Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Nam G, Singh K. Tall cell carcinoma with reverse polarity. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantspcrp.html. 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
Terminology
- 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
Epidemiology
- Rare tumor
- Women of postmenopausal age; median age 64 (Am J Clin Pathol 2017;147:399)
Sites
- Breast
Clinical features
- Usually breast mass on screening mammogram
Diagnosis
- Combination of distinct morphological and immunohistochemical findings
- Demonstration of IDH2, TET2 mutation
- Exclude metastatic thyroid carcinoma
Radiology description
- Solid mass on mammogram or ultrasound (Am J Surg Pathol 2017;41:887)
Prognostic factors
- Favorable prognosis with rare reports (2 cases) of metastases to lymph nodes and bone (Cancer Res 2016;76:7118, Am J Surg Pathol 2017;41:887)
Case reports
- 48, 65 and 77 year old women (Chi Path Soc 2015;7:5)
- 55 year old woman with Lynch syndrome (J Clin Pathol 2018;71:1031)
- 65 year old woman (Pathologica. 2017;109:162)
- 66 year old woman with palpable breast mass (Breast J 2009;15:531)
- 79 year old woman presented with retroareolar mass (Int J Surg Pathol 2015;23:217)
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
- Usually solid irregular mass, median size: 0.9 cm (Cancer Res 2016;76:7118)
- Sometimes cystic with translucent, colloid-like area resembling thyroid tissue (Int J Surg Pathol 2015;23:217)
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
Cytology description
- Highly cellular; cells dispersed, in nests and with papillary formation; nuclear grooves (Int J Surg Pathol 2006;14:79)
Positive stains
- CK 5 / 6: mosaic cytoplasmic expression (similar to intraductal papilloma with usual ductal hyperplasia) (Mod Pathol 2018;31:1367)
- IDH 1 / 2 mutant R132 / R172
- E-cadherin: strong lateral membrane expression with absent apical or basal expression
- MUC1: highlights the apical membranes of columnar epithelial cells (Cancer Res 2016;76:7118)
- Ki67 < 5 % (Mod Pathol 2018;31:1367)
- GCDFP-15, mammaglobin, S100 and calretinin
Negative stains
Molecular / cytogenetics description
- IDH2 R172 hotspot mutations in 77 - 100% (Cancer Res 2016;76:7118)
- PIK3CA hotspot mutations in 67% (Histopathology 2018;73:339)
- TET2 truncating mutation
- PRUNE2 mutation (Mod Pathol 2018;31:1367)
- ATM, KIT and MET alterations (Am J Clin Pathol 2017;147:399)
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
- Solid papillary carcinoma
- Lack of reverse polarity of nuclei
- Strongly ER positive, variable CK 5 / 6
- Plasmacytoid cells with neuroendocrine differentiation may be present (chromogranin and synaptophysin positive)
- Intracellular mucin may be present
- Encapsulated papillary carcinoma
- Intraductal papilloma with usual ductal hyperplasia
- Metastatic thyroid carcinoma
- Psammoma bodies, giant cells and optically clear Orphan Annie nuclei
- TTF1 and thyroglobulin positive
- BRAF and RET / PTC molecular alterations
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?
- BRAF mutation
- CDH1 mutation
- IDH2 R172 hotspot mutations
- RET mutation
- TET2 truncating mutation
Board review style answer #1
C. IDH2 R172 hotspot mutations
Reference: Breast malignant, males, children - Solid papillary carcinoma with reverse polarity (SPCRP)
Comment here
Reference: Breast malignant, males, children - Solid papillary carcinoma with reverse polarity (SPCRP)
Comment here
Board review style question #2
An IHC panel that would differentiate solid papillary carcinoma from recently described solid papillary carcinoma with reverse polarity is
- ER, PR and HER2
- E-cadherin and p120
- GATA3 and TTF1
- CK7, CK18 and ckit
- 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
Reference: Breast malignant, males, children - Solid papillary carcinoma with reverse polarity (SPCRP)
Comment here