1- Circumstances of discovery:
• Sometimes the spleen is sought before the typical functional signs: splénalgie (left upper quadrant pain increased to the deep and radiating inspiration ramp to the left shoulder) or pain type postprandial heaviness, fullness gastric or digestive disorders bastards.
• Sometimes the discovery of splenomegaly was guided by a suggestive clinical picture (signs of portal hypertension, enlarged lymph nodes, fever or infectious table, impaired general condition), or sometimes fortuitous in a clinical or radiological systematic review.
• Sometimes, complications can be revealing:
– Splenic infarction (left base of the thorax pain exacerbated the inspiration associated with a triangular hypodensité on the scanner);
– Subcapsular hematoma (diagnosed by ultrasound) may precede a splenic rupture (signs of hemorrhagic shock resulting in emergency surgery);
– Complications can be purely organic as hypersplenism: moderate hemorrhagic event without thrombocytopenia, leukopenia moderate with unchanged blood count; of peripheral origin (rich marrow) related to the stasis of blood cells in spleen capillaries.
2- Clinical diagnosis:
• It is usually easier by the percussion dullness between the 8th and the 11th rib, or by palpation supine or lying on right side, with a mass of typical left upper quadrant by its anteromedial edge embattled and its former seat him conférantun mobile character on deep inspiration, not giving lumbar touch.
• Sometimes palpation is difficult because the spleen is small or extremely important the contrary, very mobile with a lower pole difficult to palpate because occupying the entire left flank.
Differential diagnosis :
• It is easy, in most cases, eliminate a large left kidney because clinically, this is a posterior lumbar giving the mass contact, immobile on deep inspiration; a tumor of the anterior enough but still colic angle, with a badly limited lower pole and a leading edge non embattled; but also a mesenteric cyst; a cyst or tumor in the tail of the pancreas; gastric tumor or left hepatic lobe.
• Sometimes the iconographic exams can be helpful to confirm the diagnosis referred to palpation:
– On a plain abdominal good, splenic shadow is easily visible in the left upper quadrant;
– Abdominal ultrasound provides confirmation of the nature of the splenic mass palpated and information about its shape (spherical and not concave), homogeneity (cyst, hematoma), its size, its vasculature and the presence of accessory spleens;
– CT scan shows loss of concavity, the density and homogeneity of the parenchyma, and the presence of lymph nodes or other associated masses.
The orientation of the etiological diagnosis will be made by a careful examination, a complete clinical examination and by analyzing some simple laboratory tests such as complete blood count with reticulocyte and careful study of smear, liver function tests (transaminases, alkaline phosphatase, gamma GT), looking for signs of hemolysis (free bilirubin, haptoglobin and lactate dehydrogenase), an inflammatory syndrome (erythrocyte sedimentation rate, serum protein electrophoresis, fibrinogen, triglycerides, ferritin), and a chest X-ray.
A- Causes related to macrophage filter function:
1- infectious splenomegalies:
• The septicemic bacterial infections can be a moderate splenomegaly, accompanied by a febrile illness (fever, chills).The pathogen is highlighted by blood cultures and (or) serological arguments. It is usually infections:
– Germs in intracellular growth type salmonellosis, brucellosis, rickettsial disease, tularemia, especially mentioned that the blood count (CBC) shows a leukoneutropenia or absence of leukocytosis;
– More rarely, septicemia pyogenic cutaneous lesions sometimes septico-pyoémiques, Osler’s nodes, associated with splenic abscess, with leukocytosis with neutrophilia (ultrasound or scan found nodules intrasplenic hypodenses or Fluid);
– Hematopoietic TB is to evoke systematically before any febrile splenomegaly whatever aspect of NFS: myelemia, pancytopenia … (interest intradermal tests, spinal cord and liver aspiration biopsies and the demonstration of the BK by myéloculture).
• Infections fungal sepsis.
• Viral infections mentioned in context with an infectious, the NFS mononucleosis:
– Infectious mononucleosis is suspected in angina associated with cervical lymphadenopathy in an adolescent;splenomegaly is present in half of the cases associated with the positivity of a test MNI confirmed by the reaction of Paul Bunnel-Davidsohn;
– Viral hepatitis are discussed in front of liver enzymes signs; serology specify the virus;
– CMV, Rubella and eruptive fevers recognized by their skin manifestations;
– HIV causes moderate splenomegaly, in a third of cases associated with clinically polyadenopathy, impaired general condition with fever, night sweats, prolonged diarrhea, and biologically lymphopenia with decreased CD4 / CD8 ratio.
