Breast-Nonmalignant

Painful, erythematous, subareolar mass, may have fistulous tract; associated with smoking (Int J Clin Pract 2005;59:1045), possibly pituitary adenomas and increased prolactin levels (AJSP 1988;12:130)

Recurrences may cause nipple inversion or discharge, resembling carcinoma

Late stage is ductitis obliterans or mastitis obliterans with total occlusion of ducts (Breast J 2007;13:599)

Case reports: causing bloody nipple discharge in 2 year old boy (Turk J Pediatr 2005;47:379), 13 year old girl (J Natl Med Assoc 2004;96:543), associated with Bechet’s disease (Saudi Med J 2001;22:1030)

Treatment: excise duct and fistulous tract in continuity

Gross: nipple discharge in 20%; skin retraction from fibrosis may mimic cancer; dilated large ducts with fatty (cheesy) material in lumen

Micro: dilated large ducts with fibrous thickening of wall, elastic fibers in wall and foamy macrophages in lumen; often calcifications; keratin goes deep within ductal system causing dilation and rupture of duct with intense chronic and granulomatous inflammation; may have associated epithelial hyperplasia or apocrine metaplasia

Cytology: paucicellular, with few scattered, cohesive clusters of ductal epithelial cells with mild atypia and peripheral myoepithelial cells; also CD68+ macrophages with finely vacuolated cytoplasm (Acta Cytol 2001;45:1027)

Micro images: AFIP - ducts are dilated with sparse secretions, lower duct is partially disrupted releasing material into stroma and causing periductal fibrosis and elastosis; dilated duct has amorphous stasis material and lymphoid nodules at sites of secondary duct branching; periductal lymphocytes, thickened basement membrane and lack of cells in duct contents; narrowed duct lumen due to periductal collagen and elastic tissue

other - dilated ducts with foamy macrophages and periductal inflammatory infiltrate; late stage with hemosiderin-laden macrophages; foamy macrophages below luminal epithelium; other images #1; #2; #3; #4; periductal scarring (late) #1; #2

References: Stanford University

Fat necrosis of breast

top Home Page

Simulates carcinoma clinically and mammographically

May be associated with duct ectasia, fibrocystic change, trauma (including surgery), brachytherapy or radiation (Int J Radiat Oncol Biol Phys 2007;69:724), injections of Depixol (J BUON 2002;7:281), low molecular weight heparin (Age Ageing 2005;34:193) or methylene blue dye (Int Semin Surg Oncol 2005;2:26)

Frozen sections difficult to obtain due to high fat content of specimen

Clinical images: skin and fat necrosis due to methylene blue dye; due to coumadin

Gross: opaque, bright yellow

Gross images: hemorrhagic fat necrosis

Micro: partially necrotic adipose tissue with foamy macrophages, multinucleated giant cells and chronic inflammatory cells; often hemosiderin deposits, fibrosis and calcification; occasional metaplastic squamous epithelium

Micro images: giant cells and microcalcification; necrotic adipocytes and calcification; with metaplastic squamous epithelium with keratin whorls (AFIP); irregular fatty spaces and foamy macrophages; foamy macrophages and calcifications #1; #2; #3; #4; giant cells; giant cells engulfing lipid; pap stain (inset Giemsa)

Cytology images: fat necrosis #1; #2; #3

Virtual slides: traumatic fat necrosis

Videos: traumatic fat necrosis

Foreign body reaction of breast

top Home Page

Also called biopsy site changes

Usually localized; occurs 1-2 weeks after trauma, surgery or radiation

Clinically resembles carcinoma due to skin retraction

Case reports: injections - carbon for biopsy tracking (Clin Radiol 1998;53:845), gear oil (Indian J Pathol Microbiol 2007;50:373), hydrophilic polyacrylamide gel (Hong Kong Med J 2007;13:137), paraffin (Breast 2006;15:540), petroleum jelly (South Med J 2008;101:422)

Gross: localized to subcutaneous tissue; may be nodular, fibrotic, orange-brown (due to hemosiderin); up to 1 cm

Micro: not encapsulated; fibrosis, foreign body giant cells, chronic inflammatory cells, fat necrosis, calcification, cholesterol clefts (needle like empty spaces, due to substances dissolved during processing), hemosiderin; may see a foreign body

Micro images: foreign body reaction to suture material; biopsy site changes with fibrosis and hemosiderin deposition; fibrosis and multinucleated giant cells; small blood vessel proliferation and giant cells; collagen plug inside biopsy cavity #1; #2; asteroid body; granulation tissue; post-gunshot wound

Virtual slides: foreign body reaction to silicon

Videos: foreign body reaction

Fungal infections of breast

top Home Page

Report of saline filled breast implant contaminated with Curvularia in 5 patients (J Infect Dis 2005;192:170)

Case reports: immunosuppressed patient with breast nodule due to coccidiomycosis (Archives 1991;115:1064), cryptococcus in HIV+ patient (J Infect 2008;57:82), fusarium (Indian J Med Microbiol 2005;23:198), Histoplasma capsulatum causing granulomatous mastitis (Hum Path 1989;20:47, Archives 2006;130:e1), bilateral male breast enlargement due to Trichophyton rubrum (Breast 2006;15:263)

Micro images: Fusarium - clinical image and FNA smears; Histoplasma capsulatum - fig 1: necrotizing granulomatous inflammation; fig 2/3: histiocytes contain multiple intracellular organisms with peripheral clearing; fig 4: GMS shows yeast with narrow-based buds and nonbudding yeast

Giant cell arteritis of breast

top Home Page

Usually post-menopausal women with firm mass that mimics carcinoma

May be systemic manifestations, but no temporal artery involvement

Case reports: 56 year old woman with breast tenderness but no systemic complaints (Med Princ Pract 2004;13:234), bilateral involvement (Am J Med Sci 2008;335:489)

Micro: involvement of small and medium sized arteries with transmural and perivascular infiltrate of lymphocytes, histiocytes and giant cells; elastic stain shows fragmentation of elastic fibers in vessel wall

Micro images: AFIP - intramammary arterial lumen is mostly obliterated by subintimal and mural inflammation, including giant cells (arrows); transmural necrotizing inflammation of medium sized mammary vessels, with elastic stain showing partial destruction of elastic layer

DD: polyarteritis nodosa, Wegener’s granulomatosis

References: Hum Path 1987;18:1186

Granulomatous mastitis (idiopathic)

top Home Page

Rare; young women with inflammatory breast processes (Ann NY Acad Sci 2007;1108:603)

Diagnosis of exclusion

Median age 36 years, not related to smoking (J Am Coll Surg 2008;206:269)

Possibly due to Corynebacterium (Pathology 2003;35:109, J Clin Microbiol 2007;45:1666)

Case report: 20 year old woman with large ulcer (The Internet Journal of Surgery 2007;13(2)), 35 year old woman with tender breast mass (Jpn J Clin Oncol 1997;27:274), 36 year old woman with mass (Int Semin Surg Oncol 2007;4:21)

Treatment: no consensus-observation, glucocorticoids, surgery (Am Surg 2007;73:798); may recur or be locally aggressive

Clinical images: appearance of second lump post-biopsy; firm mass with multiple sinuses

Gross: firm/hard faintly nodular mass

Gross images: resembles infiltrating ductal carcinoma; ulcer replaces breast tissue

Micro: granulomatous inflammation centered on lobules with lymphocytes, plasma cells, epithelioid histiocytes, multinucleated giant cells; may be neutrophils; necrosis in 11%

Cytology: abundant epithelioid histiocytes and neutrophils, variable granulomas, usually no necrosis (J Clin Path 2003;56:519)

Micro images: granulomatous inflammation centered on breast lobules #1; #2; #3; inflammatory reaction in lobules with giant cells (AFIP); nonnecrotizing granulomas with giant cells #1; #2; multinucleated giant cells; granulomatous inflammation

Cytology images: epithelioid histiocytes in an inflammatory background #1; #2; #3; atypical cells, suspicious for carcinoma

Negative stains: GMS and PAS for fungi or mycobacteria

DD: systemic granulomatous disease (Wegener's granulomatosis, sarcoidosis), infections (mycobacteria, fungi, cat scratch disease, Archives 1989;113:473), granulomatous angiopanniculitis (involves subcutis and extends into breast, Hum Path 1989;20:1084), foreign body reaction, fat necrosis

References: Archives 1994;118:822, Pathology 2004;36:254

Hemorrhagic necrosis in breast

top Home Page

Unusual complication of warfarin therapy (Ann Surg 1972;175:647)

Warfarin causes hemorrhagic necrosis of skin in 0.1 to 1.0% of patients (Br J Plast Surg 2000;53:624)

Rapid onset after initiation of therapy

Associated with protein S/C deficiency

Case reports: resembling inflammatory carcinoma (J Postgrad Med 2004;50:268)

Treatment: may require mastectomy

Clinical images: hemorrhagic necrosis of breast

Micro: widespread necrosis with multiple small vessel thrombi

Micro images: venous thrombosis and necrotizing arteritis; necrotizing arteritis; intimal necrosis of artery

Infarct in breast

top Home Page

Associated with intraductal papilloma, fibroadenoma, pregnancy-like hyperplasia, lactating adenoma, phyllodes tumor

May be spontaneous (J Clin Pathol 1975;28:937), but also associated with fine needle aspiration (Archives 1996;120:1069)

Special stains (reticulin or trichrome) may demonstrate residual fibrous structure

Case reports: infarcted lactating adenoma (AJR Am J Roentgenol 1999;173:933)

Clinical images: infarcted lactating adenoma

Micro: necrosis and ghost cells, hemosiderin; usually no thrombi are identified

Cytology: initially degenerated cells with smudged nuclei, ghost cells and necrotic debris; later fibroblasts, ductal cells and necrotic debris (Diagn Cytopathol 2006;34:373)

Micro images: AFIP - infarct in post-partum breast with lactational change #1; #2 with outlines of ductules in infarcted tissue other - sharply circumscribed border; partial infarction of hyperplastic lobules; coagulative necrosis of hyperplastic lobules (reticulin stain); infarct with foamy macrophages; partial luminal obliteration of medium sized vessels (elastic stain); organizing thrombus in vein; infarcted lactating adenoma #1; #2 (note zonal pattern); #3

Lupus mastitis

top Home Page

A subset of breast-limited lupus panniculitis

Case reports: 33 year old woman with SLE and acute breast pain (J Obstet Gynaecol Res 2008;34:919), 44 year old woman with lupus nephritis but no systemic disease (AJR Am J Roentgenol 2002;178:1233)

Treatment: usually medical, not surgical

Micro: necrotizing vasculitis, fat necrosis with microcalcifications

Micro images: perivascular lymphocytic infiltrate; dense fibrosis with calcifications

Lymphocytic mastitis

top Home Page

Also called diabetic mastopathy or sclerosing lymphocytic mastitis/lobulitis if prominent fibrosis

Uncommon; usually women; often associated with type I / insulin dependent diabetes (Diabetes Care 2000; 25:121) or other autoimmune disease, but may occur in type II diabetes or non-diabetes

May occur in men, associated with gynecomastia (Pathol Res Pract 1997;193:197)

Rarely associated with DCIS

No increased risk of lymphoma

Case reports: 66 year old woman with multiple bilateral masses (AJSP 2006;30:1330), associated with lymphoepithelioma-like carcinoma (Archives 2001;125:669)

Treatment: excision; often recurs (30%, AJCP 2000;113:541)

Gross: clinically palpable mass, usually subareolar; gray-white, smooth cut surface; often bilateral

Micro: ill defined lesion of dense intralobular, perilobular and perivascular lymphocytes with lobular atrophy and sclerosis (keloidal fibrosis), B cell lymphoepithelial lesions, lymphoid follicles with germinal centers; also histiocytes and fibroblasts; epithelioid fibroblasts may be mistaken for carcinoma or granular cell tumor (Mod Path 1994;7:49); variable fat necrosis, noncaseating granulomas; no changes in overlying epidermis

Cytology: clusters of ductal cells, lymphocytes and epithelioid fibroblasts in fragments of dense connective tissue (Acta Cytol 1997;41:1349)

Micro images: perivascular lymphocytic infiltrate sparing lobules (AFIP); keloid-like fibrosis and prominent lymphoid infiltrate around breast ducts/lobules #1; #2; #3; lymphoepithelial lesion; keloidal fibrosis; CD20+/CD3- lymphocytes (B, not T cells); various images

findings in men - periductal lymphocytes and dense collagenous stroma #1; #2

Positive stains: B cell markers

Molecular: lymphocytes are not clonal (Mod Path 2003;16:223)

DD: MALT lymphoma (clonal), sinus histiocytosis with massive lymphadenopathy, gigantomastia (perilobular lymphocytic infiltrate is CD3+, different clinical findings, J Clin Endocrinol Metab 2005;90:5287)

References: Hum Path 1994;25:819, Hum Path 1992;23:780, Mod Path 1995;8:349, Radiology 2001;219:797 (similar clinical findings in men), Stanford University

Mondor’s disease of breast

top Home Page

Rare; thrombophlebitis of superficial veins of breast and adjacent thoracoabdominal wall

Sudden onset of firm, painful, nodular cord beneath skin

Self-limited, only rarely recurs

May be related to trauma, such as radical mastectomy, but not associated with breast cancer

Case reports: after core biopsy (AJR Am J Roentgenol 2002;179:185)

