Sclerosing Hemangioma of the Lung: Radiographic and Pathological Study Kenji Sugio, MD, Hideki Yokoyama, MD, Satoshi Kaneko, MD, Teruyoshi Ishida, MD, and Keizo Sugimachi, MD Department of Surgery 11, Faculty of Medicine, Kyushu University, Fukuoka, Japan
The clinical, radiographic, and pathological features of 10 patients with sclerosing hemangioma of the lung seen between 1974 and 1990 were reviewed. The incidence of sclerosing hemangioma was 22.2% of benign tumors surgically resected during that time. There were 2 male and 8 female patients aged 15 to 77 years at operation, and 9 patients were asymptomatic. All 10 patients had a solitary tumor with a well-defined homogeneous round or oval shadow on chest roentgenograms. Chest computed tomography revealed a homogeneous soft-density mass in 4 patients and a low-density portion within the tumor because of a cystic change in 1 patient. Microscop-
ically, 5 patients had a preponderantly solid pattern, 3 had a preponderantly papillary pattern, and 1 patient had a preponderantly sclerotic pattern. One patient had an equal mixture of solid and papillary patterns. Nine of the 10 tumors consisted of a mixture of at least three of the four major patterns. Regarding treatment, thoracotomy is indicated for a definite diagnosis. If a benign tumor is suspected at operation, an intraoperative frozen section is recommended. Once the diagnosis has been established as sclerosing hemangioma, a limited resection is indicated. (Ann Thorac Surg 1992;53:295-300)
S
medical records and the findings of the radiological and histological examinations were also reviewed.
clerosing hemangioma, first described by Liebow and Hubbell [l]in 1956, is a rare benign lung tumor. It is characterized microscopically by four major histological patterns-solid, papillary, sclerotic, and hemangiomatous-in varying The histogenesis of the . _ proportions. _ tumor is still unknown, although many investigators [2-81 have studied its origin using either an electron microscope or immunohistochemical methods. Clinically, the tumor shows a striking preponderance in middle-aged women, and in almost all patients with sclerosing hemangioma, the chest roentgenogram reveals a coin lesion that has a well-defined homogeneous margin and is considered to be benign. However, it is difficult to make a definite diagnosis preoperatively . We present the radiographic features in relation to the pathological findings in 10 patients with surgically resected sclerosing hemangioma of the lung, emphasizing the diagnosis and treatment of the disease.
Material and Methods During the period 1974 to 1990, 919 patients underwent surgical treatment of lung tumors at the Department of Surgery II, Faculty of Medicine, Kyushu University. Of these patients, 874 had malignant neoplasms (750 primary and 124 metastatic), and 45 had benign tumors or tumorlike lesions. There were 10 patients (22.2%)with sclerosing hemangioma among the 45 with benign tumors; the other 35 had hamartoma (n = 22), inflammatory pseudotumor (n = 9), and other benign tumors (n = 4). Their Accepted for publication Aug 13, 1991. Address reprint requests to Dr Sugio, Department of Surgery 11, Faculty of Medicine, Kyushu University, Higashi-ku, Fukuoka 812, Japan.
0 1992 by The Society of Thoracic Surgeons
Results Clinical Features There were 2 male and 8 female patients with sclerosing hemangioma. They ranged from 15 to 77 years of age (average age, 42.0 years) at the time of operation, and more were in the fourth decade of life than any other. The clinical data are summarized in Table 1. Of the 10 patients, 9 were asymptomatic. In 7 of these 9 patients, the tumor was discovered on routine chest roentgenograms and in 2, on chest roentgenograms during follow-up for other diseases. Only 1 patient had symptoms. This patient had been asymptomatic when the tumor was incidentally detected on chest roentgenogram. It was diagnosed as pulmonary tuberculosis and treated. The tumor had grown somewhat when a bout of cough and blood-tinged sputum occurred 12 years later. The period from detection of the tumor to operation ranged from 2 months to 12 years in these patients.
Radiographic Manifestations All of the patients had a solitary tumor (Fig 1). It was located in the right upper lobe in 1 patient, the right middle lobe in 2 patients, the left upper lobe in 3 patients, and the left lower lobe in 4 patients. The greatest diameter of the tumor on the chest roentgenogram ranged from 13 to 82 mm; in 7 patients, it was less than 30 mm in diameter. The tumor doubling time in 2 representative patients was 660 days (patient 3) and 1,250 days (patient 7). The plain chest roentgenograms showed a well0003-4975/92/$5.00
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SUGIO ET AL SCLEROSING HEMANGIOMA OF LUNG
Table 1. Clinical Data on Patients With Sclerosing Hemangioma of the Lung Patient No.
