Spleen
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Table of contents
Primary references, normal anatomy, normal histology, biopsy, grossing, massive splenomegaly, rupture, splenectomy, splenosis
Congenital anomalies: accessory spleen, asplenia, hepatolienal fusion, polysplenia, splenic-gonadal fusion, splenorenal fusion, wandering spleen
Cysts: echinococcal, epithelial, mesothelial, pseudocyst
Infectious/inflammatory disorders: abscess, acute splenitis, AIDS, foamy macrophages, follicular hyperplasia, granulomatous inflammation, hantavirus, infectious mononucleosis, malaria, mycobacteria, parvovirus, sarcoidosis, Splendore-Hoeppli phenomenon, typhoid fever, Wegener’s granulomatosis
Other non-neoplastic disorders: amyloidosis, congestive splenomegaly, Gaucher’s disease, hemolytic anemia, hereditary spherocytosis, hypersplenism, immune thrombocytopenic purpura, infarction, lipid histiocytoses, Niemann-Pick disease, peliosis, perisplenitis, radiation injury, sickle cell disease, thrombotic thrombocytopenic purpura, Wiskott-Aldrich syndrome
Hematogenous neoplasms: lymphoma-general, angioimmunoblastic T cell lymphoma, Castleman’s disease, chronic myelogenous leukemia, diffuse large B cell lymphoma, fibroblastic reticulum cell tumor, follicular dendritic cell tumor, follicular lymphoma, hairy cell leukemia, hepatosplenic alpha-beta T cell lymphoma, hepatosplenic gamma-delta T cell lymphoma, histiocytic lymphoma/sarcoma, Hodgkin’s lymphoma, interdigitating dendritic cell sarcoma, Langerhans’ cell histiocytosis, lymphoplasmacytic lymphoma, mantle cell lymphoma, marginal zone B cell lymphoma, mastocytosis, myelodysplasia, myelofibrosis, peripheral T cell lymphoma, plasmacytoma, prolymphocytic leukemia, small lymphocytic lymphoma
Vascular neoplasms: angiosarcoma, bacillary angiomatosis, hamartoma, hemangioendothelioma, hemangioma, hemangiopericytoma, littoral cell angioma, lymphangioma, sclerosing angiomatoid nodular transformation
Other tumors: ectopic adrenal myelolipoma, inflammatory myofibroblastic tumor, malignant fibrous histiocytoma, metastases, mucinous cystadenocarcinoma
American Journal of Surgical Pathology (AJSP), March 1977 to December 2004
Archives of Pathology and Laboratory Medicine (Archives), January 1976 to December 2004
Human Pathology (Hum Path), March 1970 to October 2004
Modern Pathology (Mod Path), January 1988 to December 2004
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); 2004
Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004
Journal search terms: spleen, splenic
Please refer to these primary references for more detailed discussions and photographs
Largest lymphoid tissue of human body, accounting for 25% of total lymphocytes
Lies between fundus of stomach and diaphragm
Filters foreign matter including old/damaged blood cells; participates in immune response to blood borne antigens; major repository of mononuclear phagocytic cells in red pulp, lymphoid cells in white pulp and platelets; produces new blood cells in infants / children or adults with severe anemia
Normally 150g with thin capsule
Gross: malpighian (splenic) follicles of white pulp are identifiable
Composed of red pulp and white pulp separated by marginal zone
Red pulp: filters old / damaged red blood cells; traversed by thin walled venous sinusoids lined by littoral cells, a type of endothelial cell which also stains with histiocytic markers and has a discontinuous wall, allowing passing of red blood cells between sinus and cords; sinuses are separated by splenic cords (cords of Billorth) containing a labyrinth of splenic macrophages, which filter red blood cells and ingest old (normal lifespan is 120 days), damaged (hereditary spherocytosis, sickle cell anemia) or antibody coated red blood cells; also remove Heinz bodies or other red blood cell inclusions (peripheral blood has Howell-Jolly bodies if no functional spleen is present)
White pulp: forms sheaths of lymphoid cells around arteries (periarteriolar lymphatic sheath), composed of T cells and lymphoid follicles (B cells); traps antigens for processing
In young infants, immature marginal zone may contribute to increased susceptibility to bacterial infections or sudden infant death syndrome (Hum Path 2004;35:113)
Blood flow: arteries terminate in fine penicilliary arterioles surrounded by lymphocytes, then enter red pulp sinusoids, then to splenic veins
Rare because may cause hemorrhage and often not useful
Fine needle aspiration may have high yield with low risk and be useful for obtaining specimens for flow cytometry
Fresh tissue preferable for special studies and flow cytometry
Section specimen every 3-5 mm
Obtain imprints after blotting with a towel to remove excess blood
Blocks should be thin for adequate fixation, since fixative penetrates spleen slowly
Describe apparent white pulp disorders (nodules), red pulp disorders (diffusely enlarged spleen without follicles or nodules), or other
Spleen > 1000g
Due to chronic myeloid leukemia, Gaucher’s disease, hairy cell leukemia, marginal zone B cell lymphoma, myelofibrosis, plasmacytoma, prolymphocytic leukemia
Due to blunt trauma or abdominal surgery, causing hemoperitoneum and emergency splenectomy
Only rarely ruptures spontaneously (associated with infectious mononucleosis, malaria, typhoid fever, leukemia / lymphoma, other tumors, subacute bacterial endocarditis, peliosis lienis, acute splenitis, pregnancy)
Case reports: pancreatic cancer presenting with splenic rupture (Archives 2004;128:1146), splenic pregnancy (Archives 2004;128:e146)
