, Fan Lin1 and Jun Zhang2
(1)
Department of Laboratory Medicine, Geisinger Health System, Danville, PA, USA
(2)
Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA
Keywords
Invasive carcinoma of no special type (NST) (pleomorphic carcinoma, carcinoma with osteoclast-like stromal giant cells, carcinoma with choriocarcinomatous features, carcinoma with melanotic features)Invasive lobular carcinoma (classic lobular carcinomaSolid lobular carcinomaAlveolar lobular carcinomaPleomorphic lobular carcinomaTubulolobular carcinomaMixed lobular carcinoma)Tubular carcinomaCribriform carcinomaMucinous carcinomaCarcinoma with medullary features (medullary carcinomaAtypical medullary carcinomaInvasive carcinoma NST with medullary features)Carcinoma with apocrine differentiationCarcinoma with signet-ring-cell differentiationInvasive micropapillary carcinomaMetaplastic carcinoma NST (low-grade adenosquamous carcinomaFibromatosis-like metaplastic carcinomaSquamous cell carcinomaSpindle cell carcinomaMetaplastic carcinoma with mesenchymal differentiation)Mixed metaplastic carcinomaMyoepithelial carcinomaCarcinoma with neuroendocrine features (neuroendocrine tumorwell-differentiatedNeuroendocrine carcinomapoorly differentiated (small cell carcinoma)Carcinoma with neuroendocrine differentiation)Secretory carcinomaInvasive papillary carcinomaAcinic cell carcinomaMucoepidermoid carcinomaPolymorphous carcinomaOncocytic carcinomaLipid-rich carcinomaGlycogen-rich clear cell carcinomaSebaceous carcinomaCylindroma, clear cell hidradenoma, pleomorphic adenoma, adenomyoepitheliomaAdenomyoepithelioma with carcinomaAdenoid cystic carcinoma, DCIS, lobular neoplasiaLobular carcinoma in situAtypical lobular hyperplasiaUDHColumnar cell lesions, including flat epithelial atypiaADHIntraductal papillomaIntraductal papillary carcinomaEncapsulated papillary carcinomaSolid papillary carcinomaSclerosing adenosisApocrine adenosisMicroglandular adenosisRadial scar/complex sclerosing lesionAdenomas (tubular adenoma, lactating adenoma, apocrine adenoma, ductal adenoma)Nodular fasciitisMyofibroblastomaDesmoid-type fibromatosisInflammatory myofibroblastic tumorBenign vascular lesions (hemangioma, angiomatosis, atypical vascular lesions)Pseudoangiomatous stromal hyperplasiaGranular cell tumor, neurofibroma, schwannoma, lipoma, angiolipomaLiposarcomaAngiosarcomaRhabdomyosarcomaOsteosarcomaLeiomyomaLeiomyosarcomaFibroadenomaPhyllodes tumorHamartoma, Nipple adenomaSyringomatous tumorPaget disease of the nippleLymphomaDiffuse large B-cell lymphomaBurkitt lymphomaT-cell lymphomaAnaplastic large cell lymphomaExtranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, follicular lymphoma, gynecomastia, carcinoma, metastasisERPRHER2p63calponinSMM-HCLMWCKsHMWCKsCK7CK20CK5CK14CK5/6S100GATA3MGBGCDFP15ChromograninSynaptophysinCD10p120 cateninE-cadherinp53MIB-1 (Ki67)Summary of Pearls and Pitfalls
Fine needle aspiration (FNA) cytology and core needle biopsy (CNB) of breast lesions are the key components of the triple test for detecting breast malignancies.
The advantages of FNA cytology are its rapid, cost-effective and, in experienced hands, highly sensitive and specific as well.
The major limitations of FNA of breast lesions are the need for expertise in cytology for the interpretation of FNA material, inability to differentiate atypical ductal hyperplasia (ADH) from ductal carcinoma in situ (DCIS ), limited ability to diagnose invasion, and often inadequate sample (and/or inadequate preparation of the material) for hormonal analyses in cases of carcinomas.
For nonpalpable breast lesions, CNB has become the standard procedure for pathologic diagnosis.
