AJCP / Original Article
Significant Histologic Features Differentiating Cellular
Fibroadenoma From Phyllodes Tumor on Core Needle
Biopsy Specimens
Saba Yasir, MBBS,1 Roberto Gamez, MD,2 Sarah Jenkins, MS,3 Daniel W. Visscher, MD,1
and Aziza Nassar, MD4
From the 1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; 2Department of Pathology and Laboratory Medicine, Loyola
University, Chicago, IL; 3Department of Health Sciences Research, Mayo Clinic, Rochester, MN; and 4Department of Laboratory Medicine and Pathology,
Mayo Clinic, Jacksonville, FL.
Key Words: Phyllodes tumor; Fibroadenoma; Needle cores; Biopsy specimens; Fibroepithelial lesions
Am J Clin Pathol September 2014;142:362-369
DOI: 10.1309/AJCPZUZ96RESGPUP
ABSTRACT
Objectives: Cellular fibroepithelial lesions (CFELs) are
a heterogeneous group of tumors encompassing cellular
fibroadenoma (CFA) and phyllodes tumor (PT). Distinction
between the two is challenging on core needle biopsy (CNB)
specimens. The objective of this study was to evaluate
histologic features that can help distinguish PT from CFA on
CNB specimens.
Methods: Records of all patients diagnosed with CFELs on
CNB specimens with follow-up excision between January
2002 and December 2012 were retrieved. Histopathologic
stromal features were evaluated on CNB specimens,
including mitoses per 10 high-power fields (hpf), overgrowth,
increased cellularity, fragmentation, adipose tissue
infiltration, heterogeneity, subepithelial condensation, and
nuclear pleomorphism.
Results: Twenty-seven (42.2%) of 64 were diagnosed as PT
(24 benign PTs and three borderline PTs) and 37 (57.8%) as
CFA on excision. All features except for increased stromal
cellularity were statistically significant. The average number
of histologic features seen in PT and CFA was 3.9 and 1.4,
respectively (odds ratio [OR], 7.27; 95% confidence interval
[CI], 2.44-21.69; P = .0004). The average number of mitoses
per 10 hpf was 3.0 for PT compared with 0.8 for CFA (OR,
2.14; 95% CI, 1.18-3.86; P = .01).
Conclusions: The presence of mitoses (three or more) and/or
total histologic features of three or more on CNB specimens
were the most helpful features in predicting PT on excision.
362 Am J Clin Pathol 2014;142:362-369
362 DOI: 10.1309/AJCPZUZ96RESGPUP
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Cellular fibroepithelial lesions (CFELs) of the breast
are commonly encountered in clinical daily practice. They
comprise a heterogeneous group of neoplasms composed of
cellular fibroadenoma (CFA) and phyllodes tumor (PT). The
core needle biopsy (CNB) is used as a part of triple approach,
along with radiology and clinical examination, to make the
primary diagnosis on breast lesions. The distinction between
CFA and benign phyllodes tumor (BPT) is challenging on
CNB specimens due to morphologic overlap in most of
those cases. However, it carries a significant impact on
clinical management decisions. CFA behaves in an indolent
fashion without significant risk of local recurrence1-3 and
may be either clinically monitored or treated by simple
surgical removal (enucleation). On the other hand, BPT
has an unpredictable biologic behavior and carries a risk
of local recurrence without distant metastatic potential.4
The reported rate of local recurrence for BPT is 20% in old
literature series.4-6 Therefore, the current standard treatment
is surgical excision.
The extent of surgery remains controversial. Most
authors believe that BPT should be widely excised to reduce
the risk of local recurrence.7-9 These management decisions
are mainly based on the reported observations that surgical
margins are the single most important predictor of local
recurrence, and BPT should be completely excised with
adequate margins.5,10-12 However, data from other studies
showed that BPT may be followed up if incompletely
removed at the first excision, with wide excision only
after recurrence.13 Hence, improvement in preoperative
diagnostic accuracy is crucial in the treatment of patients
with CFELs on CNB specimens. Furthermore, a substantial
proportion of CFEL cases were identified as PT on excision,
© American Society for Clinical Pathology