Treatment: anti-inflammatory drugs, excision of thrombosed vein or no treatment (Eur J Gynaecol Oncol 2005;26:213)

Clinical images: cord on lateral breast #1; #2; cords between breast and abdomen; 53 year old man #1; #2; shallow linear depression

Micro: phlebitis with thrombosis; late recanalization occurs

References: eMedicine

Nephrogenic systemic fibrosis in breast

top Home Page

Previously called nephrogenic fibrosing dermopathy

Recently described systemic fibrosing disorder primarily affecting patients with chronic renal insufficiency

Skin involvement may resemble peau d'orange

Only one case reported to date involving breast

Case reports: bilateral breast changes resembling inflammatory carcinoma (Archives 2007;131:145)

Micro images: fibrocollagenous thickening of dermis with clefts in reticular dermis and perivascular plasmacytic dermal infiltrate; fibroblast like cells and stromal mucin (Alcian blue+); spindle cells are CD68+ and CD34+

Plasma cell mastitis

top Home Page

Considered a variant of periductal mastitis/duct ectasia with prominent plasma cell component

Associated with pregnancy, occurs a mean 4 years after cessation of lactation

Resembles carcinoma clinically

Very few recent articles in English medical literature using this terminology

Clinical: firm mass, 2-3 cm, with nipple discharge and retraction; often axillary adenopathy

Case reports: 35 year old woman with breast abscess (Postgrad Med J 1958;34:654), bilateral involvement (Br Med J 1949;1:94)

Treatment: excision to avoid ulceration and fistulas

Gross: dilated ducts with creamy secretion

Micro: hyperplasia of ductal epithelium with markedly diffuse plasma cell infiltrate of ducts and lobules; often granulomatous reaction

Cytology: prominent plasma cells and histiocytes; also hyperplastic epithelial cells

Micro images: infiltrate of plasma cells, macrophages, lymphocytes (AFIP)

Polyarteritis nodosa of breast

top Home Page

See also giant cell arteritis of breast

Also called periarteritis nodosa

Case reports: two cases (Histopathology 1993;23:535), presenting as an isolated breast lesion (Br J Dermatol 1999;141:1117)

Micro: vasculitis of medium and small arteries; medium arteries have intimal fibroplasia, fragmentation of internal elastic lamina and inflammatory cellular infiltration; small arteries have fibrinoid vasculitis

Micro images: site unknown-intimal hyperplasia

Reactive spindle cell nodule of breast

top Home Page

Usually after core biopsy or fine needle aspiration

Similar tumors in bladder, prostate, other GU sites, but few publications in breast

Associated with biopsy of complex sclerosing lesions and papillary lesions (AJCP 2000;113:288)

May be due to exuberant reparative process

Gross: up to 1 cm, nodular, not encapsulated

Micro: spindle cells with mild/moderate nuclear pleomorphism, small vessel proliferation, foam cells, lymphocytes, hemosiderin; no/rare mitotic figures

Positive stains: spindle cells - smooth muscle actin, muscle specific actin

DD: inflammatory myofibroblastic tumor, nodular fasciitis, myofibroblastoma, fibromatosis, low grade spindle cell carcinoma, low grade sarcoma

Sarcoidosis of breast

top Home Page

Abnormal breast examinations or mammograms in 2% of sarcoidosis patients, granulomas in 1% (Sarcoidosis Vasc Diffuse Lung Dis 2001;18:301)

Occasionally begins in breast and remains localized for long periods

Note: sarcoidosis may also mimic metastatic breast cancer (Clin Breast Cancer 2007;7:804)

Case reports: systemic disease and breast mass (Eur Rev Med Pharmacol Sci 2006;10:47, free full text)

Micro: noncaseating, epithelioid granulomas with multinucleated giant cells; no/rare necrosis

Cytology: epithelioid cells and lymphocytes

Micro images: stromal granulomas sparing lobules (AFIP); non-necrotizing granulomatous inflammation #1; #2; #3; #4

DD: mycobacteria, fungi, foreign material, granulomatous mastitis

References: Archives 1984;108:673, Hum Path 1985;16:851, Hum Path 1985;16:185

Silicone breast implants

top Home Page

Used for breast construction post-mastectomy or for breast augmentation

Do not cause systemic disease, but can leak and rupture, causing local scarring, infection and disfigurement

Recommended to photograph and describe surface of removed implant for possible litigation (Mod Path 2000;13:1050)

Can chemically identify silicon inclusions with Raman spectroscopy (Mod Path 1999;12:714)

Several reports of anaplastic large cell lymphoma adjacent to implants (Mod Path 2008;21:455, Archives 2003;127:e115, AJSP 2008;32:1265)

Case reports: capsular synovial metaplasia mimicking silicone leak of breast prosthesis (J Med Case Reports 2008;2:277), leaky implant associated with Kikuchi-Fujimoto disease (Archives 1996;120:380), synovial metaplasia of periprosthetic breast capsule (Archives 1994;118:249); follicular lymphoma and adjacent granulomatous response to foreign material next to silicone implant (AJSP 1995;19:712)

Gross images: silicon implant (diagrams)

Micro: chronic inflammatory response (plasma cells, B and T cells and foamy macrophages) with fibrotic capsule around the implant causing contracture of prosthesis; lining cells may resemble synovium (synovial metaplasia, Mod Path 1994;7:310), gel may seep through intact implant shells; may have foreign body reaction with sinus tracts; numerous cystic spaces and vacuoles may exist where silicon dissolves during processing

Micro images: injected silicone (AFIP) - refractile silicone and giant cell reaction #1; #2 (arrow at doubly-refractile silicon) polyurethane implant (AFIP) - polyurethane (arrow) and silicone (round globules)

silicone implants - dense fibrosis and chronic inflammatory cells in capsule (AFIP); giant cell reaction and silicone #1; #2; #3; #4; #5; capsular synovial metaplasia

Virtual slides: foreign body reaction

References: AJSP 1995;19:433, Mod Path 1999;12:706, Mod Path 1994;7:728, Hum Path 1985;16:19, eMedicine, Wikipedia

Axillary lymph nodes and silicone

top Home Page

Due to implantation of bag-gel prosthesis for mammary augmentation or migration of injected silicone

Either an incidental finding or causes painful / enlarged lymph node

Case reports: rupture of high cohesive gel implant (J Plast Reconstr Aesthet Surg 2006;59:885), evidence of silicon migration (Br J Plast Surg 2005;58:1027)

Micro: usually foamy macrophages (scattered or sheets), refractile droplets of clear material consistent with silicone, granulomatous inflammation (Histol Histopathol 1997;12:1003), occasionally foreign polygonal fragments consistent with polyurethane

Cytology: birefringent material with foreign body giant cells in lymphoid background (Acta Cytol 1999;43:1163)

Micro images: fig 1b: histiocytes with variably sized cytoplasmic vacuoles

DD: sinus histiocytosis with massive lymphadenopathy

References: AJSP 2005;29:506, AJSP 1988;12:484, Archives 1981;105:371

Tuberculosis of breast

top Home Page

Rare in general, but common in India (The Internet Journal of Tropical Medicine 2005;2(2))

Usually unilateral without pulmonary involvement (ANZ J Surg 2006;76:234)

For breast cancer patients with granulomatous axillary lymphadenitis, PCR may be required to rule out TB in endemic regions (Pathol Res Pract. 2007;203:699)

Case reports: coexisting with ductal carcinoma (World J Surg Oncol 2008;6:29), mimicking breast cancer (J Med Case Reports 2008;2:34)

Clinical images: resembles breast carcinoma

Gross: multiple sinuses

Micro: granulomas with Langhans giant cells and caseous necrosis (often)

Cytology: foamy histiocytes, neutrophils, necrotic debris

Micro images: AFIP - granulomatous inflammation of major lactiferous duct with epithelial necrosis; granulomatous inflammation and Langhans giant cells

other - granuloma with central necrosis and epithelioid histiocytes #1; #2-also Langhans giant cells and prominent lymphocytes; acid-fast bacilli; ductal carcinoma plus epithelioid granuloma (upper right)

Fibrocystic disease of breast

Fibrocystic disease of breast - general

top Home Page

Also called fibrocystic change

A general category for numerous entities, detailed below

Cystic features are usually prominent, but there may not be fibrosis

Not necessarily a disease that requires treatment, but Rosai favors "fibrocystic disease" over “fibrocystic change” because the constellation of findings fulfills the criteria for a disease, similar to nodular hyperplasia of the prostate

Common in women ages 25-45 years, more common in Americans/Europeans than Japanese or South American women

More common in women with polycystic ovaries (based on radiology, not histology, Minerva Ginecol 2000;52:321)

Benign, not neoplastic, but may be confused with malignancy

Usually bilateral, although one breast may be affected more than the other

Associated with hormonal imbalance (increased estrogen to progesterone ratio); decreased risk with oral contraceptives, perhaps due to balanced supply of estrogens and progesterone

Either proliferative (adenosis, hyperplasia) or nonproliferative (cysts)

The specific proliferative disease present determines the relative risk for subsequent carcinoma, varying from 1x (no increased risk) to 5x for atypical ductal hyperplasia (AJSP 2003;27:836)

Gross images: cysts surrounded by fibrous tissue #1; #2; #3

Micro: primarily affects the terminal duct lobular unit, not the large ducts; see specific types below

Micro images: various images

Virtual slides: #1

Apocrine metaplasia of breast

top Home Page

Common, associated with dilated ducts and cysts

Apocrine cysts may contain fluid under pressure

Benign, but risk factor (low) for cancer (Cancer Epidemiol Biomarkers Prev 2007;16:467)

Highly complex papillary apocrine change: rare, often coexists with ADH (Cancer Epidemiol Biomarkers Prev 1996;5:29)

Micro: cells resemble apocrine sweat glands, are enlarged with abundant eosinophilic cytoplasm and apical snouts, often supranuclear vacuoles, medium sized nucleus but prominent nucleoli; changes may be partial/incomplete; may have more atypical features in sclerosing adenosis

Cytology: atypical apocrine metaplasia with signet ring cells (such as from sclerosing papilloma) may resemble mucinous carcinoma (Acta Cytol 2002;46:749)

Micro images: subgross #1; #2; apocrine metaplasia #1; #2; #3; #4; #5; #6; #7; #8; #9; #10; #11; with epithelial hyperplasia; papillary epithelial hyperplasia; papillary proliferation; strong androgen receptor staining #1; #2; #3; CK19+; GCDFP-15+; negative for ER alpha; negative for progesterone receptor (positive internal control in normal breast at upper left); highly complex papillary apocrine change #1; #2; #3

Cytology images: apocrine metaplasia #1; #2; #3; #4

Positive stains: PAS (coarse glycolipid granules), GCDFP-15, androgen receptor (J Clin Pathol 1999;52:838); c-myc (nuclear staining, but no amplification by FISH, Breast 2002;11:466)

Negative stains: ER, PR, p53, low Ki-67 (Mod Path 2000;13:13)

Molecular: loss of heterozygosity in 53% (Am J Pathol 2000;157:323)

Chronic inflammation of breast

top Home Page

Common

Associated with cyst rupture and release of secretions into stroma

DD: mammary duct ectasia, foreign body reaction, lymphocytic mastitis

Collagenous spherulosis of breast

top Home Page

Rare variant of epithelial ductal hyperplasia first described in 1987 (AJSP 1987;11:411)

Almost always an incidental finding, only rarely presents as a mass

Associated with intraductal papilloma, sclerosing adenosis and radial sclerosing lesions

Benign, but often mistaken for intraductal or invasive carcinoma

Also seen in salivary gland tumors

Case reports: involvement by LCIS (AJSP 1995;19:1366), in adenomyoepithelioma (J Clin Pathol 2004;57:83), with DCIS (Pathologica 2002;94:317)

Gross: usually multifocal, 1 to 3 mm

Micro: intraluminal clusters of eosinophilic or rarely basophilic (“mucinous spherulosis”, Archives 1999;123:626), collagen-rich spherules within spaces between epithelial and myoepithelial cells or intraductal; usually an incidental finding; associated with LCIS (25%) and microcalcifications (25%, AJSP 2006;30:20)

Cytology: hyaline pink globules surrounded by benign myoepithelial cells in Giemsa stained smears (Cytopathology 2002;13:116)

mucinous spherulosis - cribriform structures with lightly basophilic material embedded in loosely mucinous acellular background; intermediate to large, round hyaline spherules are naked or surrounded by myoepithelial cells; Diff-Quik stain shows fibrillary radial appearance (Diagn Cytopathol 2006;34:626)

Micro images: AFIP - collagenous spherulosis #1; #2

other - collagenous spherulosis #3; #4; #5; #6; #7; basophilic spherules (mucinous spherulosis); tubular adenosis with features of collagenous spherulosis; adenoid cystic carcinoma (first column) vs. collagenous spherulosis (second column); p63; c-kit

Positive stains: myoepithelial cells - smooth muscle actin, smooth muscle myosin heavy chain, calponin, p63 (nuclear staining, examine at high power, Mod Path 2006;19:1351)

Negative stains: myoepithelial cells - c-kit/CD117

EM: epithelial cells and myoepithelial cells plus associated basement membrane-like material (Breast J 2000;6:199)

EM images: fig 7B: amorphous material with thick fibrils showing periodic banding