For palpable lesions, FNA is still utilized but has rapidly declined in popularity in recent years.
At the current time, the common indications for FNA of breast lesions are as follows: (a) an expected benign cyst by ultrasound; (b) a sonographic lesion in a pregnant or postpartum patient or a patient with contraindications for CNB; (c) a sonographic lesion in a location unsuitable for CNB, such as behind the nipple or close to the chest wall; (d) to confirm an inoperable and locally advanced malignancy; (e) a suspected recurrence or metastasis; and (f) preoperative staging of axillary lymph nodes.
Complications are rare, with the most common being bleeding.
Normal Cytology of Breast
The female mammary gland is composed of 15–20 (or 25) lobes or segments that converge on the nipple in a radial pattern.
Each lobe consists of a lactiferous duct, lactiferous sinus, segmental collecting duct, subsegmental duct, ductule (terminal duct), and acini (terminal ductules).
The terminal duct lobular units (TDLUs) are comprised of ductile and acini, as shown in Fig. 5.1a, b, which is the most hormone-sensitive, therefore, the major site of origin of breast pathology.
Fig. 5.1
(a, b) Normal terminal duct lobular unit (TDLU) . (a) Histology, H&E; (b) cytology, Pap stain
The smears of benign non-neoplastic glandular tissue are usually low cellularity, arranged in tight small, large or branching clusters, as well as monolayer sheets.
The cells are cohesive; uniform; with small, round-to-oval, hyperchromatic nuclei; inconspicuous or very small nucleoli, and scant cytoplasm without distinct cell borders.
The nuclei are irregularly distributed within the clusters to impart a crowded, overlapping appearance, as shown in Fig. 5.2a.
Fig. 5.2
(a, b) Benign ductal and lobular epithelial cells. (a) Benign ductal cells in crowded cluster, Diff-Quik; (b) benign ductal cells in monolayer sheet, Pap stain
Myoepithelial cells or stromal cells are appreciated at the periphery or admixed within the clusters.
Naked bipolar nuclei (myoepithelial cells) may be seen in the background.
Figure 5.2b illustrates a sample of benign glandular epithelial cells in a monolayer sheet.
Nipple Discharge Cytology
A spontaneous nipple discharge in a non-lactating or pregnant woman is abnormal and may suggest an underlying breast lesion (such as papilloma/papillomatosis or carcinoma) or hormonal abnormalities. However, nipple discharge cytology has a low sensitivity for detecting an underlying malignancy. Cases with unilateral, serous, bloody nipple discharge from a single duct are pathological and frequently associated with papillary lesions. In addition, the probability of detecting an underlying malignancy is increased in those specimens.
Cytological Features
Benign Nipple Discharge
Usually sparsely cellular.
Scattered foamy histiocytes.
Rare benign ductal cells in small clusters.
Inflammatory cells may be present.
Proteinaceous debris in background.
Figure 5.3a, b.
Fig. 5.3
(a, b) Contents of benign nipple discharge. Sparsely cellular smear contains few foam histiocytes and proteinaceous debris. (a) histiocytes, Diff-Quik; (b) degenerated histiocytes and rare crystals in a background of proteinaceous debris, Diff-Quik
Atypical or Malignant Nipple Discharge
Significant increase of cellularity.
Clusters or isolated ductal cells with enlarged and pleomorphic nuclei displaying nucleoli.
Stripped nuclei.
Papillary groups may be seen.
Necrosis may present.
Acute inflammation and bloody background.
Figure 5.4.
