Splenic Hamartoma MARK L SILVERMAN, M.D., AND VIRGINIA A. LiVOLSI, M.
Silverman, Mark L., and LiVoIsi, Virginia A.: Splenic hamartoma. Am J Clin Pathol 70: 224-229, 1978. This paper describes five cases of splenic hamartoma, a benign lesion, usually found incidentally in the spleen at autopsy. The current practice of laparotomy for staging of malignant lymphomas, especially Hodgkin's disease, has increased the numbers of surgically removed spleens. Because splenic hamartomas may be confused histologically with Hodgkin's disease involving the spleen, the authors have reviewed this entity, stressing the importance of recognizing and distinguishing it from a malignant process. (Key words: Spleen; Hamartoma; Hemangioma; Hodgkin's disease.)
From the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
6,000 with a normal differential, erythrocyte sedimentation rate 18 mm per hour; other routine chemistries were normal. Chest x-ray, abdominal lymphangiogram, and liver spleen scan were interpreted as normal. Bone marrow aspiration and biopsy disclosed no tumor. Exploratory laparotomy and splenectomy were performed.
SPLENIC HAMARTOMAS, first described more than 100 years ago by Rokitansky, 21 usually represent incidental findings at autopsy or operation.3-4,18'20'25'29 A few of these lesions, however, have been associated with clinical symptoms. 2 ' 5 ' 8 - 11 ' 14 ' 19 ' 23 - 26 ' 28,30 Although several theories of pathogenesis have been proposed, 3 ' 418 none has been accepted universally. Thus, these lesions have been diagnosed as hamartomas,5'8,13'18'26 neoplasms such as splenomas, lymphangiomas, or hemangiomas, 315 congenital anomalies, 3 - 4 and postraumatic scars. 1 1 0 2 7 All reports of this entity have stressed its benign nature. In the era of laparotomy and splenectomy for staging of malignant lymphoma, especially for Hodgkin's disease, 9 awareness of the splenic hamartoma attains heightened significance, since it must be differentiated from more ominous lesions. This paper reviews the entity of splenic hamartoma and reports five new cases, including two found in specimens from staging laparotomy for Hodgkin's disease.
The lymph nodes, liver and bone marrow biopsies showed no involvement by tumor. The disease was therefore staged IIA and treated with radiotherapy. A year after therapy the patient remains free of disease. Case 2
Clinical Data and Pathologic Findings Case 1 A 19-year-old asymptomatic male patient was seen in late 1975 with a right supraclavicular mass. Biopsy of a cervical lymph node showed Hodgkin's disease, nodular sclerosing type. Upon referral to Yale New Haven Hospital, right supraclavicular and mild bilateral axillary adenopathy were found on physical examination. Pertinent laboratory data included hematocrit 38%, leukocyte count Received July 8, 1977; received revised manuscript September 14, 1977; accepted for publication September 14, 1977. Dr. Silverman's present address is the Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts 02114. Address reprint requests to Dr. LiVolsi: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510. 0002-9173/78/0800/0224 $00.75 © Ai
An asymptomatic 40-year-old man was evaluated for cervical lymphadenopathy of recent onset. Laboratory tests including complete blood count, urinalysis, and liver function tests disclosed normal values. A diagnosis of Hodgkin's disease, nodular sclerosing type, was established by lymph-node biopsy. Roentgenograms of the chest, bone marrow aspirate and biopsy, and lymphangiogram demonstrated normal findings. Staging laparotomy and splenectomy were performed.
The spleen, which weighed 195 g, measured 12.5 cm in greatest dimension and had a smooth capsule. Cut surface showed normal splenic pulp with tiny malpighian corpuscles; no gross lesion was identified. Microscopically, however, in one of the splenic sections a 0.7-cm lobulated hamartoma was recognized (Fig. 2). At the periphery of this nodule, small clusters of eosinocan Society of Clinical Pathologists
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The spleen, which weighed 124 g and measured 10 cm in greatest dimension, had a smooth capsule. On sectioning, a 1-cm white, firm circumscribed nodule was found in the center of the splenic parenchyma. Microscopically, the lesion appeared ovoid and lobulated. Although no true capsule was present, the surrounding parenchyma was slightly compressed. At higher power, the mass was found to be composed of a whorled plexus of vascular channels within fibrous tissue (Fig. 1). Irregular slit-like spaces lined by plump endothelial cells were seen. A few lymphocytes were scattered in and around the nodule, but no eosinophils, plasma cells, Reed-Sternberg cells or variants were identified after extensive search. The remainder of the spleen showed no abnormality.
