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:

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

23/243, 5/2716, 15/2021, 27/2922

 

 0/113

 

High MW cytokeratin

10/181, 12/1617, 14/2019

14/181 

0/1810/519

27/181 

AE1/AE3

85% (8/181, 4/243, 15/193, 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

8/181, 3/243, 0/64, 6/77, 7/88 , 4/414, 12/2715, 9/1417, 5/56, 22/2716, 8/2019, 4/1022

14/181, 5/56

 

0/2810/519

28/281

EMA

10/2322

 

 

 

CK5

9/181, 14/2019

14/181

0/281, 0/519

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

18/2019

 

0/519

 

14-3-3s

11/2019

 

0/519

 

Maspin

9/2019

 

0/519

 

Calponin

4/2019

 

0/519 

 

Desmin

1/1522

 

 

 

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

1/15918

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

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 nodes21,22. 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