Fig. 5.4
Contents of atypical nipple discharge, showing a tight cluster of atypical ductal epithelial cells with enlarged nuclei, hyperchromatic chromatin, and moderate nuclear pleomorphism, Pap stain
Fat Necrosis
Key Clinical Features
The result of various injuries, such as trauma, previous procedure, chemoradiation therapy, and rupture of cyst
Mimics breast carcinoma clinically, such as a firm mass, skin retraction, or thickening
Key Radiological Features
Variable, may mimic breast carcinomas radiographically
Cytological Features
Degenerated adipose tissue, giant cells, and foamy histiocytes
Dirty background with amorphous or granular debris, fat droplets, and normal or degenerating adipose tissue
Reactive stromal cells and occasional inflammatory cells
Paucity of epithelial cells
Figure 5.5a, b
Fig. 5.5
(a–d) Fat necrosis . (a, b) Cytology, showing foamy histiocytes including multinucleated forms and debris (a, Diff-Quik; b, Papanicolaou [Pap] stain); (c, d) histology, abundant foam histiocytes including multinucleated forms, fat and fibrous tissue, hematoxylin, and eosin (H&E)
Differential Diagnosis
Infectious panniculitis
Invasive lobular carcinoma
Histology
Usually a well-demarcated area of vacuolated fat admixed with infiltrates of foamy histiocytes, multinucleated giant cells, lymphocytes, and plasma cells.
Hemosiderin-laden macrophages and occasional cholesterol clefts are present.
Granulation tissue with fibrosis and reactive ductal epithelial cells are occasionally identified.
Representative image is illustrated in Fig. 5.5c, d.
Immunohistochemistry
Fat necrosis is mainly a histological diagnosis.
Immunohistochemistry (IHC) is rarely applied on post-procedural specimens from breast carcinoma patients when the histiocytes show significant atypia; cluster of differentiation 68 (CD68) decorates histiocytes, while cytokeratin (CK) AE1/3 is nonreactive.
Subareolar Abscess
Key Clinical Features
Also called “recurrent subareolar abscess”
In the subareolar region, starts as a localized inflammation to form abscess, with subsequent healing and squamous metaplasia of the lactiferous ducts, then keratin plugging, dilatation and rupture of the ducts, as well as sinus tract formation
Cytological Features
Abundant anucleated squames and neutrophils (Fig. 5.6a–d).
Fig. 5.6
(a–d) Subareolar abscess , cytology. There are abundant anucleated squamous epithelial cells, neutrophils, and dirty debris (a, b, Diff-Quik). Occasional multinucleated giant cells with adjacent keratin debris are seen (c, Pap stain), may form granulomatous aggregate (d, Pap stain)
Keratin debris, cholesterol crystals, and strips of squamous epithelial cells may be present.
Rare ductal cells.
Reactive stromal cells and giant cells.
Differential Diagnosis
Epidermal inclusion cyst: peripheral and periareolar location
Histology
Breast tissue is displaced by chronic active inflammation with numerous neutrophils and a scant mixture of plasma cells and histiocytes.
In recurrent cases, dilated duct with inflamed wall, granulation tissue, and intraluminal debris is present; may form a fistula.
Representative images are shown in Fig. 5.7a, b.
Fig. 5.7
(a, b ) Subareolar abscess , histology. (a) Breast tissue with chronic active inflammation with numerous neutrophils and a scant mixture of plasma cells and histiocytes, H&E; (b) dilated duct with inflamed wall, granulation tissue, and intraluminal debris, including abundant anucleated squamous epithelial cells, H&E
Immunohistochemistry
Immunohistochemistry is usually not applied for the diagnosis of subareolar abscess.
Fibrocystic Change
Fibrocystic change is the most common breast disorder, characterized by any combination of small/large cysts, apocrine metaplasia, fibrosis, adenosis, and duct hyperplasia.
Key Clinical Features
Usually palpable nodularity in women of 20–50 years of age.
The nodules are not well-defined, usually tender or even painful, changing with menstrual cycle.
Generally multifocal, may be bilateral.
May be more localized to produce a palpable mass: the most common mass-producing lesion in women older than 30 years.
May come to attention due to calcifications on mammogram.
Radiological Features
Nodular densities or solitary, round or ovoid, and/or well-circumscribed masses of low-to-intermediate density on mammogram; may have microcalcifications.
Simple cysts show lack of internal echoes and increased echogenicity of the posterior tissue on ultrasound.
