Breast

Other benign tumors

Nipple adenoma



Last author update: 28 August 2023
Last staff update: 28 August 2023

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PubMed Search: Nipple adenoma

Thomas Sabljic, M.D., M.Sc., Ph.D.
Miralem Mrkonjic, M.D., Ph.D.
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Cite this page: Sabljic T, Mrkonjic M. Nipple adenoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastnipplead.html. Accessed February 26th, 2024.
Definition / general
  • Nipple adenoma is a benign epithelial proliferation with a variety of morphological patterns that arise near the collecting ducts of the nipple and may be continuous with the overlying epidermis
Essential features
  • Benign, often florid, epithelial proliferation with retained myoepithelial cell layer involving superficial ducts of the nipple; the proliferation may extend and replace the overlying squamous epithelium resulting in erosion, hemorrhage and inflammation
  • Histologic patterns include a mix of sclerosing adenosis, papillary hyperplasia and usual ductal hyperplasia
Terminology
  • Synonym: nipple duct adenoma
  • Not recommended: florid papillomatosis of the nipple, erosive adenomatosis of the nipple, papillomatosis of the nipple, superficial papillary adenomatosis, papillary adenoma of the nipple
ICD coding
  • ICD-O: 8506/0 - adenoma of nipple
  • ICD-11:
    • 2F30.Y - other specified benign neoplasm of breast
    • XH7GN3 - adenoma of nipple
Epidemiology
  • Rare; occurs in males and females
  • Most common in women in the fifth decade of life but has a wide age range (5 months to 89 years)
Sites
  • Breast; superficial duct orifices of the nipple, the associated stroma and often the adjacent overlying epidermis
Etiology
  • Unknown
Clinical features
  • Detected when small due to skin changes
  • Clinically, epidermal involvement mimics the appearance of Paget disease
  • On physical examination, small, palpable dermal nodule
    • Nipple may appear eroded and erythematous as glandular epithelium replaces squamous epithelium
    • Bleeding and exudative crust may be interpreted as nipple discharge
  • If left untreated for years, may develop into large pedunculated mass (World J Surg Oncol 2014;12:91)
Diagnosis
  • Diagnosis can be made on biopsy (often of the skin due to clinical presentation) or cytology specimen and confirmed on excision
  • Imaging findings are generally nonspecific (see Radiology description)
Radiology description
Radiology images

Images hosted on other servers:
Mammography, ultrasound and MRI of palpable left nipple mass with clear nipple discharge Mammography, ultrasound and MRI of palpable left nipple mass with clear nipple discharge Mammography, ultrasound and MRI of palpable left nipple mass with clear nipple discharge

Mammography, ultrasound and MRI of palpable left nipple mass with clear nipple discharge

Mammography, sonography and MRI images of nipple adenoma

Mammography, sonography and MRI images of nipple adenoma

Prognostic factors
  • Can recur if not completely excised
  • Risk of developing a subsequent breast cancer is comparable to other proliferative lesions of the breast (Am J Surg Pathol 1986;10:87)
Case reports
Treatment
Clinical images