and consequently, surgical excision has been recommended
for complete evaluation of all these lesions.14,15
Several studies involving CFELs on CNB specimens
have been performed to identify histologic features that can
predict BPT on subsequent excision16-19; however, the results
are somewhat controversial. Therefore, the purpose of this
study is to evaluate several histologic features of CFELs on
CNB specimens that can help differentiate the two entities and
predict BPT on subsequent excision.
Materials and Methods
All patients diagnosed with CFELs on CNB
specimens at the Mayo Clinic in Rochester, Minnesota,
were retrieved from the Mayo Clinic anatomic pathology
database from January 2002 through December 2012.
Since our study focused on evaluating histologic features
of indeterminate CFELs on CNB specimens, all patients
with clear-cut diagnoses of CFA and BPT on CNB
specimens were excluded. All patients without subsequent
surgical excision after the initial core biopsies were also
excluded from the study. The study was approved by the
Mayo Clinic Institutional Review Board (IRB 12-006492;
August 13, 2012).
Pathology Review
Histologic slides of initial core biopsy specimens and
surgical excisions were retrieved on all selected cases and
reviewed by two breast pathologists (A.N. and S.Y.) blinded
to the original diagnoses on core biopsy and surgical excision
specimens. The following histologic features were evaluated
on both core biopsy and excisional specimens:
1. Stromal mitoses were counted in 10 high-power fields
(hpf) at ×40 ❚Image 1A❚.
2. Stromal overgrowth was defined as the presence
of a merely stromal component/absence of an epithelial
component. Stromal overgrowth was evaluated at ×10 for
core biopsy specimens ❚Image 1B❚ and at ×4 for excision
specimens ❚Image 1C❚.
3. Increased stromal cellularity was categorized as
absent or present. Assessment of stromal cellularity was
made on the most cellular areas of the specimen (0, when
the stromal cellularity was not increased; 1, when there
was a definitive increase in the density of the stromal cells,
in the form of stromal nuclear crowding or overlapping)
❚Image 1D❚.
4. Stromal fragmentation was defined as detached
stromal fragments completely covered by the ductal
epithelium ❚Image 1E❚. Stromal fragmentation corresponded
to an exaggerated intracanalicular growth pattern and leaf-
like architecture.
© American Society for Clinical Pathology
AJCP / Original Article
5. Adipose tissue infiltration or fat entrapment ❚Image 1F❚
was defined as an extension of the stromal cells into the
surrounding adipose tissue in an infiltrative pattern. It was
considered a feature of a noncircumscribed lesion.
6. Stromal heterogeneity was defined as the overall
heterogeneous appearance of a stromal component. This
was demonstrated as a difference in stromal cellularity or
atypia in different areas of the same tumor ❚Image 1G❚ and
❚Image 1H❚. Similarly, the stromal component of an individual
case showed a hypocellular fibrotic/myxoid appearance
(Image 1G) in one area and a hypercellular appearance in
another area (Image 1H).
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7. Subepithelial stromal condensation was defined as an
enhancement of stromal density adjacent to or underneath the
ductal epithelium ❚Image 1I❚.
8. Stromal nuclear pleomorphism or cellular atypia was
defined as absent when the stromal cells had small uniform
nuclei with evenly distributed chromatin and inconspicuous
nucleoli or present when the stromal cells had variability in
nuclear size and shape with nuclear membrane irregularity
and conspicuous nucleoli ❚Image 1J❚.
Final diagnoses of CFA or BPT/borderline PT were
made on the excisional specimens based on the previously
established histologic criteria, including stromal mitoses,
stromal overgrowth, stromal cellularity, infiltration into
the surrounding adipose tissue, and stromal atypia.18 The
evaluation of excision specimens was performed blinded
to the histopathologic features evaluated on a respective
CNB specimen. All histologic features evaluated on CNB
specimens were then correlated in a retrospective manner
with the diagnoses on excision specimens to determine which
features on CNB specimens would be helpful in predicting
the diagnosis of BPT on a subsequent excision.
Clinical Characteristics
The patients’ clinical records were reviewed to collect
demographic and clinical information in a blinded manner,
including age of the patient, site and size of the lesion, and
other information.
Statistical Analysis
Patient characteristics and tumor features were
summarized with median and range (or mean and standard
deviation, as appropriate) for continuous data and with
frequencies and percentages for categorical data. As a
way to incorporate each of seven features into a single
summary measure, the total number of features present
(among seven) was calculated for each tumor specimen.
In calculating the total number of features, each was
given equal weight regardless of univariate significance,
so as not to bias this measure based on the limited data
available. Data were compared by diagnosis (BPT vs CFA)
Am J Clin Pathol 2014;142:362-369 363
363 DOI: 10.1309/AJCPZUZ96RESGPUP 363
Yasir et al / Fibroepithelial Lesion Features

