Radiological Approach to Splenomegaly: Etiologies, Pathophysiologies, and Diagnostic Strategies

Abstract

The spleen is frequently referred to as the “silent and forgotten” organ of the abdomen by clinicians and radiologists, primarily because of the secondary nature of most splenic pathologies and their relative rarity compared with hepatic diseases. Nevertheless, the term splenomegaly frequently appears in radiological reports. Although it is often reported in the context of a known underlying cause, it is also commonly used as a purely descriptive term without reference to the underlying etiology. Although splenomegaly may occasionally be idiopathic, it commonly represents an underlying pathological condition. Therefore, radiologists are instrumental in accurately identifying splenomegaly, evaluating plausible differential diagnoses, and guiding appropriate clinical management and workups. Given the wide spectrum of etiologies and overlapping imaging features, a systematic approach is essential to enhance the diagnostic accuracy and clinical relevance. Here, we present a comprehensive literature review of splenomegaly from a radiological perspective, with causes categorized according to pathophysiological mechanisms.

INTRODUCTION

The spectrum of diseases associated with splenomegaly is extensive; however, primary splenic disorders are rare, and splenomegaly is almost always secondary to a systemic disease [1]. Therefore, when splenomegaly is identified, a systematic approach is required to determine whether it is an incidental finding or if further evaluation is necessary. Although the presence of splenomegaly has traditionally been determined through physical examination or plain radiography, the advent and widespread use of advanced imaging modalities such as ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) have enabled more accurate identification of splenomegaly and comprehensive evaluation of accompanying radiological findings, thereby facilitating the investigation of its underlying causes. The detection of splenomegaly using imaging modalities combined with relevant radiological and clinical findings on US, CT, or MRI is crucial for narrowing down the differential diagnosis and guiding patient evaluation. An in-depth understanding of the underlying pathophysiology further refines the diagnostic accuracy.

ANATOMY AND HISTOLOGY

The spleen is in the left hypogastric quadrantof the abdomen and is fixed intraperitoneally by the splenorenal, splenocolic, splenogastric, and phrenicosplenic ligaments [2]. The splenic capsule is relatively thin, and an enlarged spleen is susceptible to rupture.

The splenic artery supplies the end arteries that branch into small arterioles. The spleen has two distinct circulatory pathways, closed and open (Fig. 1). In closed circulation, a fraction of blood flows from the arterioles connected directly to the sinusoids and then directly into the splenic veins, exiting the spleen; the blood is always enclosed by the endothelium. In contrast, in open circulation, capillaries from the arterioles are uniquely open-ended, delivering blood into the stroma of the splenic cords. This accounts for a larger proportion of the blood flow that moves slowly through the macrophage-lined splenic cords and sinuses before eventually reaching the venous sinusoids [3,4]. Histologically, the spleen is composed of structurally distinct compartments that correspond to its functional roles [3,5,6]. The white pulp, a secondary lymphoid structure, consists of lymphoid tissue surrounding central arterioles and features periarteriolar lymphoid sheaths and nodules containing proliferating B cells within these sheaths, thereby playing a key role in immune surveillance [7]. The red pulp is a network of splenic cords and sinusoids lined by reticuloendothelial macrophages where blood circulates. The narrow, tortuous sinusoids of the red pulp significantly slow blood flow, enhancing filtration efficiency and facilitating the removal of particulate matter and aged or damaged cells. With this unique histological feature, the spleen performs several functions that can be broadly categorized into filtration, immune, and hematopoietic processes. The coexistence of the closed and open circulatory pathways, together with the distinct histologic organization of the red and white pulp, is thought to contribute to the characteristic heterogeneous enhancement of the spleen during the arterial phase, commonly referred to as the “zebra pattern” [3].

Fig. 1. Schematic view of blood circulation and structure of the spleen.

