Illustrative Case Series

Incidental Splenic Mass

By Bindu Kanapuru, MD, Institute for Advanced Studies in Aging and Geriatric Medicine, Falls Church, VA. Dr. Kanapuru reports no financial relationships relevant to this field of study.

A 61-year-old female was evaluated for intermittent upper abdominal discomfort. A non-contrast enhanced CT revealed 5x3x4 cm lesion in the spleen that appeared to be cystic. Another lesion that appeared to be contiguous with the previous lesion but was solid and hypo-echoic was reported, and a recommendation was made to rule out lymphoma or other primary tumors of the spleen. The imaging studies were negative for abdominal or thoracic lymphadenopathy. No other lesions were identified. The patient was referred for further evaluation to an oncologist. Past history included severe osteoporosis, multiple spinal surgeries, and a prior fracture of the right leg with repair. Her medications included iron, vitamin B12 supplementation, and pain medications. She denied any smoking history, alcohol use, or intravenous drug abuse. There was no personal history of prior cancer. How should this patient be evaluated to rule out a neoplastic process?

Case Discussion

Although tumors of the spleen are uncommon, they occasionally are discovered during evaluation of other medical problems or in asymptomatic patients. The splenic tissue consisting of red pulp and white pulp can give rise to primary vascular tumors as well as lymphoid tumors. In addition, although uncommon, the spleen also can be involved with metastasis from other primary cancers. Evaluation of an abnormal splenic mass presents a significant diagnostic challenge, as specific diagnostic features on imaging that would distinguish malignant from benign processes are most frequently lacking.

Hemangiomas are the most common benign vascular neoplasms with prevalence ranging from less than 0.5% to 15% in the general population.1 These typically are found incidentally and only occasionally involve the spleen, but can present as a large non-tender palpable mass in the left upper quadrant. Laboratory evaluation is usually normal but anemia, thrombocytopenia, and coagulopathy may be seen in Kasabach-Meritt syndrome, typically in very young patients. On CT they appear as hypo- or iso-attenuating solid or complex cystic masses that enhance homogenously after intravenous contrast administration.

Hamartomas are extremely rare tumors that can present as an asymptomatic splenic mass. Splenic hamartomas can be associated with tuberous sclerosis and Wiskott-Aldrich syndrome. Ultrasound is the most sensitive imaging test for hamartoma on which they appear as a homogeneous mass. On CT they appear as solid hypo-dense lesions with prolonged enhancement after contrast administration.2

Littoral cell angioma is another primary vascular tumor of the spleen of uncertain malignant potential. Such angiomas occasionally are encountered during the workup of cytopenias thought to occur as a consequence of "hypersplenism." Clinical features may mimic a malignant lymphomatous process with the presence of fever, fatigue, and weakness. In addition, confirmation of littoral cell angioma by splenectomy does not rule out absence of primary malignant disease, as association between littoral cell angiomas and gastrointestinal and renal malignancies have been described. They are more likely to present with splenomegaly with multiple hypo-attenuating lesions on CT imaging.3

Peliosis is yet another consideration in evaluating splenic mass, although it almost always is associated with peliosis hepatitis and may occur in patients with aplastic anemia and cancer. This lesion can occur on the splenic surface and result in splenic hemorrhage. On CT, peliosis appears as multiple well-defined hypo-attenuating lesions with significant contrast enhancement.

Malignant vascular tumors of the spleen include hemangiopericytomas and angiosarcomas. Although the spleen is not the most common location for hemangiopericytomas, when they originate in the spleen they can be asymptomatic or associated with splenomegaly. Abdominal hemangiopericytomas are aggressive tumors with high rates of local recurrence after wide excision. Lung and bone are the usual sites of distant metastasis. Hemangiopericytoma appears as a large splenic mass with smaller lesions distributed throughout the parenchyma. Angiosarcoma is the most common primary non-lymphoid malignant lesion of the spleen; however, its annual incidence is only about 0.25 cases per million persons. It too is a very aggressive tumor that spreads to liver, lung, bone, and brain. Symptoms range from constitutional (weight loss and malaise) to those associated with splenic expansion (pain) or rupture. Ultrasound reveals splenomegaly with masses containing both solid and cystic components. CT also shows splenomegaly with solitary or multiple nodular masses with irregular margins with heterogeneous low attenuation and occasional peripheral enhancement.4 For each of these conditions, splenectomy is both diagnostic and therapeutic.

Non-Hodgkin's lymphoma is the most common lymphoid malignancy involving the spleen. For non-Hodgkin's lymphoma patients with splenic involvement, splenomegaly is frequently present, although isolated splenic masses without splenic enlargement may also be seen in up to 30% of cases.5 In 50%-80% of cases, the spleen is involved as part of a disseminated process and the diagnosis is made by lymph node biopsy, not splenectomy. Splenic lymphomas involving only the spleen or splenic hilar nodes are very rare, occurring in only 0.6% of lymphoma cases. Bone marrow involvement has been reported in 97.3% of low-grade splenic lymphomas and in 85% of high-grade lymphomas.6 Another study of low-grade lymphomas of the spleen identified bone marrow involvement at diagnosis in 102 (99.0%) and leukemic conversion (LC) in 85 (83.3%) patients, respectively.7

In a series of 122 patients who underwent diagnostic splenectomy, diffuse large B cell lymphoma was diagnosed in 29% of patients with splenic mass and in about 10% of cases with splenomegaly. A diagnosis of marginal zone lymphoma was identified in 17% of cases with splenomegaly.8 Hairy cell leukemia, T cell large granular lymphocytic leukemia, lympho-plasmocytic lymphomas, mantle cell lymphomas, and follicular lymphoma also can present with primary splenic involvement. Although Hodgkin's lymphoma commonly involves the spleen, it is uncommon to have isolated splenic involvement without supradiaphgramatic lymphadenopathy.