Gross: rupture may be a very small capsular tear, often in superior pole or hilum
Micro: neutrophils below capsular tear with intraparenchymal hemorrhage; also lymphoid hyperplasia with prominent marginal zone
References: Mod Path 1997;10:1214
Usually performed for traumatic rupture
Usually no clinical consequence in adults (case report of post-splenectomy pneumococcemia at Archives 1980;104:258)
In children, associated with increased incidence and severity of infections, particularly encapsulated bacteria such as Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae; overwhelming infections may begin days to years after splenectomy, without an identifiable focus, and have 50-80% mortality despite antibiotics
In children, splenectomy is avoided in favor of splenic repair, partial splenectomy or splenic autotransplant
Must consider possibility of accessory spleen(s) if splenectomy is performed for hematologic disorders
Laboratory: Howell-Jolly bodies are evidence of no splenic function
Autotransplantation of splenic tissue on peritoneal surface, abdominal wall or elsewhere after rupture or splenectomy
Usually affects young men
Common; may affect 67% of those with trauma to spleen
May also implant within pleural cavity, lung parenchyma or brain
Case reports: cerebral splenosis in 20 year old man, 15 years after post-traumatic splenectomy (AJSP 1998;22:894)
Micro: red and white pulp, resembling accessory spleen
Congenital anomalies
Accessory (supernumerary) spleen
Present in 20-33% of autopsies
Usually small (up to 4 cm), resembles normal spleen macroscopically and microscopically
Near splenic hilum, gastrosplenic ligament, tail of pancreas
Important to document or find in patients with splenectomy for hematologic disease
May contain epithelial cysts
Case reports: lymphoepithelial cyst and epidermoid cyst in accessory spleen located in pancreas (Mod Path 1998;11:1171)
DD: lymph nodes (clinically), splenosis
Asplenia (congenital absence of spleen)
Rare, associated with cardiac malformations (80%, usually involving atrioventricular endocardial cushion and ventricular outflow tract), situs inversus, anomalies of blood vessels, lung, abdominal viscera
Fusion of liver and spleen (Hum Path 1978;9:234)
Associated with extrahepatic biliary atresia (Archives 1980;104:212)
Rare congenital anomaly in which ectopic splenic tissue unites with a gonad (< 200 cases reported)
Continuous or discontinuous
Continuous: spleen connected to ectopic splenic mass by cord of splenic and fibrous tissue
Discontinuous: no connection between spleen and ectopic splenic mass
90% in males; usually left sided; usually less than 20 years old
20% of continuous types associated with other congenital defects, including peromelus (fetus with malformed limbs) and micrognathia; also testicular ectopia, inguinal hernia
Diagnosis: technetium Tc 99m sulfur colloid scan
Treatment: surgical excision of ectopic splenic tissue to prevent testicular atrophy, torsion or infarction and preserve fertility
Case reports: 56 year old man with asymptomatic testicular mass (Archives 2003;127:e277); 27 year old man with bilateral cryptorchidism and nonseminomatous germ cell tumor in intraabdominal splenic-gonadal mass (Archives 2002;126:1222), woman with discontinuous type (Hum Path 1989;20:486)
Gross: ectopic splenic tissue is well demarcated from gonad, only rarely is intermingling of tissue
Micro: normal splenic parenchyma, but may have thrombosis, calcification, fibrosis, fat degeneration, hemosiderin deposits; testicular tissue also normal, but may have atrophy or fibrosis of seminiferous tubules, increased Leydig cells, thrombosis of spermatic vessels
May be due to splenosis after splenic trauma or splenectomy, or less commonly, be a developmental anomaly resulting in fusion of splenic and renal tissue
May present as a renal mass or with symptoms of hypersplenism
Case report: 51 year old woman with renal mass (Archives 2003;127:e1)
Due to congenital loss / weakness of ligaments (link)
Cysts
Usually liver, occasionally in spleen
Usually children or young adults
Solitary or multiple; may be associated with accessory spleen
Called “epithelioid” if squamous lining
Origin unknown; may derive from metaplasia in mesothelial cysts
Often large and requires splenectomy
Gross: glistening inner surface with marked trabeculation
Micro: lined by squamous, columnar, cuboidal or mesothelial-like epithelium; no skin adnexae; rarely mucinous associated with pseudomyxoma peritonei
Positive stains: CEA, CA19-9
References: AJSP 1998;22:704, AJSP 1988;12:275
Also called solitary splenic lymphangioma
May be due to trauma
Micro: subcapsular, multicystic; may resemble lymphangioma
Positive stains: keratin, HBME-1
Negative stains: factor VIII-related antigen, CD31, CD34
DD: lymphangioma
References: AJSP 1997;21:334
75% of nonparasitic splenic cysts
Usually due to trauma; some may be epithelial cysts with denuded epithelial lining
Usually solitary, asymptomatic
Wall composed of dense fibrous tissue without an epithelial lining, often calcified
Often contains blood and necrotic debris
Rupture may cause massive hemoperitoneum
Infectious / inflammatory disorders
Very rare
Due to trauma, subacute bacterial endocarditis or infection from another site
Abscess often walled off
Also called acute splenic tumor or septic spleen
Although traditionally associated with bacteremia, only known study shows no correlation (Archives 2001;125:888)
Gross: splenic parenchyma may “flow” from cut surface