DEFINING SPLENOMEGALY

US is the most validated modality for assessing splenomegaly. The splenic volume is calculated using the formula for a prolate ellipse (0.52 × length × anteroposterior dimension × width) [8]. However, given the strong correlation between the splenic length and volume [9], a simple measurement of the longest dimension along the oblique craniocaudal axis is preferred. In contrast, CT and MRI, which provide images on predefined planes, may underestimate splenic size because of challenges in accurately measuring the longest craniocaudal dimension. Chow et al. [9] conducted a study aimed at defining individualized normal values for splenic length and volume. They found that splenic size correlates with height, weight, and sex: it tends to be larger in taller, heavier individuals and in males. Notably, the frequently cited upper limit of normal for splenic length (12 cm) was exceeded by 26% of males and 6% of females. This finding highlights the need for corrected upper limits to prevent unnecessary workups in otherwise healthy individuals whose splenic length surpasses the published normal values [9]. They also proposed validated algorithms to determine the percentiles of individual splenic sizes and introduced an application to facilitate clinical use (for iOS [https://itunes.apple.com/us/app/splenocalc/id1005559584?mt=8] and Android [https://play.google.com/store/search?q=splenocalc]).

With advances in deep learning, automated segmentation of the spleen for volume measurement using CT or MRI is feasible and particularly useful in patients requiring assessment of changes in splenic volume [10,11]. In volumetric measurements, weight-based thresholds have been shown to define splenomegaly more accurately [10,11].

IMAGING MODALITIES FOR EVALUATION OF SPLENIC LESIONS

A recent meta-analysis evaluating the diagnostic accuracy of various imaging modalities for differentiating between benign and malignant lesions found that positron emission tomography (PET) had the highest accuracy at 92% [12]. However, contrast-enhanced ultrasound, CT, and MRI also demonstrated comparable performance, with areas under the receiver operating characteristic curve of 91.4%, 90.9%, and 85.3%, respectively, which were not statistically significant compared with that of PET [12]. Another meta-analysis focusing on contrast-enhanced imaging modalities identified specific imaging characteristics that help distinguish malignant from benign splenic lesions. These include portal phase hypoenhancement, hypovascular enhancement patterns, and restricted diffusion on diffusion-weighted imaging, all of which are strong predictors of malignancy [13].

However, for the staging and surveillance of lymphoma, ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET-CT has been recognized as a primary imaging modality because of its higher sensitivity and specificity than conventional anatomical imaging for nodal and extranodal diseases [14,15].

Although splenic biopsy has traditionally been avoided because of concerns regarding the risk of bleeding, histological confirmation is sometimes necessary. Recent studies have shown that image-guided percutaneous core needle biopsy of the spleen can be performed safely, with low complication rates and relatively high diagnostic yield [16,17,18]. The reported complication rates following splenic biopsy are generally <10%, with major complications requiring treatment in only approximately 1%–2% of patients. Splenic biopsy has also been shown to be safe and effective in patients with non-mass-forming isolated splenomegaly suspected of having malignant lymphoma [19]. The independent risk factors associated with major hemorrhage include the targeting of smaller lesions, higher systolic blood pressure, lower platelet count, and the absence of ultrasound guidance [16,20].

KEY PATHOPHYSIOLOGICAL CONCEPTS IN SPLENOMEGALY

Hypersplenism

Splenic enlargement is often associated with the accentuation of splenic function, known as the hypersplenic state. Hypersplenism is a group of syndromes involving splenomegaly and peripheral cytopenia with various causes. The underlying cause of primary hypersplenism remains unclear; however, secondary hypersplenism can occur in association with any medical condition that causes splenomegaly [21]. The most common form of hypersplenism is secondary to cirrhotic portal hypertension following post-viral hepatitis. Several mechanisms have been proposed for the pathogenesis of hypersplenism-induced peripheral cytopenia, including the splenic retention of blood cells due to congestion or hyperemia, enhanced phagocytosis by overactivated splenic macrophages, and cytokine-mediated immune modulation and marrow suppression. These mechanisms have been supported by various molecular, histological, and imaging studies [21].

