Fine Needle Aspiration Biopsy Cytology of Breast : A Diagnostic Approach Based on Pattern Recognition

Clinical Features

Cysts can present as palpable, sometimes painful breast masses and are rounded on mammography and ultrasound, where they can be mimicked by fibroadenomas, papillomas, medullary carcinomas, or mucinous carcinomas. Typically, cysts completely disappear on ultrasound and mammography after aspiration, but attempted aspiration may leave residual fluid or a residual mass may be palpable. These lesions should be re-needled. Some “complex” cysts on the ultrasound have a heterogeneous pattern with possible internal structures or wall thickenings, possibly related to the density of the cyst contents, a large number of siderophages, inflammation, scarring, or a proliferative focus and may yield thick material due to inspissation or aseptic inflammation. Similar aspirated fluid that is thick, resembling pus and reflecting its high cellularity, or bloodstained or dark brown due to old hemorrhage, can be obtained from carcinomas that are necrotic or partially cystic, including the uncommon encysted papillary carcinoma. On the other hand, the commonest cause of freshly bloodstained cyst fluid is incidental hemorrhage due to the FNAB. For all these reasons, in our experience, the fluid from ALL cystic lesions, not just bloodstained fluids, should be assessed by cytology.

Cytopathology

“Cyst contents” is reported when only a proteinaceous background with histiocytes is present (see Figs. 5-11 and 5-12 ). The proteinaceous background is best seen in Pap smears because it often washes off the air-dried Giemsa smears, and it can be thin or thick and obscuring, finely granular, or colloidal. It may contain cholesterol crystals, laminated round bodies (Liesegang rings) (see Fig. 5-34 ), and calcific debris. The calcifications can be granular and blue in the Giemsa and grayish black in the Pap smears, clear calcium oxalate birefringent angulated fragments, or occasional small psammomatous calcifications (see Figs. 5-27 to 5-32 ).

Histiocytes are usually seen singly but sometimes in aggregates. They have small, round, kidney-shaped or irregular, indented nuclei and copious, finely vacuolated or granular cytoplasm (see Fig. 5-13 ), which may contain bluish black (Giemsa) or yellow-brown (Pap) hemosiderin pigment (“hemosiderophage”) representing previous hemorrhage (see Fig. 5-40 ). Multinucleated histiocytes and siderophages are frequently seen ( Fig. 5-33 ).

Metaplastic apocrine cells occur in flat sheets of evenly spaced polygonal cells with clearly defined cytoplasmic margins and have a large amount of finely granular cytoplasm, which is grayish blue with fine red granules in the Giemsa smears ( Fig. 5-35 ), and green with varying dark green to reddish brown granules in the Pap stain ( Fig. 5-36 ). Apocrine cells have single or binucleated round central nuclei and often quite large single nucleoli and can show columnar differentiation or spindling in small sheets, consistent with the attenuated lining of cysts ( Figs. 5-37 and 5-38 ). Apocrine cells can have intracytoplasmic lumina, containing eosinophilic material in the Pap smear or bluish purple material in the Giemsa smear, and there may be nuclear enlargement, pleomorphism, and hyperchromasia, possibly related to degeneration, when the chromatin becomes blurred ( Fig. 5-39 ).

Such apocrine atypia can be pronounced and associated with marked dispersal or hyperplastic sheets or micropapillary tissue fragments, when apocrine intraduct carcinoma enters the differential diagnosis (DD) ( Figs. 5-40 to 5-42 ). A moderate to high N:C ratio with still considerable eosinophilic granular cytoplasm and marked pleomorphism of nuclei with coarse chromatin showing perinucleolar clearing, spiculated large nucleoli, and loss of the flat sheet architecture favor apocrine intraduct carcinoma, which can be cribriform or high grade and associated with necrosis and calcifications or apocrine carcinoma.

Large numbers of neutrophils are seen in “inflamed cysts” in cases where cyst rupture has produced an inflammatory reaction that may or may not have caused pain or redness. The neutrophils and histiocytes in the proteinaceous background resemble pus and raise the possibility of a septic abscess that can be excluded by culture of the aspirate. Sheets of apocrine cells and ductal epithelial cells infiltrated by neutrophils and showing inflammatory atypia may be present ( Figs. 5-43 to 5-44 ), along with fragments of myxoid granulation tissue with branched, anastomosing capillaries ( Fig. 5-45 ). The N:C ratio usually remains low in these inflamed epithelial cells, and within the sheets there is a uniform increase in nuclear size and uniform chromatin, despite the hyperchromasia and atypia. A neutrophilic infiltrate is found uncommonly in carcinomas.

