Other carcinoma subtypes, WHO classified
Tall cell carcinoma with reverse polarity

Topic Completed: 7 June 2019

Minor changes: 25 November 2020

Copyright: 2019,, Inc.

PubMed Search: Solid papillary carcinoma with reverse polarity

Gahie Nam, M.D.
Kamaljeet Singh, M.D.
Page views in 2020: 4,658
Page views in 2021 to date: 260
Cite this page: Nam G, Singh K. Tall cell carcinoma with reverse polarity. website. Accessed January 25th, 2021.
Definition / general
  • Papillary carcinoma of breast that histologically resembles tall cell variant of papillary thyroid carcinoma and shows distinct IDH2 R172 hotspot mutation or a mutually exclusive TET2 somatic mutation
  • Not included in current WHO classification
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
  • Presumed low malignant potential
  • Solid papillary carcinoma with reverse polarity
  • 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-10: C50 - malignant neoplasm of breast
  • Breast
Clinical features
  • Usually breast mass on screening mammogram
  • Combination of distinct morphological and immunohistochemical findings
  • Demonstration of IDH2, TET2 mutation
  • Exclude metastatic thyroid carcinoma
Radiology description
Prognostic factors
Case reports
  • 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 (Am J Surg Pathol 2017;41:887)
  • Cuboidal, columnar or tall columnar cells with abundant eosinophilic cytoplasm; nuclei located away from basal pole giving the impression of reverse nuclear polarity
  • Amphophilic colloid-like secretion may be seen
  • Bland nuclear features
  • Histiocyte aggregates may be present
  • Nuclear grooves with pseudo-inclusions
Microscopic (histologic) images

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

Solid epithelial nodules

Solid papillae

Papillae with histiocytes

Reverse polarity

Papillae with reverse polarity

Petite papillae

CK 5 / 6






Cytology description
Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Right breast, 9 o'clock; excisional biopsy:
    • Solid papillary carcinoma with reverse polarity, see comment
    • Comment: The invasive tumor is a papillary carcinoma with histological and immunohistochemical features (p63, SMMHC, ER and 5 / 6 negative) consistent with a solid papillary carcinoma with reverse polarity. The distinct histological features of this tumor include papillary architecture and abnormal/reverse polarity of the tumor cells. Frequently these tumors show IDH2 R172 hot spot mutations. It is a recently described special histologic subtype of invasive breast carcinoma with overall favorable prognosis.
Differential diagnosis
Board review style question #1
A 59 year old woman had a 1.0 cm spiculated breast mass, represented below. Tumor cells express GCDFP-15, mammaglobin, S100 and calretinin. Hormone receptors (ER / PR / HER2) are triple negative. 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
Board review style question #2
An IHC panel that would differentiate solid papillary carcinoma from recently described solid papillary carcinoma with reverse polarity is

  1. ER, PR and HER2
  2. E-cadherin and p120
  3. GATA3 and TTF1
  4. CK7, CK18 and ckit
  5. CK 5 / 6 and ER
Board review style answer #2
E. CK 5 / 6 and ER. Solid papillary carcinoma with reverse polarity is usually ER negative and may show variable loss of keratin 5 / 6. In contrast solid papillary carcinoma shows negative CK 5 / 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 solid papillary carcinoma with reverse polarity.

Reference: Breast malignant, males, children - Solid papillary carcinoma with reverse polarity (SPCRP)

Comment here
Back to top
Image 01 Image 02