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phils were found. However, no polymorphic cell infiltrates or Reed-Sternberg cells were identified in the spleen. On the basis of the laparotomy findings, the lesion was staged IIA. The patient was treated with standard radiotherapy, and six months following the diagnosis shows no evidence of disease. Case 3
The spleen weighed 500 g and contained in its center a nodular hard mass 10 cm in diameter. It appeared dark red, was circumscribed but not encapsulated; on cutting it bulged slightly from the surrounding splenic parenchyma. Multiple sections of the splenic tumor showed a rounded, almost lobulated, interface of the lesion with the surrounding spleen, which was compressed (Fig. 3). No true capsule was identified. The fibrous trabeculae that formed the lesion contained vascular spaces lined by plump endothelial cells. Uninvolved spleen appeared normal. Postoperatively, the patient recovered normal hematologic function. Subsequently, he was lost to follow up. Case 4 A 72-year-old woman was found to have chronic lymphocytic leukemia in 1970. Without treatment she did well. However, in 1973, because of an increasing leukocyte count and an enlarging spleen, she was treated with chlorambucil, prednisone, and splenic irradiation. Despite this therapy, the patient's condition deteriorated, a disseminated herpes simplex infection developed, and the patient died.
At autopsy the spleen weighed 800 g and was covered with calcified plaques. On section, the splenic parenchyma was partly replaced by an infiltrating nodular process. Microscopically, numerous Gamna-Gandi bodies were present. In addition, a 0.4-cm, fibrous lesion composed of slit-like spaces lined by endothelial cells was identified (Fig. 4). This nodule, which was clearly demarcated from the splenic parenchyma, was not encapsulated. In areas away from this splenic lesion
Case 5 A 67-year-old man initially sought medical treatment for pain in the right chest and intermittent hemoptysis. Work-up included a roentgenogram of the chest, which disclosed a large mediastinal mass. Biopsy demonstrated infiltrating adenocarcinoma. Because of mediastinal involvement, the patient was considered inoperable, and was treated with irradiation and adjuvant chemotherapy. However, his condition deteriorated and he died approximately a year after diagnosis.
At autopsy, metastatic adenocarcinoma was identified in the left lung, peritoneum, liver, diaphragm and brain. The spleen, which weighed 90 g, was described as firm, and contained a 3-mm white nonencapsulated nodule within its parenchyma. Grossly, this lesion resembled a metastasis. Microscopically, it was a splenic hamartoma. The lesion was composed of lobulated clusters of vascular spaces lined by endothelium. It lacked a capsule but slightly compressed the surrounding splenic tissues. Discussion Splenic hamartomas occur with equal frequency in males and females. They have been found most often in older people, but have also been found in adolescents and children. The preponderance in older people may be attributed to the relative infrequencies of both abdominal surgical procedures and death in the younger age groups. The splenic hamartoma has been described to occur in association with many and diverse disease states. 2_5 8.11,12.14.15.18.20.23-26.28-30
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lesions culled from the literature, 74 were incidental findings. Most of the reported cases have been included in autopsy series.3,4,18,2° In all, eight cases were found in individuals who had malignant disease. 31418 Few patients initially manifested hematologic abnormalities 2-8.11.12.22.23.28 The size of the lesion apparently relates to the associated clinical state. Thus, large tumors (more than 2 cm) were uncommon in autopsy series3,418,20 but form the majority of those lesions examined surgically for symptomatic disease.2,8,14,22_26,28,30 In a few instances, small lesions were found in enlarged spleens removed surgically for mass-related symptoms.5,14 In patients with large lesions and relevant "splenic" symptomatology, that is, hypersplenism, direct incrimination of the hamartoma as the cause of the symptoms has not been well defined.2,n12,22,23,28 These lesions may represent innocent bystanders in a diseased spleen. Noting the preponderance of cases in which the splenic hamartoma played no obvious pathophysiologic role,
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A 9-year-old boy was admitted to the hospital for elective orchiopexy. Past history disclosed an episode of widespread petechial cutaneous lesions at the age of 2 years. This syndrome was accompanied by thrombocytopenia. Complete recovery followed without apparent hematologic relapse. It was felt that this probably reflected an unusual response to an infection, albeit of undetermined etiology. During the present admission hepatosplenomegaly was evident. Laboratory data included a hematocrit of 30% with a hemoglobin of 10.2 g/dl. The peripheral blood smear showed microcytosis. Further studies revealed reduced erythrocyte survival time. Extensive hematologic work-up, however, failed to disclose a reason for the anemia except for the splenomegaly. A splenoportogram demonstrated a large relatively avascular mass within the substance of the spleen. Splenectomy with splenorenal shunt was performed.
the spleen showed infiltration by lymphocytic leukemia and foci of herpes-infested cells.
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FIG. 1 (upper). The center of splenic hamartoma is illustrated. Lobulation is evident. The lesion is composed of numerous endothelial cells embedded in a fibrous stroma. Hematoxylin and eosin. x240. FIG. 2 (lower). One lobule of a hamartoma is shown. Note vascular slits. Lymphocytes can be seen in and abutting the periphery of the lesion. Hematoxylin and eosin. x 100.
