JOURNAL READING

Bladder Metastases from Breast Cancer:

Managing the Unexpected.
A Systematic Review

By : dr. *
Supervisor : dr. **
*
**
Abstract
Breast cancer (BrC)
- Highest incidence, most
common cause of death
- Rapidly spread to other
organs in spite of proper
treatment  ↑ mortality
Bladder metastasis:
rare
Aim: discuss the critical points
- Systematic literature
This article:
review  draw clinical &
Current knowledge in
pathological profile
- Incidence
- Most bladder metastasis
- Clinical presentation
from BrC: secondary
lobular Ca - Diagnosis
- Prognosis
- Mimics a rare variant of - Treatment
urothelial Ca
- Immunohistochemistry is
mandatory

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 1. INTRODUCTION
Breast cancer (BrC)
▷ the most frequently diagnosed ▷ leading cause of death for cancer in
malignancy in women women
○ 1.67 million new cancer cases diagnosed ○ Due to great metastatic potential
worldwide (25% of all cancers) ○ Unusual site of BrC metastasis 
○ Variable incidence rates across countries urinary bladder
 discrepancies in early dx & risk factors ■ Rarely reported
entity; highest in more developed
countries ■ May be a source of dx and
therapeutic pitfalls

 Reviewed the reported cases to identify clue

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 2. METHODS
1950 -- 2017

PubMed, Medline and Google case reports, case series and

Scholar databases review articles

“bladder metastasis,” “breast Data: epidemiology, histotypes, route

cancer,” “pathology,” and pattern, signs and symptoms,
diagnostic workup, pathology features,
“oncology” hormonal status, management and
outcome

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 3. EPIDEMIOLOGY
Bladder metastasis (BM)
- Rare: 4,5% of bladder neoplasm
▷ BrC
4/167
represents
(2.4%) metastatic
the primary
BrCs
site(Abraham
in 2.4% cases
et.al., 1950) of all
- Mostly due to direct extension
▷ BMs
4/341 (1.2%) cases who died of advanced BrCs
- From distant organ: extremely ▷ (Goldstein,
3/142 (2.1%)1967)
BMs arose from BrC (Klinger, 1951)
Lack
rare; most common are of metastases
stomach, ▷
▷ 6/85
9/2,502
may
(7%) bespecimens
due
autopsies
bladder
to:were BMBrCs
of widespread (Pontes and
of BrC (Melicow,
lung, & skin1. Missed examination of 1955)
(melanoma) breast masses during autopsy
Oldford, 1970)

2. Absence of screening▷ 8/166

▷and
7/282 early (4,8%) autopsies
BMsdiagnosis
arose of BrCs
from programs
BrC (Hagemeister et.al., 1980)
(Bates and Baithun, 2000)
▷
▷ No BMBM
3/11 / 43 autopsies
were of metastatic
breast-primary BrCs (Saphir and
(Xiao et.al., 2012)
Parker, 1941)
- From BrC: extremely rare, only ▷ No BM / 162 metastatic BrCs (Warren and Witham, 1933)
54 cases in literature

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 4. HISTOTYPE, ROUTE, AND PATTERN
BrC
▷ Histologically heterogenous
○ Infiltrating ductal carcinoma (IDC) : 90%
○ Infiltrating lobular carcinoma (ILC) : 10%
■ still 2x of invasive cervical Ca
■ equal of ovarian Ca
■ increasing in post-menopausal
women
▷ small round cells that infiltrate the
breast stroma in a single-file
(“Indian-file”) pattern, tend to
surround benign mammary ducts
and lobules in a targetoid fashion,
without forming glandular
aggregates
▷ Multifocal, multicentric
distribution in both breasts
▷ Fails to form a distinct mass in the
breast  early detection is
challenging
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▷ Metastates
3—10% have metastatic disease at initial diagnosis; 30% during follow-up

ILC is of the serosal type: predilection to

ILC IDC
spread to the gastrointestinal and
▷ Distant metastatic pattern: diffuse gynaecological
▷ often metastasizessystems
to the lung, liver,
thickening of mucosa bone, and brain
▷ tends to spread to GI tract, genitourinary ▷ 0.6%
▷ Notof 2605 cases
common, of BrC
could bemetastasised
due to
tract, peritoneum, retroperitoneum, & to perperitoneum-retroperitoneum
minute viable tumour emboli (Borst
and Ingold, 1993)
leptomeninges
▷ Postulation: ILC loss of E-cadherin 
▷ 33% of BMs from BrC were ILC (Feldman et.al., facilitates metastatic porcess
2002)

▷ 3.1% of 2605 cases of BrC metastasised

to perperitoneum-retroperitoneum (Borst Positive lymph node at first diagnosis or
and Ingold, 1993)
with steroid therapy  likely develop
▷ metastasises to bladder via BM
retroperitoneal involvement (Pontes and
Oldford, 1970; a postulation)
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 5. SIGNS AND SYMPTOMS
▷ Complaints are rare
○ Symptoms appear when tumour penetrates mucosal lining  late
○ Metastasis is diagnosed only by imaging in routine follow-up in asymptomatic patients

