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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
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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
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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
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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
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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
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Study Design (3)
• Patient information and clinical follow-up obtained from e-medical records– Age at presentation– Age at menarche– Race– Laterality– Family history
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Patient Population (1)FELsN=53
Patients N=47 F
Solitary FEL 42Multiple FEL 5 3 ipsilateral 1
2 ipsilateral 2 bilateral 2
Race N=23White 16
African-American 7
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Patient Population (1)FELsN=53
Patients N=47 F
Solitary FEL 42Multiple FEL 5 3 ipsilateral 1
2 ipsilateral 2 bilateral 2
Race N=23White 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
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Patient Population (2)
Laterality N=53Right 33Left 20
Presentation of FEL N = 42Palpable Mass 41
Ultrasound 1*
PatientsFamily History of Breast CA 13
*Pt undergoing US for ipsilateral FEL
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53 Fibroepithelial LesionsUsual
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
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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
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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)
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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
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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)
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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)
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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)
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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%)
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Usual Fibroadenoma, N=11 (21%)
• Increased stromal cellularity: 3/11 (27%)
• No stromal nuclear atypia
• Epithelial hyperplasia: 2/11 (18%)
• 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
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Usual Fibroadenoma, N=11 (21%)
• Increased stromal cellularity: 3/11 (27%)
• No stromal nuclear atypia
• Epithelial hyperplasia: 2/11 (18%)
• 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
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Usual Fibroadenoma, N=11 (21%)
• Increased stromal cellularity: 3/11 (27%)
• No stromal nuclear atypia
• Epithelial hyperplasia: 2/11 (18%)
• 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
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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
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Juvenile Fibroadenoma, N=23 (43%)
• Increased stromal cellularity: 14/23 (61%)
• No stromal nuclear atypia
• Epithelial hyperplasia: 7/23 (30%)
• Mean mitotic count / 10 HPF: 1.8 (0-7)
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Juvenile Fibroadenoma, N=23 (43%)
• Increased stromal cellularity: 14/23 (61%)
• No stromal nuclear atypia
• Epithelial hyperplasia: 7/23 (30%)
• Mean mitotic count / 10 HPF: 1.8 (0-7)
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Juvenile Fibroadenoma, N=23 (43%)
• Increased stromal cellularity: 14/23 (61%)
• No stromal nuclear atypia
• Epithelial hyperplasia: 7/23 (30%)
• Mean mitotic count / 10 HPF: 1.8 (0-7)
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Juvenile Fibroadenoma, N=23 (43%)
SMAα
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Juvenile Fibroadenoma• A distinctive type of FA
– Collagenized and cellular stroma– Pericanalicular growth pattern– Lobular arrangement– +/- Florid ductal hyperplasia
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Juvenile Fibroadenoma:Variation in Morphology
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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
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Juvenile Fibroadenoma, Variant Pattern (N=8/23)
Problems in Breast Pathology, Azzopardi, 1979 Case from our series
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Juvenile Fibroadenoma: Variant Pattern & Intratumoral Heterogeneity (N=4/23)
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Juvenile Fibroadenoma: Variant Pattern & Intratumoral Heterogeneity (N=4/23)
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Distinguishing FeaturesJuvenile Fibroadenoma Benign Phyllodes Tumor
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Distinguishing FeaturesJuvenile Fibroadenoma Benign Phyllodes Tumor
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Distinguishing Features
Mean Mitotic Count: 1.8 (0-7) Mean Mitotic Count: 3.1 (1-7)
Juvenile Fibroadenoma Benign Phyllodes Tumor
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Original Diagnosis
Usual
FA
Cellula
r FA
Juve
nile F
A
FEL (w/ d
escri
ption
)
Benign
PT
LG M
align
ant P
T
Malign
ant P
T
Tubula
r Ade
noma
Adeno
sis0
5
10
15
20
25
14
810
2
13
13
1 1
Original
FEL
N
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Reclassification
Usual
FA
Cellula
r FA
Juve
nile F
A
FEL (w/ d
escri
ption
)
Benign
PT
LG M
align
ant P
T
Malign
ant P
T
Tubula
r Ade
noma
Adeno
sis0
5
10
15
20
25
14
810
2
13
13
1 1
11
0
23
0
15
13
0 0
OriginalReclassified
FEL
N
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Follow-Up
• 37 patients (41 FELs)– Mean follow-up: 40 months
• From less than a month to 278 months
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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
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1992-2011: 46 Consecutive Fibroepithelial Lesions
Usual Fibroadenoma24%, N=11
Juvenile Fibroadenoma46%, N=21
Benign Phyllodes
Tumor26%, N=12
Malignant Phyllodes Tumor4%, N=2
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Conclusions
• FEL in adolescents– Benign in two-thirds of cases
• Juvenile FA 46%, Usual FA 24%
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Conclusions
• FEL in adolescents– Benign in two-thirds of cases
• Juvenile FA 46%, Usual FA 24%– Frequent stromal mitoses
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Conclusions
• FEL in adolescents– Benign in two-thirds of cases
• Juvenile FA 46%, Usual FA 24%– Frequent stromal mitoses
• Juvenile FA is the most common FEL– Distinctive morphology
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Conclusions
• FEL in adolescents– Benign in two-thirds of cases
• Juvenile FA 46%, Usual FA 24%– Frequent stromal mitoses
• Juvenile FA is the most common FEL– Distinctive morphology – +/- Stromal expansion and intratumoral
heterogeneity (fibroadenoma variant)
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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.
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