Cytological Features
Nonproliferative Fibrocystic Changes
Low-to-moderate cellularity
A mixture of cellular components: cohesive groups or sheets of bland ductal cells, myoepithelial cells, apocrine cells, and histiocytes
Scattered naked bipolar nuclei, fat, stromal tissue, and proteinaceous fluid in the background
Figure 5.8a–d
Fig. 5.8
(a–d) Nonproliferative fibrocystic changes . (a) Benign ductal cells in cohesive cluster with appreciable myoepithelial cells and stromal fragment, Diff-Quik; (b) myoepithelial cells are easily identified, in addition, few macrophages are seen, Pap stain; (c) Cohesive groups and sheet of benign ductal epithelial cells in a background of many bipolar naked stromal nuclei, Pap stain; (d) cluster of bland-looking ductal epithelial cells admixed with adipocytes and myoepithelial cells, Pap stain
Proliferative Fibrocystic Change
Ductal Proliferative Lesion Without Atypia
Sheets and tight clusters of cells without significant nuclear overlap
Finely granular chromatin pattern
Inconspicuous to small nucleoli
Ductal Proliferative Lesion with Atypia
Sheets and tight clusters of cells with significant nuclear overlap, loss of polarity, punched-out spaces, and mitosis
Finely to coarsely granular chromatin
Prominent to multiple nucleoli
Figure 5.9a, b
Fig. 5.9
(a, b) Ductal proliferative lesion with atypia . (a) Cluster of atypical ductal epithelial cells with monotonous enlarged nuclei, coarsely granular chromatin pattern, nucleoli, and punched-out spaces, suggesting ductal carcinoma in situ. Myoepithelial cells are identified at the periphery, Pap stain; (b) group of atypical ductal cells with appreciable punched-out spaces, myoepithelial cells identified focally, Pap stain
Differential Diagnosis
Ductal Proliferative Lesion Without Atypia
Intraductal papilloma
Fibroadenoma
Ductal Proliferative Lesion with Atypia
ADH and/or DCIS
Ductal carcinoma
Histology
Fibrocystic change refers to a complex of lesions, including dilated ducts/cysts, stromal fibrosis, apocrine metaplasia, blunt duct adenosis, mild sclerosing adenosis, and usual ductal hyperplasia (UDH).
Atypical ductal proliferative lesions show ADH or DCIS .
Immunohistochemistry
Nonproliferative fibrocystic change is mainly a histomorphological diagnosis.
IHC comes to play a role only when a ductal hyperplasia is present and the morphological features border on UDH and ADH.
UDH is a hyperplastic process, with high expression of basal cell-type keratin or high molecular weight cytokeratin (HMWCK) and scattered ER expression.
ADH/DCIS is neoplastic with a clonal proliferation of luminal epithelial cells, showing loss or focal weak expression of basal cell-type keratin or HMWCK and diffuse ER positivity.
By application of ADH5, a breast marker cocktail consisting of CK5 , CK14 , p63 , CK7, and CK18, UDH exhibits a mosaic staining pattern, and ADH/DCIS shows a clonal proliferation of luminal epithelial cells with negative HMWCK (basal cell type) staining, as shown in Fig. 5.10a–d, respectively.
Fig. 5.10
(a–d) Differential immunophenotype of atypical ductal hyperplasia (ADH)/ductal carcinoma in situ (DCIS ) vs usual ductal hyperplasia (UDH). (a) UDH, H&E; (b) UDH, ADH5 shows a mosaic pattern, both CK903 and luminal cytokeratin staining pattern, IHC; (c) ADH, H&E; (d) ADH, loss of expression for HMWCK, CK903, ADH5 staining, IHC
Tumors of the Breast
The World Health Organization (WHO) classifications of tumors of the breast are summarized in Table 5.1.
