Metaplastic (sarcomatoid) carcinoma and the differential diagnosis of spindle cell tumours of the breast

Synonyms

Carcinosarcoma, sarcomatoid carcinoma, (low-grade fibromatosis-like) spindle cell carcinoma, carcinoma with pseudosarcomatous metaplasia, matrix-producing carcinoma.

Histopathology

Metaplastic carcinomas may be biphasic or purely composed of non-glandular elements. Most cases consist of spindle cells with or without a squamous component. The atypical cells form ill-defined fascicles, separated by variable amounts of densely collagenous stroma. The degree of anaplasia is highly variable, from fibromatosis-like lesions to high grade sarcoma. The presence of an in-situ or invasive ductal or lobular carcinomatous component is also variable. Three subtypes have been recognised:

• Pure spindle cell, sometimes growing around non-neoplastic ducts. This periductal growth is characteristic of low-grade spindle cell carcinomas²². There may be a mixed inflammatory cell infiltrate and osteoclast-like giant cells may be present²².

• Spindle cell with heterologous elements; rhabdomyosarcoma. chondrosarcoma or osteosarcoma²².

• Carcinosarcoma, with a high grade ductal carcinomatous component set in a sarcomatoid spindle cell background.

Variant: low-grade adenosquamous carcinoma is a variant of metaplastic carcinoma²⁰. There are solid cords and hollow tubules within a desmoplastic stroma resembling fibromatosis. There is usually focal squamous differentiation. The tumours are locally invasive but metastases to axillary lymph nodes are rare.

Immunohistochemistry and differential diagnosis

In normal breast, strong CD34 staining is seen in perilobular stroma and, to a lesser extend, in interlobular stroma². Lymphocytes, normal epithelium and occasional perilobular spindle cells are positive for bcl-2.

Negativity for cytokeratins and positivity for markers of myoepithelial differentiation (SMA and S100) in metaplastic carcinoma of the breast may be misleading. Positivity for CD34 and bcl-2 in phyllodes tumors may be helpful in distinguishing them from metaplastic spindle cell carcinoma.

Low-grade (fibromatosis-like) spindle cell tumour of the breast has a somewhat different range of differentials.

	metaplastic carcinoma		phyllodes tumour
	spindle cells	epithelial / myoepithelial cells	spindle cells	epithelial / myoepithelial cells
Wide spectrum screening keratin	23/24 (polyclonal, Dako, Moll numbers 4, 5,6,8,14,16)3, 5/27 (smaller range of keratins than for reference 3)16, 15/20 (using a panel of AE1/AE3, Cam5.2, CK8 and CK18. all 8 pure spindle cell tumours were positive, ranging between 10% and 100% of the tumour cells. Of 9 cases with a small invasive carcinomatous component, 6 were positive, ranging from 10% to 95% of tumour cells. 1 of 3 cases with DCIS but no invasive carcinomatous component was positive).21, 27/2922		0/113
High MW cytokeratin	10/18(34bE12)1, 12/1617, 14/20(34bE12)19	14/18(34bE12)1	0/18(34bE12)1, 0/5 (34bE12)19	27/18(34bE12)1
AE1/AE3	85% (8/181, 4/24 (with protease antigen retrieval)3, 15/19 (with steam EDTA antigen retrieval)3, 0/64, 0/25, 7/88, 1/19, 11/1310, 1/111, 59/6012, 10/1613 , 4/414, 23/2716, 10/1117), 7/1722	13/181	1/281	28/281
MNF116	17/2019		0/519
Low MW cytokeratins	8/18 (Cam5.2)1, 3/24 (Cam5.2)3, 0/6 (Cam5.2)4, 6/7 (Cam5.2)7, 7/8 (Cam5.2)8 , 4/4 (Cam5.2)14, 12/27 (Cam5.2)15, 9/14 (Cam5.2)17, 5/5 (CK8 & 18)6, 22/27 (CK8 & 18)16, 8/20 (5D3)19, 4/10 (Cam5.2)22	14/18 (Cam5.2)1, 5/5 (CK8 & 18)6	0/28 (Cam5.2)1, 0/5 (5D3)19	28/28 (Cam5.2)1
EMA	10/2322
CK5	9/181, 14/20(CK5/6)19	14/181	0/281, 0/5(CK5/6)19	28/281
CK7	9/181, 5/1117	14/181	0/281	28/281
CK14	9/181, 13/2019, 9/1022	13/181	0/281, 0/519	28/281
CK17	14/2019		0/519
CK19	4/181	12/181	0/281	28/281
EMA	35% (7/213, 0/77, 7/88, 11/1310, 11/4812, 4/1213, 8/2615, 7/2716, 4/817)	3/77
S100	10/181, 1/111, 4/64, 9/2019, 1/2322	8/181, 4/64	2/281, 0/519	28/281
SMA	13/181, 12/2019, 15/2122	3/181	19/281, 0/519	25/281
CD10	16/2019		1/519
positive for at least two of SMA, CD10, p63	16/2019
CD29	18/20 (staining was predominantly membrane)19		0/519
14-3-3s	11/20 (staining was predominantly cytoplasmic)19		0/519
Maspin	9/2019		0/519
Calponin	4/2019		0/519
Desmin	1/15 (positivity was within a heterologous rhabdomyosarcomatous component)22
GFAP	1/2019, 0/2122		0/519
SM-M	1/2019		0/519
CD34	0/181, 0/112	0/181	27/281, patchy (26 cases, median 75% of spindle cells staining. Staining is less in malignant cases)2	0/281
bcl-2	1/181, negative (11 cases)2	7/181	12/281, positive (26 cases)2	25/281, positive in minority of spindle cells (26 cases)2
mCEA	0/64	0/64
Vimentin	21/243, 1/111, 4/64, 7/77, 19/2019	2/64	5/519
p63	12/2122

