Splenosis: a review.

Abstract: Splenosis is a common benign condition that occurs after splenic rupture via trauma or surgery. Splenosis is usually found incidentally and unless symptomatic, therapy is not indicated. However, since radiographically it can mimic malignancy, most patients have an extensive workup. The diagnostic method of choice is nuclear scintigraphy, specifically, a heat-damaged red blood cell scan. Splenosis usually occurs within the abdominal and pelvic cavities, but patients have been described with intrathoracic, subcutaneous, intrahepatic and intracranial lesions.

Key Words: splenosis, thoracic splenosis, abdominal/pelvic/thoracic nodules 

Case Report

A 54-year-old Caucasian male was referred to the pulmonary clinic for multiple lung nodules found on a computed tomographic (CT) scan of the chest. He had no systemic symptoms, but complained of left-sided pleurisy that started a month before evaluation. His past medical history included shrapnel wounds sustained in Vietnam, resulting in a perforated viscus as well as splenic and diaphragmatic rupture. His physical examination was normal, and routine blood work demonstrated no significant lab abnormalities. A peripheral smear was not obtained. His chest x-ray (CXR) (Fig. 1) showed left-sided residual shrapnel and a pleural-based scar. His CT scan of the chest (Fig. 2) showed multiple left-sided pleural-based lesions, and a 2 cm mass in the left hemithorax adjacent to the heart. Given the history of splenic and diaphragmatic trauma, a diagnosis of thoracic splenosis was considered and a subsequent heat-damaged red blood cell scan was obtained (Fig. 3). The test revealed uptake by all the nodules consistent with a diagnosis of thoracic splenosis. He was given oral pain medication with resolution of his pleurisy and has had no further complications.

Splenosis Versus Accessory Spleens

Ectopic splenic tissue can be found in the body as two distinct forms: accessory spleens and splenosis. Accessory spleens are congenital and arise from the left side of the dorsal mesogastrium during the embryological period of development. (1) Splenosis, on the other hand, is an acquired condition defined as autotransplantation of viable splenic tissue throughout different anatomic compartments of the body. It occurs after traumatic or iatrogenic rupture of the spleen.

The inherent differences between an accessory spleen and splenosis are quite distinct and can help differentiate between these two conditions. Accessory spleens are usually few in number, totaling six or less. On the other hand, 100 or more individual splenic nodules are commonly found in splenosis and greater than 400 have been reported. (2,3) An accessory spleen has normal splenic histology with its blood supply uniformly arising from a branch of the splenic artery. The blood supply in splenosis however, is derived from the surrounding tissues and vessels, without any association to the splenic artery. (4) The tissue in splenosis usually reveals distorted architecture with no hilum, a poorly formed capsule and tissue of any shape or size. Furthermore, the histology of splenosis can be quite varied. Most reports describe the tissue as lacking trabecular structures, having less elastic tissue than a normal spleen, and poorly formed or deficient white pulp with normal-appearing red pulp. (5,6) Carr and Turk, (6) however, reported two cases of splenosis with histology and immunohistochemistry that was indistinguishable from that of normal splenic tissue. (5,6) The location of the splenic tissue may also help differentiate accessory spleens from splenosis. Accessory spleens are usually located near the splenopancreatic or gastrosplenic ligament. Even when they have been reported within the pancreas, kidney, scrotum and as an adnexal mass, they always conform to their embryological geographic limits. (2,3,7-9) Splenosis tissue on the other hand, can be found in any intraperitoneal or extraperitoneal location. The most common areas are the peritoneum, omentum and mesentery. (10) However, splenosis has also been reported in the pericardium, subcutaneous tissue and even in the occipital pole of the brain. (11-13) Finally, the prevalence of the two conditions also differs. Accessory spleens have been found in up to 40% of patients undergoing autopsies. (3) The incidence of splenosis in the general population remains unknown, but given its requirement for splenic injury before development, the prevalence is undoubtedly much lower. The remainder of this review will focus on the topic of splenosis with the understanding that accessory spleens are a congenital normal variant.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

