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Invasive breast carcinoma of no special type and variants

Medullary

Authors: Shannon Mingo Welter, M.D., Emil Racila, M.D.

Editorial Board Member: Julie M. Jorns, M.D.

Deputy Editor-in-Chief: Gary Tozbikian, M.D.

Last author update: 25 April 2022

Last staff update: 25 April 2022

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed Search: Invasive breast carcinoma of no special type with medullary pattern

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Table of Contents

Cite this page: Welter SM, Racila E. Medullary. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantmedullary.html. Accessed April 24th, 2024.

Definition / general

Medullary pattern is a histological pattern that can be applied to an invasive breast carcinoma of no special type that contains pushing borders, syncytial growth, high grade nuclei and prominent lymphoid infiltrate
Represents one end of the spectrum of tumor infiltrating lymphocyte (TIL) rich invasive breast carcinomas of no special type rather than a distinct morphological subtype

Essential features

Medullary pattern of invasive breast carcinoma no special type has 4 characteristic histological features (ideally, all 4 should be present for the diagnosis):
- Pushing border
- Syncytial growth pattern
- High grade nuclei
- Prominent lymphoid infiltrate

Terminology

Preferred term according to WHO: invasive breast carcinoma of no special type with medullary pattern
Historically described as medullary carcinoma, atypical medullary carcinoma, medullary features

ICD coding

ICD-O: 8500/3 - infiltrating duct carcinoma, NOS
ICD-11: 2C61.0 & XH7KH3 - invasive carcinoma of breast, NOS & infiltrating duct carcinoma, NOS

Epidemiology

Often present earlier in life, median age of 53 (45 - 62) years (JAMA Netw Open 2021;4:e214123)
Rare: less than 5% of all invasive breast cancers

Sites

Breast

Pathophysiology

Basal-like molecular subtype
Same as molecular subtype matched invasive breast carcinoma of no special type (Breast Cancer Res Treat 2013;142:257)

Etiology

Same as invasive breast carcinoma of no special type

Clinical features

Younger age
Soft, palpable, circumscribed mass
May have lymphadenopathy (due to hyperplasia rather than metastasis, which is uncommon)

Diagnosis

Diagnostic steps are identical to invasive breast carcinoma (screening mammogram, diagnostic mammogram, ultrasound, core biopsy, etc.)

Radiology description

Round, oval or lobulated mass on mammography
Hypoechoic mass on ultrasound with thick echogenic halo

Radiology images

Contributed by Julie M. Jorns, M.D. and Mark R. Wick, M.D.

Mammogram

Prognostic factors

Prognostic factors identical to invasive breast carcinoma of no special type: patient age, tumor histological grade, tumor stage, lymphovascular invasion, ER, PR and HER2 status, molecular subtype
Additional prognostic factors:
- Triple negative breast cancers have more unfavorable prognosis then nontriple negative breast cancer (JAMA Netw Open 2021;4:e214123)
- Similar prognosis to stage matched grade 3 ductal carcinoma with prominent inflammation
- Better prognosis than grade 3 ductal carcinoma without prominent inflammation (Eur J Cancer 2009;45:1780)
- Tumor infiltrating lymphocytes have been shown to be of prognostic value (Ann Oncol 2015;26:259)

Case reports

38 year old woman who presented with a lump in both breasts for 3 months (J Cancer Res Ther 2012;8:129)
72 year old woman with invasive breast carcinoma with medullary pattern that had spontaneous pathological complete regression (Pol J Pathol 2019;70:139)

Treatment

Identical to treatment options for invasive breast carcinoma of no special type with considerations for targeted therapy based on ER, PR, HER2 status
Tumor infiltrating lymphocytes do not alter therapy currently

Gross description

Well circumscribed, 2 - 3 cm in size, soft and fleshy (may resemble fibroadenoma)
Homogenous with white to gray appearance

Gross images

Contributed by Mark R. Wick, M.D.

White mass

Microscopic (histologic) description

Well circumscribed pushing border
Cells in syncytial growth pattern with no glandular structures
High histologic grade, high grade nuclei with prominent nucleoli
Prominent tumor infiltrating lymphocyte infiltrate

Microscopic (histologic) images

Contributed by Shannon M. Welter, M.D. and Julie M. Jorns, M.D.

Circumscribed tumor

Prominent lymphoid infiltrate

Syncytial growth pattern

Stromal lymphocytes

High grade nuclei

Numerous mitotic figures

Biopsy site and circumscription

Syncytial growth and lymphoplasmacytic infiltrate

Lymphoplasmacytic
infiltrate

Virtual slides

Images hosted on other servers:

Breast cancer with medullary pattern

Cytology description

Hypercellular specimen
Numerous isolated cells and loose clusters
Markedly enlarged, vesicular nuclei
Prominent, often irregular macronucleolus
Many lymphocytes and some plasma cells

Positive stains

Variably expresses basal markers such as CK5/6, CK14, EGFR (HER1) and p53
Higher rate of PDL1 expression (83.1%) as compared to other triple negative breast cancers (Eur J Breast Health 2019;15:235)

Negative stains

Most often negative for hormone receptors (ER and PR) and HER2 (triple negative breast cancer)

Molecular / cytogenetics description

Genomic instability is common
Majority of these tumors fall within the basal-like molecular profile
Approximately 15% of tumors in BRCA1 mutation carriers are classified as invasive breast carcinoma with medullary pattern (J Natl Cancer Inst 1998;90:1138)

Sample pathology report

Breast, right, segmental mastectomy:
- Invasive breast carcinoma of no special type with medullary pattern (see synoptic report)
- Carcinoma contains 90% stromal tumor infiltrating lymphocytes

Differential diagnosis

Metastatic high grade carcinoma to the breast from another site:
- Lacks a coexistent in situ component
- May be within a lymph node or have abundant associated angiolymphatic invasion
- Immunohistochemistry is often needed for distinction
Lymph node:
- Contains capsule or subcapsular sinus; both may have germinal centers
Lymphoma:
- Tumor cells will stain with lymphoid markers, cytokeratin negative

Additional references

WHO Classification of Tumours Editorial Board: Breast Tumours, 5th Edition, 2019, International TILs Working Group: International Immuno-Oncology Biomarker Working Group on Breast Cancer [Accessed 25 April 2022]

Board review style question #1

The tumor in the above image is found in the breast of a 45 year old woman. The tumor was round and soft on palpation and had pushing borders on microscopy. What is the most likely diagnosis?

Ductal carcinoma in situ
Invasive breast carcinoma with medullary pattern
Invasive lobular carcinoma
Secretory carcinoma

Board review style answer #1

B. Invasive breast carcinoma with medullary pattern

Comment Here

Reference: Invasive breast carcinoma of no special type with medullary pattern

Board review style question #2

Which of the following is a feature of invasive breast carcinoma with medullary pattern?

Extensive surrounding ductal carcinoma in situ
Low histologic grade
Present as calcifications on mammography
Prominent lymphocytic infiltrate

Board review style answer #2

D. Prominent lymphocytic infiltrate

Comment Here

Reference: Invasive breast carcinoma of no special type with medullary pattern

Board review style question #3

This breast tumor most often falls into which molecular profile?

Basal-like
HER2 enriched
Luminal A
Luminal B

Board review style answer #3

A. Basal-like

Comment Here

Reference: Invasive breast carcinoma of no special type with medullary pattern

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