Symptomatic Splenic Hamartoma: Case Report and Literature Review

ABSTRACT. An 11-year-old girl with low-grade fever, In 1953, Videbaek6 first reported the association of night sweats, thrombocytopenia, and an 8-year history of splenic hamartoma with hematologic disorders in a progressive splenomegaly underwent an elective sple- 30-year-old woman who had onset of symptoms in nectomy. Pathologic diagnosis was multiple splenic childhood. Thirty such symptomatic cases have been hamartoma. The patient’s symptoms resolved after the reported since then. Symptoms reported most fre- splenectomy. Since first described by Rokitansky in quently include pancytopenia, anemia, and throm- 1861, ϳ140 cases of splenic hamartoma have been de- scribed in the literature. Most of the splenic hamartomas bocytopenia. Less commonly, fever, malaise, and were discovered incidentally. A minority of these lesions weight loss have been reported. Nine cases of symp- were associated with hematologic symptoms such as pan- tomatic splenic hamartoma have been described in cytopenia, anemia, and thrombocytopenia. Only 20 of the pediatric patients. The symptoms observed in the reported cases of splenic hamartoma occurred in pediat- pediatric patients are similar to those in the adult ric patients. However, compared with the adult patients, patient population. In addition, growth retardation, nearly half of these cases in pediatric patients was asso- night sweats, and recurrent infections have been re- ciated with symptoms. Splenectomy and partial splenec- ported in the pediatric patient population.7 Here, we tomy have relieved these symptoms. With advances in report an example of symptomatic splenic hamar- imaging, splenic hamartomas are being discovered with toma in a pediatric patient who had an 8-year span of increasing frequency. A multimodal radiologic work-up has enabled some cases of splenic hamartoma to be di- clinical course from the time of initial presentation to agnosed preoperatively. Inclusion of this benign entity the time of diagnosis. in the differential diagnoses of symptomatic splenomeg- aly in a pediatric patient is important in the preoperative CASE REPORT management and counseling of the patient and family. In patients who have discrete lesions, consideration of this The patient was an 11-year-old girl with an 8-year history of progressive splenomegaly who was admitted for elective splenec- entity preoperatively may avoid total splenectomy. tomy. She was first seen in 1988 at 3 years of age for splenomegaly. Pediatrics 1998;101(5). URL: http://www.pediatrics.org/ Complete blood count findings were normal. She then developed cgi/content/full/101/5/e10; splenic hamartoma, pancytope- severe thrombocytopenia. Work-up revealed both direct and in- nia, hypersplenism, splenomegaly, hemangiomas. direct platelet antibodies. Antinuclear antibody (ANA) was Ͻ1:20. A bone marrow aspirate showed abundant marrow megakaryo- cytes. A liver spleen scan demonstrated splenomegaly, without a ABBREVIATIONS. ANA, antinuclear antibody; CT, computed to- shift in radionuclide uptake. Computed tomography (CT) images mography; EBV, Epstein–Barr virus; MRI, magnetic resonance showed splenomegaly. Immune thrombocytopenia subsequently imaging. was diagnosed. The patient responded to intravenous gamma- globulin therapy with a rise in platelet count from 11 000/mm3 to 152 000/mm3 in 3 days. Biopsies of a subcutaneous buttock mass okitansky, according to Friedreich, first de- and a left axillary lymph node revealed capillary hemangioma and scribed splenic hamartomas1 Ͼ100 years ago reactive hyperplasia, respectively. During the next several years, in 1861. Since then, ϳ140 cases of true hamar- the spleen continued to enlarge. There were intervening episodes R of urinary tract infection at 4 years of age, Epstein–Barr virus tomas have been reported or mentioned in the liter- (EBV) infection (documented by EBV IgG titer of 640, EBV-EA titer ature. of 320, and EBNA antibody titer of 40), and unclassified glomer- Synonyms have included splenomas, spleen ulonephritis at 7 years of age. Sonograms and repeat CT images within a spleen,2 hemangiomas, posttraumatic scars,3 showed splenomegaly and no focal lesions. fibrotic nodules,4 and hyperplastic nodules. They are When seen in March 1996 at 11 years of age, the patient had symptoms of periodic low-grade fever and night sweats. Physical usually asymptomatic, particularly in the adult pop- examination showed both weight and height to be less than the ulation, and are discovered either incidentally dur- fifth percentile for age. The spleen was then 11 cm below the left ing work-up of other problems or during postmor- costal margin (Fig 1). White blood count was 3800/mm3, with a tem examination. It appears that Von Falkowski normal differential. The hemoglobin was 7.8 g/dL, and the he- matocrit was 22.8%. The red cell indices were as follows: mean reported the first case of splenic hamartoma in a corpuscular volume 70.2 fL, mean corpuscular hemoglobin 24.1 5 pediatric patient in 1914. Approximately 20 of the pg, and mean corpuscular hemoglobin concentration 34.3 dL. The reported cases of splenic hamartoma have been in platelets count was 90 000/mm3. The reticulocyte count was 6%. pediatric patients (Ͻ16 years of age). An association The erythrocyte sedimentation rate was elevated at 54 mm/h. with hematologic disorders or other symptoms is Prothrombin time was 44.6 and partial thromboplastin time 39.9. Lactate dehydrogenase was normal. Total bilirubin was slightly rarely reported. Therefore, splenic hamartomas are elevated at 1.4 mg/dL, with direct fraction of 0.1 mg/dL. Bone seldomly included in the differential diagnoses of a marrow findings were consistent with the diagnosis of hyper- left upper quadrant mass in pediatric patients. splenism. Chest x-ray was normal. Tuberculin skin test, coccidio- mycoses, and ANA serology were noncontributory. A splenic arteriogram showed irregular distribution of contrast material and Received for publication Jul 22, 1997; accepted Jan 14, 1998. marked splenomegaly (Fig 2). The patient underwent elective Reprint requests to (T.C.H.) Department of Pathology, Methodist Women’s splenectomy in March 1996. During the operation, the spleen was and Children’s Hospital, 8109 Fredericksburg Rd, San Antonio, TX 78229. noted to be enlarged. An accessory spleen was identified at the PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad- hilum, along with large perisplenic lymph nodes. The postopera- emy of Pediatrics. tive course was uneventful, and the platelet count increased to http://www.pediatrics.org/cgi/content/full/101/5/Downloaded from www.aappublications.org/newse10 by guestPEDIATRICS on September Vol.28, 2021 101 No. 5 May 1998 1of6 Fig 1. The enlarged spleen was out- lined, and the tip was measured to be 11 cm below the left costal margin.

