Phyllodes Tumors of the Breast - · PDF file–Malignant changes involve the conective...
Transcript of 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
Phyllodes Tumors of the Breast
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Phyllodes Tumor
Diagnosis
Postgrad Med J 2001;77:428-435
• 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
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
• 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
Dra. Isabel Alvarado_Cabrero
Phyllodes Tumors of the Breast
• 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
Dra. Isabel Alvarado_Cabrero
Phyllodes Tumors of the Breast
• 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
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Cancer 1967;20:2090-2099
Phyllodes Tumors of the Breast
• 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
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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:
Dra. Isabel Alvarado_Cabrero
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
Norris and Taylor series:
Dra. Isabel Alvarado_Cabrero
Norris and Taylor series:
• 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
Dra. Isabel Alvarado_Cabrero
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
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Dra. Isabel Alvarado_Cabrero
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Dra. Isabel Alvarado_Cabrero
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• Stromal overgrowth:
– “Absence of an epitelial component in at least
one microscopic field (10X ocular objective
and 4X microscopic lens objective)”
Phyllodes Tumors of the Breast
198- Rosen
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Phyllodes Tumors of the Breast
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
Dra. Isabel Alvarado_Cabrero
Tan et al series:
Phyllodes Tumors of the Breast
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
Dra. Isabel Alvarado_Cabrero
• 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
Phyllodes Tumors of the Breast
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
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 Tumors of the Breast
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
Tan et al series:
Phyllodes Tumors of the Breast
43 women (12.8%), recurrences
Two Three Four
21% 9% 2%
2 patients metastases
Am J Clin Pathol 2005;123:529-540
Spinal Lungs
Dra. Isabel Alvarado_Cabrero
• 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
Phyllodes Tumors of the Breast
Am J Clin Pathol 2005;123:529-540
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
Phyllodes Tumors of the Breast
• 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
Postgrad Med J 2001;77:428-435
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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%
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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
Dra. Isabel Alvarado_Cabrero
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