Extramedullary Hematopoiesis

Extramedullary hematopoiesis (EMH) is defined as the production of blood cells outside the bone marrow when the production of blood cells in the bone marrow is inadequate [22]. In adults, hematopoiesis normally occurs in the marrow of long bones, ribs, and vertebrae. When the primary sites of hemopoiesis in adults fail, such as in primary myelofibrosis or infiltrative disease, various extramedullary sites contribute to blood formation [23]. EMH also arises in hemoglobinopathies because of the poor quality of blood elements [23].

In the thorax, EMH most commonly presents as paravertebral fat-containing masses, which are typically located and often demonstrate fat attenuation, making the diagnosis relatively straightforward (Supplementary Fig. 1). In contrast, abdominal EMH usually manifests as hepatosplenomegaly, with or without focal soft tissue masses in the liver, spleen, perirenal space, or peritoneum (Supplementary Fig. 2) [12], potentially mimicking lymphoma or metastatic disease. When presenting as focal mass-like lesions, EMH has variable signal intensity on MRI depending on its activity [24]. Clinical correlation is essential, and a biopsy may be required for a definitive diagnosis.

CAUSES OF SPLENOMEGALY AND IMAGING MANIFESTATIONS

Splenomegaly can be classified into the following categories based on its underlying pathophysiological mechanisms: congestive, infectious, non-malignant infiltrative, rheumatic, hematologic neoplasms, non-neoplastic benign hematologic diseases related to the clearance of blood cells, and non-hematologic neoplasms. The pathophysiological basis and characteristic imaging findings of each category are discussed in detail. An overview of this classification is provided in Table 1.

Table 1. Etiological classification of splenomegaly.

Category	Groups	Examples
Congestive		Cirrhosis, splenic/portal vein thrombosis or obstruction, congestive cardiac failure, other conditions that can lead to a congestive state in the systemic or portal circulation
Infectious	Acute	Infectious mononucleosis, cytomegalovirus, human immunodeficiency virus, toxoplasmosis
	Tropical/parasitic	Malaria, leishmaniasis, schistosomiasis
Infiltrative (non-malignant)	Substance	Gaucher’s disease, Niemann-Pick disease, amyloidosis
	Granulomatous	Sarcoidosis
Rheumatic		Felty’s syndrome (severe subset of seropositive rheumatoid arthritis complicated by neutropenia and splenomegaly), systemic lupus erythematosus
Hematological neoplasms	Myeloproliferative	Polycythemia vera, essential thrombocytosis, myelofibrosis (primary or postpolycythemia vera/essential thrombocytosis)
	Lymphoma	Non-Hodgkin lymphoma, Hodgkin lymphoma
	Leukaemia	Acute leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, hairy cell leukemia, prolymphocytic leukemia
Non-neoplastic benign hematological disease related to clearance of blood cells	Congenital	Hereditary spherocytosis, thalassemia, sickle cell disorder
	Autoimmune	Immune thrombocytopenia, autoimmune hemolysis
	Metabolic	Megaloblastic anemia
Non-hematological neoplasm	Primary, benign	Lymphangioma, hemangioma, hamartoma, sclerosing angiomatoid nodular transformation, littoral cell angioma, inflammatory pseudotumor
	Primary, malignancy	Angiosarcoma
	Secondary	Metastasis

Congestive

Because the splenic blood flow drains into the portal vein via the splenic vein, congestive splenomegaly is primarily due to portal hypertension or obstruction of the splenic vein. Contributing factors include obliteration or thrombosis of the splenic or portal vein, liver disease, and heart disease, all of which impair venous drainage, leading to splenic congestion (Supplementary Fig. 3) [11]. The pathogenesis of congestive splenomegaly is characterized not only by congestion of the splenic red pulp but also by vascular proliferation, fibrosis, and lymphoid hyperplasia with activation. Spleen volume gradually increases as cirrhosis progresses to end-stage liver disease with the progression of liver fibrosis, which likely reflects portal hypertension.