Micro: criteria are ill defined, but traditionally are acute congestion of red pulp with numerous neutrophils in red and white pulp; necrosis of follicles occurs with group A streptococcal infection; no capsular invasion by immunoblasts
DD: infectious mononucleosis
Prior to highly active antiretroviral therapy (HAART), typical findings were white pulp depletion, hemosiderin deposition, spindle cell proliferation and perivascular hyalinization; also infectious and malignant infiltrates
Post-HAART findings include less frequent white pulp depletion, but similar rates of splenic involvement by atypical mycobacteria and CMV in those with systemic disease
References: Mod Path 2002;15:406
Due to ingestion of exogenous mineral oil (in packaging of foodstuffs in North America, also in liver and abdominal lymph nodes), immune thrombocytopenic purpura, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, chronic granulomatous disease, thalassemia, hyperlipidemia
Follicular hyperplasia
Also called reactive follicular hyperplasia
Focal or diffuse
Normal in children
In adults, due to systemic infection (measles, typhoid fever, virus, malaria, other), immune-mediate disorders (immune thrombocytopenic purpura, hemolytic anemia, rheumatoid arthritis)
Often associated with congestion and plasmacytic proliferation
Associated with hypersplenism in Zaire, Nigeria and New Guinea, where spleens also show extramedullary hematopoiesis and marked sinusoidal dilation; may be related to malaria
Note: graft rejection and AIDS are associated with reactive nonfollicular hyperplasia, which may resemble lymphoma but has heterogeneous lymphocytic population without atypia and without clonality
Felty syndrome (rheumatoid arthritis): no granulocytic phagocytosis but expansion of red pulp cords and sinuses with macrophages
Gross: may have enlarged spleen with multiple small, pale-tan nodules or solitary large nodules resembling lymphoma
Micro: resemble nodal reactive follicles, with mixed follicular center population and tingible-body macrophages; usually mature lymphocytes and plasma cells in red pulp
References: AJSP 1983;7:373
Common in splenectomy specimens
Either (a) large active granulomas with epithelioid and Langhans giant cells, with or without central necrosis, (b) widespread small, sarcoid-like epithelioid granulomas with rare giant cells and no necrosis, (c) inactive granulomas with fibrosis and calcification
Granulomas usually associated with systemic disease involving liver, bone marrow and lymph nodes; also chronic uremia, IgA deficiency, infectious mononucleosis
Granulomas may be present in Hodgkin’s lymphoma, hairy cell leukemia, non-Hodgkin’s lymphoma, although granuloma itself does not mean spleen in involved by tumor
Active granulomas: in adults, associated with fever, weight loss, hepatosplenomegaly and hypersplenism
Inactive granulomas: associated with histoplasmosis
Treatment: splenectomy for symptoms of hypersplenism
References: Archives 1977;101:518
Rare but deadly disease transmitted to humans through aerosolized virus from rodent urine, droppings or saliva
Usually causes pulmonary syndrome with acute respiratory distress syndrome
Gross: dense, rubbery and heavy lungs floating within yellow serous fluid within pleural cavity; no specific splenic findings
Micro: spleen - generalized capillary dilation and edema, immunoblasts in red pulp and periarteriolar sheaths of spleen, occasional prominent and swollen endothelial cells
References: Centers for Disease Control information
May cause spontaneous splenic rupture and death, often 10-21 days after disease onset
Rupture may be due to increased intrasplenic pressure due to congestion and weakening of splenic capsule from infiltration by immunoblasts
Micro: expansion of red pulp with immunoblastic proliferation; immunoblasts may infiltrate subintima of intratrabecular veins, resemble Reed-Sternberg cells, occasionally exhibit hemophagocytosis
Positive stains: immunoblasts are positive for B and T cell markers, EBV by in situ hybridization, variable CD30
DD: Hodgkin’s or non-Hodgkin’s lymphoma
Small, weakly gram positive bacteria that are acid fast (due to mycolic acid in cell wall) and slow growers (3-4 weeks to develop a visible colony)
Mycobacterium avium complex (MAC) consists of M. avium and M. intracellulare, which cause disseminated disease associated with advanced HIV; cause pulmonary disease and cervical lymphadenitis in immunocompetent individuals
Disseminated MAC is the most common systemic bacterial infection in HIV+ patients
Treatment: clarithromycin or azithromycin plus ethambutol, for life
Case report: 37 year old white man with advanced HIV and splenomegaly (Archives 2001;125:697)
Causes “fifth” disease in children, a mild illness with a “slapped cheek” facial rash
Pregnant women may pass virus to fetus, where it causes marked fetal anemia and hydrops
Attacks erythroblasts, affecting those with minimal reserve (sickle cell patients, fetuses)
Abscess containing brightly eosinophilic, pseudomycotic structures composed of necrotic debris and immunoglobulin in starburst pattern
In US, usually due to Staphylococcus aureus or Pseudomonas aeruginosa; in tropics, due to schistosomiasis, microfilariae, various fungi
Case reports: 61 year old woman with CLL for 10 years with Nocardia asteroides in spleen (Archives 2001;125:1515)
Due to Salmonelli typhi infection
Causes inflammatory destruction of GI tract mucosa
Bacteremic phase may cause splenomegaly with destruction of splenic vessels
Splenic involvement rarely diagnosed during life, but occurs more frequently than clinically evident