Recurrent subareolar abscesses (Suska disease) are a distinct entity associated with chronic inflammation and squamous metaplasia in the lactiferous ducts, and smears show pus with considerable keratinous debris and squamous cells, which may show inflammatory atypia. These lesions are differentiated from inflamed epithelial cysts of the skin of the breast by their location within and deep to the nipple and by their history.

Granulomatous mastitis can be seen in specific infections such as tuberculosis involving the breast but also in a nonspecific inflammatory process, where multinucleated giant cells, plentiful histiocytes occasionally in vague granulomas, and lymphocytes are seen in a proteinaceous background with mildly atypical ductal tissue fragments. Similar findings can be seen in granulomas in the breast and axillary lymph nodes reacting to silicon derived from breast prostheses, where the histocytes have foamy cytoplasm (silicon is not birefringent [ Figs. 5-46 and 5-47 ]). Culture and polymerase chain reaction to exclude mycobacterial infection are mandatory in granulomatous mastitis.

Dilated ducts with periductal sclerosis and inflammation, known as periductual mastitis or duct ectasia when deep to the nipple, produce a proteinaceous background, with histiocytes, lymphocytes, plasma cells, granular debris, multinucleated histiocytes, and usually some apocrine or ductal epithelium. The distinction from a cyst relies on ultrasound findings.

Fat necrosis can be seen in a previous biopsy or operative site, in sites of trauma, or can occur incidentally and be unsuspected on imaging. Giemsa-stained smears show multicolored yellow to orange to blue to black, punctate, and irregular granular debris and degenerate cells, with multinucleated and single histiocytes and siderophages ( Figs. 5-48 and 5-49 ), and fragments of fat, some of which will be necrotic with the reticular outline of fat cells lacking nuclei ( Fig. 5-50 ). If fat necrosis is associated with large numbers of multinucleated histiocytes with bubbly vacuolated cytoplasm, the possibility of a reaction to silicon, which is not birefringent, from implants should be considered. “Oil cysts,” seen on ultrasounds, can produce viscous yellow to white colloidal material on the unstained smears, but only a little debris is seen after fixation and staining.

In the postoperative setting where there has been adjuvant radiotherapy, scattered cohesive epithelial tissue fragments may show radiation changes characterized by occasional prominent enlarged cells, with pleomorphic, large hyperchromatic nuclei with vacuoles and smudged dark chromatin, low to moderate N:C ratio, and considerable vacuolated cytoplasm, often in a background of debris and possible fat necrosis, with plump atypical fibroblastic cells. Any increase in epithelial cellularity or dispersal of atypical cells with preserved chromatin should suggest residual carcinoma, and core biopsy should be recommended.

Galactoceles usually occur in lactating women and resemble cysts on imaging. They have a proteinaceous background that variably resembles cyst fluid or milk, with fat globules in thin proteinaceous material, with scattered histiocytes. Lactational change and lactational nodules (sometimes referred to inappropriately as “lactating adenomas”) show a milky background of microvesicular and macrovesicular fat globules in a thin casein proteinaceous background, along with small numbers of acinar cells in sheets and occasionally singly. The acinar cells have pale vacuolated fragile cytoplasm and round nuclei containing a single central nucleolus ( Fig. 5-51 ). Stripped, round, nucleolated acinar cell nuclei and large lobules in which the terminal ductules are expanded ( Fig. 5-52 ) are seen as well. Acinar cells can show marked dispersal, but the milky background and lack of nuclear atypia help in the distinction from lobular and rare secretory carcinoma.

Clinical Features

Granular cell tumor is an S100-positive tumor arising from nerve sheath Schwann cells, occurring in many sites in both males and females including the breast, where it often presents clinically and radiologically as a suspicious firm and spiculated mass sometimes attached to skin or chest wall.

Cytopathology

The DD includes fibrocystic change with apocrine cells and histiocytes, as well as apocrine carcinoma. If necrosis is present, the possibility of a malignant granular cell tumor should be considered and excision biopsy recommended.

Ancillary Diagnostic Tests

In cell blocks, the granular cell tumor cells are S100 and vimentin positive, and cytokeratin is negative.