Age (Y)
Sex
Symptoms
2 3 4 5
54 38 77 45 34
F F M F F
6 7 8 9 10
15 31 45 30 51
F M F F F
None None None None Cough, bloodtinged sputum None None None None None
1
a
Time from Detection to Opera tion
Location
3 mo ly3mo 3y7mo 6y2mo 12 Y
LLL (S9) RML (S4) LLL (S6) RUL (S3) LUL (S3)
28 40 82 23 25
RML (9) LLL (S9) LUL (S4) LUL (S4) LLL (S10)
23 X 36 X 13 X 24 X 18 x
3Y 7Y lylmo
3Y 2 mo
Size" (mm) x 27 x 35 X
77
x 23 x 25
20 28 12 21 18
Operation Lobectomy Lobectomy Lobectomy Lobectomy Enucleation Partial resection Lobectomy Partial resection Lobectomy Lobectomy
This refers to the size of the tumor on plain chest roentgenogram.
LLL = left lower lobe;
LUL
=
left upper lobe;
Rh4L = right middle lobe;
defined, homogeneous round or oval shadow in all patients. Chest computed tomography was performed in 5 patients (patients 6 through 10) who had surgical resection after 1982 (Fig 2). Four had a homogeneous soft-density shadow with a smooth surface, and 1 showed a slightly irregular surface and a radiolucent portion within the
RUL
=
right upper lobe;
S = bronchial segment.
tumor because of a cystic change, confirmed in the resected specimen.
Preoperative Diagnosis In only 1 patient (patient 10) was sclerosing hemangioma suggested by a bronchoscopic brushing cytological examination, which revealed that the tumor cells had fine
Fig 1 . Tomogram of the left chest in (A) patient 7 and ( B ) patient 10 revealed a solitary homogeneous lesion with a well-defined margin.
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297
Fig 2 . (A) (Patient 7.) Computed tomogram demonstrated a radiolucent lesion within the tumor, and an irregular margin was noted. ( B ) (Patient 10.)Computed tornogram revealed a homogeneous round mass adjacent to the artery.
granular hemosiderin in the cytoplasm and no atypical changes (Fig 3). Radiographic imaging indicated that nine tumors were benign.
Operative Findings An intraoperative frozen section examination was performed on 3 patients (patients 6, 8, and 10) and led to a diagnosis of sclerosing hemangioma. An intraoperative cytological examination was performed on 3 patients (patients 5, 7, and 9). In 2 patients, no malignant cells were found, and in the other (patient 9), a carcinoid tumor was suspected. A lobectomy was performed in 7 patients because the tumor was located near the hilar region in 6 and was a suspected carcinoid tumor in 1. A partial resection was performed in 2 patients and enucleation, in 1 patient. None of the 10 patients has experienced recurrence during follow-up ranging from 1 year to 16 years for the 7 patients treated by lobectomy and from 3 to 14 years for the 3 treated by limited resection.
Fig 3. (Patient 10.) Bronchoscopic cytological examination showed no atypical changes and fine granular hemosiderin (arrow) in the cytoplasm.
Pathological Findings Microscopically, the histological features of sclerosing hemangioma varied, and four major histological patterns were found in the same histological section: solid, papillary, hemangiomatous, and sclerotic patterns (Table 2). Five patients had a preponderantly solid pattern, characterized by large nests and sheets of round cells (Fig 4A), and 4 of the 5 had a marked hemangiomatous or hemorrhagic pattern (Fig 48). Three patients had a preponderantly papillary pattern (Fig 4C), and 1 patient had a preponderantly sclerotic pattern, which was composed of loosely arranged spindle cells (Fig 4D). In only 1 patient was an equal mixture of solid and papillary patterns observed with sclerotic and hemorrhagic zones. Nine of the ten tumors contained a mixture of at least three of the four major patterns. Hemosiderin deposits were found in 6 patients, necrosis in 2, and a cystic change in 3.
Comment Benign tumors of the lung are much less common than malignant tumors; their incidence ranges from 1% to 5% of lung tumors [9, lo]. Tengan and colleagues [lo] reported that 15 of 48 benign tumors, excluding adenoma and inflammatory tumor, were sclerosing hemangiomas. The most common symptoms of patients with sclerosing hemangioma are cough, blood-tinged sputum, and chest pain, but 50% to 87% of patients in the literature [ 1 3 , 111 were asymptomatic. Sclerosing hemangioma is noted to have some clinical characteristics, such as female preponderance and occurrence mostly in the fifth decade [ 2 4 ] . In the review of the clinical features of 196 patients with sclerosing hemangioma in Japanese patients by Kimura and associates [ll],the average age was 46 years and the male to female ratio was 26:142. In our study, 80% of the patients were female, and 80% of the patients were in their fourth to sixth decade. The reason for the preponderance in women, however, remains unknown. Katzenstein and co-workers [2] reported that the lesions were present on chest roentgenograms from 1 year to 14
298
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Table 2. Pathological Findings in 10 Patients With Sclerosing Hernangioma of the Lung Patient
Size"
1 2 3 4
5
6 7 8
9 10 a
Solid
(mm)
No.
