Female 45 years presented with short history of mass in left breast UOQ which was lobulated on mammogram. The specimen contained a well defined mucoid looking tumour 1.1cm diameter abutting the inked margin.
ADENOID CYSTIC CARCINOMA
This tumour, uncommon in the breast, is similar to its counterpart in the salivary gland. However, in the breast it is associated with a good prognosis(1-3). On superficial examination the tumour can resemble cribriform carcinoma (either in situ or invasive), but a co-proliferation of two cell types, luminal epithelial and myoepithelial cells, can be discerned. Mucin stains show the large cystic spaces to contain hyaluronidase-sensitive alcian-blue-positive mucin, whereas the small, indistinct, true glandular spaces contain PAS-positive diastase-resistant mucin. Immunohistochemistry with antibodies to basement membrane components delineate the pseudocystic spaces and antibodies which label luminal and myoepithelial cells highlight the dual cell population(4,5). This tumour was oestrogen (ER) and progesterone (PR) receptor negative but some examples can be positive (3). The high nuclear grade and extensive necrosis seen in the symposium is unusual in these tumours.
References
1. Peters, G. N. and Wolff, M. Adenoid cystic carcinoma of the breast. Report of 11 new cases: review of the literature and discussion of biological behaviour, Cancer. 52: 680-686, 1983.
2. Friedman, B. A. and Oberman, H. A. Adenoid cystic carcinoma of the breast. Am J Clin Pathol. 54: 1-14, 1970.
3. Kleer, C. G. and Oberman, H. A. Adenoid cystic carcinoma of the breast, Am J Surg Pathol. 22: 569-575, 1998.
4. d'Ardenne, A. J., Kirkpatrick, P., Wells, C. A., and Davies, J. D. Laminin and fibronectin in adenoid cystic carcinoma, J Clin Pathol. 39: 138-144, 1986.
5. Rosen, P. P. Adenoid cystic carcinoma of the breast. A morphologically heterogeneous neoplasm. In: P. P. Rosen and R. E. Fechner (eds.), Pathology Annual, Vol. 24, pp. 237-254. Norwalk, Connecticut: Appleton and Lange, 1989.
63 year old presented with 6 month history of a breast mass, which on removal was 8 cm diameter and had a cut surface reminiscent of a fibroid.
METAPLASTIC OR SARCOMATOID CARCINOMA (PSEUDOSARCOMATOUS CARCINOMA)
Biphasic carcinomas showing extensive 'metaplastic' changes to squamous cells, spindle cells and heterologous mesenchymal elements are well recognised in the breast. In most of these tumours areas of conventional infiltrating ductal carcinoma, even though sometimes very small and focal, can be found, though that wasn't the case for the symposium example. Several methods of sub-classification have been recommended (1-8). There is considerable debate as to the prognosis of these tumours, some series showing a generally poor outcome with little variation between subgroups(2,8) and others claiming that sub-classification will delineate tumours with different prognoses(3-7) The syposium example best fits the subgroup termed "spindle cell carcinoma" in that it is composed predominantly of bipolar spindle cells of relatively bland appearance, with only mild to moderate atypia, arranged in interweaving bundles(4,9). Such tumours frequently also contain areas of squamous metaplasia. As in this case, these spindle cell tumors can be so bland that they mimic benign spindle cell proliferations such as fibromatosis(10). It is not surprising that immunohistochemistry is of value in the differential diagnosis; the pseudosarcomatous elements stain positively with vimentin and sometimes with other mesenchymal markers. It is nearly always possible to demonstrate epithelial markers in at least occasional cells(1,3-8) and the symposium case was positive for both CAM 5:2 and LP34. Mucin is not usually present, elastosis is rare. Reticulin stains show the characteristic "maze-like" pattern of carcinoma. Electron microscopy may confirm epithelial credentials of the cells(2,3) Metastases may contain carcinomatous or sarcomatous components. The incidence of lymph node metastases from these tumours is low with blood stream more common. Metaplastic carcinomas are an interesting pathological example of epithelial/mesenchymal transformation; a phenomenon commonly seen during development. Ha -ras is implicated in this transition(11) as are genes for the matrix degrading enzymes, the stromolysins(12, 13).