DD: adenoid cystic carcinoma (denser and tightly nodular material is rarely degenerated, stromal invasion, CD117+ luminal cells, calponin and smooth muscle actin negative, may have collagenous spherulosis like structures, Pathol Int 2004;54:332), signet ring carcinoma

References: Stanford University

Columnar cell lesions of breast

top Home Page

See also flat epithelial atypia

Also called blunt duct adenosis, columnar alteration with prominent apical snouts and secretions, columnar metaplasia, enlarged lobular units with columnar alteration (AJSP 2005;29:105)

Frequent finding in breast biopsies for mammographic calcifications (AJSP 1998;22:1521); may be associated with lobular neoplasia in these patients (AJCP 2008;130:254)

May be associated with atypical hyperplasia, but otherwise no significantly increased risk of breast carcinoma (Cancer 2008 Sep 24 [Epub ahead of print])

Appears to be a clonal (neoplastic), nonobligate, intermediate step in development of some forms of low grade DCIS and invasive carcinoma (AJSP 2005;29:734); present in 95%+ cases of tubular carcinoma (AJSP 2007;31:417, Adv Anat Pathol 2008;15:140)

Recommended to merely note the presence of this lesion if no atypia, to identify ADH or DCIS if present, and to submit additional tissue / obtain additional levels if atypia is present (AJSP 2002;26:1095)

Classifications below with atypia (types 3-6) have lowest diagnostic reproducibility (J Clin Pathol 2005;58:705)

Classification: Schnitt (Adv Anat Path 2003;10:113) modified by Simpson (AJSP 2005;29:734)

[All have variable dilated acini, cytoplasmic snouts and intraluminal secretions; several types may coexist in same breast]

Type 1 (columnar cell change): 1-2 cell layers; columnar cells have uniform ovoid/elongated nuclei perpendicular to basement membrane; no/inconspicuous nucleoli; may have apical snouts but usually not prominent

Type 2 (columnar cell hyperplasia): >2 stratified cell layers with variable nuclear crowding and cellular micropapillations, but no complex architectural patterns (i.e. no rigid bars, bridges or well-formed micropapillary structures); cytology similar to type 1 but may have hobnail cells; associated with intraluminal calcification

Type 3 (columnar cell hyperplasia with architectural atypia): >2 stratified cell layers with complex architectural patterns (micropapillary, tufts, fronds, arcades, rigid bridges or punched out spaces); type 2 cytology

Type 4 (columnar cell hyperplasia with cytologic atypia): type 2 architecture; mild to moderate cytologic atypia, may resemble tubular carcinoma

Type 5 (columnar cell hyperplasia with cytologic and architectural atypia): type 3 architecture; type 4 cytology

Type 6 (columnar cell change with cytologic atypia): 1-2 cell layers; type 4 cytology

Columnar cell lesion of breast (continued)

top Home Page

Xray: ossifying-type calcifications-a peculiar, infrequent type of calcification found in mammary duct lumina, with a central core of calcification and a rim of ossifying-type matrix reminiscent of osseous tissue but not lined by osteoblasts or osteocytes (Archives 2002;126:995)

Treatment: excision is recommended if atypia found at core biopsy (Am Surg 2007;73:984)

Micro: distended, unfolded terminal duct lobular units lined by tightly packed columnar epithelial cells with prominent apical cytoplasmic snouts and intraluminal secretions; cells may have clear cytoplasm; variable cytologic atypia and architectural complexity (see classification); may be associated with ADH or low grade DCIS

Cytology: flat sheets of cells with enlarged nuclei, distinct cell borders, finely granular cytoplasm; usually few myoepithelial cells; resembles papillary neoplasms and well differentiated adenocarcinoma (Diagn Cytopathol 2007;35:73)

atypical features: cohesive 3D clusters of enlarged polygonal epithelial cells mixed with myoepithelial cells centrally and palisading columnar cells peripherally; often bipolar nuclei and apical snouts (Diagn Cytopathol 2004;31:370)

Micro images: columnar cell change - #1; #2; #3; #4; #5; #6; #7; #8; with microcalcifications #1; #2; #3; #4; ossifying-type calcifications (dense basophilic, smooth, round calcifications surrounded by ossifying matrix); with calcium oxalate crystals #1; #2; ”blunt duct adenosis” #1; #2; adenosis with columnar cell change #1; #2; with DCIS

columnar cell hyperplasia - #1; #2; #3; #4; #5; #6; psammomatous calcification; in mucocele-like tumor #1; #2

columnar cell hyperplasia with atypia - #1; #2; columnar cell change with flat epithelial atypia #1; #2

Virtual slides: columnar cell change with atypia

Positive stains: ER (strong, Breast J 2005;11:326), PR, CK19; also bcl2, Ki-67 increased but less than carcinoma (Hum Path 2007;38:284)

Negative stains: CK 5/6, CK14, 34betaE12, HER2, p53

Molecular: no mutational changes in simple columnar change; progressive accumulation of allelic damage with atypia, DCIS or invasive carcinoma, involving 9q, 10q, 17p and 17q (Mod Path 2006;19:344)

DD: cystic hypersecretory hyperplasia (secretions, but no apical snouts), apocrine metaplasia

References: Stanford University

Cystic hypersecretory hyperplasia of breast

top Home Page

Associated with pregnancy-like (pseudolactational) hyperplasia (AJSP 2000;24:1670)

Either asymptomatic with mammographic abnormality or palpable mass

May coexist with atypia or DCIS of cystic hypersecretory type, so sample generously

Case reports: 48 year old woman with mass exhibiting atypia (Archives 2003;127:e389)

Treatment: wide excision (Cancer 1988;61:1611); if atypia present at core biopsy, excise entire lesion because DCIS is often present (AJSP 2004;28:789)

Gross: resembles juvenile papillomatosis of the breast; large, ill-defined, firm to rubbery, spongy mass of fibrous tissue containing multiple small cysts; also abundant thick, sticky mucin within the cysts

Gross images: dilated cysts with gelatinous type material #1; #2

Micro: cystically dilated ducts of various sizes with colloid-like material, often with parallel fracture lines, retraction halo and overlapping due to processing; ducts are lined by flat, orderly, columnar epithelial cells with eosinophilic cytoplasm, nuclei are round/oval, vesicular, bland; atypical features are epithelial crowding, enlarged nuclei lacking normal polarization, hyperchromasia and rare mitotic figures

Micro images: cysts lined by flat cuboidal epithelium contain eosinophilic material #1 (AFIP); #2; #3; #4; intraluminal secretions show fine, parallel cracks and shrinkage of the cyst content with peripheral scalloping

atypia - focal atypical epithelium between cysts (AFIP) #1; #2 (AFIP); fig A: MRI shows 5 cm mass; fig B: dilated epithelial cysts with colloid-like material; fig C: epithelium is flat or cuboidal; fig D: focal areas of cellular atypia and mitotic figures

DD: cystic hypersecretory DCIS or invasive carcinoma

Cysts of breast

top Home Page

Very common

May arise from lobular acini that coalesce

Usually multifocal and bilateral

Associated with calcifications, apocrine metaplasia

Cysts with cloudy or turbid cyst fluid should have cytologic analysis

Excision required after aspiration if no fluid, bloody or tenacious fluid, or mass persists (Am Fam Physician 2003;68:1983)

Blue dome cysts: based on gross appearance

Type 1 cysts: Na/K ratio of 3 or less; increased breast cancer risk; associated with higher levels of estrogen, melatonin, epidermal growth factor and DHEA-S and lower levels of TGF-B2 than type 2 cysts (Breast Cancer Res Treat 2007;103:331)

Type 2 cysts: Na/K above 3: reduced breast cancer risk, although patients may have both types of cysts, and type 2 cysts can be associated with cancer (Breast 2005;14:37)

Gross: variable size, usually visible grossly, contains clear or yellow fluid

Gross images: unopened cyst #1; #2; #3; large hemorrhagic cysts #1; #2; extensive cystic disease; cyst and fibrous tissue #1; #2

Micro: lined by double layer of flat/cuboidal cells or no lining, may rupture and elicit inflammatory response with foamy macrophages, cholesterol clefts, fibrosis; variable apocrine metaplasia

Micro images: subgross #1; #2 (arrow points to terminal duct of fully unfolded epithelial cyst filled with secretion, other cyst is partially unfolded); two cysts hanging from duct tree; early cystic change #1; #2 (arrows point to broken walls of distended ductules); multiple broken walls in lobule converting into cyst; multiple dilated cysts #1; #2; papillary hyperplasia; squamous metaplasia of epithelium lining cyst (AFIP); calcifications in cystically dilated ducts

Virtual slides: multiple dilated cysts

DD: duct ectasia (elastic tissue in wall, macrophages in lumen), cystic hypersecretory hyperplasia (colloid-like secretions)

References: Am Fam Physician 2003;68:1983 (aspiration procedure)

Epithelial ductal hyperplasia of breast

top Home Page

Definition: benign ductal proliferative lesion that typically has secondary lumens and streaming of central proliferating cells

Also called usual ductal hyperplasia, intraductal hyperplasia, hyperplasia of usual type, papillomatosis (but this term may be confused with papillomas or florid papillomatosis of nipple), epitheliosis

May be due to increase in mitotic rate of epithelial cells compared to apoptotic rate, causing an increased number of epithelial cells within preexisting glandular components (Hum Path 1998;29:1539, Breast Cancer Res 2001;3:276)

Appears to derive from a CK5+ committed stem cell lesion with the same differentiation potential as normal breast, in contrast to ADH/DCIS, which display a differentiated glandular immunophenotype (CK8/18/19+, CK5-, J Pathol 2002;198:458)

Overall may have slightly increased risk for invasive carcinoma with relative risk of 1.5-2.0 (Archives 1998;122:1053); high ERalpha/ERbeta ratio lesions are more likely to progress to breast cancer (AJSP 2005;29:1593)

Micro: streaming (parallel arrangement) of central cells with indistinct cell borders; irregularly shaped and sized secondary lumens, often peripheral; tufts of cells project into lumina; peripheral elongated clefts (not round, not central), irregularly shaped bridges connect opposite portions of wall with nuclei parallel to long axis of the bridge (not Roman bridges); cells have acidophilic and granular cytoplasm, oval normochromatic nuclei with slight overlap, small or indistinct nucleoli; myoepithelial cells and foamy macrophages are present; individual cells are well supported by their stroma; variable apocrine metaplasia, intraluminal or stromal calcifications, intranuclear round eosinophilic bodies (helioid inclusions); occasional fibrosis, elastosis or chronic inflammation; rarely necrosis; no/minimal mitotic figures; no psammoma bodies, no atypia, no prominent nucleoli

Perineural invasion is rare, usually associated with sclerosing adenosis or radial scar (Hum Path 2001;32:785, Archives 2000;124:465)

Mild hyperplasia: 2-4 epithelial layers; no increased risk for invasive carcinoma

Moderate hyperplasia: 4 or more epithelial layers; 1.5 to 2x increased risk for invasive carcinoma, higher if age 50+ years

Florid hyperplasia: epithelium almost completely fills duct but with fenestrations (irregular lumina at periphery) and papillomatosis; 1.5 to 2x increased risk for invasive carcinoma

Gynecomastia-like hyperplasia: micropapillary, resembles gynecomastia of male breast

Thyroid-like hyperplasia: resembles tall cell variant of papillary thyroid carcinoma (see also Tall cell-like tumors in Breast-malignant chapter)

Epithelial ductal hyperplasia (continued)

top Home Page

Cytology: may rarely be hyperchromatic with increased N/C ratio and loss of 2 cell layers; however, be cautious if radiologic imaging and physical exam are not definitive for malignancy (Breast Cancer 2007;14:388)

Micro images: AFIP - distention of duct by cellular proliferation with irregular and slit-like spaces; oval/spindled epithelial cells mixed with elongated myoepithelial cells with dense chromatin #1; #2; spindled epithelial cells are parallel to long axis of intraductal cellular bridges, cell bridges merge to form secondary lumina, myoepithelial cells are present along borders of duct; micropapillary ductal hyperplasia with parallel arrangement of most cells and uniform nuclei; secondary lumina have irregular shapes; apocrine metaplasia forming secondary lumina with foam cells; secondary lumina adjacent to basement membrane are more rounded than smaller central lumina, and cell population is heterogeneous

other - perineural invasion; more epithelial hyperplasia #1; #2; #3; #4; #5; #6; #7; #8; #9; #10; usual ductal hyperplasia (CK903+) versus ADH (CK903-)

Cytology images: ductal hyperplasia #1; #2; #3-incorrectly called malignant (fig 1A/2A); with apocrine metaplasia #1; #2; #3

Virtual slides: epithelial hyperplasia

Videos: epithelial hyperplasia

Positive stains: 34betaE12 keratin (strong, AJSP 1990;14:939), CK 5/6 (Hum Path 2006;37:787), E-cadherin, S100 (weak), ER

Fibroadenomatoid change of breast

top Home Page

Also called fibroadenomatoid hyperplasia, fibroadenomatoid mastopathy

An incidental finding, usually in a background of fibrocystic change

Incidence of 11% (Pathology 1987;19:393, Malays J Pathol 1991;13:101)

Radiology: suspicious, granular, clustered microcalcifications on screening mammography (AJR Am J Roentgenol 1998;171:1331)

Micro: resembles microscopic foci of fibroadenoma without an actual mass and without the typical circumscription of a fibroadenoma; exhibits proliferation of intralobular connective tissue; often coexists with dilated ducts, epithelial hyperplasia, adenosis, calcifications