20 30 70 30 25 22 35
x 20 x 20 x 25 x 25 x 70 x 70
Marked Marked Scanty
20 X 20 x 20 X 30 X 10 x 20 x 9 x
Absent Scanty Marked
X
x X X
10 x 20 x 12x
20 20 15 30 10 20 9
Papillary
Sclerosis
Hemangiomatous
Scanty
Moderate
Scanty
Marked Marked
Marked
Absent
Scanty
Scanty Scanty Marked
Absent
Absent Absent Marked Marked Absent Marked
Marked
Absent
Marked Moderate
Absent Moderate
Scanty Scanty Moderate
Moderate Marked Moderate
Hemosiderin
Necrosis
cystic
Change
Moderate Marked Moderate Moderate
This is the size of the tumor in the resected specimen.
years before operation in 14 patients. In our study, the average age of the patients at the time of operation was 42.0 years, although the average age at first detection of the tumor was 38.6 years. Therefore, we assume that many patients with sclerosing hemangioma underwent various lengths of follow-up with periodic chest roentgenograms because the tumors were suggested radiographically to be benign or because the growth rate of the tumors was very slow. The tumor doubling time of sclerosing hemangioma in our representative patients was markedly longer than that of lung cancer, which has been reported to be about 5.5 months for adenocarcinoma and about 3 months for squamous cell carcinoma [12]. The greatest diameter of the lesion ranged from 0.4 to 8.0 cm in the reported cases, and about 90%of the lesions were less than 5.0 cm [13]. In our study, 70%of the lesions were less than 3.0 cm on chest roentgenograms. However, a smaller-sized tumor or a slow-growing tumor in itself does not exclude the possibility of malignant disease, as smaller-sized lung cancer tumors sometimes have no malignant findings radiographically. Toomes and colleagues [14] reported that a preoperative diagnosis of coin lesion of the lung, whether a benign or malignant tumor, could not be established in 32% of patients with a lesion smaller than 2 cm. Radiographic features of sclerosing hemangioma usually include a well-defined, homogeneous round or oval shadow, which is quite different from that of malignant tumors. A lesion with an ill-defined margin, spicular radiation, pleural indentation, or vascular convergence is normally considered to be malignant. Such findings are usually never demonstrated in sclerosing hemangioma. Therefore, the feature of an irregular margin is very important in the differential diagnosis. However, in rare cases, pleural indentation [lo] and spicular radiation [13] have been found. Sometimes a small radiolucent or radiopaque portion, which is due to a cystic formation or calcification, is observed in the tumor and is clearly demonstrated on the chest computed tomogram. We found three instances of cystic formation, but no instance
of calcification was observed. Katzenstein and associates [2] reported that 41% of sclerosing hemangiomas had calcification. In general, evidence of calcification in a tumor is a radiological assurance that it is benign. Bronchial arteriography is sometimes useful for diagnosing sclerosing hemangioma [101 by demonstrating a characteristic vascular network wrapped around the tumor. The surface of the tumor is hypervascular, but no definite tumor stain within the lesion is noted. Bronchoscopic cytological and pathological examinations are useful for malignant neoplasms. For benign tumors, however, great caution is needed to make a definite diagnosis when only these methods are used, because the absence of malignant cells does not always exclude malignant disease. Liebow and Hubbell [l], the first to describe sclerosing hemangioma, suggested this tumor was an endothelial proliferation, and some investigators [15,16] confirmed an endothelial origin by electron microscopic studies. Other studies have shown evidence of a mesothelial origin [17]. However, based on ultrastructural studies and recent immunohistochemical analysis, some investigators [3-8, 181 now consider this tumor to be primarily a proliferation of epithelial cells. The results of positive staining for epithelial membrane antigen and surfactant apoprotein, which are the markers of epithelial cells [4, 6, 71, and the results of negative staining for factor VIII-related antigens for endothelial cells [6, 81 suggest that the origin of sclerosing hemangioma might be type I1 pneumocytes. In spite of these studies, the exact histogenesis of sclerosing hemangioma remains uncertain. Sclerosing hemangioma should be recognized as a distinct clinicopathological entity. We need to consider sclerosing hemangioma as one of the differential diagnoses, especially when the patient is female and a relatively young adult with a well-defined, homogeneous round shadow on the chest roentgenogram. Thoracotomy
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299
Fig. 4 . Four major histological features in sclerosing hemangioma: (A) solid cellular pattern (patient lo), ( B ) hemangiomatous pattern (patient 8), (C) papillary pattern (patient 7); and (D)sclerotic pattern (patient 3). (Hematoqlin and eosin; x210 before 3% reduction.)
is indicated for a definite diagnosis because it is difficult to make a definite diagnosis preoperatively. If a benign tumor is suspected at operation, an intraoperative frozen
section is recommended. Once sclerosing hemangioma has been diagnosed, complete removal of the tumor by limited resection, if possible, should be performed.