The term splenic lymphoma3 has also been used; it is the opinion of the present authors that this is extremely misleading, since "lymphoma" has come to be synonymous with malignancy. These lesions do not resemble Gamna-Gandi bodies, which are calcium- and iron-encrusted scars often found in spleens near infarcts or following traumatic episodes with hemorrhage.17 Gamna-Gandi bodies often contract the splenic capsule and produce parenchymal retraction characteristic of scar tissue. They do not compress nearby spleen, as do the lesions we are describing. In our Case 4, Gamna-Gandi bodies were recognized in the splenic parenchyma removed from the nodule; the patient had received splenic irradiation, however. Some large splenic hamartomas have been associated with infarcts and siderotic bodies.2,11,12,22,28 The latter can be explained solely on the basis of large spleen size and are probably not related to the hamartoma. Are these lesions hamartomas? Hamartoma is defined as "a benign tumor-like nodule composed of an overgrowth of mature cells and tissues that normally occur in the affected part." 6 The term "splenoma" 2 implies a tumor of the splenic endothelium. The lesions in our series most closely resemble disordered splenic sinusoids embedded in a fibrous stroma. Unfortunately, fresh tissue was not available in any of our cases for enzymatic histochemical studies that could have differentated between splenic and vascular endothelium.16 If the endothelium in these cases showed a splenic pattern, we believe this technic might help answer the question of the hamartomatous nature of the lesion. Darden and associates5 and Van Heerden and colleagues26 reported the cases of patients with tuberous sclerosis who were found to have multiple splenic hamartomas. The association of different varieties of hamartomas in different organ systems is noteworthy. Although we cannot ascribe their pathogenesis to a hamartomatous origin, we believe that this remains a valuable operative concept and underscores the overall benignity of this lesion. The current practice of staging laparotomy9 in the management of Hodgkin's disease demands detailed and careful examination of splenectomy specimens.7 Splenic lesions that might otherwise go undetected can become the crux of important diagnostic decisions that may influence the course of further therapy. Two of
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it is tempting to speculate that the large size observed reflected some pathologic factor causing splenic enlargement. Follow up in those patients who were symptomatic shows that most recover from the hematologic abnormality following splenectomy.812,28 Such followup information, however, is quite sparse, since in most cases long-term evaluation is not recorded.211,22 It is probable that recovery was due to removal of a diseased spleen, not necessarily related to the hamartoma. The pathologic features of the surrounding splenic parenchyma are poorly described in many instances; when described, the splenic parenchyma has been normal, or has shown rare foci of extramedullary hematopoiesis.2",12,22,28 To our knowledge, none of the cases that were associated with hematologic abnormalities was evaluated for the presence of marrow-depressive or toxic substances in the splenic lesion.3 Clearly the data at hand are too sparse to resolve this issue. Splenic hamartomas consist of rounded and unencapsulated lesions that compress the surrounding splenic parenchyma. Microscopically, the dominant pattern is characterized by the presence of slit-like vascular channels lined by plump endothelial cells embedded in a fibrous background. Erythrocytes are found frequently within the vascular spaces. Variable numbers of lymphocytes and occasionally eosinophils are seen in the fibrous matrix. The hamartomas examined in this series contained focal accumulations of hemosiderin; most of the latter were located at the peripheries of the lesions. The most commonly pathogenetic mechanisms for the formation of splenic hamartoma include congenital,:iA neoplastic,315 posttraumatic110,27 and hamartomatous.5,8,13,18,25 Berge3 summarized various diagnoses used for this lesion. Many intimated a neoplastic derivation: thus, terms such as splenoma, fibrous splenoma, and splenoadenoma have been used. Others have considered this lesion to be a hemangioma' 10 or lymphangioma.3 True hemangiomas of the spleen occur, but the latter resemble cavernous hemangiomas elsewhere.110 The lesion we are discussing shows a pattern of sclerosing angioma. However, the vascular pattern in these cases appears slit-like and tortuous. Trichrome and elastic stains fail to demonstrate pre-existing vessel walls. In addition, the compression of the surrounding splenic parenchyma is not easily explained on the basis of a fibrotic and retracting hemangioma.
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FIG. 3 (upper). This low-power photomicrograph illustrates a non-encapsulated, lobulated hamartoma on the left. The compressed splenic parenchyma appears normal. Case 3. Hematoxylin and eosin. x 1. FIG. 4 (lower). Higher-power illustration demonstrates the vascular slits lined by occasionally plump endothelial cells. Hematoxylin and eosin. x240.