Traditionally, liver findings have been the primary imaging markers used in the radiological assessment of the severity of portal hypertension. However, the splenic parameters also provide valuable information. Spleen stiffness, measured using magnetic resonance elastography or ultrasound elastography, correlates with the severity of portal hypertension [25,26]. In addition, a lower liver-to-spleen volume ratio on CT is reportedly associated with advanced liver fibrosis, the presence of portal hypertension, and increased risk of hepatic decompensation [27,28]. Gamna–Gandy bodies may be observed in congestive splenomegaly and represent organized focal hemorrhages within the spleen secondary to portal hypertension. These lesions, typically measuring <10 mm in size, are the most sensitively detected on MRI. The composition of hemosiderin, calcium, and fibrous tissue results in signal loss across all pulse sequences [29].

Splenic enlargement can be observed under various medical and physiological conditions, even in the absence of a known primary liver disease or venous obstruction. It is often associated with conditions that induce a congestive state through diverse mechanisms. For example, post-hepatectomy splenomegaly is a well-documented finding. One study suggested that splenic enlargement following donor hepatectomy results from splenic engorgement secondary to relative portal hypertension as well as the influence of a shared growth factor affecting the spleen and liver [30]. Additionally, chemotherapy-induced hepatopathy may cause portal hypertension and subsequent splenic enlargement, which has been reported to be partially irreversible [31]. During pregnancy, a significant overall increase in splenic area with advancing gestational age has been observed, which may have resulted from transient portal hypertension secondary to increased maternal blood volume [32].

Infectious

Spleen infections are rare, and immunosuppression is a major predisposing factor. They can be caused by viruses, bacteria, parasites, or fungi. In most infections, splenic abscesses develop and can be detected by CT with approximately 96% sensitivity [33]. They typically present as multinodular lesions representing microabscesses, predominantly cystic lesions or, rarely, mass-forming solid parenchymal lesions [34].

However, in some infections, splenomegaly may develop without the formation of a splenic abscess due to secondary immune activation rather than direct microbial infection of the spleen. Rapid splenic enlargement under these conditions occasionally induces rupture [34]. Infectious mononucleosis is one of the most common infectious diseases and presents as splenomegaly without a splenic abscess (Fig. 2). It is most commonly caused by the Epstein–Barr virus and primarily affects young adults, with splenomegaly and hepatomegaly observed in approximately 50% and 10% of patients, respectively [35]. CT findings include generalized lymphadenopathy, hepatosplenomegaly, and focal low-attenuation splenic lesions suggestive of partial splenic ischemia [36]. In addition to the Epstein–Barr virus, cytomegalovirus, human immunodeficiency virus, and toxoplasmosis may cause mononucleosis-like syndrome, and the patient presents with diffuse splenomegaly without focal parenchymal involvement. Other less-common causes of diffuse splenic enlargement include infective endocarditis, typhoid fever, brucellosis, and secondary syphilis [34]. Additionally, in well-known parasitic diseases, such as malaria and leishmaniasis, the patient may present with massive splenomegaly. Malaria is a serious mosquito-borne infectious disease caused by Plasmodium spp. Studies have demonstrated that splenomegaly is a common finding on CT, with splenic enlargement observed in approximately 95%–100% of patients during the acute phase [37]. Following antimalarial treatment, splenic size typically regresses over days to weeks. In addition to generalized splenomegaly, focal low-attenuation areas suggestive of partial splenic ischemia and spontaneous splenic rupture may be observed on imaging (Supplementary Fig. 4) [38].

Fig. 2. Twenty-six-year-old female who presented with fever and was diagnosed with EBV-associated infectious mononucleosis. A: Coronal contrast-enhanced abdominal CT image shows splenomegaly without visible focal splenic lesions. No significantly enlarged lymphadenopathy was observed in the abdominopelvic area. B: Contrast-enhanced CT image of the neck demonstrates multiple enlarged cervical lymph nodes (arrows). Histopathological examination of the neck node confirmed EBV-associated infectious mononucleosis. EBV = Epstein–Barr virus, CT = computed tomography.

