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Evaluation of splenomegaly and other splenic disorders in adults

Evaluation of splenomegaly and other splenic disorders in adults
Author:
Robert Bona, MD
Section Editor:
Robert T Means, Jr, MD, MACP
Deputy Editor:
Jennifer S Tirnauer, MD
Literature review current through: Dec 2022. | This topic last updated: Oct 26, 2022.

INTRODUCTION — The spleen is a highly vascular organ that participates in hematologic and immune homeostasis. Its vascularity, location, and functions make the spleen susceptible to several conditions that may be challenging to evaluate and treat.

This topic provides an overview of normal splenic size and function and an approach to evaluating splenic abnormalities in adults. The evaluation of splenomegaly in children and considerations related to elective or traumatic splenectomy are discussed separately.

Splenomegaly in children – (See "Approach to the child with an enlarged spleen".)

Elective splenectomy – (See "Elective (diagnostic or therapeutic) splenectomy".)

Splenic trauma – (See "Management of splenic injury in the adult trauma patient" and "Surgical management of splenic injury in the adult trauma patient".)

TERMINOLOGY — The following terminology is used to refer to normal and pathologic processes related to the spleen:

Accessory spleen – A separate region of splenic tissue in the abdomen, present in approximately 15 percent of individuals.

Asplenia – Absence of the spleen or absent splenic function (also called functional asplenia or autosplenectomy). This may be caused by surgical splenectomy (traumatic or atraumatic) or a condition such as sickle cell disease (SCD) in which splenic infarction early in life causes loss of splenic function. (See 'Asplenia or hyposplenia' below.)

Hyposplenia – Also called hyposplenism; refers to reduced splenic function. Milder forms of SCD such as hemoglobin SC disease or sickle-beta+ thalassemia may cause hyposplenia. An autoimmune disorder in which T or B lymphocyte function is impaired may affect antibody production and/or cell-mediated immunity without impacting other functions. (See 'Function' below.)

Splenomegaly – Increased spleen size. As discussed below, the normal range for splenic size is only an estimate, and mild deviations from this normal range do not necessarily imply a pathologic condition. (See 'Splenomegaly' below.)

Hypersplenism – Splenic sequestration and/or destruction of blood cells (red blood cells [RBCs], white blood cells [WBCs], and platelets) extensive enough to cause one or more cytopenias. (See 'Hypersplenism' below.)

Splenosis – Seeding of the abdominal cavity with splenic cells that can occur during surgery or trauma. (See 'Splenosis' below.)

Terminology for splenic anatomy is discussed below. (See 'Size and anatomy' below.)

PROPERTIES OF THE NORMAL SPLEEN

Location — The spleen lies within the peritoneal cavity in the posterior portion of the left upper quadrant, below the diaphragm and adjacent to the lower ribs (9 through 11), the stomach (figure 1), the splenic flexure of the colon (figure 2), and left kidney (figure 3), with its hilum in close approximation to the tail of the pancreas (figure 4). The splenic artery, derived from the celiac artery, supplies arterial blood to the spleen with little collateral flow. The splenic vein combines with the superior mesenteric vein to become the portal vein. The spleen is attached to the stomach and kidney via the gastrosplenic and splenorenal ligaments, respectively (figure 5). This location in close proximity to these structures and their vascular supplies facilitates its blood filtering function but presents challenges when splenectomy is required. (See "Elective (diagnostic or therapeutic) splenectomy", section on 'Surgical approach'.)

Size and anatomy — The size of the spleen correlates with a person's height, weight, and sex; it is slightly larger in taller and heavier individuals and in men than women. Use of height- and sex-corrected values when reporting spleen size may help reduce patient anxiety and avoid unnecessary evaluations, especially when splenic measurement is done on an imaging study obtained for another purpose.

A study in 1230 healthy volunteer stem cell donors (ages, 18 to 55 years) used ultrasound measurements and height and weight data to determine height- and sex-corrected values for splenic length and volume [1]. The median spleen length across the entire cohort was 10.9 cm (4.3 inches), with a mean volume of 166 cm3. The upper limits of normal for the tallest females and males were approximately 12.3 and 14.5 cm (4.8 and 5.7 inches), respectively. The authors noted that use of an upper limit of normal of 12 cm, which is common in many radiology departments, would inadvertently classify 6 percent of women and 26 percent of men in the cohort as having splenomegaly when in fact they did not. The formula derived from these data was used to create a smartphone application (SplenoCalc) that can determine the upper limit of normal for splenic length based on an individual's sex and height [2]. This analysis was performed exclusively in White people; data for other populations are awaited.

There is less of a consensus on how to describe spleen size in children. One study evaluated the spleen in 317 White children and adolescents ages 0 to 18 years and found no difference in size between males and females. They also noted that while spleen size increased with age, the ratio of spleen volume to abdominal volume decreased with age [3]. The study also noted that several parameters were associated with spleen volume, including body weight, height, body surface, age, waist circumference, and xiphopubic distance.

It is worth noting that the diagnostic criteria for various disease states have historically been built on measures of spleen size determined by physical examination, while imaging methods have been available for a shorter period of time. Radiologic methods of determining spleen size may be more accurate than physical examination, especially in individuals with truncal obesity, but the clinical or diagnostic significance of a spleen that is modestly enlarged on an imaging scan but is not palpable (ie, "scanomegaly") is uncertain. Evaluation of an enlarged spleen is discussed below. (See 'Splenomegaly' below.)

The spleen is organized into structurally distinct compartments that reflect its functions [4-7].

White pulp – The white pulp is a major secondary lymphoid compartment that contains approximately one-fourth of the lymphocytes in the body (figure 6). Lymphocytes exit the spleen via efferent lymph vessels and migrate into splenic lymph nodes [5]. The white pulp is organized as lymphoid sheaths with T and B cell areas surrounding the arterioles. The peri-arteriole lymphoid sheaths (PALS) contain mostly T cells while the follicular enlargements contain mostly B cells. The marginal zone is an important area where cells that leave the bloodstream and enter the white pulp transit. Some of these cells migrate to the venous sinuses. Marginal zone macrophages efficiently bind polysaccharide antigens [8]. The ratio of white pulp to red pulp increases during aging as antigenic exposures accumulate and lymphocytes proliferate. Lymphocyte development, antigen exposure, and antibody production in the spleen and other lymphoid organs are discussed separately. (See "Normal B and T lymphocyte development" and "The adaptive humoral immune response".)

Red pulp – The red pulp is the site of blood filtration and accounts for three-fourths of the splenic volume (figure 6). It is composed of a loose reticular network of capillaries and venous sinuses that have bulb-like extensions ending into cord tissue. The sinusoids are lined by reticuloendothelial macrophages through which the blood flows. The sinusoids are tortuous and their diameter is very small (2 to 3 microns), which causes the rate of blood flow to slow and allows more time for the macrophages to phagocytose foreign substances (eg, bacteria) as well as red blood cells (RBCs) that have become damaged, are less able to deform, or have been opsonized by antibodies. Antibody-coated platelets or white blood cells (WBCs) may also be removed from the circulation. The red pulp also contains aggregates of B and T lymphocytes. In autoimmune disorders with significant phagocytosis such as autoimmune hemolytic anemia (AIHA), the spleen can become enlarged due to expansion of the red pulp. Vascular engorgement due to hepatic disease (eg, cirrhosis) can also cause splenic engorgement and enlargement. (See 'Causes (splenomegaly)' below.)

The spleen is encased in a capsule of fibrous tissue and smooth muscle. Blood enters via the splenic artery, which branches into smaller (trabecular) arteries (figure 5). Approximately 90 percent of the blood enters the venous sinuses, with the remainder circulating into the white pulp. Surgical considerations related to the splenic vascular anatomy are discussed separately. (See "Surgical management of splenic injury in the adult trauma patient", section on 'Anatomy of the spleen'.)

Function — The spleen has a number of functions that broadly can be divided into filtering, immune, and hematopoietic processes [4,9,10].

Filtering – The markedly reduced rate of blood flow in the narrow splenic sinusoids lined with reticuloendothelial macrophages facilitates robust filtering of the blood and removal of various particulates. This generally occurs in the cords of Billroth in the red pulp. The normally slow flow of blood through the cords permits highly selective action on the blood cells by macrophages, which have receptors that can detect alterations in deformability (such as those that occur with normal RBC aging or certain disease states) or surface changes such as presence of complement component C3b or immunoglobulins. Extensive deformability is required for RBCs with a normal diameter of approximately 7 microns to squeeze through slits with a diameter of 2 to 3 microns. The macrophages can retard and modify (pit) or remove RBCs. This deformability requires a higher surface area-to-volume (SA/V) ratio than occurs in spherocytes.

