Breast malignant, males, children
Other malignancies
Metastases to breast

Editor-in-Chief: Debra Zynger, M.D.
Gary Tozbikian, M.D.

Topic Completed: 30 April 2019

Revised: 1 May 2019

Copyright: 2001-2019, PathologyOutlines.com, Inc.

PubMed Search: Carcinoma [title] "metastases" to breast

Gary Tozbikian, M.D.
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Cite this page: Tozbikian G. Metastases to breast. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantmet.html. Accessed November 22nd, 2019.
Definition / general
  • Metastasis to the breast from a malignancy arising outside the breast
Essential features
  • Rare, < 1% of breast malignancies (Eur J Surg Oncol 2003;29:854, Cancer 2007;110:731, J Clin Pathol 2007;60:1333)
  • Can be initially misdiagnosed due to nonspecific / overlapping clinical, radiologic, morphologic and immunophenotypic features with primary breast carcinoma, especially if inadequate clinical history is provided
  • Accurate identification of extramammary metastases is critical to avoid unnecessary surgery and inappropriate treatment
Terminology
  • Nonmammary metastases to the breast, extramammary metastases to the breast
ICD coding
  • ICD-10: C80.0 - disseminated malignant neoplasm, unspecified
Epidemiology
Etiology
Clinical features
Diagnosis
  • Possibility of a nonmammary metastasis should be considered when encountering a breast lesion with unusual clinical, radiologic or histomorphologic features
  • Clinical history is critical to establish the correct diagnosis; there is often history of advanced stage, non breast malignancy
  • Biopsy is performed if clinical and imaging are inconclusive regarding primary versus metastasis
  • Identification of a definitive in situ component can be useful to rule out a metastasis and confirm a breast primary
  • Absence of an in situ component does not conclusively exclude a nonmammary metastasis, as an in situ component is not present in all primary mammary carcinomas
  • Immunohistochemical work up is generally required for confirmation of the diagnosis
Radiology description
Radiology images

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Gastric signet ring cell carcinoma

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Malignant melanoma

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Ovarian serous carcinoma

Prognostic factors
Case reports
Treatment
  • Primary therapeutic approach is systematic treatment that is specific and appropriate to the primary lesion
  • Generally, surgical excision is not indicated for metastatic tumors to the breast, unless performed to palliate symptoms (e.g. bulky, ulcerated lesions)
  • It is critically important for the pathologist to recognize the metastatic nature of the lesion, as the treatment and prognosis differ significantly from primary breast cancer and misdiagnosis can result in unnecessary surgery and inappropriate treatment (Mod Pathol 2013;26:343)
Gross description
  • Generally well circumscribed
Gross images

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Malignant melanoma

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Pulmonary adenocarcinoma

Microscopic (histologic) description
  • General
    • Often morphologic features are unusual for a primary mammary tumor (J Clin Pathol 2007;60:1333)
    • Lack of an in situ component (J Clin Pathol 2007;60:1333)
    • Metastatic tumors with certain morphologies (e.g. spindle cell, mucinous, squamous, clear cell, neuroendocrine) may show significant morphologic overlap with primary breast malignancies
  • Malignant melanoma
    • Wide range of histologic appearances, may be amelanotic
    • Generally high grade cytology
    • Pigment, spindle cell morphology, intranuclear inclusions can suggest melanoma (Histopathology 2000;36:387)
  • Pulmonary carcinoma
    • Wide range of histologic appearances, including cystic papillary and glandular architecture
    • Small cell features can suggest pulmonary site of origin
  • Ovarian carcinoma
    • Usually serous type, less commonly mucinous or clear cell types
    • Wide range of histologic appearances, including papillary, glandular and solid architecture
    • May show necrosis and high grade cytology
    • Papillary morphology, psammomatous calcifications can suggest ovarian serous carcinoma (Am J Surg Pathol 2004;28:1646)
    • Often morphologic overlap with breast primary
  • Gastrointestinal carcinoma
    • If mucinous morphology, can show histologic overlap with mucinous subtype of breast carcinoma
    • If signet ring cell morphology, can show histologic overlap with lobular subtype of breast carcinoma
    • If neuroendocrine / carcinoid, can show histologic overlap with neuroendocrine carcinoma of the breast
  • Renal cell carcinoma
    • Clear cell features can suggest renal site of origin
    • If spindle cell and sarcomatoid morphology, can show histologic overlap with metaplastic breast carcinoma
  • Prostatic adenocarcinoma
    • Can show morphologic overlap with breast primary
Microscopic (histologic) images

