Chinese Medical Journal 2006;119(16):1403-1408
Splenic hamartoma: case report and review of literature
Splenic hamartoma is a benign malformation composed of an anomalous mixture of normal splenic elements.1 Approximately half of the patients with the tumor are asymptomatic and diagnosed accidentally by autopsy or splenectomy.2-5 The tumor-related renal hematological and dermatological abnormalities can be treated by removal of the tumor.1 Splenic hamartoma which is related to renal diseases including extra- membranous glomerulonephritis, membrano- proliferative glomerulonephritis and renal adenocarcinoma has been reported previously.1,6 In December 2002, we treated a patient with splenic hamartoma complicated by renal pelvic stone detected accidentally by ultrasonography.
A 29-year-old man was admitted to our hospital because of renal colic at the left abdomen. Plain X-ray of the abdomen showed a 9-mm stone in the left renal pelvis. Ultrasonography revealed an enlarged spleen, containing two round clearly demarcated hypoechoic masses (4 cm and 2.9 cm in diameter respectively) with an anechoic dark fluid area under the splenic capsule. Splenomegaly was found on CT scan, with two round clearly demarcated and slightly hypodense masses (4 cm and 2.5 cm in diameter) within the splenic pulp. On physical examination, the patient was afebrile without abnormal vital signs and weight loss. His skin and sclera were not jaundiced. No lymph nodes were palpable, nor tenderness was felt over the left upper quadrant of the abdomen. Routine urine examination showed microscopic hematuria without protein and white blood cells. Total bilirubin (14.4 µmol/L, normal range: 1.6－20.6), direct bilirubin (3.2 µmol/L, 0－6.4), alkaline phosphatase (89.0 U/L, 35－150), γ-GT (58 U/L, 0－60), aspartate aminotransferase (21.0 U/L, 0－40), alanine aminotransferase (29 U/L, 0－40) were within normal limits. Hypoalbuminemia [total protein (73.6 g/L, 60－85) and albumin (41.5 g/L, 35－55) respectively] were not shown. Sodium (135.7 mmol/L, 135－145), chloride (101.1 mmol/L, 101－111) and potassium (3.74 mmol/L, 3.5－5.5) were within normal ranges. Blood cell counts were normal hemoglobin (154 g/L, 110－150), erythrocyte (5.07×1012/L, 3.5－5.5), hemoleukocyte (9×109/L, 3.5－10) and platelet (224×109/L, 100－300). The patient had no significant medical history.
The patient was diagnosed as having a left renal pelvic stone associated with splenic hamartoma and treated by antibiotics. One week later, his symptoms were eliminated, and exploratory laparotomy was performed. During the operation, an enlarged spleen (2 cm3) with a palpable mass was detected on the upper pole of the spleen, and splenectomy was done subsequently. Perioperative fluid therapy, antibiotic therapy and transfusion were prescribed.
Gross pathological examination showed that the spleen was 15 cm×9 cm×3 cm in size with two large well-defined brownish-red nodular lesions inside, which were well demarcated from the surrounding splenic parenchyma. Normal splenic tissues were compressed and deformed by the lesions. Light microscopy found that the cells of the lesions were widely separated by a disorganized stroma. The lesions were composed of a splenic red pulp with proliferated reticuloendothelial cells and entrapped red blood cells, focal extramedullary hematopoiesis, lympho-plasmacytosis, and fibrosis. Intranodular small T- and B-cell lymphoid aggregated but no organized secondary follicles or periarteriolar sheaths were seen. It was diagnosed as splenic hamartoma (nodular hyperplasia) of pulpar type histologically (Figs. 1 and 2). The patient was discharged from the hospital 11 days after splenectomy. One year later, his left renal stones were removed by extracorporeal shock wave lithotripsy (ESWL). He is doing well without any complication on follow-up.