A B

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C D

E F

❚Image 1❚ A, Stromal mitotic activity (H&E, ×40). B, Stromal overgrowth (absence of epithelial component) identified in a core
needle biopsy specimen (H&E, ×10). C, Stromal overgrowth (absence of epithelial component) on an excision specimen (H&E,
×4). D, Increased stromal cellularity (H&E, ×20). E, Stromal fragmentation. Stromal fragments completely lined by epithelial cells
(H&E, ×4). F, Adipose tissue infiltration (H&E, ×4).

364 Am J Clin Pathol 2014;142:362-369 © American Society for Clinical Pathology

364 DOI: 10.1309/AJCPZUZ96RESGPUP
 AJCP / Original Article

G H

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I J

❚Image 1❚ (cont) G and H, Stromal heterogeneity. Two different areas of the same tumor demonstrate heterogeneity in terms
of difference in stromal cellularity and stromal atypia. The stroma is fibrotic (G) in one area and hypercellular in another area
(H) (H&E, ×20). I, Subepithelial stromal condensation (H&E, ×10). J, Stromal cells demonstrate moderate to severe nuclear
pleomorphism and hyperchromasia (H&E ×40).

using two-sample t tests (age, mitoses, and total features) Results

and with c2 tests (or Fisher exact tests, as appropriate) for
categorical features. Logistic regression modeling was
used for further univariate and multivariable analysis. The
C statistic was reported for each logistic regression model
as a measure of predictive accuracy (equivalent to area
under the receiver operating characteristic curve). Values
of 0.5 indicate that the model does no better than chance,
and values of 1 indicate perfect predictive accuracy. All
analyses were performed using SAS version 9 (SAS
Institute, Cary, NC). P values less than .05 were considered
statistically significant.
Our initial search identified 73 patients (76 cases) with
a diagnosis of CFELs on CNB specimens. Twelve patients
were excluded from the study cohort (five patients without
subsequent excision, two patients with hamartoma on excision,
and five patients with no residual CFELs on excision). Finally,
a total of 61 patients met our study criteria. There were 64
CNB and excision specimens, since three patients had bilateral
disease and underwent two CNBs and subsequent excision of
those lesions. The mean age of the entire study cohort was 41
years (range, 15-83 years). Of the 64 specimens, 27 (42.2%)
were diagnosed as PT, including 24 BPTs and three borderline

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Yasir et al / Fibroepithelial Lesion Features

