Disorders of the Spleen

Splenic Rupture

Splenic rupture can be classified as spontaneous or delayed. Spontaneous splenic rupture is more common in males and typically occurs in relation to infarction, thrombocytopenia, tumors, lymphoma, or leukemia. Delayed splenic rupture is defined as development of splenic hemorrhage more than 7 days after an injury and is thought to be the result of an evolving initial splenic contusion. Symptoms of acute or delayed splenic rupture include abdominal pain with referred shoulder pain, abdominal distention, and signs of bleeding or shock. Ruptured spleens, even those removed acutely, characteristically show reactive white pulp changes in addition to subcapsular hemorrhage. Emergent splenectomy is the only definitive therapy.

Splenosis

One consequence of splenic rupture is splenosis, which is dissemination of splenic tissue to a separate anatomic site. This phenomenon is also a common sequela of trauma or surgery. It occurs in up to 75% of trauma patients undergoing splenectomy and is thought to result from seeding or hematogenous spread of tissue, or both. Splenosis usually occurs in the abdominal and pelvic cavities, but intrathoracic, subcutaneous, intrahepatic, and intracranial cases have been described. The heterotopic splenic tissue generally demonstrates abnormal histology; it lacks trabecular structures and has poorly formed white pulp, although the red pulp is normal. Functionally these splenosis nodules are capable of clearing senescent erythrocytes but do not offer protection against encapsulated bacteria. Splenosis nodules are often detected on computed tomography (CT), raising concern for malignancy; however, they are benign and removal is required only in symptomatic cases.

Accessory Spleen

A relatively common congenital variation is that of an accessory spleen, which is seen in up to 20% of otherwise healthy individuals and is found in greater frequency (up to 30%) in patients with hematologic disorders. It is thought to result from inadequate fusion of primary lobules during the second or third trimester of fetal development. Most patients with an accessory spleen have only one, although multiples are not uncommon. In the majority of cases, an accessory spleen is found near the hilum or in the supporting ligaments or greater omentum. Other notable locations are (in order of frequency) the gastrocolic ligament, pancreatic tail, greater omentum, greater curvature of the stomach, the splenocolic ligament, the small and large bowel mesentery, the left broad ligament in women, and the left spermatic cord in men. Accessory spleens are histologically and functionally identical to the native spleen. As such, if a patient fails therapeutic splenectomy, the possibility of an accessory spleen should be considered.

Asplenia

Asplenia is congenital or acquired. Congenital asplenia is rare and inherited in a predominantly autosomal-dominant pattern. It may first be detected due to pneumococcal sepsis in an infant or newborn. Although it can occur in isolation, it is also associated with heterotaxy syndromes. The most common of these syndromes is the Ivemark syndrome, in which right-sided organs are duplicated and organs that are normally present on the left side are absent. Other associated conditions include Pearson syndrome, Stormorken syndrome, Smith-Fineman-Myers syndrome, ATR-X syndrome, Fanconi anemia, and autoimmune polyendocrine syndrome type 1. However, the most common cause of asplenia is secondary to trauma, infarction, or surgery. Regardless of etiology, the most important consequence of asplenia is increased susceptibility to infection by encapsulated organisms, most commonly Streptococcus pneumoniae. Neisseria meningitidis, Escherichia coli, Haemophilus influenzae, Staphylococcus species, and Streptococcus, which occur at rates ranging from 7% to 12% in asplenic patients. Interestingly, this increased susceptibility is caused by defective immunoglobulin (Ig) M and opsonin production.

Asplenia is evident in the peripheral blood smear, which demonstrates anisopoikilocytosis of red blood cells including acanthocytes, echinocytes, and target cells as well as red blood cell inclusions such as Pappenheimer and Howell-Jolly bodies.

Splenic-Gonadal Fusion

Another congenital anomaly is that of splenic-gonadal fusion, which results from fusion of the splenic anlage with the gonadal mesoderm of the left urogenital fold ( Fig. 22.2 ). Typically a disorder of young males (male-to-female ratio, 20 : 1), it often manifests as a scrotal mass identified during physical examination for cryptorchidism or during inguinal hernia repair. The condition exists in two forms. The first more common form is characterized by a continuous cord of splenic or fibrous tissue between the normal spleen and ectopic mass. The second, discontinuous type, shows no connection between the spleen and a mass. Associated cryptorchidism, micrognathia, and limb defects are commonly associated with continuous splenic-gonadal fusion but are rarely seen with the discontinuous form. Less commonly, cardiac defects, spina bifida, cleft palate, and imperforate anus can be seen. Typically, the ectopic splenic tissue is confined to the tunica vaginalis. It is well demarcated from the gonad and has a fibrous capsule and a burgundy red-to-purple cut surface. Histologically it is identical to the native spleen, although fibrosis, thrombosis, calcification, fat degeneration, or hemosiderin deposits can be observed.

