Evaluation of splenomegaly

Diseases

Summary

Splenomegaly generally denotes a palpably enlarged spleen. However, it may also refer to an enlarged spleen detected by an imaging test. It is not uncommon for a radiologist interpreting a chest x-ray to comment that the spleen seems enlarged (usually considered an incidental finding). Splenomegaly can be found in 3% of the general population.[1]

An average human spleen is 10 cm long and weighs 150 grams.[2] It may be difficult to palpate an enlarged spleen in the settings of obesity, a muscular abdominal wall, or the inability to sufficiently relax the abdominal musculature. In these cases, spleen size may need to be determined by imaging.

Approach to splenomegaly

It is difficult to create a stepwise algorithmic approach to the patient with splenomegaly.[1] [3] Urgent presentations include sudden pain associated with splenomegaly, splenic sequestration crisis of sickle cell anemia, and splenic vein or portal vein thrombosis. Otherwise, presentation is often incidental on physical exam or imaging. Categorization by presentations such as massive splenomegaly, isolated splenomegaly, or accompanying symptoms could be considered. However, these categories encompass diverse diagnoses. For example, thalassemia, chronic myeloid leukemia, Gaucher disease, hairy cell leukemia, myelofibrosis, and malaria may all present with a markedly enlarged spleen. Isolated splenomegaly is a feature of diagnoses such as splenic marginal lymphoma or benign splenic neoplasms. Accompanying symptoms are nonspecific; for example, fever may occur with lymphomas, malaria, endocarditis, or infectious mononucleosis.

Library

Classic periorbital purpura
Congo red stain blood vessel in a bone marrow biopsy demonstrating green birefringence pathognomonic of amyloidosis
Bone marrow aspirate showing a typical Gaucher cell
ECG of a patient with infective endocarditis. Note the first-degree AV block, nonspecific intraventricular conduction delay, and nonspecific ST-T wave abnormalities
BCR-ABL translocation
Peripheral blood film of a patient with acute myeloid leukemia showing myeloid blasts with an Auer rod
Peripheral blood smear showing leukoerythroblastic reaction: teardrop red blood cells (black arrows), and myelocyte (red arrow) and promyelocyte (blue arrow)
Red cells in sickle cell disease

Citations

Key Articles

Gertz MA. Waldenström macroglobulinemia: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017 Feb;92(2):209-17.[Abstract][Full Text]
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19;127(20):2375-90.[Abstract][Full Text]
Shakoory B, Geerlinks A, Wilejto M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ann Rheum Dis. 2023 Oct;82(10):1271-85.[Abstract][Full Text]
Kowdley KV, Brown KE, Ahn J, et al. ACG clinical guideline: hereditary hemochromatosis. Am J Gastroenterol. 2019 Aug;114(8):1202-18.[Abstract][Full Text]