References
1. Eusebi, V., Cattani, M. G., Ceccarelli, C., and Lamovec, J. Sarcomatoid carcinomas of the breast: an immunocytochemical study of 14 cases. In: C. Fenoglio-Preiser, M. Wolff, and F. Rilke (eds.), Progress in Surgical Pathology, Vol. 10, pp. 83-99,1989.
2. Oberman, H. A. Metaplastic carcinoma of the breast, Am J Surg Pathol. 11: 918- 929, 1987.
3. Wargotz, E. S. and Norris, H. J. Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma, Human Pathol. 20: 628-635, 1989.
4. Wargotz, E. S., Deos, P. H., and Norris, H. J. Metaplastic carcinomas of the breast.II Spindle cell carcinoma, Human Pathol. 20: 732-740, 1989.
5. Wargotz, E. S. and Norris, H. J. Metaplastic carcinomas of the breast. III. Carcinosarcoma, Cancer. 64: 1490-1499, 1989.
6. Wargotz, E. S. and Norris, H. J. Metaplastic carcinomas of the breast. IV. Squamous cell carcinoma of ductal origin, Cancer. 65: 272-276, 1990.
7. Wargotz, E. S. and Norris, H. J. Metaplastic carcinomas of the breast. V. Metaplastic carcinoma with osteoclastic giant cells, Human Pathol. 21: 1142-1150, 1990.
8. 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. 95: 623-632, 1991.
9. Gersell, D. J. and Katzenstein, A.-L. Spindle cell carcinoma of the breast. A clinicopathologic and ultrastructural study, Human Pathol. 12: 550-561, 1981.
10. Al-Bozom, I. A. and Abrams, J. Spindle cell carcinoma of the breast, a mimicker of benign lesions, Archives in Pathological Laboratory Medicine. 120: 1066-1068, 1996.
11. Lozano, E. and Cano, A. Induction of mutual stabilisation and retardation of tumor growth by coexpression of plakoglobin and E-cadherin in mouse spindle carcinoma cells, Molecular carcinogenesis. 21: 273-287, 1998.
12. Lochter, A., galosy, S., Muschler, J., Freedman, N., Werb, Z., and Bissell, M. J. Matrix metalloproteinase stromolysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-mesenchymal conversions and a premalignant phenotype in mammary epithelial cells, The Journal of cell biology. 139: 1861- 1872, 1997.
13. Ahmad, A., Hanby, A. M., Poulsom, R., Dublin, E. A., Smith, P., Barnes, D. M., Bassett, P., Bellocq, J. P., and IR, I. R. H. Stromelysin 3; an independent prognostic factor for relapse-free survival in node-positive breast cancer and demonstration of novel breast carcinoma cell expression, Am J Path. 152: 721-728, 1998.
A 51-year-old woman presented with a lump above the right breast, which she had noticed for about 4 months. On clinical examination, a solid lump, 2 cm in diameter, was found in the 'supra-mammary pectoral region'. The breast itself felt normal and a mammogram was also reported as normal. No lymph nodes were felt in the axilla. At operation, a discrete solid lump attached to the pectoral sheath was found and was easily removed with sharp dissection. The specimen received at the Pathology Lab was a well-defined firm greyish nodule, 2cm in maximum dimension.
