VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a severe, treatment-refractory, monogenic, multiorgan, autoinflammatory condition with vasculitic and hematological complications.
VEXAS syndrome is likely to be rare, but also likely to be underdiagnosed...
Bone marrow reconversion generates a red bone marrow pattern that is in reverse to the normal yellow-to-red distribution.
Bone marrow reconversion occurs when there is increased hematopoietic demand, which may be 1,2:
high endurance athlet...
Focal nodular marrow hyperplasia is a rare, benign condition where there is a localized conversion of red/hematopoietic from yellow/fatty bone marrow. Its main relevance is of having a pseudotumor appearance mimicking skeletal metastases on MRI 1.
Most commonly located in t...
Cyanosis (plural: cyanoses) is a physical sign represented by bluish discolouration of the skin. It indicates there is reduced oxygen bound to red blood cells in the bloodstream. Diagnosis of the underlying cause of cyanosis is based on a thorough history and physical examination.
Birbeck granules refer to unusual rod-shaped structures specific to Langerhans cells. Their origin and function remain undetermined. Langerin is a crucial component within Birbeck granules.
History and etymology
Birbeck granules were first described by Michael S Birbeck in 1961 3.
Lymphoplasmacytic lymphoma (LPL) is an uncommon type of B-cell non-Hodgkin lymphoma. In this condition, the affected tissues (usually bone marrow) become infiltrated by small lymphocytes, plasmacytoid lymphocytes, and plasma cells.
Some publications state this condition synonymous with Waldens...
Autoimmune hemolytic anemia is a group of hemolytic anemias characterized by an antibody response to red blood cells. It can present as acute or chronic anemia. It can be idiopathic or can occur with other disorders.
Several types have been described:
warm-antibody type anemia (WAIHA)
Peripheral T cell lymphoma is an uncommon, heterogeneous group of lymphoma. It can account for around 5-15% of non-Hodgkin lymphoma (NHL).
The word "peripheral" does not mean involvement in the extremities but refers to tumor cells that arise from lymphoid tissue outside of the bon...
Unicentric Castleman disease (UCD) is considered the more common form of Castleman disease and involves one or more enlarged lymph nodes in a single region of the body that demonstrates histopathologic features that have features of Castleman disease. A subset of patients can have systemic symp...
Night sweats, also known as sleep hyperhidrosis, are a common clinical complaint and may herald malignancy, especially lymphoma, or infections. Patients typically report waking up in the night with sweating so severe that their clothes and bed sheets are soaked through ("drenching sweats") and n...
A blast crisis or lymphoid blast crisis refers to the transition of chronic or accelerated phase chronic myeloid leukemia to acute leukemia. It is usually characterized by
≥30% blasts in the bone marrow or peripheral blood
development of extramedullary disease outside of the spleen
Felty syndrome is a rare condition that involves rheumatoid arthritis, decreased white blood cell count and spleen enlargement.
A mnemonic to remember the basic components of Felty syndrome is:
A: arthritis (rhe...
A mnemonic to remember the commonest causes of thrombocytopenia is:
P: platelet disorders (DIC, TTP, ITP)
E: enlarged spleen
L: liver disease
T: toxicity (heparin, aspirin, chemotherapy, benzene)
A mnemonic to remember the commonest causes of anion gap metabolic acidosis is:
G: glycols (ethylene glycol and propylene glycol)
R: renal failure
Platelets, also known as thrombocytes, are an essential constituent of the cellular component of blood. They play a key role in normal hemostasis. Normal platelet levels in adult patients are 150-400 x 109/L.
Platelets are tiny (2-4 μm) cells that lack nuclei 1-3. They are mass prod...
Immune thrombocytopenia (ITP) was historically known as idiopathic thrombocytopenic purpura (see Terminology section). It is characterized by an immune-mediated decrease in platelet numbers to <100x109/L and in most cases is primary, i.e. no underlying cause is found.