Reference 1. Benjamin BI, Nohler DN, Sandusky WR: Hemangioma of the spleen. Arch Intern Med 115:280-284, 1965 2. Bhagwat AG, D'Atta DV, Mitra S, et al: Splenoma with portal hypertension. Br Med J 1:520, 1975 3. Berge TH: Splenoma. Acta Pathol Microbiol Scand 63:333-339, 1965 4. Coe JI, von Drashek S: Hamartoma of the spleen. A report of four cases. Am J Pathol 28:663-671, 1952 5. Darden JW, Teeslink R, Parrish RA: Hamartoma of the spleen, a manifestation of tuberous sclerosis. Am Surg 41:564-566, 1975 6. Dorland's Illustrated Medical Dictionary, Philadelphia, W. B. Saunders, 1974 7. Farrer-Brown G, Bennett MH, Harrison CV, et al: The diagnosis of Hodgkin's disease in surgically excised spleens. J Clin Pathol 25:294-300, 1972
8. Fisher H: Splenomegalie infolge multipler pulposer splenome. Deutsche Z Chirurg 248:552-562, 1936 9. Glatstein E, Guernsey JM, Rosenberg SA, et al: The value of laparotomy and splenectomy in the staging of Hodgkin's disease. Cancer 24:709-718, 1969 10. Graham JC, Weidner WA, Vinik M: The angiographic features of organizing splenic hematoma. Am J Roentgenol 107:430433, 1969 11. Gupta PCS: Hamartoma of the spleen. J Indian Med Assoc 41:610, 1963 12. Hardmeier T: Hypersplenismus bei einem hamartom de milz. Schweiz Med Wochenschr 92:1270-1274, 1962 13. Henke F, Lubarsch O: Handbuch der speziellan pathologischen anatomie und histologic I, Part 2. Berlin, Julius Springer. 1927, pp 695-697 14. Kirkland WG, McDonald J: Hamartoma of the spleen, report of three surgical cases. Arch Pathol 45:371-379, 1948 15. Komaki S, Gombas OF: Angiographic demonstration of a calcified splenic hamartoma. Radiology 121:77-81, 1976 16. Loffler H: Cytochemischer Nachweis von unspezifischer esterase in ausstrichen beitrage zur technik und ergebnisse in blutausstrich des menschen. Klin Wochenschr 39:1220-1227, 1961 17. MacPherson AIS, Richmond J, Stuart AE: The Spleen. Springfield, 111., Charles C Thomas, 1973 18. Mordasini E: Uber Splenome (Hamartome) der milz. Virchows Arch Pathol Anat 298:594-615, 1936 19. Nanba K, Soban EJ, Bowling MC, et al: Splenic pseudosinuses and hepatic angiomatous lesions. Am J Clin Pathol 67:415426, 1977 20. Raper, AB: Fibrotic nodules of the spleen. J Pathol Bacteriol 78:1-16, 1959 21. Rokitansky K: Uber splenome. Lehrbuch der Pathol Anat Bd 3, 1861 22. Ross CF, Schiller KFR: Hamartoma of the spleen associated with thrombocytopenia. J Pathol 105:62-64, 1971 23. Schrijver H, Verdonk GJ: Hamartoma of the spleen with inhibition of the bone marrow. Acta Med Scand 143:235-237, 1957 24. Sweet RH, Warren S: Hamartoma of the spleen, report of a case. N Engl J Med 226:757-758, 1942 25. Teates CD, Seale DL, Allen MS: Hamartoma of the spleen. Am J Roentgenol 116:419-422, 1972 26. Van Heerden JA, Longo MF, Cardona F, et al: The abdominal mass in the patient with tuberous sclerosis. Arch Surg 95:317-319, 1967 27. Vere Nicoll JA: Splenic haematoma after spontaneous rupture of the spleen. Am J Surg 116:117-119, 1968 28. Videbaek A: Hypersplenism associated with hamartomas of the spleen. Acta Med Scand 141:275-288, 1953 29. Wallach JB, Nakao N: Hamartoma of the spleen. J Med Soc NJ 59:75-79, 1962 30. Wexler L, Abrams HI: Hamartoma of the spleen: Angiographic observations. Am J Roentgenol 92:1150-1155, 1964
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the cases in this report are of particular interest in this regard. Both splenic hamartomas were incidental findings in patients with Hodgkin's disease undergoing staging procedures. In view of the low-power impression of an almost granulomatous nature, as well as the finding of lymphocytes and occasional eosinophils, the differential diagnosis of splenic involvement by Hodgkin's disease was entertained by some observers. The features that distinguish the hamartoma from Hodgkin's disease include the intrinsically vascular nature of the lesions, which can be appreciated on careful examination; the compression of the surrounding splenic parenchyma rather than replacement of splenic cords by tumor; the lack of a truly characteristic Hodgkin's infiltrate; and the absence of Reed-Sternberg cells or their variants. Hence, we believe the benign splenic lesion that we are describing can be differentiated from Hodgkin's disease by careful microscopic study. The lesions we are describing are found infrequently. We recognized three cases in our surgical pathology files, covering 17 years and encompassing almost 200,000 specimens. Two other examples were identified from among 1,500 autopsy cases. However, although it is rare, recognition of this splenic lesion is important for the modern surgical pathologist.