Micro images: fig 1/2

Fibrosis of breast

top Home Page

Also called hyaline fibrosis of stroma

Common finding (2-7% of core needle biopsies, Radiology 2000;216:255, AJR Am J Roentgenol 2001;177:573); also associated with diabetes (Gen Diagn Pathol 1997;143:49), radiation therapy (Eur J Cancer 2008 Aug 29 [Epub ahead of print]), Cowden’s syndrome (Exp Dermatol 1998;7:380)

May be associated with a reduced risk for progression to breast cancer (Clin Cancer Res 2007;13:5474)

Gross images: fibrosis

Micro: stromal proliferation with obliteration of ducts and acini

Micro images: fibrous tissue with dilated ducts and reduced lobules; mass-like fibrosis with entrapped ducts and lobules #1; #2; #3; discrete lobulocentric focus of fibrous tissue (arrows); narrow bands of fibrous tissue (arrow) surrounding ducts (arrowhead) and lobules; irregular patches of fibrous tissue (arrows) mixed with fat; stromal fibrous nodule #1; #2-subgross

Microcalcifications of breast

top Home Page

Presence of microcalcifications on mammography has led to detection of breast tumors as small as 1-2 mm

Microcalcifications are present in 50% of carcinomas versus 20% of benign breast disease, but only 20% of “suspicious” microcalcifications are actually malignant

Microcalcifications are either calcium phosphate (basophilic, nonbirefringent) or calcium oxalate (seen with polarized microscopy, not H&E, AJSP 1990;14:961, Archives 1989;113:1367, Mod Path 1992;5:146)

Pathologists must detect microcalcifications in glass slides that correspond to those in radiographs - if not present, submit additional tissue, obtain additional levels or use polarized microscopy to look for calcium oxalate (Pathologica 2007;99:5); exhaustive searching for microcalcifications yields a small increase in specific diagnostic information but with a high technical cost (Mod Path 2001;14:350)

Note: microcalcifications may be missing from biopsy due to retrieval failure (Radiology 2006;239:61)

Note: recommended to examine all vacuum assisted breast biopsy specimens histologically, even those without microcalcifications (Eur Radiol 2008;18:925)

Detection of calcium phosphate microcalcifications is reduced with glyoxal fixative (Hum Path 2004;35:1058)

Calcium oxalate microcalcifications of breast

Calcium oxalate crystals are typically within benign cysts or terminal ductules that are histologically apocrine or GCDFP-15 positive; are associated with LCIS, but only rarely with invasive carcinoma (AJSP 1991;15:586)

Calcium oxalate crystals may be present in centrifuged fixative (AJSP 1997;21:255)

Radiologic BI-RADS (Breast Imaging Reporting and Data System of American College of Radiology) classification:

Category 0 - need additional imaging evaluation; category 1 - negative; category 2 - benign finding; category 3 - probably benign finding-short term interval followup suggested; category 4 - suspicious abnormality-biopsy should be considered; category 5 - highly suggestive of malignancy-appropriate action should be taken

References: American College of Radiology

Microcalcifications of breast (continued)

top Home Page

LeGal classification of microcalcifications

Type 1 - annular; type 2 - regularly punctiform; type 3 - too fine for precizing the shape, type 4 - irregularly punctiform; type 5 - vermicular (Bull Cancer 1984;71:57)

Xray images: DCIS #1; #2

Case reports: Case of the week #25, gold salts within intramammary nodes may simulate microcalcifications (Hum Path 1988;19:992)

Micro images: calcium oxalate calcifications - with polarized light (AFIP) #1; #2; without polarized light (AFIP) #1; #2; #3; #4

mammography category 3 (probably benign) - Xray and histology images (figs 2-4, 7)

calcium phosphate calcifications - #1

benign lesions with microcalcifications - AFIP - ADH; sclerosing adenosis #1; #2; other - columnar cell change #1; #2; cystically dilated ducts; fat necrosis; mucocele-like lesion;

malignant lesions with microcalcifications - DCIS-comedo type; LCIS involving adenosis; invasive ductal carcinoma with DCIS

Virtual slides: microglandular adenosis with microcalcifications

Positive stains: von Kossa for calcium phosphate

References: eMedicine

Pseudolactational (pregnancy-like) hyperplasia of breast

top Home Page

Women, mean age 44 years, range 38-52 years, not lactating, not pregnant

Identified in needle localization and core biopsies due to calcifications or presence of a mass (overall, 2-3% of breast biopsies)

Often multifocal

Associated with phenothiazine or other medications (AJCP 1987;87:23)

Associated with / may merge with cystic hypersecretory hyperplasia

May have associated ADH or DCIS (AJCP 2004;122:714) but invasive carcinoma is rare (AJSP 2004;28:789); recommend excision if atypia found in core biopsy (AJSP 2000;24:1670)

Micro: glands and terminal ducts with little or no secretion; glandular cells are swollen with abundant pale or clear, finely granular or vacuolated cytoplasm; luminal cytoplasmic borders of glandular cells are frayed with small cytoplasmic blebs extending into lumen that may contain nuclei; small, uniform, round and darkly stained nuclei

Micro images: AFIP - expanded acinar glands; cells have abundant pale cytoplasm but no secretion; micropapillary pattern of columnar cells with luminal cytoplasmic buds

other - cells have finely vacuolated cytoplasm #1; #2

References: Stanford University

Radial scar of breast

top Home Page

Definition: benign lesion with stellate architecture and prominent fibroelastosis that resembles invasive carcinoma

Initially described in 1977 (AJSP 1977;1:155)

Also called complex sclerosing lesion (larger lesions), sclerosing ductal lesion, sclerosing adenosis with pseudoinfiltration

Common; incidence has increased with mammography (J Clin Pathol 2003;56:721)

Associated with 2x increased risk of breast cancer, may be due to coexisting proliferative disease (Cancer 2006;106:1453, Breast Cancer Res Treat 2008;108:167 but see N Engl J Med 1999;340:430); may be associated with metaplastic carcinoma (Mod Path 2003;16:893)

Xray: stellate abnormalities (“black star”) may resemble invasive ductal carcinoma or tubular carcinoma; often bilateral

Xray images: characteristic findings

Treatment: local excision and follow up or possibly vacuum assisted excision (Breast 2008 Sep 29 [Epub ahead of print])

Core biopsy: excision recommended since associated carcinoma is relatively common (AJSP 2004;28:1626, AJSP 2002;26:1095, Breast Cancer Res Treat 2008;107:371)

Case reports: with DCIS and invasive carcinoma (Breast Cancer 2006;13:107)

Gross: stellate with central sclerosis and elastosis, resembles invasive ductal carcinoma, usually 1 cm or less; may be firm, irregular, with yellow streaks and flecks (due to elastotic stroma)

Gross images: central sclerosis and elastosis resembling carcinoma; subgross image

Micro: “flower head” pattern on low power; high power shows central fibroelastotic zone of basophilic elastic material in walls of obliterated ducts and elsewhere, with radiation of compressed tubular structures with 2 cell layers (including myoepithelium) and hyalinized stroma; variable amounts of epithelial hyperplasia, adenosis and cysts; perineural invasion occasionally noted

Cytology: fine needle aspiration often inadequate (J BUON 2002;7:137); bland epithelial clusters and bipolar naked nuclei; also frequent apocrine cells, papillary clusters, foam cells and fibrillary elastoid material; features are nonspecific, but suggest benign diagnosis (Diagn Cytopathol 1997;17:353); may also be atypical / malignant features if additional lesions present

Radial scar of breast (continued)

top Home Page

Micro images: central fibrosis and elastosis with radiating fibrous bands and dilated ducts #1; #2; #3; #4; #5; #6; fibrosis, elastosis and ductal hyperplasia; various images #1; #2; with tubulolobular carcinoma

AFIP - adenosis surrounds central area of fibrosis and elastosis with entrapped ducts; cysts are commonly present at periphery; squamous metaplasia; central angular glands are suggestive of tubular carcinoma, but peripheral duct hyperplasia and cysts are not typical; elastic stain highlights central elastosis

Virtual slides: case report (#1a)

Positive stains: elastic stains (von Gieson); myoepithelial cells - p63, CD10 and 1A4 (Appl Immunohistochem Mol Morphol 2006;14:71)

DD: invasive carcinoma, tubular carcinoma (no peripheral duct hyperplasia and cysts, negative for myoepithelial markers)

References: Stanford University

Benign (usually) tumors / tumor like-changes

Angiolipoma of breast

top Home Page

Definition: nodule composed of mature adipocytes, thin walled vessels and fibrin thrombi

May be cellular; adipose tissue component may be minimal

Usually subcutaneous nodules on extremities and trunks of young adults, rare in breast

Usually NO pain, unlike these tumors elsewhere

Case reports: 70 year old woman with breast mass (Radiology 2003;227:773), cellular angiolipoma (Breast J 2002;8:47, Mod Path 1993;6:497), multiple bilateral tumors (Aust NZ J Surg 1982;52:614)

Treatment: simple excision

Gross: encapsulated yellow nodule(s) up to 2 cm

Micro: well circumscribed lesion of mature adipose tissue and capillary sized vessels; hyaline thrombi in vessels; usually non-infiltrative; no necrosis, no atypia, no hemorrhage, no mitotic figures

Cytology: hypocellular, mature adipose tissue in hemorrhagic background; rare benign appearing spindled endothelial cells in clusters or strands resembling capillaries (Cancer 1999;87:359)

Micro images: mature adipose tissue and capillaries in fibrous stroma; anastomosing capillaries lined by inconspicuous endothelial cells (AFIP)

site unknown - mature adipose tissue and capillaries; capillary proliferation between adipocytes; soft tissue - mature adipose tissue and prominent vasculature (AFIP); prominent vascular thrombi (AFIP) #1; #2; #3

Apocrine adenoma of breast

top Home Page

Definition: rare adenoma that is (a) composed exclusively of benign apocrine cells (homogeneous), (b) sharply demarcated from surrounding breast tissue; (c) contains only epithelial proliferative elements; and (d) has minimal supportive stroma

Case reports: simultaneous occurrence with invasive ductal carcinoma (Pathol Res Pract 2007;203:809), 45 year old man with 3 mm tumor (Archives 2003;127:1498), 47 year old woman (W V Med J 2008;104:16)

Micro: benign glands with abundant granular, eosinophilic cytoplasm, apical luminal blebs and decapitation secretion; may contain calcifications (Pathology 2001;33:149)

Micro images: apocrine adenoma #1; #2; fig 1: 3 mm subareolar density; fig 2: well circumscribed nodule of small eosinophilic glands; fig 3: uniform eosinophilic cells with apocrine snouts, consistent with decapitation secretion

DD: prominent apocrine changes as a part of fibrocystic changes, well differentiated apocrine carcinoma

References: Stanford University

Atypical or benign vascular proliferations post-radiation of breast

top Home Page

Develops after external radiotherapy for breast carcinoma, within field of radiation (AJCP 1994;102:757)

Mean age 61 years, develops 1-12 years (mean 6 years) after therapy in radiation field

May recur within radiation field (Cancer 2007;109:1584); may progress to angiosarcoma, particularly vascular type (see below, AJSP 2008;32:943)

May have lymphatic origin (Histopathology 1999;35:319)

Treatment: complete excision with careful followup for recurrence

Gross: one or more circumscribed papules, small vesicles or erythematous plaques, usually in irradiated field, median 0.5 cm; frequently multiple synchronous lesions with discoloration

Micro: relatively well circumscribed, anastomosing growth pattern of irregular slit-like vascular spaces dissecting dermal collagen but not extending into subcutis; lined by single layer of endothelial cells without atypia; often micropapillary tufts; no necrosis, no mitotic figures, no blood lakes; resembles benign lymphangioendothelioma or patch-stage Kaposi's sarcoma

Lymphatic type: predominantly thin walled, variably anastomosing lymphatics primarily in superficial dermis

Vascular type: predominantly small, irregularly dispersed, capillary type vessels, invested by pericytes, often blood filled, in superficial or deep dermis; associated with extravasated red blood cells or hemosiderin, minor lymphatic type component

Positive stains: CD31, D2-40 (lymphatic marker), variable CD34

DD: well differentiated angiosarcoma (may be part of morphologic continuum with atypical vascular lesions, J Am Acad Dermatol 2007;57:126), hobnail hemangioma, benign lymphangioendothelioma

References: AJSP 2002;26:328, AJSP 2005;29:983

Carney’s syndrome and breast

top Home Page

Autosomal dominant syndrome of myxomas / myxoid lesions in skin, subcutis and breast (AJSP 1991;15:713), spotty pigmentation present from birth, endocrine overactivity, psammomatous melanotic schwannomas, and intraductal breast adenoma composed of long, straight, narrow, roughly parallel tubules with distinct epithelial and myoepithelial cells (AJSP 1991;15:722)

Linked to PRKARIA gene at 17q23-24 (found in 46% of Carney’s syndrome cases) and CNC2 gene at 2p16 (J Med Genet 2003;40:268)

References: eMedicine, Atlas of Genetics and Cytogenetics

Chondrolipoma of breast

top Home Page

Rare

See also Soft Tissue Chapter-chondroid lipoma

Case reports: 66 year old woman (Archives 1977;101:149), detected by mammography (Archives 1989;113:369)

Gross: well demarcated, islands of cartilage project from cut surface, resembles fibroadenoma (Breast 2006;15:425)