Hairy cell leukemia is a rare and indolent form of small mature B-cell leukaemias.
Its annual incidence is estimated at around 0.3 cases per 100 000, and the disease comprises 2-3% of all leukaemias. There is a recognized male predilection of around 4:1 with a median age of around...
Thrombocytosis (plural: thrombocytoses) is a general term and is defined as a rise in platelet count to over two standard deviations above the normal range. Its exact quantitative definition is variable, but generally equates to a platelet count greater than 400-450x109 cells/L.
Lymphoma of the bone may represent lymphoma that has originated within that bone itself i.e. primary, or metastasized there from another organ/tissue, i.e. secondary. Secondary forms of bone lymphoma are much more common than the primary bone form.
primary osseous lymphoma
secondary osseous ly...
Myelodysplastic syndrome / myeloproliferative neoplasm (MDS/MPN) overlap syndromes refer to a group of chronic clonal myeloid malignancies in which there are features of both myelodysplastic syndrome and myeloproliferative neoplasm at the time of presentation.
Entities that can fall into this g...
The YEARS criteria is a diagnostic algorithm that determines the risk of pulmonary embolism (PE) derived from three items in the Wells score that are most predictive of PE1. Unlike the Wells score, it uses a variable D-dimer threshold based off clinical pre-test probability. The YEARS criteria i...
The bright band sign is a sonographic sign found in the context of splenic infarction.
It consists of highly hyperechoic linear-shaped bands within splenic infarct lesions of different ages 1.
Histological examinations of spleens with the sign suggest it might be caused by preserved fibrous tr...
CD34 or hematopoietic progenitor cell antigen CD34 is an intercellular adhesion protein and cell surface glycoprotein and a frequently used marker of hematopoietic progenitor cells and endothelial cells. It is also expressed by many other non-hematopoietic cell types including multipotent mesenc...
Tumor lysis syndrome (TLS) is an entity representing a constellation of laboratory and clinical derangements inclusive of:
It is considered an oncological emergency and can occur following treatment of malignancies with high cell...
Primary hypogammaglobulinemia is a congenital/non-acquired form of hypogammaglobulinaemia and can be of heterogeneous etiology.
The condition is characterized by low levels of serum immunoglobulins and impaired antibody responses.
The majority of cases of primary hypogammaglobulinemia are repr...
Primary cutaneous lymphomas represent a group of extranodal non-Hodgkin lymphomas (T- or B-cell) primarily confined to the skin with no evidence of extracutaneous disease at the time of diagnosis (cf. secondary involvement of the skin).
Mycosis fungoides is the most prevalent type of primary c...
Hepatic manifestations of common variable immunodeficiency are not uncommon and can be primarily related to nodular regenerative hyperplasia.
For a general discussion of the underlying condition, please refer to the article on common variable immunodeficiency (CVID).
Agranulocytosis refers to a situation where the absolute neutrophil count (ANC) falls to less than 100 neutrophils per microliter of blood. It predisposes to a very high risk of severe infection.
It can be hereditary or acquired.
hereditary: usually due to genetic mutations in the ...
Splenic histoplasmosis can manifest with splenomegaly and splenic hypoattenuation. It is more common in immunosuppressed patients (e.g. HIV/AIDS), particularly in endemic areas (e.g. central USA) 1,2. Healed splenic histoplasmosis is one of the causes of diffuse splenic calcifications 2.
The hematinics are nutrients that are required by the body for erythropoiesis, i.e. the production of red blood cells 1,2.
List of hematinics
Clinically, the most important hematinics are vitamin B12, iron and folic acid because deficiency states of these three substances are much more common ...
Red blood cells (RBCs), also known as erythrocytes (or rarely haematids), are cells that carry oxygen by means of hemoglobin, and form part of the cellular component of blood as it circulates throughout the body. These extremely common cells are typically made in the bone marrow in a process cal...
Lymphopenia (also known as lymphocytopenia, hypolymphemia and sublymphemia) is a deficiency of circulating lymphocytes 1. It may be either primary or secondary.