Referenced Articles

1. Lichtin AE, Cook JR. Diseases of the spleen. In: Young NS, Gerson SL, High KA, eds. Clinical hematology. 1st ed. Philadelphia, PA: Elsevier; 2006:697-705.
2. McKenzie CV, Colonne CK, Yeo JH, et al. Splenomegaly: pathophysiological bases and therapeutic options. Int J Biochem Cell Biol. 2017 Dec 2;94:40-3.[Abstract]
3. Sjoberg BP, Menias CO, Lubner MG, et al. Splenomegaly: a combined clinical and radiologic approach to the differential diagnosis. Gastroenterol Clin North Am. 2018 Sep;47(3):643-66.[Abstract]
4. Willner IR, Reuben A. Alcohol and the liver. Curr Opin Gastroenterol. 2005 May;21(3):323-30.[Abstract]
5. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: chronic lymphocytic leukemia/small lymphocytic lymphoma [internet publication].[Full Text]
6. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: B-cell lymphomas [internet publication].[Full Text]
7. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: hodgkin lymphoma [internet publication].[Full Text]
8. Advani R, Rosenberg SA, Horning SJ. Stage I and II follicular non-Hodgkin's lymphoma: long term follow-up of no initial therapy. J Clin Oncol. 2004 Apr 15;22(8):1454-9.[Abstract][Full Text]
9. Koc O, Wilson WH. Non-Hodgkin's lymphoma. In: Young NS, Gerson SL, High KA, eds. Clinical hematology. 1st ed. Philadelphia, PA: Elsevier; 2006:579-95.
10. Blum KA, Lozanski G, Byrd JC. Adult Burkitt leukemia and lymphoma. Blood. 2004 Nov 15;104(10):3009-20.[Abstract][Full Text]
11. Gavriatopoulou M, Musto P, Caers J, et al. European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias. Leukemia. 2018 Sep;32(9):1883-98.[Abstract]
12. Gertz MA. Waldenström macroglobulinemia: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017 Feb;92(2):209-17.[Abstract][Full Text]
13. Frater JL. T-cell prolymphocytic leukemia: review of an entity and its differential diagnostic considerations. Int J Lab Hematol. 2020 Jun;42 Suppl 1:90-8.[Abstract]
14. Licata MJ, Janakiram M, Tan S, et al. Diagnostic challenges of adult T-cell leukemia/lymphoma in North America - a clinical, histological, and immunophenotypic correlation with a workflow proposal. Leuk Lymphoma. 2018 May;59(5):1188-94.[Abstract]
15. Kutok JL, Fletcher CD. Splenic vascular tumors. Semin Diagn Pathol. 2003 May;20(2):128-39.[Abstract]
16. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19;127(20):2375-90.[Abstract][Full Text]
17. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: hairy cell leukemia [internet publication].[Full Text]
18. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: myeloproliferative neoplasms [internet publication].[Full Text]
19. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: acute lymphoblastic leukemia [internet publication].[Full Text]
20. Rawstron AC, Bennett FL, O'Connor SJ, et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008 Aug 7;359(6):575-83.[Abstract][Full Text]
21. Cortes JE, Talpaz M, O'Brien S, et al. Staging of chronic myeloid leukemia in the imatinib era: an evaluation of the World Health Organization proposal. Cancer. 2006 Mar 15;106(6):1306-15.[Abstract]
22. Mughal TI, Goldman JM. Chronic myeloid leukemia: current status and controversies. Oncology. 2004 Jun;18(7):837-44.[Abstract]
23. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med. 2000 Apr 27;342(17):1255-65.[Abstract]
24. Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013 Sep;27(9):1874-81.[Abstract][Full Text]
25. Lachmann HJ, Goodman HJ, Gilbertson JA, et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med. 2007 Jun 7;356(23):2361-71.[Abstract][Full Text]
26. Canna SW, Marsh RA. Pediatric hemophagocytic lymphohistiocytosis. Blood. 2020 Apr 16;135(16):1332-43.[Abstract][Full Text]
27. Allen CE, McClain KL. Pathophysiology and epidemiology of hemophagocytic lymphohistiocytosis. Hematology Am Soc Hematol Educ Program. 2015;2015:177-82.[Abstract][Full Text]
28. Jordan MB, Allen CE, Greenberg J, et al. Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: recommendations from the North American Consortium for Histiocytosis (NACHO). Pediatr Blood Cancer. 2019 Nov;66(11):e27929.[Abstract][Full Text]
29. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019 Jun 6;133(23):2465-77.[Abstract][Full Text]
30. Shakoory B, Geerlinks A, Wilejto M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ann Rheum Dis. 2023 Oct;82(10):1271-85.[Abstract][Full Text]
31. Fardet L, Galicier L, Lambotte O, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014 Sep;66(9):2613-20.[Abstract][Full Text]
32. Henter JI, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31.[Abstract]
33. Grabowski GA. Recent clinical progress in Gaucher disease. Curr Opin Pediatr. 2005 Aug;17(4):519-24.[Abstract]
34. Imrie J, Vijayaraghaven S, Whitehouse C, et al. Niemann-Pick disease type C in adults. J Inherit Metab Dis. 2002 Oct;25(6):491-500.[Abstract]
35. World Health Organization. WHO Guidelines for malaria. Mar 2023 [internet publication].[Full Text]
36. Griffith KS, Lewis LS, Mali S, et al. Treatment of malaria in the United States: a systematic review. JAMA. 2007 May 23;297(20):2264-77.[Abstract]
37. Leoni S, Buonfrate D, Angheben A, et al. The hyper-reactive malarial splenomegaly: a systematic review of the literature. Malar J. 2015 Apr 29;14:185.[Abstract][Full Text]