Filtering can remove the following:

Bacteria and other microorganisms.

Portions of RBCs such as nuclear remnants (Howell-Jolly bodies), insoluble globin precipitates (Heinz bodies), and endocytic vacuoles. The membrane can re-anneal, and the remainder of the RBC can continue to circulate as an intact cell. If sufficient membrane has been removed, the surface area to volume ratio is reduced, producing a spherocyte (see "Red blood cell membrane: Structure, organization, and dynamics", section on 'Surface area to volume ratio (SA/V)'). This process may be referred to as "pitting" (removal of membrane pits). If splenic function is impaired, pits become apparent. (See 'Peripheral blood smear' below.)

Senescent RBCs and RBCs with reduced deformability (eg, spherocytes).

Opsonized (antibody-coated) RBCs, WBCs, or platelets.

During exercise, splenic and splanchnic blood volume decrease. At any point in time the spleen may contain approximately one-third or more of the total body supply of platelets [11].

Immunity – The spleen is a secondary lymphoid organ in which B lymphocytes, T lymphocytes, and plasma cells mature and reside in the white pulp. Mature B cells interact with T cells in the spleen during the antigen-dependent phase humoral immune response, which leads to antibody production and release. (See "Normal B and T lymphocyte development".)

Hematopoiesis – Hematopoiesis does not occur in the spleen of healthy adults. However, the spleen is a site of hematopoiesis in certain disorders associated with extramedullary hematopoiesis (thalassemia or primary myelofibrosis). This may be a consideration when contemplating splenectomy in these disorders. (See "Elective (diagnostic or therapeutic) splenectomy", section on 'Preoperative considerations'.)

The importance of these functions becomes apparent in individuals who have undergone splenectomy. Splenectomy can lead to reduced hemolysis in some disorders (eg, hereditary spherocytosis [HS]), increased risk of infection, and the appearance of Howell-Jolly bodies or thrombocytosis (increased platelet number) on the peripheral blood smear. (See "Hereditary spherocytosis", section on 'Management' and "Elective (diagnostic or therapeutic) splenectomy", section on 'Infection' and 'Peripheral blood smear' below.)

HOW TO EXAMINE THE SPLEEN

Physical examination — Examination of the spleen includes assessment of size, texture, and tenderness.

The normal spleen is not usually palpable because it is located beneath the rib cage in the left upper abdomen. The splenic texture is soft, and it is not firmly attached to other structures and is thus easily pushed away by palpation. The spleen may be palpable in children, adolescents, and some thin adults [12,13].

Examination of the spleen may be somewhat dependent on the expertise of the examiner, although not all studies evaluating the examination have found such differences [13-16].

A spleen becomes palpable when it is enlarged and/or when its texture changes. As an example, a spleen infiltrated with lymphoma or one that is carrying out extramedullary hematopoiesis is much firmer than a normal spleen and thus is easier to feel.

Despite enlargement or change in texture, an enlarged spleen may be challenging to palpate.

A mildly enlarged spleen may not extend far beyond the rib cage. It has been suggested that the spleen must be increased in size by at least 40 percent to become palpable [17].

A massively enlarged spleen may extend so far into the pelvis that it is difficult to identify its lower edge.

Abdominal obesity and/or tense abdominal musculature may obscure the splenic borders.

Other common barriers to accurate examination of the spleen involve incomplete relaxation of the patient's abdominal musculature or excessive tension in the examiner's hands (pressing too hard on the patient's abdomen). The following maneuvers may assist in reducing these barriers:

Place the patient in a supine position, with the arms at the sides (not overhead); the knees may be bent if this improves relaxation of the abdominal muscles.

Allow the patient to place their hand on the examiner's hand (on the abdomen). Do not suddenly increase pressure, as this may cause pain, guarding, and tensing of the abdominal muscles.

It may help to place the patient in the right lateral decubitus position with the knees and neck flexed. This maneuver increases relaxation of the abdominal muscles and rotates the spleen to a more anterior position. One study suggested that adding this maneuver was not useful after examination of the patient in the supine position [13]. However, it is this authors' experience that some spleens not palpable with the patient in the supine position can be palpated with the patient in the right lateral decubitus position.

Percussion of Traube's space (the tympanitic area overlying the gastric bubble in the left lateral hemithorax) or Castell's spot (lowest intercostal space in the anterior axillary line) may reveal downward displacement of the spleen in an individual with splenomegaly [18]. However, this finding is not extremely sensitive or specific. False positives may occur with hepatic enlargement or a recent meal, and false negatives may occur in obese individuals [19].

The use of bedside ultrasound may increase the sensitivity and specificity of the traditional physical examination in determining if the spleen is enlarged [20].

A minimally enlarged spleen will be mobile with respiration and may be palpable only at the end of inspiration. A minimally enlarged spleen may be felt as a rounded edge with the consistency of normal liver that slips under the examiner's fingers at the end of inspiration when using a light touch with the skin depressed under the left costal margin. Some minimally enlarged spleens may not be felt under any circumstance.

With greater degrees of enlargement, the spleen rotates to a more anterior and rightward position and may extend downward into the pelvis. Under these circumstances, splenomegaly is appreciated either by palpating at successively lower levels on the left side of the abdomen or by palpating the medial edge of the spleen. In more extreme cases, the enlarged spleen may even be palpable in the right upper quadrant.

A palpable spleen usually implies significant splenomegaly. However, not all palpable spleens are abnormal [21]. In many disorders associated with splenomegaly, palpation is sufficient to determine that splenomegaly is present. The degree of splenic enlargement does not always correlate with the presence of symptoms, which may include chronic abdominal pain, abdominal discomfort, early satiety, pain while lying on the side, or attacks of acute colicky left upper quadrant pain, but the presence of the symptoms in the setting of an enlarged spleen is often sufficient to proceed with appropriate therapy [22]. Imaging to confirm splenic enlargement may not be necessary.

In contrast, imaging is appropriate if assessment of splenic size is needed to assess the extent of disease or to document a response to therapy or if there are findings such as acute tenderness that suggest a focal lesion. (See 'Imaging and biopsy' below and 'Focal splenic lesions' below.)

Tenderness may indicate infarction, rupture, or acute infection. (See 'Evaluation (splenomegaly)' below.)

Imaging and biopsy — Imaging is appropriate if there is unexpected splenomegaly on physical examination or if there is a need to determine splenic size or involvement in a patient with a known hematologic condition (eg, for determining response to therapy).

Imaging may also be appropriate in individuals with a suspected splenic infarct, abscess, or other pathology. In contrast, exact measurement of splenic size is not required for individuals known to have splenomegaly or those in whom splenomegaly is documented by physical examination, and exact size measurement will not alter management.

Imaging to determine spleen size may be helpful in monitoring disease activity (progression or regression), such as in myeloproliferative neoplasms (MPNs). (See "Prognosis and treatment of polycythemia vera and secondary polycythemia".)

Several imaging methods can be used to assess splenic size and intrasplenic lesions: these include ultrasound, computed tomography (CT), positron emission tomography with CT (PET-CT), and magnetic resonance imaging (MRI). The choice of modality depends on the reason for testing and patient characteristics [7].

Assessing spleen size – Ultrasound is the best validated modality for assessing splenomegaly, with a standardized measurement of the longest dimension in an oblique cranial-caudal axis. As noted above, some criteria for the upper limit of normal for splenic size may be too stringent, and sex- and height-based adjustments may reduce unnecessary evaluations and patient anxiety. (See 'Size and anatomy' above.)

Spleen size may also be estimated by other methods such as CT or MRI performed for other reasons; however, criteria for spleen length are not as well validated by these methods as for ultrasound [23]. Most radiologists perform a similar measurement along the craniocaudal axis and use similar criteria for normal ranges as used for ultrasound. Intravenous contrast is not required to measure the spleen using these modalities.

Spleen size may vary when measured by different methods or even by the same method at different times, due to changes in hydration status, body position, or measurement approach. Generally, a variation by 10 to 20 percent is not considered significant unless there is a trend over time.

Evaluating infiltrative or focal lesions – CT or MRI can be used to evaluate splenic involvement by a systemic process or a focal lesion such as those mentioned below (see 'Focal splenic lesions' below). Normally, the spleen is homogenous with an appearance similar to a lymph node on imaging studies. CT and MRI are both effective in identifying focal lesions, although MRI may be more useful to characterize a lesion that has been identified and requires further evaluation. Consultation with the radiologist regarding the best imaging modality is helpful in some cases.

