Nipple Lesions

and Aysegul A. Sahin2

Division of Pathology, Singapore General Hospital, Singapore, Singapore

The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA


AdenomaSyringomatous tumourPaget diseaseToker cellsSquamous carcinomaNipple

The nipple is a pigmented, nodular protuberance on the breast into which lactiferous ducts open. It is rimmed circumferentially by the areola, which is also pigmented. It comprises fibrous connective tissue with bundles of smooth muscle fibres disposed around lactiferous ducts, which contract for milk expression during lactation. The epidermis of the nipple and its surrounding areola consists of stratified squamous epithelium. Sebaceous glands are present in the areola. Skin lesions can therefore occur in the nipple and areolar region.

Squamous Metaplasia of Lactiferous Ducts


Squamous metaplasia of lactiferous ducts (SMOLD) refers to replacement of lactiferous ductal epithelium by keratinising squamous epithelium, extending deeper than the squamocolumnar junction where lactiferous ducts open onto the nipple skin. SMOLD often occurs in conjunction with subareolar abscesses and fistula formation, secondary to keratin plugs and obstruction, a condition referred to as Zuskas disease.

Clinical and Epidemiological Features

Pain, redness, swelling, and purulent discharge from the nipple-areolar region are clinical symptoms. SMOLD mostly occurs in women, but rare cases in men are described [1].

Imaging Features

Imaging reveals mixed solid–cystic masses or abscesses at the superficial periareolar or subareolar region. Fistulous formations to the overlying skin can sometimes be seen on sonography. Dilated ducts may communicate with these inflammatory masses, and there are signs of inflammation such as oedema and increased vascularity in the surrounding breast tissue [2].

Pathologic Features

Macroscopic Pathology

The nipple may be retracted and ulcerated, with necrotic discharge, mimicking malignancy.

Microscopic Pathology

Squamous metaplasia of lactiferous ducts is present, with accompanying keratin plugs, surrounding inflammation, abscess formation, and granulation tissue-lined fistulation of the lactiferous ducts to the areola (Figs. 13.1, 13.2, 13.3, 13.4, 13.5, and 13.6). The nipple epidermis is frequently eroded or ulcerated.


Fig. 13.1
Squamous metaplasia of lactiferous ducts. Microdochectomy specimen shows the profiles of several lactiferous ducts with surrounding haemorrhage. In the upper and mid-fields (arrows), there is squamous epithelium with keratinous flakes


Fig. 13.2
Squamous metaplasia of lactiferous ducts shows accumulation of keratin and surrounding squamous epithelium extending between portions of lactiferous ducts. Periductal chronic inflammation is present


Fig. 13.3
Squamous metaplasia of lactiferous ducts. Keratin plug with squamous epithelium


Fig. 13.4
Periductal chronic inflammation along the lactiferous duct in the vicinity of the keratin plug and squamous metaplasia


Fig. 13.5
Squamous metaplasia of a lactiferous duct. Pavemented squamous epithelium with polygonal cells containing vesicular nuclei, discernible nucleoli, and pink cytoplasm replaces part of the duct wall. Several foamy histiocytes are also seen


Fig. 13.6
Squamous metaplasia of lactiferous ducts, with part of the duct wall replaced by pavemented squamous epithelium, facing the opposite duct wall of columnar epithelium. Relatively intense chronic inflammation is seen in the periductal stroma

Differential Diagnosis

Squamous Papilloma

In a squamous papilloma, exophytic verrucous projections are covered by benign stratified squamous epithelium (Figs. 13.7, 13.8, 13.9, 13.10, and 13.11). Inflammation is not a key feature, unlike with SMOLD. Keratin formation in a squamous papilloma occurs on the surface, in contrast to SMOLD, in which keratinous plugs are found in the deeper portions of the dilated lactiferous ducts, which have undergone squamous metaplasia.


Fig. 13.7
Squamous papilloma overlying a nipple adenoma. At scanning magnification, a verrucous squamous lesion is seen on the nipple surface, featuring exophytic papillomatosis, acanthosis, and hyperkeratosis. A few cysts containing laminated keratin are present. Closely associated with the cysts and occurring within the nipple stroma is a proliferation of closely packed glands constituting the adenoma


Fig. 13.8
Squamous papilloma overlying a nipple adenoma. Another view of the squamous papilloma with keratin layers and squamous invaginations into the stroma, intermingling with the glands of the adenoma


Fig. 13.9
Squamous papilloma overlying a nipple adenoma. The nipple adenoma deep to the nipple squamous papilloma shows crowded glands of varying sizes, some of which are dilated and display luminal epithelial folds. The squamous epithelium merges with the glandular proliferation


Fig. 13.10
Squamous papilloma with nipple adenoma. Immunohistochemistry for p63 shows positive nuclear staining of the squamous epithelial cells. Myoepithelial cells around glands of the nipple adenoma are also decorated


