<\/a><\/p>\n BREAST Introduction<\/strong><\/p>\n The breast is composed of fat and stroma that support glandular tissue, a branching ductal system that leads to 6-10 main ducts, which open onto the nipple. Both benign and malignant lesions develop in the breast. In young women fibroadenomas are common lesions but as women get older, fibrocystic changes tend to be more common. Other benign lesions include fat necrosis and inflammatory conditions such as breast abscess and mastitis. Less common benign lesions such as hamartomas and pseudoangiomatous hyperplasia can occur. Ductal hyperplasia forms part of fibrocystic changes. Atypical ductal hyperplasia can be difficult to distinguish from low grade ductal carcinoma in situ and these lesions represent a spectrum of disease that can develop into breast carcinoma. Radiation changes can produce a mass, which may appear atypical on aspiration cytology. Similarly, pregnancy and lactational changes can also be mistaken for malignancy on aspirates hence clinical information is essential for an accurate cytological diagnosis.<\/p>\n Malignancies in the breast may be primary or metastatic Those metastatic to the breast include lymphoma, malignant melanoma and other secondary tumors such as renal, bronchial, ovarian or pulmonary carcinomas. Most significant from a diagnostic perspective is primary breast carcinoma is the ductal type, not otherwise specified (NOS). The second most common primary mammary neoplasm is lobular carcinoma. Ductal carcinoma in situ and lobular carcinoma in situ are easily diagnosed on excision biopsies but are more difficult to diagnose with confidence on cytology.<\/p>\n Breast cytology has a role for both screening and diagnostic purposes. Any lesion detected on mammographic screening can be sampled with a fine needle, by direct aspiration if palpable or by stereotactic or ultrasound guidance if non-palpable. If the cytology sample is unsatisfactory or equivocal, core biopsy or frozen section can be utilized. Palpable breast masses are easily aspirated and can be quickly processed for a rapid diagnosis.<\/p>\n Fine-needle aspiration cytology is a useful tool in the diagnosis of breast lesions, both palpable and non-palpable. It is a safe, quick, inexpensive (as compared to core biopsies), and relatively painless procedure, and can be performed by clinicians as well as pathologists. In the hands of cytopathologists the inadequacy rate is low as rapid stains can be performed to evaluate specimen adequacy and the procedure repeated if necessary. Cyto-histological correlation is excellent in the hands of experienced cytopathologists. One minor disadvantage of fine-needle aspirates is that it is not always possible to distinguish between invasive and in situ lesions, but core biopsies too have similar problems in some cases.<\/p>\n The material aspirated is either smeared on a glass slide or expelled into Cytolyt\u00ae<\/sup> solution, and the needle is rinsed with the same solution for each pass made. The fluid can be used to make several almost identical slides thus enabling the lab to save material for special stains such as estrogen and progesterone receptors and HER2\/neu protein over-expression.<\/p>\n CYTOLOGICAL FEATURES <\/strong> Mastitis and breast abscess<\/em><\/strong> aspirates contain abundant neutrophils, histiocytes, multinucleated giant histiocytes, a few degenerating epithelial cells and proteinaceous material that can mimic necrosis. They are not uncommon findings in lactating women. Fat necrosis<\/strong> develops after trauma, either because of a direct blow to the breast or following surgery or radiation therapy. Clinically and mammographically fat necrosis mimics breast carcinoma, with a hard, irregular mass. However, the aspirate is diagnostic, as it is composed of degenerating adipocytes with abundant lipophages.<\/p>\n Fibroadenoma<\/strong><\/em> presents as a firm, smooth, mobile breast mass. It usually feels rubbery and grips the needle tip. Aspirates are usually cellular with large branching sheets of benign ductal cells, with a sprinkling of ‘sesame seeds’ on the surface \u2013 myoepithelial cells. In ThinPrep smears the single background myoepithelial cells tend to accumulate adjacent to the ductal cells. The ductal cells often show overlapping, suggesting an element of ductal hyperplasia. Stromal fragments of varying sizes are seen, containing spindled nuclei.<\/p>\n Low grade phyllodes tumors<\/strong><\/em> are also fibroepithelial in composition, with the glandular element closely mimicking that of fibroadenoma. However, ductal hyperplasia is much more common in phyllodes tumors. The stromal component tends to be prominent, with large stromal fragments that are hypercellular. Abundant stromal cell groups may also be noted. Malignant phyllodes tumors show unequivocal features of malignancy.