So-called "Sclerosing Hemangioma" Osamu Matsubara, M.D. National Defense Medical College Tokorozawa, Japan

Clinical History: The patient was a 67 years old Japanese woman with a history of sigmoidectomy for sigmoid colon cancer. Pathological examination revealed that sigmoid colon cancer was well differentiated adenocarcinoma with invasion into the subserosal layer. Two months later, a chest X-ray and CT scans of the thorax showed a coin lesion in the right lower lobe. She underwent tumorectomy by video-assisted thoracosurgery (VATS). The clinical diagnosis was metastatic lung cancer. Figure 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: So-called "Sclerosing Hemangioma" Gross and Microscopic Features: Grossly there was a 1.5 cm red to tan, round tumor mass situated in the peripheral lung parenchyma, deep to the pleural surface. Low power view shows a typically mixed solid, papillary, sclerotic and hemorrhagic architecture. On high power view the tumor comprises cuboidal lining cells, which resemble type II pneumocytes, and more round stromal cells that have either eosinophilic or clear cytoplasm. Immunohistochemical staining for thyroid transcription factor-1 (TTF-1) and epithelial membrane antigen (EMA) shows positivity in both the round cells and the cuboidal surface cells. Only the surface tumor cells stain for cytokeratin. Definition: A lung tumor with a distinctive constellation of histological findings including: solid, papillary, sclerotic, and hemorrhagic patterns. Hyperplastic type II pneumocytes line the surface of the papillary structures. Cholesterol clefts, chronic inflammation, xanthoma cells, hemosiderin, calcification, laminated scroll-like whorls, necrosis, and mature fat may be seen. Synonyms and related terms are "Pneumocytoma," "Papillary pneumocytoma," "Papillary adenoma," "Alveolar adenoma," "Clara cell adenoma." This lesion was first described by Liebow and Hubbell in 1956. The term "sclerosing hemangioma" was applied because of the cavernous spaces containing blood that resembled a cavernous hemangioma. Current consensus favors a benign or very low-grade neoplasm arising from primitive respiratory epithelium. Clinical Features: Sclerosing hemangioma predominantly affects middle-aged adults with a female predominance. More than 80% of patients with this disease are female. Most patients are asymptomatic (80%), but hemoptysis, cough, and thoracic pain may occur. Radiographically and grossly, the tumors appear as solitary, circumscribed mass which occasionally may be calcified and cystic. They measure 2-3 cm, although larger cases, up to 8 cm, have been reported. CT scans show a well-circumscribed mass with marked contrast enhancement and foci of sharply marginated low attenuation and calcification. Histopathology: The histological features of the current case has the typical microscopic features of so-called "sclerosing hemangioma" of the lung. Four different histological patterns are described including solid, papillary, sclerotic and hemorrhagic regions: Papillary pattern: complex papillae lined by cuboidal surface cells. The stalk of the papillary projections contains the round cells. It can be sclerotic or occasionally myxoid. Sclerotic pattern: dense foci of hyaline collagen at the periphery of the hemorrhagic areas, within papillary stalks, or within the solid areas. Solid pattern: sheets of round cells, with scattered cuboidal surface cells forming small tubules. The predominant cell type consists of sheets of round cells with relatively uniform nuclei and eosinophilic cytoplasm. Superimposed clear cell change may also be found in these regions. The nuclei display occasional folds and grooves, and mitotic activity is not seen. In other hand, the cuboidal surface cells lining the surface of the papillae contain abundant vacuolated, foamy cytoplasm and round nuclei that may have intranuclear inclusions. Hemorrhagic pattern: large blood-filled spaces lined by epithelial cells or foci of hemorrhage and debris containing hemosiderin deposits, foamy macrophages, and cholesterol clefts rarely surrounded by granulomatous and chronic inflammation. It is common for multiple patterns to exist, although not every example shows all four. On closer examination, there are two fundamental cell types making up sclerosing hemangiomas. In addition a variety of associated histological features may be observed including chronic inflammation, calcification, whorls, necrosis, and mature fat. Mast cells may be numerous. Immunohistochemjstry: Round cells express thyroid transcription factor-1 (TTF-1) and epithelial membrane antigen (EMA), but are pancytokeratin negative. Cuboidal surface cells express TTF-1, EMA, surfactant apoprotein A and pancytokeratin. Antibodies against TTF-1 have been used to demonstrate that both cell types are of pulmonary epithelial origin, while the stains for thyroglobulin are uniformly negative. EMA is also expressed by both cell types, although somewhat less intensely by the round cells. On the basis of the female predominance, studies have been done to find estrogen and progesterone receptors. Although progesterone receptor expression has been detected, estrogen receptor expression has been generally only focally and faintly stained by immunohistochemical examinations. Differential Diagnosis: The differential diagnosis includes clear cell tumors involving the lung (metastatic renal cell carcinoma, clear cell sugar tumors, and clear cell carcinomas of the lung), carcinoid tumors, papillary pulmonary epithelial neoplasms and inflammatory pseudotumors. Benign clear cell tumors differ from this tumor in that the tumor cells have clear, glycogen-rich cytoplasm and the delicate vascular spaces are thin-walled and sinusoidal. Sclerosing hemangiomas differ from papillary carcinomas by the presence of the distinct round cells within the papillary stalks as well as the characteristic solid, hemorrhagic or sclerotic patterns. Low-grade mucoepidermoid carcinomas differ from sclerosing hemangiomas in that an intimate admixture of mucinous and squamous epithelium. Intravascular sclerosing bronchoalveolar tumor (IVBAT) differs from this tumor by the relative circumscription of the lesion, the absence of alveolar filling by the cells at the periphery of the lesion, and the character of the cells themselves. Metastatic renal cell carcinoma may have tumor cells with clear cytoplasm which can resemble sclerosing hemangiomas; however renal cell carcinoma often shows malignant cytological features, and generally lacks the distinct various patterns seen in sclerosing hemangiomas. Sclerosing hemangiomas differ from carcinoid tumors in that they lack the organoid, trabecular, rosette, or spindle cell histological patterns and they do not have neuroendocrine features by immunohistochemtstry. Sclerosing hemangiomas differ from inflammatory pseudotumor which lacks the distinct epithelioid cells, papillary growth, and vascular spaces of sclerosing hemangiomas but consists primarily of a mass of inflammatory and fibrous tissue. Pulmonary nodules are frequently first diagnosed by frozen section, immediately followed by lobectomy or other procedures. The frozen section diagnosis of pulmonary nodules is sometimes very difficult, especially in case of this tumor. It should be noted that the mesenchymal element of this tumor is key to the diagnosis. Histogenesis: For many years the origin of sclerosing hemangioma has remained obscure with numerous studies supporting widely varied hypotheses including vascular, mesothelial, menchymal, epithelial, and neuroendocrine origins. Immunohistochemical findings have suggested that this peculiar tumor derives from primitive, undifferentiated respiratory epithelium. Molecular studies have demonstrated the same monoclonal pattern in both the round and surface cells. This also suggests sclerosing hemangioma is a true neoplasm rather than a hamartoma. Dacis et al. have reported an interesting result that loss of heterozygosity patterns of this tumor and bronchioloalveolar carcinoma indicates a similar molecular pathogenesis. Prognosis: Sclerosing hemangioma behaves in a clinically benign fashion. No recurrence or disease-related deaths have been reported. 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