	fibroadenoma	myofibroblastoma	pseudoangiomatous hyperplasia	myoid hamartoma
CD34	positive in 100% of spindle cells in most of 15 cases2	positive in a median of 75% in 2 cases	uniformly positive (5 cases)	positive in 10% of spindle cells (1 case)
bcl-2	positive in spindle cells and epithelium(15 cases)2

	p63 shows a high degree of sensitivity and specificity for metaplastic carcinoma
	metaplastic carcinoma	spindle cell	10/1018, 14/2019
		squamous cell	2/218
		chondroid	1/318
	invasive non-metaplastic carcinoma	invasive ductal carcinoma	1/159 (one case showed positivity, but in only 10% of cells)18
		invasive lobular carcinoma	0/1018
		mixed ductal and lobular carcinoma	0/518
	Phyllodes tumour	benign	0/418
		malignant	0/618, 1/519
	Primary sarcomas	fibrosarcoma	0/118
		liposarcoma	0/218
		osteosarcoma	0/118
		high-grade NOS	0/118

Differential diagnosis

• Phyllodes tumour with stromal overgrowth or sarcoma arising in a phyllodes tumour. Phyllodes tumours are positive for CD34.

• Spindle cell carcinoma: fibromatosis, myofibroblastic tumours, pseudoangiomatous stromal hyperplasia, nodular fasciitis. Spindle cell carcinomas are positive for cytokeratins.

• Low-grade adenosquamous carcinoma: nipple adenoma (if near the nipple): tubular structures entrapped in a radial scar.

• Myoepithelial carcinoma: a more aggressive tumour: requires electron microscopy, which shows pinocytotic vesicles and microfilaments²¹.

Prognosis

Those tumours which lack or have a minimal invasive overtly epithelial component may behave more like sarcomas, showing local recurrence and metastasizing to lung rather than to lymph nodes^21,22. These are reportedly aggressive tumours²².

References

¹ Dunne BM, Lee AHS, Pinder SE, Bell J, Ellis IO. An immunohistochemical study of spindle cell tumours of breast. Pathological Society, July 2002, abstract no 120.

² T Moore and AHS Lee. Expression of CD34 and bcl-2 in phyllodes tumours, fibroadenomas and spindle cell lesion of the breast. Histopathology 2001; 38: 62-67.

³ Adem, C., Reynolds, C., Adlakha, H., Roche, P.C. and Nascimento, A.G. Wide spectrum screening keratin as a marker of metaplastic spindle cell carcinoma of the breast: an immunohistochemical study of 24 patients. Histopathology 2002;40:556-62.