<\/p>\n Fibrocystic<\/strong><\/em> change<\/strong> is a fairly common lesion encompassing cystic change with apocrine metaplasia, ductal hyperplasia of usual type, and other forms of epitheliosis. Cytological appearances include sheets and groups of overlapping benign ductal cells with myoepithelial cells, apocrine metaplasia, foamy macrophages and calcium. The features can mimic those of fibroadenoma cytologically, but the typical clinical finding is an ill-defined thickening or ridge rather than the smooth mobile mass of fibroadenoma. Cystic changes can progress to form palpable cysts which are easily aspirated. The fluid may be clear and colorless or turbid, brown, green or bloodstained. Cyst fluids contain proteinaceous material, benign ductal cells that may appear degenerated or mildly atypical, apocrine metaplastic cells, and foamy macrophages. Brown or green cyst fluid usually indicates prior bleeding and this is confirmed by the presence of hemosiderin-laden macrophages on the slide. Apocrine metaplastic cells have abundant granular cytoplasm, round nuclei and prominent nucleoli. They can be binucleate and may appear atypical as the nuclear size is variable.<\/p>\n Collagenous spherulosis<\/strong> is a benign lesion that may accompany ductal or lobular hyperplasia. Aspirates show globules of extracellular material (which stain pale blue with the Papanicolaou stain and magenta with DiffQuik), benign ductal, apocrine metaplasia and myoepithelial cells. The differential diagnosis includes adenoid cystic carcinoma.<\/p>\n Malignant<\/strong> Ductal carcinoma<\/strong> tends to be unilateral. It presents as a firm to hard, irregular mass clinically, with a characteristic mammographic appearance of a mass, a spiculated lesion or microcalcifications. Although ductal carcinoma in situ is thought to precede invasive ductal carcinoma, it may also accompany invasive lobular carcinoma. Similarly, lobular carcinoma in situ may be associated with ductal carcinoma as well as invasive lobular carcinoma. Ductal carcinoma in situ aspirates show malignant features but may also display myoepithelial cells overlying the cell clusters. Invasive ductal carcinoma (NOS) yields cellular aspirates composed of large, often pleomorphic tumor cells. Low grade ductal carcinomas can be difficult to distinguish from benign ductal cells. Invasion is suggested by the presence of tumor cells infiltrating between adipocytes.<\/p>\n Lobular carcinoma <\/strong>is often bilateral. Clinically the tumor is ill-defined and has no typical mammographic appearance. Lobular carcinoma in situ is seen as rounded clusters of small malignant cells, some with intracytoplasmic vacuoles, often with overlying myoepithelial cells. Invasive lobular carcinoma aspirates are scant, often resulting in an ‘unsatisfactory’ or ‘atypical’ report. The cells are smaller than in ductal carcinoma, often single with eccentric nuclei and intracytoplasmic vacuoles. Nucleoli are not usually seen. The cells often lie in a single file. Signet ring cells may be seen in lobular carcinoma aspirates.<\/p>\n There are also special types of ductal carcinoma that occur such as tubular, colloid (mucinous), metaplastic, medullary, apocrine and squamous. The definition of many of these special types of breast tumors is based on evidence that more than 90% of the lesion shows the typical characteristics of that type. As cytology samples only part of the tumor it is not accurate to categorize these tumors as tubular or mucinous cytologically. The suspicion can be raised in the report by including a description such as “ductal carcinoma with mucinous or tubular features” rather than a definite type, which might possibly differ from that of the excision specimen. Tubular carcinomas are composed of tubular and acinar structures. Mucinous carcinoma aspirates are often grossly mucoid and show abundant mucin on the smear. Certain rarities such as adenoid cystic carcinoma, identical to that seen in the salivary gland, may also develop. This tumor mimics benign collagenous spherulosis in that it also contains extracellular hyaline material with the same staining characteristics, but in the form of both globules and tubular or cylindrical structures. The accompanying tumor cells are small and bland with little cytoplasm, but benign ductal, apocrine and metaplastic cells are not seen.<\/p>\n References<\/strong><\/p>\n Breast FNA, Fat. Breast FNA, Benign ductal cells. Breast FNA, Fibroadenoma. Breast FNA, Fibroadenoma. Breast FNA, Fibroadenoma. Breast FNA, Fibroadenoma. Breast FNA, Fibroadenoma. Breast FNA, Low grade phyllodes tumor. Breast FNA, Fibrocystic changes. Breast FNA, Fibrocystic changes. Breast FNA, Fibrocystic changes. Breast FNA, Breast cyst. Breast FNA, Breast cyst. Breast FNA, Breast cyst. Breast FNA, Apocrine metaplasia. Breast FNA, Apocrine metaplasia. Breast FNA, Cystic papillary lesion. Breast FNA, Cystic papillary lesion.