Examples of imaging in specific settings include the following [7]:

In suspected abscess or infarct, CT with contrast or MRI is appropriate; MRI can be performed without contrast if the patient has a contrast allergy or lacks venous access. On ultrasound, an abscess appears as a poorly defined hypoechoic or cystic lesion [24,25]. On CT, abscesses are ill-defined and have low attenuation. Central, higher attenuation and/or ring enhancement can also be seen. Multiple lesions may represent microabscesses or disseminated fungal disease, especially in immunocompromised individuals or individuals with endocarditis [24,25]. Infarction can cause areas of low attenuation with ring enhancement [26]. (See 'Abscess and infarction' below.)

Solid masses include benign and malignant tumors and inflammatory lesions such as sarcoidosis [27]. PET with 18F-fluorodeoxyglucose combined with CT (PET-CT) may be used to determine the likelihood of malignancy; PET-avid lesions are most likely to be malignant or to contain granulomas [28]. In most types of lymphoma, PET-CT is typically used for staging and monitoring of disease response. (See "Pretreatment evaluation and staging of non-Hodgkin lymphomas", section on 'Imaging' and "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma", section on 'PET/CT'.)

The most common tumors to metastasize to the spleen include breast, lung, ovary, stomach, prostate, and melanoma. Peritoneal implants on the splenic surface may occur in ovarian, gastrointestinal, and pancreatic cancer. Any of the modalities can be used for evaluating tumor metastases, depending on the degree of resolution required. (See 'Tumor cells or metastases' below.)

Cystic lesions include simple congenital cysts or post-traumatic pseudocysts, hemangiomas and other vascular lesions, and abscess or hydatid disease from echinococcus larva [27]. Suspected hematomas in individuals with trauma or acute pain can be imaged using contrast-enhanced CT or MRI. By CT, they appear as high-density, non-enhancing collections of fluid and can be classified according to one of several grading scales [25].

Simple cysts and hemangiomas appear as well-defined, hypoechoic lesions [24,25]. Pseudocysts, which typically occur after trauma, may have calcified walls. For complex cysts, hemangiomas, or lymphangiomas, MRI may provide greater resolution and/or give greater confidence in the likely diagnosis. Hydatid disease from echinococcus larva can produce homogenous cysts or cysts with internal debris, calcifications, or inflammatory features; in some cases, small peripheral cysts can be seen [25,29]. (See 'Cystic lesions' below.)

Other types of imaging such as radiography (plain films) or liver-spleen colloid scanning using radionuclides are not typically used to determine spleen size or to identify splenic lesions because they are less accurate, but such testing may reveal abnormalities when done for another purpose. These studies were helpful in determining splenic blood flow in patients with disorders affecting splenic function, and a "shift of colloid" to the bone marrow has been used to identify liver cirrhosis (rather than another condition such as portal hypertension) as a cause of splenomegaly [30-35]. (See 'Asplenia or hyposplenia' below.)

Biopsy of the spleen is not frequently performed due to its extensive vascularity and associated risk of bleeding. Splenic biopsy may be used in cases of isolated splenic lesions of unknown cause for which there is no other tissue more amenable to biopsy or if biopsies from other sites have been unrevealing [27]. It is generally done using ultrasound or CT guidance under controlled circumstances, with surgical support available in case emergency splenectomy due to bleeding is required.

A meta-analysis from 2011 that evaluated fine needle aspiration of the spleen reported a sensitivity of 87 percent, specificity of 96 percent, and complication rate of 2.2 percent (mostly bleeding and pain) [36]. The rate of bleeding appeared to correlate with the size of the biopsy needle, with less frequent complications when the needle bore size was <18 gauge. An earlier study that used a 14 gauge needle reported that 4 of 32 individuals (12.5 percent) had bleeding severe enough to lead to transfusion, and one required conversion to splenectomy [37].

A large series (nearly 400 patients) that evaluated ultrasound-guided biopsy of the spleen found an overall accuracy of 91 percent [38]. As would be expected, core biopsy was better for diagnosing lymphoma than fine needle aspirate (accuracy, 90.9 versus 68.5 percent), whereas the two methods provided similar accuracy for non-lymphoma diagnoses. Complications were seen in 5.3 percent (mostly pain and bleeding, in some cases requiring transfusion).

Other studies of the safety and efficacy of splenic biopsy have reported similar findings, in which a tissue diagnosis was often obtained, but complications (pain and bleeding, sometimes severe) were in the range of 3 to 8 percent [39-43].

Peripheral blood smear — The peripheral blood smear can provide clues to the presence or absence of normal splenic function. Individuals who have undergone splenectomy or have reduced splenic function can have the following findings on the blood smear [44]:

Red blood cell (RBC) abnormalities including Howell-Jolly bodies (picture 1) or nucleated RBCs (NRBCs)

RBCs with membrane pits (requires separate microscopy capabilities)

Thrombocytosis (increased platelet number)

Increased neutrophils, lymphocytes, and/or monocytes

Findings associated with the underlying condition that caused splenic dysfunction (eg, sickled cells in sickle cell disease [SCD], abnormal lymphocytes in chronic lymphocytic leukemia [CLL] or hairy cell leukemia [HCL])

Howell-Jolly bodies and NRBCs are seen on standard peripheral blood smears stained with Wright and/or Giemsa stain; pits (small membrane defects) are appreciated by a light microscopy technique such as interference contrast (Nomarski) microscopy, which is not routinely used in clinical laboratories [10]. These changes are relatively nonspecific, and the RBC findings are observer-dependent.

The sensitivity and specificity of RBC pitting or Howell-Jolly bodies for determining splenic dysfunction is challenging to determine as the percent of cells with these findings is a continuous variable, and it is not clear where to set the cutoff [45,46]. In a series of 63 individuals with various degrees of splenic function (some who had undergone splenectomy, some with presumed functional hyposplenism, and some healthy volunteers), blinded counting of Howell-Jolly bodies and pitted RBCs correlated somewhat with clinical status, with findings present in all of the splenectomized individuals, some of the presumed hyposplenic individuals, and one of the healthy volunteers [45]. The percentage of pitted cells in individuals who underwent splenectomy varied widely from <10 percent to >50 percent. Howell-Jolly bodies were present in individuals with >8 percent pitted RBCs and absent in those with <8 percent.

For those with an underlying hemolytic anemia for which splenectomy was performed (eg, hereditary spherocytosis, thalassemia), the proportion of abnormal RBCs may increase following splenectomy, demonstrating the role of the spleen in removing abnormally shaped or poorly deformable cells.

Rarely, an individual who has undergone splenectomy may develop splenic implants or have growth of an accessory spleen that may cause these typical findings on the blood smear to lessen or disappear.

Reduction in RBC pitting and Howell-Jolly bodies has also been reported in young children with SCD following chronic transfusion, hydroxyurea therapy, or hematopoietic cell transplantation, possibly due to partial restoration of splenic function [47-52].

SPLENOMEGALY

Causes (splenomegaly) — There are many potential causes of an enlarged spleen (table 1) [25]. Most of the mechanisms reflect passive engorgement with blood due to vascular pressure, increase in size due to hemolysis, or enlargement due to infiltration by cells or other material.

The distribution of specific causes of splenomegaly differs in different populations; liver disease and hematologic malignancy are common in most groups. A retrospective series of 449 individuals with splenomegaly from the 1970s to the 1990s found liver disease and hematologic malignancy in approximately one-third each, with infection in approximately one-fourth [53]. Other studies from the same time period have reported similar findings, with many of the infections related to HIV/AIDS [54].

Liver disease – The spleen can become engorged with blood when there is increased pressure due to parenchymal liver disease (eg, fibrosis, cirrhosis). The exact mechanism is not known. Contributing factors include portal congestion, altered hemodynamics, and inflammatory mediators [55]. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis".)

Vascular obstruction – Reduced blood flow caused by vascular obstruction (eg, portal, hepatic, or splanchnic vein thrombosis) can cause the spleen to enlarge due to increased pressure. In individuals with sickle cell disease (SCD), vaso-occlusion in the spleen can cause rapid expansion with enough of the blood volume to compromise hemodynamic parameters (ie, splenic sequestration crisis). (See "Etiology of the Budd-Chiari syndrome" and "Overview of the clinical manifestations of sickle cell disease", section on 'Splenic sequestration crisis'.)

Hematologic malignancies – Hematologic malignancies can cause focal lesions or diffuse splenic infiltration by neoplastic cells:

Hairy cell leukemia (HCL) – (See "Clinical features and diagnosis of hairy cell leukemia", section on 'Clinical features'.)

Large granular lymphocyte (LGL) leukemia – (See "Clinical manifestations, pathologic features, and diagnosis of T cell large granular lymphocyte leukemia".)

Splenic marginal zone lymphoma – (See "Splenic marginal zone lymphoma".)

Hepatosplenic T cell lymphoma (HSTL) – (See "Clinical manifestations, pathologic features, and diagnosis of hepatosplenic T cell lymphoma".)