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SUGIOETAL SCLEROSING HEMANGIOMA OF LUNG
We thank Dr Brian T. Quinn for critical comments.
References 1. Liebow AA, Hubbell DS. Sclerosing hemangioma (histiocytoma, xanthoma) of the lung. Cancer 1956;9:53-7. 2. Katzenstein A-LA, Gmelich JT, Camngton CB. Sclerosing hemangioma of the lung: a clinicopathologic study of 51 cases. Am J Surg Pathol 1980;4:343-56. 3. Chan K-W, Gibbs AR, Lo WS, Newman GR. Benign sclerosing pneumocytoma of lung (sclerosing haemangioma). Thorax 1982;3740&12. 4. Nagata N, Dairaku M, Sueishi K, Tanaka K. Sclerosing hemangioma of the lung: an epithelial tumor composed of immunohistochemically heterogenous cells. Am J Clin Pathol 1987;88:552-9. 5. Navas Palacios JJ, Escribano PM, Toledo J, Garzon A, Larru E, Palomera J. Sclerosing hemangioma of the lung: an ultrastructural study. Cancer 1979;44:949-55. 6. Haimoto H, Tsutsumi Y, Nagura H, Nakashima N, Watanabe K. Immunohistochemical study of so-called sclerosing haemangioma of the lung. Virchows Arch [Pathol Anat] 1985;407419-30. 7. Yousem SA, Wick MR, Singh G, et al. So-called sclerosing hemangiomas of lung: an immunohistochemical study supporting a respiratory epithelial origin. Am J Surg Pathol 1988;12:582-90. 8. Nagata N, Dairaku M, Ishida T, Sueishi K, Tanaka K. Sclerosing hemangioma of the lung: immunohistochemical
characterization of its origin as related to surfactant apoprotein. Cancer 1985;55:116-23. 9. Amgoni MG, Woolner LB, Bernatz PE, Miller WE, Fontana RS, Minn R. Benign tumors of the lung: a ten-year surgical experience. J Thorac Cardiovasc Surg 1970;60:589-99. 10. Tengan 1, Suemasu K, Eguchi K, et al. Benign tumors and tumor-like lesions (excluding adenomas) of the lung: radiological and clinicopathological analysis of 48 cases. Jpn J Clin Oncol 1981;11:343-52. 11. Kimura H, Kusajima Y, Konishi I, et al. A case of sclerosing hemangioma of the lung and review of 196 cases in the Japanese literature. J Jpn SOCClin Surg 1988;49:14034. 12. Geddes DM. The natural history of lung cancer: a review based on rates of tumor growth. Br J Dis Chest 1979;73:1-17. 13. Dail DH. Uncommon tumors. In: Dail DH, Hammer SP, eds. Pulmonary pathology. New York: Springer-Verlag, 1988: 879-89. 14. Toomes H, Delphendahl A, Manke H-G, Vogt-Moykopf I. The coin lesion of the lung: a review of 955 resected coin lesions. Cancer 1983;51:53&7. 15. Haas JE, Yunis EJ, Totten R. Ultrastructure of a sclerosing hemangioma of the lung. Cancer 1972;30:512-8. 16. Kay S, Still WJS, Borochovitz D. Sclerosing hemangioma of the lung: an endothelial or epithelial neoplasm? Hum Pathol 1977;8:~a74. 17. Katzenstein A-LA, Fulling K, Weise DL, Battifora H. Socalled sclerosing hemangioma of the lung: evidence for mesothelial origin. Am J Surg Pathol 1983;7:3-14. 18. Kennedy A. “Sclerosing haemangioma” of the lung: an alternative view of its development. J Clin Pathol 1973;26: 792-9.
INVITED COMMENTARY Pulmonary sclerosing hemangioma is an enigmatic neoplasm that has a characteristic clinical presentation as reflected in this report by Sugio and associates. The tumor typically is seen in middle-aged asymptomatic women as a solitary peripheral, well-circumscribed nodule, which may be partially calcified. By gross examination it is frequently hemorrhagic, and this observation led to the hypothesis by Leibow and Hubbell that these tumors were endothelial-derived. The evolution of our understanding since its description has been both clinical and pathogenetic. We now recognize that pulmonary sclerosing hemangioma may be seen as solitary or multiple nodules, that there may be malignant variants, and that the right middle lobe is not the sole site of occurrence. Immunohistochemical studies have also led to new conclusions: the proliferative cell is
probably not a mesenchymal cell, but rather a primitive respiratory epithelial cell showing cellular differentiation akin to the cells of the peripheral airways and alveolar septa. This is suggested by the expression of cytokeratin filaments, epithelial membrane antigen, and surfactant apoprotein. Consequently, pulmonary sclerosing hemangioma is currently believed to represent an epithelial proliferation-an alveolar pneumocytoma-that is usually clinically benign and surgically curative.