Clinical Features

Fibrocystic change is common in FNAB of women of all ages and can produce palpable masses and mammographic and ultrasound abnormalities. Histologically, small and large cysts arising from the terminal duct lobular unit and usually associated with apocrine metaplasia are seen with intralobular and interlobular fibrosis. Fibrocystic change and proliferative breast disease such as epithelial hyperplasia are often lumped together in histopathology reports, but an attempt should be made in both cytology and histology to distinguish these entities, so as to improve correlation with imaging, maximize the role of the triple test, and avoid false-positive diagnoses.

Cytopathology

The diagnosis of “cyst contests” is made when there is only a proteinaceous background with histiocytes and there is correlation with imaging findings, particularly complete drainage under ultrasound real-time imaging or when FNAB of palpable lesions leaves no residual mass (see Figs. 5-11 and 5-12 ). When apocrine sheets are present in a proteinaceous background a diagnosis of “cyst with apocrine cells” is appropriate (see Plate 5-2 ; Figs. 5-56 and 5-57 ). When ductal epithelial tissue fragments with myoepithelial cells are also present with apocrine cells and histiocytes in a proteinaceous background, the term fibrocystic change is used ( Fig. 5-58 ). The aim is to allow close correlation with imaging, especially ultrasound findings.

Ductal epithelial cells can show a transition to apocrine metaplasia that can be associated with nuclear enlargement, atypia, and dispersal ( Fig. 5-59 ). Apocrine cells have well-defined cell margins, a large amount of granular cytoplasm that is magenta to gray in the Giemsa stain and khaki to light green in the Pap stain with red granules, and a central round nucleolus and single prominent nucleolus (see Figs. 5-35 and 5-36 ).

A small number of bare bipolar nuclei are usually present but often diluted by the proteinaceous background and may be scant. They must be distinguished from stripped apocrine cell nuclei, which are round with a single nucleolus. Microcalcifications can be seen in the proteinaceous background as in cysts (see Figs. 5-27 to 5-29 ).

Differential Diagnosis

Apocrine sheets have scant to no myoepithelial cells. In some cases dispersal of apocrine cells can be marked and, when associated with nuclear degeneration, may cause some concern. But the overall cellularity is low, the N:C ratio is low, and the marked anisonucleosis, increase in nuclear size, and hyperchromasia and large and irregular nucleoli of apocrine carcinoma are not seen.

Histiocytes have granular copious cytoplasm and at times may resemble apocrine cells, particularly degenerate desquamated apocrine cells but the distinction is of little importance.

At times apocrine metaplasia can be associated with marked papillary hyperplasia, and features of an intraductal papilloma such as meshwork or stellate “papillary” or true papillary tissue fragments with fibrovascular cores can be seen, matching the apocrine papillary hyperplasia seen histologically ( Fig. 5-60 ). Apocrine dispersal can be present in these cases, but the individual apocrine cells are usually bland and the lesions clearly benign.

Clinical Features

Epithelial hyperplasia is commonly seen in the context of fibrocystic change and can be associated with palpable lumps, mammographic asymmetry and architectural disturbances and calcifications, and ultrasound abnormalities that are usually regarded as “fibrocystic change.” Epithelial hyperplasia can also be seen in intraductal papillomas and in fibroadenomas and phyllodes tumors, and it is the presence of other features such as stromal fragments that allow a more specific diagnosis to be made.

Cytopathology

Once large tissue fragments are seen in a breast FNAB smear, the pattern is regarded as a large tissue fragment pattern, even though there may be a mix of small tissue fragments and dispersed cells, as this aids the pattern recognition approach and DD.

The myoepithelial cells have small, perfectly oval nuclei with uniform fine chromatin and no nucleoli and sit at a focal plane above that of the epithelial cells in the bimodal sheets. They are more obvious at the edge of the tissue fragments. These features are perhaps more easily seen in the Pap-stained slides (see Fig. 5-62 ). Myoepithelial cells must be distinguished from irregular apoptotic debris found in the same focal plane as the nuclei in large sheets and tissue fragments from intraductal carcinomas and some carcinomas. The bare bipolar nuclei or myoepithelial nuclei in the background similarly must be perfectly oval in shape with fine, even chromatin and no nucleoli to separate them from stripped malignant nuclei (see Figs. 5-5 and 5-6 ).