Micro: mature fibrous stroma, adipose tissue, breast ducts, mature cartilage

Micro images - soft tissue (not breast) - AFIP: well circumscribed tumor; clusters of small to medium cells with vacuolated cytoplasm #1; #2; mature fat cells are present

Clear cell “sugar” tumor of breast

top Home Page

Rare; differentiates towards Perivascular Epithelioid Cell; other PEComas are angiomyolipoma, lymphangiomyoma, lymphangioleiomyomatosis, renal capsuloma and clear cell myomelanocytic tumor of the falciform ligament / ligamentum teres

Treatment: excision

Case reports: 16 year old girl (AJSP 2002;26:670)

Micro: epithelioid to spindle cells with clear cytoplasm and distinct cell borders

Micro images: other sites - rectum #1; #2; focal HMB45+

Positive stains: HMB45, Melan-A, PAS diastase sensitive (glycogen), PR, vimentin (focal)

Negative stains: S100, keratin (AE1-AE3, CAM5.2), desmin, ER

EM images: rectal tumor shows premelanosomes

Cylindroma (dermal type) of breast

top Home Page

Very rare in breast; resembles dermal counterpart (AJCP 2005;123:866)

May be associated with turban tumor syndrome (Brooke-Spiegler syndrome)

Case reports: 63 year old woman with lobular carcinoma and incidental cylindroma (AJSP 2001;25:823)

Gross: small, well dermacated; often near nipple and lactiferous ducts (AJSP 2004;28:1070)

Micro: jigsaw pattern of epithelial basaloid islands with focal squamous and myoepithelial differentiation; islands bordered by thickened basement membrane, contain hyaline globules; also reactive dendritic Langerhans cells that permeate islands, clusters of sebaceous cells and a few eccrine ducts; no nuclear pleomorphism, no mitotic figures

Cytology: small uniform cells with finely granular cytoplasm and oval nuclei; some cells are arranged around cylinders of dense acellular material, resembles adenoid cystic carcinoma (Acta Cytol 2004;48:853)

Micro images: skin, not breast - epithelioid basaloid islands

Positive stains: basement membrane and hyaline globules - PAS and type IV collagen

central basaloid cells - CK7

peripheral myoepithelial cells - SMA

eccrine ducts - EMA and CEA

Langerhans cells - S100 and CD1a

Negative stains: GCDFP-15, ER, PR, CK20

DD: solid variant of adenoid cystic carcinoma (atypia, mitotic figures, invasive growth; no continuous thickened basement membrane, AJCP 2005;123:866), basal cell carcinoma

References: eMedicine (skin)

Ductal adenoma of breast

top Home Page

Definition: well circumscribed, benign glandular proliferation in part within a duct lumen

Also called sclerosing papilloma

First described in 1984 (J Pathol 1984;144:15)

Uncommon; usually age 60+ years

May occur as part of Carney’s complex (AJSP 1991;15:722, AJSP 1996;20:1154)

Presents as palpable lump or mammographic abnormality

May resemble carcinoma at imaging, frozen or permanent section (Breast Cancer 2006;13:354)

May evolve by sclerosis of intraductal papillary lesion (Hum Path 1989;20:903)

Case reports: with chondromyxoid change (Pathol Int 2002;52:239)

Gross: single or multiple rounded lesions; gritty texture and elastic streaks mimic carcinoma

Micro: well circumscribed, bounded by dense fibrous wall of medium to large duct from which it arises; composed of proliferating epithelial tubules but no papillary component; has both epithelial and myoepithelial cell types; may have pseudoinfiltrative pattern due to compressed tubules; also focal dilated tubules, epithelial hyperplasia, cysts, squamous or apocrine metaplasia, myxoid change, calcification

Cytology: may resemble lactating adenoma, intraductal papilloma or carcinoma; highly cellular with monolayered sheets of ductal cells with cytoplasm vacuoles that are small and punched out; numerous large fragments of purple stroma are adjacent to epithelial cells, forming finger-like hyaline structures or globules between cells; nuclei are round/oval with bland chromatin; occasional cells have enlarged nuclei with prominent nucleoli; also naked oval nuclei (Diagn Cytopathol 1994;10:143, Diagn Cytopathol 1995;13:252)

Micro images: AFIP - central fibrosis and peripheral bland ducts; nodular lesion composed primarily of spindle cells; spindle cells mixed with residual ducts; spindled myoepithelial cells surround a peripheral duct; ducts lined by apocrine cells, may be confused with carcinoma

other - ductal adenoma, partially sclerosed

Positive stains: tubular luminal cells - keratin; tubular basal cells - S100, actin, p63; basement membrane - laminin, type IV collagen; stromal spindle cells (myofibroblasts) - actin and vimentin (Pathol Res Pract 1993;189:515)

References: Stanford University

Eccrine spiradenoma of breast

top Home Page

Very rare

Benign, rarely undergoes malignant transformation (Archives 1996;120:501)

Arises from cutaneous sweat glands

Case reports: 43 year old woman with 3 local recurrences (AJCP 1996;106:665), periumbilical malignant tumor metastatic to axillary node (Breast Cancer 2008;15:175)

Treatment: wide local excision

Micro: circumscribed with lobulated pattern; lobules contain packed, monotonous, basaloid epithelial cells with scant cytoplasm and round/oval nuclei; at periphery are smaller cells with dark nuclei

Cytology: bland groups of uniform cuboidal cells with scant cytoplasm, round/oval nuclei, indistinct nucleoli; occasional rosette-like structures (Diagn Cytopathol 1992;8:366)

Positive stains: keratin, EMA, ER, PR, Ki-67

Negative stains: vimentin, muscle specific actin, GFAP, S100, CEA

References: eMedicine (skin)

Fibroadenoma of breast

top Home Page

Definition: benign biphasic tumor, usually women age 30 years or less

Most common benign tumor of female breast

May have neoplastic stromal component with polyclonal epithelial component

Hormonally responsive, grows during pregnancy and late luteal phase, regresses after menopause (Am J Epidemiol 2002;156:599)

Associated with mildly increased risk of carcinoma, especially with ductal hyperplasia or family history of breast carcinoma

Rarely coexists with DCIS (2%, AJCP 2001;115:736) or LCIS (Archives 1984;108:590)

Infarction is associated with pregnancy, lactation, fine needle aspiration (Archives 1996;120:1069), but rarely is spontaneous (Pediatr Radiol 2004;34:988)

“Fibroadenomatosis”: multifocal disease, associated with cyclosporin A for kidney transplants (50% of females post-transplant, Ren Fail 2005;27:721, Archives 2003;127:375)

Association with EBV in immunosuppressed is controversial (Mod Path 2002;15:759-yes, Mod Path 2003;16:1242-no)

Xray: heavy, coarse calcifications

Case reports: Case of the Week #37 (bizarre stromal giant cells), atypia due to chickenpox (Acta Cytol 2008;52:337), man with bilateral fibroadenomas with digital fibroma-like inclusions (Archives 2007;131:1126), with microinvasive ductal carcinoma (Acta Radiol 2006;47:643), with adenoid cystic carcinoma (Ann Diagn Pathol 2005;9:157), with invasive mucinous carcinoma (Pathologica 2008;100:199)

Treatment: excision (completely excise if 4 cm or more, enlarging over time and infiltrative border; after core biopsy, excise if cellular stroma found and phyllodes tumor cannot be excluded), cryoablation (Am J Surg 2005;190:647), anti-estrogens (World J Surg 2007;31:1178)

Gross: sharply circumscribed with smooth, rounded border, freely movable spherical nodule, usually 3 cm or less; often in upper outer quadrant; gray-white, bulging cut surface with numerous slits; 20% multifocal

Gross images: well circumscribed gray-white mass #1; #2; #3; #4; #5; #6; #7; #8; #9; multiple fibroadenomas

Micro: rounded contour, overgrowth of fibrous and glandular tissue; intralobular stroma (delicate, cellular, myxoid or fibrotic) encloses glandular spaces; may infarct, become inflamed, calcify; 15% have apocrine metaplasia; no necrosis, no elastic tissue, no anaplasia, no mitotic figures

Pericanalicular: open glandular spaces vs intracanalicular: compressed glandular spaces [no clinical significance to this distinction]

Glands are composed of cuboidal/low columnar epithelium and adjacent myoepithelium, but no atypia

May have myxoid change (suggests Carney’s syndrome), sclerosing adenosis, epithelial hyperplasia or other fibrocystic change

Rarely has pleomorphic, bizarre multinucleated giant cells (Archives 2000;124:1721, Diagn Pathol 2008;3:33, AJSP 1986;10:823, Archives 1994;118:912), squamous metaplasia, smooth muscle or adipose tissue, metaplastic cartilage, DCIS or LCIS

Fibroadenoma of breast (continued)

top Home Page

Cytology: staghorn pattern of spindled or columnar epithelial cells and scattered crowded groups of epithelial cells (AJCP 1988;89:707); also multilayered fragments of epithelium (Acta Cytol 1997;41:1483); rarely has bizarre multinucleated stromal giant cells (Acta Cytol 2002; 46: 535); may appear malignant (Chirurgia (Bucur) 2008;103:227)

myxoid fibroadenoma - highly cellular with moderate mucoid material and numerous bare nuclei

Micro images: whole mount; well circumscribed; fibroblastic stroma surrounding compressed ducts #1; #2; #3; #4; #5; #6; #7; #8; mild hypercellularity; with apocrine change; atypical stromal cells #1; #2; pericanalicular #1; #2; epithelial hyperplasia #1; #2; myxoid stroma #1; #2; bizarre stromal giant cells #1; #2; stromal edema #1; #2; #3; with atypical lobular hyperplasia #1; #2; with DCIS #1; #2; #3; core biopsies; digital fibroma like inclusions; various immunostains; fig 2: fibroadenoma, fig 3: giant cells, fig 4: vimentin; LMP1+ (EBV+) tumor; ER-beta staining of stromal cells (fig a-b); with papillary carcinoma

AFIP - with adenosis #1; #2; focal smooth muscle; squamous metaplasia; with epithelial hyperplasia #1; #2; with LCIS #1; #2

Cytology images: fibroadenoma #1; #2; #3; #4; #5; #6; with fibrocystic changes; with stromal edema #1; #2; fig 1: multiple masses in mammogram; fig 2/3: FNA shows sheets and clusters of ductal cells and myoepithelial cells with background myxoid stroma; fig 4: classic features at core biopsy

Virtual slides: fibroadenoma #1; #2; #3; #4; #5; ALH and ADH involving a fibroadenoma

Videos: fibroadenoma

Positive stains: PR (100%), ER-beta in stroma of cellular fibroadenomas (Mod Path 2006;19:599), CD34 (spindle cells)

EM: basal lamina around epithelial and endothelial cells

Molecular: clonal chromosomal aberrations in 20%

DD: phyllodes tumor at excision: more cellular stroma, more mitotic figures, more Ki-67 staining (AJCP 2005;124:342)

phyllodes tumor at core biopsy: increased stromal cellularity by 50% compared with typical fibroadenoma, stromal overgrowth [10x field with no epithelium), fragmentation, adipose tissue within stroma (Histopathology 2007;51:336)

may resemble papillary carcinoma at FNA (Archives 2000;124:1667)

References: eMedicine

Cellular (juvenile) fibroadenoma of breast

top Home Page

Usually black females, median age 15 years (range 10-39 years)

Either solitary or multiple/successive lesions; recurrences usually cease in 20’s

Grows rapidly but benign behavior

Not associated with subsequent carcinoma

“Giant” fibroadenoma: terminology used inconsistently; refers to size, not a histopathologic entity

Case reports: 13 year old girl (The Internet Journal of Surgery 2007;12(1)), 12 year old girl (American Society of Breast Disease Winter 2005), bilateral tumors in 15 year old girl

Treatment: conservative excision (preserve as much normal breast tissue as possible, Saudi Med J 2007;28:137, Breast J 2000;6:418)

Gross images: well circumscribed lobulated mass #1; #2

Micro: resembles fibroadenoma with pericanalicular pattern but more cellular; stromal and epithelial balance is not altered; epithelium may have tufted pattern characteristic of gynecomastia; may have epithelial atypia (AJSP 1987;11:184); no increase in periductal cellularity (seen in phyllodes tumors); no/rare mitotic figures

Micro images: AFIP - cellular fibroadenoma in 24 year old woman; 13 year old girl with rapidly growing 5 cm mass and epithelial hyperplasia

other - stromal and epithelial hyperplasia #1; #2; #3; #4; #5; #6; #7; #8; #9; #10; #11; calponin; p63

Virtual slide: #1

DD: phyllodes tumor (prominent stromal overgrowth, intracanalicular growth pattern, periductal concentration of cells, variable atypia and mitotic figures)

References: Archives 1987;111:427, Stanford University

Fibromatosis of breast

top Home Page

Rare (< 0.2% of primary breast tumors)

Usually women of childbearing age, may be associated with trauma

Infiltrative, locally recurrent if positive margins (25%) but nonmetastasizing (AJSP 1979;3:501, AJSP 1987;11:38)

May arise in mammary gland or in chest wall musculoaponeurotic tissue and extend into breast

Gene expression patterns are seen in a subset of breast carcinoma patients with longer survival, ER+, lower grade (Lab Invest 2008;88:591)

Case reports: resembling carcinoma (Archives 1985;109:260, World J Surg Oncol 2006;4:57), 47 year old man