Splenic Cyst

One of the most common benign tumors of the spleen is the splenic cyst. These tumors have a male predominance and typically appear in the third decade of life. They are designated as primary (true) or secondary (false). Primary cysts represent approximately 20% of all splenic cysts. They are unilocular and have a firm, fibrous, trabecular wall that is lined by mesothelial cells or squamous epithelium ( Fig. 22.3 ). Notably, the epithelial lining of primary cysts may be patchy, with denuded areas present that may simulate a secondary cyst. Primary cysts can be further subdivided into parasitic and nonparasitic types. Parasitic cysts, though uncommon, are typically attributable to Echinococcus species and are readily identified by the presence of parasite scolices in the cyst contents. Nonparasitic primary cysts appear to arise from congenital inclusions of capsular mesothelium. Interestingly, patients with primary cysts may have elevations of CA19-9 and carcinoembryonic antigen. Treatment in symptomatic cases requires a complete splenectomy because incomplete resection often leads to recurrence.

Secondary cysts represent approximately 80% of splenic cysts and are often associated with a history of abdominal trauma. These cysts are unilocular and thin walled and differ from primary cysts by the complete absence of an epithelial lining; therefore they are unlikely to recur even if only partially resected.

Follicular Hyperplasia

Germinal center formation in the white pulp is a normal finding in the childhood spleen, but its presence is abnormal in adults (see Fig. 22.1B ). Reactive follicular hyperplasia can be seen as a result of a systemic infection as in bacterial sepsis, measles, typhoid fever, and acquired immunodeficiency syndrome (AIDS). In addition, autoimmune conditions such as rheumatoid arthritis and idiopathic thrombocytopenic purpura (ITP) can lead to follicular hyperplasia. The histologic findings are those of a balanced and proportional expansion of all lymphoid compartments: follicles, mantle zone, marginal zone, and peripheral arteriolar sheaths. Disproportionate expansion of B cells in the mantle or marginal zones should be cautiously evaluated, because these can be subtle indications of lymphoma involvement.

Splenic Abscess

Splenic abscesses are rare, with a predicted frequency of less than 0.7% based on autopsy studies, and may be single or multiple. The most common etiology is hematogenous seeding of bacteria from a secondary site (e.g., heart, lung, urinary tract). Other well-known predisposing conditions are splenic trauma and hemoglobinopathies. Most abscesses are well circumscribed with a thick nonepithelialized fibrous wall and central accumulation of necrotic tissue associated with acute inflammatory cells. Preserved splenic tissue surrounding the abscess may show white pulp hyperplasia. All abscesses should be cultured for bacterial and fungal organisms; however, most cases are associated with gram-negative bacilli, Staphylococcus aureus, or Streptococcus species, although Salmonella species is commonly seen in patients with sickle cell disease. Fungal infection, though rare, can be seen. Candida, Aspergillus, and Cryptococcus species are the most common culprits.

Infectious Mononucleosis in the Spleen

Nearly half of all patients with infectious mononucleosis demonstrate splenomegaly. Although most patients show no significant complications, a well-known adverse outcome from Epstein-Barr virus (EBV) infection of the spleen is splenic rupture secondary to trauma; however, in most cases of rupture the severity is minor. The morphologic findings of infectious mononucleosis are varied, but the spleen can enlarge because of expansion of the red pulp and white pulp with a spectrum of immunoblasts, reactive lymphocytes, and plasma cells. In dramatic cases, Reed-Sternberg–like cells may be seen. In such cases, evaluation of these cells with immunohistochemical stains for CD30 and CD15 must be made with caution, because CD30 will be positive in the reactive immunoblasts. These cells should generally not express CD15. In addition, the histologic picture can mimic that of other non-Hodgkin lymphomas. In these cases, careful evaluation of the splenic architecture should provide necessary information, because lymphomas will unequally expand the spleen, unlike infectious mononucleosis, in which the underlying balance of white and red pulp elements will be retained.

Granulomas

Infection with mycobacteria, fungus, Brucella species, or EBV can result in extensive necrotizing granulomas that typically involve the white pulp and are generally well circumscribed. However, granulomas can also be seen as malignancies such as hairy cell leukemia and both Hodgkin and non-Hodgkin lymphomas. In addition, sarcoidosis, uremia, and selective IgA deficiency can result in splenic granulomas. Finally, lipogranulomas—collections of vacuolated histocytes surrounded by plasma cells and lymphocytes—are a relatively common benign finding in North America but not so in other parts of the world. Such geographic stratification together with other correlative data have led to the hypothesis that lipogranulomas are caused by differences in dietary intake or packaging of foods, ultimately resulting in absorption of mineral oils through the intestine and distribution throughout the body and to the spleen.