Fig. 13.11
Squamous papilloma with nipple adenoma. The nipple adenoma deep to the squamous papilloma shows usual ductal hyperplasia; the epithelial proliferation shows heterogeneous staining for the high-molecular-weight keratin CK5/6

Squamous Cell Carcinoma, Invasive

Squamous cell carcinoma of the nipple is extremely rare. It can present as an exophytic nipple mass (Fig. 13.12) [3] or as a scaly lesion [4]. It has been described occurring after radiation treatment for breast carcinomas treated with conservative surgery [5]. Histologically, the superficial portions of the tumour may resemble a squamous papilloma (Fig. 13.13). Reactive atypia of squamous epithelium in Zuska’s disease may raise concern for a neoplastic lesion and mimic squamous cell carcinoma. Examination of the deeper portions of the tumour identifies invasive islands (Figs. 13.14, 13.15, and 13.16). Depending on histological grade, keratinisation may or may not be prominent. A well-differentiated squamous cell carcinoma may resemble a keratoacanthoma, but the latter is vanishingly rare, with only one case reported in the nipple [6].


Fig. 13.12
Nipple squamous cell carcinoma, invasive. Gross appearance of the fungating, ulcerated tumour arising from the nipple with overhanging rolled edges. The nipple is completely destroyed by the tumour, leaving an intact areolar rim


Fig. 13.13
Nipple squamous cell carcinoma, invasive. A hyperkeratotic, verrucous tumour with an exophytic growth pattern may resemble a squamous papilloma at scanning magnification


Fig. 13.14
Nipple squamous cell carcinoma, well differentiated, shows anastomosing, confluent islands of squamous cells with keratinisation, surrounding lactiferous ducts. The pavemented squamous islands show irregular tongue-like protrusions into the inflamed fibrotic stroma


Fig. 13.15
Nipple squamous cell carcinoma, invasive. Tumour islands comprising polygonal cells with vesicular nuclei, distinct nucleoli, pink cytoplasm, intercellular bridges, and occasional mitoses are juxtaposed to benign ducts


Fig. 13.16
Nipple squamous cell carcinoma, invasive. Irregular tongues of invasive squamous cell carcinoma with occasional squamous whorls are seen within the inflamed stroma

Prognosis and Therapy Considerations

Surgical excision of affected ducts and fistula in Zuska’s disease is curative [7].

Nipple Adenoma


The nipple adenoma is a benign epithelial proliferation centred around the lactiferous ducts, comprising closely arranged tubules with occasional papillary infoldings [8].

Clinical and Epidemiological Features

Nipple adenomas usually occur in adult women over a wide age range, though cases in paediatric patients and men have been described. Clinical symptoms are nipple discharge, erosion (Fig. 13.17), or nodule.


Fig. 13.17
Nipple adenoma. Nipple shows a haemorrhagic erosion. Excision confirmed the presence of a nipple adenoma histologically (Courtesy of Dr. Karen Yap)

Imaging Features

Nipple adenomas are usually small and are not seen on mammography. They may be detected as well-circumscribed, hypervascular nodules within the nipple on sonography.

Pathologic Features

Macroscopic Pathology

Erosion of the nipple associated with the nipple adenoma may resemble Paget disease. The nipple adenoma can also be macroscopically observed as a nodular lesion in the nipple stroma. Sometimes, no gross abnormalities are discernible.

Microscopic Pathology

Commonly, the histological appearance is that of closely packed tubules with sclerosing adenosis and variable cystic dilatation. Some tubules may demonstrate luminal papillary folds, hence the synonymous term of florid papillomatosis of the nipple, though the current preferred terminology is nipple adenoma. The myoepithelial layer is preserved. Although the lesion may appear relatively circumscribed at low magnification, no capsule is present, and epithelial nests may stream into the surrounding stroma. Usual ductal hyperplasia can be seen, with occasional necrosis and epithelial mitoses (Figs. 13.18, 13.19, 13.20, 13.21, and 13.22). Increased numbers of Toker cells in the overlying epithelium may lead to confusion with Paget disease [8].


