fibroepithelial lesions in the breast of adolescent females: a clinicopathological profile of 53...

Fibroepithelial Lesions in the Breast of Adolescent Females:

A Clinicopathological Profile of 53 Cases

DS Ross,1 DD Giri,1 MM Akram,1 JP Catalano,1

KJ Van Zee,2 E Brogi1

1Department of Pathology, Memorial Sloan-Kettering Cancer Center, NYC, NY2Department of Surgery, Memorial Sloan-Kettering Cancer Center, NYC, NY

Background

Fibroepithelial lesions (FELs): • Most common breast abnormality in

adolescent females (< 18 years-old)• Referred to as:- Fetal fibroadenoma- Cellular fibroadenoma- Juvenile fibroadenoma- Giant fibroadenoma- Fibroadenoma variant

- Tubular adenoma- Hamartoma- Cystosarcoma phyllodes- Phyllodes tumor

Study Aims

• Investigate the morphology and clinical behavior of FELs in adolescents

• Standardize the diagnostic terms used for FELs in adolescents based upon histologic criteria

Study Design (1)

• Search of MSKCC pathology database– Age < 18 years-old– Excision or mastectomy between 1992-

2011

– Diagnosis of any fibroepithelial lesion

• 7 FELs from a prior series were also included (1975-1983)

Barrio AV et al. Ann Surg Oncol 2007

Study Design (2)

• 3 pathologists reviewed all available slides• Features noted:

• Gross & microscopic size• Borders / margin status• Growth pattern• Stromal overgrowth

• Stromal cellularity• Nuclear pleomorphism• Epithelial hyperplasia• Stromal cell mitoses

• Smooth muscle actin-α (1A4, DAKO) staining performed on available tissue

Study Design (3)

• Patient information and clinical follow-up obtained from e-medical records– Age at presentation– Age at menarche– Race– Laterality– Family history

Patient Population (1)FELsN=53

Patients N=47 F

Solitary FEL 42

Multiple FEL 5

3 ipsilateral 1

2 ipsilateral 2

bilateral 2

Race N=23

White 16

African-American

7

Patient Population (1)FELsN=53

Patients N=47 F

Solitary FEL 42

Multiple FEL 5

3 ipsilateral 1

2 ipsilateral 2

bilateral 2

Race N=23

White 16

African-American

7

Age (years)

Mean Age at Diagnosis 15.4 (10-18)

Mean Age for Menarche*- Median time from Menarche to Dx**

12.0 (10-14)48 mo

*Information available for 26 patients**1 patient presented 12 mo prior to menarche

Patient Population (2)

Laterality N=53

Right 33

Left 20

Presentation of FEL N = 42

Palpable Mass 41

Ultrasound 1*

Patients

Family History of Breast CA 13

*Pt undergoing US for ipsilateral FEL

53 Fibroepithelial Lesions

Usual Fi-

broade-noma21%, N=11

Juvenile Fi-

broade-noma43%, N=23

Benign Phyllodes

Tumor28%, N=15

Low Grade

Malignant Phyllodes

Tumor2%, N=1

Malignant Phyllodes Tumor6%, N=3

Malignant Phyllodes Tumor (8%), Low Grade N=1,High Grade N=3

• Gross size*: 4 & 25cm

• Infiltrative borders**

• Stromal overgrowth– All high grade tumors

*Gross size available for 2 cases**Borders assessable in 2 case

Malignant Phyllodes Tumor (8%), Low Grade N=1,High Grade N=3

• Increased stromal cellularity

• Moderate-marked stromal nuclear atypia

• Mean mitotic count / 10 HPF: – Low grade: 10– High grade: 17 (12-20)

Benign Phyllodes Tumor, N=15 (28%)

• Mean gross size*: 4 cm (1-13 cm)

• Borders**:– Circumscribed: 11/14 (79%)– Infiltrative: 3/14 (21%)

• Stromal overgrowth: 13% (2/15)

• Growth pattern– Intracanalicular: 10/15 (67%)– Pericanalicular: 5/15 (33%)

*Gross size available for 11 cases**Borders assessable in 14 cases

Benign Phyllodes Tumor, N=15 (28%)

• Increased stromal cellularity

• Mild-moderate stromal nuclear atypia

• Epithelial hyperplasia: 7/15 (47%)

• Mean mitotic count / 10 HPF: 3.1 (1-7)

Usual Fibroadenoma, N=11 (21%)

• Mean gross size: 2.6 cm (0.7-4.5 cm)

• Circumscribed borders

• Growth pattern– Intracanalicular: 10/11 (91%) – Pericanalicular: 1/11 (9%)

Usual Fibroadenoma, N=11 (21%)

• Increased stromal cellularity: 3/11 (27%)

• No stromal nuclear atypia


• Mean mitotic count / 10 HPF: 1.3 (0-6)– 6 mit / 10 HPF in pt pregnant 1y before; FA w/

focal lactational changes– Mean mitotic count w/o above pt is 0.8

Juvenile Fibroadenoma, N=23 (43%)

• Mean gross size*: 3.1 cm (0.5-7 cm)

• Circumscribed borders

• Growth pattern– Pericanalicular– Floridly glandular– Retention of lobular structure