Fig 2. Splenic arteriogram with nonionic iodinated contrast.

within normal range. Examination of the patient 9 months later Histologically, the nodules were less defined and showed an increase in both height and weight and resolution of merged imperceptibly with the surrounding splenic fever and night sweats. The complete blood count and erythrocyte sedimentation rate returned to within normal range. parenchyma. The nodules were composed of irregu- larly arranged sinusoids admixed with intervening PATHOLOGIC FINDINGS pulp cord-like elements (Fig 4). Endothelial cells sim- The resected spleen weighed 921 g (expected ilar to sinusoidal lining cells lined these channels. weight for height is 128 g) and measured 20 ϫ 15 ϫ These lining cells, by immunoperoxidase stains, 8 cm. The hilum showed several lymph nodes at Յ8 showed reactivity for CD8 and factor VIII-related mm each. An accessory spleen, measuring 1.5 cm, antigen, consistent with splenic type endothelium. was present. Cut surface of the spleen showed sev- There was no reactivity to CD34, which highlights eral large bulging circumscribed solid nodules that the cord capillaries. The pulp-like elements consisted measured up to 4.5 cm (Fig 3). The largest nodule of lymphocytes and macrophages along with few contained a central tan–white stellate scar. Numer- immunoblasts (Fig 5). There was focal stromal scle- ous similar but smaller nodules ranging from a few rosis, hyalinization, and hemosiderosis. Foreign millimeters to 1.2 cm were noted throughout the body giant cells were present with engulfed pig- spleen. ments. Foci of extramedullary hematopoiesis were

2of6 SYMPTOMATICDownloaded SPLENIC HAMARTOMAfrom www.aappublications.org/news by guest on September 28, 2021 Fig 3. A cut surface of the spleen showing circumscribed nodules of var- ious sizes.