Acute lymphoblastic leukemia (ALL) – (See "Clinical manifestations, pathologic features, and diagnosis of B cell acute lymphoblastic leukemia/lymphoma".)

Chronic lymphocytic leukemia (CLL) – (See "Clinical features and diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma", section on 'Splenomegaly'.)

Polycythemia vera (PV) – (See "Clinical manifestations and diagnosis of polycythemia vera", section on 'Overview of signs and symptoms'.)

Primary myelofibrosis (PMF) – (See "Clinical manifestations and diagnosis of primary myelofibrosis", section on 'Splenomegaly'.)

Chronic myeloid leukemia (CML) – (See "Clinical manifestations and diagnosis of chronic myeloid leukemia", section on 'Clinical manifestations'.)

Multiple myeloma (unusual) – (See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis", section on 'Spectrum of disease'.)

Many of these disorders can cause massive splenomegaly, especially the splenic lymphomas and the myeloproliferative neoplasms. In PMF and late PV, the spleen may become the primary site for extramedullary hematopoiesis, which may be a concern when considering splenectomy to control symptoms. (See "Elective (diagnostic or therapeutic) splenectomy", section on 'Conditions in which splenectomy is generally contraindicated'.)

Autoimmune cytopenias – Autoimmune destruction of red blood cells (RBCs), platelets, or neutrophils (autoimmune hemolytic anemia [AIHA], immune thrombocytopenia [ITP], and immune neutropenia, respectively) can also cause the spleen to enlarge. In some cases, these disorders produce cytopenias significant enough to cause serious complications. Felty syndrome (rheumatoid arthritis with autoimmune neutropenia and splenomegaly) can increase the risk of infectious complications. (See "Warm autoimmune hemolytic anemia (AIHA) in adults" and "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis" and "Immune neutropenia" and "Clinical manifestations and diagnosis of Felty syndrome".)

Extramedullary hematopoiesis – The spleen can become enlarged due to areas of blood cell production, referred to as extramedullary hematopoiesis. This typically occurs in disorders with severely impaired production of blood cells in the bone marrow. Primary myelofibrosis, secondary myelofibrosis, and transfusion-dependent thalassemia are common causes. (See "Clinical manifestations and diagnosis of primary myelofibrosis" and "Diagnosis of thalassemia (adults and children)".)

Infection – Infectious organisms associated with splenomegaly include:

Babesiosis – (See "Babesiosis: Clinical manifestations and diagnosis".)

Bartonellosis – (See "South American bartonellosis: Oroya fever and verruga peruana" and "Clinical features, diagnosis, and treatment of Bartonella quintana infections".)

Brucellosis – (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Epstein-Barr virus (infectious mononucleosis) – (See "Infectious mononucleosis".)

Histoplasmosis – (See "Diagnosis and treatment of disseminated histoplasmosis in HIV-uninfected patients".)

HIV/AIDS – (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)

Leptospirosis – (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Malaria (also called tropical splenomegaly syndrome) – (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children".)

Mycobacteria – (See "Overview of nontuberculous mycobacterial infections" and "Tuberculosis: Natural history, microbiology, and pathogenesis".)

Schistosomiasis – (See "Schistosomiasis: Epidemiology and clinical manifestations".)

Visceral leishmaniasis (kala-azar) – (See "Visceral leishmaniasis: Clinical manifestations and diagnosis".)

Infiltrative disorders – Infiltrative disorders cause splenic enlargement by other types of cells or other substances. In addition to the hematologic malignancies and infections listed above, the following disorders can cause splenomegaly:

Sarcoidosis – (See "Extrapulmonary manifestations of sarcoidosis", section on 'Lymph nodes, liver, and spleen'.)

Amyloidosis – (See "Overview of amyloidosis".)

Transient myeloproliferative disorder of Down syndrome – (See "Transient abnormal myelopoiesis (TAM) of Down syndrome (DS)".)

Gaucher disease (picture 2) – (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Visceral disease'.)

Systemic lupus erythematosus (SLE) – (See "Hematologic manifestations of systemic lupus erythematosus".)

Hemophagocytic lymphohistiocytosis (HLH) – (See "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis".)

Lymphoproliferative disorders such as autoimmune lymphoproliferative syndrome (ALPS) – (See "Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis".)

Tumor metastases (eg, melanoma, breast, lung) – (See "Imaging studies in melanoma", section on 'Less common sites of metastatic involvement'.)

Focal lesions– In some cases, focal lesions may bleed or expand to the degree that they cause splenomegaly. This has been reported with splenic hematomas, cysts, hemangiomas, hamartomas, and primary vascular tumors such as hemangiosarcoma [56,57]. (See 'Focal splenic lesions' below.)

G-CSF – Mild increases in spleen size have been reported in individuals treated with granulocyte colony-stimulating factor (G-CSF) such as for severe congenital neutropenia, hematopoietic stem cell mobilization, or other conditions [58-60]. The mechanism is unknown.

Evaluation (splenomegaly) — The evaluation of splenomegaly depends on the patient's clinical status and the reason that splenomegaly was identified. This may range from immediate bone marrow aspiration and biopsy (and other testing) in an acutely ill individual with massive splenomegaly and abnormalities on the peripheral blood smear to observation without an extensive workup in an otherwise asymptomatic healthy individual with incidentally discovered mild splenomegaly on an imaging study.

Initial testing — The first question to be answered is whether the individual truly has a disorder involving the spleen and does not simply have a slightly large spleen on an imaging study without any associated pathology ("scanomegaly"). (See 'Size and anatomy' above.)

Findings in splenic disorders may include the following:

Symptoms – Individuals are more likely to have such a disorder if they have symptoms attributable to splenomegaly (eg, early satiety, abdominal fullness or distention, pain referred to the chest or left shoulder). Pharyngitis, especially in a young adult, suggests infectious mononucleosis. Individuals with B symptoms or weight loss may have a malignancy (eg, lymphoma, myeloproliferative neoplasm, metastatic solid tumor). Those with significant alcohol intake or nonalcoholic fatty liver disease (NAFLD) may have hepatic fibrosis or cirrhosis. Those who reside in endemic areas may be at risk for pathogens listed above. (See 'Causes (splenomegaly)' above.)

Physical examination – Fever may be seen with infection or hematologic malignancy. Splenic tenderness suggests the possibility of infarction, rupture, or acute infection. Ascites or peripheral edema may be seen if there is severe liver disease and/or vascular obstruction. A ruddy complexion may be seen in PV.

The size of the spleen may be somewhat helpful in suggesting certain diagnoses but by itself does not have very high sensitivity or specificity. A massively enlarged spleen that crosses the midline or extends into the pelvis is often cited as a characteristic finding in myeloproliferative neoplasms, lymphoma, HCL, transfusion-dependent thalassemia, Gaucher disease, or tropical splenomegaly syndrome.

CBC and blood smear – Abnormalities on the complete blood count (CBC) and blood smear can typically suggest a class of hematologic disorders.

Immature or abnormal white blood cells (WBCs) – Lymphoproliferative or myeloproliferative disorders

Cytopenias – Liver disease with hypersplenism, AIHA, ITP, Felty syndrome, or congenital disorders (eg, hereditary hemolytic anemias)

Teardrop cells – Myelofibrosis or thalassemia

Spherocytes – AIHA or hereditary spherocytosis

Less commonly, parasitic organisms may be seen on the blood smear. Examples include Ehrlichia species (picture 3) in WBCs; or Bartonella, Babesia (picture 4 and picture 5), or malarial organisms (picture 6) in RBCs.

Other initial testing – Liver function tests are often helpful in determining the contribution of liver disease; however, mild elevations are nonspecific and may be a result of infection or hepatic involvement by another disorder.

HIV testing may be appropriate if no other cause of splenomegaly is immediately apparent.

Blood cultures are obtained if infection is suspected.

Serologies may be used to diagnose certain pathogens.

Chest radiography may be useful, as pleural effusion may accompany a splenic abscess or other infectious disease [61].

Gaucher disease is identified or excluded using a glucocerebrosidase assay on peripheral blood leukocytes. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Enzyme analysis'.)

Further testing in individuals with abnormal initial evaluation — In individuals with one or more of the findings described above, splenomegaly is likely to be due to a clinically significant disorder. Subsequent testing is guided by the acuity of the symptoms and details of the findings. As examples:

An acutely ill individual will likely be admitted to the hospital and tested for various infections as well as malignancy and possible splenic rupture. (See "Causes of abdominal pain in adults".)