38. Kan FK, Tan CC, Von Bahr Greenwood T, et al. Dengue infection complicated by hemophagocytic lymphohistiocytosis: experiences from 180 patients with severe dengue. Clin Infect Dis. 2020 May 23;70(11):2247-55.[Abstract][Full Text]
39. Giang HTN, Banno K, Minh LHN, et al. Dengue hemophagocytic syndrome: a systematic review and meta-analysis on epidemiology, clinical signs, outcomes, and risk factors. Rev Med Virol. 2018 Nov;28(6):e2005.[Abstract]
40. Mohandas N, Gallagher PG. Red cell membrane: past, present, and future. Blood. 2008 Nov 15;112(10):3939-48.[Abstract][Full Text]
41. Schechter AN. Hemoglobin research and the origins of molecular medicine. Blood. 2008 Nov 15;112(10):3927-38.[Abstract][Full Text]
42. Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med. 2006 May 11;354(19):2034-45.[Abstract]
43. Shmueli H, Flint N, Pollick C, et al. Spleen size and appearance by transesophageal echocardiography in patients with suspected infective endocarditis. JACC Cardiovasc Imaging. 2020 Apr;13(4):1082-3.[Abstract][Full Text]
44. Yung L, Linch D. Hodgkin's lymphoma. Lancet. 2003 Mar 15;361(9361):943-51.[Abstract]
45. Tenner S, Baillie J, DeWitt J, et al. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013 Jul 30;108(9):1400-15.[Abstract][Full Text]
46. American Society for Clinical Pathology. Choosing wisely: testing for amylase. Sep 2016 [internet publication].[Full Text]
47. Cessford T, Meneilly GS, Arishenkoff S, et al. Comparing physical examination with sonographic versions of the same examination techniques for splenomegaly. J Ultrasound Med. 2018 Jul;37(7):1621-9.[Abstract]
48. Sigrist RMS, Liau J, Kaffas AE, et al. Ultrasound elastography: review of techniques and clinical applications. Theranostics. 2017;7(5):1303-29.[Abstract][Full Text]
49. Gary SE, Ryan E, Steward AM, et al. Recent advances in the diagnosis and management of Gaucher disease. Expert Rev Endocrinol Metab. 2018 Mar;13(2):107-18.[Abstract][Full Text]
50. Batur A, Alagoz S, Durmaz F, et al. Measurement of spleen stiffness by shear-wave elastography for prediction of splenomegaly etiology. Ultrasound Q. 2019 Jun;35(2):153-6.[Abstract]
51. İmamoğlu H, Zararsız G, Özdemir M, et al. The orthogonal measurements approach in estimating spleen size on CT images. Diagn Interv Radiol. 2020 Jan;26(1):5-10.[Abstract][Full Text]
52. Indiran V, Vinod Singh N, Ramachandra Prasad T, et al. Does coronal oblique length of spleen on CT reflect splenic index? Abdom Radiol (NY). 2017 May;42(5):1444-8.[Abstract]
53. Kucybała I, Ciuk S, Tęczar J. Spleen enlargement assessment using computed tomography: which coefficient correlates the strongest with the real volume of the spleen? Abdom Radiol (NY). 2018 Sep;43(9):2455-61.[Abstract][Full Text]
54. Gunes SO, Akturk Y. Determination of splenomegaly by coronal oblique length on CT. Jpn J Radiol. 2018 Feb;36(2):142-50.[Abstract]
55. Huo Y, Liu J, Xu Z, et al. Robust multicontrast MRI spleen segmentation for splenomegaly using multi-atlas segmentation. IEEE Trans Biomed Eng. 2018 Feb;65(2):336-43.[Abstract][Full Text]
56. Huo Y, Xu Z, Bao S, et al. Splenomegaly segmentation on multi-modal MRI using deep convolutional networks. IEEE Trans Med Imaging. 2019 May;38(5):1185-96.[Abstract][Full Text]
57. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2019 Jan;94(1):133-43.[Abstract][Full Text]
58. Cetin G, Ozkan T, Turgut S, et al. Evaluation of clinical and laboratory findings with JAK2 V617F mutation as an independent variable in essential thrombocytosis. Mol Biol Rep. 2014 Oct;41(10):6737-42.[Abstract]
59. Karaköse S, Oruç N, Zengin M, et al. Diagnostic value of the JAK2 V617F mutation for latent chronic myeloproliferative disorders in patients with Budd-Chiari syndrome and/or portal vein thrombosis. Turk J Gastroenterol. 2015 Jan;26(1):42-8.[Abstract][Full Text]
60. Thurmes PJ, Steensma DP. Elevated serum erythropoietin levels in patients with Budd-Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis. Eur J Haematol. 2006 Jul;77(1):57-60.[Abstract]
61. Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Nov 6;69(1):394-419.[Abstract][Full Text]
62. Chapman MH, Thorburn D, Hirschfield GM, et al. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut. 2019 Aug;68(8):1356-78.[Abstract][Full Text]
63. Kowdley KV, Brown KE, Ahn J, et al. ACG clinical guideline: hereditary hemochromatosis. Am J Gastroenterol. 2019 Aug;114(8):1202-18.[Abstract][Full Text]
64. Mehta A, Kuter DJ, Salek SS, et al. Presenting signs and patient co-variables in Gaucher disease: outcome of the Gaucher Earlier Diagnosis Consensus (GED-C) Delphi initiative. Intern Med J. 2019 May;49(5):578-91.[Abstract][Full Text]
65. Deshwal R. Clinical and laboratory profile of hospitalized malarial patients: an Agra-based study. J Assoc Physicians India. 2016 Aug;64(8):44-7.[Abstract][Full Text]
66. Guo C, Zhou Z, Wen Z, et al. Global epidemiology of dengue outbreaks in 1990-2015: a systematic review and meta-analysis. Front Cell Infect Microbiol. 2017;7:317.[Abstract][Full Text]
67. World Health Organization, Special Programme for Research and Training in Tropical Diseases (TDR). Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. Oct 2009 [internet publication].[Full Text]
68. Ferreira BDC, Correia D. Ultrasound assessment of hepatobiliary and splenic changes in patients with dengue and warning signs during the acute and recovery phases. J Ultrasound Med. 2019 Aug;38(8):2015-24.[Abstract]