Infiltrative (Non-Malignant)

Splenic involvement occurs in various systemic diseases, and splenomegaly may result from the infiltration of abnormal substances or cells. Amyloidosis is a group of pathophysiological diseases caused by the extracellular deposition of abnormal fibrillary proteins called amyloids [39]. Progressive deposition of amyloids compresses and replaces normal tissues, leading to organ dysfunction and various clinical syndromes [40]. The key abdominal radiological findings in systemic amyloidosis are hepatomegaly, a heterogeneous appearance of the liver, and peri-portal involvement [39], with the main radiological finding of splenic involvement being splenomegaly, which occurs in 4%–13% of patients with amyloidosis [40]. Reduced contrast enhancement, particularly on contrast-enhanced CT, is commonly associated with diffuse parenchymal amyloid infiltration (Fig. 3) [39]. On MRI, splenic amyloidosis typically exhibits high signal intensity on T1-weighted images and low signal intensity on T2-weighted images, which likely reflects reduced blood content due to amyloid deposition [41,42].

Fig. 3. Forty-eight-year-old male who presented with upper abdominal discomfort and was diagnosed with amyloidosis. A, B: Axial (A) and coronal (B) contrast-enhanced computed tomography images show splenomegaly and decreased enhancement of the spleen. Hyperattenuating fluid is present in the peritoneal cavity, with particularly high attenuation in the perisplenic space (arrows), suggestive of hemoperitoneum secondary to splenic rupture. Splenectomy was performed, and histopathological examination confirmed amyloidosis.

Gaucher disease is a rare genetic disorder characterized by a deficiency in the enzyme glucocerebrosidase, which leads to the accumulation of undegraded glucosylceramide in the reticuloendothelial system of the bone marrow, spleen, and liver, resulting in various symptoms and complications [43]. Hepatosplenomegaly occurs in most patients with Gaucher disease and remains one of the few conditions that can cause massive splenomegaly, with one study reporting an average splenic enlargement of approximately 2,200% [44,45]. Occasionally, splenic nodules may present as hypodense lesions on CT, as isointense signals on T1-weighted MR images, and as hypointense signals on T2-weighted MR images [45].

Sarcoidosis is a systemic inflammatory disease of unknown origin characterized by the formation of non-caseating granulomas. The lungs and mediastinal nodes are most commonly affected. Extrapulmonary involvement, which occurs in approximately 30% of patients, frequently includes the liver, spleen, lymph nodes, and kidneys [46]. Notably, abdominal sarcoidosis may be present even in the absence of pulmonary or lymphatic disease. Hepatic and splenic involvement in sarcoidosis demonstrates similar patterns, most commonly presenting as hepatosplenomegaly and may be accompanied by multiple focal lesions, which are more frequently observed in the spleen than in the liver [47]. Most focal splenic lesions are small, measuring approximately 1.0 cm in size, and over 50% are accompanied by hepatic lesions and concomitant abdominal lymphadenopathy (Fig. 4). On MRI, splenic lesions typically appear hypointense on T1- and T2-weighted images and are relatively hypoenhancing [47].

Fig. 4. Forty-eight-year-old male, diagnosed with sarcoidosis. A, B: Axial portal venous (A) and delayed phase (B) contrast-enhanced abdominal CT images show hepatosplenomegaly with numerous fine nodules diffusely distributed throughout the liver and spleen, demonstrating minimal enhancement on the delayed phase. Multiple enlarged retroperitoneal lymph nodes are also observed (arrow). C: Coronal CT image shows similar-appearing multiple nodules in both kidneys (arrows). D: Coronal contrast-enhanced CT image of the chest shows multiple symmetric hilar and mediastinal lymphadenopathies. Endobronchial ultrasound-guided biopsy revealed non-caseating granulomas, consistent with sarcoidosis. CT = computed tomography.

Rheumatic

Because it functions as a key immunological organ, the spleen is frequently affected in patients with systemic rheumatic diseases. Splenomegaly is a common feature of uncomplicated rheumatoid arthritis (RA), with clinically detectable enlargement observed in approximately 5%–10% of patients [48]. Felty’s syndrome, a rare extra-articular manifestation of RA with an estimated lifetime risk of approximately 1%, is defined by the triad of seropositive RA, splenomegaly, and neutropenia [49]. In some patients, Felty’s syndrome may be accompanied by massive splenomegaly, potentially leading to severe complications. Splenomegaly represents one of the diverse abdominal manifestations of systemic lupus erythematosus, with a prevalence of 10%–46% when evaluated by physical examination (Fig. 5) [50,51]. Furthermore, it is more frequently observed during periods of increased disease activity.