Silverman, Mark L., and LiVoIsi, Virginia A.: Splenic hamartoma. Am J Clin Pathol 70: 224-229, 1978. This paper describes five cases of splenic hamartoma, a benign lesion, usually found incidentally in the spleen at autopsy. The current practice of laparotomy for staging of malignant lymphomas, especially Hodgkin's disease, has increased the numbers of surgically removed spleens. Because splenic hamartomas may be confused histologically with Hodgkin's disease involving the spleen, the authors have reviewed this entity, stressing the importance of recognizing and distinguishing it from a malignant process. (Key words: Spleen; Hamartoma; Hemangioma; Hodgkin's disease.)
From the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
6,000 with a normal differential, erythrocyte sedimentation rate 18 mm per hour; other routine chemistries were normal. Chest x-ray, abdominal lymphangiogram, and liver spleen scan were interpreted as normal. Bone marrow aspiration and biopsy disclosed no tumor. Exploratory laparotomy and splenectomy were performed.
SPLENIC HAMARTOMAS, first described more than 100 years ago by Rokitansky, 21 usually represent incidental findings at autopsy or operation.3-4,18'20'25'29 A few of these lesions, however, have been associated with clinical symptoms. 2 ' 5 ' 8 - 11 ' 14 ' 19 ' 23 - 26 ' 28,30 Although several theories of pathogenesis have been proposed, 3 ' 418 none has been accepted universally. Thus, these lesions have been diagnosed as hamartomas,5'8,13'18'26 neoplasms such as splenomas, lymphangiomas, or hemangiomas, 315 congenital anomalies, 3 - 4 and postraumatic scars. 1 1 0 2 7 All reports of this entity have stressed its benign nature. In the era of laparotomy and splenectomy for staging of malignant lymphoma, especially for Hodgkin's disease, 9 awareness of the splenic hamartoma attains heightened significance, since it must be differentiated from more ominous lesions. This paper reviews the entity of splenic hamartoma and reports five new cases, including two found in specimens from staging laparotomy for Hodgkin's disease.
The lymph nodes, liver and bone marrow biopsies showed no involvement by tumor. The disease was therefore staged IIA and treated with radiotherapy. A year after therapy the patient remains free of disease. Case 2
Clinical Data and Pathologic Findings Case 1 A 19-year-old asymptomatic male patient was seen in late 1975 with a right supraclavicular mass. Biopsy of a cervical lymph node showed Hodgkin's disease, nodular sclerosing type. Upon referral to Yale New Haven Hospital, right supraclavicular and mild bilateral axillary adenopathy were found on physical examination. Pertinent laboratory data included hematocrit 38%, leukocyte count Received July 8, 1977; received revised manuscript September 14, 1977; accepted for publication September 14, 1977. Dr. Silverman's present address is the Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts 02114. Address reprint requests to Dr. LiVolsi: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510. 0002-9173/78/0800/0224 $00.75 © Ai
An asymptomatic 40-year-old man was evaluated for cervical lymphadenopathy of recent onset. Laboratory tests including complete blood count, urinalysis, and liver function tests disclosed normal values. A diagnosis of Hodgkin's disease, nodular sclerosing type, was established by lymph-node biopsy. Roentgenograms of the chest, bone marrow aspirate and biopsy, and lymphangiogram demonstrated normal findings. Staging laparotomy and splenectomy were performed.
The spleen, which weighed 195 g, measured 12.5 cm in greatest dimension and had a smooth capsule. Cut surface showed normal splenic pulp with tiny malpighian corpuscles; no gross lesion was identified. Microscopically, however, in one of the splenic sections a 0.7-cm lobulated hamartoma was recognized (Fig. 2). At the periphery of this nodule, small clusters of eosinocan Society of Clinical Pathologists
224
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
The spleen, which weighed 124 g and measured 10 cm in greatest dimension, had a smooth capsule. On sectioning, a 1-cm white, firm circumscribed nodule was found in the center of the splenic parenchyma. Microscopically, the lesion appeared ovoid and lobulated. Although no true capsule was present, the surrounding parenchyma was slightly compressed. At higher power, the mass was found to be composed of a whorled plexus of vascular channels within fibrous tissue (Fig. 1). Irregular slit-like spaces lined by plump endothelial cells were seen. A few lymphocytes were scattered in and around the nodule, but no eosinophils, plasma cells, Reed-Sternberg cells or variants were identified after extensive search. The remainder of the spleen showed no abnormality.