Table 5.1
WHO Classification of Tumors of the Breast, 2012
Epithelial tumors |
Microinvasive carcinoma |
Invasive breast carcinoma |
Invasive carcinoma of no special type (NST) |
Pleomorphic carcinoma |
Carcinoma with osteoclast-like stromal giant cells |
Carcinoma with choriocarcinomatous features |
Carcinoma with melanotic features |
Invasive lobular carcinoma |
Classic, solid , alveolar , pleomorphic , tubulolobular , mixed lobular carcinomas |
Tubular carcinoma |
Cribriform carcinoma |
Mucinous carcinoma |
Carcinoma with medullary features |
Medullary carcinoma |
Atypical medullary carcinoma |
Invasive carcinoma NST with medullary features |
Carcinoma with apocrine differentiation |
Carcinoma with signet-ring-cell differentiation |
Invasive micropapillary carcinoma |
Metaplastic carcinoma NST |
Low-grade adenosquamous carcinoma |
Fibromatosis-like metaplastic carcinoma |
Squamous cell carcinoma |
Spindle cell carcinoma |
Metaplastic carcinoma with mesenchymal differentiation |
Chondroid, osseous, other types of mesenchymal differentiations |
Mixed metaplastic carcinoma |
Myoepithelial carcinoma |
Rare types |
Carcinoma with neuroendocrine features |
Neuroendocrine tumor, well-differentiated |
Neuroendocrine carcinoma, poorly differentiated (small cell carcinoma) |
Carcinoma with neuroendocrine differentiation |
Secretory carcinoma |
Invasive papillary carcinoma |
Acinic cell carcinoma |
Mucoepidermoid carcinoma |
Polymorphous carcinoma |
Oncocytic carcinoma |
Lipid-rich carcinoma |
Glycogen-rich clear cell carcinoma |
Sebaceous carcinoma |
Salivary gland/skin adnexal-type tumors |
Cylindroma , clear cell hidradenoma |
Epithelial-myoepithelial tumors |
Pleomorphic adenoma |
Adenomyoepithelioma |
Adenomyoepithelioma with carcinoma |
Adenoid cystic carcinoma |
Precursor lesions |
DCIS |
Lobular neoplasia |
Lobular carcinoma in situ |
Classic or pleomorphic lobular carcinoma in situ |
Atypical lobular hyperplasia |
Intraductal proliferative lesions |
UDH |
Columnar cell lesions, including flat epithelial atypia |
ADH |
Papillary lesions |
Intraductal papilloma |
Intraductal papillomas with ADH, or DCIS , or LCIS |
Intraductal papillary carcinoma |
Encapsulated papillary carcinoma |
Encapsulated papillary carcinoma with invasion |
Solid papillary carcinoma |
In situ, invasive |
Benign epithelial proliferations |
Sclerosing adenosis |
Apocrine adenosis |
Microglandular adenosis |
Radial scar/complex sclerosing lesion |
Adenomas |
Tubular, lactating, apocrine, ductal adenomas |
Mesenchymal tumors |
Nodular fasciitis |
Myofibroblastoma |
Desmoid-type fibromatosis |
Inflammatory myofibroblastic tumor |
Benign vascular lesions |
Haemangioma, angiomatosis, atypical vascular lesions |
Pseudoangiomatous stromal hyperplasia |
Granular cell tumor |
Benign peripheral nerve sheath tumors |
Neurofibroma , schwannom a |
Lipoma |
Angiolipoma |
Liposarcoma |
Angiosarcoma |
Rhabdomyosarcoma |
Osteosarcoma |
Leiomyoma |
Leiomyosarcoma |
Fibroepithelial tumors |
Fibroadenoma |
Phyllodes tumor |
Benign, borderline, malignant, periductal stromal sarcoma, low grade |
Hamartoma |
Tumors of the nipple |
Nipple adenoma |
Syringomatous tumor |
Paget disease of the nipple |
Malignant lymphoma |
Diffuse large B-cell lymphoma |
Burkitt lymphoma |
T-cell lymphoma |
Anaplastic large cell lymphoma , anaplastic lymphoma kinase (ALK) negative |
Extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type |
Follicular lymphoma |
Metastatic tumors |
Tumors of the male breast |
Gynecomastia |
Carcinoma |
Invasive carcinoma, in situ carcinoma |
Clinical patterns |
Inflammatory carcinoma |
Bilateral breast carcinoma |
Fibroepithelial Tumors
Fibroadenoma
Key Clinical Features
Most common benign tumor
Asymptomatic or a mobile, painless, well-defined breast nodule/mass
In premenopausal women, usually in their second or third decades
Usually solitary
Occasionally multifocal and bilateral, reported in Afro-Caribbean women
Key Radiological Features
Well-defined mass, with or without microcalcifications
Homogeneous, hypoechoic, and well-circumscribed mass on ultrasound
Cytological Features
Cohesive benign ductal epithelial cells arranged in a branching antler-horn configuration in a background of many naked bipolar or spindled nuclei
Myoepithelial cells at periphery
Hypocellular myxoid stroma
Focal ductal cells with apocrine changes
Figure 5.11a–d
Fig. 5.11
(a–f) Fibroadenoma , cytology and histology. (a, b) Branching antler-horn benign ductal cells in a background of many bipolar or spindled naked nuclei and rare stromal tissue, Diff-Quik; (c) benign ductal epithelial cells and stromal tissue, Pap stain; (d) Antler-horn fragment of benign ductal epithelial cells and scant stroma. Myoepithelial cells are present, Pap stain; (e) pericanalicular pattern, H&E; (f) Intracanalicular pattern, H&E
Differential Diagnosis
Benign proliferative fibrocystic changes
Phyllodes tumor
Mammary hamartoma
Tubular adenoma
Histology
Fibroadenomas are composed of both epithelium and stroma with a well-demarcated, lobulated, or smooth border.