CARCINOMA IN ABERRANT BREAST TISSUE
The section shows a well-defined tumour mass composed of nodules separated by broad fibrous tissue bands. Each nodule consists of variable sized groups and sheets of mostly large pleomorphic cells with large vesicular nuclei and indistinct cell borders, surrounded by fibrous tissue stroma very heavily infiltrated with lymphocytes. Mitotic activity is prominent. A part of the tumour is mucinous. Immunoperoxidase stains were positive for pan-keratin but negative for oestrogen receptors. The over-all impression is of a metastatic carcinoma in a lymph node, possibly from a grade 3 invasive ductal carcinoma of the breast. However, although there is a heavy lymphocytic infiltration, no normal lymph node pattern is identifiable in the form of a capsule, subcapsular sinuses or properly arranged lymphoid follicles. On closer inspection, normal-looking mammary acini are present at the periphery of the lesion surrounded by, and continuous with the same heavy lymphocytic infiltration surrounding the tumour cells. A few normal mammary ducts are also present in the fatty tissue adjacent to the tumour. These features suggest that the tumour is most likely to be arising locally from supra-mammary aberrant breast tissue. Further investigations including clinical examination of the head and neck region, repeated mammography, chest x-rays and body scans were all negative. Right axillary lymph node dissection was carried out, and all the lymph nodes dissected were free of tumour. The patient has since received radiotherapy and chemotherapy, and is currently well 9 months after diagnosis.
Ectopic breast tissue, i.e. mammary glandular tissue present beyond the usual anatomic extent of the breast, is usually divided into two types: supernumerary breasts and aberrant breast tissue (1). Supernumerary breasts refer to extra-mammary glandular breast tissue present along the milk line which extends from mid axilla to the vulva. It is more commonly found in the axilla, and the overlying skin may show a nipple and areola. On the other hand, the term aberrant breast tissue refers to mammary glandular tissue present beyond the usual anatomic extent of the breast or milk line. This usually becomes clinically apparent only if it is involved in a pathologic process (1).
Pathological lesions, including carcinoma, arising from ectopic breast tissue within the axilla (2, 3), thoracic wall (4) and vulva (3, 5-8) have been described in several reports.On the other hand, pathological lesions developing within aberrant breast tissue are not commonly reported. Petrek et al described ectopic breast carcinomas arising in the clavicular and anterior axillary regions, over the sternum, and in the upper abdominal skin outside the milk lines (1,9), and O'hara and Page described an ectopic lactational adenoma in an unspecified part of the chest wall (3).
To make a diagnosis of carcinoma arising in ectopic or aberrant breast tissue, in contrast to metastatic carcinoma, either normal or in situ malignant epithelial breast elements have to be present in coexistence with the lesion (1). The case described here fulfils the criteria for a breast carcinoma arising within aberrant breast tissue. The lesion was present within a background of normal mammary ducts and acini, clinically distinctly separate and away from the normal breast and the site of the milk line. However, as normal breast tissue sometimes extends as a thin layer up to the clavicle (10), it is possible that the tumour arose in a peripheral extension of the breast, rather than from aberrant breast tissue completely separate from the right breast. Distinction between these two situations is not possible (1).
The case highlights two important points. First, for a tumour that looks like a breast carcinoma occurring outside, but in the vicinity, of the breast, or along the milk line, including the axilla, a careful search for coexisting normal epithelial mammary elements or foci of in situ breast carcinoma, is warranted, as their presence would confirm the ectopic primary nature of the lesion. This would be particularly important in the absence of lesions within the breast tissue proper. Second, the case stresses the point that even total mastectomy in some patients might not be enough to guarantee the removal of all breast tissue that may be susceptible to pathological changes (11), although admittedly the risk of carcinoma would be much reduced (12).