Samuel A . Yousem, M D Department of Pathology Presbyterian-University Hospital DeSoto at O‘Hara Streets Pittsburgh, PA 15213
The clinical, radiographic, and pathological features of 10 patients with sclerosing hemangioma of the lung seen between 1974 and 1990 were reviewed. The incidence of sclerosing hemangioma was 22.2% of benign tumors surgically resected during that time. There were 2 male and 8 female patients aged 15 to 77 years at operation, and 9 patients were asymptomatic. All 10 patients had a solitary tumor with a well-defined homogeneous round or oval shadow on chest roentgenograms. Chest computed tomography revealed a homogeneous soft-density mass in 4 patients and a low-density portion within the tumor because of a cystic change in 1 patient. Microscop-
ically, 5 patients had a preponderantly solid pattern, 3 had a preponderantly papillary pattern, and 1 patient had a preponderantly sclerotic pattern. One patient had an equal mixture of solid and papillary patterns. Nine of the 10 tumors consisted of a mixture of at least three of the four major patterns. Regarding treatment, thoracotomy is indicated for a definite diagnosis. If a benign tumor is suspected at operation, an intraoperative frozen section is recommended. Once the diagnosis has been established as sclerosing hemangioma, a limited resection is indicated. (Ann Thorac Surg 1992;53:295-300)
S
medical records and the findings of the radiological and histological examinations were also reviewed.
clerosing hemangioma, first described by Liebow and Hubbell [l]in 1956, is a rare benign lung tumor. It is characterized microscopically by four major histological patterns-solid, papillary, sclerotic, and hemangiomatous-in varying The histogenesis of the . _ proportions. _ tumor is still unknown, although many investigators [2-81 have studied its origin using either an electron microscope or immunohistochemical methods. Clinically, the tumor shows a striking preponderance in middle-aged women, and in almost all patients with sclerosing hemangioma, the chest roentgenogram reveals a coin lesion that has a well-defined homogeneous margin and is considered to be benign. However, it is difficult to make a definite diagnosis preoperatively . We present the radiographic features in relation to the pathological findings in 10 patients with surgically resected sclerosing hemangioma of the lung, emphasizing the diagnosis and treatment of the disease.
Material and Methods During the period 1974 to 1990, 919 patients underwent surgical treatment of lung tumors at the Department of Surgery II, Faculty of Medicine, Kyushu University. Of these patients, 874 had malignant neoplasms (750 primary and 124 metastatic), and 45 had benign tumors or tumorlike lesions. There were 10 patients (22.2%)with sclerosing hemangioma among the 45 with benign tumors; the other 35 had hamartoma (n = 22), inflammatory pseudotumor (n = 9), and other benign tumors (n = 4). Their Accepted for publication Aug 13, 1991. Address reprint requests to Dr Sugio, Department of Surgery 11, Faculty of Medicine, Kyushu University, Higashi-ku, Fukuoka 812, Japan.
0 1992 by The Society of Thoracic Surgeons
Results Clinical Features There were 2 male and 8 female patients with sclerosing hemangioma. They ranged from 15 to 77 years of age (average age, 42.0 years) at the time of operation, and more were in the fourth decade of life than any other. The clinical data are summarized in Table 1. Of the 10 patients, 9 were asymptomatic. In 7 of these 9 patients, the tumor was discovered on routine chest roentgenograms and in 2, on chest roentgenograms during follow-up for other diseases. Only 1 patient had symptoms. This patient had been asymptomatic when the tumor was incidentally detected on chest roentgenogram. It was diagnosed as pulmonary tuberculosis and treated. The tumor had grown somewhat when a bout of cough and blood-tinged sputum occurred 12 years later. The period from detection of the tumor to operation ranged from 2 months to 12 years in these patients.
Radiographic Manifestations All of the patients had a solitary tumor (Fig 1). It was located in the right upper lobe in 1 patient, the right middle lobe in 2 patients, the left upper lobe in 3 patients, and the left lower lobe in 4 patients. The greatest diameter of the tumor on the chest roentgenogram ranged from 13 to 82 mm; in 7 patients, it was less than 30 mm in diameter. The tumor doubling time in 2 representative patients was 660 days (patient 3) and 1,250 days (patient 7). The plain chest roentgenograms showed a well0003-4975/92/$5.00
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Table 1. Clinical Data on Patients With Sclerosing Hemangioma of the Lung Patient No.