The spelling lymphopaenia is erroneous and should never be used.
Afibrinogenemia, also called congenital afibrinogenemia, is a rare autosomal recessive inherited blood disorder due to deficiency of the clotting protein fibrinogen. The disorder is associated with increased risk of spontaneous hemorrhage1.
Afibrinogenemia has an estimated prevale...
A mnemonic to remember the radiological features of hemochromatosis is:
P's for primary and S's for secondary
P: parenchymal (liver, myocardium, thyroid and synovium)
P: poor liver (organ dysfunction and malignancy)
The lymphatic system (also known as the lymphoid system or systema lymphoideum in Terminologia Anatomica) is the collective term given to the lymphatic vessels and lymphoid tissues in the body 1,4.
Occasionally the lymphatic system is considered with the reticuloendothelial system ...
Episodic angioedema with eosinophilia (EAE), also known as Gleich syndrome, is a rare condition presenting as a self-limiting cyclic urticaria, fever, angioedema, weight gain and marked eosinophilia, with 3-4 weekly episodes 1.
Episodic angioedema with eosinophilia is rare, only a...
Eosinophilia is defined as an abnormally high level of eosinophils in the blood, this is usually defined as >500 cells/μL (normal eosinophil level: <450 cells/μL). Hypereosinophilia is defined as >1500 cells/μL and is usually due to hematological malignancy 1,2.
This article includes recommenda...
The lymphoid organs represent sites in the body in which lymphocytes are concentrated. They are divided into primary and secondary lymphoid organs 1.
Primary lymphoid organs are responsible for the generation of new lymphocytes:
Secondary (a.k.a. periph...
The lymph nodes (commonly shortened to nodes, and known as nodus lymphoideus in TA 4) collectively form one of the secondary lymphoid organs.
Macroscopically, a normal lymph node is a small ellipsoid structure, approximately 0.1 to 2.5 cm in maximal length 2,3. Nodes often possess a reniform mo...
Plasma cell leukemia (PCL) is a rare and aggressive form of leukemia and plasma cell dyscrasia. It can be divided into primary (pPCL) and secondary (sPCL) following previously diagnosed multiple myeloma. It is also considered clinically and genetically distinct from multiple myeloma.
The B symptoms (a.k.a. inflammatory symptoms) are a triad of systemic symptoms associated with more advanced disease and a poorer outcome in lymphoma 1,2:
>10% unintentional decrease in body weight in the 6 months preceding the diagnosis
B symptoms are ...
Anaplastic large cell lymphoma (ALCL) is a form of hematological malignancy. It was first described in 1985 as a large-cell neoplasm with anaplastic morphology immunostained by the Ki-1 antibody, which recognizes CD30.
There are two main subtypes:
anaplastic large-cell lymphoma, ALK-positive
Percutaneous splenic biopsy, using either ultrasound or CT guidance, is an accurate and reliable method of acquiring splenic tissue for histopathological assessment and has been proposed as an alternative for splenectomy in selected patients.
Although the procedure has been historically feared ...
Autoimmune lymphoproliferative syndrome (ALPS) is a rare lymphoproliferative condition.
It presents with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage cytopenias in an otherwise healthy child.
It represents a failure of apoptotic mechanis...
Hemoglobin (Hb) is the oxygen-carrying molecule in red blood cells.
Hemoglobin is a tetrameric protein molecule composed of four subunits. Each subunit consists of an iron-containing cyclic heme component linked to a polypeptide chain, the polypeptides are together known as globin. E...
Hemoglobin SC (HbSC) disease is a hemoglobinopathy, and a common variant of sickle cell disease (SCD). There is coinheritance of one HbS gene and one HbC gene, resulting in a milder phenotype than full-blown sickle cell disease. It most commonly manifests with a proliferative retinopathy. Painfu...