Characteristics

The mechanism behind autotransplantation begins with splenic rupture, either from trauma or surgical removal. It is presumed that spillage of the damaged splenic pulp into the adjacent cavities begins the seeding process. (4) It is likely that the subsequent number of nodules in a case of splenosis is related to the severity of the splenic injury as well as the amount of pulp and tissue released into the abdominal and pelvic cavities. (2) A second mechanism is the hematogenous spread of splenic pulp, as suggested by case reports of intrahepatic, as well as intracranial splenosis. (3,12,13,15) One recent theory hypothesizes that splenic erythrocytic progenitor cells enter the liver via the portal vein, and then grow in response to tissue hypoxia. (16) Once considered a rare condition, abdominal or pelvic splenosis is now thought to occur in upwards of 65% of splenic rupture cases. (17) Thoracic splenosis occurs much less frequently, in possibly 18% of postsplenic rupture cases. The most likely explanation is the anatomic boundaries of the abdominal and thoracic cavities. (14,18) In fact, all cases of reported thoracic splenosis have had diaphragmatic rupture as well as splenic rupture. Similarly, due to the spleen's anatomic location, thoracic splenosis arises almost exclusively in the left hemithorax. Subcutaneous splenosis is quite rare, with less than 14 reported cases, and there is only one case report of intracerebral splenosis in the medical literature. (12,13,15) Not surprisingly, all cases of subcutaneous splenosis have occurred in or at the site of a surgical or traumatic scar, most frequently, gunshot wounds. (15)

[FIGURE 3 OMITTED]

The autotransplanted splenic tissue of splenosis, similar to accessory spleens, is thought to perform normal splenic function. (19) Therefore, Howell-Jolly and Heinz bodies, siderocytes and other abnormal red blood cells may not be present on a peripheral smear, despite these patients having a history of splenectomy. (20) It has also been postulated that patients are less prone to overwhelming sepsis due to the continued, though limited, immune functions of the remaining splenic tissue. (19) Further evidence of functioning splenic tissue comes from two case reports. The first is of a 25-year-old woman who developed idiopathic thrombocytopenic purpura due to splenosis, 12 years after splenectomy. An exploratory laparotomy found splenosis, and after removal of the splenic implants, her thrombocytopenia resolved. (21) The second is a case report of a patient who developed a recurrence of Felty syndrome two years after splenectomy. This patient underwent subsequent laparotomy with removal of an accessory spleen as well as 40 splenic implants on the omentum. After the procedure, his blood work showed a typical postsplenectomy erythrocyte pattern, including Howell-Jolly bodies. (22) Finally, both amyloid deposits and miliary tuberculosis have been recovered from splenosis implants, suggesting a functional reticuloendothelial system within the implants. (23)

The average interval reported between trauma and abdominal or pelvic splenosis is 10 years with a range of 5 months to 32 years. (22,24) The average reported time delay in thoracic splenosis is 21 years, with a range of 3 to 45 years. (14) Most patients with splenosis are asymptomatic. The abnormality is usually found incidentally, either by a screening test or a diagnostic procedure in the investigation of a separate problem. Radiological examinations such as CXRs, CT scans and ultrasounds as well as invasive laparotomies are all well documented ways of incidentally uncovering asymptomatic splenosis. When splenosis does cause symptoms, it is usually located in the abdominal or pelvic cavity. Pain secondary to infarction, intestinal obstruction due to the adhesive bands of the splenic implants, gastrointestinal hemorrhage, hydronephrosis secondary to a growing mass exerting pressure on the ureter, as well as an enlarging abdominal mass with associated infection have all been reported. (3,22,25-29) With thoracic splenosis, the only two reported symptoms in the literature are pleurisy and hemoptysis. (30,31)

Splenosis can occur with either single or multiple nodules--upwards of 400 in some cases. The nodules are of a reddish-blue appearance grossly, and can vary in shape (sessile to pedunculated), as well as in size (ranging from a few millimeters to 12 cm). (17,22) The size is limited mostly by blood supply, which usually restricts the nodules to less than 3 cm in diameter. (22) A review of splenosis found that almost all cases, 93%, were the result of trauma with subsequent splenectomy, and that 70% of these patients suffer the trauma during their teenage years. (2,22) A similar review of 38 cases of thoracic splenosis found that the diagnosis was more common in males than females, possibly reflecting the higher incidence of trauma in young males. (14)

In thoracic splenosis, the nodules may develop on either the parietal or visceral pleura and appear to draw their blood supply from the surrounding tissue, although bronchial and intercostal arteries have been implicated. (31) Cases of intraparenchymal splenosis have been reported, but are usually associated with parenchymal lacerations. (30,32,33)

Before making a definitive diagnosis, the finding of multiple nodules raises the concern for malignancy. Abdominal and pelvic splenosis are often mistaken for abdominal lymphoma, metastatic disease, carcinomatosis, primary renal or hepatic malignancy, adenomas, endometriosis or simple adenopathy. (2,22) Similarly, the differential diagnosis of pleural-based nodules includes primary and metastatic cancers such as lung, breast, pancreas, gastrointestinal tract, kidney, lymphoma, melanoma, mesothelioma, invasive thymoma, and neurogenic tumors, as well as benign conditions including fibrous tumors, extramedullary intrathoracic hematopoiesis, infections and asbestos-related pleural plaques. (10,14,17) The differential diagnosis of cutaneous splenosis includes differentiated cutaneous lymphoma, lymphocytoma, nodular Kaposi sarcoma, and subcutaneous vascular malformations. (12)