\nGrace T. McKee, MD <\/em><\/p>\n
\nBenign
\nNormal breast<\/em> <\/strong>yields only fat, stroma and a few benign ductal cells. Benign normal breast is rarely aspirated unless the actual lesion is missed by the needle. In fact, aspirates from normal breast would not comply with the widely observed criterion for an adequate breast aspirate: at least five to six clusters of epithelial cells. Exceptions to this rule include fat necrosis and inflammatory lesions.<\/p>\n
\nFeatures that are suggestive of malignancy include loss of cell cohesion, increase in cell and\/or nuclear size, irregularity of the nuclear membrane, clumping and uneven distribution of chromatin, as well multiple, abnormal nucleoli. Single nucleoli may be seen in reactive conditions and are not a criterion of malignancy on their own. Myoepithelial cells, which are abundant in benign proliferative lesions, are not seen in aspirates of invasive breast carcinoma.<\/p>\n\n
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\nfor an enlarged view.<\/strong><\/p>\n
\n![\"Image](\"\/gallery\/images_large\/slide1101.jpg\" "\\"Click")
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\nFat cells, or adipocytes, are large spherical cells with translucent cytoplasm and small eccentric nuclei. They are seen in both benign and malignant aspirates. 40x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Fat.<\/strong>
\nFat cells, or adipocytes, are large spherical cells with translucent cytoplasm and small eccentric nuclei. They are seen in both benign and malignant aspirates.
\n40x<\/div>\n
\n<\/a><\/p>\n
\nNormal breast aspirates yield benign ductal cells, often accompanied by myoepithelial cells. 40x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Benign ductal cells.<\/strong>
\nNormal breast aspirates yield benign ductal cells, often accompanied by myoepithelial cells.
\n40x<\/div>\n
\n<\/a><\/p>\n
\n<\/strong>
\nBreast FNA, Abscess.
\nFine-needle aspirates of breast abscesses do not usually show epithelial cells. Cellular debris, lysed red cells and neutrophils are common features. 40x<\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Abscess.<\/strong>
\nFine-needle aspirates of breast abscesses do not usually show epithelial cells. Cellular debris, lysed red cells and neutrophils are common features.
\n40x<\/div>\n
\n<\/a><\/p>\n
\n<\/strong>
\nBreast FNA, Fibroadenoma.<\/strong>
\nA large stromal fragment is present, containing a few small spindle-shaped nuclei. Stromal fragments may be seen in aspirates of benign breast tissue as well as in fibroepithelial lesions such as fibroadenoma. Stromal fragments from phyllodes tumors are much more cellular. Note the small group of benign ductal cells also present.
\n40x<\/div>\n
\n<\/a><\/p>\n
\nA large branching sheet of cohesive, uniform benign ductal cells is seen overlying a stromal fragment. Note the small, somewhat spindled stromal cell nuclei within the stromal fragment. 20x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Fibroadenoma.<\/strong>
\nA large branching sheet of cohesive, uniform benign ductal cells is seen overlying a stromal fragment. Note the small, somewhat spindled stromal cell nuclei within the stromal fragment.