Fig. 5. Thirty-eight-year-old male with SLE under follow-up who presented with worsening abdominal pain. A, B: Axial (A) and coronal (B) portal venous phase contrast-enhanced abdominal computed tomography images show interval development of edematous wall thickening in the stomach, small bowel, and gallbladder, along with engorgement of mesenteric vessels and increased ascites compared with prior imaging. These findings are consistent with increased disease activity of SLE. The spleen also shows interval enlargement, with its long axis increasing from 10.2 to 12.7 cm. SLE = systemic lupus erythematosus.

Hematologic Neoplasms

Splenomegaly is commonly observed in hematologic neoplasms and may have prognostic significance. In lymphoma, splenic involvement upstages the disease from Stage II to Stage III, according to the modified Ann Arbor staging system. Similarly, in chronic myeloid leukemia, increased splenic size has been associated with higher risk categories and poorer prognosis, as reflected in the scoring systems [52]. Hematologic neoplasms can be broadly categorized into myeloproliferative disorders, lymphomas, and leukemias, each of which is associated with splenomegaly via multiple mechanisms [53]. The first is through the abnormal proliferation of malignant cells in the spleen, resulting in enlargement. Neoplastic infiltration is the primary cause of splenomegaly in lymphomas and leukemias, wherein malignant white blood cells accumulate within the spleen. Another is through EMH, which is particularly prevalent in myeloproliferative disorders, in which the spleen resumes or augments its role in blood cell production outside the bone marrow. Finally, through increased splenic workload, the spleen enlarges owing to heightened functional demands, such as increased sequestration or blood cell phagocytosis.

Splenic involvement in lymphoma is common and can present in four imaging patterns, in decreasing order of frequency: homogeneous splenomegaly without focal lesions (Fig. 6), diffuse infiltration with miliary lesions, multiple nodular lesions, and a large solitary mass [53]. Splenomegaly alone is an unreliable indicator of splenic involvement in lymphoma, as 30% of normal-sized spleens exhibit tumor infiltration; conversely, splenomegaly may be present without tumor infiltration [53,54]. The imaging findings of leukemia include lymphadenopathy, splenomegaly, and low-attenuation miliary splenic lesions, which are challenging to differentiate from fungal microabscesses using imaging alone [53]. In myeloproliferative neoplasms, splenomegaly is a major clinical manifestation, often presenting as massive enlargement, and is directly associated with extramedullary splenic hematopoiesis (Supplementary Fig. 2) [55].

Fig. 6. Sixty-eight-year-old woman diagnosed with mantle cell lymphoma. A: Arterial phase contrast-enhanced CT image shows homogeneously enlarged spleen without the normal heterogeneous parenchymal enhancement. B: Portal venous phase image demonstrates multiple enlarged retroperitoneal lymph nodes (*). C: PET-CT reveals diffuse ¹⁸F-fluorodeoxyglucose uptake throughout the spleen, consistent with lymphomatous infiltration. D: Post-chemotherapy arterial phase image shows marked reduction in splenomegaly with restoration of the normal heterogeneous parenchymal enhancement, as well as interval decrease in the size of the retroperitoneal lymph nodes. CT = computed tomography, PET = positron emission tomography.