Splenosis nodules are benign and removal is not required in asymptomatic cases. However, due to the rarity of this condition and the concern for malignancy with the growth of the nodules over time, a tissue diagnosis is usually pursued--most often intraoperatively. (34) The low density of splenic tissue makes it difficult to visualize on standard x-rays. CT scanning reveals the number, shape and size, but not the identity of the nodules, and standard magnetic resonance imaging (MRI) is not useful in narrowing the differential diagnosis. (35) Recent case reports have shown ferumoxides-enhanced MRI as a novel technique for diagnosing splenosis. (24,36) Ferumoxides are superparamagnetic iron oxides that are removed from circulation by the reticuloendothelial system. (37) Normal splenic tissue, as well as Kupffer cells of the liver, predominantly filters these superparamagnetic iron oxides, rendering the contrast agent tissue specific. There have been only three case reports in the literature describing the use of this radiological technique for splenosis: two for abdominal or pelvic disease and one for thoracic splenosis. (22,36,38) Given the relative paucity of data and the cost of the test, it is unclear what role ferumoxides-enhanced MRI will play in the future diagnostic algorithm of splenosis.

The current diagnostic modality of choice for splenosis is noninvasive nuclear scintigraphy. The Technetium-99m sulfur colloid test of the liver and spleen was first used to diagnose splenosis due to the ability of the radio-labeled colloid to localize in the reticuloendothelial system. (39) However, scintigraphy using Technetium-99m heat-damaged erythrocytes (RBC) or Indium 111-labeled platelets is more sensitive and specific for splenic uptake, making these tests the current diagnostic tools of choice. (16,40) In a comparison between the sulfur colloid scintigraphy versus heat-damaged RBC cell scintigraphy, Gunes and colleagues (41) demonstrated that the RBC scintigraphy had a 32% greater diagnostic yield when directly compared with the sulfur colloid test. One reason for the better accuracy with RBC scintigraphy may be that the spleen takes up only about 10% of the injected sulfur colloid, while it takes up greater than 90% of damaged red blood cells. (41) RBC scintigraphy has also been shown to be more sensitive in early splenosis, cases where minimal splenic tissue is present, functional hyposplenism or poor splenic uptake, as well as when the liver and spleen overlap, causing poor visualization of splenic tissue by the sulfur colloid test. (41,42)

Once splenosis is confirmed, no further workup is necessary unless the patient is symptomatic. No cases of death secondary to splenosis have been reported, but abdominal obstruction, GI bleeding or intussusception need prompt evaluation and therapeutic intervention. Interestingly, most patients who have an exploratory laparotomy for abdominal pain have cessation of that pain after the procedure, regardless of whether the splenic nodules have been removed. (43) All reported cases of subcutaneous splenosis have been asymptomatic and found on autopsy or evaluated out of fear for malignancy. (15) With thoracic splenosis, the symptom of pleurisy usually resolves or is easily controlled with medications. Hemoptysis secondary to hypervascular nodules have been treated successfully with surgery. (31) Similar to abdominal splenosis, no long-term adverse sequelae or deaths have been reported in association with thoracic splenosis. (43)

Conclusion

Splenosis should be included in the differential diagnosis in all patients with abdominal, pelvic, thoracic or subcutaneous nodules with a history of splenic trauma or spleen removal. Some patients may not know the reason for their splenectomy, but this history is paramount and should immediately broaden a clinician's differential. Once considered, the diagnostic workup for this mostly benign condition is simple, inexpensive, noninvasive, and may prevent future stress and procedures. A judicious use of the nuclear medicine department combined with a comprehensive history will diagnose a patient with splenosis without subjecting a patient to unnecessary invasive diagnostic techniques.

References

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I haven't failed, I've found 10,000 ways that don't work
--Thomas Edison

Richard D. Fremont, MD and Todd W. Rice, MD, MSc

From the Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.

Reprint requests to Richard D. Fremont, T-1218 MCN, Nashville, TN 37232-2650. Email: [e-mail]

The authors report that they have no financial conflicts of interests, nor any commercial or proprietary interests in regards to this submission.

Accepted December 6, 2006.

RELATED ARTICLE: Key Points

* Splenosis is a benign condition that occurs after splenic rupture via trauma or surgery.

* Splenosis is usually found incidentally and unless symptomatic, therapy is not indicated.

* As splenosis can mimic malignancy, workup is generally extensive, and usually consists of nuclear scintigraphy.

* Splenosis usually occurs within the abdominal and pelvic cavities, but patients have been described with intrathoracic, subcutaneous, intrahepatic and intracranial lesions.