Micro: necrotizing granulomatous inflammation, vasculitis with fibrinoid necrosis, vascular thrombosis, diffuse hyalinization of blood vessels, infarction, microcalcifications, hemosiderin deposition
References: Archives 1996;120:974
Other non-neoplastic disorders
Usually secondary; rarely localized splenic nodules
Even with diffuse involvement, spleen may still retain “pitting” function that prevents appearance of Howell-Jolly bodies in peripheral blood smears (Archives 1995;119:252)
Case reports: amyloid tumor in lymphoma patient (AJSP 1987;11:723), associated with malignant GIST of stomach (Archives 2003;127:470)
DD: hyaline adventitial thickening of splenic vessels (normal, AIDS associated)
Caused by portal hypertension, which may be due to cirrhosis, Budd-Chiari syndrome (thrombosis of hepatic veins), thrombosis of splenic veins, other thrombosis, portal vein stenosis or congestive heart failure
Portal vein thrombosis may be due to inflammation, trauma, tumor, inflammatory induced extrinsic pressure or idiopathic
Portal vein stenosis may be due to extension of obliterative process at birth in umbilical vein and ductus venosus into portal vein
Banti’s syndrome: idiopathic portal hypertension; controversial entity, cases in Japan and India, associated with fibroelastosis in portal tracts, dilated capillaries, phlebosclerosis; associated with hypersplenism and anemia, leukopenia and thrombocytopenia
Treatment: splenectomy; no shunt needed if coronary vein joins portal system central to point of obstruction; otherwise shunt is needed; possible shunts include splenic vein to renal vein and portal vein to vena cava
Gross: large, firm, dark with fibrosis of capsule
Micro: dilated veins and sinuses, fibrosis of red pulp, hemosiderin-laded macrophages; iron and calcium containing fibrotic nodules (Gamna-Gandy bodies) secondary to hemorrhage; no prominent lymphoid follicles
Autosomal recessive disease, due to accumulation of glucocerebroside (a sphingolipid) in reticuloendothelial cells in liver, spleen and bone marrow, due to a defect in lysosomal beta-glucocerebrosidase
Increased risk (14x) of hematologic malignancies and 4x for other malignancies
Type 1 - chronic nonneuronopathic form - often completely asymptomatic; disease discovered incidentally; does not involve the nervous system, high prevalence among Ashkenazi Jews (1/12 are carriers)
Type 2 - fatal neurodegenerative disorder of infancy, similar to Tay-Sachs disease
Type 3 - slowly progressive neurologic disease with survival into adulthood
Treatment: glucocerebrosidase (enzyme replacement therapy)
Case reports: Gaucher’s patient with splenic marginal zone lymphoma that progressed to diffuse large B cell lymphoma (Archives 2003;127:e242)
Gross: massively enlarged spleens up to 10 kg
Micro: marked expansion of red pulp; large number of histiocytes with finely fibrillar cytoplasm (crinkled or wrinkled paper-like), particularly in splenic cords; white pulp remains intact
Positive stains: iron, PAS (but weak)
Negative stains: phospholipids stains, acid-fast stains
DD: chronic myelogenous leukemia (similar looking cells)
Congenital (hereditary spherocytosis, sickle cell) or acquired
Acquired cases are usually due to deposition of immune complexes on red blood cell membranes; also bacterial hemolysins, plasma lipid abnormalities, parasites
Immune related cases often due to leukemia, Hodgkin’s lymphoma, sarcoidosis, SLE (lupus), tuberculosis, brucellosis
Coombs test: detects acquired cases via detection of surface immune complexes; first wash patient’s red blood cells, then add antihuman globulin rabbit serum, agglutination implies acquired hemolytic anemia
Direct Coombs test: detects antibody attached to red blood cells (above)
Indirect Coombs test: detects serum antibodies (i.e. antibodies NOT attached to red blood cells)
Treatment: steroids or immunosuppressives; splenectomy if unresponsive
Gross: firm, deep red tissue, thin capsule, no grossly identifiable malpighian follicles, 100-1000g
Micro: congestion in cords and sinuses, hemosiderin deposition, extramedullary hematopoiesis, erythrophagocytosis with neutrophils
Congenital hemolytic anemia due to genetically determined abnormal spectrin and ankyrin molecules, leading to defects in red blood cell membrane, causing spherical shape and lack of plasticity
Red blood cells become trapped within spleen and have less than usual 120 day lifespan
Splenic function is normal
Osmotic fragility: increased; basis for diagnostic testing
Treatment: splenectomy (prolongs survival of red blood cells, although they still have membrane defects)
Gross: firm, deep red tissue, thin capsule, no grossly identifiable malpighian follicles, 100-1000g
Micro: marked congestion in cords; sinuses appear empty but actually contain ghost red blood cells; may have prominent endothelial lined sinuses, hemosiderin deposition, erythrophagocytosis
Also called dysplenism
Enlarged spleen leads to removal of cellular blood components (some or all), causing thrombocytopenia, neutropenia, hemolytic anemia or pancytopenia
Often due to widening of splenic cords with increase in macrophages or connective tissue, causing premature destruction of normal blood components (congestive splenomegaly, Gaucher’s disease, leukemia / lymphoma, Langerhans’ cell histiocytosis, hamartoma, hemangioma, other conditions diffusely involving red pulp)
Infectious causes include infectious mononucleosis, tuberculosis, typhoid, CMV, brucellosis, syphilis, malaria, histoplasmosis, toxoplasmosis, trypanosomiasis, schistosomiasis, leishmaniasis, echinococcus
