Breast
Invasive breast carcinoma of no special type and variants
Medullary
Topic Completed: 1 December 2017
Minor changes: 21 June 2020
Copyright: 2003-2019, PathologyOutlines.com, Inc.
PubMed Search: Medullary [title] carcinoma breast NOT thyroid
Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Clinical features | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Molecular / cytogenetics description | Videos | Differential diagnosis | Additional references | Board review style question #1 | Board review answer #1Cite this page: Podoll MB, Reisenbichler ES. Medullary. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantmedullary.html. Accessed November 25th, 2020.
Definition / general
- Carcinoma with medullary features (CMF) includes medullary carcinoma, atypical medullary carcinoma and invasive carcinoma, no special type (NST) with features of pushing borders, syncytial growth, high grade nuclei and prominent lymphoid infiltrate
- Subset of triple negative (ER-, PR-, HER2-) breast carcinoma
- Medullary carcinoma represents < 1%, however up to 20% of invasive breast cancers reportedly have some medullary features
- Most common type of breast carcinoma in patients with BRCA1 germline mutation
- Show increased expression of cell adhesion proteins
Essential features
- Well circumscribed, composed of high nuclear grade cells with syncytial or large sheet-like growth, pushing borders, prominent lymphoplasmacytic infiltrate, scant fibrous stroma, no glandular structures and minimal DCIS
- Circumscribed borders mimic benign lesions on imaging
- Soft in consistency due to the lack of desmoplastic response
Terminology
- WHO Classification of Tumors of the Breast (2013) recommends using the term Carcinoma with medullary features (CMF) rather than medullary carcinoma or atypical medullary carcinoma
- This terminology is recommended due to the lack of reproducibility in the diagnosis of medullary carcinoma and to avoid undertreatment of aggressive triple negative tumors lacking some diagnostic features of medullary carcinoma
- Considered a type of basal-like carcinoma (Breast Cancer Res 2007;9:R24, Am J Surg Pathol 2007;31:501)
- "Medulla" refers to soft structure of marrow (tumors are often soft)
Epidemiology
- Most commonly affects women 45 - 52 years
- Accounts for 30 - 60% of breast tumors in patients with BRCA1 germline mutation
- Rare in patients with BRCA2 germline mutation
Clinical features
- Typically present as a soft palpable circumscribed mass which may appear benign
- Lymphadenopathy may be present (due to hyperplasia rather than metastasis, which is uncommon)
Radiology description
- Round, oval or lobulated mass on mammography
- Hypoechoic mass on ultrasound with thick echogenic halo is commonly seen
Prognostic factors
- Tumors with dense lymphocytic infiltrates are more likely to respond to chemotherapy
- CMF has better prognosis than stage matched triple negative carcinoma
- 10 year survival rates can be > 80%
- Favorable prognosis may not apply to tumors > 3 cm, with nodal metastases or with BRCA1 mutations
- When lymph node metastasis are present (≥ 4 nodes), recurrence / death within 5 year period is common
- Slightly better prognosis than invasive ductal carcinoma NOS, even though high grade, aneuploid, ER / PR negative, p53 positive and high proliferation rates (Hum Pathol 1988;19:1340, Int J Radiat Oncol Biol Phys 2005;62:1040)
- Better prognosis may be due to prominent inflammation (Eur J Cancer 2009;45:1780, Mod Pathol 2010;23:1357)
Case reports
- 18 year old woman with medullary breast carcinoma (Diagn Cytopathol 2014;42:445)
- 38 year old woman with synchronous bilateral medullary carcinoma (J Cancer Res Ther 2012;8:129)
Treatment
- Complete excision is recommended
- Adjuvant chemotherapy and radiation are recommended similar to other triple negative tumors and invasive carcinoma respectively
Clinical images
Contributed by Mark R. Wick, M.D.
Mammogram
Gross description
- Well circumscribed, 2 - 3 cm in size, soft and fleshy (may resemble fibroadenoma)
- Homogenous with white to gray appearance
- May show areas of necrosis with are focal and can cause cystic degeneration
Gross images
Contributed by Mark R. Wick, M.D.