The ductal cells show small, round to oval to mildly pleomorphic indented nuclei with fine chromatin, single nucleoli, and occasional nuclear pseudoinclusions and grooves, arranged in a relatively uniform pattern when seen in a flat sheet (see Fig. 5-62 ), but more haphazardly in a multilayered overlapping pattern in the thicker 3-D tissue fragments (see Figs. 5-63 to 5-65 ). At the margins of the cohesive epithelial sheets, the cytoplasm of cells can be pulled out or tufted as the cells remain firmly attached to the tissue fragment but respond to the forces of smearing. The nuclei can be large, with prominent single nucleoli, but the N:C ratio remains low, and these “switched-on” nuclear features are usually uniform or predictable throughout a particular tissue fragment or sheet. Nuclear hyperchromasia or irregular chromatinic clearing such as perinucleolar clearing and prominent nuclear envelope abnormalities are not usually seen. The nucleoli can be quite large and prominent, particularly in younger women, possibly related to the proliferative phase of the menstrual cycle or to the oral contraceptive pill ( Fig. 5-66 ).

Differential Diagnosis

If a proteinaceous background, histiocytes, and apocrine sheets are also present, the appropriate diagnosis is “fibrocystic change with epithelial hyperplasia,” noting that the proteinaceous background may dilute the bare bipolar nuclei and apocrine hyperplasia may also be present ( Fig. 5-67 ). If large or scalloped or irregular or myxoid stromal fragments are present, then fibroadenoma or perhaps phyllodes tumor can be diagnosed, and if meshwork or stellate papillary tissue fragments are present, intraductal papilloma is diagnosed. Correlation with imaging findings is required.

Partial apocrine metaplasia (see Fig. 5-59 ) can be associated with nuclear enlargement and hyperchromasia in ductal cells that are larger, show increased but not typical copious granular apocrine cytoplasm, and can disperse singly. Seeing the transition from ductal to apocrine cells in sheets is often a clue to this benign process, and myoepithelial cells and bare bipolar nuclei are usually present. Cytologic atypia should be correlated with imaging and clinical findings, but if there is significant atypia (Code 3), then repeat FNAB or core biopsy is required, even if imaging is negative.

Columnar cell change can present incidentally or in FNAB for mass lesions or calcifications. Histologically, the terminal ductules of the lobules are grossly dilated and lined by columnar cells, which often feature a luminal apical bleb of cytoplasm and show a range of simple columnar cell change to columnar cell hyperplasia where the columnar cells are multilayered but still orientated. There is a spectrum with flat epithelial atypia, where the nuclei of the thickened epithelium lining the ballooned terminal duct lack orientation to the lumen and show nuclear atypia. Calcifications including calcium oxalate crystals are frequently present, and the columnar cell change is also often mixed with fibrocystic change and epithelial hyperplasia in adjacent lobules. The FNAB usually produces a cohesive large epithelial tissue fragment pattern with myoepithelial cells and bare bipolar nuclei in a proteinaceous background, but it is variable and can include large ballooned tissue fragments of ductal epithelial cells ( Figs. 5-68 to 5-70 ). These tissue fragments are not papillary and represent the ballooned terminal ductules of the involved lobules. They have an orderly array of nuclei but fewer myoepithelial cells and a central lumen, which can be demonstrated by focusing up and down on the tissue fragment. Large flat sheets and smaller 3-D ductal tissue fragments may have an ordered columnar array with apical snouts at their luminal edge. A small number of dispersed columnar cells, bare bipolar nuclei, and in some cases calcifications are present in a proteinaceous background ( Figs. 5-71 and 5-72 ). Micropapillary and cribriform tissue fragments are not seen. The degree of epithelial hyperplasia and nuclear atypia varies with the spectrum of columnar cell lesions, and in some cases the tissue fragment architecture may suggest cribriform or micropapillary low-grade intraduct carcinoma or the nuclear atypia may be more marked leading to an atypical diagnosis. Core biopsy is required.