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phils were found. However, no polymorphic cell infiltrates or Reed-Sternberg cells were identified in the spleen. On the basis of the laparotomy findings, the lesion was staged IIA. The patient was treated with standard radiotherapy, and six months following the diagnosis shows no evidence of disease. Case 3
The spleen weighed 500 g and contained in its center a nodular hard mass 10 cm in diameter. It appeared dark red, was circumscribed but not encapsulated; on cutting it bulged slightly from the surrounding splenic parenchyma. Multiple sections of the splenic tumor showed a rounded, almost lobulated, interface of the lesion with the surrounding spleen, which was compressed (Fig. 3). No true capsule was identified. The fibrous trabeculae that formed the lesion contained vascular spaces lined by plump endothelial cells. Uninvolved spleen appeared normal. Postoperatively, the patient recovered normal hematologic function. Subsequently, he was lost to follow up. Case 4 A 72-year-old woman was found to have chronic lymphocytic leukemia in 1970. Without treatment she did well. However, in 1973, because of an increasing leukocyte count and an enlarging spleen, she was treated with chlorambucil, prednisone, and splenic irradiation. Despite this therapy, the patient's condition deteriorated, a disseminated herpes simplex infection developed, and the patient died.
At autopsy the spleen weighed 800 g and was covered with calcified plaques. On section, the splenic parenchyma was partly replaced by an infiltrating nodular process. Microscopically, numerous Gamna-Gandi bodies were present. In addition, a 0.4-cm, fibrous lesion composed of slit-like spaces lined by endothelial cells was identified (Fig. 4). This nodule, which was clearly demarcated from the splenic parenchyma, was not encapsulated. In areas away from this splenic lesion
Case 5 A 67-year-old man initially sought medical treatment for pain in the right chest and intermittent hemoptysis. Work-up included a roentgenogram of the chest, which disclosed a large mediastinal mass. Biopsy demonstrated infiltrating adenocarcinoma. Because of mediastinal involvement, the patient was considered inoperable, and was treated with irradiation and adjuvant chemotherapy. However, his condition deteriorated and he died approximately a year after diagnosis.
At autopsy, metastatic adenocarcinoma was identified in the left lung, peritoneum, liver, diaphragm and brain. The spleen, which weighed 90 g, was described as firm, and contained a 3-mm white nonencapsulated nodule within its parenchyma. Grossly, this lesion resembled a metastasis. Microscopically, it was a splenic hamartoma. The lesion was composed of lobulated clusters of vascular spaces lined by endothelium. It lacked a capsule but slightly compressed the surrounding splenic tissues. Discussion Splenic hamartomas occur with equal frequency in males and females. They have been found most often in older people, but have also been found in adolescents and children. The preponderance in older people may be attributed to the relative infrequencies of both abdominal surgical procedures and death in the younger age groups. The splenic hamartoma has been described to occur in association with many and diverse disease states. 2_5 8.11,12.14.15.18.20.23-26.28-30
T h u s
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,
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lesions culled from the literature, 74 were incidental findings. Most of the reported cases have been included in autopsy series.3,4,18,2° In all, eight cases were found in individuals who had malignant disease. 31418 Few patients initially manifested hematologic abnormalities 2-8.11.12.22.23.28 The size of the lesion apparently relates to the associated clinical state. Thus, large tumors (more than 2 cm) were uncommon in autopsy series3,418,20 but form the majority of those lesions examined surgically for symptomatic disease.2,8,14,22_26,28,30 In a few instances, small lesions were found in enlarged spleens removed surgically for mass-related symptoms.5,14 In patients with large lesions and relevant "splenic" symptomatology, that is, hypersplenism, direct incrimination of the hamartoma as the cause of the symptoms has not been well defined.2,n12,22,23,28 These lesions may represent innocent bystanders in a diseased spleen. Noting the preponderance of cases in which the splenic hamartoma played no obvious pathophysiologic role,
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
A 9-year-old boy was admitted to the hospital for elective orchiopexy. Past history disclosed an episode of widespread petechial cutaneous lesions at the age of 2 years. This syndrome was accompanied by thrombocytopenia. Complete recovery followed without apparent hematologic relapse. It was felt that this probably reflected an unusual response to an infection, albeit of undetermined etiology. During the present admission hepatosplenomegaly was evident. Laboratory data included a hematocrit of 30% with a hemoglobin of 10.2 g/dl. The peripheral blood smear showed microcytosis. Further studies revealed reduced erythrocyte survival time. Extensive hematologic work-up, however, failed to disclose a reason for the anemia except for the splenomegaly. A splenoportogram demonstrated a large relatively avascular mass within the substance of the spleen. Splenectomy with splenorenal shunt was performed.
the spleen showed infiltration by lymphocytic leukemia and foci of herpes-infested cells.
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FIG. 1 (upper). The center of splenic hamartoma is illustrated. Lobulation is evident. The lesion is composed of numerous endothelial cells embedded in a fibrous stroma. Hematoxylin and eosin. x240. FIG. 2 (lower). One lobule of a hamartoma is shown. Note vascular slits. Lymphocytes can be seen in and abutting the periphery of the lesion. Hematoxylin and eosin. x 100.