References
1. Rosen PP, Oberman HA. Tumours of the mammary gland. 1993,Washington, DC, Armed Forces Institute of Pathology, pp 20-21 & 270-271
2. Cogswell HD, Czerny EW. Carcinoma of aberrant breast of axilla. Am Surg 1961; 27: 388-390
3. O'Hara MF, Page DL. Adenomas of the breast and ectopic breast under lactational influences. Human Path 1985; 16: 707-712 J Roy Soc Med 1990; 83: 799-800
4. Livesey JR, Price BA. Metstatic accessory breast carcinoma in a thoracic subcutaneous nodule. J Roy Soc Med 1990; 83: 799-800
5. Guerry RL, Pratt-Thomas, HR. Carcinoma of supernumerary breast of vulva with bilateral mammary cancer. Cancer 1976; 38: 2570-2574
6. Cho D, Buscema J, Rosenshein NB, Woodruff JD. Primary breast cancer of the vulva. Obstet Gynecol 1985; 66: 79S-81S
7. Simon KE, Dutcher JP, Runowicz CD, Wiernik PH. Adenocarcinoma arising in vulvar breast tissue. Cancer 1988; 62: 2234-2238
8. Rose PG, Roman LD, Reale FR, Tak WK, Hunter RE. Primary adenocarcinoma of the breast arising in the vulva. Obstet Gynecol 1990; 76: 537-539
9. Petrek J, Rosen PP, Robbins GF. Carcinoma of aberrant breast tissue. Clin Bull 1980; 10: 13-15
10. Holleb AI, Montgomery R, Farrow JH. The hazard of incomplete simple mastectomy. Surg Gynecol Obstet 1965; 121: 819-822
11. Eldar S, Meguid MM, Beatty JD. Cancer of the breast after prophylactic subcutaneous mastectomy. Am J Surg 1984; 148: 692-693
12. Schrag D, Kuntz KM, Garber JE, Weeks JC. Decision analysis-Effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations. N Engl J Med 1997; 336: 1465-1471
A 59-year-old woman presented with a hard lump in the left breast, which the patient had for two years but has recently started to show an alarming increase in size. There was no family history of breast cancer. On examination, there was a hard irregular painless lump, 4 cm in diameter, within the left breast, and fixed to the pectoralis muscle. The overlying skin was normal and there was no nipple discharge.
A mammogram, an ultrasound and a CT scan showed a well-circumscribed lesion present entirely within the pectoralis major, with no evidence of extension into the surrounding soft tissue or bone. There was no axillary or mediastinal lymphadeopathy. A fine needle aspirate showed collections of spindle-shaped cells and a striking number of large multinucleated giant cells. No ductal cells were present. A breast core biopsy suggested a soft tissue tumour rich in giant cells, possibly benign.
At operation, the tumour was found to be completely contained within the middle of the pectoralis major. The tumour was excised together with the sternal head and body of the left pectoralis major. No axillary lymph nodes were removed.
The specimen received weighed 80 g. and measured 13x8x5 cm. On sectioning, there was a well-circumscribed, firm, yellowish brown tumour within the muscle, measuring 3.7 cm in maximum dimension, which appeared completely excised.
MALIGNANT FIBROUS HISTIOCYTOMA, GIANT CELL TYPE, OF THE BREAST
Microscopically, the tumour consists mainly of closely packed plump mostly spindle shaped cells with a moderate degree of nuclear pleomorphism and high mitotic rate (6/10 HPF), but with no abnormal mitoses. Large numbers of scattered osteoclast-like multi-nucleated giant cells, some containing lipid vacuoles and haemosiderin, are present. Foci of vacuolated, xanthoma, cells are also seen as well as many scattered lymphocytes and haemosiderin deposits. No osteoid tissue and no necrosis is evident. The tumour is seen infiltrating surrounding skeletal muscle. No normal mammary glandular tissue is present in the specimen.
The most striking positive Immunoperoxidase staining was seen with CD68 (pG-M1, Dako) which is a monclonal antibody directed against a fixative-resistant epitope on the macrophage-restricted form of the CD68 molecule, normally present in human monocytes and macrophages. All tumour cells, including the multinucleated giant cells, were strongly positive; the latter being more strongly stained than the spindle-shaped cells. All cells also showed positive staining for alpha-1-antitrypsin, and cells positive for lysozyme, myoglobin and desmin were also present. A stain for keratin also showed scattered single positive cells; but no positive cell groups or glandular structures were seen. The features were thus considered consistent with malignant fibrous histiocytoma, giant cell type. The main differential diagnosis is metaplasic spindle cell carcinoma of the breast. Immunoperoxidase stain for keratin in the latter tumour would show many keratin-positive spindle cells, and a careful search may show scattered neoplastic glandular elemens within the lesion.