Although ¹⁸F-FDG-PET is predominantly used for staging and response monitoring in lymphoma, accurate detection of splenic involvement is influenced by the lymphoma subtype and treatment-related alterations in splenic glucose metabolism [54]. Consequently, recent studies have explored the use of CT and MRI to assess splenic involvement in lymphoma. Several imaging features have been proposed to support this assessment. These include a low spleen-to-liver attenuation ratio during the portal venous phase and obliteration of the normal heterogeneous enhancement of the spleen during the arterial phase on contrast-enhanced CT (Fig. 6) [54,56]. These findings are based on the hypothesis that attenuation differs between normal and lymphoma-infiltrated splenic parenchyma. Additional parameters such as the extracellular volume fraction, radiomic signatures on contrast-enhanced CT, and the presence of diffusion restriction on MRI also help identify splenic infiltration by lymphoma [57,58,59]. Therefore, in patients with splenomegaly, particularly when ¹⁸F-PET-CT is unavailable or when contrast-enhanced CT or MRI are used as an adjunct to ¹⁸F-PET-CT, these imaging findings may serve as valuable indicators of splenic involvement.

Non-Neoplastic Benign Hematologic Disease Related to Clearance of Blood Cells

The unique histological architecture of the spleen enables key physiological functions, including erythrocyte quality control via the removal of abnormal red blood cells and immune surveillance through the clearance of bacteria and antibody-coated blood cells [4]. Various congenital, autoimmune, and metabolic disorders cause structural or functional abnormalities in blood cells, leading to increased splenic clearance of these defective cells and, consequently, varying degrees of splenomegaly (Fig. 7). Diagnosis is primarily established using peripheral blood smears and clinical correlations, whereas imaging studies contribute to the detection of associated complications. Imaging findings may vary depending on the disease severity, ranging from no detectable abnormalities to isolated splenomegaly and complications resulting from severe blood cell destruction. For instance, in sickle cell disease, imaging studies have demonstrated findings associated with repeated vascular occlusion caused by abnormally shaped erythrocytes, leading to recurrent episodes of ischemia, infarction, and eventual progressive ischemic organ damage, including autosplenectomy [60]. Secondary iron overload in these patients is mainly due to repeated red blood cell transfusions for disorders such as β-thalassemia major and sickle cell disease. Iron deposition typically occurs in the liver, spleen, and bone marrow of the reticuloendothelial system. On MRI, it appears as a low signal intensity on T2- and T2*-weighted images due to T2 shortening and decreased signal intensity on in-phase images compared with that on out-of-phase images [61]. In immune thrombocytopenia and autoimmune hemolytic anemia, imaging findings are typically limited to splenomegaly in the absence of complications such as hemorrhage, and the diagnosis is primarily guided by clinical history and laboratory evaluation.

Fig. 7. Thirty-four-year-old male with known hereditary spherocytosis who presented for evaluation of anemia. A: Contrast-enhanced abdominal coronal computed tomography shows splenomegaly without focal lesions. B: Spleen scintigraphy using Tc-99m sulfur colloid reveals normal tracer uptake localized to the spleen, without evidence of accessory spleens or ectopic reticuloendothelial tissue. Therapeutic splenectomy was performed, and postoperatively, the patient showed improvement in the anemia.

Non-Hematologic Neoplasms

As splenic lesions increase in size, they may cause splenomegaly, leading to complications such as hypersplenism, spontaneous rupture, or abdominal discomfort. Because the splenic parenchyma normally exhibits heterogeneous enhancement in the arterial phase, lesions can be mistaken for normal tissue, requiring additional phases or imaging modalities for an accurate diagnosis. Splenic neoplasms are most often discovered incidentally and typically occur without associated findings in other organs, making radiological assessment crucial for diagnosis. When integrated with clinical and laboratory findings, characteristic imaging features on CT or MRI usually allow diagnostic categorization without requiring an invasive biopsy [62,63].

Splenic lesions can be broadly categorized into cystic and solid types, each of which may be solitary or multiple lesions. Solitary cystic splenic lesions include epithelial cysts, pseudocysts, and echinococcal cysts. Lymphangioma presents as a solitary cyst but more commonly presents as multiple cystic lesions (Fig. 8). It can also be a component of diffuse lymphangiomatosis involving the spleen, which may expand and replace the splenic parenchyma, occasionally leading to splenomegaly [62,63].