In an asymptomatic or mildly symptomatic individual with characteristic findings on the blood smear, outpatient evaluation and hematologist consultation are reasonable. In some cases, cytopenias may be due to sequestration of blood cells in an enlarged spleen (hypersplenism); in others, they may be caused by bone marrow involvement of a hematologic condition that interferes with hematopoiesis. (See 'Hypersplenism' below and 'Indications for referral or biopsy' below.)

In an individual with sickle cell disease (SCD), splenic sequestration crisis is a potential concern, especially in those with an acute decline in hemoglobin or signs of hypovolemia. (See "Overview of the clinical manifestations of sickle cell disease", section on 'Splenic sequestration crisis'.)

For those with suspected malignancy or infiltrative disease involving the spleen, the spleen is rarely the appropriate organ/tissue to biopsy due to its vascularity; bone marrow aspirate and biopsy is appropriate in most cases of suspected hematologic malignancy. Other alternatives include lymph node biopsy or testing of peripheral blood using flow cytometry (for lymphoid neoplasms) or genetic testing (for myeloproliferative neoplasms). For suspected rheumatologic conditions or hemolytic anemias, laboratory testing for autoantibodies or abnormal RBC proteins may provide diagnostic confirmation, as discussed in the topic reviews listed above (see 'Causes (splenomegaly)' above). Hematologist consultation may be obtained if there is a question about appropriate testing and/or a need for bone marrow evaluation. (See 'Indications for referral or biopsy' below.)

For those with abnormal liver function tests and suspected liver disease, ultrasound imaging or ultrasound-based elastography may be used, with liver biopsy in cases in which a tissue diagnosis is indicated. (See "Approach to the patient with abnormal liver biochemical and function tests" and "Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and imaging examinations" and "Noninvasive assessment of hepatic fibrosis: Ultrasound-based elastography".)

For those with ascites or peripheral edema and suspected venous thromboembolism affecting the hepatic or splenic circulation, vascular ultrasound is usually appropriate. (See "Acute portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management" and "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management" and "Budd-Chiari syndrome: Epidemiology, clinical manifestations, and diagnosis".)

If none of the additional testing reveals a diagnosis, imaging with computed tomography (CT) of the chest, abdomen, and pelvis may be performed to identify lymphadenopathy or other areas to biopsy, and bone marrow aspirate and biopsy may be performed [53]. Diagnostic splenectomy is reserved as a last resort for those thought to have clinically significant splenic disease in whom none of the other diagnostic testing reveals a diagnosis. (See "Elective (diagnostic or therapeutic) splenectomy", section on 'Indications'.)

Expectant management in those with normal initial findings — People with incidentally discovered mild splenomegaly, either by imaging or palpation, who have none of the above findings may be observed clinically. Many such individuals may have no splenic pathology and may never require invasive testing or interventions [62,63].

An imaging scan (typically ultrasound) should be performed to document splenomegaly and can be repeated in a year to determine if the spleen size is increasing, especially if there is a greater concern for underlying pathology on the part of the patient or physician.

If the initial determination of splenomegaly was by CT or magnetic resonance imaging (MRI), obtaining an ultrasound allows a more standardized measurement and future studies without intravenous contrast. Periodic re-evaluation should focus on new symptoms, especially weight loss or constitutional symptoms, and possible mild liver or vascular disease.

As noted above, small deviations in measurements of less than 10 to 20 percent may represent measurement error rather than a true increase in spleen size. (See 'Imaging and biopsy' above.)

Indications for referral or biopsy — Hematologist referral is appropriate if there is concern about a hematologic malignancy that may require specialized testing or suspicion for an infection that is best diagnosed by bone marrow evaluation.

Examples of possible indications for biopsy include the following:

Bone marrow biopsy

Splenomegaly with leukocytosis, abnormal lymphocytes, or immature WBCs on the peripheral blood smear. (See "Clinical features and diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma" and "Clinical manifestations and diagnosis of chronic myeloid leukemia".)

Splenomegaly with thrombocytosis or erythrocytosis. (See "Overview of the myeloproliferative neoplasms" and "Diagnosis and clinical manifestations of essential thrombocythemia" and "Diagnostic approach to the patient with erythrocytosis/polycythemia".)

Lymph node biopsy – Splenomegaly with lymphadenopathy. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma" and "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults" and "Evaluation of peripheral lymphadenopathy in adults", section on 'Etiologies'.)

Liver biopsy – Referral to a hepatologist is appropriate if there is concern about liver disease that requires liver biopsy or specialized therapy for liver disease. (See "Approach to liver biopsy".)

Consultation with a radiologist is appropriate if splenomegaly is thought to be due to a focal lesion that requires further imaging. In rare cases, image-guided splenic biopsy may be performed, either as a fine needle aspiration or a core needle biopsy (see 'Imaging and biopsy' above). Biopsy caries a risk of bleeding that may be severe enough to require emergency splenectomy; as a result, this approach is reserved for cases in which biopsy of a more accessible site cannot be performed or is unrevealing, and the benefits are expected to outweigh this risk. However, biopsy may be preferable to diagnostic splenectomy if no other site is amenable to biopsy and/or if bone marrow aspirate and biopsy are unrevealing. (See 'Further testing in individuals with abnormal initial evaluation' above.)

Management (splenomegaly) — Management depends on the cause of splenic enlargement. Treatment of the underlying condition may reduce splenic size and lead to symptomatic improvement. (See 'Causes (splenomegaly)' above.)

Sports participation and fall risk — Splenomegaly in the setting of infectious mononucleosis carries a small but increased risk of splenic rupture that is potentially life threatening. As a result, all athletes should refrain from sports and other activities with a high risk of splenic injury. A 2016 literature review suggested that the risk may exist for up to eight weeks after onset of symptoms of infectious mononucleosis, and refraining from vigorous activity for eight weeks seems prudent [64].

If there is concern about persistent splenomegaly during recovery, ultrasound can be used to determine spleen size, but ultrasound is not routinely done. Details are discussed separately. (See "Infectious mononucleosis", section on 'Splenomegaly and splenic rupture' and "Infectious mononucleosis", section on 'Avoiding splenic rupture'.)

While splenic rupture is less well characterized in other conditions, avoidance of high-risk contact sports is prudent.

In a survey of hepatologists, 13 cases of splenic rupture were reported, 11 of which were associated with trauma [65]. Falling, rather than sports participation, was the most common triggering event. Interventions to reduce fall risk are discussed separately. (See "Falls: Prevention in community-dwelling older persons".)

Role of splenectomy — Splenectomy is rarely pursued as the first choice for managing symptomatic splenomegaly due to the associated risks of infection and thrombosis. However, if other interventions have proven ineffective, splenectomy may be appropriate for some individuals. In a retrospective study in which 68 individuals underwent splenectomy for unexplained splenomegaly, half had a neoplastic disease, with splenic marginal zone lymphoma the most common malignancy [66]. This subject is discussed in detail separately. (See "Elective (diagnostic or therapeutic) splenectomy".)

The role of splenectomy and splenic artery embolization to control hypersplenism is discussed below. (See 'Hypersplenism' below.)

DISORDERS OF SPLENIC FUNCTION

Hypersplenism — Hypersplenism refers to splenic pooling or sequestration of blood cells to a degree that causes one or more cytopenias. These might be associated with a known underlying condition or identified when a complete blood count (CBC) is performed for another reason. All of the normal splenic functions are thought to be accentuated in an enlarged spleen. (See 'Properties of the normal spleen' above.)

Typically, the cytopenias are relatively mild and transfusions are rarely indicated. The spleen is often enlarged (splenomegaly) and congested with blood (see 'Splenomegaly' above), but hypersplenism and splenomegaly do not always coexist.

Hypersplenism rarely causes clinically important complications because the cytopenias are mild. Bleeding due to thrombocytopenia is rare because the total body platelet mass is normal (figure 7) [67].

Conditions that cause hypersplenism and their mechanisms include liver disease, especially cirrhosis with increased portal pressure, and portal or hepatic vein thrombosis with portal hypertension. In addition to evaluation for these conditions, management should focus on identifying and treating other causes of cytopenias, which may include autoimmune destruction; deficiencies of iron, vitamin B12, or folate; or bone marrow abnormalities. (See "Approach to the adult with pancytopenia".)

Management of hypersplenism is usually supportive, with treatment of the underlying cause and avoidance of interventions that could further worsen hepatic or splenic function. For individuals with significant splenomegaly, avoiding high-impact activities and reducing the risk of falls may be indicated. (See 'Management (splenomegaly)' above.)

Other interventions that may be appropriate in selected, clinically severe cases include splenic artery embolization or splenectomy. For the most part, these remain investigational and are reserved for severe cases or refractory symptoms. (See "Ascites in adults with cirrhosis: Diuretic-resistant ascites", section on 'Splenic artery embolization'.)