Fig. 1. Hamartoma is widely separated by disorganized stroma, and contains other pulp spindle cells, scattered lymphocytes, entrapped red blood cells, and fibrosis. (HE, original magnification × 200)
Splenic hamartoma is a rare benign lesion, with an incidence of 0.13% at autopsy.7 The average age of the occurrence of hamartoma and its diameter are older or greater in women than in men,2 suggesting that hormonal factors may influence tumor growth. The diameter of the tumor ranges from a few millimeters to several centimeters. Being either multiple or singular, the multiplicity of the tumor has proved to be not related to the extent of hematologic symptoms.2 Symptoms of hamartoma seem to depend on its size,2,4,8,9 and symptomatic hamartoma is described to be of the red pulposal type.4,8
Histologically, hamartoma is a benign tumor-like nodule composed of an overgrowth of mature cells and tissues. There are two types of splenic hamartoma: follicular or pulposal and fibrous. The latter is most frequent while the former rare. The fibrous type is considered to be the result of fibrous degeneration of the follicular or pulposal type.3-4 Splenic hamartoma is either of the pulposal type resembling a splenic red pulp, or less frequently, a lymphoid type resembling a white pulp. Symptomatic cases are invariably of the red pulposal variety. The hamartoma of pulposal type has an increased number of vascular channels, which can sequester blood cells and produce hypersplenism, manifested by anemia, thrombocytopenia, or pancytopenia.3-4 Splenic hamartoma occurs either as solitary or multiple nodules within the splenic parenchyma. Being nonencapsulated, the tumor often compresses the surrounding parenchyma into a pseudocapsule.4-5 In our case, focal extramedullary hematopoiesis was noted, but the results of hematological examination were within normal limits. Extramedullary hematopoiesis as a compensatory response to deficient bone marrow cells predominantly affects the spleen and liver. Although diffuse infiltration is demonstrated microscopically, there may be focal mass like involvement of the liver and spleen.10
Splenic hamartoma is associated with few of lesions such as hypersplenism,3,11-12 liver cirrhosis,13 tuberous sclerosis,14 hepatic angiomyolipoma,15 renal hematological and dermatological abnormalities,1 extramembranous glomerulone- phritis, membranoproliferative glomerulonephritis,1,6 renal adenocarcinoma,1,6 and spontaneous splenic rupture with consequent emergency surgical treatment.3,13,16-17
Splenic tumors are relatively rare, most of them are cysts and benign tumors including hemangioma, lymphangioma, and hamartoma, malignant tumors in the spleen, such as lymphoma, leukemia, angiosarcoma, plasmocytoma, neoplasms of mesenchymal tissue, and metastasis of any primary tumor, are extremely rare, which mostly arise from the skin (melanoma), bronchial system, and mamma. Hence, splenic hamartoma must be differentiated from various splenic tumors. Recent advances in imaging techniques have allowed preoperative detection of splenic tumors during a screening for splenomegaly or other diseases.8,13,18-19
Different findings are shown by plain X-ray, ultrasonography, CT scan, angiography, and nuclear scintigraphy. Angiographic results are similar to those found in hematoma, hemangioma, and hemangiosarcoma.3,8,15,20 Plain X-ray of the abdomen rarely demonstrates calcification and is not informative. In a small number of patients,3,7,21 hypoechoic,22-23 hyperechoic,23 and isoechoic lesions were found by ultrasonography. In most patients, hamartomas are isodens on CT scan and MRI,6,18,24-25 without enhancement after application of contrast medium. They could be missed on abdominal CT scan.25 Moreover, hypodens are found on CT scan, with prolonged enhancement after use of contrast medium.18,23 In our patients, two hypoechoic masses were detected by ultrasono- graphy and routine abdominal CT. Recent studies suggested that the diagnosis of hamartoma is feasible with the use of radioisotopes and radionuclide imaging.23,26-28 Serial nuclear scintigraphy is not helpful in diagnosis, but increased radiocolloid 99mTc pertechnetate-uptake8,23 as well as no uptake is reported.24,29 A splenic hamartoma can be detected with plain X-ray, angiography, ultrasonography, MRI, and nuclear scanning, but malignancy can not be excluded.3,7-8,15,18,20-29
Needle aspiration of splenic lesions has been rarely reported.26 This could be due to the rarity of the splenic lesions or to the resultant compli- cations.26,30-32 In splenic hamartoma, abnormal cells could be derived from endothelial cells or hematological precursor cells, such as erythroblasts or atypical lymphocytes.26 Lee33 reported that a combination of cytological features and immunopathological results from the aspirate cytoblock along with the salient clinical information make an accurate preoperative diagnosis of splenic hamartoma possible. Bench-top fine-needle aspiration biopsy (FNAB) was performed to correlate cytological features with histological findings, and with immunopathological studies to establish a preoperative diagnosis of splenic hamartoma. The postoperative bench-top aspirate of splenic hamartoma yielded small and large clusters of plump, spindly to polygonal cells in the blood-stained background with scattered small lymphocytes, comparable with the preoperative echo-guided FNAB.
