1
RARE VARIANTS OF INVASIVE
BREAST CARCINOMA OF NO
SPECIAL TYPE (IBC-NST)
• The prior WHO (4
th
ed. 2012) classied several
tumors as separate entities (listed below). Breast
tumors with these “special morphological
patterns” now fall under the umbrella category
of IBC-NST and are no longer considered to be
the following clinically distinct subtypes:
oncocytic, lipid-rich, glycogen-rich, clear cell,
sebaceous, carcinomas with choriocarcinoma-
tous and pleomorphic patterns, melanocytic,
and carcinomas with osteoclast-like stromal
giant cells.
INVASIVE BREAST CARCINOMA
WITH MEDULLARY PATTERN
• Medullary carcinoma, atypical medullary
carcinoma, and carcinoma with medullary
features were listed as special subtypes of breast
carcinoma in the prior WHO. This diagnostic
category has poor interobserver reproducibility;
these tumors also show overlapping histologic
features with carcinomas that have basal-like
molecular proles and carcinomas with BRCA1
Issue 18 || May 2022
WHAT’S NEW IN BREAST
PATHOLOGY 2022:
WHO 5
th
EDITION AND
BIOMARKER UPDATES
Kristen Muller,
1
Julie M. Jorns,
2
and
Gary Tozbikian
3
1
Department of Pathology and Laboratory Medicine,
Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
2
Department of Pathology, Medical College of Wisconsin,
Milwaukee, WI, USA
3
Department of Pathology, The Ohio State University
Wexner Medical Center, Columbus, OH, USA
Corresponding Author: Kristen Muller, DO
Department of Pathology and Laboratory Medicine,
Dartmouth-Hitchcock Medical Center, Lebanon,
NH, USA
E-mail: kristen.e.muller@hitchcock.org
ORCID
Kristen Muller
https://orcid.org/0000-0003-3166-4523
Julie M. Jorns
https://orcid.org/0000-0002-7777-6670
Gary Tozbikian
https://orcid.org/0000-0002-5941-5652
Abstract
The 5th edition WHO Classication of Breast
Tumours (2019) has introduced changes to our
practices. Highlights are presented below, with a
focus on modications to morphological subtype
categorization. In addition, we summarize impor-
tant updates to ER and PR testing made in the
2020 ASCO/CAP guidelines, and briey discuss
PD-L1 and Ki-67 testing in breast cancer.
mutations.
• Tumor inltrating lymphocytes (TILs) may
explain the good prognosis of these cancers.
• Carcinomas with a basal-like or medullary
pattern (i.e., well-circumscribed, high-grade,
syncytial architecture, necrosis, prominent
TILs, Fig. 1) now represent one end of the
spectrum of TIL-rich IBC-NST; “IBC-NST
with medullary pattern” has been proposed to
replace “medullary carcinoma.”
NEUROENDOCRINE TUMORS
• True primary neuroendocrine (NE) neoplasms
of the breast are rare. They are classied as
well-differentiated NE tumors (carcinoid-like
and atypical carcinoid-like) and poorly
differentiated NE carcinomas (small cell
neuroendocrine carcinoma and large cell
neuroendocrine carcinoma).
• Distinct NE features and expression of NE
markers by IHC are needed for diagnosis, since
varying degrees of NE differentiation may be
seen in IBC-NST, mucinous carcinomas, solid
papillary carcinomas, and others.
• Metastasis must be ruled out before considering
a primary breast NE tumor.
• Routine staining on IBC-NST that lacks
characteristic NE morphological features is not
recommended, due to the lack of clinical
relevance.
WELL-DIFFERENTIATED
LIPOSARCOMA IN PHYLLODES
TUMOR
• Malignant heterologous elements are among
the diagnostic criteria for malignant phyllodes
tumor.
• Adipocytic differentiation in the stromal
component of phyllodes tumor, that is morpho-
logically indistinguishable from well-differenti-
PathologyOutlines.com
WHAT’S NEW
IN PATHOLOGY?
Sponsored by an unrestricted grant from Roche
Fig. 1. IBC-NST with medullary pattern. High-grade
tumor with a syncytial growth pattern and prominent
TILs.