\n20x<\/div>\n
\n<\/a><\/p>\n
\nTypically, fibroadenoma aspirates contain large branching sheets of benign ductal cells as seen in this illustration. 20x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Fibroadenoma.<\/strong>
\nTypically, fibroadenoma aspirates contain large branching sheets of benign ductal cells as seen in this illustration.
\n20x<\/div>\n
\n<\/a><\/p>\n
\nThis is another example of the branching appearance of ductal cells in fibroadenoma. 20x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Fibroadenoma.<\/strong>
\nThis is another example of the branching appearance of ductal cells in fibroadenoma.
\n20x<\/div>\n
\n<\/a><\/p>\n
\nIn some instances the ductal cell groups have small rounded projections as seen here rather than the long branches noted in the prior two figures. 20x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Fibroadenoma.<\/strong>
\nIn some instances the ductal cell groups have small rounded projections as seen here rather than the long branches noted in the prior two figures.
\n20x<\/div>\n
\n<\/a><\/p>\n
\n<\/strong>
\nBreast FNA, Fibroadenoma.<\/strong>
\nIn this field the edges of the ductal group are not smooth as the previous two images above, possibly due to the liquid-based processing. Within the group of ductal cells, and at the upper edge, a few myoepithelial cells are noted. With ThinPrep processing myoepithelial cells tend to be seen adjacent to the ductal groups rather than scattered in the background as seen in conventional smears.
\n40x<\/div>\n
\n<\/a><\/p>\n
\nA branching sheet of benign ductal cells with overlying myoepithelial cells produce the characteristic ‘sesame seed on a bun’ appearance. 40x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Fibroadenoma.<\/strong>
\nA branching sheet of benign ductal cells with overlying myoepithelial cells produce the characteristic ‘sesame seed on a bun’ appearance.
\n40x<\/div>\n
\n<\/a><\/p>\n
\n<\/strong>
\nBreast FNA, Low grade phyllodes tumor.<\/strong>
\nPhyllodes tumors are, like fibroadenomas, also fibroepithelial lesions. However even the low grade lesions have the capability of recurring if not excised with a wide margin. The glandular component is similar to that seen in fibroadenoma although it can be much more cellular and hyperplastic appearing. This illustration shows a three-dimensional group of ductal cells showing nuclear overlapping and crowding, suggestive of hyperplastic changes.
\n40x<\/div>\n
\n<\/a><\/p>\n
\nThis stromal fragment is hypercellular and contains crowded plump spindle cells. Many single spindled stromal cells may also be seen in the background in this lesion. 60x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Low grade phyllodes tumor.<\/strong>
\nThis stromal fragment is hypercellular and contains crowded plump spindle cells. Many single spindled stromal cells may also be seen in the background in this lesion.
\n60x<\/div>\n
\n<\/a><\/p>\n
\nThis field shows a tight cluster of benign ductal cells with foamy macrophages at each end, with secretory material in the background. 40x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Fibrocystic changes.<\/strong>
\nThis field shows a tight cluster of benign ductal cells with foamy macrophages at each end, with secretory material in the background.
\n40x<\/div>\n
\n<\/a><\/p>\n
\nThis small group of benign ductal cells is from an aspirate of fibrocystic changes. 40x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Fibrocystic changes.<\/strong>
\nThis small group of benign ductal cells is from an aspirate of fibrocystic changes.
\n40x<\/div>\n
\n<\/a><\/p>\n
\nBackground secretion, blood and apocrine metaplastic cells are seen in fibrocystic changes. 20x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Fibrocystic changes.<\/strong>
\nBackground secretion, blood and apocrine metaplastic cells are seen in fibrocystic changes.
\n20x<\/div>\n
\n<\/a><\/p>\n
\nThis cluster of benign ductal cells shows mild atypia in the form of visible nucleoli and slight nuclear enlargement. Such minimal changes are often noted in breast cyst fluids. 60x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Breast cyst.<\/strong>
\nThis cluster of benign ductal cells shows mild atypia in the form of visible nucleoli and slight nuclear enlargement. Such minimal changes are often noted in breast cyst fluids.