May also be due to abnormal cellular blood components (hereditary spherocytosis)
Immune thrombocytopenic purpura
Formerly called idiopathic thrombocytopenic purpura
Due to antiplatelet IgG produced in spleen, which binds to platelets; platelets are then removed by macrophages in spleen and liver
Associated with SLE (lupus), viral infection, drug hypersensitivity, CLL, Hodgkin’s lymphoma
May be related to microcirculatory changes that increase exposure of platelets to splenic macrophages and increase platelet destruction
Prognostic factors: patients without prominent secondary reactive follicular hyperplasia or ceroid histiocytosis have poorer response to splenectomy
Treatment: steroid or immunosuppressive therapy, splenectomy if unresponsive
Gross: normal or mildly enlarged spleen, prominent malpighian follicles
Micro: secondary follicles with well developed germinal centers, histiocytes and neutrophils in red pulp, dilated sinuses, germinal centers contain platelet antigen CD41 and show phagocytosis of nuclear debris and periarterial fibrosis; usually mild myeloid metaplasia or extramedullary hematopoiesis (due to megakaryocytes); variable plasma cells in marginal zone, variable foamy or ceroid-laden macrophages in red pulp (due to ingestion of phospholipids from platelets); steroid treatment diminishes prominence of follicles; rarely periarterial fibrosis (Archives 1986;110:1152)
EM: increased vascularization of white pulp and marginal zones, absence of marginal sinuses
References: Archives 1995;119:533
Due to thrombosis of splenic vein, usually secondary to cardiac emboli
Also associated with Wegener’s granulomatosis (may cause splenic rupture), massive splenomegaly, idiopathic
Gross: wedge shaped white-gray infarct involving capsule; infarcts heal as large, depressed scars
Includes ceroid (sea-blue) histiocytosis, Gaucher’s disease and other inherited diseases, hyperlipoproteinemia, light chain deposition disease, chronic myelogenous leukemia, immune thrombocytopenic purpura, follicular (mineral oil) lipidosis (due to lipid in packaging of food, Hum Path 1984;15:724)
Ceroid: benign histiocytes with abundant, foamy, vacuolated cytoplasm due to ingestion of sphingomyelin and other phospholipids
Sea-blue histiocyte syndrome (OMIM 269600): autosomal recessive, may be related to adult Niemann-Pick disease (Hum Path 1982;13:1115)
Micro: histiocytes diffusely within splenic cords; may separate the white pulp but don’t diminish its size
Positive stains: fat stains, acid-fast stains, PAS diastase
Also called peliosis lienis
Multiple blood filled cystic spaces
Usually associated with peliosis hepatis, but may be independent
May cause splenic rupture and death, particularly in patients with tuberculosis, carcinomatosis, recipients of anabolic-androgenic steroids, chronic leukemia, post-liver transplantation
Case reports: 62 year old man with peliosis and splenic rupture secondary to untreated chronic myelomonocytic leukemia (AJSP 1983;7:197)
Micro: blood filled sinuses with reduced lining cells, similar to hairy cell leukemia
Thick fibrous plaques coating splenic surface
Incidental finding at autopsy or associated with portal hypertension
Secondary to treatment for lymphoma
Gross: wrinkled and thick capsule with parenchymal collapse
Micro: diffuse fibrosis of red pulp, lymphocyte depletion
May have “autosplenectomy” due to recurrent infarctions
Gamna-Gandy bodies common
Thrombotic thrombocytopenic purpura
Often associated with splenomegaly
Micro: thrombi in arteries and arterioles without inflammation (90%); also PAS+, diastase resistant hyaline subendothelial deposits of platelet and platelet-related material (100%), secondary germinal centers (67%), periarteriolar concentric fibrosis (58%), hemosiderin laden macrophages (92%), hemophagocytosis (83%), extramedullary hematopoiesis (42%); no blood lakes, no microaneurysms, no infarcts
References: AJSP 1990;14:223
X linked disorder with thrombocytopenia, eczema, immunodeficiency of variable severity
Due to mutations in WASp gene
Micro: depletion of white pulp with reduction in marginal zone thickness, loss of small lymphocytes from T cell areas, presence of atypical plasma cells and extramedullary hematopoiesis
References: AJSP 1999;23:182, Hum Path 1981;12:821
Hematogenous neoplasms
Most common malignancy of spleen, although lymphomas restricted to the spleen are uncommon
Usually due to lymphoma elsewhere, particularly SLL/CLL, lymphoplasmacytic lymphoma, mantle cell lymphoma, follicle center cell lymphoma, marginal zone lymphoma; often involvement of splenic hilar or abdominal lymph nodes
Occasionally is primary site of lymphoma - most common types are diffuse large B cell lymphoma and marginal zone lymphoma
Patterns are homogenous, miliary, multiple masses or solitary mass
All subtypes are also described in the Lymphoma chapter
Angioimmunoblastic T cell lymphoma
Uncommon in spleen
Resembles atypical lymphoid hyperplasia
Micro: white pulp expansion with increased vessels and polymorphous infiltrate into red pulp
Positive stains: CD3, CD10
Molecular: clonality with gene rearrangement studies
Also called angiofollicular lymph node hyperplasia
Usually no prominent splenomegaly
Micro: usually plasma cell type with white pulp hyperplasia and prominent plasmacytosis; also hyaline-vascular type with white pulp hyperplasia and numerous atrophic and hyaline-vascular germinal centers, only rare plasma cells
References: AJSP 1988;12:176
See also under Myeloproliferative disorders
