Pulmonary sclerosing haemangioma, sclerosing pneumocytoma

Epidemiology

Sclerosing hemangioma is a rare pulmonary lesion. Originally thought to be a type of haemangioma, then of mesenchymal or neuroendocrine origin, it is now thought that it is probably derived from type II pneumocytes. The polygonal cells are accepted as neoplastic. The lining cells have variously been considered as neoplastic or as entrapped pneumocyte, but microdissection and clonality studies indicate that they are of the same clonality as the lining cells³. Conversely, it has been suggested that the surface cuboidal cells are reactive type II pneumocytes, while the polygonal cells are the true neoplastic cells, derived from multipotential respiratory epithelium⁴.

Clinical features

This is a tumour found in adults across a wide age range. There is a female predominance and patients are often Asian.

Radiology

There is often calcification.

Histopathology

This tumour forms a well-circumscribed but unencapsulated lesion composed of round cells with bland nuclei, interspersed with papillary and tubular structures lined by cuboidal surface cells. Four patterns have been described: papillary, sclerotic, solid and haemorrhagic: most tumours show a combination of at least three of these patterns but some only two³. Two populations of cells can be identified: bland polygonal/round cells with abundant pale cytoplasm growing in solid sheets and cuboidal cells lining the papillary structures. There is often calcification and/or ossification. Giant lamellar bodies may occur.

Variants

• Sclerosing haemangioma may form a combined tumour, for example with a carcinoid tumour³.

• Rarely, cystic degeneration occurs³.

Immunohistochemistry

	surface cells	polygonal/round cells
Pancytokeratin (AE1/AE3+CK1)	47/471	0/471
Pancytokeratin MNF116	16/162, 1/23	0/162, 0/33
Low molecular weight cytokeratin	>75% of cells positive (based on a study of 30 cases)4	negative (based on a study of 30 cases)4
High molecular weight cytokeratin	50-75% of cells positive (based on a study of 30 cases)4	<10% of cells positive (based on a study of 30 cases)4
Cam5.2	22/301	5/301
Keratin 903	0/261	0/261
Cytokeratin 7	32/321	10/321
Cytokeratin 20	0/271	0/271
EMA	44/44 (predominantly cytoplasmic)1, 16/16 (membranous and cytoplasmic)2, 2/23, 50-75% of cells positive (based on a study of 30 cases)4	41/44 (predominantly membranous)1, 16/16 (membranous and cytoplasmic)2, 3/33, <10% of cells positive (based on a study of 30 cases)4
Cytokeratin 5/6	0/181	0/181
Calretinin	0/181	0/181
Chromogranin A	0/37 (polyclonal)1, 0/16 (clone LK2H10)2, negative (based on a study of 30 cases)4	0/37 (polyclonal)1, 0/16 (clone LK2H10)2, <10% of cells positive (based on a study of 30 cases)4
Synaptophysin, polyclonal	0/351, 0/162, negative (based on a study of 30 cases)4	4/351, 0/162, variably <10-50% of cells positive (based on a study of 30 cases)4
NSE	negative (based on a study of 30 cases)4	variably 10-75% of cells positive (based on a study of 30 cases)4
ACTH	negative (based on a study of 30 cases)4	variably <10-75% of cells positive (based on a study of 30 cases)4
Leu-7	0/351	0/351
Prosurfactant-associated protein A	23/251, 16/162	0/251, 0/162
Prosurfactant-associated protein B	25/251, >75% of cells positive (based on a study of 30 cases)4	0/251, negative (based on a study of 30 cases)4
Clara cell protein	14/181	0/181
TTF-1	36/371, 16/162, 2/23, >75% of cells positive (based on a study of 30 cases)4	34/37 (somewhat weaker than the surface cells)1, 16/162, 3/33, >75% of cells positive (based on a study of 30 cases)4
Oestrogen receptor	0/281	2/28 (both positive cases were from women)1
Progesterone receptor	0/281	17/28 (15 of the positive cases were from women)1
SMA (the stromal cells of sclerotic areas are positive)	0/61, 0/23	0/61, 0/33
Desmin	0/23	0/33
Vimentin	2/71, 0/23, negative (based on a study of 30 cases)4	6/71, 2/33, 10-50% of cells positive (based on a study of 30 cases)4
CD34	0/23, negative (based on a study of 30 cases)4	0/33, negative (based on a study of 30 cases)4
CD56	0/23	0/33
CD68	negative (based on a study of 30 cases)4	negative (based on a study of 30 cases)4
S-100, polyclonal (scattered dendritic cells are positive)	0/41, 0/23	0/41, 0/33
CEA	2/7 (polyclonal)1, <10% of cells positive (based on a study of 30 cases)4	0/7 (polyclonal)1, negative (based on a study of 30 cases)4
Mast cell trypsin	negative (based on a study of 30 cases)4	negative (based on a study of 30 cases)4
Human growth hormone	negative (based on a study of 30 cases)4	<10% of cells positive (based on a study of 30 cases)4
Calcitonin	negative (based on a study of 30 cases)4	negative (based on a study of 30 cases)4
Factor VIII, polyclonal	0/111	0/111