Clinical diagnosis of hamartoma is very difficult without histological, immunopathological and enzyme histochemical studies. The structures of splenic red pulp could be identified by immuno- and enzyme-histochemical markers reacting with sinus endothelium including factor VIII-related antigen, proteinase inhibitors, and non-specific esterase.34 The histopathology and immunopathology of splenic hamartoma from the bench-top aspirate cytoblock and splenectomy tissue were comparable, unveiling the red pulp tissue consisting of wider cord stromal tissue than its normal counterpart with sinus-like vascular channels lined by endothelial cells. The cells were positive for CD8, CD34, factor VIII-related antigen, vimentin, but negative for muscle-specific actin, CD21, CD68, and cytokeratin, scattered dispersed CD3- and CD45RO-positive T lymphocytes. Small clusters of CD20-positive B lymphocytes were noted, with a dearth of fibrous trabeculae and organized white-pulp lymphoid tissue.26,30-33
Splenic hamartoma is difficult to distinguish from splenic hemangioma both radiographically and histologically. Microscopically, a hamartoma and a capillary hemangioma both contains numerous vascular channels. However, the endothelial cells of splenic hamartoma react with antibodies to both CD8 and factor VIII-related antigen. On the other hand, the endothelial cells of a splenic hemangioma are factor VIII-positive but CD8-negative35 or only focally positive for CD34,35-38 which provides a reliable means to distinguish a hemangioma from a hamartoma.35-38 Enzyme histochemical studies of splenic hamartoma revealed that, in contrast to splenic hemangiomas, endothelial cells in hamartoma did not contain alkaline phosphatase and stained for non-specific esterases with both α- naphthyl acetate and naphthol-acid-phosphate as substrate.34
The presence of a clonal chromosomal abnormality in splenic hamartoma favors a neoplastic, but hamartomatous process.39 Pulmonary chondroid hamartoma40-43 and mesenchymal hamartoma of the liver44-47 are traditionally considered to be of hamartomatous origin, but the above two lesions are also considered benign neoplasms. Pulmonary chondroid hamartoma results from transformation of primitive mesenchymal cells that are differentiated from chondroid, adipose and smooth muscle pathways.42 Immunophenotypic studies of hepatic mesenchymal hamartoma support its mesenchymal derivation.48-49 Donner et al39 reported a case of splenic tumor diagnosed as splenic hamartoma by non-cytogenetic examination, whereas this diagnosis was excluded by cytogenetic examination. They found a clonal population with the karyotype 47 approximately 58, XX, +X, +4, +5, +5, +6, +10, +12, +14, der(16) dic(16;21) (p13.3;p11.2), dic(16;21) del(16) q11.1), +17, +19, +20, －21. It seems that the dicentric (16;21) is a unique abnormality, unlike that previously reported. This tumor is neoplastic, but not of hamartomatous origin.39 Except for lymphoid cells, fibroblasts and myofibroblasts of the fibrotic area, none of the other components (stroma, littoral cells, pericytic cells, and macrophages of the sheathed capillaries) can be excluded.39 We are not clear about what type or types of cells in a splenic hamartoma are cytogenetically abnormal. Hamartoma is traditionally defined as a mass with disorganized tissue indigenous to a particular site.50 This concept is obsolete and needs critical review. In our case, the diagnosis of splenic hamartoma was confirmed pathologically, but the origin of this tumor was not elucidated. Immunohistochemistry and cytogenetic examinations are needed for further diagnosis and for elucidation of the origin of the tumor.
Surgical procedures for splenic hamartoma include splenectomy, partial splenectomy,5,51,52 laparoscopic splenectomy53 and hand-assisted laparoscopic splenectomy.19,54 However, detection rate of hamartoma varies with multi-imaging modalities. Splenectomy is also important in patients with an incidentally discovered mass in the spleen when a malignant tumor cannot be ruled out. Splenic hamartoma with systemic or primary symptoms is rare, but often associated with hematological disorders, which can be cured by splenectomy.5, 51-52
Laparoscopic splenectomy is preferred to resect the spleen because of short hospital stay, less pain, good cosmesis and no requirement of blood transfusion.19,54,55 Focal lesions of the spleen should be removed intact to allow a complete histological examination and to avoid peritoneal dissemination in case of malignancy.19,54,55 The hand-assisted laparoscopic splenectomy makes possible the removal of an unminced organ and is advantageous as a purely laparoscopic technique,19,54,55 but application of laparoscopic splenectomy for splenic hamartoma is quite controversial because the final histological diagnosis may be affected if the spleen is fragmented during retrieval of specimens.19, 54,55
On the risk of overwhelming post-splenectomy infection,34 the merits of splenic preservation in children have been clearly documented.5,19 The decision depends on the patient’s age, the size of the mass, on whether complete or partial splenectomy is performed. Havlik et al5 reported that partial splenectomy should be done if there is a possibility that the organ could be salvaged. Mignon et al52 reported that preoperative embolization makes partial splenectomy with en-bloc resection of a splenic tumor possible under optimal surgical conditions. Although this partial splenectomy has few complications and hospital stay is short, this procedure is safe for treatment of splenic benign tumor.5,8,17,52 We reported the first case of splenic hamartoma associated with a left renal pelvic stone, which was removed by splenectomy. Etiologically, splenic hamartoma and left renal pelvis stone are two different diseases. There is no evidence to indicate that the cause that splenic hamartoma and left renal pelvis stones develop at the same time. They must appear coincidently.
In summary, trans-abdominal complete splenectomy is the most frequent treatment for hamartoma of the spleen. Partial splenic resection is the preferred surgery particularly for children with splenic hamartoma to avoid the potential risks of total splenectomy. Immunohistochemistry and genetic profiling are important both for elucidation of the origin and the diagnosis of splenic tumor. And it benefits the studies of the type and cell types of a splenic hamartoma cytogenetically.
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