Treatment: wide local excision with careful attention to negative margins, although may recur even with negative margins (Ann Surg Oncol 2008;15:274)

Gross: ill defined, white-tan-gray fibrous tissue

Gross images: residual fibromatosis along inferior aspect of biopsy cavity; en bloc resection of underlying chest wall musculature, ribs, and parietal pleura for recurrent tumor

Micro: irregular, nonencapsulated proliferation of spindle cells forming interlacing fascicles with variable collagen deposition and cellularity; usually extends into surrounding fat and glandular parenchyma; may have focal lymphoid aggregates at periphery; may contain eosinophilic inclusions similar to those of infantile digital fibromatosis; no/rare mitotic figures; no epithelial component

Cytology: hypocellular, spindle cells with no/rare glandular elements

Micro images: AFIP - neoplastic infiltrate surrounds ducts and lobules; sparsely cellular collagenous area with lymphocytes; spindle cells with uniform nuclei and no mitotic activity; keloidal collagen surrounds atrophic duct; spindle cells in myxoid stroma; focally cells have large hyperchromatic nuclei

other - long interlacing fascicles of bland spindle cells with moderate collagen deposition and focal hyalinization; bland fibroblasts entrapping benign ducts and fat; fibromatosis with adjacent mammary ductal epithelium; myofibroblastic spindle cells with indistinct cytoplasm, vesicular nuclei, small nucleoli and interstitial collagen #1; #2; fibromatosis invading into adjacent skeletal muscle; bland fibroblasts of moderate cellularity; fig 1: moderately cellular spindle cell proliferation; fig 2: fibrous lesion with keloid-like band of collagen; fig A: infiltration into adjacent breast tissue; fig B: infiltration into skeletal muscle; fig C: monotonous, bland spindle cells with abundant extracellular collagen, occasional small nucleoli; smooth muscle actin+; cytokeratin negative

Positive stains: smooth muscle actin (focal)

Negative stains: ER, PR, androgen receptor (Archives 2000;124:276, but see Archives 1987;111:870)

Molecular: nuclear accumulation of beta-catenin in stromal tumor cells (82%), somatic alterations of APC/beta-catenin pathway (79%, Hum Path 2002;33:39)

EM: fibroblasts and myofibroblasts

DD: stromal component of phyllodes tumor, metaplastic carcinoma, inflammatory pseudotumor, nodular fasciitis, fibrous histiocytoma

Galactocele of breast

top Home Page

Milk filled cavity beneath areola, usually due to abrupt suppression of lactation

Case reports: arising in accessory breast tissue in axilla (Arch Gynecol Obstet 2007;276:379), due to augmentation mammoplasty (Aesthetic Plast Surg 2005;29:274), in postmenopausal woman (Breast Cancer Res 2000;2:A53)

Treatment: aspiration

Clinical images: large cystic cavity

Micro: dilated, anastomosing, epithelium lined channels, often with secretory activity; cyst contents may leak into adjacent tissue and cause lipogranulomatous reaction with foamy macrophages

Cytology: occasional foam cells and benign epithelium displaying lactational change; abundant background of lipid micelles and proteinaceous material; rarely crystals (Acta Cytol 1997;41:863)

Micro images: various images

Granular cell tumor of breast

top Home Page

Definition: tumor whose cells have granular eosinophilic cytoplasm and bland small nuclei

More common in women in 40’s; may be more common in African-American women

Resembles invasive carcinoma clinically, but almost always benign

Appears to derive from Schwann cells of peripheral nerves (at all sites)

Xray: suggestive of malignancy due to apparent infiltration

Case reports: 2 cm tumor (Cases J 2008;1:142), with DCIS and invasive ductal carcinoma (Archives 2002;126:731), two lesions with features of granular cell tumor and traumatic neuroma (Archives 2000;124:709), 10 year history of breast mass (Archives 2003;127:1525), malignant chest wall tumor with recurrence in breast and axilla (Archives 1992;116:206)

Treatment: local excision

Gross: firm, homogenous, gray-white-yellow, usually 3 cm or less and ill-defined

Gross images: firm tumor with irregular borders, suggestive of carcinoma; dense pale homogenous tumor with infiltrating margins (AFIP); circumscribed tumor

Micro: infiltrating sheets/cords of polygonal bland cells with well-defined cell borders and abundant eosinophilic granular cytoplasm; round/oval nuclei with prominent nucleoli; collagenous stroma; may be close to small nerve bundles and have infiltrative margins; occasional multinucleation, rare mitotic figures; no/mild atypia

Cytology: highly cellular, large cohesive groups and single cells mixed with connective tissue; cells have ill defined, abundant granular cytoplasm and bland small nuclei with inconspicuous nucleoli; no mitotic figures, no necrosis (Diagn Cytopathol 2007;35:725)

Micro images: core biopsy; clusters of tumor cells infiltrate between collagen bundles; cells have abundant, eosinophilic granular cytoplasm #1; #2; #3; S100+; with DCIS and invasive ductal carcinoma #1; #2 (keratin and S100); granular cell traumatic neuroma; fig 1/2: mass with ill defined borders; fig 3: nests of cells with eosinophilic and granular cytoplasm and no atypia, within fibrohyaline stroma

AFIP - #1; infiltration into fat; S100+ tumor cells and myoepithelial cells

Positive stains: PAS (diastase resistant), S100, CD68 (due to phagolysosomes), focal CEA and vimentin

Negative stains: keratin, EMA, mucin, alpha-1-antitrypsin, myoglobin, ER, PR

EM: myelin figures, lysosomes

DD: apocrine carcinoma (usually ductal carcinoma also present, keratin+, mucin+, S100-), histiocytic tumors, granulomatous inflammation, alveolar soft part sarcoma, melanoma, renal cell carcinoma

References: Archives 1984;108:897, eMedicine

Gynecomastia-like changes of female breast

top Home Page

0.15% of female breast lesions (Archives 2001;125:506, Archives 2000;124:844)

Mean age 32 years, patients present with palpable mass associated with fibrocystic changes in adjacent breast

Micro: poorly circumscribed areas of ductal hyperplasia with periductal stromal fibrosis or edema and slight lymphocytic infiltrate, involves one low power field or entire core fragment of at least 1 cm, without terminal duct-lobular units present (same as male gynecomastia); no associated mammary hamartomatous changes, no areas of juvenile hyperplasia, no juvenile fibroadenoma

Micro images: proliferation of ducts with periductal fibrosis but without lobules #1; #2; #3; #4; #5; #6; #7; #8

DD: hamartoma (sharply circumscribed, has lobules, variable smooth muscle or cartilage, no periductal stromal changes), fibroadenoma with adipose tissue, juvenile hypertrophy (pre-pubertal patients, massive involvement)

References: Stanford University

Hamartoma of breast

top Home Page

Definition: well circumscribed, often encapsulated mass composed of all components of breast tissue

Also called fibroadenolipoma, adenolipoma

Rare; may be a malformation, not a neoplasm

Mean age 45 years

Xray: clearly demarcated lesion on mammography

Case reports: bilateral tumors in axillary accessory mammary glands (APMIS 2006;114:77), with atypical stromal cells (Pathologica 2007;99:434), with adenofibroma/ALH or infracted fibroadenoma (Archives 2003;127:e151), choristoma (Hum Path 1985;16:739), with DCIS (J Clin Path 2002;55:541), with DCIS and infiltrating ductal carcinoma (Breast J 2006;12:368), with LCIS and invasive lobular carcinoma (J Clin Path 2002;55:76)

Treatment: excision; does not recur

Gross: well circumscribed mass of firm, rubbery, white tissue, 1-8 cm, more distinctive grossly than microscopically

Gross images: ovoid yellow-white mass; fat, glandular elements and stroma in pregnant patient; smooth and glistening mass

Micro: sharply circumscribed mass of disordered breast ducts and lobules; ducts often dilated, accompanied by fibrosis; may have smooth muscle, adipose tissue, hyaline cartilage, pseudoangiomatous hyperplasia; may resemble gynecomastia due to lack of ducts

Myoid hamartoma: also has smooth muscle stroma; may contain epithelioid cells (Archives 1996;120:676, Hum Path 1985;16:212)

Cytology: moderately cellular, sheets of bland ductal cells and lobular units, bipolar stromal nuclei, varying amounts of adipose tissue, less prominent stromal fragments, occasional apocrine and foamy cells, no atypia; findings are not specific (Cancer 2003;99:255, Cytopathology 2003;14:195)

Micro images: dilated ducts and fibrous stroma; breast ducts and adipose tissue (adenolipoma); rounded border and fibrous capsule; epithelial and mesenchymal components; well circumscribed mass with adipose tissue, normal lobules, cystically dilated ducts; mature adipose tissue and cartilage; various images; with LCIS and invasive lobular carcinoma; with high grade DCIS; fig A: ultrasound of mass; fig B: 11 cm mass with central cyst; fig C: H&E of hamartoma; fig D: associated fibroadenoma; fig E: micropapillary hyperplasia within wall of cyst

AFIP - well defined fibrous tumor with ducts separated by connective tissue; adipose tissue plus ducts resembling gynecomastia; with ductal hyperplasia resembling gynecomastia; smooth muscle bundles (arrows) mixed with fibrous tissue; hyaline cartilage and adipose tissue;

myoid hamartoma - #1; #2; #3; smooth muscle actin+

Cytology images: intact lobular units, less prominent than ductal cells; adipose tissue is present in varying amounts; multinucleated histiocytes are occasionally seen

DD: gynecomastia-like changes (merges gradually with normal breast tissue, no lobules present), fibroadenoma, lipoma, fat necrosis, galactocele

References: J Clin Path 2002;55:951, Stanford University

Hemangioma and angiomatosis of breast

top Home Page

Definition: benign tumor or malformation of blood vessels

Must completely excise any benign vascular lesion for accurate diagnosis (Stanford University)

Usually 2 cm or less

Angiomatosis: very rare; hemangioma and lymphangioma-like channels growing diffusely in breast tissue but sparing lobules and without nuclear atypia (AJSP 1985;9:652); associated with smoking (Arch Dermatol 2006;142:343); may respond to isotretinoin (J Am Acad Dermatol 2001;45:462); may recur (Cancer 1988;62:2392)

Atypical hemangioma: benign vascular lesion with nuclear pleomorphism, focal anastomosing vascular channels, microthrombi or rare mitotic figures, but no significant endothelial growth patterns of angiosarcoma (AJSP 1992;16:553); benign behavior; FNA shows numerous atypical spindle cells in hemorrhagic background, suggesting malignancy (Diagn Cytopathol 2001;24:215)

Cavernous hemangioma: large dilated vessels; case reports of 15 cm tumor in 60 year old man (Breast Cancer 2005;12:231), axillary tumor clinically suspicious for malignancy (South Med J 2008;101:1051)

Capillary hemangioma: composed largely of capillary sized vessels

Perilobular hemangioma: usually 2 cm or less (AJSP 1985;9:491); well circumscribed lesion composed of dilated congested capillaries in perilobular location; may have atypia with nuclear hyperchromasia, but no extensive complex anastomoses, no papillary endothelial tufting, no mitotic figures (Stanford University); found at autopsy in 11% (Br J Cancer 1985;51:271, Archives 1983;107:308)

Venous hemangioma: 1-5 cm, circumscribed, disorderly proliferation of venous channels (AJSP 1985;9:659)

Clinical images: diffuse dermal angiomatosis

Gross images: angiomatosis composed of vessels and breast parenchyma (vessels at arrows-AFIP)

Hemangioma and angiomatosis of breast

top Home Page

Micro images:

angiomatosis: AFIP - dilated vascular channels in breast tissue; anastomosing vascular channels lined by flat endothelial cells without smooth muscle; other - diffuse dermal angiomatosis (H&E and CD31)

atypical hemangioma: AFIP - cavernous hemangioma above and branching vascular channels below; cavernous vessels infiltrating into fat; branching vascular channels lined by bland endothelium; other - various images

capillary hemangioma: capillary lobules of variable size; complex branching vessels suggestive of granuloma pyogenicum but without inflammation (AFIP); vascular spaces lined by unremarkable endothelium #1; #2; #3; various images

cavernous hemangioma: AFIP - well circumscribed with dilated vascular channels; lobular-like pattern of dilated vessels but no anastomosing channels; vascular spaces are lined by inconspicuous endothelium; organizing clot with recanalization; “feeding” vessels present at left-center; other - 17 cm tumor in 60 year old man; negative/rare Ki-67 staining

perilobular hemangioma: AFIP - thin walled vessels are congested and extend into adjacent fat; lesion in stroma not associated with lobules or ducts; atypical perilobular hemangioma #1 with compact vascular proliferation associated with terminal duct; #2 with extension into fat and no distinct congested capillary channels; #3 with inconspicuous slit-like vascular spaces lacking red blood cells; #4 with hyperchromatic endothelial nuclei

Virtual slides: hemangioma

Videos: hemangioma

References: Stanford University

Hemangiopericytoma of breast

top Home Page

Definition: circumscribed area of bland spindled cells with branching and staghorn vessels

Very rare; usually women 33-67 years

Painless, nontender nodules

Low grade behavior

Case reports: malignant tumor (Arch Gynecol Obstet 2008;277:357)

Treatment: complete local excision with breast preservation; mastectomy may be necessary for large lesions (Mod Path 1988;1:98)