Fig. 13.18
Nipple adenoma. Low magnification shows a proliferation of glands deep to the nipple epidermis, some of which are cystically dilated. Sclerosis is present in part of the adenoma where there is a solidified appearance


Fig. 13.19
Nipple adenoma. Medium magnification shows bilayered tubules, some of which contain luminal pink secretions. Dilated glands with luminal foam cells are present. The stroma around the glands is fibrotic and hyalinised


Fig. 13.20
Nipple adenoma. Sclerosing adenosis within a nipple adenoma. The compressed, pseudoinvasive tubules may mimic a low-grade invasive carcinoma. The presence of myoepithelial cells, intact basement membranes and lack of invasion into surrounding tissue support a benign process


Fig. 13.21
Nipple adenoma. (a, b) At low magnification, the nipple lesion shows a vaguely rounded configuration, with solid epithelial nests, cystic dilatation of ducts, and luminal projections of epithelium. Communication of the lesion with the nipple epidermis may lead to nipple discharge and the appearance of nipple erosion


Fig. 13.22
Nipple adenoma. Usual ductal hyperplasia, including luminal papillary infoldings and foamy histiocytes, is present

Differential Diagnosis

Intraductal Papilloma

As the nipple adenoma may sometimes feature papillary luminal folds, it can resemble the intraductal papilloma. Conversely, intraductal papilloma can become sclerosed and comprise compressed tubules mimicking nipple adenoma. Whereas nipple adenoma consists predominantly of proliferating glands and tubules, intraductal papilloma shows a lesional core composed of arborescent papillary fronds arising from the walls of lactiferous ducts and projecting into the ductal lumen (Figs. 13.23, 13.24, and 13.25).


Fig. 13.23
Intraductal papilloma in the retroareolar region, presenting as a nipple-areolar lump. At scanning magnification, the lactiferous duct shows cystic dilatation and a partially solid–cystic epithelial mass


Fig. 13.24
Intraductal papilloma. Medium magnification shows arborescent papillary fronds that are supported by congested fibrovascular septa. The fibrous wall of the cystically dilated duct shows a few entrapped epithelial nests and glands


Fig. 13.25
Intraductal papilloma. There is usual ductal hyperplasia with overlapped nuclei of a heterogeneous epithelial population. Irregular slit-like spaces are present

Syringomatous Tumour

In contrast to the nipple adenoma which has a rounded configuration at low magnification and comprises closely packed tubules, the syringomatous tumour consists of patent, angulated tubules and epithelial nests with a permeative pattern, located within the stroma and extending into smooth muscle bundles of the nipple and areola. Individual cell keratinisation and squamous whorls may be observed (see section “Syringomatous Tumour”).

Invasive Carcinoma

As the nipple adenoma may incorporate sclerosing adenosis, its pseudo-infiltrative pattern can resemble an invasive process usually of low histological grade. Recognisable bilayered tubules tend to constitute a significant component of the nipple adenoma.

Adnexal-Type Tumours

A variety of adnexal (sweat gland)-type epithelial tumours may arise in the nipple, including the nodular hidradenoma and syringocystadenoma papilliferum. These may be mistaken for nipple adenoma (Figs. 13.26, 13.27, 13.28, 13.29, 13.30, 13.31, and 13.32).


Fig. 13.26
Adnexal-type (eccrine) tumour with a solid–cystic papillary architecture, occurring in the nipple-areolar region and resembling a hidradenoma. Low magnification shows resemblance to an intraductal papillary lesion


Fig. 13.27
Adnexal-type tumour. Medium magnification shows collections of clear cells interspersed with polygonal cells harbouring pink cytoplasm, which form solid sheets of epithelial cells that are punctuated by ducts lined by flattened epithelium. The ducts contain pink secretions


Fig. 13.28
(a) Adnexal-type tumour shows pale and pink polygonal cells surrounding elongated duct spaces lined by flattened epithelial cells. (b) High magnification of a duct lined by flattened epithelium, surrounded by pavemented epithelial cells with pink and clear cytoplasm. Several smaller, less conspicuous ducts are also seen (arrows)


Fig. 13.29
Adnexal-type tumour. (a) Immunohistochemistry for oestrogen receptor (ER) is weakly and patchily positive. (b) High magnification shows scattered nuclear reactivity of the epithelial cells for ER


Fig. 13.30
Adnexal-type tumour. (a) Immunohistochemistry for p63 shows diffuse positivity of the epithelial cells, with sparing of the ductal lining epithelium. (b) High magnification of epithelial nuclei demonstrating intense p63 reactivity, contrasting against the negatively stained ductal epithelium


Fig. 13.31
Adnexal-type tumour. CK14 immunohistochemistry shows diffuse staining, with more intense reactivity observed for the ductal epithelium


Fig. 13.32
An unusual nipple lesion with some appearances resembling a syringocystadenoma papilliferum with inflamed, broad stromal folds covered by epithelium. Portions of lactiferous ducts cut transversely are seen, as well as islands of squamous epithelium

Prognosis and Therapy Considerations

Complete excision is curative. Recurrences may occur if the lesion is incompletely removed.

Syringomatous Tumour


Syringomatous tumour is an uncommon, locally permeative tumour that shows sweat duct differentiation. These tumours were previously referred to as syringomatous adenoma, but the term tumour is preferred because of its histologic invasive appearance and the propensity for local recurrence.

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Aug 26, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Nipple Lesions

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