The distinction of epithelial hyperplasia from atypical ductal hyperplasia and low-grade intraductal carcinoma is difficult in histopathology, where there is considerable interobserver variability. Ducts showing epithelial hyperplasia, atypical ductal hyperplasia, and low-grade intraductal carcinoma are often intermingled and vary as a lesion is cut through. Pure atypical ductal hyperplasia is seldom seen in histology, making any study that attempts to correlate it with a cytologic diagnosis of “atypical epithelial hyperplasia” problematic. It is not surprising therefore that the diagnosis of “atypical ductal hyperplasia” on cytology is not possible and that the cytologic diagnosis of “epithelial hyperplasia with atypia” correlates poorly with histologic “atypical ductal hyperplasia,” although it is arguable that most cases of atypical ductal hyperplasia probably produce such a cytologic finding. The cytopathologist should decide if the lesion’s features are within the range acceptable for epithelial hyperplasia or whether they are atypical and suggestive of low-grade intraductal carcinoma. In other words, there is no rationale for attempting to make a cytologic diagnosis of “atypical ductal hyperplasia.”

“Atypia” in a breast FNAB report should refer to a pattern of increased dispersed cells or increased architectural complexity of tissue fragments including rigid nuclear arrays and cribriform and micropapillary architecture, or it may refer to nuclear features such as increased size, anisonucleosis, irregularity or hyperchromasia of chromatin, and enlargement or spiculation of nucleoli. However, there are no standardized criteria among cytopathologists for “atypia.” Despite this, lesions with these features require biopsy and are associated in most institutions with increased risks of carcinoma.

Awareness of the characteristic cytologic features of the histologic spectrum from fibrocystic change to proliferative breast disease, which includes epithelial hyperplasia, fibroadenomas, intraductal papillomas, columnar cell change, adenosis, sclerosing adenosis, radial scars, florid epithelial hyperplasia, and so-called “papillomatosis,” allows the cytopathologist in many cases to make a specific diagnosis and at least assess where a particular case should be placed in the spectrum. Each FNAB should be clearly described and, if possible, a specific diagnosis made. If the conclusion raises a DD, including the possibility of low-grade intraductal carcinoma, a core biopsy or, in some cases, excision biopsy is required.

Proliferative breast lesions in the spectrum from epithelial hyperplasia to low-grade intraductal carcinoma produce highly cellular smears. The smear pattern shifts from Pattern 5-3 with large cohesive 3-D tissue fragments with myoepithelial cells and ductal cells with small nuclei and minimal nuclear atypia, which stream around irregular slitlike secondary lumenal holes with bare bipolar nuclei and only focally dispersed cells in the background (see Plate 5-3 [i] ; Figs. 5-61 to 5-67 ), to Pattern 4 where there is a mix of predominantly large but increasing number of small epithelial tissue fragments showing varying degrees of nuclear enlargement and atypia (see Plate 5-4 ). In low-grade intraduct carcinoma the nuclei may show a more rigid organization and cribriform holes and micropapillary extensions may be present with few if any myoepithelial cells (see Plate 5-4 ). Pattern 5-4 can be associated with prominent cell dispersal showing mild to moderate nuclear atypia and scant or no bare bipolar nuclei. The cribriform pattern of intraductal carcinoma should have nuclear orientation to the punched-out lumina, rather than the streaming of nuclei as seen in epithelial hyperplasia ( Figs. 5-73 and 5-74 ), but this can be difficult to assess, particularly in Giemsa smears, where cribriform tissue fragments appear cratered or pockmarked, rather than having punched-out holes (see further discussions and Figs. 5-119 and 5-120 ) in section on low-grade intraductal carcinoma).

Plate 5-1

Pattern 1 Predominantly Small Cohesive Epithelial Tissue Fragments With Myoepithelial Cells and Bare Bipolar Nuclei

Plate 5-1 Table

Pattern 1: Predominantly Small Cohesive Epithelial Tissue Fragments With Myoepithelial Cells and Bare Bipolar Nuclei

Entities in the Differential Diagnosis i) Normal breast ii) Undersampled or sclerotic papillomas and fibroadenomas

Plate 5-2

Pattern 2 Proteinaceous Background

Plate 5-2 Table

Pattern 2: Proteinaceous Background

Entities in the Differential Diagnosis i) Cysts ii) Fibrocystic change iii) Galactocele iv) Inflamed cysts v) Lactating breast (milky proteinaceous background with microvesicular fat) vi) Others including fibrocystic change with epithelial hyperplasia, radial scars, papillomas, and granular cell tumors

Plate 5-3 (i)

Pattern 3 (i) Predominantly Large Epithelial Tissue Fragments With Myoepithelial Cells and Bare Bipolar Nuclei, a Variable Number of Cohesive Smaller Epithelial Tissue Fragments, and Few Dispersed Epithelial Cells: Stereotypical Lesion Is Epithelial Hyperplasia