PTs. Thirty-seven (57.8%) of 64 cases were diagnosed as CFA.
The final diagnoses of PT and CFA were based on histologic
features on excisional specimens.
Patients’ demographic information and histologic
characteristics on CNB specimens were tabulated across the
excisional diagnoses ❚Table 1❚. The mean age of patients
diagnosed with PT and CFA was 40.7 and 40.6 years,
respectively (P = .98). The mean tumor size in the PT and
CFA groups was 2.9 and 1.8 cm, respectively (P = .03). The
increase in stromal cellularity was seen in 26 (96.3%) of
27 PTs and 32 (86.5%) of 37 CFAs (P = .39). The stromal
cells demonstrated cytologic/nuclear atypia in 20 (74.1%)
of 27 PTs and 12 (32.4%) of 37 CFAs (P = .001). Stromal
overgrowth was seen in 11 (42.3%) of 27 PTs and only two
(5.4%) of 37 CFAs (P = .0004). Twenty-four (88.9%) women
with PT and 18 (48.6%) women with CFA showed stromal

❚Table 1❚
Univariate Analysis of Clinicopathologic Features With Final Excisional Diagnosis (CFA and BPT)a

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Characteristic PT (n = 27) CFA (n = 37) Total (n = 64) P Value C Statistic

Age, y .9807b 0.51

Mean (SD) 40.7 (15.3) 40.6 (14.5) 40.7 (14.7)
Range 18.0-69.0 15.0-83.0 15.0-83.0
Tumor size, cm .0293b 0.70
Mean (SD) 2.9 (2.2) 1.8 (1.1) 2.2 (1.7)
Median (range) 2.3 (0.8-12.0) 1.5 (0.6-5.4) 1.8 (0.6-12.0)
Q1, Q3 1.5, 3.5 1.0, 2.2 1.1, 2.7
Mitoses/10 hpf <.0001b 0.83
Mean (SD) 3.0 (1.7) 0.8 (1.3) 1.8 (1.8)
Median (range) 3.0 (0.0-6.0) 0.0 (0.0-5.0) 1.0 (0.0-6.0)
Q1, Q3 2.0, 4.0 0.0, 1.0 0.0, 3.0
Mitoses/10 hpf: categorical, No. (%) <.0001c 0.83
0 4 (14.8) 22 (59.5) 26 (40.6)
1-2 3 (11.1) 11 (29.7) 14 (21.9)
≥3 20 (74.1) 4 (10.8) 24 (37.5)
Mitoses/10 hpf (≤2 vs ≥3), No. (%) <.0001c 0.82
0-2 7 (25.9) 33 (89.2) 40 (62.5)
≥3 20 (74.1) 4 (10.8) 24 (37.5)
Stromal overgrowth, No. (%) .0004d 0.69
Missing 1 0 1
Absent (0) 15 (57.7) 35 (94.6) 50 (79.4)
Present (1) 11 (42.3) 2 (5.4) 13 (20.6)
Increased stromal cellularity, No. (%) .3877c 0.55
Absent (0) 1 (3.7) 5 (13.5) 6 (9.4)
Present (1) 26 (96.3) 32 (86.5) 58 (90.6)
Stromal fragmentation, No. (%) .0011c 0.70
Absent (0) 3 (11.1) 19 (51.4) 22 (34.4)
Present (1) 24 (88.9) 18 (48.6) 42 (65.6)
Infiltration into fat, No. (%) .0058d 0.66
Absent (0) 14 (51.9) 31 (83.8) 45 (70.3)
Present (1) 13 (48.1) 6 (16.2) 19 (29.7)
Stromal heterogeneity, No. (%) .0002d 0.73
Absent (0) 8 (29.6) 28 (75.7) 36 (56.3)
Present (1) 19 (70.4) 9 (24.3) 28 (43.8)
Subepithelial condensation, No. (%) .0001d 0.73
Absent (0) 10 (37.0) 31 (83.8) 41 (64.1)
Present (1) 17 (63.0) 6 (16.2) 23 (35.9)
Stromal pleomorphism, No. (%) .0010d 0.71
Absent (0) 7 (25.9) 25 (67.6) 32 (50.0)
Present (1) 20 (74.1) 12 (32.4) 32 (50.0)
Combined histologic features excluding mitotic
activity (of seven possible from above), No. <.0001b 0.94
Mean (SD) 3.9 (1.2) 1.4 (1.0) 2.5 (1.6)
Median (range) 4.0 (2.0-6.0) 1.0 (0.0-4.0) 2.0 (0.0-6.0)
Q1, Q3 3.0, 5.0 1.0, 2.0 1.0, 4.0
Combined histologic features excluding mitotic
activity, categorized, No. (%) <.0001d 0.88
0-2 features 4 (14.8) 33 (89.2) 37 (57.8)
3-7 features 23 (85.2) 4 (10.8) 27 (42.2)