A 2017 meta-analysis of partial splenic artery embolization versus splenectomy for treatment of hypersplenism related to hepatic cirrhosis identified 10 studies that included over 700 patients who underwent one of these procedures [68]. Indications for intervention were not clearly stated, but prevention of bleeding due to thrombocytopenia was the implied indication, with mean platelet counts prior to the intervention of approximately 40,000 to 50,000/microL. Both groups (embolization and splenectomy) had an improvement in cytopenias, with a greater improvement in the splenectomy group and shorter operative time and length of hospital stay in the embolization group.

Several studies have explored different splenic artery embolization techniques [69-71]. However, a benefit in patient-important outcomes (reduced bleeding, reduced transfusions) has not been demonstrated in clinical trials, and for most individuals, expectant management is appropriate.

Other interventions under investigation for hypersplenism include thermal ablation using microwaves or focused ultrasound [72,73].

Asplenia or hyposplenia — Absent or reduced splenic function (asplenia and hyposplenia, respectively) can be due to anatomic absence of the spleen (eg, following splenectomy) or an underlying disorder associated with splenic infarction or infiltration. Disorders associated with reduced splenic function and their mechanisms are summarized in the table (table 2). Some of the more common causes include sickle cell disease (SCD) and infiltrative disorders (eg, sarcoidosis, leukemia, lymphoma, or amyloidosis) [44]. Neonates are considered hyposplenic.

Rare cases of congenital asplenia or hyposplenia have been reported [74,75]. These may come to medical attention due to abnormalities on the CBC (thrombocytosis) or blood smear (Howell-Jolly bodies) or as an incidental finding.

In contrast to those with SCD, individuals with thalassemia are not considered functionally asplenic or hyposplenic unless they have undergone splenectomy. (See "Diagnosis of thalassemia (adults and children)", section on 'Hepatosplenomegaly' and "Management of thalassemia", section on 'Role of splenectomy'.)

Absent or reduced splenic function may be suspected in individuals with conditions known to affect the spleen or if characteristic red blood cell (RBC) findings such as Howell-Jolly bodies, RBC pits, or nucleated RBCs (NRBCs) are on the blood smear [76]. However, as noted above, these findings are relatively nonspecific. (See 'Peripheral blood smear' above.)

Studies in certain rheumatologic conditions such as rheumatoid arthritis and systemic lupus erythematosus (SLE) have demonstrated absent splenic uptake of a radiolabeled tracer, suggesting that repeated infarction or other injury has led to significant splenic impairment [33,77]. However, this testing is not routinely used.

A meta-analysis of studies in individuals with celiac disease found a slightly increased risk of pneumococcal infection during hospitalization (odds ratio [OR], 1.66; 95% CI 1.43-1.92), but most of the included studies were retrospective cohort analyses, and some of the data came from the era prior to the availability of pneumococcal vaccinations [78].

The major implication for management of documented or suspected splenic impairment is the increased risk of infection, which includes encapsulated organisms and other pathogens that would normally be cleared by the filtering function of the spleen or by the cell-mediated immune response (see 'Function' above). Important aspects of treatment and prevention of infection in these individuals are discussed in separate topic reviews:

Treatment of infection – (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function".)

Immunizations and prophylactic antibiotics – (See "Prevention of infection in patients with impaired splenic function".)

Other potential complications of splenectomy such as an increased risk of venous thromboembolism are also discussed separately. (See "Elective (diagnostic or therapeutic) splenectomy", section on 'Postoperative risks'.)

FOCAL SPLENIC LESIONS — A focal splenic lesion may be symptomatic (especially with abscess or infarction) or may be identified as an incidental finding on abdominal imaging. The evaluation and management depend on the patient's underlying medical disorder(s) and the likelihood of a serious complication. Information about the optimal imaging modality and the radiographic appearances of different types of focal splenic lesions is presented above. (See 'Imaging and biopsy' above.)

Abscess and infarction

Risk factors and presenting findings (abscess/infarction) — Splenic abscess is an uncommon infection that typically results from endocarditis or another source of hematogenous seeding such as pneumonia, gastrointestinal perforation, or arteriovenous malformation (table 3) [24,25,79].

In a series of 564 patients with documented endocarditis, splenic abscess was reported in 27 (4.8 percent) [80]. Other series have reported higher frequencies of splenic abscess in individuals with endocarditis (up to 20 percent) [80-83]. (See "Complications and outcome of infective endocarditis", section on 'Metastatic abscess' and "Overview of neutropenic fever syndromes", section on 'Fungal pathogens' and "Chronic disseminated candidiasis (hepatosplenic candidiasis)".)

Multiple fungal microabscesses can occur in individuals with prolonged febrile neutropenia. (See "Overview of neutropenic fever syndromes", section on 'Fungal pathogens'.)

Presenting features in splenic abscess include the following [61,79-82,84]:

Fever is common and may recur or persist despite antibiotics.

Left upper quadrant abdominal pain or left flank pain are often present.

Pleuritic chest pain may occur and there may be a left-sided pleural effusion.

There may be left shoulder pain or hiccups from diaphragmatic irritation.

Abdominal distention may occur, sometimes with splenomegaly.

Staphylococcus, streptococcus, and occasionally enterococcus are commonly seen with endocarditis.

In abscess seeded from other sites, the organisms reflected the site of origin (eg, respiratory versus gastrointestinal) and region of the world. Isolates included aerobic or anaerobic bacteria, yeast, or polymicrobial species.

Radiographic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) may show characteristic changes. (See 'Imaging and biopsy' above.)

Splenic infarction may have a similar presentation as splenic abscess and some of the same risk factors and causes (table 3); in some cases, an abscess may form at the site of a previous infarct [25,80,81,85,86]. Common presenting findings include pain, fever, nausea or vomiting, and splenomegaly; some individuals may have leukocytosis and some may lack symptoms altogether (ie, splenic infarct as an incidental finding) [85,87,88].

Risk factors for splenic infarction include:

Splenomegaly, especially due to hematologic conditions. (See 'Causes (splenomegaly)' above.)

Septic emboli (eg, in endocarditis). (See "Complications and outcome of infective endocarditis", section on 'Septic embolization'.)

Thromboemboli associated with atrial fibrillation, valvular heart disease, or an atrial septal defect [13,81,89]. (See "Patent foramen ovale", section on 'Other'.)

Sickle cell disease (SCD) or sickle cell trait (the latter especially at high altitudes). (See "Overview of the clinical manifestations of sickle cell disease", section on 'Infection' and "Sickle cell trait", section on 'Vaso-occlusive phenomena'.)

Prothrombotic states such as antiphospholipid syndrome (APS), heparin-induced thrombocytopenia (HIT), or cancer [90]. (See "Clinical manifestations of antiphospholipid syndrome", section on 'Arterial thrombosis' and "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Thrombosis'.)

The breadth of presentations and causes, and the frequency of specific underlying conditions, was illustrated in a large retrospective review that included 232 adults with splenic infarction identified from a radiology database, with medical record review for underlying risk factors [88]. A review of the 163 acute infarcts identified expected sources (cardioembolic, hematologic) as well as frequent abdominal inflammatory and infectious conditions (16 percent, including pancreatitis in 6 percent). Other common underlying conditions included celiac or splenic artery atherosclerosis (21 percent), malignancy (20 percent), and sepsis (17 percent). Only 33 (20 percent) of the patients presented with left upper quadrant pain; more common presenting symptoms included other sites of abdominal pain (47 percent) or no abdominal pain (33 percent; eg, as an incidental finding). In 40 percent of cases, more than one plausible risk factor was identified.

Prior, smaller studies have identified hematologic, cardioembolic, and prothrombotic disorders, sometimes identified prior to the splenic infarct and in others at the time of or after the infarct [86,91].

For patients with fever, it may be necessary to treat them for splenic abscess. Treatment for infection while the evaluation proceeds is common in individuals with SCD.

Management (abscess/infarction)

Antibiotics – Splenic abscesses are treated with broad-spectrum antibiotics. Antibiotic spectrum is narrowed once a microbiologic diagnosis is made and antibiotic sensitivities are determined. Splenic infarction is not treated with antibiotics.

Drainage, excision, or splenectomy – Options for removing the fluid collection include percutaneous drainage, local excision, or splenectomy. The choice among these is guided by local expertise, the patient's clinical status, the size and location of the abscess, and whether there is a single abscess or multiple lesions. The choice between drainage or splenectomy is individualized.

Drainage or resection of a splenic abscess is less invasive and is ideal when possible, with splenectomy reserved for cases that cannot be treated with drainage or excision.

In some cases with multiple small lesions, a course of prolonged antibiotic therapy without drainage, excision, or splenectomy may be a reasonable approach, with the caveat that a procedure may be needed if the lesions do not resolve with antibiotics.