• Parasitic infections, raised in an ethnic context or travel back home or a recent immigrant; may be:
– Malaria: malaria episodes from the first, splenomegaly is associated with fever. In the chronic phase, splenomegaly is often very important. Diagnosis is made by the study of smear and thick drop during febrile then by immunofluorescence;
– Visceral leishmaniasis or kala-azar: splenomegaly rule is very large, associated with persistent fever, anarchic and a significant deterioration of general condition, sometimes with a few lymph nodes. The diagnosis is suggested by a polyclonal hypergammaglobulinemia on protein electrophoresis and confirmed on the detection of the parasite on the medullary smears. The diagnosis should be considered in Mediterranean areas;
– Bilharzia must be sought before splenomegaly associated with eosinophilia. The diagnosis is confirmed by the presence of eggs of Schistosoma mansoni, japonicum haematobium in the rectal or liver biopsy or stool. In advanced cases, a portal hypertension syndrome worsens splenomegaly;
– More rarely, other parasitic diseases: trypanosomiasis, fluke, splenic hydatid disease where the appearance of the spleen is cystic or toxoplasmosis.
2- splenomegalies inflammatory:
In a context of febrile arthralgia, cutaneous or renal manifestations, immunological assessment is to perform consistently to splenomegaly as several collagen can be mentioned:
– Felty’s syndrome associated splenomegaly, severe rheumatoid arthritis and profound neutropenia frequently associated with infectious revealing incidents. He is currently assigned to a proliferation of such granular lymphocytes CD3 +, CD8 +, CD16 +, CD57 + and CD3, CD16 +, CD58 + (natural killer cells);
– Still’s disease in children, rarely in adults is associated with splenomegaly in 40% of cases and often leukocytosis neutrophils;
– Systemic lupus erythematosus, especially if there is an autoimmune hemolysis associated is to evoke systematically in the presence of neutropenia and will be confirmed by the positivity of anti-native DNA;
– FMF associating joint pain and abdominal to febrile attacks is frequently accompanied by splenomegaly becomes constant if there is an associated amylose;
– Sarcoidosis, hence the interest of the control chest X-ray that found the typical médiastinothoracique appearance;
– Serum sickness, in a context of antigenic stimulation;
– Separately, the macrophage activation syndrome must be sought before any febrile splenomegaly associated with immunosuppression Course (transplants, AIDS, lupus) or lymphoid disease (lymphoma T). Biologically, are evocative: pancytopenia often with thrombocytopenia and cell phagocytosis of images on the marrow smears, ferritin, an isolated hypertriglyceridemia, hypofibrinogenemia no signs of disseminated intravascular coagulation (DIC) associated with excessive activity of macrophages . A recent viral stimulation is frequently found: Epstein-Barr virus (EBV), cytomegalovirus (CMV);
– Finally, splenomegaly called idiopathic in tropical or not, related to strong dysimmune reactions.
3- splenomegalies overload:
• lipid or dyslipoïdoses Surcharges: family background is often already known, the diagnosis is made early before age 18. Splenomegaly is very large, is accompanied by hepatomegaly, cutaneous signs, bone and neurological signs.Infiltration can be diverse:
– Gaucher disease (linked to a deficiency in glucocerebrosidase) is autosomal recessive. The diagnosis will be made by highlighting the bone marrow large Gaucher cells laminated cytoplasm. The diagnosis is important to do because these patients may benefit from replacement therapy enzymatic synthesis by genetic engineering;
– Niemann-Pick disease (linked to a deficiency in sphingomyelinase) autosomal recessive will be raised before the presence of foam cells in the marrow, liver, or lymph nodes;
– Disease blue histiocytes.
• Other storage diseases: amyloidosis, hemochromatosis.
B- Causes linked to vascular filter function:
1- splenomegalies sequestration:
All forms of haemolysis, congenital or acquired, the destruction of erythrocyte seat is extravascular, are accompanied by splenomegaly. That is, with jaundice and pallor, one of the three signs of hemolytic triad. Erythrocyte isotopic tests can confirm the diagnosis in difficult cases. The hemolysis (high reticulocytosis> 150,000 / mm3, collapsed haptoglobin, indirect bilirubin and elevated LDH) are to be found in the etiological diagnosis of any isolated splenomegaly. It can be a:
• Constitutional hemolytic anemia:
– Membrane-Chauffard Pathology Minkowski’s disease when splenomegaly is present in 75-80% of cases, is suspected in a spherocytosis on the blood smear and a decrease in osmotic resistance. It is confirmed by the study ektacytométrique erythrocyte membrane proteins. Splenectomy is effective when performed in children over 8 years, if hemolysis is common and disabling.