BPT, benign phyllodes tumor; CFA, cellular fibroadenoma; PT, phyllodes tumor; Q1, quartile 1; Q3, quartile 3.
a Histologic features include stromal mitotic activity, stromal overgrowth, increased stromal cellularity, stromal fragmentation, infiltration into fat, stromal heterogeneity,

subepithelial stromal condensation, and stromal nuclear pleomorphism/cellular atypia.

b Unequal variance t test.
c Fisher exact test.
d c2 test.

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 AJCP / Original Article

fragmentation (P = .001). Stromal heterogeneity was observed
in 19 (70.4%) of 27 PTs and nine (24.3%) of 37 CFAs (P =
.0002). Prominent adipose tissue infiltration was seen in 13
(48.1%) of 27 PTs and six (16.2%) of 37 CFAs (P = .006).
Subepithelial condensation was prominent in 17 (63%) of 27
PTs and six (16.2%) of 37 CFAs (P = .0001). The average
mitotic figures per 10 hpf were 3 and 0.8 in the PT and CFA
groups, respectively (P < .0001). In 27 PTs, 20 (74.1%) cases
had three or more mitoses per 10 hpf, three (11.1%) had one
to two mitoses per 10 hpf, and four (14.8%) had no mitotic
activity. In contrast, among 37 CFA cases, most (22 [59.5%])
had no mitotic activity, 11 (29.7%) had one to two mitoses
33 (89.2%) had zero to two features (P < .0001). In general,
the likelihood of PT increases as the total number of features
increases. Among those with zero to one feature, none were
PT. The percentage with PT increased from 23.5% to 70.0%
to 87.5% to 100% for two, three, four, and five to six features,
respectively (no case had seven total features). Furthermore,
the estimated odds ratio of PT for each additional increase
in features was 7.8 (95% confidence interval [CI], 2.8-21.4;
P < .0001).
With respect to the predictive accuracy of each measure
or feature, the total number of evaluated histologic features
performed the best (C statistic for continuous version, 0.94),

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per 10 hpf, and only four (10.8%) cases had three or more
mitoses per 10 hpf. The data on mitotic activity were also
analyzed based on two categories (zero to two and three or
more), which showed that 20 (74.1%) of 27 PTs had three or
more mitoses per 10 hpf, and 33 (89.2%) of 37 CFAs had zero
to two mitoses per 10 hpf (P < .0001).
On univariate analysis, except for increased stromal
cellularity, all histologic features, including stromal mitotic
activity of three or more per 10 hpf, stromal overgrowth,
stromal fragmentation, adipose tissue infiltration, stromal
heterogeneity, subepithelial condensation, and stromal atypia/
pleomorphism, were seen in a significantly higher proportion
of women in the PT group than in the CFA group.
When the total numbers of evaluated histologic features
were calculated for each individual case, it was found that
PT cases had more features on average compared with CFA
cases. The average number of features seen in PT was 3.9
compared with 1.4 in CFA (P < .0001; data shown in Table 1).
Among 27 PT cases, 23 (85.2%) had three to seven features
and four (14.8%) had zero to two features. In contrast, of 37
CFA cases, only four (10.8%) had three to seven features, and
followed by mitoses (C statistic, 0.83). Most of the remaining
features performed similarly (C statistic range, 0.66-0.73),
with the exception of increased stromal cellularity (C statistic,
0.55) and age (C statistic, 0.51), which had essentially no
predictive accuracy. Stromal heterogeneity and subepithelial
condensation appear to be the best predictors for PT (C
statistic, 0.73 each), followed by stromal pleomorphism (C
statistic, 0.71) (see Table 1).
A multivariable logistic regression model was estimated,
including mitoses and total number of other histologic features
(stromal overgrowth, increased stromal cellularity, stromal
fragmentation, infiltration into fat, stromal heterogeneity,
subepithelial stromal condensation, and stromal nuclear
pleomorphism) ❚Figure 1A❚ and ❚Figure 1B❚. Each variable
was statistically significant (mitoses, P = .01; total histologic
features, P = .0004). The C statistic for this model was
0.95, and this indicates excellent discrimination between
these two groups based on this model. The odds ratio for
PT (compared with CFA) for mitoses was 2.14 (adjusted for
total features; 95% CI, 1.18-3.86); the odds ratio for total
number of histologic features was 7.27 (adjusted for mitoses;