The term splenic lymphoma3 has also been used; it is the opinion of the present authors that this is extremely misleading, since "lymphoma" has come to be synonymous with malignancy. These lesions do not resemble Gamna-Gandi bodies, which are calcium- and iron-encrusted scars often found in spleens near infarcts or following traumatic episodes with hemorrhage.17 Gamna-Gandi bodies often contract the splenic capsule and produce parenchymal retraction characteristic of scar tissue. They do not compress nearby spleen, as do the lesions we are describing. In our Case 4, Gamna-Gandi bodies were recognized in the splenic parenchyma removed from the nodule; the patient had received splenic irradiation, however. Some large splenic hamartomas have been associated with infarcts and siderotic bodies.2,11,12,22,28 The latter can be explained solely on the basis of large spleen size and are probably not related to the hamartoma. Are these lesions hamartomas? Hamartoma is defined as "a benign tumor-like nodule composed of an overgrowth of mature cells and tissues that normally occur in the affected part." 6 The term "splenoma" 2 implies a tumor of the splenic endothelium. The lesions in our series most closely resemble disordered splenic sinusoids embedded in a fibrous stroma. Unfortunately, fresh tissue was not available in any of our cases for enzymatic histochemical studies that could have differentated between splenic and vascular endothelium.16 If the endothelium in these cases showed a splenic pattern, we believe this technic might help answer the question of the hamartomatous nature of the lesion. Darden and associates5 and Van Heerden and colleagues26 reported the cases of patients with tuberous sclerosis who were found to have multiple splenic hamartomas. The association of different varieties of hamartomas in different organ systems is noteworthy. Although we cannot ascribe their pathogenesis to a hamartomatous origin, we believe that this remains a valuable operative concept and underscores the overall benignity of this lesion. The current practice of staging laparotomy9 in the management of Hodgkin's disease demands detailed and careful examination of splenectomy specimens.7 Splenic lesions that might otherwise go undetected can become the crux of important diagnostic decisions that may influence the course of further therapy. Two of
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it is tempting to speculate that the large size observed reflected some pathologic factor causing splenic enlargement. Follow up in those patients who were symptomatic shows that most recover from the hematologic abnormality following splenectomy.812,28 Such followup information, however, is quite sparse, since in most cases long-term evaluation is not recorded.211,22 It is probable that recovery was due to removal of a diseased spleen, not necessarily related to the hamartoma. The pathologic features of the surrounding splenic parenchyma are poorly described in many instances; when described, the splenic parenchyma has been normal, or has shown rare foci of extramedullary hematopoiesis.2",12,22,28 To our knowledge, none of the cases that were associated with hematologic abnormalities was evaluated for the presence of marrow-depressive or toxic substances in the splenic lesion.3 Clearly the data at hand are too sparse to resolve this issue. Splenic hamartomas consist of rounded and unencapsulated lesions that compress the surrounding splenic parenchyma. Microscopically, the dominant pattern is characterized by the presence of slit-like vascular channels lined by plump endothelial cells embedded in a fibrous background. Erythrocytes are found frequently within the vascular spaces. Variable numbers of lymphocytes and occasionally eosinophils are seen in the fibrous matrix. The hamartomas examined in this series contained focal accumulations of hemosiderin; most of the latter were located at the peripheries of the lesions. The most commonly pathogenetic mechanisms for the formation of splenic hamartoma include congenital,:iA neoplastic,315 posttraumatic110,27 and hamartomatous.5,8,13,18,25 Berge3 summarized various diagnoses used for this lesion. Many intimated a neoplastic derivation: thus, terms such as splenoma, fibrous splenoma, and splenoadenoma have been used. Others have considered this lesion to be a hemangioma' 10 or lymphangioma.3 True hemangiomas of the spleen occur, but the latter resemble cavernous hemangiomas elsewhere.110 The lesion we are discussing shows a pattern of sclerosing angioma. However, the vascular pattern in these cases appears slit-like and tortuous. Trichrome and elastic stains fail to demonstrate pre-existing vessel walls. In addition, the compression of the surrounding splenic parenchyma is not easily explained on the basis of a fibrotic and retracting hemangioma.
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Vol. 70 • No. 2
SPLENIC HAMARTOMA
229
FIG. 3 (upper). This low-power photomicrograph illustrates a non-encapsulated, lobulated hamartoma on the left. The compressed splenic parenchyma appears normal. Case 3. Hematoxylin and eosin. x 1. FIG. 4 (lower). Higher-power illustration demonstrates the vascular slits lined by occasionally plump endothelial cells. Hematoxylin and eosin. x240.