⁴ Meis, J.M., Ordonez, N.G. and Gallager, H.S. Sarcomatoid carcinoma of the breast: an immunohistochemical study of six cases. Virchows Arch A Pathol Anat Histopathol 1987;410:415-21.

⁵ Oberman, H.A. Metaplastic carcinoma of the breast. A clinicopathologic study of 29 patients. Am J Surg Pathol 1987;11:918-29.

⁶ Santini, D., Bazzocchi, F., Paladini, G., Gelli, M.C., Ricci, M., Mazzoleni, G. and Martinelli, G. Intermediate-sized filament proteins (keratin, vimentin, desmin) in metaplastic carcinomas, carcinosarcomas and stromal sarcomas of the breast. Int J Biol Markers 1987;2:83-6.

⁷ Ellis, I.O., Bell, J., Ronan, J.E., Elston, C.W. and Blamey, R.W. Immunocytochemical investigation of intermediate filament proteins and epithelial membrane antigen in spindle cell tumours of the breast. J Pathol 1988;154:157-65.

⁸ Merino MJ et al. Spindle-cell carcinoma of the breast: a clinicopathologic, ultrastructural and immunohistochemical study of eight cases. Surg Pathol 1988;1:193-201.

⁹ Santeusanio, G., Pascal, R.R., Bisceglia, M., Costantino, A.M. and Bosman, C. Metaplastic breast carcinoma with epithelial phenotype of pseudosarcomatous components. Arch Pathol Lab Med 1988;112:82-5.

¹⁰ Wargotz, E.S. and Norris, H.J. Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma. Hum Pathol 1989;20:628-35.

¹¹ Raju, G.C. and Wee, A. Spindle cell carcinoma of the breast. Histopathology 1990;16:497-9.

¹² Wargotz, E.S., Deos, P.H. and Norris, H.J. Metaplastic carcinomas of the breast. II. Spindle cell carcinoma. Hum Pathol 1989;20:732-40.

¹³ Wargotz, E.S. and Norris, H.J. Metaplastic carcinomas of the breast: V. Metaplastic carcinoma with osteoclastic giant cells. Hum Pathol 1990;21:1142-50.

¹⁴ Goddard, M.J., Wilson, B. and Grant, J.W. Comparison of commercially available cytokeratin antibodies in normal and neoplastic adult epithelial and non-epithelial tissues. J Clin Pathol 1991;44:660-3.

¹⁵ Pitts, W.C., Rojas, V.A., Gaffey, M.J., Rouse, R.V., Esteban, J., Frierson, H.F., Kempson, R.L. and Weiss, L.M. Carcinomas with metaplasia and sarcomas of the breast. Am J Clin Pathol 1991;95:623-32.

¹⁶ Christensen, L., Schiodt, T. and Blichert-Toft, M. Sarcomatoid tumours of the breast in Denmark from 1977 to 1987. A clinicopathological and immunohistochemical study of 100 cases. Eur J Cancer 1993;13:1824-31.

¹⁷ Gobbi, H., Simpson, J.F., Borowsky, A., Jensen, R.A. and Page, D.L. Metaplastic breast tumors with a dominant fibromatosis-like phenotype have a high risk of local recurrence. Cancer 1999;85:2170-82.

¹⁸ Koker, M. M. and C. G. Kleer (2004). "p63 expression in breast cancer: a highly sensitive and specific marker of metaplastic carcinoma." Am J Surg Pathol 28(11): 1506-12.

¹⁹ Leibl S, Gogg-Kammerer M, Sommersacher A, et al. Metaplastic breast carcinomas: are they of myoepithelial differentiation?: immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial markers. Am J Surg Pathol 2005; 29:347-53

²⁰ Putti TC, Pinder SE, Elston CW, et al. Breast pathology practice: most common problems in a consultation service. Histopathology 2005; 47:445-57

²¹ Davis WG, Hennessy B, Babiera G, et al. Metaplastic sarcomatoid carcinoma of the breast with absent or minimal overt invasive carcinomatous component: a misnomer. Am J Surg Pathol 2005; 29:1456-63

²² Carter MR, Hornick JL, Lester S, et al. Spindle cell (sarcomatoid) carcinoma of the breast: a clinicopathologic and immunohistochemical analysis of 29 cases. Am J Surg Pathol 2006; 30:300-9

This page last revised 10.4.2006

©SMUHT/PW Bishop