Age (Y)
Sex
Symptoms
2 3 4 5
54 38 77 45 34
F F M F F
6 7 8 9 10
15 31 45 30 51
F M F F F
None None None None Cough, bloodtinged sputum None None None None None
1
a
Time from Detection to Opera tion
Location
3 mo ly3mo 3y7mo 6y2mo 12 Y
LLL (S9) RML (S4) LLL (S6) RUL (S3) LUL (S3)
28 40 82 23 25
RML (9) LLL (S9) LUL (S4) LUL (S4) LLL (S10)
23 X 36 X 13 X 24 X 18 x
3Y 7Y lylmo
3Y 2 mo
Size" (mm) x 27 x 35 X
77
x 23 x 25
20 28 12 21 18
Operation Lobectomy Lobectomy Lobectomy Lobectomy Enucleation Partial resection Lobectomy Partial resection Lobectomy Lobectomy
This refers to the size of the tumor on plain chest roentgenogram.
LLL = left lower lobe;
LUL
=
left upper lobe;
Rh4L = right middle lobe;
defined, homogeneous round or oval shadow in all patients. Chest computed tomography was performed in 5 patients (patients 6 through 10) who had surgical resection after 1982 (Fig 2). Four had a homogeneous soft-density shadow with a smooth surface, and 1 showed a slightly irregular surface and a radiolucent portion within the
RUL
=
right upper lobe;
S = bronchial segment.
tumor because of a cystic change, confirmed in the resected specimen.
Preoperative Diagnosis In only 1 patient (patient 10) was sclerosing hemangioma suggested by a bronchoscopic brushing cytological examination, which revealed that the tumor cells had fine
Fig 1 . Tomogram of the left chest in (A) patient 7 and ( B ) patient 10 revealed a solitary homogeneous lesion with a well-defined margin.
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297
Fig 2 . (A) (Patient 7.) Computed tomogram demonstrated a radiolucent lesion within the tumor, and an irregular margin was noted. ( B ) (Patient 10.)Computed tornogram revealed a homogeneous round mass adjacent to the artery.
granular hemosiderin in the cytoplasm and no atypical changes (Fig 3). Radiographic imaging indicated that nine tumors were benign.
Operative Findings An intraoperative frozen section examination was performed on 3 patients (patients 6, 8, and 10) and led to a diagnosis of sclerosing hemangioma. An intraoperative cytological examination was performed on 3 patients (patients 5, 7, and 9). In 2 patients, no malignant cells were found, and in the other (patient 9), a carcinoid tumor was suspected. A lobectomy was performed in 7 patients because the tumor was located near the hilar region in 6 and was a suspected carcinoid tumor in 1. A partial resection was performed in 2 patients and enucleation, in 1 patient. None of the 10 patients has experienced recurrence during follow-up ranging from 1 year to 16 years for the 7 patients treated by lobectomy and from 3 to 14 years for the 3 treated by limited resection.
Fig 3. (Patient 10.) Bronchoscopic cytological examination showed no atypical changes and fine granular hemosiderin (arrow) in the cytoplasm.
Pathological Findings Microscopically, the histological features of sclerosing hemangioma varied, and four major histological patterns were found in the same histological section: solid, papillary, hemangiomatous, and sclerotic patterns (Table 2). Five patients had a preponderantly solid pattern, characterized by large nests and sheets of round cells (Fig 4A), and 4 of the 5 had a marked hemangiomatous or hemorrhagic pattern (Fig 48). Three patients had a preponderantly papillary pattern (Fig 4C), and 1 patient had a preponderantly sclerotic pattern, which was composed of loosely arranged spindle cells (Fig 4D). In only 1 patient was an equal mixture of solid and papillary patterns observed with sclerotic and hemorrhagic zones. Nine of the ten tumors contained a mixture of at least three of the four major patterns. Hemosiderin deposits were found in 6 patients, necrosis in 2, and a cystic change in 3.
Comment Benign tumors of the lung are much less common than malignant tumors; their incidence ranges from 1% to 5% of lung tumors [9, lo]. Tengan and colleagues [lo] reported that 15 of 48 benign tumors, excluding adenoma and inflammatory tumor, were sclerosing hemangiomas. The most common symptoms of patients with sclerosing hemangioma are cough, blood-tinged sputum, and chest pain, but 50% to 87% of patients in the literature [ 1 3 , 111 were asymptomatic. Sclerosing hemangioma is noted to have some clinical characteristics, such as female preponderance and occurrence mostly in the fifth decade [ 2 4 ] . In the review of the clinical features of 196 patients with sclerosing hemangioma in Japanese patients by Kimura and associates [ll],the average age was 46 years and the male to female ratio was 26:142. In our study, 80% of the patients were female, and 80% of the patients were in their fourth to sixth decade. The reason for the preponderance in women, however, remains unknown. Katzenstein and co-workers [2] reported that the lesions were present on chest roentgenograms from 1 year to 14
298
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Table 2. Pathological Findings in 10 Patients With Sclerosing Hernangioma of the Lung Patient
Size"
1 2 3 4
5
6 7 8
9 10 a
Solid
(mm)
No.