Contributed by Gary Tozbikian, M.D.
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Metastatic ovarian serous carcinoma

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Metastatic leiomyosarcoma

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Metastatic malignant melanoma

Cytology description
  • Malignant melanoma
    • Dispersed polygonal and plasmacytoid cells with a moderate amount of granular and vacuolated cytoplasm, can show spindle cell morphology (Diagn Cytopathol 2017;45:446)
  • Pulmonary adenocarcinoma
  • Ovarian carcinoma
    • Medium sized cells arranged in papillary clusters with round nuclei with evident nucleoli and a moderate quantity of greyish cytoplasm, psammomatous microcalcifications (Ann Oncol 2008;19:682)
Cytology images

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Metastatic ovarian serous carcinoma

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Metastatic lung adenocarcinoma

Positive stains
Negative stains
Sample pathology report
  • Breast, left, 2:00 Zone 2, ultrasound guided core biopsy:
    • Metastatic carcinoma, consistent with a metastasis of Müllerian origin, see comment
    • Comment: Per the electronic medical record, the patient’s history of ovarian cancer is noted. Immunohistochemical stains show that the tumor cells are positive for CK7, estrogen receptor, PAX8 and WT1 and are negative for GATA3, BRST2 and mammaglobin. The findings are consistent with a metastasis of Müllerian origin (ovarian serous carcinoma).
Differential diagnosis
Board review question #1
    A 55 year old woman with history of cutaneous malignant melanoma presents with a solitary, palpable, rapidly enlarging breast mass. Ultrasound guided core biopsy shows a high grade malignant neoplasm. What panel of immunohistochemical stains would be most useful in distinguishing metastatic melanoma versus a primary breast malignancy?

  1. Cytokeratin and estrogen receptor
  2. Cytokeratin, HMB45 and MelanA
  3. Estrogen receptor and S100
  4. SOX10 and estrogen receptor
  5. SOX10 and S100
Board review answer #1
B. A panel of cytokeratins and melanoma markers (e.g. S100, HMB45, MelanA) would be most useful. 20% of breast cancers will be negative for estrogen receptor. A negative result for estrogen receptor would not rule out a breast primary. SOX10 can be expressed in both melanoma as well as triple negative breast cancer.

Comment Here

Reference: Metastases to breast
Board review question #2
    A 45 year old BRCA+ woman with a history of estrogen receptor positive primary ductal carcinoma of the breast cancer 5 years ago now presents with ascites and omental caking. Peritoneal biopsy shows a high grade malignant neoplasm with glandular and papillary features. Given the history, an initial panel of breast biomarkers is performed. The tumor is strongly positive for estrogen receptor and progesterone receptor and is negative for HER2. What panel of additional immunohistochemical stains would be most useful in the diagnosis?

  1. CK20 and CDX2
  2. Cytokeratin, S100, MelanA and HMB45
  3. GATA3 and androgen receptor
  4. PAX8 and WT1
  5. TTF1 and Napsin
Board review answer #2
D. Given the clinical presentation, hormone receptor positivity and history of BRCA mutation, a metastasis from a gynecological primary (e.g. ovarian carcinoma) is the main concern. The most appropriate immunohistochemical stain panel would include PAX8 and WT1.

Comment Here

Reference: Metastases to breast
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