Reference 1. Benjamin BI, Nohler DN, Sandusky WR: Hemangioma of the spleen. Arch Intern Med 115:280-284, 1965 2. Bhagwat AG, D'Atta DV, Mitra S, et al: Splenoma with portal hypertension. Br Med J 1:520, 1975 3. Berge TH: Splenoma. Acta Pathol Microbiol Scand 63:333-339, 1965 4. Coe JI, von Drashek S: Hamartoma of the spleen. A report of four cases. Am J Pathol 28:663-671, 1952 5. Darden JW, Teeslink R, Parrish RA: Hamartoma of the spleen, a manifestation of tuberous sclerosis. Am Surg 41:564-566, 1975 6. Dorland's Illustrated Medical Dictionary, Philadelphia, W. B. Saunders, 1974 7. Farrer-Brown G, Bennett MH, Harrison CV, et al: The diagnosis of Hodgkin's disease in surgically excised spleens. J Clin Pathol 25:294-300, 1972
8. Fisher H: Splenomegalie infolge multipler pulposer splenome. Deutsche Z Chirurg 248:552-562, 1936 9. Glatstein E, Guernsey JM, Rosenberg SA, et al: The value of laparotomy and splenectomy in the staging of Hodgkin's disease. Cancer 24:709-718, 1969 10. Graham JC, Weidner WA, Vinik M: The angiographic features of organizing splenic hematoma. Am J Roentgenol 107:430433, 1969 11. Gupta PCS: Hamartoma of the spleen. J Indian Med Assoc 41:610, 1963 12. Hardmeier T: Hypersplenismus bei einem hamartom de milz. Schweiz Med Wochenschr 92:1270-1274, 1962 13. Henke F, Lubarsch O: Handbuch der speziellan pathologischen anatomie und histologic I, Part 2. Berlin, Julius Springer. 1927, pp 695-697 14. Kirkland WG, McDonald J: Hamartoma of the spleen, report of three surgical cases. Arch Pathol 45:371-379, 1948 15. Komaki S, Gombas OF: Angiographic demonstration of a calcified splenic hamartoma. Radiology 121:77-81, 1976 16. Loffler H: Cytochemischer Nachweis von unspezifischer esterase in ausstrichen beitrage zur technik und ergebnisse in blutausstrich des menschen. Klin Wochenschr 39:1220-1227, 1961 17. MacPherson AIS, Richmond J, Stuart AE: The Spleen. Springfield, 111., Charles C Thomas, 1973 18. Mordasini E: Uber Splenome (Hamartome) der milz. Virchows Arch Pathol Anat 298:594-615, 1936 19. Nanba K, Soban EJ, Bowling MC, et al: Splenic pseudosinuses and hepatic angiomatous lesions. Am J Clin Pathol 67:415426, 1977 20. Raper, AB: Fibrotic nodules of the spleen. J Pathol Bacteriol 78:1-16, 1959 21. Rokitansky K: Uber splenome. Lehrbuch der Pathol Anat Bd 3, 1861 22. Ross CF, Schiller KFR: Hamartoma of the spleen associated with thrombocytopenia. J Pathol 105:62-64, 1971 23. Schrijver H, Verdonk GJ: Hamartoma of the spleen with inhibition of the bone marrow. Acta Med Scand 143:235-237, 1957 24. Sweet RH, Warren S: Hamartoma of the spleen, report of a case. N Engl J Med 226:757-758, 1942 25. Teates CD, Seale DL, Allen MS: Hamartoma of the spleen. Am J Roentgenol 116:419-422, 1972 26. Van Heerden JA, Longo MF, Cardona F, et al: The abdominal mass in the patient with tuberous sclerosis. Arch Surg 95:317-319, 1967 27. Vere Nicoll JA: Splenic haematoma after spontaneous rupture of the spleen. Am J Surg 116:117-119, 1968 28. Videbaek A: Hypersplenism associated with hamartomas of the spleen. Acta Med Scand 141:275-288, 1953 29. Wallach JB, Nakao N: Hamartoma of the spleen. J Med Soc NJ 59:75-79, 1962 30. Wexler L, Abrams HI: Hamartoma of the spleen: Angiographic observations. Am J Roentgenol 92:1150-1155, 1964
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the cases in this report are of particular interest in this regard. Both splenic hamartomas were incidental findings in patients with Hodgkin's disease undergoing staging procedures. In view of the low-power impression of an almost granulomatous nature, as well as the finding of lymphocytes and occasional eosinophils, the differential diagnosis of splenic involvement by Hodgkin's disease was entertained by some observers. The features that distinguish the hamartoma from Hodgkin's disease include the intrinsically vascular nature of the lesions, which can be appreciated on careful examination; the compression of the surrounding splenic parenchyma rather than replacement of splenic cords by tumor; the lack of a truly characteristic Hodgkin's infiltrate; and the absence of Reed-Sternberg cells or their variants. Hence, we believe the benign splenic lesion that we are describing can be differentiated from Hodgkin's disease by careful microscopic study. The lesions we are describing are found infrequently. We recognized three cases in our surgical pathology files, covering 17 years and encompassing almost 200,000 specimens. Two other examples were identified from among 1,500 autopsy cases. However, although it is rare, recognition of this splenic lesion is important for the modern surgical pathologist.
