Carcinoma with medullary features (CMF)

Breast malignant
Carcinoma subtypes
Carcinoma with medullary features (CMF)

Senior Author: Emily S. Reisenbichler, M.D.

Topic Completed: 1 December 2017

Revised: 17 September 2019

Copyright: 2003-2019, PathologyOutlines.com, Inc.

PubMed Search: Medullary [title] carcinoma breast NOT thyroid

Page views in 2018: 16,861

Page views in 2019 to date: 15,574

Table of Contents

Cite this page: Podoll MB, Reisenbichler ES. Carcinoma with medullary features (CMF). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantmedullary.html. Accessed October 16th, 2019.

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

Tumor invades fat; is not well circumscribed

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

CK8 and CK18
CK5 / 6 (94%), p53 (77%)
High Ki67 index (often > 50%)
CD3 and CD8 in the lymphocytic infiltrate
p53 (TP53 mutation in 60 - 80%)
Epidermal growth factor receptor (HER1) in approximately 70%
Adhesion molecules (E-cadherin, P-cadherin, Beta-catenin)
HLA-DR, S100

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

Stanford University: Medullary Carcinoma of the Breast [Accessed 12 December 2017]

Board review question #1

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.