A B
6 6

5 5
No. of Mitoses/10 hpf

Total No. of Features

4 4

3 3

2 2

1 1

0 0
BPT CFA BPT CFA

❚Figure 1❚ The boxplots show the difference in mitoses (A) and total number of histologic features (B) between the groups.
Note how little they overlap. To interpret the boxplots, the outlined boxes show the middle 50% of the data (between the 25th
and 75th percentiles), along with the median shown as the horizontal line in the middle of the box—note that the median and
25th percentile are equal among those with cellular fibroadenoma (CFA) for each of these two measures. The mean is shown by
the diamond. BPT, benign phyllodes tumor.

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Yasir et al / Fibroepithelial Lesion Features
95% CI, 2.44-21.69). The odds ratio can be interpreted as
the multiplicative increase in odds of PT for each one-unit
increase in the predictor. In a separate model that included
tumor size, similar results were found, and tumor size was not
statistically significant (data not shown).
The sensitivity and specificity values for mitotic activity
and total number of histologic features were calculated. The
sensitivity for detecting PT with mitoses of three or more was
74.1%. Similarly, the sensitivity for detecting PT with total
histologic features of three or more was 85.2%. Among those
who had CFA, the specificity of mitoses of two or less was
89.2%, and the specificity of total histologic features of two
or less was also 89.2%.
Discussion
CFELs on CNB specimens are commonly encountered
entities in everyday practice, and differential diagnosis includes
CFA or PT. Distinction between the two is often challenging
due to significant morphologic overlap and lack of consensus
on objective criteria and clear cutoff values. In other words,
there are no uniform or standardized distinguishing features
that discriminate between CFA and PT on CNB specimens.
Most of the previous studies focused on identifying
individual histologic features for differentiation between
the two entities. Similarly, our data highlight important
histologic features on CNB specimens that can help predict
PT on subsequent excision. On univariate analysis, except
for increased stromal cellularity, all other histologic features
evaluated, including stromal mitoses of three of more per 10
hpf, stromal overgrowth, stromal fragmentation, adipose tissue
infiltration, stromal heterogeneity, subepithelial condensation,
and stromal nuclear pleomorphism, were statistically
significant features that discriminated PT from CFA.
Jara-Lazaro et al20 showed that moderate to severe
stromal cellularity, stromal overgrowth, moderate nuclear
atypia, stromal mitoses of two or more per 10 hpf, and ill-
defined lesional borders on CNB specimens were exclusive
to the diagnosis of PT on excision. Lee et al21 reported that
an increase in stromal cellularity of at least 50% greater than
typical fibroadenoma, stromal overgrowth, fragmentation, and
adipose tissue infiltration were significantly more common
in the CNB specimens of PT. Similar results were reported
in another study as well.15 Gould et al22 found additional
interesting features that are more associated with PT on
excision after a diagnosis of fibroepithelial neoplasm in CNB
specimens: larger tumor diameter (mean, 4.0 cm; P < .002)
and increased hyperechoic mass density (P < .001) on
preoperative imaging, in addition to Hispanic ethnicity.
In agreement with other studies,15,20 we found that the
presence of stromal overgrowth evaluated at ×10 was a useful
368 Am J Clin Pathol 2014;142:362-369
368 DOI: 10.1309/AJCPZUZ96RESGPUP
feature. In comparison with other studies,15,20 we found that
increased stromal cellularity was not a helpful feature (seen