20 30 70 30 25 22 35
x 20 x 20 x 25 x 25 x 70 x 70
Marked Marked Scanty
20 X 20 x 20 X 30 X 10 x 20 x 9 x
Absent Scanty Marked
X
x X X
10 x 20 x 12x
20 20 15 30 10 20 9
Papillary
Sclerosis
Hemangiomatous
Scanty
Moderate
Scanty
Marked Marked
Marked
Absent
Scanty
Scanty Scanty Marked
Absent
Absent Absent Marked Marked Absent Marked
Marked
Absent
Marked Moderate
Absent Moderate
Scanty Scanty Moderate
Moderate Marked Moderate
Hemosiderin
Necrosis
cystic
Change
Moderate Marked Moderate Moderate
This is the size of the tumor in the resected specimen.
years before operation in 14 patients. In our study, the average age of the patients at the time of operation was 42.0 years, although the average age at first detection of the tumor was 38.6 years. Therefore, we assume that many patients with sclerosing hemangioma underwent various lengths of follow-up with periodic chest roentgenograms because the tumors were suggested radiographically to be benign or because the growth rate of the tumors was very slow. The tumor doubling time of sclerosing hemangioma in our representative patients was markedly longer than that of lung cancer, which has been reported to be about 5.5 months for adenocarcinoma and about 3 months for squamous cell carcinoma [12]. The greatest diameter of the lesion ranged from 0.4 to 8.0 cm in the reported cases, and about 90%of the lesions were less than 5.0 cm [13]. In our study, 70%of the lesions were less than 3.0 cm on chest roentgenograms. However, a smaller-sized tumor or a slow-growing tumor in itself does not exclude the possibility of malignant disease, as smaller-sized lung cancer tumors sometimes have no malignant findings radiographically. Toomes and colleagues [14] reported that a preoperative diagnosis of coin lesion of the lung, whether a benign or malignant tumor, could not be established in 32% of patients with a lesion smaller than 2 cm. Radiographic features of sclerosing hemangioma usually include a well-defined, homogeneous round or oval shadow, which is quite different from that of malignant tumors. A lesion with an ill-defined margin, spicular radiation, pleural indentation, or vascular convergence is normally considered to be malignant. Such findings are usually never demonstrated in sclerosing hemangioma. Therefore, the feature of an irregular margin is very important in the differential diagnosis. However, in rare cases, pleural indentation [lo] and spicular radiation [13] have been found. Sometimes a small radiolucent or radiopaque portion, which is due to a cystic formation or calcification, is observed in the tumor and is clearly demonstrated on the chest computed tomogram. We found three instances of cystic formation, but no instance
of calcification was observed. Katzenstein and associates [2] reported that 41% of sclerosing hemangiomas had calcification. In general, evidence of calcification in a tumor is a radiological assurance that it is benign. Bronchial arteriography is sometimes useful for diagnosing sclerosing hemangioma [101 by demonstrating a characteristic vascular network wrapped around the tumor. The surface of the tumor is hypervascular, but no definite tumor stain within the lesion is noted. Bronchoscopic cytological and pathological examinations are useful for malignant neoplasms. For benign tumors, however, great caution is needed to make a definite diagnosis when only these methods are used, because the absence of malignant cells does not always exclude malignant disease. Liebow and Hubbell [l], the first to describe sclerosing hemangioma, suggested this tumor was an endothelial proliferation, and some investigators [15,16] confirmed an endothelial origin by electron microscopic studies. Other studies have shown evidence of a mesothelial origin [17]. However, based on ultrastructural studies and recent immunohistochemical analysis, some investigators [3-8, 181 now consider this tumor to be primarily a proliferation of epithelial cells. The results of positive staining for epithelial membrane antigen and surfactant apoprotein, which are the markers of epithelial cells [4, 6, 71, and the results of negative staining for factor VIII-related antigens for endothelial cells [6, 81 suggest that the origin of sclerosing hemangioma might be type I1 pneumocytes. In spite of these studies, the exact histogenesis of sclerosing hemangioma remains uncertain. Sclerosing hemangioma should be recognized as a distinct clinicopathological entity. We need to consider sclerosing hemangioma as one of the differential diagnoses, especially when the patient is female and a relatively young adult with a well-defined, homogeneous round shadow on the chest roentgenogram. Thoracotomy
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Fig. 4 . Four major histological features in sclerosing hemangioma: (A) solid cellular pattern (patient lo), ( B ) hemangiomatous pattern (patient 8), (C) papillary pattern (patient 7); and (D)sclerotic pattern (patient 3). (Hematoqlin and eosin; x210 before 3% reduction.)
is indicated for a definite diagnosis because it is difficult to make a definite diagnosis preoperatively. If a benign tumor is suspected at operation, an intraoperative frozen
section is recommended. Once sclerosing hemangioma has been diagnosed, complete removal of the tumor by limited resection, if possible, should be performed.
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We thank Dr Brian T. Quinn for critical comments.
