Tall cell carcinoma with reverse polarity

Breast

Other carcinoma subtypes, WHO classified

Authors: Gahie Nam, M.D., Kamaljeet Singh, M.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Topic Completed: 7 June 2019

Minor changes: 25 November 2020

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Solid papillary carcinoma with reverse polarity

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Table of Contents

Cite 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

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

p63

SMMHC

E-cadherin

MUC1

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

Hormone receptors (ER, PR, HER2): generally negative; ER or PR can be focally positive
Myoepithelial markers (p63, SMMHC, calponin)
TTF1, thyroglobulin

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
- Solid or cystic circumscribed papillary lesion with thick fibrous capsule
- Lacks reverse polarity
- CK 5 / 6 negative and ER positive epithelial cells
Intraductal papilloma with usual ductal hyperplasia
- Myoepithelial cells present (highlighted by CK 5 / 6, SMMHC, p63, p40)
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

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