A 2022 systematic review identified 46 retrospective studies of splenic abscess treatment, representing 589 patients; 301 were treated with percutaneous drainage and 288 with splenectomy [92]. Percutaneous drainage was associated with trends toward lower mortality (8 percent [95% CI 4-13 percent] versus 12 percent [95% CI 8-17 percent]) and fewer complications (10 percent [95% CI 4-17 percent] versus 26 percent [95% CI 16-37 percent]). However, neither of these trends was statistically significant, and the differences may have represented imbalances in the patient populations or local expertise rather than the relative efficacy of the two approaches. Some of the studies were decades old, raising the possibility that improvements in surgical or postoperative management over time may have affected results.

Surgical bleeding is the immediate risk of splenectomy. Long-term risks include immunosuppression and venous thromboembolism. (See "Elective (diagnostic or therapeutic) splenectomy", section on 'Postoperative risks'.)

Pain control – Analgesics may be required for pain associated with abscess or infarction.

Anticoagulation – Treatment of splenic infarction depends upon the underlying cause and usually involves anticoagulation.

Anticoagulation is generally appropriate if the underlying cause is a hypercoagulable state such as antiphospholipid syndrome (APS), heparin-induced thrombocytopenia (HIT), a cardioembolic source, malignancy, or an inherited thrombophilia. It is appropriate to consider these conditions and perform appropriate evaluations in an individual with otherwise unexplained splenic infarction.

If an underlying cause cannot be identified (ie, truly cryptogenic infarction), anticoagulation is likely to be prudent.

Anticoagulation is generally well tolerated; however, a case of splenic rupture following anticoagulant has been described [93]. (See 'Atraumatic rupture' below.)

Anticoagulation generally is not used in splenic infarction due to vaso-occlusion in SCD. Therapies directed at vaso-occlusion may be indicated, such as oxygenation and/or transfusion. (See "Acute vaso-occlusive pain management in sickle cell disease".)

Anticoagulation is less commonly used in children, unless they have a clear hypercoagulable state such as those listed above.

Splenic artery aneurysm — The splenic artery is the third most common site for abdominal artery aneurysm, after the aorta and iliac arteries. Overall, however, splenic artery aneurysms (SAA) are rare, with an incidence of approximately 0.06 to 0.12 percent in the general population [94]. Most occur in women over the age of 50 years; presentation in pregnancy is also observed. Contributing conditions may include atherosclerosis, portal hypertension, inflammatory conditions, cirrhosis, and certain inherited vascular and connective tissue disorders, as discussed separately. (See "Overview of visceral artery aneurysm and pseudoaneurysm".)

SAAs can present with abdominal pain or discomfort, left shoulder pain, nausea, or they may be detected incidentally on plain radiographs or abdominal imaging performed for another reason. SAAs are often calcified, making them more readily apparent on imaging studies; sometimes this is referred to as the Chinese dragon sign (see 'Calcification and granulomas' below). CT-angiography may be helpful in distinguishing true aneurysms from pseudoaneurysms or aneurysms in other organs (image 1) [95].

SAAs are clinically important because of the possibility of rupture, which is associated with a high mortality rate, especially during pregnancy and/or in patients with portal hypertension [96,97]. The double rupture phenomenon, which is rare, describes initial rupture into the lesser sac causing abdominal pain associated with a period of stability, followed by rupture into the peritoneal capsule with more severe pain and hemodynamic compromise.

Optimal management has not been established. Options for unruptured SAAs include serial monitoring, surgical resection with vascular reconstruction, stenting of the vessel, or endovascular coil/glue ablation techniques [98-100]. Treatment is generally recommended to reduce the risk of rupture, especially for individuals with symptomatic disease, individuals who are pregnant, those with an SAA larger than 2 cm in diameter, or those with an expanding aneurysm. Ruptured SAAs typically require laparotomy to control the bleeding and splenectomy. (See "Overview of visceral artery aneurysm and pseudoaneurysm", section on 'Management' and "Treatment of visceral artery aneurysm and pseudoaneurysm".)

Other vascular lesions — Other vascular lesions include hemangiomas and sclerosing angiomatoid nodular transformation (SANT); both of these are benign and usually do not produce symptoms [24]. They have a typical radiographic appearance and generally do not require biopsy. (See 'Imaging and biopsy' above.)

In rare cases, hemangiomas may undergo infarction or hemorrhage with rupture. Large hemangiomas can be complicated by the Kasabach-Merritt phenomenon, in which endothelial changes cause thrombocytopenia and a consumptive coagulopathy. (See "Tufted angioma, kaposiform hemangioendothelioma (KHE), and the Kasabach-Merritt phenomenon".)

Tumor cells or metastases — As noted above, many of the hematopoietic neoplasms can cause splenic infiltration with splenomegaly and/or discrete splenic lesions. (See 'Causes (splenomegaly)' above.)

The non-hematologic tumors most likely to metastasize to the spleen include breast, lung, ovary, stomach, prostate, and melanoma [7,101]. Peritoneal implants on the splenic surface may occur in ovarian, gastrointestinal, and pancreatic cancer.

The prevalence of splenic metastasis is not well established. In a series of 148 splenectomies performed at a cancer center because a splenic mass was identified on preoperative imaging, the final pathologic diagnosis was malignancy in 63 percent [102]. However, these individuals were pre-selected for concern about possible malignancy, so the study was not interpreted to mean that most splenic masses are malignant. As noted above, in a retrospective study of individuals who underwent diagnostic splenectomy for splenomegaly, approximately half had malignancy as a cause, with lymphoma as the most common diagnosis. (See 'Role of splenectomy' above.)

In some individuals with solid tumors who have known intraabdominal metastasis affecting other organs, it may not be necessary to establish a definite pathologic diagnosis of a splenic lesion. However, an isolated splenic lesion in an individual who otherwise has limited disease may warrant biopsy or diagnostic splenectomy. Discussion between the radiologist, oncologist, surgeon, and patient may focus on the likelihood of tumor metastasis versus a benign lesion, the risks and benefits of the procedure, and the potential impact of splenectomy on curing the disease.

Angiosarcoma is a rare, aggressive, highly metastatic malignancy that arises from the endothelial lining of splenic blood vessels [103-105]. Resection may be possible for isolated lesions; metastatic disease is treated with chemotherapy. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma" and "Systemic treatment of metastatic soft tissue sarcoma".)

Cystic lesions — A splenic cyst (or cysts) may cause symptoms of left upper quadrant pain, left shoulder pain, abdominal enlargement, or splenomegaly or may be noted as an incidental finding on an imaging study done for another purpose.

There are many causes of splenic cysts [25,27,106,107]:

Post-traumatic cysts/pseudocysts, including cystic splenosis

Hydatid (echinococcal) cysts

Congenital cysts

Epidermoid, mesothelial cysts

Hemangioma or SANT (see 'Other vascular lesions' above)

Lymphangioma

Polycystic kidney disease with splenic cysts

Splenic peliosis (cystic, blood-filled cavities)

Cystic metastasis to the spleen

Non-parasitic splenic cysts are rare, and there is no evidence-based information regarding their optimal surgical management [108]. In most cases, the cyst(s) can be monitored with periodic imaging to determine whether they are stable or enlarging. Some splenic cysts may remain unchanged for many years, while others may enlarge slowly, enlarge to massive proportions, rupture, bleed, or become secondarily infected.

For those with symptomatic cysts or cysts that are enlarging over time, a number of radiologic and surgical procedures are available for diagnosis [108-110]. Available treatment options for those with non-parasitic cysts include percutaneous procedures (eg, biopsy, aspiration, drainage) or more direct surgical interventions such as decapsulation/cyst wall unroofing or partial or total splenectomy. Only splenectomy provides diagnostic certainty, but this is rarely clinically justified.

Treatment of echinococcal cysts is discussed separately. (See "Echinococcosis: Treatment".)

Calcification and granulomas — Calcification may be noted in the splenic parenchyma or vasculature. A number of conditions may cause calcification, including phleboliths, splenic artery aneurysm, sickle cell disease (SCD), tumors (eg, hemangioma, hemangiosarcoma, lymphoma), and infections (eg, histoplasmosis, brucellosis, echinococcosis, candidiasis, tuberculosis) [111-120].

Splenic artery calcification can occur in the setting of aging, systemic disorders (eg, diabetes mellitus), or splenic artery aneurysms [94,121]. In a series of 395 asymptomatic, community-dwelling adults who underwent total-body CT scanning, 46 (11.6 percent) had evidence of splenic artery calcification; a similar proportion had calcification of the internal and external iliac arteries [121]. There did not appear to be any association between splenic artery calcification and overall mortality during 9.4 years of follow-up. The splenic artery is very tortuous, and calcification can cause a radiographic appearance referred to as the Chinese dragon sign [122,123]. (See 'Splenic artery aneurysm' above.)