Plate 5-3 (i) Table

Pattern 3(i): Predominantly Large Epithelial Tissue Fragments With Myoepithelial Cells and Bare Bipolar Nuclei, a Variable Number of Cohesive Smaller Epithelial Tissue Fragments, and Few Dispersed Epithelial Cells

Entities in the Differential Diagnosis i) Epithelial hyperplasia: stereotypical lesion for this pattern ii) Epithelial hyperplasia with fibrocystic change, demonstrated by apocrine sheets, histiocytes, and proteinaceous background iii) Radial scars show high cellularity with epithelial hyperplasia, apocrine sheets, histiocytes, proteinaceous background, and occasional sclerotic stromal tufts iv) Papillomas show epithelial hyperplasia, plus meshwork, stellate papillary, and true papillary tissue fragments in a proteinaceous background with apocrine sheets and siderophages v) Fibroadenomas have hyperplastic and branched epithelial tissue fragments, plus rounded or irregular stromal fragments and plentiful bare bipolar nuclei vi) Benign and borderline phyllodes tumors have hyperplastic epithelial tissue fragments, plus hypercellular stromal fragments and increased dispersed spindle cells vii) Gynecomastia in the male breast

Plate 5-3 (ii)

Pattern 3 (ii) Predominantly Large Epithelial Tissue Fragments With Myoepithelial Cells and Bare Bipolar Nuclei, a Variable Number of Cohesive Smaller Epithelial Tissue Fragments, and Few Dispersed Epithelial Cells: Fibrocystic Change With Epithelial Hyperplasia

Plate 5-3 (ii) Table

Pattern 5-3 (ii): Predominantly Large Epithelial Tissue Fragments With Myoepithelial Cells and Bare Bipolar Nuclei, a Variable Number of Cohesive Smaller Epithelial Tissue Fragments, and Few Dispersed Epithelial Cells: Fibrocystic change With Epithelial hyperplasia.

Entities in the Differential Diagnosis i) Fibrocystic change with epithelial hyperplasia. ii) Radial scars

Plate 5-3 (iii)

Pattern 3(iii) Predominantly Large Epithelial Tissue Fragments With Myoepithelial Cells and Bare Bipolar Nuclei, a Variable Number of Cohesive Smaller Epithelial Tissue Fragments, and Few Dispersed Epithelial Cells: Intraductal Papilloma

Plate 5-3 (iv)

Pattern 3(iv) Predominantly Large Epithelial Tissue Fragments With Myoepithelial Cells and Bare Bipolar Nuclei, a Variable Number of Cohesive Smaller Epithelial Tissue Fragments, and Few Dispersed Epithelial Cells: Fibroadenoma

Plate 5-3 (iv) Table

Pattern 5-3 (iv): Predominantly Large Epithelial Tissue Fragments with Myoepithelial Cells and Bare Bipolar Nuclei, a Variable Number of Cohesive Smaller Epithelial Tissue Fragments, and Few Dispersed Epithelial Cells: Fibroadenoma

Entities in the Differential Diagnosis i) Fibroadenoma ii) Phyllodes tumors

Plate 5-4

Pattern 4 Predominantly Large Epithelial Tissue Fragments, a Variable Number of Discohesive Smaller Epithelial Tissue Fragments, and Plentiful Dispersed Epithelial Cells

Plate 5-4 Table

Pattern 4: Predominantly Large Epithelial Tissue Fragments With Scant Myoepithelial Cells and Bare Bipolar Nuclei, a Variable Number of Discohesive Smaller Epithelial Tissue Fragments, and Plentiful Dispersed Epithelial Cells

Entities in the Differential Diagnosis i) Low- and intermediate-grade intraductal carcinoma ii) Some infiltrating ductal carcinomas

Plate 5-5

Pattern 5 Predominantly Small Discohesive Epithelial Tissue Fragments With Plentiful Dispersed Cells

Plate 5-5 Table

Pattern 5: Predominantly Small Discohesive Epithelial Tissue Fragments With Plentiful Dispersed Cells

Entities in the Differential Diagnosis i) Invasive ductal carcinoma ii) Invasive micropapillary carcinoma iii) Carcinoma with medullary features iv) Tubular carcinoma v) Metaplastic carcinomas vi) Metastatic carcinomas and melanoma (NOTE: Angiosarcomas can present with epithelioid tissue fragments and dispersed cells.)