– Pathology of hemoglobin. Thalassemia, a or b, referred to a Mediterranean or Asian ethnicity, microcytosis on blood smears, will be confirmed by hemoglobin electrophoresis. Splenomegaly is constant for homozygous forms.Splenectomy improves the transfusion recovery in case of voluminous splenomegaly with hypersplenism. Sickle cell hemoglobinopathies or where moderate splenomegaly is due to successive thrombotic type of splenic infarction resulting in a functional asplenia state. Diagnosis is done on the hemoglobin electrophoresis.
– Enzymatic Pathology. In G6PD deficiency, splenomegaly is very moderate and ineffective because splenectomy is intravascular hemolysis and triggered by certain drug intake and intake of beans to avoid.
On the contrary, the pyruvate kinase deficiency where splenectomy is beneficial because the splenic destruction is predominant.
• Acquired haemolytic anemia:
– Or autoimmune origin, giving a picture with chronic hemolysis positivity Coombs. The search for an underlying etiology is successful in 50% of cases lymphoproliferative disorders, collagen diseases, infectious diseases (MNI, Mycoplasma pneumoniae …). The spleen is large. Splenectomy can be proposed in case of failure of corticosteroids.Reduced control in cold hemagglutinin disease;
– Is rarely a non-immune hemolytic anemia: paroxysmal nocturnal hemoglobinuria or Marchiafava-Micheli syndrome characterized by a deficiency of membrane proteins CD55 and CD59 detected by flow cytometry.
2- vascular splenomegalies: portal hypertension
Portal hypertension, caused by any obstruction on the door system, whatever its cause, causes splenomegaly at any age, even in children. The clinic is evocative when there is collateral abdominal circulation, esophageal varices at the gastroesophageal endoscopy. Sometimes the diagnosis is more difficult when it is an isolated splenomegaly associated with hypersplenism. Liver explorations are essential. The various causes can be classified according to the seat of the obstacle:
• liver obstacles either présinusoïdaux (schistosomiasis, sarcoidosis, Wilson’s disease, congenital hepatic fibrosis) or post-sinusoidal related to the presence of regenerative nodules (alcoholic cirrhosis, post-hepatitic, primary biliary cirrhosis, hemochromatosis);
• infrahépatiques obstacles at the splenic vein or trunk splénomésaraïque causing segmental portal hypertension.These are cavernomas, thrombosis doors or splenic vein and cuts extrinsic a pancreatic tumor or an arteriovenous fistula;
• suprahépatiques obstacles: the Budd-Chiari syndrome due to thrombosis of hepatic veins causing an increase in pressure in the portal and sinusoidal territories with hepatic ischemia followed by necrosis leaving starry centrilobular fibrosis and scar areas periportal nodular regeneration. The diagnosis is suspected in weight gain, painful hepatomegaly with jaundice and polyserositis and confirmed by liver biopsy ponction-. Among the causes, look myeloproliferative syndrome, paroxysmal hemoglobinuria, a constitutional or acquired thromboembolism (circulating anticoagulant, antithrombin III deficiency), constrictive pericarditis, right heart failure and veno-occlusive disease related to obstruction centrilobular veins occurring during allo- or autografts in heavily treated patients with prior chemotherapy or radiotherapy.
C- Causes linked to immune function:
Before splenomegaly, hematological must dread. Especially after 40 years, this is the first diagnosis to evoke, especially the spleen is large, of recent onset and associated with lymphadenopathy. We must look for even if there is a febrile context as sepsis or non-specific fever may be indicative of blood disease. So you need to quickly check the count with careful study of smear, if in doubt myelogram, chest radiography and abdominal CT. It may be two types of malignancies.
• lymphoid Hematologic: in the presence or absence of lymphadenopathy, lymphocytosis any blood must perform a morphological study with accurate typing in cytofluorometry lymphocytes.
– Chronic lymphocytic leukemia in more than 50 patients with a hematopoietic tumor syndrome homogeneous device consists of polyadenopathies symmetrical, bilateral, affecting all areas ganglion is the most common diagnosis. The count showed lymphocytosis often greater than 15,000 / mm3, consists of small mature lymphocytes immunophenotype CD19 + B, CD5 +, CD23 +, CD10- both on blood smear and on the cord. The study of surface immunoglobulin shows a monotype of kappa / lambda and low surface density. There is sometimes a positive Coombs test may lead splenomegaly somewhat larger, and hypogammaglobulinemia.