The patient was given a course of radiotherapy post-operatively. She is being followed up every 3-months, and she appeared in good health when last seen 9 months post-operatively.
Soft tissue sarcomas of the breast comprise less than one percent of all malignant mammary tumours (1). Like breast carcinoma, the disease is much more common in female than in male breasts, with most large series including only one male case each (1-4). The tumour can arise de novo or after radiotherapy (5-10). The commonest histological type arising de novo seems to be malignant fibrous histiocytoma, which formed 44% of all breast sarcomas in one series (1) and 60% in another series which included cases arising in phyllodes tumour (4). However, in two other large series of 32 (2) and 60 (11) cases, only 15% and 10% of cases, respectively, were diagnosed as malignant fibrous histiocytomas, while the majority of cases were considered fibrosarcomas or stromal sarcomas. In another recent series, 32 cases were reported under the combined title of "fibrosarcoma- malignant fibrous histiocytoma of the breast", and were classified as low or high grade tumours according to the degree of nuclear atypia and mitotic activity (12). Although there is no specific immunohistochemical stain for malignant fibrous histiocytoma, a positive staining for CD68, lysozyme and alpha-1-antitrypsin and a negative staining for S100, as seen in our case, would support that diagnosis (13). Focal positivity for myoglobin and desmin are not against that diagnosis (13), niether is the minimal keratin staining seen in our case (4, 14). Prognosis seems to be related to the grade and size of the tumour, with high grade tumours (12) and tumours larger than 5 cm in diameter (11) usually having a bad prognosis that would necessitate a more aggressive therapeutic approach.
This case is unusual because although it presented as a breast lump, we believe that it has primarily arisen within the chest wall. This is supported by the pre-operative radiological investigations, the operative finding of the total presence of the tumour within the pectoralis muscle, and the complete absence of normal or abnormal mammary glandular tissue in the excised specimen by microscopic examination. These findings would be against the tumour arising in the breast and invading the chest wall. Whether this is a unique case or that some of the other breast soft tissue tumours reported in the literature have a similar origin, is difficult to know retrospectively. Only appropriate investigation of future cases would help in finding out the true incidence of primary chest wall sarcomas presenting as breast lumps.
References
1. Pollard, SG, Marks PV, Temple LN, Thompson HH. Breast Sarcoma. A clinicopathologic review of 25 cases. Cancer 1990; 66: 941-944
2. Callery CD, Rosen PP, Kinne DW. Sarcoma of the breast. A study of 32 patients with reappraisal of classification and therapy. Ann Surg 1985; 201: 527-532
3. Christensen L, Schiodt T, Blishert-Toft M, Hansen JPH, Hansen OH. Sarcomas of the breast: A clinico-pathological study of 67 patients with long term follw-up. Eur J Surg Oncol 1988; 14: 241-247
4. Terrier Ph, Terrier-Lacombe MJ, Mouriesse H, Friedman S, Spielmann M, Contesso G. Primary breast sarcoma: A review of 33 cases with immunohistochemistry and prognostic factors. Breast Cancer Res Treat 1989; 13: 39-48
5. Hatlinghus S, Rode L, Christensen I, Vaage S. Sarcoma following irradiation for breast cancer. Report of three unusual cases including one malignant mesenchymoma of bone. Acta Radiol Oncol 1986; 25: 39-242