Blood is a connective tissue usually found in a liquid phase; it comprises a fluid component called plasma (about 55% of the total volume), in which lies the cellular component, comprising several cell lineages, primarily the white blood cells, red blood cells and platelets. In an average adult ...
Diathesis (plural: diatheses) is a term used to describe a state in which there is an increased chance of something happening. Contemporaneously, the word is used as a synonym for the word predisposition; however the term predates a modern understanding of genetics or pathology 1.
The typical clinical manifestations of multiple myeloma can be recalled using the mnemonic:
R: renal failure
B: bone disease
The CRAB mnemonic can help differentiate multiple myeloma from its precursor diseases - monoclonal gammopathy of undetermin...
Porphyrias are a group of rare metabolic diseases in which heme metabolism is altered.
Porphyria is rare, with some forms being extremely rare. Estimates for the prevalence of the disease vary in the literature and could reflect differing geographic distribution and/or incomplete ...
Diffuse large B cell lymphoma is the most common subtype of non-Hodgkin lymphoma.
Diffuse large B cell lymphoma is sometimes associated with immunodeficiency, including acquired immunodeficiency syndrome.
In 2016 WHO classification of lymp...
The concentric target sign is a typical sign for cerebral toxoplasmosis. It is seen on T2 weighted MR imaging as a deep parenchymal lesion showing a series of concentric rings with hyperintense and hypointense/isointense signal alternatingly. Strong perifocal edema is usually visible on T2/FLAIR...
Leishmaniasis refers to zoonoses caused by parasites of the genus Leishmania. There are three main forms of leishmaniasis:
visceral (also known as kala-azar or dum-dum fever)
Leishmaniasis is a truly global disease with a higher burden in t...
Dyscrasia (plural: dyscrasias) was used historically in medicine to refer to an imbalance of the four bodily humors 1. It is now used as a synonym for disease, and is only found as part of the terms "blood dyscrasia" or "plasma cell dyscrasia".
Blood dyscrasia refers to any disease of the blood...
White blood cells or leukocytes are one of the main cell types found in normal human blood. They are actually colourless (but appear white on light microscopy) and are divided into granular and non-granular types.
Types of white blood cell:
Hypovitaminosis K (also known as vitamin K deficiency) is caused by a lack of vitamin K in the body.
The main symptoms and signs are related to a clotting dyscrasia as vitamin K is vital as a cofactor for the enzymatic activation of several key components of the clotting...
Anaplastic lymphoma kinase (ALK) gene rearrangements are known to occur in association with several tumors. The genes code for an enzyme called anaplastic lymphoma kinase (ALK) or ALK tyrosine kinase receptor (also known as CD246) which is thought to play a role in brain development and exerts i...
Hepatosplenomegaly is simply the simultaneous presence of a pathologically-enlarged liver (hepatomegaly) and spleen (splenomegaly).
Many infections can produce a mild concurrent enlargement of the liver and spleen. This list is by no means exhaustive.
Vitamin B6 deficiency (also known as hypovitaminosis B6) is rare, as the B6 vitamers are present in many commonly-consumed foodstuffs. It is most commonly seen in the context of chronic ethanol excess, although many other risk factors are known. In children, deficiency may manifest as seizures. ...
Lactate dehydrogenase (LDH or LD) is a key enzyme in most cells, catalyzing the reversible conversion of pyruvate to L-lactate. Its contemporaneous main clinical uses are limited primarily to the investigation of hemolysis, serous collections and as a tumor marker.
Gallbladder cholesterol polyps are the most common subtype of gallbladder polyps, representing more than 50% of all polyps. They are frequently seen in middle-aged women and are benign lesions, with no malignant potential.
For further details, please refer to the parental article on gallbladde...
Pyrexia (or fever) is a clinical sign, indicated by an abnormally elevated core body temperature, which is defined by several medical societies as ≥38.3°C (≥≈101°F). The temperature elevation may be persistent or episodic. If the body temperature is greater than 41.5°C - a rare phenomenon - it i...