Images hosted on other servers:
Nipple erythema and induration

Nipple erythema and induration

Eroded crusted nipple adenoma

Eroded crusted nipple adenoma

Nipple nodule with erosion

Nipple nodule with erosion

Pedunculated papillomatous nipple adenoma

Pedunculated papillomatous nipple adenoma


Accessory breast nipple adenoma

Accessory breast nipple adenoma

Erosion and bloody discharge

Erosion and bloody discharge

Nipple adenoma, preoperative and postconservative excision

Nipple adenoma, preoperative and postconservative excision

Gross description
  • Rubbery; white to gray; 0.5 cm to > 4 cm
Gross images

Images hosted on other servers:
Complete nipple resection

Complete nipple resection

Frozen section description
  • Glandular nests of various sizes with diffuse growth within ducts lined by myoepithelial cells; complex and irregular structure may falsely mimic invasion (Chin Med J (Engl) 2007;120:630)
Microscopic (histologic) description
  • Nodular florid epithelial proliferation of the lactiferous ducts of the nipple with papillary hyperplasia / adenosis / sclerosis / mixed pattern
  • Epithelium is cytologically bland
  • Myoepithelial cell layer is preserved uniformly (Mod Pathol 1990;3:288)
  • 4 major morphologic patterns:
    • Sclerosing papillary hyperplasia pattern:
      • Intraductal papillary growth with prominent stromal proliferation (collagenous bands, myxoid change or elastosis)
      • Focal central necrosis may be present
      • Squamous cysts can be present in duct orifices
    • Papillary hyperplasia pattern:
      • Papillary growth in large ducts with less prominent stromal proliferation and focal necrosis
      • Replacement of epidermis with glandular epithelium
    • Adenosis pattern:
      • Small duct proliferation with a pattern resembling sclerosing adenosis and may be pseudoinfiltrative
      • Necrosis is uncommon
    • Mixed pattern:
  • May be in continuity with the skin surface, which may appear eroded or ulcerated
  • Fairly well circumscribed but unencapsulated (Br Med J 1963;1:563)
  • Other features often seen:
    • Squamous metaplasia and superficial keratin cysts
    • Acanthosis
    • Toker cell hyperplasia in the epidermis
    • Multinucleated giant cells
    • Apocrine metaplasia (Oncol Lett 2014;7:1839)
  • In rare cases, ductal carcinoma in situ involving an adenoma or a contiguous invasive carcinoma have been reported (Mod Pathol 1995;8:633)
Microscopic (histologic) images

Contributed by Hal Berman, M.D., Ph.D., Miralem Mrkonjic, M.D., Ph.D. and Mary Ann Gimenez Sanders, M.D., Ph.D.
Epidermal involvement Epidermal involvement

Epidermal involvement

Focal ulceration Focal ulceration

Focal ulceration

Shave biopsy of nipple

Shave biopsy of nipple

Nipple duct involved by benign papillary proliferation

Nipple duct involved by benign papillary proliferation


Well circumscribed epithelial proliferation

Well circumscribed epithelial proliferation

Epithelial hyperplasia and epidermal ulceration

Epithelial hyperplasia and epidermal ulceration

Usual ductal hyperplasia with focal squamous metaplasia

Usual ductal hyperplasia with focal squamous metaplasia

Prominent squamous hyperplasia

Prominent squamous hyperplasia

Ductal carcinoma in situ Ductal carcinoma in situ

Ductal carcinoma in situ


Prominent epithelial proliferation with papillary architecture and tufting

Prominent epithelial
proliferation with
papillary architecture
and tufting

Nipple section Nipple section

Nipple section

Missing Image

Mixed pattern on mastectomy

Sclerosing adenosis

Sclerosing adenosis

Papillary growth within ducts

Papillary growth within ducts


Mixed pattern on punch biopsy

Mixed pattern on punch biopsy

Florid usual ductal hyperplasia

Florid usual ductal hyperplasia

Small tubules

Small tubules

Prominent epithelial proliferation Prominent epithelial proliferation Prominent epithelial proliferation

Prominent epithelial proliferation

Virtual slides

Images hosted on other servers:
Nipple adenoma sclerosing

Nipple adenoma sclerosing

Nipple adenoma adenosis pattern

Nipple adenoma adenosis pattern

Nipple adenoma papillomatous pattern

Nipple adenoma papillomatous pattern

Nipple adenoma florid usual ductal hyperplasia

Nipple adenoma florid usual ductal hyperplasia

Cytology description
  • Obtained by fine needle aspiration (FNA), brush cytology or tumor imprint cytology
  • Reported features vary; benign when myoepithelial cells are detected
  • FNA:
    • Large cell clusters with a papillary or sheet structure, as well as small clusters and solitary epithelial cells in a necrotic background
    • Duct epithelial and myoepithelial 2 cell pattern in the clusters
    • Round to oval or spindle nuclei, fine and bland chromatin
  • Brush cytology (Diagn Cytopathol 2015;43:664):
    • Small papillary clusters with attached myoepithelial cells and solitary epithelial cells in a hemorrhagic or neutrophilic background
    • Round to oval nuclei, with smooth contour, bland and granular chromatin
    • Squamous metaplasia-like cells present
  • Cytology often classified as atypical or suspicious, especially in the presence of coagulative necrosis (ANZ J Surg 2015;85:444)
Positive stains
Negative stains
Molecular / cytogenetics description
  • Activating PIK3CA mutations reported in 12/24 cases
  • KRAS (1/24 cases) and BRAF mutations (2/24 cases) (Histopathology 2017;70:195)
Videos