Gross: large, dark red, diffuse involvement with no identifiable malpighian follicles; often infarcts
Micro: polymorphous infiltrate of myeloid cells in all stages of differentiation; mainly affects splenic red pulp cords and sinuses, obliterates white pulp; rarely blastic transformation (Richter’s syndrome)
Positive stains: naphthol-AS-D chloroacetate esterase stain, myeloperoxidase
DD: hairy cell leukemia, myeloid hyperplasia (secondary to granulocyte colony stimulating factor, Mod Path 1998;11:1138)
Most frequent splenic lymphoma (50%), usually due to secondary dissemination from other sites
Splenomegaly, left upper quadrant pain, fever, weight loss, elevated erythrocyte sedimentation rate; also hypersplenism
May be associated with HIV
Commonly metastasizes to hilar and retroperitoneal lymph nodes
May coexist with SLL/CLL
Treatment: splenectomy, chemotherapy
Gross: large or small nodules or diffuse red pulp infiltration, may invade splenic capsule and adjacent structures
Micro: sheets of pleomorphic large cells (centroblasts, immunoblasts, anaplastic) with frequent mitotic figures, often plasmacytoid features; T cell/histiocyte rich tumors mimic reactive lesions
Patterns: macronodular (60%, usually stage I, usually favorable outcome, bcl6+), micronodular (30%, advanced clinical stage and often death due to disease, bcl6+, includes T cell rich B cell subtype), diffuse red pulp infiltration (10%, advanced clinical stage and often death due to disease, bcl6+)
macronodular - homogenous compact masses of large lymphocytes effacing splenic architecture, usually necrosis, often sclerosis; tumor cells usually centroblasts, also immunoblasts and polylobated cells; often macrophages, occasional epithelioid histiocytes
micronodular - includes T cell / histiocyte rich B cell lymphoma; uniform miliary pattern with focal coalescence of splenic white pulp micronodules; variable infiltration of red pulp; nodules composed of large B cells with occasional small T cells and CD68+ histiocytes; no residual mantle zone, no follicular dendritic cell network; small areas of necrosis and macrophages occasionally seen; may mimic reactive conditions
diffuse red pulp infiltration - diffuse tumor infiltration of red pulp cords and sinusoids with scattered residual white pulp islands; no pseudosinuses; tumor cells are centroblastic, polylobated or pleomorphic; usually no necrosis
Positive stains: bcl6, CD19 / CD20, bcl6; variable bcl2, CD30 and EMA
Negative stains: CD10 (usually), CD138, EBV, keratin (rarely positive, AJSP 1996;20:346)
DD: granulomas, Hodgkin’s lymphoma (CD15+, CD30+, prominent eosinophils, negative for B cell markers and bcl6), follicular lymphoma (nodular but different cytology, most cells are CD20+, CD10+), T cell lymphoma (T cells usually involve red pulp, are atypical, don’t form nodules)
References: AJSP 2003;27:895 (patterns), AJSP 2003; 27:903 (micronodular pattern)
Fibroblastic reticulum cell tumor
Very rare
Dendritic/reticular cells are immune system cells, subdivided into follicular dendritic cells, interdigitating dendritic cells (and closely related Langerhans cells) and fibroblastic reticulum cells
Fibroblastic reticulum cells are stromal support cells located in the parafollicular and deep cortex of lymph nodes and in extrafollicular areas of spleen and tonsils
Case reports: 61 year old woman with multiple hepatic lesions 2 years after splenectomy for tumor (Hum Path 2003;34:954)
Micro: whorled pattern of oval and spindle cells in collagenous background; also lymphocytes and plasma cells
Positive stains: vimentin, smooth muscle actin, desmin, CD68 (focal)
Negative stains: CD21, CD35, S100, EBV
Follicular dendritic cell tumor
Rare; usually affects lymph nodes and extranodal sites
Micro: fascicles, sheets, storiform or whorled patterns of oval and spindled cells; may have lymphocytes and plasma cells
Positive stains: CD21, CD35; EBV by in situ hybridization; variable S100 and CD68
Negative stains: CD1a
Inflammatory pseudotumor-like variant
Usually women, frequently with systemic symptoms
Indolent behavior
Localizes in liver, spleen
Associated with EBV
Prominent lymphoplasmacytic infiltration
References: AJSP 2001;25:721
Usually also involves other lymphoid sites besides spleen
Spleen may be clinically normal but still involved by lymphoma in most white pulp segments
Gross: extensive white pulp nodules
Micro: relatively homogenous, multicentric involvement of almost all white pulp areas, usually with centrocytes; no tingible body macrophages in neoplastic areas, no/reduced mantle zone, no associated plasmacytosis in red pulp; may have conspicuous marginal zone
Positive stains: bcl2 in germinal centers
Molecular: t(14;18) usually present
Rare; formerly known as leukemic reticuloendotheliosis
Older (mean age 50 years) white men (80% men) with pancytopenia (50%), massive splenomegaly with obliteration of white pulp and involvement of red pulp (common), infections (30%)
Chronic leukemia with splenomegaly (1 kg) and minimal lymphadenopathy; associated with frequent atypical mycobacterial infection with monocytopenia, weakness, weight loss
Treatment: splenectomy, 2-chlorodeoxyadenosine, interferon; cause apparent cures
Case reports: 42 year old man with WBC count of 98,000 (Archives 2003;127:253), blastic transformation (Archives 1997;121:707), with fatal periarteritis nodosa syndrome (Archives 1983;107:583)
Gross: diffuse and marked enlargement of spleen without nodules
