phyllodes tumors of the breast - · pdf file–malignant changes involve the conective...

Dra. Isabel Alvarado_Cabrero

ISABEL ALVARADO_CABRERO MD PhDHOSPITAL DE ONCOLOGIA

CENTRO MEDICO NACIONAL “SIGLO XXI”

IMSS, MEXICO

[email protected]

Phyllodes Tumors of the Breast


Phyllodes Tumors (PTs) of the Breast

Postgrad Med J 2001;77:428-435

• First described by Johannes Müller in 1838,

he coined the term:

– Cystosarcoma phyllodes

• Misleading description:

– Tumors are rarely cystic

– Majority follow a benign clinical course

• More than 60 synonyms have been reported


Phyllodes Tumor

Diagnosis


• Triple assessment by clinical, radiological,

cytological or histologic examination:

– Basis for the evaluation of all breast tumors

• In patients with PTs:

– All three aspects individually

– Low sensitivity

• Even in combination diagnostic accuracy is

often poor


• As many as 62 different synonyms (past 150 years)

• The term PT was introduced for the first time in

1960, Lemonaco

• 1931 (100 year after original report)

• Lee and Pack: first example of a malignant PT

• Foote y Stewart:

– Malignant changes involve the conective tissue

elements

• Treves and Sunderland: separated PT in 3

categories

Phyllodes Tumor

J Clin Pathol 2006;59:454-459



• Size:

– Average 4 to 5 cm ( 1cm to 20cm)

• In a study of 293 pts:

– 66% Benign (≤3 cm)

– 67% low-grade and malignant: >3cm

Rosen. Breast Pathology 2012



• Size:

– Study of 605 pts

• Mean tumor size: 5.2cm

– Tumors smaller than 5.2

cm:

• Benign pts: 56.7%

• Low-grade: 8.9%

• High-grade: 2.6%

Am J Clin Pathol 2005;123:529-540


Cancer 1967;20:2090-2099


• Histologic features and behavior

• Norris and Taylor:

– Greater degree of stromal cellularity than

fibroadenomas

– Marked variation in the stroma within a single

tumor

– Periphery of the tumor: pushing or infiltrating

– Cellular atypism (1+ 3+)

– Mitoses:

• Greatest mitotic activity in terms of 10 hpf


Cellular Fibroadenoma

• Focal or diffuse stromal cellularity when present

may warrant the diagnosis of cellular

fibroadenoma

• However, there are no agreed upon criteria for

defining “hypercellularity”

• Differential with Benign PTs can be difficult

(CNB or excisional specimens)

Arch Pathol Lab Med 2014; 138:25-36


Phyllodes Tumor

Cancer 1967;20:2090-2099

Atypia No of

patients

Recurrence DOD

No. % No. %

1+ 30 8 27 2 7

2+ 33 12 36 8 24

3+ 20 8 40 5 25

Norris and Taylor series:


Phyllodes Tumor

Cancer 1967;20:2090-2099

Mitoses

(10HPF)

No of

patients

Recurrence DOD

No. % No. %

0-2 23 4 17 0 -

3-4 11 2 18 2 18

5-8 13 4 31 2 15

9-12 12 5 42 2 17

13-16 9 4 44 2 22

17-20 10 4 40 3 30

>20 9 5 55 4 44




• Unpredictable to categorize on the basis

of any single feature

• Histologic features related to metastatic

potential: taken together

– Contour and size

– Mitotic activity

– Cellular atypia

Phyllodes Tumor

Cancer 1967;20:2090-2099


Clinicopathologic Features of Phyllodes

Tumors Correlated with Recurrence

Feature No Recurrence Recurrence P

Mean age (y) 49 52 0.64%

Grade

Benign (n:176)

Borderline (n:54)

Malignant (n:30)

146

22

9

30

32

21

0.04*

Mean tumor size (mm) 55 62 0.34

Gross margins

Well-circumscribed

Poorly-circumscribed

208

52

49

39

0.02*

Mitotic Activity

0-4 (n:204)