Gaucher Disease

The most common of the lysosomal storage diseases is Gaucher disease, which is an autosomal recessively inherited deficiency of glucocerebrosidase (β-glucosidase). The spleen is typically diffusely enlarged, and the cut surface is pale and filled with large collections of Gaucher cells, which are histiocytes with eccentric nuclei, and abundant tissue paper–like blue-gray foamy cytoplasm ( Fig. 22.4A ). These cells are best appreciated on smear or touch preparations. The major differential diagnosis is that of other lysosomal storage diseases and, in particular, Niemann-Pick disease; however, one should also consider hematologic malignancies, many of which demonstrate Gaucher-like cells. Prognosis is variable and depends on the subtype of Gaucher disease. Patients can undergo recombinant enzyme replacement therapy to prevent complications.

Niemann-Pick Disease

Niemann-Pick disease is rare, occurring in an estimated 1/120,000 live births; it is inherited in an autosomal-recessive pattern. It results from a deficiency of either acid sphingomyelinase (types A and B) or Niemann-Pick C proteins (types C and D). Although Niemann-Pick disease can be typed according to enzyme deficiency, the disease is also separated into five categories based on clinical features (type IA, IS, IC, IIS, and IIC). In the case of types IA and IS, the spleen is characteristically massively enlarged, often 10 times normal size. Cut cross sections demonstrate homogeneously pale tissue. Microscopic examination reveals diffuse expansion of the red pulp by sphingomyelin-laden foamy macrophages with characteristic small, uniform, mulberry-like cytoplasmic globules.

Other Metabolic Diseases Involving the Spleen

The mucopolysaccharidoses (MPS) are progressive diseases resulting from the inability to effectively process glycosaminoglycan. These are inherited autosomal recessively with the exception of MPS 2, or Hunter syndrome, which is X-linked recessive. Hepatosplenomegaly is a common presentation. Microscopic examination of the spleen will demonstrate plump vacuolated histiocytes. A diagnosis can generally be made by urinanalysis, which reveals increased concentration of glycosaminoglycan fragments. Most patients can be screened initially with an enzyme assay and by sequencing known mutations. Tangier disease, which is caused by defective cholesterol transport, presents in childhood with hepatosplenomegaly and premature coronary atherosclerosis. Tissues demonstrate accumulation of foamy cholesterol-laden macrophages, particularly in the spleen. In Tay-Sachs disease, hexosaminidase A deficiency, there is accumulation of GM2 ganglioside in the heart, liver, and spleen leading to plump vacuolated histiocytes. Involvement of the central nervous system with vacuolated neurons is also predominant. In addition, nondescript foamy histiocytes are seen in many other metabolic diseases, including Fabry disease, Wolman disease, and von Gierke disease. Finally, sea blue histiocytes may be found nonspecifically in many lysosomal storage disorders and in Hermansky-Pudlak syndrome, chronic myeloid leukemia, red blood cell disorders, and autoimmune disorders. These histiocytes are associated with massively increased cell destruction, and in these cases the macrophage cytoplasm is filled with insoluble lipid pigment, called ceroid (see Fig. 22.4B ). Compared with Gaucher cells, these cells are stained more intensely blue with Wright-Giemsa, and the inclusions are globular rather than fibrillary.

Idiopathic Thrombocytopenic Purpura

Therapeutic splenectomy is occasionally performed on patients refractory to medical therapy in order to raise platelet counts. The spleen in ITP is generally unremarkable in gross appearance. Characteristically the white pulp demonstrates attenuated mantle zones with hyperplastic marginal zones containing increased immunoblasts and plasma cells. In cases of ITP, the presence of splenic congestion or white pulp expansion should raise suspicion for infarction or lymphoma, respectively.

Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare adult disorder with an incidence of approximately 4 per 100,000 (see Chapter 2 ). Treatment involves fresh frozen plasma, and splenectomy is uncommonly performed for refractory or relapsing patients. Grossly, the spleens of patients with TTP are not typically splenomegalic (mean weight, 214 g). The histologic features are somewhat varied, but common characteristics are subendothelial deposits, hemophagocytosis, arteriolar thrombi, B-cell hyperplasia, and periarteriolar concentric fibrosis. Hemosiderosis also occurs and can be highlighted with a Prussian blue stain. Less typical findings include extramedullary hematopoiesis, endothelial cell proliferation, infarcts, and blood lakes.

Congestive Splenomegaly

Portal hypertension ultimately results in congestive splenomegaly. Most cases are the result of splenic, hepatic, or portal vein thrombosis, congestive heart failure, or cirrhosis. Rarely, cases of portal hypertension-associated splenomegaly have no discernible cause and are termed idiopathic portal hypertension . Grossly, the spleen appears large, firm, and dark. On histologic analysis, the white pulp is decreased and there is marked sinusoidal and venous dilatation with numerous hemosiderin-laden macrophages and red pulp fibrosis. Focal hemorrhage is often seen, sometimes with development of sclerotic nodules. Resolution of splenomegaly is achieved by treating the underlying condition.