Breast

Other invasive carcinoma subtypes, WHO classified

Tall cell carcinoma with reverse polarity


Editorial Board Member: Kristen E. Muller, D.O.
Deputy Editor-in-Chief: Gary Tozbikian, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Grace Kwon, M.D., Ph.D.
Kamaljeet Singh, M.D.

Last author update: 27 December 2022
Last staff update: 27 December 2022

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PubMed Search: Tall cell carcinoma with reverse polarity

Grace Kwon, M.D., Ph.D.
Kamaljeet Singh, M.D.
Page views in 2023: 5,436
Page views in 2024 to date: 960
Cite this page: Kwon G, Nam G, Singh K. Tall cell carcinoma with reverse polarity. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantspcrp.html. Accessed February 26th, 2024.
Definition / general
  • Rare subtype of papillary carcinoma of breast that histologically resembles tall cell variant of papillary thyroid carcinoma and frequently shows distinct IDH2 R172 hotspot mutations
Essential features
  • Histologic subtype of papillary carcinoma of breast, first described in 2003 (Am J Surg Pathol 2003;27:1114)
  • Solid nodules of columnar epithelial cells, many with thin fibrovascular cores, leading to solid papillary architecture
  • Epithelial cells contain abundant glassy eosinophilic cytoplasm and show abnormal apically located nucleus giving the impression of reverse nuclear polarity
  • Frequent IDH2 R172 hotspot mutations
  • Triple negative phenotype with presumed low malignant potential
Terminology
  • Not recommended per WHO:
    • Solid papillary carcinoma with reverse polarity (SPCRP)
    • Breast tumor resembling tall cell variant of papillary thyroid carcinoma
    • Solid papillary breast carcinoma resembling tall cell variant of papillary thyroid neoplasm
ICD coding
  • ICD-O: 8509/3 - tall cell carcinoma with reversed polarity
  • ICD-11: 2C6Y - other specified malignant neoplasms of breast
Epidemiology
Sites
  • Breast
Pathophysiology
Clinical features
  • Typically presents as a mammographic or palpable breast mass
Diagnosis
  • Tissue biopsy or surgical excision specimen showing the key histologic and immunohistochemical features
  • Demonstration of IDH2 or TET2 mutation
  • Exclusion of metastatic disease (i.e., thyroid carcinoma)
Radiology description
Prognostic factors
Case reports
Treatment
  • Surgical excision is mainstay treatment (Am J Surg Pathol 2017;41:887)
  • Lack of evidence for sentinel lymph node procedure, radiation or systemic therapy
Gross description
Microscopic (histologic) description
  • Solid circumscribed nodules of epithelial cells with thin, petite papillae in a dense fibrous stroma (Am J Surg Pathol 2017;41:887)
  • Cuboidal, columnar or tall columnar tumor cells with abundant eosinophilic cytoplasm; bland nuclear features with nuclei located at the apical pole rather than the basal pole, giving the impression of reverse nuclear polarity
  • Variable presence of nuclear grooves with intranuclear pseudoinclusions
  • True papillae and cystic spaces with amphophilic colloid-like secretions may be seen
  • Foamy histiocyte aggregates often present within fibrovascular cores
  • Mitotic figures rare
Microscopic (histologic) images

Contributed by Koorosh Haghayeghi M.D., Sonja Chen M.D. and Yihong Wang M.D.

Solid epithelial nodules

Solid papillae

Papillae with histiocytes

Reverse polarity

Papillae with reverse polarity

Petite papillae


CK5/6

p63

SMMHC

E-cadherin

MUC1

ER

Cytology description
Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Right breast, 9 o'clock, excisional biopsy:
    • Tall cell carcinoma with reverse polarity (see comment)
    • Comment: Sections show circumscribed nests of a solid, papillary and partially cystic neoplasm comprised of low to intermediate nuclear grade columnar epithelial cells with abundant cytoplasm, irregular nuclear contours and scattered nuclear grooves. The columnar cells appear to show apical localization, so called reverse polarization. Myoepithelial immunostains are negative. The lesional cells are strongly and diffusely immunoreactive for cytokeratin 5 and negative for ER, PR and HER2. Concurrent molecular analysis revealed IDH2 and PIK3CA mutations. Overall, the morphologic, immunohistochemical and molecular findings are compatible with a tall cell carcinoma with reverse polarity.
Differential diagnosis
Board review style question #1

A 59 year old woman had a 1.0 cm spiculated breast mass, represented above. Tumor cells express GCDFP-15 and mammaglobin. The tumor cells are negative for ER, PR and HER2. Myoepithelial markers (p63 and SMMHC) are also negative. Other negative markers include TTF1 and thyroglobulin. What is the most common molecular alteration seen in these tumors?

  1. BRAF mutation
  2. CDH1 mutation
  3. IDH2 R172 hotspot mutations
  4. RET mutation
  5. TET2 truncating mutation
Board review style answer #1
C. IDH2 R172 hotspot mutations

Comment here

Reference: Tall cell carcinoma with reverse polarity
Board review style question #2
Which of the following IHC panels would differentiate solid papillary carcinoma from recently described tall cell carcinoma with reverse polarity?

  1. CK5/6 and ER
  2. CK7, CK18 and KIT
  3. E-cadherin and p120
  4. ER, PR and HER2
  5. GATA3 and TTF1
Board review style answer #2
A. CK5/6 and ER. Tall cell carcinoma with reverse polarity is usually ER negative and may show variable loss of keratin 5/6. In contrast, solid papillary carcinoma shows negative CK5/6 and strong ER staining. Both tumors show loss of myoepithelial cells by p63 and smooth muscle myosin heavy chain. ER, PR and HER2 (biomarkers), E-cadherin and p120 (ductal versus lobular), GATA3 and TTF1 (primary breast versus metastasis), and CK4, CK14, CK18 and KIT (adenoid cystic carcinoma) do not help in distinguishing solid papillary carcinoma and tall cell carcinoma with reverse polarity.

Comment here

Reference: Tall cell carcinoma with reverse polarity
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