in 96.3% and 86.5% of PT and CFA cases, respectively).
This difference could be related to our lower threshold for
increased stromal cellularity.
Most of the individual histologic features assessed in
this study were seen in both PT and CFA groups. Therefore,
the use of a combination of histologic features would be
desirable and more helpful. Our data highlight an important
aspect of our review that the total number of histologic
features seen in an individual case of PT was significantly
more than in those with CFA, regardless of which particular
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features were seen. Most PT cases (85.2%) demonstrated
a combination of more than three histologic features. In
contrast, most CFA cases (89.2%) showed fewer than three
histologic features. In our cohort, the mean (SD) number of
histologic features seen in PT was 3.9 (1.2), whereas it was
1.4 (1.0) in CFA. In other words, there was very little overlap
in the number of features seen in PT and CFA groups. This
is statistically significant (P < .0001) and helpful in real
practice, since it provides a clear- cut number of histologic
features that are in favor of PT.
Our data support that the presence of any three or more
evaluated histologic features (stromal overgrowth, increased
stromal cellularity, stromal fragmentation, infiltration into fat,
stromal heterogeneity, subepithelial stromal condensation,
and stromal nuclear pleomorphism) on CNB specimens
favors PT over CFA on multivariate analysis. The likelihood
or probability of BPT increases with every one-unit increase in
the number of histologic features assessed on CNB specimens.
In particular, the constellation of stromal heterogeneity,
subepithelial condensation, and stromal pleomorphism
appears to be the best predictors for PT (Table 1).
Furthermore, our data showed that the stromal mitotic
activity of three or more by itself was very helpful in
discriminating PT based on a multivariable logistic regression
model. Both mitotic activity (P = .01) and the total number of
histologic features (P = .0004) were statistically significant.
The patients’ age was not helpful in distinguishing PT from
CFA on univariate (data shown in Table 1) and multivariate
analysis, respectively (data not shown). Although tumor size
was significantly different between the groups on univariate
analysis (Table 1), this was no longer helpful in distinguishing
PT from CFA on multivariate analysis (after adjusting for
mitoses and number of features). In contrast to previous
studies, we showed that patients’ age as well as tumor size is
not a useful clinical parameter in the distinction of PT.7,22-24
In conclusion, two important significant findings in
the current study are in favor of the diagnosis of PT on
follow-up excision. The finding of prominent mitotic activity
(≥3/10 hpf) is by itself adequate to favor PT over CFA based
on multivariate analysis. On the other hand, if there is no
© American Society for Clinical Pathology

stromal mitotic activity, the constellation of other (at least
three) histologic features (stromal overgrowth, increased
stromal cellularity, stromal fragmentation, infiltration into fat,
stromal heterogeneity, subepithelial stromal condensation,
and stromal nuclear pleomorphism) in a CNB specimen are
more predictive of PT than CFA.
Address reprint requests to Dr Nassar: Dept of Laboratory
Medicine and Pathology, 4500 San Pablo Rd S, Mayo 3-160S,
Jacksonville, FL 32224; Nassar.aziza@mayo.edu.
  Acknowledgments: We thank Victoria L. Jackson, MLIS
(Academic and Research Support, Mayo Clinic, Jacksonville, FL),
for editorial assistance.
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Am J Clin Pathol 2014;142:362-369 369
369 DOI: 10.1309/AJCPZUZ96RESGPUP 369