▷ Gross hematuria + history of BrC 

▷ painless hematuria (microscopic > gross)
 most common
▷ stress and urge incontinence
▷ urinary frequency and nocturia
▷ difficulty in voiding
▷ back pain
investigate thoroughly; may be easily
dismissed as cystitis secondary to
chemotherapy
▷ Detrusor involvement
○ Voiding symptoms; may occur
earlier than hematuria
○ Ureteral obstruction 
hydronephrosis & renal failure

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Bladder ultrasound
- First-line in BrC + voiding
symptoms
CT-scan
- Negative finding in US &
persistent symptoms
MRI/PET-CT
- revealing other
metastatic site
- MRI: precise local Ca
staging, exclusion of
adjacent structure
involvement
6. DIAGNOSTIC WORKUPS
11C-Choline If bladder lesion is visualised:
- New effective tracer for
cystoscopy and cold-cup biopsy or,
the bladder wall (lacks
better still, transurethral resection
urinary excretion)
of the lesion is mandatory to
obtain a definite diagnosis
Serum CA15-3
- most sensitive tumour
marker in BrC follow-up
Biopsies are recommended even
Findings:
- to monitor patient
- in thetumour,
solid case of negative
non- specific
response to treatment
cystoscopic
inflammatoryfindings.
patches,
and watch for cancer
abnormally thickened bladder
recurrence
wall with intact overlying
mucosa, irregular lesion,
mucosal nodularity, or plaque
with telangiectasias 9

▷ Raised possibility of BrC metastasis:
○ Bladder neoplasm presents with
epithelial infiltration in the form of cords
or individual cells involving the lamina
propria, with no associated overlying
papillary urothelial proliferation or “flat”
CIS
○ presence of unusual monomorphic
growth patterns without accompanying
conventional urothelial carcinoma
features
○ appearance of tumour cells invading
towards the luminal surface from the
outside
7. PATHOLOGY
Secondary lobular carcinoma of the
breast mimics very closely the rare
variant of UC with lobular carcinoma-
like features
o Differential diagnosis: rare variants
of UC (micropapillary,
lymphoepithelioma-like and
plasmacytoid variants of UC)
o Obtain proper information on the use
of immunohistochemistry
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 Immunohistochemistry is an indispensable
adjunct in the correct diagnosis of metastatic
tumours in all sitesz

▷ #1: CK7/CK20 expression

▷ bladder-associated markers  expressed in BrC:
○ high-molecular weight cytokeratin 34betaE12
○ Thrombomodulin
○ GATA3
▷ Positive staining for ER & PR  dd primary bladder adenoCa and BM
▷ GCDFP-15: high specificity, low sensitivity

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 8. HORMONAL STATUS

o Between primary and metastatic tissues: differences in hormonal (ER, PR) & HER2
expression
o discordance rates ranging from 24 to 39%
o Heterogenicity maybe due to:
o the BrC cells are polyclonal
o ER and PR expression may shift after endocrine therapy, due to the elimination
and growth of ER- and PR-positive or negative cells or due to gene mutations

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 9. MANAGEMENT AND OUTCOME
▷ BM from BrC may occur in the mean time of
90 months (ranging from the first diagnosis
of BrC until 30 years)
▷ Transurethral resection of the vesical lesion:
○ As diagnostic purposes
○ ameliorating urinary symptoms
○ facilitate ureteral stenting in case of
ureteral obstruction  otherwise requires
percutaneous nephrostomy
▷ Local radiotherapy: stops hematuria + local
disease control
▷ Combination of chemotherapy and
hormonal treatment (anti-oestrogen)
▷ Very limited survival: 1 month – 2 years, few
reports > 5 years
▷ 7/11 patients have other metastases
besides the bladder (Xiao et.al., 2012)
▷ A patient with bladder as the only metastatic
site  relapsed in 3 years (Lin and Chen, 2003)
▷ A patient with lobular cancer developed
simultaneous BM and local recurrence of her
BrC 6 years after initial BrC diagnosis  did
not survive even after chemotherapy (Luczyńska
et.al., 2010)
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Conclusion
▷ BMs from BrC are rare but the literature reveals an increase of such
occurrence over the last few years  better imaging techniques
▷ Most cases: diagnosed years after the primary BrC, associated with other
metastatic sites
▷ Most cases present with voiding symptoms
▷ Serum CA15-3 maybe useful
▷ Bladder lesion in imaging  perform transurethral resection 
immunohistochemical study
▷ Chemotherapy and hormonal treatment represent the standard therapy,
with radiotherapy being used only to control bladder bleeding
▷ The prognosis is usually poor unless BM represents the only metastatic site

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