Pulmonary sclerosing haemangioma, sclerosing pneumocytoma

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 cells7. 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 predominance10 and patients are often East Asian5. Presentation is often incidental but may be with a cough5.

Radiology

There is often calcification. Tumours show hypermetabolism on (18)F-fluorodeoxyglucose positron emission tomography ("PET scan")6.

Macroscopic appearance

Rarely, pulmonary sclerosing hemangioma may present as an endobronchial polyp11.

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 , 11/115, 15/1510	0/162, 0/33 , 1/115, 0/1510
Pancytokeratin	1/1(a case with lymph node metastases)9	0/1(a case with lymph node metastases)9
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, 2/78
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 , 11/115, 9/98, 1/1(a case with lymph node metastases)9, 15/1510	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 , 10/115, 9/98, 1/1(a case with lymph node metastases)9, 15/1510
MUC1	15/1510	15/1510
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, 0/1(a case with lymph node metastases)9	0/37(polyclonal)1, 0/16(clone LK2H10)2 , <10% of cells positive(based on a study of 30 cases)4, 0/1(a case with lymph node metastases)9
Synaptophysin, polyclonal	0/351, 0/162 , negative(based on a study of 30 cases)4, 0/1(a case with lymph node metastases)9, 0/1510	4/351, 0/162 , variably <10-50% of cells positive(based on a study of 30 cases)4, 0/1(a case with lymph node metastases)9, 0/1510
NSE	negative(based on a study of 30 cases)4, 0/1(a case with lymph node metastases)9	variably 10-75% of cells positive(based on a study of 30 cases)4, 0/1(a case with lymph node metastases)9
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
PE-10 (surfactant)	8/88	5/88
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 , 11/115, 9/98, 1/1(a case with lymph node metastases)9, 15/1510	34/371, 16/162, 3/33, >75% of cells positive(based on a study of 30 cases)4 , 11/115, 9/98, 1/1(a case with lymph node metastases)9, 15/1510
EGFR	7/75	6/75
Oestrogen receptor	0/281, 0/1(a case with lymph node metastases)9, 0/1510	2/28(both positive cases were from women)1, 0/1(a case with lymph node metastases)9, 0/1510
Progesterone receptor	0/281 , 1/1(a case with lymph node metastases)9, 0/1510	17/281 , 1/1(a case with lymph node metastases)9, 0/1510
HER2	0/75	0/75
SMA (the stromal cells of sclerotic areas are positive)	0/61, 0/23, 0/1(a case with lymph node metastases)9	0/61, 0/33, 0/1(a case with lymph node metastases)9
Desmin	0/23, 0/1(a case with lymph node metastases)9	0/33, 0/1(a case with lymph node metastases)9
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 , 1/1(a case with lymph node metastases)9
CD31	0/98	0/98
CD34	0/23, negative(based on a study of 30 cases)4	0/33, negative(based on a study of 30 cases)4
CD44v6	15/1510	0/1510
CD56	0/23, 0/1510	0/33, 0/1510
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, 0/1(a case with lymph node metastases)9	0/41, 0/33, 0/1(a case with lymph node metastases)9
CEA	2/7(polyclonal)1, <10% of cells positive(based on a study of 30 cases)4, 0/1(a case with lymph node metastases)9	0/7(polyclonal)1, negative(based on a study of 30 cases)4, 0/1(a case with lymph node metastases)9
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
Thomsen-Freidenreich antigen	11/1510	0/1510
Factor VIII, polyclonal	0/111	0/111

Immunoreactivity was considered positive if more than 10% of cells showed staining1,2.

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 rare3,9. Rare cases show nodal metastases of the polygonal cell component2.

References

1 M 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.

2 Chan, 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.

3 Nicholson, 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.

4 Wang, 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.

5 Sartori G, Bettelli S, Schirosi L, et al. Microsatellite and EGFR, HER2 and K-RAS analyses in sclerosing hemangioma of the lung. Am J Surg Pathol 2007; 31:1512-20

6 Neuman J, Rosioreanu A, Schuss A, et al. Radiology-pathology conference: sclerosing hemangioma of the lung. Clin Imaging 2006; 30:409-12

7 Niho, 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. FULL TEXT

8 Illei PB, Rosai J,Klimstra DS Expression of thyroid transcription factor-1 and other markers in sclerosing hemangioma of the lung. Arch Pathol Lab Med 2001; 125:1335-9

9 Kim KH, Sul HJ,Kang DY Sclerosing hemangioma with lymph node metastasis. Yonsei Med J 2003; 44:150-4 FULL TEXT

10 Yoo SH, Jung KC, Kim JH, et al. Expression patterns of markers for type II pneumocytes in pulmonary sclerosing hemangiomas and fetal lung tissues. Arch Pathol Lab Med 2005; 129:915-9 FULL TEXT

11 Devouassoux-Shisheboran M, de la Fouchardiere A, Thivolet-Bejui F, et al. Endobronchial variant of sclerosing hemangioma of the lung: histological and cytological features on endobronchial material. Mod Pathol 2004; 17:252-7

This page last revised 19.11.2008.