Micro: spleen - red pulp involvement by bland tumor cells larger than small lymphocytes, with modest, pale blue agranular cytoplasm with threadlike extensions seen with phase contrast microscope, round or folded nuclei, no distinct nucleoli; residual follicles often present; no/rare mitotic figures; no phagocytosis; also increase in volume, surface and length of red pulp arterial vessels, pools (lakes) of blood in red pulp lined by hairy cells and simulating dilated sinuses or hemangiomas; tumor cells may aggregate in subendothelial spaces of trabecular veins; white pulp may be atrophic or obliterated; may have extramedullary hematopoiesis or large necrotizing granulomas secondary to atypical mycobacterial infection
Bone marrow - acellular aspirate due to reticulin fibers; “fried egg” appearance of hairy cells, which have abundant cytoplasm, distinct cell borders, bland round or oval nuclei; extravasated red blood cells common; mast cells also common
Positive stains: CD11c, CD19, CD20, CD22, CD25, CD45, CD79a, CD103, TRAP (tartrate resistant acid phosphatase), PCA-1 (plasma cell antigen-1), FMC7, surface IgH, DBA-44; also CD74, CD11b, CD68, cyclin D1; TIA1 (55%, small, dot-like, granular expression in cytoplasm)
Negative stains: CD5, CD10, CD15, CD23, CD30, granzyme B, perforin
Molecular: no specific chromosomal anomalies
EM: prominent cytoplasmic villous projections
DD: nodal marginal zone B cell lymphoma (focal, has tumor nodules in white pulp), mastocytosis (tryptase+), chronic myeloid leukemia, chronic lymphoblastic leukemia (also has blood lakes)
References: Mod Path 2004;17:840 (TIA1 expression)
Variant type
10% of cases, more aggressive; poor response to interferon
Mean age 70 years, often men with massive splenomegaly, marked lymphocytosis without infection, successful marrow aspirates
A Japanese variant also exists
Case reports: CD10+, CD25+, CD103-, poor response to interferon (Archives 2000;124:1710), 77 year old man, also with polycythemia vera (Archives 2003;127:e209)
Micro: medium/large leukemic cells, some with cytoplasmic projections; large, central nuclei with prominent nucleoli, occasionally with cloverleaf-like nuclei; fried egg appearance in bone marrow; may lack blood lakes
Positive stains: CD11c (bright by flow), variable CD25, variable CD103, variable TRAP; also CD22
Negative stains: CD10
DD: B cell prolymphocytic leukemia (no cytoplasmic projections), splenic marginal zone lymphoma (smaller cells may have short cytoplasmic projections, clumpy chromatin, indistinct nucleoli, different staining pattern)
References: AJSP 1989;13:671 (cloverleaf-like nuclei)
Hepatosplenic alpha-beta T cell lymphoma
Rare; <50 cases reported
Similar clinical presentation as hepatosplenic gamma-delta T cell lymphoma; also aggressive
79% female (although some reports indicate male predominance), wider age distribution than gamma-delta (some children, some age 50+ years)
Usually no significant nodal involvement
Peripheral blood involvement late in disease; may have blastic transformation
Case reports: 20 year old woman with S100+ tumor (Archives 2003;127:e119)
Micro: involves splenic red pulp, hepatic sinusoids and periportal areas, interstitial bone marrow; medium size tumor cells with scant-moderate cytoplasm, round-oval nuclei, inconspicuous nucleoli, occasionally abundant cytoplasm, irregular chromatin with nucleoli
Positive stains: CD3, CD8 (61%), CD45RO, NK antigens (CD16-44%, CD56, CD57-40%), occasionally EBV
Molecular: T cell receptor rearrangements, some with isochromosome 7q
References: AJSP 2001;25:285, AJSP 2001;25:970, AJSP 2000;24:1027, AJSP 2000;24:459
Hepatosplenic gamma-delta T cell lymphoma
Very rare, <100 cases reported
Hepatosplenomegaly, B symptoms, moderate anemia, marked thrombocytopenia, no lymphadenopathy
Young adults, 86% males
Often associated with renal transplant recipients (AJCP 2001;116:41, AJCP 2000;113:487, Hum Path 2002;33:253, AJSP 1997;21:781)
Aggressive, most die within 2 years
Gross: very large spleen with uniform cut surface and no identifiable malpighian follicles
Micro: lymphoid infiltrates in splenic red pulp composed of medium sized tumor cells with scant to moderate cytoplasm, round/oval nuclei with possible folds, slightly dispersed chromatin, inconspicuous nucleoli; liver and bone marrow tumor cells have intrasinusoidal distribution
Positive stains: CD2, CD3, CD7, CD56 or CD57, TIA-1, Fas ligand, gamma-delta T cell receptor
Negative stains: CD4, CD5, variable CD8, alpha-beta T cell receptor
Molecular: isochromosome 7q, trisomy 8; T cell receptor gamma gene rearrangements (AJCP 2001;116:410)
DD: hairy cell leukemia (blood lakes, negative for T cell markers, no T cell receptor rearrangement)
Rare to initially involve the spleen; usually arises in GI tract or skin
Must exclude diffuse large B cell or T cell lymphomas, anaplastic large cell lymphomas
Called malignant histiocytosis if disseminated
Case reports: 14 year old with mediastinal immature teratoma and malignant histiocytosis developing during chemotherapy (Hum Path 1996;27:1099)
Micro: diffuse sinusoidal infiltration of red pulp by neoplastic histiocytes with extension into cords; may be multinucleated giant atypical cells; often erythrophagocytosis; inconspicuous white pulp; no nodules or tumor masses
Positive stains: CD68, alpha-1-antitrypsin, alpha-1-antichymotrypsin, lysozyme, vimentin
EM: dilated sinuses lined by large atypical histiocytic cells with prominent erythrophagocytosis
DD: hepatosplenic T cell lymphoma
Most common site of extranodal involvement is spleen, but primary disease in spleen is rare