Plate 5-6

Pattern 6 Dispersed Cells

Plate 5-6 Table

Pattern 6: Dispersed Cells

Entities in the Differential Diagnosis i) Lobular carcinoma ii) High-grade invasive ductal carcinoma iii) Lymphoma iv) Intramammary lymph nodes v) Dispersed apocrine cells and histiocytes in a proteinacous background in fibrocystic change

Plate 5-7

Pattern 7 Prominent Necrosis

Plate 5-7 Table

Pattern 7: Prominent Necrosis

Entities in the Differential Diagnosis i) High-grade intraductal carcinoma has necrosis and microcalcifications with discohesive epithelial tissue fragments showing high nuclear grade ii) High-grade infiltrating ductal carcinoma including basal-like carcinomas iii) Metaplastic carcinoma iv) Fat necrosis, which usually has no epithelium

Plate 5-8

Pattern 8 Mucinous Background

Plate 5-8 Table

Pattern 8: Mucinous Background

Entities in the Differential Diagnosis i) Mucinous carcinoma ii) Secretory carcinoma iii) Myxoid change in a fibroadenoma iv) Mucocele-like lesions with mucin from inspissated ducts or cysts

Microcalcifications can be seen in epithelial hyperplasia, columnar cell change (see Figs. 5-71 and 5-72 ), and low-grade intraductal carcinoma (see Fig. 5-31 ).

Hyperplastic ductal epithelial tissue fragments may contain small, rounded magenta (Giemsa) or pale green (Pap) globules known as collagenous spherulosis ( Fig. 5-75 ), whose only significance is their differentiation from the generally larger and more numerous hyaline globules seen in adenoid cystic carcinoma. In some cases there may be plentiful globules, usually more variable in size ringed by myoepithelial cells within hyperplastic tissue fragments of bland epithelial cells with scattered bare bipolar nuclei.

Adenoid cystic carcinoma occurring in the breast can show similar variation in grade to those seen in the salivary glands but tends to show more dispersal, nuclear crowding and atypia, and larger, rounded, more plentiful globules than collagenous spherulosis, but the DD can be problematic. If a small number of spherules are seen in a background typical of fibrocystic change or papilloma or fibroadenoma, then the diagnosis of collagenous spherulosis can be made. If such a background is not present and the globules are frequent, or associated with nuclear atypia or prominent dispersal, core biopsy should be recommended to exclude adenoid cystic carcinoma (see section on adenoid cystic carcinoma for further discussion and Figs. 5-200 to 202 ).

Clinical Features

These mammographically detected stellate proliferative lesions are difficult on ultrasound and mammography to distinguish from small carcinomas, leading to frequent excision biopsy. Histologically, radial scars show central and radiating sclerosis, containing distorted tubules, ductal epithelial hyperplasia with or without atypia, apocrine change, adenosis, sclerosing adenosis, and in some cases, atypical ductal hyperplasia, low-grade intraduct carcinoma, or tubular carcinomas.

It is essential to recognize their cytologic features to avoid false-positive diagnoses because they often present to the cytopathologist with a malignant diagnosis on imaging. Alternatively, a mammographic “radial scar” may on FNAB reveal cancer, advancing the management of a particular patient.

Cytopathology

The cytologic features resemble florid fibrocystic change with epithelial hyperplasia.

Differential Diagnosis

The DD includes fibrocystic change with epithelial hyperplasia; intraductal papillomas with epithelial hyperplasia, which can coexist in radial scars, and have distinctive meshwork, stellate “papillary,” and true papillary tissue fragments (see Plate 5-3 [iii] ); fibroadenomas with branching hyperplastic epithelium, rounded stromal fragments, and plentiful bare bipolar nuclei (see Plate 5-3 [iv] ); low-grade intraductal carcinoma, which may have micropapillary or cribriform tissue fragments and increased dispersal of single cells with nuclear atypia (see Plate 5-4 ); and tubular carcinoma, which is a major imaging DD but has distinctive cytology of mild to moderate cellularity with predominantly small, angulated crowded tubules showing moderate nuclear atypia, a lack of myoepithelial cells and bare bipolar nuclei, and more frequent dispersed atypical cells with nuclear atypia in the background.