Immunoreactivity was considered positive if more than 10% of cells showed staining^1,2.

Ultrastructure

Surface cuboidal cells have short microvilli and cytoplasmic lamellar bodies⁴. Polygonal cells have sparse neuroendocrine granules and abundant microfilaments⁴.

Differential diagnosis

The combination of EMA positivity and cytokeratin negativity of the polygonal/round cells is helpful in distinguishing from other tumors.

Carcinoma, primary or metastatic.

• Mesothelioma

  Carcinoid tumour. Strong diffuse positivity for synaptophysin and chromogranin favours carcinoid. Negativity for TTF-1 is more likely in typical carcinoid. Carcinoid tumourlets have been reported adjacent to sclerosing haemangioma and a combined tumour has been reported³.

• If clear cells are prominent, metastatic renal cell carcinoma or primary clear cell ("sugar") tumour³.

• Rare cases may have a large number of foamy clear cells: there may be an overlap with alveolar adenoma³. Negativity of the stromal cells for TTF-1 would favour alveolar adenoma.

• In cystic cases, congenital cyst, vascular malformation or endothelial neoplasm³.

• Inflammatory pseudotumour / Inflammatory myofibroblastoma

• Pulmonary papillary adenoma

• Bronchoalveolar carcinoma

• Paraganglioma

Prognosis

These tumour are low-grade malignancies, but metastatic behaviour is rare³. Rare cases show nodal metastases of the polygonal cell component : the metastasis was TTF-1 positive, EMA positive, cytokeratin negative and apoprotein A negative².

References

¹M Devousassoux-Shisheboran et al. A clinicopathological study of 100 cases of pulmonary sclerosing hemangioma with immunohistochemical studies. Am J Surg Pathol 2000; 24: 906-916.

²Chan, A. C., Chan, J. K. Pulmonary sclerosing hemangioma consistently expresses thyroid transcription factor-1 (TTF-1): a new clue to its histogenesis Am J Surg Pathol 2000;24:1531-1536.

³Nicholson, A. G., C. Magkou, et al. (2002). "Unusual sclerosing haemangiomas and sclerosing haemangioma-like lesions, and the value of TTF-1 in making the diagnosis." Histopathology 41(5): 404-13.

³Niho, S., K. Suzuki, et al. (1998). "Monoclonality of both pale cells and cuboidal cells of sclerosing hemangioma of the lung." Am J Pathol 152(4): 1065-9.

⁴Wang, E., D. Lin, et al. (2004). "Immunohistochemical and ultrastructural markers suggest different origins for cuboidal and polygonal cells in pulmonary sclerosing hemangioma." Hum Pathol 35(4): 503-8.

This page last revised 1.5.2004.