\n60x<\/div>\n
\n<\/a><\/p>\n
\nThis field shows a small group of benign epithelial cells, one vacuolated, with cyst debris in the background. 40x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Breast cyst.<\/strong>
\nThis field shows a small group of benign epithelial cells, one vacuolated, with cyst debris in the background.
\n40x<\/div>\n
\n<\/a><\/p>\n
\nBenign ductal cells in cyst fluid may show degenerative vacuolization as illustrated here. These changes should not be interpreted as being diagnostic of carcinoma. 60x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Breast cyst.<\/strong>
\nBenign ductal cells in cyst fluid may show degenerative vacuolization as illustrated here. These changes should not be interpreted as being diagnostic of carcinoma.
\n60x<\/div>\n
\n<\/a><\/p>\n
\nBenign apocrine cells are often seen in flat sheets. They are commonly seen in breast cyst fluids and in fine-needle aspirates from areas of fibrocystic change. 40x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Apocrine metaplasia.<\/strong>
\nBenign apocrine cells are often seen in flat sheets. They are commonly seen in breast cyst fluids and in fine-needle aspirates from areas of fibrocystic change.
\n40x<\/div>\n
\n<\/a><\/p>\n
\nApocrine cells display abundant granular cytoplasm and round nuclei with prominent nucleoli. Their cytoplasmic borders are usually clearly defined. 60x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Apocrine metaplasia.<\/strong>
\nApocrine cells display abundant granular cytoplasm and round nuclei with prominent nucleoli. Their cytoplasmic borders are usually clearly defined.
\n60x<\/div>\n
\n<\/a><\/p>\n
\n<\/strong>
\nBreast FNA, Cystic papillary lesion.<\/strong>
\nAspirates from cystic papillary lesions contain epithelial cells as well as foamy macrophages. The benign ductal cells in this group are uniform in size and shape and display palisading along one edge. Note the foamy macrophage and single benign ductal cell above the group. If mild cellular atypia is present it can be difficult to distinguish a benign lesion from a malignant papillary lesion.
\n40x<\/div>\n
\n<\/a><\/p>\n
\nThis group of benign ductal cells has a rounded, palisaded edge, giving the appearance of a papillary structure, although no fibrovascular core is seen. 40x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Cystic papillary lesion.
\nThis group of benign ductal cells has a rounded, palisaded edge, giving the appearance of a papillary structure, although no fibrovascular core is seen.
\n40x<\/div>\n
\n<\/a><\/p>\n
\n<\/strong>
\nBreast FNA, Cystic papillary lesion.<\/strong>
\nA rounded papillary cluster of degenerating, vacuolated ductal cells is seen in this field, accompanied by secretory material. This appearance is best reported as atypical as it is not always possible to distinguish between benign and malignant papillary lesions. The presence of apocrine metaplastic cells is usually a clue to a benign process.
\n60x<\/div>\n
\n<\/a><\/p>\n
\nFoamy macrophages, as illustrated here, are noted in both benign and malignant cystic lesions, whether papillary or not. 60x<\/p><\/div>\n<\/div>\n
\n<\/strong>
\nBreast FNA, Cystic papillary lesion.<\/strong>
\nFoamy macrophages, as illustrated here, are noted in both benign and malignant cystic lesions, whether papillary or not.
\n60x<\/div>\n
\n<\/a><\/p>\n
\n<\/strong>
\nBreast FNA, Collagenous spherulosis.<\/strong>
\nThis is a benign lesion which is usually an incidental finding in breast biopsies. Rarely does it form a palpable mass. The aspirate contains evidence of benign ductal hyperplasia, benign ductal and apocrine metaplastic cells, myoepithelial cells, and globules of extracellular material surrounded by small benign epithelial cells. A similar picture is seen in aspirates from adenoid cystic carcinoma of the breast.
\n60x<\/div>\n