Musculoskeletal involvement of leukemia is not always apparent on imaging, although the disease is per se characterized by the bone marrow infiltration.
Leukemia is a hematological neoplasm characterized by the overproduction of immature (blasts) or abnormally differentiated cells of the hemat...
The adenoid tonsils, or often just simply the adenoids (also known as the nasopharyngeal or pharyngeal tonsils), are paired foci of lymphatic tissue located on the superoposterior wall of the nasopharynx and form part of Waldeyer's ring.
Hereditary spherocytosis (HS) (also known as Minkowski-Chauffard disease 1) is a group of hemolytic anemias due to a genetic abnormality of the erythrocyte cell membrane resulting in spherocytes. The clinical spectrum is broad, from a subclinical state to severe transfusion-dependant anemia.
Leukemic cell lysis pneumopathy, also referred to as acute lysis pneumopathy, refers to an acute respiratory failure that can occur in patients with leukemia after the initiation of chemotherapy, particularly in those with hyperleukocytosis. On imaging, it manifests with features of acute respir...
Therapy-related myeloid leukaemias, also referred to as therapy-related myeloid neoplasms, occur as a late complication after cytotoxic therapies (e.g. chemotherapy, immunosuppressive therapy, and radiation therapy) performed to treat other conditions. They represent hematological malignancies w...
Acute myeloid leukemia (AML), also referred to as acute myelogenous leukemia, is a hematological malignancy characterized by the abnormal clonal proliferation of immature myeloid precursors (myeloblasts) or poorly differentiated cells of the hematopoietic system. It primary infiltrates the bone ...
Leukemia is a hematological neoplasm characterized by the overproduction of immature (blasts) or abnormally differentiated cells of the hematopoietic system in the bone marrow that often, but not always, extends into the peripheral blood.
This article aims to provide an overview of leukemia as...
Neuroacanthocytosis syndromes (NAS), previously known collectively as Levine-Critchley syndrome, are characterized by basal ganglia degeneration, acanthocytosis, and normal serum lipoprotein.
There are four core NAS:
McLeod syndrome (MLS)
Huntington disease-like ...
Extranodal extension refers to the growth of a nodal cancer metastasis beyond the confines of the capsule of a lymph node into adjacent tissues. Less preferred synonyms include extranodal spread, extracapsular extension, or extracapsular spread.
This finding holds prognostic implications. For e...
Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, is a myeloproliferative neoplasm characterized by the overproduction of granulocytes with fairly normal differentiation.
The annual incidence is about 1 per 100,000 1,3. The typical age at presentation is ...
Lupus anticoagulant refers to an immunoglobulin that binds to phospholipids and proteins associated with cell membranes. The name lupus "anticoagulant" is in fact a misnomer where it is a prothrombotic agent. Patient's with lupus anticoagulant have a primary hypercoagulable state and a greater p...
Primary hypercoagulable states are those situations where patients have laboratory (genetic) abnormalities resulting in clinical conditions that are associated with an increased risk of thrombosis (prothrombotic states) or have recurrent thrombosis without recognisable predisposing factors (thro...
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder whereby some of the red blood cells produced are defective and are susceptible to premature destruction by the immune system, leading to hemoglobinuria.
The term comes from a mistaken 19th cen...
Disseminated intravascular coagulation (DIC), also known as consumption coagulopathy or defibrination syndrome, refers to a systemic phenomenon of overactivation of coagulation and fibrinolysis resulting in widespread clots forming inside blood vessels.
Patients present w...
Magnetic resonance lymphangiography (MRL) is an imaging technique used to visualize and map the lymphatic vessels. The technique is used for treatment planning in supermicrosurgical procedures, including lymphaticovenous anastomosis, lymphaticolymphatic bypass and vascularized lymph node transfe...
Copper deficiency (also known as hypocupremia) is unusual due to the ubiquity of copper in the normal diet.