Splenic granulomas can be caused by infection (picture 7) or infiltrative diseases such as sarcoidosis; evaluation is similar to granulomas of the liver. (See "Extrapulmonary manifestations of sarcoidosis", section on 'Lymph nodes, liver, and spleen' and "Evaluation of the adult patient with hepatic granuloma".)

Gamna-Gandy bodies are fibro-siderotic nodules impregnated with iron pigment (hemosiderin) and calcium that may appear in the spleen in congestive splenomegaly, SCD, or hemochromatosis [124]. They likely represent areas of organized hemorrhage.

TRAUMA/RUPTURE

Traumatic rupture — Blunt abdominal trauma most often results in injury to the spleen, which in over 60 percent of cases, is the only damaged intraperitoneal structure. Delayed splenic rupture can occur. This subject is discussed separately.

Patient evaluation – (See "Initial evaluation and management of blunt abdominal trauma in adults".)

Medical management and supportive care – (See "Management of splenic injury in the adult trauma patient".)

Splenectomy – (See "Surgical management of splenic injury in the adult trauma patient".)

Splenic injury may also occur as a complication of other types of abdominal surgery or colonoscopy [125,126]. The prevalence is unknown. (See "Overview of colonoscopy in adults", section on 'Complications' and "Elective (diagnostic or therapeutic) splenectomy", section on 'Cancer surgery'.)

Atraumatic rupture — Splenic rupture in the absence of trauma is uncommon but may be life threatening [127]. (See "Clinical manifestations and treatment of Epstein-Barr virus infection", section on 'Splenic rupture'.)

A systematic review of 845 cases from the literature identified the following causes [128]:

Neoplasm (eg, leukemia, lymphoma) – 30 percent

Infection (eg, infectious mononucleosis, cytomegalovirus [CMV], HIV, endocarditis, malaria) – 27 percent

Inflammatory disease/non-infectious disorders (eg, acute and chronic pancreatitis) – 20 percent

Drug and treatment related (eg, anticoagulation, granulocyte colony-stimulating factor [G-CSF], thrombolytic therapy, dialysis) – 9 percent

Mechanical causes (eg, pregnancy related, congestive splenomegaly) – 7 percent

Idiopathic (normal spleen) – 7 percent

Overall mortality was 12 percent. Risk factors for mortality included splenomegaly, age >40 years, and the presence of a neoplastic disorder. Splenectomy was performed in 84 percent of the cases, with conservative measures taken in the remainder.

Splenosis — Splenosis refers to implants of splenic tissue resulting from spillage of cells following abdominal trauma or surgery. Estimates of the frequency of splenosis vary widely, in the range of 26 to 65 percent following trauma and 16 to 20 percent following elective splenectomy for hematologic disorders [50,129-132]. There are often multiple implants, and they can be located anywhere in the peritoneal cavity. Common sites include the left upper quadrant of the abdomen (image 2); however, other sites of implantation may occur [129,133-139]. (See "Surgical management of splenic injury in the adult trauma patient", section on 'Splenosis'.)

Splenosis is generally suspected in an individual with a history of abdominal trauma or surgery. In the case of prior splenectomy, a clue to the presence of splenosis may be the absence of Howell-Jolly bodies or pitted red blood cells (RBCs) on the peripheral blood smear (see 'Peripheral blood smear' above). In rare cases, complications such as hemorrhage or small bowel obstruction may occur (image 3) [140-142].

The diagnosis may be made by radioisotope scanning; consultation with the radiologist regarding the best method is advised. In rare cases, biopsy or excision may be required. The differential diagnosis includes metastatic cancer and endometriosis [143-145]. Management is supportive.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Splenectomy (The Basics)")

Beyond the Basics (see "Patient education: Preventing infection in people with impaired spleen function (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Splenic function – The spleen is a highly vascular organ in the posterior left upper quadrant below the diaphragm and adjacent to the stomach, colon, and left kidney that participates in numerous aspects of hematologic and immune homeostasis (figure 6). The size of the spleen correlates with a person's height, weight, and sex; it is slightly larger in taller and heavier individuals and in men than women (although not all studies have shown a sex difference in spleen size). Use of height- and sex-corrected values when reporting spleen size may help reduce patient anxiety and avoid unnecessary evaluations, especially when splenic measurement is done on an imaging study obtained for another purpose. (See 'Properties of the normal spleen' above.)

Examination – The spleen is not usually palpable. Examination of the spleen is facilitated by relaxation of the abdominal muscles. Imaging is appropriate if there is unexpected splenomegaly on physical examination or if there is a need to determine splenic size or involvement in a patient with a known hematologic condition. Ultrasound is the best-validated method for determining spleen size. Computed tomography (CT) or magnetic resonance imaging (MRI) may be useful for characterizing infiltrative or focal splenic lesions. Absent or reduced splenic function can produce typical findings on the peripheral blood smear including increased cell counts and Howell-Jolly bodies, although quantification of these findings has not been well validated. (See 'How to examine the spleen' above.)

Splenic enlargement – Causes of splenomegaly are summarized in the table (table 1). The evaluation depends on the patient's clinical status and the reason splenomegaly was identified. Individuals with symptoms related to increased spleen size (early satiety, pleuritic chest pain, abdominal or left shoulder pain) and those with constitutional symptoms (fever, fatigue), signs of liver disease, or adenopathy are most likely to have splenic disorders. (See 'Causes (splenomegaly)' above and 'Evaluation (splenomegaly)' above.)

Management of splenomegaly typically involves treatment of the underlying cause. In some cases, it may be prudent to avoid contact sports or pay special attention to reducing the risk of falls. Splenectomy for symptomatic splenomegaly or to treat a primary splenic lymphoma may be appropriate in selected cases. (See 'Management (splenomegaly)' above and "Elective (diagnostic or therapeutic) splenectomy", section on 'Indications'.)

Pooling of cells in the spleen – Hypersplenism refers to splenic pooling or sequestration of blood cells to a degree that causes one or more cytopenias, which are relatively mild and rarely cause bleeding or require transfusions. Common causes include liver disease and hepatic or portal vein thrombosis. Management is usually supportive and focuses on treating the underlying cause. In rare cases, splenic artery embolization or splenectomy has been performed. (See 'Hypersplenism' above.)

Decreased splenic function – Causes of absent or reduced splenic function (asplenia or hyposplenia, respectively) include splenectomy, sickle cell disease (SCD), and infiltrative disorders (eg, sarcoidosis, leukemia, lymphoma, or amyloidosis) (table 2) (see 'Asplenia or hyposplenia' above). Separate topic reviews discuss the management and prevention of infections in asplenic or hyposplenic individuals. (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function" and "Prevention of infection in patients with impaired splenic function".)

Focal lesions – Splenic abscess and infarction have overlapping risk factors and causes (table 3), with similar clinical presentations but very different management approaches. Abscess requires aggressive antibiotic therapy; the choice between splenectomy and drainage is individualized. Infarction is often treated with anticoagulation if there is an underlying thromboembolic condition. SCD-associated infarction is generally not an indication for anticoagulation. These lesions can be painful, and appropriate analgesia should be provided. (See 'Abscess and infarction' above.)

The presentation, evaluation, and management of other focal lesions including splenic artery aneurysm, solid lesions, cysts, calcifications, and granulomas are discussed above. (See 'Splenic artery aneurysm' above and 'Tumor cells or metastases' above and 'Cystic lesions' above and 'Calcification and granulomas' above.)

Splenic rupture – The spleen is highly vascular and can rupture in the setting of trauma or surgery, especially if it is already enlarged. The most common cause of splenic rupture is blunt abdominal trauma, but in rare cases, atraumatic rupture can occur in the setting of malignancy, infection, or inflammatory disorders. Some cases of splenic trauma, rupture, or surgery can cause splenic tissue implants to be deposited in the abdomen (splenosis). (See 'Trauma/rupture' above and "Management of splenic injury in the adult trauma patient" and "Surgical management of splenic injury in the adult trauma patient".)

ACKNOWLEDGMENTS

We are saddened by the death of Stanley L Schrier, MD, who passed away in August 2019. The editors at UpToDate gratefully acknowledge Dr. Schrier's role as author on this topic, his tenure as the founding Editor-in-Chief for UpToDate in Hematology, and his dedicated and longstanding involvement with the UpToDate program.

The UpToDate editorial staff also acknowledges the extensive contributions of William C Mentzer, MD, to earlier versions of this and many other topic reviews.

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