Hematogenous neoplasms
See also Myeloproliferative disorders)
Bone marrow disorders with dysplastic changes in at least one myeloid cell line; variable myeloblasts in bone marrow and peripheral blood; due to ineffective bone marrow hematopoiesis with bone marrow hypercellularity but diminished peripheral counts
Usually no splenomegaly
Micro: variable erythrophagocytosis, red pulp plasmacytosis, extramedullary hematopoiesis, monocyte clusters
References: AJSP 1998;22:1255
Also called agnogenic (idiopathic) myeloid metaplasia (see also Myeloproliferative disorders)
Treatment: splenectomy (only produces modest results)
Gross: massively enlarged spleen, averaging 2 kg; diffusely dark red and moderately firm with multiple areas of hemorrhage
Micro: extramedullary hematopoiesis in red pulp; megakaryocytes may have atypical features and resemble Reed-Sternberg cells; also congestion, hemosiderosis, reduction in lymphoid follicles
Positive stains: granulocytes - Leder chloroacetate esterase; megakaryocytes - PAS+ cytoplasm, factor VIII related antigen
Negative stains: megakaryocytes - CD15, CD30
DD: myelolipoma (also has extramedullary hematopoiesis)
Micro: polymorphous tumor cells, often with clear cytoplasm; tumor often confined to periarteriolar lymphoid sheath and marginal zone; epithelioid histiocytic reaction
Positive stains: CD43 (T cells), lysozyme (reactive histiocytes)
Primary or secondary tumors are rare in spleen
Primary tumors may cause massive splenomegaly and rupture
Micro: mature plasma cells, plasmablasts; may be binucleated or multinucleated
Positive stains: cytoplasmic monotypic immunoglobulin, CD79a, VS38c
Negative stains: CD20
DD: diffuse large cell lymphoma (immunoblastic type)
Similar features as SLL/CLL, although 20% are T cell phenotype
Gross: massive splenomegaly; may have miliary pattern of lymphoma
Micro: larger nuclei than SLL/CLL with dispersed heterochromatin, often indented nuclei, with distinct nucleoli; also paraimmunoblast-type cells
Positive stains: CD20, surface immunoglobulin
Negative stains: CD5, CD23
DD: prolymphocytic transformation of SLL/CLL
Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL)
Many cases of idiopathic nontropical splenomegaly actually represent lymphoma
Usually associated with Stage IV disease
May transform to diffuse large B cell lymphoma (Richter syndrome)
Treatment: splenectomy, chemotherapy
Gross: millimeter sized asymmetric nodules throughout spleen (miliary pattern)
Micro: primarily white pulp involvement; prominent enlargement and coalescence of follicles, marked expansion of mantle zone, absent germinal centers, clusters of small round lymphoid cells protruding beneath endothelium of trabecular veins; extensive granulomas may mask underlying lymphoma; findings may be subtle in small spleens or spleens removed incidentally; may have prolymphocytes and paraimmunoblasts in white pulp, but without atypia
Positive stains: CD5, CD20, CD23
Negative stains: CD10, DBA.44, cyclin D1
DD: diffuse large B cell lymphoma, follicular center cell lymphoma
Vascular tumors
Most common malignant nonlymphoid tumor of spleen, but rare overall
Term also encompasses lymphangiosarcomas
Causes spontaneous splenic rupture in 13-33% of cases
May develop years after insertion of foreign body, such as a gauze sponge
Mean age 59 years, range 29-85 years
Tumors not associated with thorium dioxide, vinyl chloride or arsenic often involve liver and spleen simultaneously (Archives 1979;103:122)
Associated with microangiopathic anemia, thrombocytopenia, consumptive coagulopathy
Aggressive (median survival 6 months), almost uniformly fatal with widespread metastases to liver, bone or bone marrow; occasionally lymph nodes or brain
Case reports: 28 year old woman with Kaposi-like variant (Archives 2002;126:191), development after chemotherapy for follicular lymphoma (Hum Path 1986;17:528)
Gross: well defined hemorrhagic nodule or diffuse involvement of spleen
Gross images: hemorrhagic cut surface with focal necrosis
Micro: solid, papillary or freely anastomosing vascular channels (variable even within the same case), lined by atypical, hyperchromatic cells with intracytoplasmic hyaline globules; cells may be epithelioid; frequent hemorrhage, necrosis, hemosiderin, extramedullary hematopoiesis
Kaposi-like variant: Kaposi sarcoma-like spindle cell proliferation with slit formation and markedly dilated, spongelike vascular channels filled with red blood cells
Micro images: closely packed vascular channels lined by atypical endothelial cells