Clinical features of splenic lymphomas are usually indistinguishable from other splenic tumors and include left upper quadrant discomfort and fatigue.

Weight loss, fever, and night sweats are more typical for high-grade lymphomas such as diffuse large B cell lymphoma. A comprehensive history may identify specific risk factors, such as infection with hepatitis C or treatment with TNF alpha, both of which favor development of specific lymphoma subtypes.9 Physical examination may not be very helpful as palpable peripheral lymphadenopathy may be absent. Laboratory evaluation should include complete blood count LDH and beta-2 microglobulin levels, which help estimate the burden of disease. Serum protein electrophoresis may identify an M spike often seen with indolent splenic lymphomas. Whole body CT is the best imaging study to identify additional lymphomatous involvement elsewhere. On CT presentation, splenic lymphomas can range from diffuse splenic infiltration and splenomegaly to focal low attenuation lesions which rarely enhance. PET/CT is very accurate for identifying splenic involvement in diffuse large B cell lymphomas. However, low-grade lymphomas and mantle cell lymphomas may show low to intermediate SUV activity on PET, thus limiting the universal value of PET as a diagnostic tool in splenic lymphomas. MRI has no role in evaluating splenic lymphomas.

Since a high rate of peripheral blood involvement is seen in splenic lymphomas, peripheral blood smear examination and flow cytometry is the next appropriate step in evaluating splenic mass. Peripheral blood examination may reveal hairy cells, prolymphocytes, villous lymphocytes, or large and granular lymphocytes, and flow cytometry may be further helpful by identifying specific immunophenotypic features diagnostic of lymphomas. Bone marrow aspirate and biopsy can establish the diagnosis in splenic marginal zone lymphomas, mantle cell lymphomas, and hepato-splenic T cell lymphomas.9

However, despite these investigations, splenectomy ultimately may be needed to definitively rule out a lymphoma when the suspicion is high. Laparoscopic splenectomy can be performed safely even in patients with massive splenomegaly with complication rate around 10%, but with less than 1% mortality.

Fine needle aspiration or biopsy have been used successfully in evaluation of focal splenic lesions,8 but with major complications occurring in 10% of the cases and minor complications in 6%. Although in some hands adequate tissue for diagnosis is available in more than 90% of cases, the procedure is rarely used.

Splenic metastases are very uncommon, but when they do occur they usually are detected coincident with the primary tumor or shortly after. The most common primary malignancies spreading to the spleen are lung, melanoma, breast, and ovarian cancers. Isolated splenic metastasis from a primary cancer is very rare but has been reported, particularly in ovarian cancers and gastric cancers. Splenic metastases are usually asymptomatic.

However, abdominal pain and spontaneous rupture of the spleen also have been reported. On CT, splenic metastases appear as solid or cystic lesions that are hypo-dense with inhomogeneous enhancement on contrast. MRI may be more accurate in detecting splenic metastasis as the majority have evidence of necrosis and/or hemorrhage.

Current Case Discussion

The patient referenced above had evidence of anemia with Hb of 11.0 g/dL and thrombocytopenia with platelets of 90,000/cu mm. LDH level was normal and beta 2 microglobulin was elevated at 3.0 mg/L. No evidence for hemolysis was detected on further evaluation. The remainder of her labs were within normal limits. Whole body CT did not reveal any other lesions or lymphadenopathy. Peripheral blood smear examination also did not identify any atypical cells. A bone marrow biopsy also showed no evidence for lymphoma. The patient underwent splenectomy and was diagnosed with splenic follicular lymphoma. The patient is currently scheduled for chemotherapy with bendamustine-rituxan based on recent reports demonstrating superior activity of this combination in indolent lymphomas.

References

1. Abbott RM, et al. From the archives of the AFIP: Primary vascular neoplasms of the spleen: Radiologic-pathologic correlation. Radiographics 2004;24:1137-1163.

2. Rabushka LS, et al. Imaging of the spleen: CT with supplemental MR examination. Radiographics 1994;14:307-332.

3. Levy AD, et al. Littoral cell angioma of the spleen: CT features with clinicopathologic comparison. Radiology 2004;230:485-490.

4. Thompson WM, et al. Angiosarcoma of the spleen: I characteristics in 12 patients. Radiology 2005;235:106-115. Epub 2005 Mar 4.

5. Giovagnoni A, et al. Tumours of the spleen. Cancer Imaging 2005;5:73-77.

6. American Society of Clinical Oncology. Contemporary insights into dissemination of primary non-hodgkins lymphomas of the spleen. Meeting:2004 ASCO Annual meeting. Abstract no:6675. First Author: V. Musteata. Available at: http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=26&abstractID=476. Accessed Oct. 18, 2011.

7. Journal of Clinical Oncology. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement). 2006:17559.

8. Kraus MD, et al. The spleen as a diagnostic specimen. A review of 10 years' experience at two tertiary care institutions. Cancer 2001;91:2001-2009.

9. Lannitto E, Tripodo C. How I diagnose and treat splenic lymphomas. Blood 2011;17:2585-2595.