Gross: mean 6-9 cm, well circumscribed

Micro: thin walled, staghorn-type vessels separated by polygonal cells with indistinct margins, pale cytoplasm and small round/oval nuclei

Cytology: cellular; single and tightly packed clusters of oval to spindled cells aggregating around branched capillaries; nuclei are uniform, oval with finely granular chromatin and indistinct nucleoli; usually basement membrane material; no mitotic figures, no necrosis (Cancer 1999;87:190)

Micro images: AFIP - thin walled staghorn-type vessels separated by polygonal cells with indistinct margins, pale cytoplasm and small round/oval nuclei; reticulin stain outlines each cell

Cytology images (Diff-Quik): irregular fragments of tissue, loose cellular aggregates, single cells; uniform oval or spindled cells with high N/C ratio and indistinct borders, capillaries within tissue fragments, endothelial cells are longer and more hyperchromatic than tumor cells; tumor cells are separated from endothelial cells by metachromatic basement membrane material

Positive stains: reticulin outlines each cell

EM: pericytes associated with vessels (AJSP 1981;5:745)

Inflammatory pseudotumor of breast

top Home Page

Definition: tumor of myofibroblastic spindle cells and inflammatory cells

Also called inflammatory myofibroblastic tumor, plasma cell granuloma

Extremely rare in breast with <20 cases reported

May be part of an IgG4 related sclerosing disease (New Engl J Med 2001;344:732, World J Gastroenterol 2008;14:3948)

Case reports: 46 year old woman with IgG4 related inflammatory pseudotumor (AJSP 2005;29:275), 50 year old woman

Gross: firm, circumscribed, yellow

Micro: nodular with fibrovascular stroma containing myofibroblast-like cells and lymphoplasmacytic infiltrate; may have primarily inflammatory features (diffuse lymphoplasmacytic infiltration and lymphoid follicles), resemble myofibroblastic tumors or be hypocellular (scar-like); often mixed patterns (AJCP 1988;90:627)

Micro images: myoblastic spindle cells and inflammatory cells #1; #2; various images; CD34+

bladder - spindle cells and inflammatory cells in myxoid stroma; myofibroblastic cells and inflammatory cells in edematous stroma #1; #2; H&E and ALK1 staining; inflammatory myofibroblastic tumor composed of spindle cells and inflammatory cells with no atypia and no necrosis

Positive stains: spindle cells - smooth muscle actin, vimentin, variable keratin; plasma cells may be IgG4+

Molecular: some cases are clonal (J Pathol 2002;196:97)

DD: spindle cell carcinoma (Ann Diagn Pathol 2005;9:123)

Juvenile xanthogranuloma of breast

top Home Page

Also called nevoxanthoendothelioma

Benign histiocytic disorder of infants and children; 15% occur in adults (usually young)

Very rare in breast tissue itself (excluding overlying skin)

Case reports: Case of the week #5, 74 year old woman with prior cutaneous juvenile xanthogranulomas and breast masses (AJSP 2005;29:827)

Treatment: conservative excision

Gross: cutaneous lesions usually 0.1 to 2.0 cm, yellow-red and papulonodular

Micro: dense dermal infiltrate of lymphocytes, histiocytes, Touton giant cells (usually), eosinophils and neutrophils, which may extend into subcutis; late - epidermis thins out and the rete ridges become elongated; extracutaneous lesions may lack the Touton giant cells.

[Note: histiocytic giant cells may be Touton type [ring of nuclei surrounding foamy cytoplasm with cytoplasm usually also visible around the nuclei; Langhans type [nuclei form a horseshoe arrangement, not necessary a distinct category from Touton type] or foreign-body type [haphazard nuclear arrangement]

Micro images: Case of Week #5 - low power; medium power #1; #2; high power #1; #2

Positive stains: Touton giant cells and histiocytes - CD68, HAM56, Factor XIIIa

Negative stains: Touton giant cells and histiocytes - S100 and CD1a

DD: Langerhans cell histiocytosis (more common disorder of childhood, coffee bean nuclei/nuclear grooves, Birbeck granules on EM, no Touton giant cells, S100+, CD1a+, CD68-, HAM56-, Factor XIIIa-), xanthoma (uniform collection of foam cells and variable Touton giant cells, no other inflammatory cells, often associated with hyperlipidemia), benign fibrous histiocytoma (usually has a storiform pattern)

References: AJSP 2003;27:579, AJSP 2005;29:21

Lactating adenoma of breast

top Home Page

Usually during or shortly after pregnancy

Resembles fibroadenoma or tubular adenoma with lactational change microscopically

May actually be a coalescence of hyperplastic lobules, not a true adenoma

May develop in ectopic breast tissue in axilla, chest or vulva (along “milk line”)

May have common origin with tubular adenoma (Hum Path 1985;16:707)

May infarct or spontaneously involute (Breast J 2001;7:354)

Case reports: 21 year old woman with infarcted tumor; infracted tumor presenting as rapidly enlarging breast mass (AJR Am J Roentgenol 1999;173:933), with invasive ductal carcinoma (J Clin Path 2005;58:87)

Clinical images: enlarged right breast mass 2 months post-partum stretches overlying skin and nipple-areola; necrosis of overlying skin

Gross: well circumscribed, lobulated, solitary or multiple, gray-tan cut surface, frequent necrosis/infarction

Gross images: 14 cm tumor is mostly encapsulated, necrotic portion involves overlying skin

Micro: cuboidal cells with actively secreting, closely packed glands; resembles pregnancy-like (pseudolactational) changes; often arises in tubular adenomas or fibroadenomas

Cytology: cellular with epithelial cells scattered and in small groups; cells have foamy to finely vacuolated cytoplasm, uniform nuclei with fine chromatin and prominent nucleoli; background has abundant foamy material (Acta Cytol 1990;34:21, Indian J Pathol Microbiol 2001;44:445)

Micro images: lactating adenoma #1; #2; #3; #4; #5; #6; #7; #8; #9

infracted lactating adenoma - #1; #2; #3; #4-A: edge of infarction, B: hemosiderin laden macrophages, C: peripheral fibrosis, D: viable tumor, E: capsule; infarction (fig E)

Cytology images: increased lobular size; cytoplasmic vacuoles and background foamy material #1; #2; #3; #4

Virtual slides: #1

References: Stanford University

Leiomyoma of breast

top Home Page

Definition: benign smooth muscle tumor

Rare; usually involves nipple

Often painful (AJSP 1979;3:151)

Superficial or deep (vascular)

Usually contiguous with the muscular components of the nipple areolar complex (J La State Med Soc 1998;150:367)

Treatment: complete excision to prevent recurrence

Case reports: epithelioid leiomyoma with granular cell change (Hum Path 1993;24:1260), tumor of nipple (Breast J 2006;12:377), tumor of breast parenchyma (AJR Am J Roentgenol 2005;185:1595)

Gross: often ill-defined

Micro: interlacing bundles of spindle cells with eosinophilic cytoplasm and blunt ended, cigar shaped nuclei; may have epithelioid or granular features; no atypia, no hypercellularity, no/rare mitotic figures (<3 per 10 HPF), no necrosis

Micro images: circumscribed tumor of spindled cells without atypia (AFIP); fascicles of spindle cells with abundant eosinophilic cytoplasm and blunt ended nuclei #1; #2; smooth muscle actin positive; various images

Positive stains: smooth muscle actin, desmin, vimentin

Negative stains: S100, keratin

DD: leiomyosarcoma (Diagn Pathol 2006;1:13), fibroadenoma, hamartoma, sclerosing adenosis

Lipoma of breast

top Home Page

Definition: tumor composed of mature fat cells without atypia

See also angiolipoma, chondrolipoma

Most common benign mesenchymal tumor of breast

Recommended to confirm clinical and radiologic impression of lipoma with FNA, core biopsy or excision if necessary (Breast 2004;13:408)

Case reports: giant lipoma of underlying pectoralis muscle simulating malignancy (Ann Acad Med Singapore 2005;34:275)

Gross: well circumscribed, thinly encapsulated, usually < 5 cm

Micro: sheets of mature adipocytes without lipoblasts; resemble surrounding fat

Cytology: fat cells

Micro images: mature adipose tissue without atypia #1; #2

Spindle cell lipoma / pleomorphic lipoma of breast

top Home Page

May be closely related to myofibroblastoma (AJSP 2001;25:1022)

Case reports: 48 year old woman with 3 cm tumor (Indian J Pathol Microbiol 2008;51:234), deep tumor of breast (Pathology 1999;31:288)

Gross images: white fibrous tumor intermingling with breast tissue

Micro: thin, uniform spindle cells associated with collagen bundles, mature adipocytes and entrapped normal parenchyma, resembling an infiltrating malignancy

Cytology: pleomorphic lipoma - floret cells and mononuclear hyperchromatic cells with scalloped nuclei, which appear malignant (Acta Cytol 2000;44:255)

Micro images: spindle cells associated with collagen and adipose; spindle cells are CD34+; spindle cells are desmin negative; spindle cells are smooth muscle actin negative; cytology, H&E, CD34; male breast

Positive stains: CD34, vimentin

Negative stains: keratin, S100, desmin, smooth muscle actin, Factor VIII

Lymphangioma of breast

top Home Page

Also called cystic hygroma

Very rare; 90% present by age 2 years

Tends to infiltrate surrounding tissues

Case reports: 38 year old woman with cavernous lymphangioma (World J Surg Oncol 2007;5:69), 49 year old woman with mammographic lesion (Archives 1986;110:353)

Treatment: excision, although not always possible (Lymphology 2006;39:147)

Micro images: distended lymphatic channels interspersed with breast lobules; lymphatic channel has attenuated lining

Acquired lymphangiomas (lymphangiectasis) of breast

top Home Page

Also called lymphangioma circumscriptum - the classic lesion of lymphangioma circumscriptum appears at birth or in early years, but most cases described are post-surgery or radiation therapy

Associated with pain, chronic drainage, cellulitis (South Med J 1999;92:69)

May be related to benign lymphangioendothelioma (AJSP 2000;24:1047)

Case reports: 40 year old woman with multiple vesicles (The Internet Journal of Dermatology 2006;3(2)), 68 year old woman (Dermatology Online Journal 10:9), 48 year old woman (J Cutan Pathol 1995;22:164)

Treatment: cryosurgery, electrocautery, laser therapy to vaporize surface lymphatics (Dermatol Surg 1998;24:893); frequently recurs and causes substantial morbidity

Clinical images: vesicles on breast #1; #2; oozing of clear fluid from vesicles

Micro: dilated lymphatics involve superficial and deep dermis and possibly subcutaneous tissue, occasionally fascia and skeletal muscle; may have hemosiderin deposition

Micro images: papillary dermis shows ectatic lymphatic spaces

EM: endothelial cells have cytoplasmic microfilaments and pinocytotic vesicles; intermediate junctions are present between adjacent cells (Jpn J Clin Oncol 1991;21:129)

References: eMedicine (lymphangiectasia)

Mucocele like lesion of breast

top Home Page

May be premalignant, associated with ADH or focal mucinous carcinoma

Analogous to mucocele of minor salivary glands

Mean age 40 years, range 25-61 years (AJSP 1986;10:464)

Often appears malignant radiologically due to microcalcifications (Breast J 2005;11:15)

Case reports: with columnar cell hyperplasia (J Med Case Reports 2008;2:138)

Treatment: simple excision with examination of entire specimen (Archives 1991;115:137), excision needed to rule out mucinous DCIS or invasive mucinous carcinoma (Histopathology 2004;45:148)

Gross images: mucin filled cysts contained DCIS

Micro: mucin containing cysts that often rupture, with extravasation of mucin into surrounding stroma; epithelium lining the cysts varies from benign/flat to hyperplasia to ADH to DCIS to colloid carcinoma; calcifications often present

Cytology: poorly cellular with cohesive clusters of bland cells in two dimensional sheets with abundant mucoid background, no/rare intact single tumor cells, no atypia if mucocele only (AJSP 1999;23:552); mucinous carcinomas are usually more cellular with more single tumor cells, 3D clusters, mild/moderate nuclear atypia, and a solid mass by imaging (Cytopathology 2004;15:104), excisional biopsy is necessary to confirm diagnosis (Breast Cancer 2008 May 14 [Epub ahead of print])

Micro images: cysts contain mucin and are lined by cuboidal/columnar epithelium; mucin extravasation (arrows); microcalcifications (arrows) associated with cyst; mucocele like tumor #1; #2; with focal columnar cell hyperplasia; extravasated mucin with dense calcifications and mild ductal hyperplasia; mucocele like tumor with florid epithelial hyperplasia #1; #2; #3; with focus of ADH #1; #2; #3; #4; with DCIS; with mucinous carcinoma

DD: colloid (mucinous) carcinoma

References: AJSP 2002;26:1095 (core biopsies), Stanford University

Myoepithelioma of breast

top Home Page

Definition: bland spindle cell lesion with myoepithelial phenotype

Rare; usually benign

See also myoepithelial carcinoma in Breast-Malignant chapter

May recur locally

Case reports: with local recurrence (Tunis Med 2004;82:324), benign appearing tumor in renal dialysis patient with metastatic behavior (ANZ J Surg 2004;74:1135)

Micro: dense spindle cell neoplasm, may be arranged in storiform pattern; tumor cells have eosinophilic cytoplasm, oval and regular nuclei; may have polygonal cells with clear cytoplasm and hyperchromatic nuclei; may infiltrate fat or surround normal ducts; no mitotic figures, no necrosis, no atypia