Copper deficiency is thought to be rare, but exact numbers are difficult to ascertain.
The typical presentation of copper deficiency mimics the more ...
Sideroblastic anemia (also known as sideroachrestic anemia) is a rare cause of anemia characterized by the presence of ring sideroblasts rather than normal red blood cells in the bloodstream. Sideroblastic anemia is either congenital or acquired.
Symptoms and signs reflec...
Anemia is the presence of reduced hemoglobin in the blood. Formally, the World Health Organizatiοn (WHO) defines anemia by the hemoglobin concentration in the blood according to age and sex 1:
adult men: <130 g/L
adult women: <120 g/L
Values for pregnant women and children are different.
Iron (chemical symbol Fe) is one of the trace elements that is essential for normal human health due to its central importance in the structure and function of hemoglobin and the cytochromes.
Iron is a transition metal with atomic number 26 and an atomic weight of 55...
Ariboflavinosis is the term given to riboflavin (vitamin B2) deficiency.
Ariboflavinosis has been seen in both developed and developing countries, and across the socioeconomic spectrum. It is usually present in the context of other hypovitaminoses.
It has been found to more comm...
Folate deficiency (hypovitaminosis B9) is the most common vitamin deficiency in the Western world. It is especially important in pregnant women and common amongst alcoholics.
Deficiency arises in two distinct populations:
increased demand (pregnancy and lactation)
Hypervitaminosis E (or hypertocopherolaemia) is very rare as vitamin E has low toxicity even in large doses.
In published case reports, patients have presented with a bleeding tendency e.g. cerebral hemorrhage 1. These affected individuals have imbibed supraphysiological...
Vitamin B12 deficiency, also known as hypovitaminosis B12 or hypocobalaminemia, is not uncommon, with potentially serious sequelae if not adequately treated.
Vitamin B12 deficiency results in a reduction of two metabolic pathways 3:
conversion of L-methylmalonyl coenzym...
Pernicious anemia (PA) is the commonest cause of vitamin B12 deficiency (or hypocobalaminemia) in the world, due to an autoantibody against intrinsic factor, the cofactor required for absorption of this vitamin.
Pernicious anemia is the commonest cause of hypovitaminosis B12 globa...
Solitary plasmacytoma with minimal bone marrow involvement refers to a type of plasmacytoma with bone marrow cytology positive for monoclonal plasma cell infiltration.
In order to fulfill the International Myeloma Working Group criteria for the diagnosis of solitary plasmacytoma with ...
The Ann Arbor staging system was the landmark lymphoma staging classification system for both Hodgkin lymphoma and non-Hodgkin lymphoma. It is named after the town of Ann Arbor in the US state of Michigan where the Committee on Hodgkin's Disease Staging Classification met in 1971 to agree on it....
The Cotswolds-modified Ann Arbor classification is a lymphoma staging classification system for both Hodgkin lymphoma and non-Hodgkin lymphoma. They came about in 1988 following recommended modifications to the Ann Arbor staging system after a meeting in Cotswold, England.
This classification h...
The Lugano staging classification is the lymphoma staging system that is most commonly used in clinical practice currently. The categories for initial staging are defined in this article. See separate articles for the Lugano criteria for response assessment by PET-CT or by CT alone, as well as g...
The Lugano classification is a lymphoma staging system resulting from recommended changes in 2011 to the Cotswolds modified Ann Arbor staging. This article outlines the lesion measurement guidelines for the system:
lymph nodes: the longest diameter in axial plane should be >1....
The Lugano classification is a lymphoma staging system for non-Hodgkin and Hodgkin lymphoma. This article outlines the classification's response to treatment based on PET-CT.
Also included in the classification are staging and response to treatment based on CT.
The Lugano clas...
The Lugano classification is a lymphoma staging system resulting from recommended changes in 2011 to the Ann Arbor staging with Cotswolds modifications. This article outlines the classification's response to treatment based on CT.
Also included in the classification are staging and reponse to ...