*Gross size available for 22 cases


• Increased stromal cellularity: 14/23 (61%)

• No stromal nuclear atypia


• Mean mitotic count / 10 HPF: 1.8 (0-7)


SMAα

Juvenile Fibroadenoma

• A distinctive type of FA– Collagenized and cellular stroma– Pericanalicular growth pattern– Lobular arrangement– +/- Florid ductal hyperplasia

Juvenile Fibroadenoma:Variation in Morphology

Fibroadenoma Variant

• Characterized by collagenous and cellular stroma

• “…related to FAs in structure and composition but show sufficient difference to raise problems in precise dx and classification”– Differential dx often

includes a phyllodes tumor

Azzopardi, 1979

Juvenile Fibroadenoma, Variant Pattern (N=8/23)

Problems in Breast Pathology, Azzopardi, 1979 Case from our series

Juvenile Fibroadenoma: Variant Pattern & Intratumoral Heterogeneity (N=4/23)

Distinguishing FeaturesJuvenile Fibroadenoma Benign Phyllodes Tumor

Distinguishing Features

Mean Mitotic Count: 1.8 (0-7) Mean Mitotic Count: 3.1 (1-7)

Juvenile Fibroadenoma Benign Phyllodes Tumor

Original Diagnosis

Usual

FA

Cellula

r FA

Juve

nile

FA

FEL (w

/ des

cript

ion)

Benign

PT

LG M

align

ant P

T

Mali

gnan

t PT

Tubula

r Ade

nom

a

Adeno

sis0

5

10

15

20

25

14

810

2

13

13

1 1

Original

FEL

N

Reclassification

Usual

FA

Cellula

r FA

Juve

nile

FA

FEL (w

/ des

cript

ion)

Benign

PT

LG M

align

ant P

T

Mali

gnan

t PT

Tubula

r Ade

nom

a

Adeno

sis0

5

10

15

20

25

14

810

2

13

13

1 1

11

0

23

0

15

13

0 0

Original

Reclassified

FEL

N

Follow-Up

• 37 patients (41 FELs)– Mean follow-up: 40 months

• From less than a month to 278 months

2 Recurrent Cases

Months to Recur.

Gross Size (cm)

Borders Increased Stromal

Cellularity

Mitotic count per 10 HPF

Stromal atypia

BPT 12.2 8.5 Infiltrative Yes 4 Mild

LGMPT 18 N/A Infiltrative Yes 10 Moderate

• Information for index FEL

1992-2011: 46 Consecutive Fibroepithelial Lesions

Usual Fibroadenoma24%, N=11

Juvenile Fibroadenoma46%, N=21

Benign Phyllodes

Tumor26%, N=12

Malignant Phyllodes Tumor4%, N=2

Conclusions

• FEL in adolescents– Benign in two-thirds of cases

• Juvenile FA 46%, Usual FA 24%

Conclusions



– Frequent stromal mitoses

Conclusions




• Juvenile FA is the most common FEL– Distinctive morphology

Conclusions




• Juvenile FA is the most common FEL– Distinctive morphology – +/- Stromal expansion and intratumoral

heterogeneity (fibroadenoma variant)

References1. Amerson, J.R., Cystosarcoma phyllodes in adolescent females. A report of seven

patients. Ann Surg, 1970. 171(6): p. 849-56.

2. Ashikari, R., J.H. Farrow, and J. O'Hara, Fibroadenomas in the breast of juveniles. Surg Gynecol Obstet, 1971. 132(2): p. 259-62.

3. Azzopardi, J.G., A. Ahmed, and R.R. Millis, Problems in breast pathology. Major problems in pathology1979, Phildelphia: Saunders. xvi, 466 p.

4. Barrio, A.V., et al., Clinicopathologic features and long-term outcomes of 293 phyllodes tumors of the breast. Ann Surg Oncol, 2007. 14(10): p. 2961-70.

5. Ewing, J., Neoplastic Diseases, 2nd ed.1927, Philidelphia: W. B. Saunders.

6. Hertel, B.F., C. Zaloudek, and R.L. Kempson, Breast adenomas. Cancer, 1976. 37(6): p. 2891-905.

7. Koerner, F.C.. Diagnostic Problems in Breast Pathology. 2009, Philadelphia: Saunders.

8. Mies, C. and P.P. Rosen, Juvenile fibroadenoma with atypical epithelial hyperplasia. Am J Surg Pathol, 1987. 11(3): p. 184-90.

9. Pike, A.M. and H.A. Oberman, Juvenile (cellular) adenofibromas. A clinicopathologic study. Am J Surg Pathol, 1985. 9(10): p. 730-6.

10. Rosen, P.P., Rosen's breast pathology. 3rd ed 2008, Philadelphia: Lippincott Williams & Wilkins.

11. Tavassoli, F.A., Pathology of the breast. 2nd ed1999, Stamford, Conn.: Appleton & Lange. xi, 874

12. Wulsin, J.H., Large breast tumors in adolescent females. Ann Surg, 1960. 152: p. 151-9.

fibroepithelial lesions in the breast of adolescent females: a clinicopathological profile of 53...

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