5-9 (n:23)

≥10 (n: 23)

183

14

12

21

9

21

0.03*

Alvarado-Cabrero I et al


• Stromal overgrowth:

– “Absence of an epitelial component in at least

one microscopic field (10X ocular objective

and 4X microscopic lens objective)”


198- Rosen



Tan et al series:

• 335 women

• Ages ranged from 16 to 69 years (median 42 years)

• Tumor size:

– Benign PTs: 0.9 - 20 cm (m:4.3 cm)

– Borderline PTs: 1.2 – 22 cm (m:8.1 cm)

– Malignant PTs: 2-25 cm (m:9.2 cm)

• Necrosis:

– 13 tumors (3.9%)

Am J Clin Pathol 2005;123:529-540


Tan et al series:


Mitoses

Benign Borderline Malignant

m: 2 cm m: 8 cm m: 20 cm

0-80/10 HPF

Am J Clin Pathol 2005;123:529-540


• Tan et al:

– PASH was present in:

• 245 cases (73.1%)

– Myxoid degeneration:

• 292 cases (87.2%)

– Epithelial hyperplasia

• Mild: 36.5%

• Moderate: 28.1%

• Severe: 9.3%

Am J Clin Pathol 2005;123:529-540



Problems in the interpretation of different series

Author No. of mitoses (10 HPF)

Kleer 1

Rosen 1-2

Pietruszka 0-4

Norris and Taylor 0-3

Tan PH 0-4

Arch Pathol Lab Med 2014;138:25-36



Phyllodes Tumor

Arch Pathol Lab Med 2014;138:25-36

• Problems in the interpretation of different series:

– Tumor heterogeneity

– Sampling errors

– Lack of a standard interpretation of histological

features

• Relative proportions of:

– Benign, borderline and malignant tumors

• Percentage of malignant tumors ranges from 2% to

45%

• Some histological slides:

– 25% discordance, final histopatological typing


Tan et al series:


43 women (12.8%), recurrences

Two Three Four

21% 9% 2%

2 patients metastases

Am J Clin Pathol 2005;123:529-540

Spinal Lungs


• Tan et al:

– Among the recurrences:

• The majority of the same grade

– Metastatic disease preceded death from PT in

all cases

– Risk of recurrence was reduced by 51.3% in

women with:

• PASH and negative margins


Am J Clin Pathol 2005;123:529-540


Clinicopathologic Features of Phyllodes

Tumors Correlated with Recurrence

Feature No Recurrence Recurrence P

Stromal Atipia

Mild (n:166)

Moderate (n:62)

Marked (n:32)

183

14

12

21

9

21

0.03*

Margin Status

Focal involvement (n:14)

Diffuse involvement (n: 291)

Complete Excision (n:217)

10

1

158

4

28

59

0.04*

Alvarado-Cabrero I et al


Phyllodes Tumor. Prognosis

• Most PTs behave in a benign fashion

• Local recurrence can occur in all PTs:

– Benign: 10-17%

– Borderline: 14-25%

– Malignant: 23-30%

• About 2%, PT may metastasize

– Mainly malignant PTs

• Recurrences:

– Mirror the original tumor

– Dedifferentiation with microscopic upgrading

• 25-75% of casesANZ J Surg 2006;76:476-480


Phyllodes Tumor. Prognosis

• Distant meatastases:

– Have been reported:

• Nearly all internal organs

• Lungs and skeleton, most common sites

• Deaths from tumor within 5-8 years of diagnosis

Br J Surg 1999;86:396-399



• Unpredictable to categorize reliably into benign

or malignant on the basis of any single feature

• Even benign tumors have a tendency to recur

• Malignant phyllodes tumor

– Metastases



Fibroepithelial (FE) Lesions of the

Breast

• Juvenile Fibroadenoma

• Complex Fibroadenoma

• Cellular Fibroadenoma

• Phyllodes Tumor

– Benign

– Borderline

– Malignant

Cellular FE

Lesions

Am J Clin Pathol 2001;115:736-42


Fibroadenoma (FA) of the Breast

Kuijper A et al:

• 1984 to 1999: 426 lesions originally diagnosed

as fibroadenoma

• On review, 30 cases (7%) not classified as FA

– 28 patients (7.8%) multiple tumors, located

– 17 patients (61%) patients, ipsilaterally

– 11 patients (39%), both breasts

Am J Clin Pathol 2001;115:736-742


Diagnosis of 426 cases originally diagnosed

as fibroadenoma

Diagnosis No of cases (%)

Fibroadenoma 396 (93.0)

Sclerosing lobular

hyperplasia

5 (1.2)

Phyllodes tumor 5 (1.2)

Hamartoma 4 (0.9)

Tubular adenoma 3 (0.7)

PASH 6 (1.4)

Adenomyoepithelioma 1 (0.2)

Normal tissue 6 (1.4)

Am J Clin Pathol 2001;115:736-742


Histopathologic changes in 396 cases of

fibroadenoma

Lesion No of cases (%)

Stromal changes

Pseudoangiomatous changes 15 (3.8)

Smooth muscle 11 (2.8)

Foci of tubular adenoma 2 (0.5)

Focal phyllodes tumor 3 (0.8)

Proliferative epitelial changes 182 (46)

Squamous metaplasia 1 (0.3)

Am J Clin Pathol 2001;115:736-742


Differential Diagnosis

Cellular

Fibroadenoma

Phyllodes

Tumor

Leaf-like processes - +

< 15 years old + -

Squamous metaplasia - +

Chondroid metaplasia - +

Osseous metaplasia - +

Adipose tissue - +

Infiltrating margins - +

(-) Rare to absent (+) Present

Tavassoli FA. Pathology of the Breast 2ed. 1999


Phyllodes Tumor

• Immunohistochemistry:

– CD34, consistently expressed in benign PTs

– Markedy reduced in high-grade PT

• Panel of CKs: stromal component

• Focal patchy positivity

– CK7----------28.4%

– 34βE12----- 22%

– AE1/3-------- 8.3%

– CAM 5.2----- 1.8%

– CK14--------- 1.8%


Tse et al: ER, PR and AR expression

• 143 cases

– ER positive epithelium 83 cases (58%)

– Correlation with tumor grade

• 67% Benign

• 43% Low-grade

• 47% High grade

– ER and PR staining:

• Strong, inverse correlation with stromal mitoses

• Decreased with increasing severity of the lesion

– AR expression: <5% of the epithelium and stroma of all

pts

Phyllodes Tumor


Ki-67

• Kocova et al:

– Proportion of Ki-67 positive tumor cells:

• Significant higher in malignant than in

benign PTs

• Difference between Ki-67 indices of

benign PTs vs FAD: lower

Phyllodes Tumor

Rosen


Genetics and Molecular studies

• Karim et al

– Limitations of the morphologic classification of

PTs: genetic heterogeneity of these tumors

• At present,

– No chromosomal alterations characteristic of

PTs have been identified

Phyllodes Tumor


Genetic and Molecular Studies:

• Few studies suggest:

– Two main subgroups of PTs with different

biologic potential

– No consensus on the assignation of low

grade/borderline tumors to the “benign” or

“malignant” groups

Phyllodes Tumor

Rosen


Phyllodes Tumor

• Azzopardi:

– “This is one of the most difficult tumors of the

breast on which to make pronouncements”

– “Perhaps the only definite assertion one can

safely make is that it is a distinctive

fibroepithelial tumor of the breast without a

counterpart in any organ”

Azzopardi. Problems in Breast Pathology 1979, Saunders


Thank you

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phyllodes tumors of the breast - · pdf file–malignant changes involve the conective...

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