References 1. Liebow AA, Hubbell DS. Sclerosing hemangioma (histiocytoma, xanthoma) of the lung. Cancer 1956;9:53-7. 2. Katzenstein A-LA, Gmelich JT, Camngton CB. Sclerosing hemangioma of the lung: a clinicopathologic study of 51 cases. Am J Surg Pathol 1980;4:343-56. 3. Chan K-W, Gibbs AR, Lo WS, Newman GR. Benign sclerosing pneumocytoma of lung (sclerosing haemangioma). Thorax 1982;3740&12. 4. Nagata N, Dairaku M, Sueishi K, Tanaka K. Sclerosing hemangioma of the lung: an epithelial tumor composed of immunohistochemically heterogenous cells. Am J Clin Pathol 1987;88:552-9. 5. Navas Palacios JJ, Escribano PM, Toledo J, Garzon A, Larru E, Palomera J. Sclerosing hemangioma of the lung: an ultrastructural study. Cancer 1979;44:949-55. 6. Haimoto H, Tsutsumi Y, Nagura H, Nakashima N, Watanabe K. Immunohistochemical study of so-called sclerosing haemangioma of the lung. Virchows Arch [Pathol Anat] 1985;407419-30. 7. Yousem SA, Wick MR, Singh G, et al. So-called sclerosing hemangiomas of lung: an immunohistochemical study supporting a respiratory epithelial origin. Am J Surg Pathol 1988;12:582-90. 8. Nagata N, Dairaku M, Ishida T, Sueishi K, Tanaka K. Sclerosing hemangioma of the lung: immunohistochemical
characterization of its origin as related to surfactant apoprotein. Cancer 1985;55:116-23. 9. Amgoni MG, Woolner LB, Bernatz PE, Miller WE, Fontana RS, Minn R. Benign tumors of the lung: a ten-year surgical experience. J Thorac Cardiovasc Surg 1970;60:589-99. 10. Tengan 1, Suemasu K, Eguchi K, et al. Benign tumors and tumor-like lesions (excluding adenomas) of the lung: radiological and clinicopathological analysis of 48 cases. Jpn J Clin Oncol 1981;11:343-52. 11. Kimura H, Kusajima Y, Konishi I, et al. A case of sclerosing hemangioma of the lung and review of 196 cases in the Japanese literature. J Jpn SOCClin Surg 1988;49:14034. 12. Geddes DM. The natural history of lung cancer: a review based on rates of tumor growth. Br J Dis Chest 1979;73:1-17. 13. Dail DH. Uncommon tumors. In: Dail DH, Hammer SP, eds. Pulmonary pathology. New York: Springer-Verlag, 1988: 879-89. 14. Toomes H, Delphendahl A, Manke H-G, Vogt-Moykopf I. The coin lesion of the lung: a review of 955 resected coin lesions. Cancer 1983;51:53&7. 15. Haas JE, Yunis EJ, Totten R. Ultrastructure of a sclerosing hemangioma of the lung. Cancer 1972;30:512-8. 16. Kay S, Still WJS, Borochovitz D. Sclerosing hemangioma of the lung: an endothelial or epithelial neoplasm? Hum Pathol 1977;8:~a74. 17. Katzenstein A-LA, Fulling K, Weise DL, Battifora H. Socalled sclerosing hemangioma of the lung: evidence for mesothelial origin. Am J Surg Pathol 1983;7:3-14. 18. Kennedy A. “Sclerosing haemangioma” of the lung: an alternative view of its development. J Clin Pathol 1973;26: 792-9.
INVITED COMMENTARY Pulmonary sclerosing hemangioma is an enigmatic neoplasm that has a characteristic clinical presentation as reflected in this report by Sugio and associates. The tumor typically is seen in middle-aged asymptomatic women as a solitary peripheral, well-circumscribed nodule, which may be partially calcified. By gross examination it is frequently hemorrhagic, and this observation led to the hypothesis by Leibow and Hubbell that these tumors were endothelial-derived. The evolution of our understanding since its description has been both clinical and pathogenetic. We now recognize that pulmonary sclerosing hemangioma may be seen as solitary or multiple nodules, that there may be malignant variants, and that the right middle lobe is not the sole site of occurrence. Immunohistochemical studies have also led to new conclusions: the proliferative cell is
probably not a mesenchymal cell, but rather a primitive respiratory epithelial cell showing cellular differentiation akin to the cells of the peripheral airways and alveolar septa. This is suggested by the expression of cytokeratin filaments, epithelial membrane antigen, and surfactant apoprotein. Consequently, pulmonary sclerosing hemangioma is currently believed to represent an epithelial proliferation-an alveolar pneumocytoma-that is usually clinically benign and surgically curative.
Samuel A . Yousem, M D Department of Pathology Presbyterian-University Hospital DeSoto at O‘Hara Streets Pittsburgh, PA 15213