Fig. 8. Fifty-three-year-old female. A-C: Pre-contrast axial (A), portal venous phase axial (B), and coronal portal venous phase (C) abdominal CT images show splenomegaly with multiple cystic lesions replacing nearly the entire splenic parenchyma. D: PET-CT shows no abnormal metabolic activity within the splenic lesions. Splenectomy was performed, and gross examination revealed multiple cystic masses with clear fluid content. Histopathological examination confirmed a diagnosis of splenic lymphangiomatosis. CT = computed tomography, PET = positron emission tomography.

Among benign solid splenic lesions, hemangioma, hamartoma, sclerosing angiomatoid nodular transformation, and inflammatory pseudotumors typically present as solitary solid masses. In contrast, littoral cell angioma (LCA) and hemangiomatosis are distinct in their tendency to present as multiple lesions and are therefore often associated with splenomegaly (Fig. 9) [64,65]. LCA has most commonly been described as a benign lesion, despite some reports of LCA with malignant features: a low-grade variant, littoral cell hemangioendothelioma, and its malignant counterpart, littoral cell angiosarcoma [66]. LCA typically presents as hypoattenuating lesions with delayed enhancement on contrast-enhanced CT, low signal intensity on T1- and T2-weighted MRI, and no uptake of ¹⁸F-FDG on ¹⁸F-PET-CT; however, differentiation from other malignant splenic lesions remains challenging owing to the presence of overlapping features [66].

Fig. 9. Sixty-eight-year-old female. A, B: Contrast-enhanced computed tomography shows multiple splenic nodules with hypoattenuation on the portal venous phase (A), which demonstrate progressive enhancement and become isoattenuating relative to the adjacent parenchyma on the delayed phase (B). C-E: MRI reveals these lesions to be hyperintense on T2-weighted imaging (C), with no definite diffusion restriction on high b-value diffusion weighted imaging (b = 800) (D) and the corresponding apparent diffusion coefficient map (E). Splenectomy was performed, and histopathological examination confirmed a diagnosis of littoral cell hemangioendothelioma. F: Follow-up MRI performed 6 months after the initial MRI demonstrates numerous new T2 hyperintense nodules in the liver, consistent with hepatic metastases. MRI = magnetic resonance imaging.

Malignant neoplasms, such as angiosarcoma, lymphoma, and metastatic disease, may present as solitary or multiple solid lesions (Supplementary Fig. 5) [62,63]. These lesions are often accompanied by abnormal abdominal findings that can serve as key diagnostic clues. Metastases occur in 69%–100% of patients with splenic angiosarcoma [67], with the liver being the most common metastatic site, followed by the lungs, bones, and lymph nodes [67]. Splenic angiosarcomas often manifest as large multinodular hypervascular masses with necrosis, infarction, and hemorrhage accompanied by splenomegaly and, occasionally, splenic rupture [68]. Most splenic metastases occur as components of multivisceral metastatic diseases. The most common primary causes include breast, lung, ovarian, colorectal, and gastric carcinomas, as well as cutaneous melanoma [69].

CONCLUSION

Splenomegaly can present with a broad spectrum of underlying conditions. Although imaging findings often provide valuable diagnostic clues, their presentation is frequently non-specific, necessitating a comprehensive interpretation that integrates the clinical context and imaging features (Fig. 10). Given the potential morbidity associated with diagnostic splenectomy, noninvasive or minimally invasive strategies should be prioritized to refine the differential diagnosis of splenic pathology. In addition to US, CT, and MRI, ¹⁸F-PET-CT and image-guided splenic biopsies offer meaningful diagnostic information while minimizing patient risks. Through this approach, radiologists are instrumental in selecting the most appropriate imaging modalities, contributing to accurate diagnosis and personalized patient management.

Fig. 10. Diagnostic algorithm based on clinical and radiological features. WBC = white blood cell, CRP = C-reactive protein, MR = magnetic resonance, SI = signal intensity, WI = weighted image, RA = rheumatoid arthritis, SLE = systemic lupus erythematosus.

Supplement

The Supplement is available with this article at https://doi.org/10.3348/kjr.2025.0848.