Fig 4. The nodule is composed of ir- regularly arranged sinusoids admixed with intervening pulp cord-like ele- ments (hematoxylin–eosin, 100 ϫ).

observed. No lymphoid follicles of the white pulp bound vesicles, and mitochondria. Occasional Wei- were identified within these nodules. The rest of the bel–Palade bodies are seen in the lining cells of the spleen and the accessory spleen showed normal vascular channels (Fig 6). components of red and white pulp. The hilar lymph nodes showed mild sinus histiocytosis. DISCUSSION EBV EBER1 transcripts by in situ hybridization test Primary nonlymphomatous tumors of the spleen demonstrated a latent EBV transcript in rare lym- are uncommon. Most are either cysts or hemangio- phoid cells of the spleen and hilar lymph node. This mas. Hamartomas of the spleen are rarely reported result suggested that the patient was a virus carrier entities. The incidence of splenic hamartomas has from previous viral exposure. However, the spleno- been reported to be 3 in 200 000 splenectomies.3 With megaly was not a result of proliferation of EBV- the use of modern radiologic imaging techniques infected lymphocytes. such as sonography, CT, radionuclide scintigraphy, The vascular spaces are lined by cells with ultra- and MRI, splenic hamartoma may not be as uncom- structural features consistent with endothelial cells. mon as thought previously. In fact, one third of the These rounded cells rest on basement membrane cases reported in the past 135 years occurred just in material that is present only intermittently. At higher the last decade. magnification, the organelles of these cells are noted Approximately one sixth of these cases were de- to consist of abundant Golgi complex, membrane scribed in patients Ͻ16 years of age. The majority of

Downloaded from www.aappublications.org/newshttp://www.pediatrics.org/cgi/content/full/101/5/ by guest on September 28, 2021 e10 3of6 Fig 5. The pulp-like elements consisted of lymphocytes, macro- phages, and few immunoblasts (hematoxylin–eosin, 400 ϫ).

Fig 6. Electron micrograph (30 400 ϫ magnification) of an endothelial cell with organelles that include Weibel–Palade bod- ies (dart).

patients were asymptomatic, with the hamartoma investigators think that the two are virtually identi- being an incidental finding. A minority of the pa- cal.1,8 tients who were symptomatic had symptoms of hy- Immunohistochemical staining can be used to dis- persplenism and, less commonly, fever, night sweats, tinguish splenic hamartoma from capillary hemangi- and malaise. Additional unique symptoms noted in oma by their respective staining characteristics.9–11 the pediatric population include growth retardation Because the hamartoma is of splenic sinusoidal ori- and recurrent infections (Table 1). gin, the component cells show reactivity for T-lym- Although a hemangioma may be considered a phocytes markers, such as CD8, as well as for the form of hamartoma, the term splenic hamartoma endothelial cell markers, such as factor VIII-related usually is designated for circumscribed intrasplenic antigen. In contradistinction, the hemangioma that is lesions composed of tissue resembling normal red a tumor of vascular origin, shows reactivity for en- pulp. The capillary hemangiomas of the spleen may dothelial cell markers only. closely resemble splenic hamartoma such that some The first ultrastructural features of splenic hamar-