– The Leukemia prolymphocytes B Galton suspected in rapidly progressive splenomegaly is confirmed by the presence of large nucleoli cells (CD19 +, CD5-, CD10-, CD23-, CD103-, iglos highly expressed) on the smear.
– The starting point for splenic lymphomas must be feared and can long remain isolated in the spleen, if they are low grade. Follicular lymphomas which will be recognized by the presence of B lymphocytes slotted cores (centrocytes / centroblasts) CD19 +, CD5-, CD10 +, CD23-, bcl2 + high density of surface immunoglobulin and the presence of a translocation t (14; 18).
Lymphomas of very close look coat of follicular lymphoma but must differentiate by immunophenotype CD19 + B; CD5 +, CD10-, CD23-, BCL1 + and a specific translocation t (11; 14), adverse changes faster.
Villous lymphomas: the spleen is isolated and often voluminous, the lymphocytosis is characterized by cytoplasmic fringes, and immunophenotype CD19 + B, CD5-, CD23-, bcl1-, bcl2- but CD103 + sometimes associated with serum monoclonal immunoglobulin IgM-type.
Lymphomas gd whose starting point is the red pulp of the spleen within the sine rare lymphoma developed from an ancestral population of lymphocytes CD3 + CD4-CD8-TCRab-, RACT +, CD56 ± and dreadful prognosis.
– A disease Waldenstrom where splenomegaly is associated with serum monoclonal IgM, with an array of hemodilution and the myelogram, lymphoplasmacytic infiltration.
– More rarely, Hodgkin’s disease, especially if there is a fever in the long term, it is a form of early adult and eosinophilia on NFS.
– Finally, acute lymphoblastic leukemia can be in children for splenomegaly is usually small, but rapidly growing, so splénalgies source. The presence of large lymphoblastic cells on blood and bone marrow smears will diagnosis.
• Hairy cell leukemia: the isolated splenomegaly, is also constant, more or less voluminous. The count is evocative to moderate pancytopenia with few lymphoid cells in scalp cytoplasm (phenotype B and DBA44 +) frequently associated with profound monocytopenia. Diagnosis is made by phase contrast microscopy of blood smears and bone marrow biopsy shows lymphoid myelofibrosis. Specific treatment by analogues of pentostatin type of purines or 2CDA is very effective and has supplanted splenectomy.
D- Causes linked to the function of hematopoietic vicariousness:
Myeloproliferative disorders are diagnosed to evoke systematically before any isolated splenomegaly; the diagnosis is easy when the study of NFS.
• Chronic myeloid leukemia where the spleen is almost constant (absent in 10% of cases), it is accompanied on the count of a typical appearance of leukocytosis with myelemia without leukemic hiatus, eosinophilia and basophilia often associated. The score leukocyte alkaline phosphatase collapsed, cytogenetics is typical with the presence of the Philadelphia chromosome t (9; 22) and the transcript Bcr-Abelson detected in molecular biology in the blood.
• In polycythemia vera, splenomegaly is present in three quarters of cases. However, the clinical picture (facial reddening, blood viscosity, pruritus) is already evocative and the presence of splenomegaly attests to the primitive etiology rather than secondary polycythemia. Blood volume confirm the diagnosis suspected in an increase in hemoglobin.
• The myelofibrosis when splenomegaly is usually very large and constant, associated counts on a typical appearance of leukocytosis with myelemia and érythroblastémie associated poikilocytosis and anisocytosis. The bone marrow biopsy shows myeloid myelofibrosis.
• Essential thrombocythemia where platelets are very high, exceeding 1 million / mm3, splenomegaly is rare and moderate. The bone marrow biopsy found hyperplasia of megakaryocytes.
• Chronic myelomonocytic leukemia, where the spleen is common, sometimes associated with cutaneous and gingival signs, is in the form of leukocytosis with monocytosis. Myelogram often shows an appearance of myelodysplasia with excess blasts associated monocytosis.
E- isolated primitive splenomegalies:
It can be either a benign etiology (fibroma, dysembryome, lymphatic cyst) or malignant (fibrosarcoma, angiosarcoma, hemangioblastoma or splenic metastases). Only the splenectomy will make the diagnosis, hence the importance of not letting splenomegaly without diagnosis.