6. Souba WW, McKenna RJ Jr, Meis J, Benjamin R, Raymond AK, Mountain CF. Radiation-induced sarcomas of the chest wall. Cancer 1986; 57: 610-615
7. Squire R, Bianchi A, Jakate SM. Radiation-induced sarcoma of the breast in a female adolescent. Case report with histologic and therapeutic considerations. Cancer 1988; 60: 2444-2447
8. Taghian A, de Vathaire F, Terrier P, Le M, Auquier A, Mouriesse H, Grimaud E, Sarrazin D, Tubiana M. Long-term risk of sarcoma following radiation treatment for breast cancer. Int J Radiation Oncology Biol Phys 1991; 21: 361-367
9. Wiklund TA, Blomqvist CP, Raty J, Elomaa I, Rissanen P, Miettinen M. Postirradiation sarcoma. Analysis of a Nationwide Cancer Registry material. Cancer 1991; 68: 524-531
10. Pendlebury SC, Bilous M, Langlands AO. Sarcomas following radiation therapy: A report of three cases and a review of the literature. Int J Radiation Oncology Biol Phys 1995; 31: 405-410
11. Gutman H, Pollock RE, Ross MI, Benjamin RS, Johnston DA, Janjan NA, Ramsdahl MM. Sarcoma of the breast: Implications for extent of therapy. The M.D. Anderson experience. Surgery 1994; 116: 505-509
12. Jones MW, Norris HJ, Wargotz ES, Weiss SW. Fibrosarcoma- malignant fibrous histiocytoma of the breast. A clinicopathological study of 32 cases. Am J Surg Pathol 1992; 16: 67-674
13. Brooks JSJ. The spectrum of fibrohistiocytic tumours with special emphasis on malignant fibrous histiocytoma. Curr Diagn Pathol 1994; 1: 3-12
14. Hasan Aak, Zisman T, Schmaier AH. Identification of cytokeratin 1 as a binding protein and presentation receptor for kininogens on endothelial cells. Proc Natl Acad Scie USA 1998; 95: 3615-3620
46 year old female with history of suspicious right beat lump with nipple retraction. Asymmetry on mammogram with increased density in right breast but no focal mass noted. Ultrasound showed hyperechoic 3.5cm lobulated mass with attenuation ?hamartoma. Cytology showed an unusual appearance of stromal cells ? fibromatosis (C3). Open biopsy performed. Slide from excision of lesion post biopsy.
PRIMARY ANGIOSARCOMA OF THE BREAST (Grade II)
Histological features: Multiple, anastomosing vascular channels with plump endothelial cells and occasional mitotic figures. There is infiltration and destruction of normal breast lobules.
Differential diagnosis: Angiosarcoma, angiomatosis, Organising haematoma.
Results of special techniques: Factor VIII and CD34 (Qbend10) positive cells lining vascular channels
References:
1. Donnell RM. Rosen PP. Lieberman PH. Kaufman RJ. Kay S. Braun DW Jr. Kinne DW . Angiosarcoma and other vascular tumors of the breast. American Journal of Surgical Pathology. 5(7):629-42, 1981 Oct.
2. Merino MJ. Carter D. Berman M . Angiosarcoma of the breast. American Journal of Surgical Pathology. 7(1):53-60, 1983 Jan.
3. Rosen PP. Kimmel M. Ernsberger D . Mammary angiosarcoma. The prognostic significance of tumor differentiation. Cancer. 62(10):2145-51, 1988 Nov 15.
4. Jozefczyk MA. Rosen PP . Vascular tumors of the breast. II. Perilobular hemangiomas and hemangiomas.American Journal of Surgical Pathology. 9(7):491-503, 1985 Jul.
5. Rosen PP . Vascular tumors of the breast. III. Angiomatosis. American Journal of Surgical Pathology. 9(9):652-8, 1985 Sep.
6. Rosen PP. Jozefczyk MA. Boram LH .Vascular tumors of the breast. IV. The venous hemangioma. American Journal of Surgical Pathology. 9(9):659-65, 1985 Sep.