Splenectomy previously was part of staging procedure if low clinical stage, in which pathologic staging affects therapy; now may be replaced by radiologic imaging
May present with splenic rupture
Important to report whether 0-4 or 5+ macroscopic nodules present in spleen (affects prognosis)
Subclassification not a factor in therapy
Case reports: composite Hodgkin’s lymphoma and mantle cell lymphoma in spleen (AJSP 2003;27:1577); composite nodular lymphocyte predominant Hodgkin’s lymphoma and gamma heavy chain disease (Archives 2001;125:803)
Gross: one or more multiple nodules, may be only a few millimeters
Micro: earliest lesions are in periarterial lymphoid sheath or marginal zones; usually nodular sclerosis subtype; may have sarcoid-type granulomas even without splenic involvement; Reed-Sternberg cells difficult to identify
Interdigitating dendritic cell sarcoma
Very rare; usually involves lymph nodes
Dendritic cells: includes Langerhans’ cells, interdigitating dendritic cells, follicular dendritic cells, dermal dendrocytes, indeterminate cells and veiled cells; present in T cell areas of spleen (also lymph node, tonsil, thymus medulla); stimulate resting T cells to initiate cellular immunity
Case reports: 87 year old woman in Japan (AJSP 2002;26:530)
Gross: markedly enlarged spleen with confluent massive nodules
Micro: sheets or fascicles in red pulp, impinging on white pulp, of large cells with voluminous cytoplasm, polylobated or multiple nuclei, dispersed chromatin with clumping along nuclear membranes, often prominent eosinophilic nuclei; also erythrophagocytosis, variable pleomorphism
Positive stains: S100, CD68, vimentin, fascin
Negative stains: CD1a, CD30, CD34, CD45, B and T cell markers, HMB45, factor VIII, lysozyme
EM: complex, interdigitating cytoplasmic dendritic processes; no Birbeck granules
Langerhans’ cell histiocytosis
Almost always due to systemic disease
Usually found only at autopsy in spleen, associated with fatal thrombocytopenia due to hypersplenism
Micro: usually involves red pulp; large epithelioid-like cells with folded nuclei
Positive stains: S100, CD1a, CD68, vimentin
Associated with Waldenstrom’s macroglobulinemia
WHO definition: morphology below without features of other lymphoma types; serum IgM monoclonal protein present, monotypic B cell tumor negative for CD5, CD10, CD23
Micro: red and white pulp involvement by small lymphocytes, plasmacytoid lymphocytes, plasma cells; many cells have Russell bodies (intracytoplasmic inclusions) and Dutcher bodies (intranuclear inclusions); may have prominent epithelioid histiocytes; no proliferation centers
Positive stains: CD20
Negative stains: CD5, CD10, CD23
DD: SLL/CLL, marginal zone B cell lymphoma; other tumors may have elevated serum IgM
References: AJSP 2003;27:1104
Aggressive
Usually presents with splenomegaly and advanced disease
Blastoid variant may develop splenic rupture
Micro: confluent tumor nodules in white pulp or enlarged lymphocytic coronas surrounding germinal centers; often involvement of red pulp; small cells with irregular, often indented, hyperchromatic nuclei; no proliferation centers, no prolymphocytes; may have marginal zone-like differentiation, with more abundant, pale staining cytoplasm
Positive stains: CD5, CD20, CD43, bcl1/cyclin D1
Negative stains: CD23
Molecular: t(11,14)
Includes cases of splenic lymphoma with villous lymphocytes (older men, massive splenomegaly with atypical lymphocytes with cytoplasmic villous projections localized to one pole of cell present in peripheral blood, TRAP negative, CD103-, HC2-)
Most common splenic low grade B cell lymphoma; affects middle aged and elderly patients
Usually disseminated (as opposed to MALT lymphoma) with splenomegaly and left upper quadrant pain, paratrabecular marrow involvement in 75% causing anemia, involvement of peripheral blood, liver and often splenic hilar lymph nodes, but no peripheral nodal involvement unless it transforms
Usually indolent (5 year survival of 65%), but 13% transform, possibly related to 7q deletion (AJSP 2001;25:1268, Hum Path 1999;30:1153)
Note: cases with plasmacytic differentiation often present with monoclonal serum disorders and autoimmune disorders, including hemolytic anemia; may have Waldenstrom’s macroglobulinemia; are similar otherwise to non-plasmacytic cases (AJSP 2000;24:1581)
Case reports: blastic transformation (Archives 2000;124:748), 22 year woman (Archives 2002;126:214), associated with Gaucher’s disease with transformation to diffuse large B cell lymphoma (Archives 2003;127:e242)
Marginal zone: light zone surrounding splenic follicles; contains post-follicular center memory B cells derived after stimulation of recirculating cells from T cell dependent antigen
Gross: enlarged spleen with multiple small, grey-white nodules
Micro: massive splenic involvement, with infiltration of small atypical lymphocytes in mantle zone and medium lymphocytes with pale cytoplasm and oval clear nucleus in marginal zone, leading to mixed mantle-zone and marginal-zone involvement pattern; variable follicular colonization but definite increase in white pulp; cells are centrocyte-like, monocytoid (easily recognized with imprints) or lymphoplasmacytic; < 20% immunoblasts; may involve red pulp also; intrasinusoidal infiltration of bone marrow is a relatively specific finding
Lymph nodes: effaced, replaced by nodular infiltrate with preservation of sinuses; nodules have reactive follicular center surrounded by broad zone of small lymphocytes, partially infiltrated or totally replaced by small lymphocytes with pale cytoplasm (AJSP 1997;21:772)