Highlights to include:
• The presence of a palpable splenomegaly is a priori pathological. The positive and differential diagnosis is usually easy; etiological diagnosis covers a wide range of pathologies, reflecting the diversity of the functions of the spleen: vascular filter, macrophage function, immune function lymphoid and hematopoietic ancestral function.
Indications for splenectomy are multiple
• At referred diagnosis when no precise diagnosis has come as any splenectomy is pathological.
• At therapeutic, in hemolytic anemia Minkowski-type Chauffard, steroid-resistant autoimmune, in hypersplénismes or blood disorders, to improve the efficiency by reducing transfusion splenic sequestration.
• At referred to preventive splenic rupture suspicion, or to an evolution towards heart failure by reducing hemodilution.
• Before splenectomy, the patient should be informed of the severity of bacterial infections, excessive sensitivity of encapsulated bacteria (meningococcal and Haemophilus influenzae) and pneumococcus despite vaccination performed before surgery, and only protects against serotypes more frequent ,.
• In the immediate consequences of splenectomy, there may be leukocytosis consists of neutrophils, associated with thrombocytosis and sometimes hyperkalemia. On the smear, it is easy to recognize when a patient has been splenectomized, by the presence of body Joly and Cabot rings. In their absence, the development of an accessory spleen should be considered.
• As a “swamp on a big river,” splenic capillaries 2 microns in diameter slow the circulatory flow of the splenic artery: the rouge.Cette capillary bypass pulp can be:
– To close: the splénocontraction sending 200-300 cm3 of blood in the systemic circulation in hemorrhagic shock;
– Expand as a “sponge” in case of hypertension upstream: the spleen of portal hypertension. Blood cells remain stored in the spleen capillaries causing pancytopenia device while the medullary normal production but the amount of blood cells is abnormally distributed. This array of peripheral pancytopenia without infectious or hemorrhagic complication is called “hypersplenism”.
• As the “fishermen on the shore,” macrophages advantage of capillary circulatory slowdown, to “identify and catch” in the bloodstream abnormal circulating elements:
– Red blood cells “poorly finished” with intracytoplasmic balances: Jolly body or Cabot rings that are easily recognizable on the smear of a splenectomized patient;
– Low deformability erythrocytes as packed with pathological hemoglobin (thalassemia, sickle cell anemia) or hard-sided (Minkowsky- Chauffard where the ball-shaped red blood cells can not pass through the capillaries of 2 m) or autoantibodies bristling (anemia haemolytic autoimmune) or filled by a parasitic outbreak (malaria …)
– Monocytes and polymorphonuclear containing bacteria to intracellular growth (Koch bacillus, Salmonella …) or various infectious agents (parasites, viruses, fungi);
– All foreign elements flowing directly into the blood extracellular bacteria growth (septicemia and pyogenic abscesses).
• Finally, macrophages can be activated under the action of cytokines and phagocytose erythrocytes or platelets as in normal phagocytic activation syndrome.
• The product of macrophage phagocytosis is fragmented, digested and presented in subunit antigens in lymphocyte system that sheathes as sleeves each capillary forming “white pulp.”
• “As an army ensconced behind the shore ‘, the lymphocytic system may hyperplasier rapidly forming either a reaction splenomegaly to infectious antigenic stimulation or immune disorders (rheumatoid arthritis or lupus) or with malignant proliferation of either of different lymphocyte populations (starting point splenic lymphomas). Conversely, as is the “biggest node” of the body, there may be a “homing” of malignant lymphocytes from a ganglion or cord which secondarily localize to the spleen (splenic location lymphoid leukemia, Hodgkin or Waldenstrom).
• “The spleen has a long memory.” It was a hematopoietic organ in the 2nd part of embryonic life. In myelofibrosis, spleen may resume their haematopoietic functions (myelofibrosis). This explains the passage in the blood of immature elements of white and red lines (érythromyélémie).
• The spleen is also a vascular mesenchymal structure, lymphatic and fibrous can hypertrophy of benign or malignant manner (cysts, seromas, fibroma, fibrosarcoma or angioma, angiosarcoma).
Strong Points to remember:
• Any splenomegaly is pathological.
• The spleen is a vascular filter and macrophage.
• The spleen is an immune organ forming a nodal structure in direct contact with the blood circulation to preserve major organ: liver.
• The spleen is able to regain function of hematopoiesis
• All components can hyperplasier, pleiomorphism explaining its causes.