The epithelium shows two growth patterns: pericanalicular and intracanalicular, as illustrated in Fig. 5.11e, f.
The stroma is variable in morphology and cellularity, however homogeneous throughout in individual cases.
Immunohistochemistry
Immunohistochemistry is usually not applied for the diagnosis of fibroadenoma.
Phyllodes Tumor
Key Clinical Features
0.3–1% of all breast neoplasms
In peri- and postmenopausal women, usually their fifth decade
Presents with a palpable breast mass, usually painless, mobile, multinodular and firm, or presents with an abnormal mammography
Key Radiological Features
Well-circumscribed, lobulated mass on mammography
Solid, hypoechoic, well-circumscribed mass on ultrasound
Cytological Features
Cellular specimen
Mixed epithelial and stromal fragments
Hypercellular stromal fragments, comprised of spindle-shaped cells singly or enmeshed in stroma; significant atypia of the spindle cells with mitotic activity suggesting malignant phyllodes tumor
Many naked bipolar or spindle nuclei in the background
Occasional ductal hyperplasia with or without atypia
Figure 5.12a–c
Fig. 5.12
(a–h) Phyllodes tumor , cytology, histology, and immunophenotype. (a) Cohesive cluster of ductal epithelial cells with mild atypia and fragment of stroma, Pap stain; (b) the stromal cells are spindled with atypia and a rare mitotic figure, Diff-Quik; (c) stroma with increased cellularity and atypia, Pap stain; (d, e) leaflike pattern, highly cellular and atypical stroma with mitotic figures, H&E; (f) positive CD34 staining, IHC; (g) high expression of p53 , IHC; (h) high proliferative index (MIB-1), IHC
Differential Diagnosis
Fibroadenoma
Metaplastic carcinoma
Primary sarcoma
Sclerosing adenosis
Histology
A biphasic tumor contains epithelial and stromal components, usually with a prominent intracanalicular growth pattern to form leaf-like structures.
The stroma is usually heterogeneous in cellularity with mitotic activity.
Representative images are illustrated in Fig. 5.12d, e.
Immunohistochemistry
Immunohistochemistry does not usually contribute to the diagnosis of phyllodes tumor. However, the expression of Ki-67 and p53 correlates with tumor grade.
CD34 and B-cell CLL/lymphoma-2 (Bcl2) were reported to be positive and can be used to differentiate a malignant phyllodes tumor from metaplastic (spindle cell) carcinoma.
Representative images are illustrated in Fig. 5.12e–h.
Hamartomas
Key Clinical Features
Less than 1% of benign breast masses
Common in pre- and perimenopausal women
Presents as a mobile, painless, soft-to-firm, well-defined palpable mass
Key Radiological Features
Well-circumscribed, round-to-oval inhomogeneous mass on mammogram; characteristically, the mass is centrally dense with a radiolucent rim.
Sonographic features are variable; difficult to delineate the margins due to the resemblance to normal breast tissue; and may appear as a well-defined, solid lesion with mixed internal echotextures and without any lesional microcalcifications.