7. Rosen PP . Vascular tumors of the breast. V. Non parenchymal hemangiomas of mammary subcutaneous tissues. American Journal of Surgical Pathology. 9(10):723-9, 1985 Oct.
8. Page DL, Anderson TJ. Angiosarcoma. In: Diagnostic Histopathology of
the Breast. Churchill Livingstone, Edinburgh p335-341
Female 28 years 1993 rounded palpable lump right upper outer quadrant ?fibroadenoma. Hyperechoic 1.6cm mass on ultrasound but not completely well circumscribed. Cytology benign. This lump was removed. Re-presented 1995 with similar rounded mass in left breast medial to nipple. Ultrasound showed similar appearance of hyperechoic 1.4cm mass with slightly irregular margins. This showed similar histological features to the previous lesion. The slide is from the 1995 lesion.
COMPLEX SCLEROSING LESION WITH FLORID REGULAR HYPERPLASIA (Sclerosing papillomatosis)
Histological features: Large hyperplastic ducts with a mixed cell population Dense hyaline collagen with entrapped tubules mostly showing two cell layers, myxoid stromal response.
Differential diagnosis: Complex sclerosing lesion, sclerosing papillomatosis, tubular carcinoma, regular hyperplasia, atypical ductal hyperplasia, ductal carcinoma in-situ.
Results of special techniques: Myoepithelial cells and basement membrane present round sclerosed tubules on actin and laminin stains. Mixed cell population on S100 staining.
References:
1. Rosen PP. Subareolar sclerosing duct hyperplasia of the breast. Cancer. 59(11):1927-30, 1987 Jun 1
2. Rosen PP. Caicco JA .Florid papillomatosis of the nipple. A study of 51 patients, including nine with mammary carcinoma. American Journal of Surgical Pathology. 10(2):87-101, 1986 Feb.
3. Azzopardi JG Infiltrating Epitheliosis.in Problems in Breast Pathology 1979 WB Saunders London p174-187
4. Page DL, Anderson TJ. Radial scars and complex sclerosing lesions in Diagnostic Histopathology of the Breast, 1987, Churchill Livingstone, Edinburgh p89-103
5. Fenoglio C, Lattes R.Sclerosing papillary proliferations in the female breast. A benign lesion often mistaken for carcinoma. Cancer 1974, 33, 691-700
A 39 year old female presented with a palpable lump in the right breast. The slide is from a therapeutic excision biopsy. A moderately well circumscribed lesion 1.6cm diameter was seen on cut surface.
INVASIVE MICROPAPILLARY ADENOCARCINOMA
Histologically the lesion is composed predominantly of solid islands of pleomorphic, neoplastic cells, some with fibrovascular cores, set within clear spaces. In other areas the tumour cells apparently form tubular structures. The tumour thus scores 2 for tubule formation, 3 for pleomorphism and 3 for mitoses and is of histological grade 3. Extensive invasion of vascular spaces by tumour emboli is seen around the periphery of the tumour.
The differential diagnosis for this lesion includes invasive micropapillary adenocarcinoma of the breast and metastasis from a primary elsewhere, for example from the ovary.
Immunohistochemistry on the lesion revealed typical reverse polarity with epithelial membrane antigen displayed as linear immunoreactivity at the periphery of the tumour islands. These are seen even where the tumour is apparently forming luminal spaces which do not, themselves, show the expected EMA reactivity. A similar pattern of staining can be demonstrated with histochemistry for acid mucin. Oestrogen receptor immunohistochemistry showed strong immunoreactivity in the tumour cells (H score = 180, 90%).