Micro images: Kaposi-like variant - (1) a: splenomegaly by CT scan; b: cut surface shows diffuse swelling; c: spindle cells in fascicular pattern with slitlike channels; d: marked dilated vascular spaces filled with red blood cells; (2) a: Factor VIII+; b: CD34+; c: negative for smooth muscle actin
Additional micro images: (1) replacement of red pulp with sparing of white pulp; (2) A: slitlike spaces; B: anastomosing vascular channels have honeycomb appearance; (3) A: capillary vascular channels; B: fascicles of spindle cells resembling fibrosarcoma; (4) papillary structures with hyaline cores lined by malignant cells project into luminal spaces; focal amyloid is present; (5) epithelioid tumor; (6) A: hemophagocytosis and phagocytosis of hyaline globules; B: extramedullary hematopoiesis; (7) positive for vascular endothelial growth factor receptor 3
Positive stains: endothelial markers (CD31, CD34, factor VIII related antigen, vascular endothelial growth factor receptor 3 - use of panel is recommended) and histiocytic markers (CD68, lysozyme). variable S100
Negative stains: keratin (may be focally positive)
References: AJSP 1993;17:959; Mod Path 2000;13:978
Vascular proliferative disease of skin, lymph nodes, liver and rarely spleen, caused by Bartonella henselae in immunocompromised or AIDS patients
Micro: proliferation of histiocytoid endothelial cells forming vascular channels, associated with granular bacteria; variable peliosis
Positive stains: Warthin-Starry (highlights bacteria)
References: AJSP 1992;16:650
Also called splenoma or splenadenoma
Rare, nodular lesion of spleen of variable size, derived from splenic sinus-lining cells
May be associated with thrombocytopenia and hypersplenism, but usually an incidental finding
Case reports: 45 year old white woman with ovarian splenoma (Archives 2001;125:1483)
Micro: disorganized red pulp elements only; variable extramedullary hematopoiesis; no angiomatoid nodular pattern, no follicles, no dendritic follicular cells, only scanty fibrous trabeculae
Positive stains: factor VIII, CD31, CD8, type IV collagen
Negative stains: CD21, CD68
DD: hemangioma (CD8 negative)
Rare and controversial entity in spleen
Case reports: 3 year old boy with epithelioid and spindle cell hemangioendothelioma (AJSP 1992;16:785), 9 year old girl with epithelioid hemangioendothelioma and hyposplenism (Archives 1995;119:755), patient with chronic anemia (Archives 1992;116:1079), case report with ultrastructural study (Archives 1981;105:300)
Micro: more cellular than hemangioma, less atypical than angiosarcoma; epithelioid or spindled; ill defined vascular spaces lined by cells with mild or moderate atypia; low mitotic index
Most common primary tumor of spleen
Usually less than 2 cm, incidental
Rarely is large, multiple, or involves entire spleen (angiomatosis)
May be associated with hemangiomas at other sites
May be associated with anemia, thrombocytopenia, Kasabach-Merritt syndrome (thrombocytopenia caused by platelet sequestration and destruction in large cavernous hemangiomas, usually infants, rarely adults), splenic rupture
Micro: composed of single type of blood vessel, usually cavernous
Positive stains: factor VIII, CD31, CD43, CD68 (diffuse hemangiomas)
Negative stains: CD8, CD21
DD: hamartoma (CD8+)
Very rare
Mean age 49 years but wide age range; no gender preference
Express endothelial and histiocyte associated antigens, similar to littoral cells lining venous sinuses of normal spleen
50% present with splenomegaly, hypersplenism associated thrombocytopenia or anemia
Almost always benign behavior, but associated with Crohn’s disease and adenocarcinoma of colon and pancreas
Case reports: 38 year old man with adult polycystic kidney disease and littoral cell angiomas (Archives 2001;125:1505), 78 year old woman with bacteremia (Archives 2004;128:1183)
Gross: minute to large distinct nodules replacing entire spleen
Micro: anastomosing monotonous vascular channels resembling splenic sinuses, but lined by tall endothelial cells with variable hemophagocytosis; channels have irregular lumina, often papillary projections and cystic spaces; endothelial cells frequently detach into vascular spaces; no sclerosis, no atypia
Micro images: (1) figure A: CT scan shows cyst-like splenic lesions; B: multiple round, soft, fleshy, partially hemorrhagic nodules; C: anastomosing blood vessels of varying diameter, lined by plump endothelial cells; D: cells with intracytoplasmic eosinophilic globules, consistent with hemophagocytosis; (2) figure 1: CT shows heterogeneous spleen with multiple hypoattenuated lesions; 2: large blood-filled cystic spaces; 3: cystic spaces lined by pseudopapillary formations and fibrovascular cores; 4: lining cells CD21+
Positive stains: Factor VIII, CD31, CD68, lysozyme; variable S100 and CD21 (lining cells)