Cytology: epithelial and spindled cells; mild to moderate nuclear pleomorphism, occasional intranuclear cytoplasmic vacuoles, naked bipolar cells, metachromatic myxoid or fibrillary material; no necrosis, no mitotic figures

Micro images: AFIP - invasive dense spindle cell lesion; plump interlacing spindle cells with ovoid nuclei; occasional polygonal cells with hyperchromatic nuclei; actin+ spindle cells (positive internal control in normal duct at top)

other - broad fascicles; may resemble leiomyoma #1; #2; muscle specific actin+ spindle cells

Positive stains: keratin, EMA, smooth muscle actin, vimentin, CD10, p63, S100 (myoepithelial cell phenotype)

Negative stains: desmin, CD34

EM: activated, differentiated myoepithelial cells (cytoplasmic bundles of myofilaments, desmosomes and basal lamina), variable squamous metaplasia (AJSP 1982;6:785)

DD: adenomyoepithelioma, myoepithelial carcinoma, myofibroblastoma, metaplastic carcinoma

References: Stanford University

Nipple adenoma / florid papillomatosis of nipple

top Home Page

Definition: compact proliferation of small tubules lined by epithelial and myoepithelial cells, near collecting ducts of nipple

Uncommon benign variant of intraductal papilloma involving terminal portion of ducts

Age 30-49 years, unilateral, associated with serous/bloody nipple discharge

May clinically resemble Paget’s disease of nipple

May have associated carcinoma (Mod Path 1995;8:633) or metaplastic spindle cell lesions of variable malignancy (Mod Path 2003;16:893)

Case reports: incidental lesion (Breast Cancer 2007;14:234), with underlying carcinoma (Breast Cancer 1998;5:87)

Treatment: local excision; may recur if incompletely excised

Clinical images: small papule (arrow) on nipple

Gross: ill defined nodule of nipple

Micro: rounded outline of haphazard bilayered tubules in papillary pattern, often with fibrosis, continuous with squamous epithelium of epidermis; may resemble adenosis; peripheral clefting, oval nuclei, streaming; may have epithelial hyperplasia, keratin cysts, focal necrosis within proliferating ducts or sclerosis resembling invasive carcinoma; no atypia, no cribriform component

Associated with bland cells in epidermis that are scattered or in small aggregates, CAM5.2+, CK7+, CEA-, HER2- (AJSP 1999;23:1349)

Micro images: circumscribed lesion; proliferation of epithelial and myoepithelial cells #1; #2; various images; frozen section (fig A) resembling invasive carcinoma; p63 shows intact myoepithelial layer

AFIP - with myoepithelial hyperplasia; complex pattern of duct hyperplasia with minimal sclerosis at site of recent biopsy; branching fronds of hyperplastic epithelium without atypia in dilated duct below nipple; mixed pattern with papilloma (upper), sclerosis (center) and adenosis (right side); compact arrays of ductules in adenosis lesion beneath intact nipple epidermis; focal necrosis in hyperplastic duct; papillomatosis with adenosis; with atypical hyperplasia due to disorderly growth pattern without stroma; with DCIS and Paget’s disease (arrow) in adult man #1; #2

DD: syringomatous adenoma of nipple, subareolar sclerosing duct hyperplasia

References: AJSP 1986;10:87, Stanford University

Nodular mucinosis of breast

top Home Page

Very rare

Also called nerve sheath myxoma of breast

Benign; usually young women

Case reports: 21 year old woman with breast mass (Archives 2005;129:e58), 30 year old woman (Breast Cancer 2002;9:261)

Gross: variably circumscribed, subareolar, myxoid mass; often multiple nodules of various sizes

Micro: nodules of pink mucinous / myxoid material separated by vascularized fibrous septa; spindle cells with pale cytoplasm and indistinct borders and elongated, bland nuclei; no mitotic figures, no invasion, no epithelial components within the nodules (may be at periphery)

Micro images: fig 1: ultrasound shows isoechoic mass, fig 2: nodular myxoid tissue with bland spindle cells, fig 3A: Alcian blue+, fig 3B: removal of Alcian blue after hyaluronidase pretreatment, fig 4: smooth muscle actin+ spindle cells

Positive stains: spindle cells - vimentin, smooth muscle actin; mucin (acidic) - Hale’s colloidal iron, Alcian blue

Negative stains: PAS (stains only neutral mucins)

DD: myxoid fibroadenoma (mammary ducts, epithelial and myoepithelial cells), myxoid neurofibroma (neural cells, S100+), myxoid liposarcoma (S100+ lipoblasts), mucocele-like lesions (extension into breast stroma, PAS+ and mucicarmine+ mucin), cutaneous follicular mucinosis (either present in hair follicles or associated with cutaneous T cell lymphoma)

References: Pathol Int 1998;48:542, Stanford University

Papilloma of breast

top Home Page

Definition: intraductal proliferation of epithelial and myoepithelial cells overlying fibrovascular stalks

Common; mean age 48 years

Arises from large or small ducts

Central or peripheral

May be related to ductal adenoma

Central (large duct): close to nipple within principal lactiferous ducts, 90% solitary, 70% associated with nipple discharge; usually ages 30-49 years but any age

Peripheral: often clinically occult, discovered by mammographic calcifications; usually multiple

Single papillomas: no increased risk of subsequent malignancy with or without associated ADH/ALH (AJSP 2006;30:665)

Multiple papillomas: increased risk of subsequent malignancy, particularly if ADH/ALH is present (AJSP 2006;30:665); 5 or more papillomas are associated with coexisting atypical (ALH/LCIS, ADH) or malignant breast lesions, also recurrence and contralateral disease (Hum Path 2003;34:234)

Atypical papillomas: distinction from papillary DCIS is based on size of atypical area or % of papilloma; 4x increased risk of invasive carcinoma compared to papillomas without atypia, usually near site of original papilloma (Cancer 1996;78:258)

Papillomas may have associated metaplastic spindle cell lesions of variable malignancy (Mod Path 2003;16:893)

Case reports: with sentinel node papilloma (AJSP 2008;32:784), associated with Costella syndrome (Cir Esp 2007;81:345), male patient on long-term phenothiazines (Breast Cancer 2006;13:84)

Treatment: local excision or microdochectomy (removal of breast duct); core biopsy diagnosis of papilloma even without ADH probably requires excision (Ann Surg Oncol 2008;15:2272, AJSP 2002;26:1095, Eur J Surg Oncol 2008 Apr 24 [Epub ahead of print], AJR Am J Roentgenol 2006;186:1328), but see AJCP 2004;122:440, AJCP 2004;122:217

Gross: well circumscribed, polypoid intraductal mass, usually < 3 cm, soft, hemorrhagic; often infarcted

Gross images: polypoid intraductal mass; sclerosing papilloma; hemorrhagic cyst with tan tumor

Micro: multiple papillae in complex arborizing pattern with well-developed vascular connective tissue core surrounded by epithelial and myoepithelial cells; benign nuclei, frequent apocrine metaplasia, inflammation; may arise within a large cystic duct, have comedo-type necrosis without DCIS (Ann Diagn Pathol 2004;8:276), rarely sebaceous metaplasia (Virchows Arch 2001;438:505); infracted cases may have squamous metaplasia or appear pseudoinfiltrative due to fibrosis (Hum Path 1984;15:764)

Cytology: high positive predictive value (Diagn Cytopathol 2006;34:818)

infarcted papillomas - early stage shows numerous degenerated cells with smudged nuclei, ghost cells and necrotic debris; late stage shows clusters of fibroblasts, ductal cells and necrotic debris (Diagn Cytopathol 2006;34:373)

Papilloma of breast (continued)

top Home Page

Micro images: subgross; dilated duct containing connective tissue core with multiple fingerlike projections #1; #2; #3; #4; #5; #6; #7; #8; #9; #10; #11; #12; #13; #14; #15; epithelial and myoepithelial cells #1; #2; multiple nodules and stromal fibrosis; stromal fibrosis simulates invasion; encysted papilloma with hyperplasia; central papilloma #1; #2; central papilloma with florid ductal hyperplasia #1; #2; #3; peripheral papilloma; p63; CD10 and smooth muscle actin

AFIP - fusion of adjacent papillae creates gland-like spaces; apocrine intraductal papilloma #1; #2-large nuclei and prominent nucleoli; resembles sclerosing adenosis; with fibroblasts, fibrosis and chronic inflammatory infiltrate; small ducts surrounded by hyalinized fibrous tissue; infarcted papilloma #1; #2; squamous metaplasia #1; #2; #3; #4; with spindle cells #1; #2; #3-vessels but not spindle cells are actin+;

atypia/malignancy: papilloma with atypia; papilloma with separate focus of ADH; papilloma with ADH; papilloma with severe atypia #1; #2; #3; with micropapillary DCIS; AFIP images - with LCIS spreading in a pagetoid manner beneath ductal epithelium #1; #2; #3 (plaque-like pattern)

Cytology images: intraductal papilloma #1; #2; #3; #4; #5

Virtual slides: intraductal papilloma; peripheral papillomas and usual ductal hyperplasia

Videos: intraductal papilloma

Positive stains: epithelium - CK 5/6, CK14, 34betaE12 (Virchows Arch 2007;450:539); also CD44s (J Clin Pathol 1999;52:862)

myoepithelium - actin, S100, p63 (AJSP 2001;25:1054), calponin, smooth muscle myosin heavy chain (AJCP 2005;123:36), CD10 (Mod Path 2002;15:397)

Negative stains: neuroendocrine markers

Molecular: clonal

DD: papillary DCIS (delicate or absent fibrovascular core, often atypical nuclei or atypical mitotic figures, pseudostratification, usually no apocrine metaplasia; other DCIS may be present, 71% have no/incomplete myoepithelal layer, 76% are 34betaE12 negative, 67% are positive for neuroendocrine markers, Virchows Arch 2007;450:539), micropapillary DCIS, invasive papillary carcinoma (no myoepithelial layer)

Phyllodes Tumor of breast

top Home Page

Definition: biphasic tumor resembling fibroadenoma, but with hypercellular mesenchymal component organized in leaf-like pattern

Also called cystosarcoma phyllodes (coined by Johannes Muller but not a good term since usually benign); also spelled phylloides

Means “leaf” in Greek

1% of breast tumors

A fibroepithelial tumor, like fibroadenoma; that arises from intralobular stroma

Average age 45 years; rare in children or men (gynecomastia is more likely)

Tumors in young girls/women have similar morphology and behavior as older women (AJSP 1998;22:64)

More common in Hispanics, particularly if born in Latin America (Cancer 1993;71:3020)

Either discrete palpable mass that rapidly enlarges or non-palpable mass identified on screening mammogram

Rosai considers it a stromal tumor with the capacity to induce glandular formation

Histologically classified as benign, borderline or malignant or as benign, low grade malignant or high grade malignant (although benign appearing tumors may rarely have malignant behavior); this classification has strong prognostic value (Eur J Obstet Gynecol Reprod Biol 2008;138:217)

Positive margin status is significantly associated with recurrence (Archives 2006;130:1516)

Overall good prognosis (Jpn J Clin Oncol 2007;37:730) with only rare deaths due to disease (Ann Surg Oncol 2007;14:2961)

Important histologic features for classification: (1) character of tumor-normal interface, (2) proportion of neoplastic stroma to epithelial structures, (3) mitotic figures/10 high power fields, (4) anaplastic cytology

Rarely secretes insulin-like growth factor II causing hypoglycemia (Breast J 2007;13:189)

DD: fibroadenoma (no tissue fragmentation, no increased stromal cellularity around glands, no stromal overgrowth, no increased mitotic figures, Int J Surg Pathol 2008;16:137)

References: eMedicine, Stanford University

Benign phyllodes tumor of breast

top Home Page

Most (75%) phyllodes tumors are benign; resemble fibroadenoma but with more cellular stroma

May have benign adipose tissue as primary stromal component (lipophyllodes tumor, Archives 1994;118:91)

May recur locally, but only rare distant metastases

Treatment: excision with 1-2 cm margins (Mod Path 2001;14:185), breast preservation if possible

Case reports: three synchronous tumors including ectopic breast tissue (Archives 1990;114:624), with DCIS and LCIS (Archives 1987;111:873), with same intracytoplasmic inclusion bodies as infantile digital fibromatosis (AJSP 1994;18:506)

Gross: well circumscribed, firm, gray-white cut surface with cleft-like spaces resembling a leaf; variable cysts, hemorrhage, necrosis

Gross images: large, well circumscribed tumor #1; #2; #3; #4; multiple polypoid nodules separated by cleft-like spaces

Micro: circumscribed pushing border, stromal hypercellularity (particularly next to epithelial elements) and benign glandular elements with intracanalicular pattern, but ratio is balanced; 0-4 mitotic figures/10 HPF; stroma resembles fibroblasts and myofibroblasts; epithelial component has luminal epithelial cells resting on myoepithelial layer; may exhibit hyperplasia, squamous metaplasia; may have clusters of multinucleated giant cells (Archives 1994;118:912); variable hemorrhage, necrosis, fat, bone, cartilage and skeletal muscle; no atypia

Micro images: hyperplastic duct surrounded by cellular fibrous stroma #1; #2; #3; #4; #5; #6; #7; #8; circumscribed tumor; leaf like processes; myxoid and cellular areas;