Following diagnosis of invasive adenocarcinoma on core biopsy, the patient underwent wide local excision and axillary node sampling. As described the tumour measured 1.6 cm in maximum extent and was classified as grade 3 (2,3,3) and of invasive micropapillary type with vascular invasion. Although complete excision was obtained (the nearest margin was 15 mm distant) because of the patient's age and presence of vascular invasion in association with a grade 3 tumour, the risk of local recurrence was considered significantly high that the patient was advised to undergo conversion to mastectomy. At the time of initial surgery one of four lymph nodes contained metastatic tumour, thus the patient had stage 2 disease. The Nottingham Prognostic Index score was 5.32. A subsequent subcutaneous mastectomy showed no evidence of residual invasive carcinoma. However, high grade ductal carcinoma in situ was found in the adjacent upper outer quadrant. No further vascular invasion was seen.
The patient's Nottingham Prognostic Index score puts her at the upper end of the moderate prognostic group. The tumour is, however, strongly oestrogen receptor positive and the patient received hormone therapy. She has no evidence of disease 26 months later.
References:
1.Siriaunkgul S, Tavassoli FA. Invasive micropapillary carcinoma of the breast. Mod Pathol 1993; 6: 660-662.
2.Lunamore S, Gonzalez B, Acedo C, et al. Invasive micropapillary carcinoma of the breast - a new special type of invasive mammary carcinoma. Pathol Res Prac 1994; 190: 668-674.
3.Middleton LP, Tressera F, Frases P, Merino MJ. Infiltrating micropapillary carcinoma of the breast. Lab Invest 1996; 74: 100.
An 85 year old female presented with a palpable mass in the right breast. The slide is from a therapeutic excision biopsy in which an ill defined firm 2.2cm was identified on cut surface.
ADENOMYOEPITHELIOMA
Histologically this is a biphasic tumour with an acinar structure composed of darkly stained luminal epithelial cells and a peripheral rim of clear cells. Both cell types show a mild to moderate degree of pleomorphism with prominent nucleoli. The mitotic count is, however, very low (less than 1 mitoses per 10 high power fields at a field diameter of 0.63 mm). Histologically the lesion is largely well defined with a 'lobulated' appearance.
Focally an unusual micropapillary epithelial proliferation is seen within ducts associated with the tumour showing some features of low grade micropapillary DCIS.
The differential diagnosis includes adenomyoepithelioma, tubular adenoma and pleomorphic adenoma, but shows the typical myoepithelial proliferation of an adenomyoepithelioma.
Immunohistochemistry confirms the myoepithelial nature of the clear cells which show strong positive immunoreactivity with smooth muscle actin. Conversely, the central luminal cells show Cam 5.2 immunoreactivity.
Oestrogen receptor staining was negative (H score = 0, 0%).
The tumour was diagnosed on a needle core biopsy which showed the same biphasic acinar structures with a central epithelial cell population surrounded by a clear cell myoepithelial proliferation. It was noted that the latter shows some atypical features and an adenomyoepithelioma was diagnosed. It was noted that this showed some atypical features and local excision was advised (needle core biopsy diagnosis B3).
Subsequent excision was performed which demonstrated an ill defined firm tumour measuring 2.2 cm in maximum extent which was diagnosed as an adenomyoepithelioma. The lesion extended very close to an excision margin and in view of the presence of some myoepithelial atypia and the intraductal micropapillary epithelial proliferation, re-excision was advised. This has not yet, however, been performed, but the patient remains well seven months post surgery. No staging procedure was performed.
References:
1.Loose JH, Patchefsky AS, Hollander IJ, et al. Adenomyoepithelioma of the breast - a spectrum of biologic behavior. Am J Surg Pathol 1992;16: 868-876.
2.Tavassoli FA. Myoepithelial lesions of the breast - myoepitheliosis, adenomyoepithelioma and myoepithelial carcinoma. Am J Surg Pathol 1991; 15: 554-568.
3.Rosen PP. Adenomyoepithelioma of the breast. Hum Pathol 1987; 18:1232-1237.
4.Flinner RI, Hammond EH. The myoepithelial cell in lesion of the breast: a review. Pathol Annual 1993; 2: 145-169.