Cytological Features
Low-to-moderate cellularity specimen
Scattered sheets of benign ductal epithelial cells, some showing irregular branching
Lobular cells forming acini, presenting as an intact lobular units
Minimal-to-absent cellular discohesion or atypia
Adipose tissue in various amounts and occasional stromal fragments, may have attached epithelial cells
Frequent bipolar stromal nuclei, occasional apocrine cells, foam cells, and myoepithelial cells
Differential Diagnosis
Fibrocystic changes
Fibroadenoma
Histology
A disproportionate and disorganized growth of mature mammary tissues, including ducts, lobules, fat, fibrous connective tissue, and smooth muscle, forming well-defined nodules.
The presence of fibrous tissue within the lobules (interlobular fibrosis) or fibrous tissue and fat in the stroma should alert the pathologist to the possibility of a hamartoma.
Representative images are shown in Fig. 5.13a, b.
Fig. 5.13
(a, b) Mammary hamartoma , histology. (a) Disorganized growth of fat, fibrous connective tissue forming nodule, H&E; (b) disorganized growth of fibrous connective tissue, H&E
Immunohistochemistry
Immunohistochemistry plays no role in the diagnosis of a mammary hamartoma.
Epithelial Tumors
Benign Epithelial Proliferation
Lactating Adenoma
Lactating adenoma is a term used for a fibroadenoma with superimposed changes of lactation.
Key Clinical Features
Typically a breast mass in a young pregnant or postpartum woman
Occasionally can be large and painful
Key Radiological Features
Similar to fibroadenoma; occasionally shows atypical features on ultrasound, such as irregular margins, heterogeneous echogenicity, and posterior shadowing
Cytological Features
Cellular specimen with a milky or lipid background
Ductal epithelial cells with nuclear enlargement and conspicuous nucleoli
Ductal cells with smooth nuclear contour and evenly distributed chromatin
Many naked nuclei with small-to-prominent nucleoli
Figure 5.14a, b
Fig. 5.14
(a–d) Lactating adenoma . (a, b) Cellular smear contains loosely cohesive clusters of ductal epithelial cells with enlarged nuclei, small to prominent nucleoli, and vacuolated cytoplasm in a milky or lipid background with naked nuclei, (a) Diff-Quik; (b) Pap stain; (c, d) Hiatology, H&E; well-circumscribed, compact aggregate of lobules exhibiting secretory hyperplasia (d); the glandular cells show vacuolated cytoplasm, diffusely distributed in a sparsely cellular stroma (c)
Differential Diagnosis
Carcinoma , ductal, or lobular
Non-Hodgkin’s lymphoma
Histology
Lactating adenoma is composed of a compact aggregate of lobules exhibiting secretory hyperplasia during pregnancy or postpartum.
The glandular elements are diffusely distributed in a sparsely cellular stroma; the glandular cells show vacuolated cytoplasm.
A representative image is shown in Fig. 5.14c, d.
Immunohistochemistry
Immunohistochemistry is usually not applied for the diagnosis of lactating adenoma.
Papillary Lesions
Key Clinical Features
Intraductal papilloma : solitary, usually centrally located tumor in peri- and postmenopausal women, often presents as bloody nipple discharge; can be peripheral and multiple, may present as mass lesions
Papillary carcinoma: 1–2% of breast cancers; usually in postmenopausal women; can present as a mass; one-third of patients present with bloody nipple discharge; favorable prognosis.
Key Radiological Features
Central papillary lesions may present as a circumscribed subareolar mass with well-defined borders, without stromal distortion on mammography; an intraductal mass with associated dilated duct or a complex cystic lesion on ultrasonography. Peripheral papillary lesions present as mammographic abnormalities or may be radiographically occult.
Cytological Features
Highly cellular sample
Many groups and sheets of ductal cells with papillary fronds (Fig. 5.15a, b)
Fig. 5.15
(a–d) Papillary lesions , cytology, histology, and immunophenotype. (a) numerous papillary groups, Pap stain; (b) Papillary groups with the overlying epithelial cells showing columnar morphology; (c, d) loosely cohesive and single columnar cells with intact cytoplasm in background, Diff-Quik and Pap stain
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