Dr. Jerad Gardner presents normal nipple histology and 2 cases of nipple adenoma

3 minute overview of the presentation and histology of nipple adenomas

Sample pathology report
  • Right breast (nipple), punch biopsy:
    • Nipple adenoma (see comment)
    • Comment: Sections show ductal proliferation involving a large nipple duct with areas of papillary growth and usual ductal hyperplasia in continuity with the epidermis. Ductal epithelial cells are cuboidal to columnar with eosinophilic cytoplasm and bland nuclei. Focal areas of stromal sclerosis are identified. Immunohistochemistry for smooth muscle myosin and p63 highlights the myoepithelial cell layer while ER and CK5/6 show heterogeneous staining patterns of epithelial cells. Taken together, the histomorphology and immunohistochemistry are consistent with a nipple adenoma.
Differential diagnosis
Board review style question #1

A punch biopsy of the nipple was performed to sample a nodular lesion associated with skin changes in a 48 year old woman. What is the diagnosis?

  1. Ductal adenoma
  2. Intraductal papilloma
  3. Nipple adenoma
  4. Paget disease of the breast
  5. Tubular adenoma
Board review style answer #1
C. Nipple adenoma. Nipple adenoma is a benign epithelial proliferation in the breast, often in continuity with the epidermis of the nipple. It forms a nodular mass that can have a number of different morphologic patterns including sclerosing adenosis, papillary hyperplasia and epithelial hyperplasia. Myoepithelial cells are retained in nipple adenoma. Focal necrosis can be seen and squamous cysts can be seen superficially.

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Reference: Nipple adenoma
Board review style question #2
A fairly well circumscribed lesion associated with the nipple of a 55 year old woman and consisting of papillary growth within ducts with areas of focal central necrosis in areas of florid epithelial hyperplasia is suspected to be a nipple adenoma on needle core biopsy. What stain can be used to confirm this diagnosis?

  1. CK7
  2. ER
  3. HER2
  4. p53
  5. p63
Board review style answer #2
E. p63. Nipple adenoma is a benign epithelial proliferation of the breast that retains a myoepithelial cell layer. p63, a marker of myoepithelial cells, can be used to rule out invasive carcinoma and support the diagnosis of nipple adenoma.

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Reference: Nipple adenoma
Board review style question #3
A 54 year old woman presents with erythema, erosion and crusting of the nipple. A punch biopsy is performed showing nipple adenoma. Which of the following statements is true regarding nipple adenomas?

  1. HER2 positivity is an essential characteristic of nipple adenomas
  2. Myoepithelial cells are absent in nipple adenoma
  3. Sclerosing adenosis, papillary hyperplasia and epithelial hyperplasia can be seen in mixed patterns in a nipple adenoma
  4. The presence of necrosis excludes nipple adenoma in the differential diagnosis
  5. The skin changes that can be seen in nipple adenoma are clinically distinct from Paget disease
Board review style answer #3
C. Sclerosing adenosis, papillary hyperplasia and epithelial hyperplasia can be seen in mixed patterns in a nipple adenoma. Nipple adenoma is a benign breast lesion and can consist of sclerosing adenosis, papillary hyperplasia and epithelial hyperplasia, which can be seen in mixed patterns. Necrosis can sometimes be seen in areas of florid epithelial hyperplasia. The myoepithelial cell layer is retained and HER2 IHC is negative. Nipple adenoma can present clinically with skin changes that are very similar to Paget disease.

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Reference: Nipple adenoma
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