancer (TNBC), an aggressive, metastatic, and recurrent breast cancer subtype, currently lacks adequately described spontaneously metastatic preclinical models that faithfully reproduce the clinical scenario. Here, the authors provide an in‐depth comparative analysis of two preclinical spontaneously metastatic TNBC orthotopic models, MDA‐MB‐231‐Luc and 4T1. The results reveal a metastatic switch in both models with immune system activation and serum‐protein profile reconfiguration, which may support resistance to treatment and recurrence in TNBC. The authors also identify critical functional biomarkers and metabolomic signatures for metastatic progression that may facilitate the development of anticancer therapeutics.

Paracoccidioidomycosis (Pm) is a systemic disease, endemic in the American continent. There are two different clinical forms, the infant-juvenile or subacute form (PmS) and the chronic adult form (PmC). The human immunodeficiency virus (HIV) associated paracoccidioidomycosis (PmHIV) shares characteristics with both of the previously mentioned forms. The objective of this work was to describe the epidemiological, clinical and laboratory features of the PmHIV and to compare them with the ones of PmS and the PmC. A retrospective analysis of 119 patients with paracoccidioidomycosis was performed. Ninety four suffered the chronic form, 11 the subacute one and 14 were coinfected with HIV. Patients with PmHIV presented a CD4+ T lymphocytes median of 70.5 cells/μl, 71.4% had fever, 64.3% had a miliary pattern on the chest radiography, 64.3% had hepatosplenomegaly, 64.3% had mucosal lesions and 50% had skin lesions. One patient died during his hospitalization. The clinical presentation of Pm in patients with HIV resembled the subacute form with fever, hepatomegaly and skin lesions. However, they also tended to present mucosal lesions, positive serology for Pm and pulmonary parenchyma lesions as usually seen in PmC (9/14 PmHIV patients had overlapping features, while 4/14 PmHIV patients clinically resembled PmS and 1/14 PmC). The incidence of Pm has not changed with the burden of AIDS as it has happened with other fungal infections but it appears clinically different from the classic clinical forms of the disease.

The osteopetroses and related sclerosing bone dysplasias can have a broad range of manifestations. Especially in the milder forms, sandwich vertebrae are an easily recognizable and reliable radiological hallmark. We report on four patients from three families presenting with sandwich vertebrae and platyspondyly. The long bone phenotypes were discordant with one patient showing modeling defects and patchy osteosclerosis, while the second displayed only metaphyseal sclerotic bands, and the third and fourth had extreme metaphyseal flaring with uniform osteosclerosis. Two of the four patients had experienced pathological fractures, two had developmental delay, but none showed cranial nerve damage, hepatosplenomegaly, or bone marrow failure. According to these clinical features the diagnoses ranged between intermediate autosomal recessive osteopetrosis and dysosteosclerosis. After exclusion of mutations in CLCN7 we performed gene panel and exome sequencing. Two novel mutations in SLC29A3 were found in the first two patients. In the third family a TCIRG1 C-terminal frameshift mutation in combination with a mutation at position +4 in intron 2 were detected. Our study adds two cases to the small group of individuals with SLC29A3 mutations diagnosed with dysosteosclerosis, and expands the phenotypic variability. The finding that intermediate autosomal recessive osteopetrosis due to TCIRG1 splice site mutations can also present with platyspondyly further increases the molecular heterogeneity of dysosteosclerosis-like sclerosing bone dysplasias.

We report an uncommon case of bilateral impending central retinal vein occlusion (CRVO) in a young girl with newly diagnosed chronic myeloid leukaemia (CML) and its successful reversal with leukapheresis. A young girl presented with vomiting and fever. Examination revealed hepatosplenomegaly and multiple enlarged lymph nodes. Investigations show severe hyperleukocytosis and anaemia. Bone marrow aspirate and trephine biopsy confirmed CML in the chronic phase. She was promptly referred to the ophthalmology team for assessment of vasculopathy. Bilateral fundus showed swollen and hyperaemic optic discs. There were dilated and tortuous retinal venules with perivascular white cell extravasation, scattered intraretinal haemorrhages, and Roth spots at mid-periphery. She received four cycles of leukapheresis and, consequently, her leukocytes reduced dramatically with associated significant improvement in fundus findings. This case highlights uncommon impending CRVO in a young girl and the dramatic improvement in fundus signs following leukapheresis that halted and reversed the progression of impending CRVO.