4of6 SYMPTOMATICDownloaded SPLENIC HAMARTOMAfrom www.aappublications.org/news by guest on September 28, 2021 TABLE 1. Clinicopathologic Features of Reported Cases of Symptomatic Splenic Hamartomas in Pediatric Patients Source Age, Sex PB BM Hepato- Lymph- Spleen Number/ Others Hyperplasia megaly adenopathy Weight Size (cm) (g) of Lesions Wallach2 3.5 y, M — — — — 150 1/5.4 Fever, parotid swelling, anorexia Wexler20 4 y, M A — — — 300 1/7.0 Proteinuria Kuykendal13 11 mo, M A — — — 200 1/7.0 Exchange transfusion for Rh incompatibility Silverman3 9 y, M A — — — 500 1/10.0 History of petechiae and thrombocytopenia at 2 years of age Huff21 4 y, M T — — — — 1/1.0 Brain tumor, Wiskott–Aldrich- like syndrome Iozzo7 12 y, F P ϩϩϩ795 M/5.0 Recurrent infections, growth retardation Iozzo7 9y,M P ϩϩϩ994 M/2.5 Fever of unknown origin, weakness, weight loss, night sweats, recurrent infections Havlik15 3y,M A — ϩ 0 — 1/6.0 Growth retardation, lethargy, fever Thompson14 14 y, F P — — — 1200 1/18.0 Malaise, weakness, growth retardation Current 11 y, F T ϩ 0 ϩ 921 M/4.5 Fever, night sweats, elevated case erythrocyte sedimentation rate, growth retardation PB indicates peripheral blood; BM, bone marrow; A, anemia; T, thrombocytopenia; P, pancytopenia; N, normal; M, multiple. toma have been reported to consist of endothelial and accessory spleen is speculative because this cells with Weibel–Palade bodies.12 The current case piece of information is not available in most of the showed similar ultrastructural features, with occa- cases reported. In Morgenstern’s series,19 accessory sional Weibel–Palade bodies identified. spleens were noted in one third of the cases. The multimodal approach currently available in In summary, splenic hamartoma should be in- medicine has enabled some cases of splenic hamar- cluded in the differential diagnoses of symptomatic tomas to be diagnosed preoperatively. The first splenomegaly and of splenic nodules discovered in- such case diagnosed preoperatively was in an 11- cidentally in pediatric patients. In cases of a single month-old male reported in 1977 by Kuykendall,13 discrete splenic hamartoma, the use of multimodal using radionuclide scintigraphy, sonography, and radiologic imaging may help to pinpoint the diagno- arteriography. Recently, in 1996, Thompson14 et al sis preoperatively. In addition, single and discrete reported a case of symptomatic splenic hamartoma hamartoma may be treated by conservative partial in a pediatric patient, diagnosed preoperatively by splenectomy. using a combination of radiologic imaging, consist- ing of sonography, radionuclide scintigraphy, CT, ACKNOWLEDGMENTS and MRI. A single hamartoma was present in both We thank Ms Josie Morales for secretarial assistance in the of these cases. preparation of this manuscript and Ms Peggy Miller for prepara- Single and discrete splenic hamartoma have been tion of the electron micrograph prints. 15,16 removed by conservative surgical approach, ie, Teresa C. Hayes, MD* by partial splenectomy. In the case of symptomatic Howard A. Britton, MD‡¶ single splenic hamartoma treated by partial splenec- E. Bruce Mewborne, MD§ tomy,15 there was resolution of the patient’s symp- Dean A. Troyer, MD# toms afterward. Victor A. Saldivar, MD* In our patient, periodic sonography, radionu- Irving A. Ratner, MDʈ Departments *Pathology, ‡Pediatrics, §Radiology, and clide scintigraphy, and CT were performed during ʈ the 8-year course, along with preoperative splenic Surgery arteriography and splenoportography. All of these Santa Rosa Children’s Hospital San Antonio, TX 78207 studies only reaffirmed the clinical impression of ¶Division of Pediatric Hematology and Oncology and splenomegaly, without focal lesions identified. #Department of Pathology MRI was not performed in our case. Because our University of Texas Health Science Center patient had multiple splenic hamartomas through- San Antonio, TX 78207 out the spleen, it probably was unlikely for this diagnosis to be made preoperatively. A conserva- REFERENCES tive surgical approach likewise was not feasible in 1. Berge Th. Splenoma. Acta Pathol et Microbiol Scand. 1965;63:333–339 our patient because of the multiplicity of the le- 2. Wallach JB, Nakao K. Hamartoma of the spleen. J Med Soc NJ. 1962;59: sions. 75–79 3. Silverman ML, LiVolsi VA. Splenic hamartoma. Am J Clin Pathol. 1978; The association of splenic hamartoma with other 70:224–229 hamartomatous entities such as tuberous sclerosis is 4. Raper AB. Fibrotic nodules of the spleen. J Pathol Bacteriol. 1959;78:1–16 known.17,18 The relationship of splenic hamartoma 5. Kirkland WG, McDonald JR. Hamartoma of the spleen. Report of three

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Downloaded from www.aappublications.org/news by guest on September 28, 2021 Symptomatic Splenic Hamartoma: Case Report and Literature Review Teresa C. Hayes, Howard A. Britton, E. Bruce Mewborne, Dean A. Troyer, Victor A. Saldivar and Irving A. Ratner Pediatrics 1998;101;e10 DOI: 10.1542/peds.101.5.e10

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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 1998 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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