Negative stains: CD8, CD34 (usually)
DD: angiosarcoma
References: AJSP 2000;24:306 (small tumor), AJSP 1997;21:827 (splenic vascular tumors), AJSP 1991;15:1023 (original paper)
Usually subcapsular
May involve entire organ
Usually children, often with lymphangiomas elsewhere (AJSP 1993;17:329)
Micro: subcapsular, multicystic; lumina contain proteinaceous material, not red blood cells; endothelium form small papillary projections
Sclerosing angiomatoid nodular transformation
Also called multinodular hemangioma
2/3 women, mean age 48 years, range 22-74 years
Presents as asymptomatic splenic mass, abdominal pain or splenomegaly
May represent altered red pulp tissue entrapped by stromal proliferative process
Treatment: splenectomy appears to be curative
Gross: solitary lesion, 3-17 cm, sharply demarcated from remaining spleen; composed of coalescing red-brown nodules in dense fibrous stroma
Micro: micronodular appearance of slit-like, round or irregular shaped vascular spaces lined by plump endothelial cells with interspersed ovoid or spindle cells; smaller nodules surrounded by concentric collagen fibers; also numerous red blood cells; stroma contains myxoid to dense fibrous tissue with scattered myofibroblasts, inflammatory cells; no/minimal atypia, no/rare mitotic figures, no necrosis
Positive stains: 3 types of vessels - CD34+/CD31+/CD8- capillaries; CD34-/CD31+/CD8+ sinusoids; CD34-/CD31+/CD8- small veins
EM: small vascular spaces lined by endothelial cells with pinocytotic vesicles but no Weibel-Palade bodies
DD: nodular transformation secondary to desmoplasia from metastatic carcinoma, sarcoidosis
References: AJSP 2004;28:1268
Other tumors
Case report of myelolipoma arising within or adjacent to spleen in sickle cell disease patient (Archives 1995;119:561)
Inflammatory myofibroblastic tumor
Also called inflammatory pseudotumor
Extremely rare in children (< 10 cases reported); <50 cases reported in adults
More common in women, associated with fever of unknown origin, splenomegaly or an incidental finding
Treatment: splenectomy is curative
Case reports: 6 year old girl (Archives 2003;127:e127), 47 year old black woman (Archives 2001;125:1607)
Gross: variable size, up to 11 cm; usually solitary but may be multinodular; variegated color due to hemorrhage and necrosis
Micro: involves splenic red pulp; patterns are spindled, sclerotic, xanthogranulomatous or plasma cell granuloma; variable lymphocytes (T cells), plasma cells, eosinophils, histiocytes, myofibroblast-like cells (may be follicular dendritic cells); often central coagulative necrosis and neutrophils, cholesterol formation, hemorrhage
Micro images: (1) figure 1: multinodular tumor with extension (arrow); 2a: mixed inflammatory infiltrates separated by fibrous bands; 2b: smooth muscle actin+ in fibrous areas and vascular smooth muscle; 2c: lymphocytes, plasma cells, neutrophils, histiocytes, immunoblasts; 2d: CD20+ small lymphocytes and immunoblasts (arrow); (2) figure 1: CT scan shows hypodense splenic mass; 2: spleen with well-circumscribed, centrally-necrotic, tan, fleshy mass; 3/4: spindle cells with angulated nuclei, vesicular chromatin, single prominent nucleoli, mixed with plasma cells and lymphocytes in variably collagenous stroma
Positive stains: CD68, smooth muscle actin, often EBV
Negative stains: ALK, CD21, CD35
DD: follicular dendritic cell tumor (CD21+, CD35+, smooth muscle actin negative), mycobacterial infection in immunocompromised patients (spindle cells form nodules in red pulp, spindle cells are CD68+, contain acid-fast bacilli in cytoplasm)
References: AJSP 1984;8:375, Archives 2001;125:379, Hum Path 2001;32:1382 (claims differs from inflammatory pseudotumor because of variance in ALK staining)
Malignant fibrous histiocytoma
Case report in 41 year old man with adjacent calcified intrasplenic cyst (AJSP 1990;14:1061)
Uncommon during life, more common at autopsy
Usually carcinomas (lung, stomach, breast, pancreas, liver, colon) or melanoma
Usually macroscopic
Breast carcinoma may present as immune thrombocytopenic purpura
Rarely resembles follicular lymphoma grossly with multiple nodules
Note: metastases can coexist with primary splenic tumors
Micro: red pulp may show nodular transformation similar to splenic angiomatoid nodular transformation
References: Archives 2000;124:526 (Chinese population)
Case report of 69 year old man with splenomegaly and low grade tumor (AJSP 1992;16:903)
Resembles ovarian tumor
Elevated levels of CEA and CA19-9 returned to normal after excision
May arise from invaginated capsular mesothelium of spleen or heterotopic pancreatic or intestinal tissue within the spleen