Various images
AFIP image
Sharply defined margin
with internal nodularity
and bosselated surface
Images hosted on other servers:
Well circumscribed partly cystic gray-white
Atypical medullary carcinoma: primary and nodal metastases
Gray fleshy tumor
Tannish pink tumor with circumscribed margin
Tumor with extensive hemorrhage
Well circumscribed and may be partially cystic
Microscopic (histologic) description
- Sharply circumscribed and pushing borders
- Sheets of cells with indistinct cell borders (syncytial growth) in greater than 75% of tumor
- Moderately to poorly differentiated; no prominent tubule formation
- Pleomorphic cells with large nuclei and prominent nucleoli (cells may have multiple nucleoli)
- Numerous mitoses with atypical mitoses
- Moderate to marked lymphoplasmacytic response at periphery consists of cytotoxic T cells (CD3+ and CD8+) and IgA plasma cells
- T cell infiltrate can be seen surrounding lobules in the background breast tissue
- May contain multinucleated giant cells, squamous metaplasia, geographic necrosis, hemorrhage
- Uncommon: lymphovascular invasion, lymph node involvement, DCIS
- No desmoplastic reaction
Microscopic (histologic) images
Contributed by Mirna B. Podoll, M.D.
Carcinoma with medullary features
Prominent cellular pleomorphism
High grade features
Low power showing marked lymphocytic response
AFIP images
Medullary features
A lobule with in situ carcinoma in some lobular units
Focal areas of squamous metaplasia with keratin pearls
Contributed by Mark R. Wick, M.D.
Various images
Images hosted on other servers:
Various images
High grade syncytial pattern
Atypical medullary carcinoma
ER negative
p63
p53
HER2 staining (usually is negative, in this case, is focally 3+ [see image on right])
Cytology description
- Cellular smears
- Tumor cells in loosely cohesive sheets and single cells
- Moderate / marked nuclear pleomorphism and nuclear irregularities, mixed with mononuclear inflammation (Diagn Cytopathol 2007;35:408, Acta Cytol 2009;53:165)
Cytology images
Images hosted on other servers:
Atypical medullary carcinoma
Positive stains
Negative stains
Molecular / cytogenetics description
- Microsatellite instability is uncommon, in contrast to medullary colonic tumors (Am J Clin Pathol 2001;115:823)
- Similar genetic alterations as basal-like carcinoma
- Usually aneuploid
- Associated with BRCA1 mutations
Videos
Histopathology Breast - Medullary carcinoma
Differential diagnosis
- Collision tumor of invasive ductal NOS and MALT lymphoma: see Arch Pathol Lab Med 2004;128:99
- Lymph node in axillary tail: not circumscribed and may not be syncytial
- While germinal centers can be seen in CMF and are not evidence of lymph node, a lymph node capsule or subcapsular sinus is supportive of lymph node
- Lymphoma: primary breast lymphomas are more commonly B cell derived, CMF has predominantly T cells and plasma cells; tumor cells will stain with cytokeratins
- EBV associated lymphoepithelial-like carcinoma: will display infiltrative borders and is EBV positive while only a few cases of CMF have been found to have EBV positivity
- Undifferentiated ductal carcinoma: lacks prominent lymphoplasmacytic infiltrate, has infiltrative borders
Additional references
Board review style question #1
- Which of the following is true of invasive carcinoma with medullary features?
- Are high grade triple negative tumors.
- Have a prominent lymphocytic infiltrate of predominantly B cells.
- Most commonly present as calcifications on mammography.
- Patients usually have poor prognosis.
- They are commonly infiltrative masses.
Board review answer #1
A. Breast carcinoma with medullary features (CMF) most commonly presents as a palpable well circumscribed mass that may mimic benign lesions. They are high grade and demonstrate a prominent lymphocytic infiltrate predominantly of CD3 and CD8 positive T cells. Despite being triple negative, patients with CMF tend to have better prognosis than grade matched invasive carcinoma of no special type.
