Breast

General

WHO classification


Editorial Board Member: Julie M. Jorns, M.D.
Deputy Editor-in-Chief: Gary Tozbikian, M.D.
Indu Agarwal, M.D.
Luis Blanco, Jr., M.D.

Last author update: 24 January 2024
Last staff update: 24 January 2024

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PubMed Search: WHO classification breast tumors

Indu Agarwal, M.D.
Luis Blanco, Jr., M.D.
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Cite this page: Agarwal I, Blanco L. WHO classification. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantwhoclassification.html. Accessed April 14th, 2024.
Definition / general
  • Tumor classification is a dynamic process that integrates multiple sources of recent information
  • Based on current 5th edition, published in 2019
Major updates
  • Includes new, renamed and removed entities from the 4th edition of WHO classification along with changes to diagnostic criteria
  • Carcinomas with medullary features have been subsumed into a combined morphological subset under the category of invasive carcinoma, no special type (NST) with basal-like and medullary pattern
  • Mucinous cystadenocarcinoma has been recognized as a new entity
    • Characterized by cystic structures lined by tall columnar cells with abundant intracytoplasmic mucin, resembling pancreatobiliary or ovarian mucinous cystadenocarcinoma
  • Tall cell carcinoma with reversed polarity has been recognized as a new entity
  • Neuroendocrine neoplasms (NENs) harmonized with those of other organ systems incorporating uniform classification network (Mod Pathol 2018;31:1770)
  • Removal of well differentiated liposarcoma as a histologic criterion for malignancy in phyllodes tumor in the absence of additional supporting features
    • Abnormal adipocytes within phyllodes tumor lack MDM2 or CDK4 amplifications in contrast to extramammary well differentiated liposarcoma (Histopathology 2016;68:1040)
  • Updated information on molecular pathology, expression profiling and molecular classification of breast tumors; however, focus remains on morphologic classification
  • Conversion of mitotic count from a common denominator of 10 high power fields to a defined area expressed as mm2
WHO (2019)
Microscopic (histologic) images

Contributed by Indu Agarwal, M.D., Mirna B. Podoll, M.D. and Julie M. Jorns, M.D.
Low grade DCIS

Low grade DCIS

LCIS, classic type

LCIS, classic type

Invasive carcinoma, NOS Invasive carcinoma, NOS

Invasive carcinoma, NOS

Invasive and in situ carcinoma

Invasive and in situ carcinoma

Metastasis of lobular carcinoma

Metastasis of lobular carcinoma


Immunostain cytokeratin AE1 / AE3

Immunostain cytokeratin AE1 / AE3

Invasive carcinoma, NOS Metaplastic carcinoma

Metaplastic carcinoma

Encapsulated papillary carcinoma Encapsulated papillary carcinoma

Encapsulated papillary carcinoma


Missing Image Missing Image

Adenoid cystic carcinoma

Tall cell carcinoma with reverse polarity

Tall cell carcinoma with reverse polarity

Invasive ductal carcinoma with medullary pattern

Invasive ductal carcinoma with medullary pattern

Phyllodes tumor with liposarcomatous differentiation

Phyllodes tumor with liposarcomatous differentiation

Board review style question #1
Which of the following is a new entity in the WHO Classification of Breast Tumours, 5th edition, published in 2019?

  1. Malignant phyllodes tumor with well differentiated liposarcomatous differentiation alone
  2. Medullary carcinoma
  3. Mucinous cystadenocarcinoma
  4. Solid papillary carcinoma
Board review style answer #1
C. Mucinous cystadenocarcinoma. Tall cell carcinoma with reversed polarity (TCCRP) and mucinous cystadenocarcinoma, NOS are 2 new entities. TCRRP is a rare subtype of invasive breast carcinoma characterized by tall columnar cells with reversed nuclear polarity, arranged in solid and solid papillary patterns and most commonly associated with IDH2 p.Arg172 hotspot mutations. Mucinous cystadenocarcinoma of the breast is an invasive breast carcinoma characterized by cystic structures lined by tall columnar cells with abundant intracytoplasmic mucin, resembling pancreatobiliary or ovarian mucinous cystadenocarcinoma.

Answer A is incorrect because liposarcomatous differentiation has been removed as a histologic criterion for malignancy in phyllodes tumor in the absence of additional supporting features. Answer B is incorrect because tumors previously called as medullary carcinoma, atypical medullary carcinoma and invasive carcinoma with medullary features have been subsumed into a combined morphologic subset under the category of invasive carcinoma, NST with basal-like and medullary pattern, regarding them as a part of a spectrum of tumor infiltrating lymphocytes rich breast carcinomas. Answer D is incorrect because encapsulated papillary carcinoma and solid papillary carcinoma have been previously present in prior WHO editions.

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Reference: Breast - WHO classification
Board review style question #2

Tall cell carcinoma with reversed polarity (TCCRP) is a new entity in the WHO Classification of Breast Tumours, 5th edition, published in 2019, that has what typical prognosis and estrogen receptor (ER), progesterone receptor (PR) and HER2 / neu (HER2) profile?

  1. Good prognosis, ER / PR negative, HER2 negative
  2. Good prognosis, ER / PR positive, HER2 negative
  3. Poor prognosis, ER / PR negative, HER2 negative
  4. Poor prognosis, ER / PR positive, HER2 negative
Board review style answer #2
A. Good prognosis, ER / PR negative, HER2 negative. Tall cell carcinoma with reversed polarity (TCCPR) is a rare subtype of invasive breast carcinoma characterized by tall columnar cells with reversed nuclear polarity, arranged in solid and solid papillary patterns and most commonly associated with IDH2 p.Arg172 hotspot mutations. Despite the good prognosis and indolent course of TCCRP, this tumor typically expresses low and high molecular weight keratins, including CK5/6 and is ER / PR and HER2 negative, thus part of a group of rare good prognosis triple negative breast carcinoma (TNBC), which also includes some salivary gland type tumors (e.g., adenoid cystic carcinoma) and variants of metaplastic carcinoma (e.g., low grade fibromatosis-like carcinoma). Answers B and D are incorrect because TCCRP is not ER / PR positive. Answers C and D are incorrect because it is not a poor prognosis breast cancer subtype.

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Reference: Breast - WHO classification
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