Pathology International 1998; 48: 549-556

Case Report
Histiocytoid breast carcinoma: Histological,
immunohistochemical, ultrastructural, cytological and
clinicopathological studies

Satoru S h i m i ~ u , Hajime
~ , ~ ~ ~Kitamura,’ Takaaki lto? Takeshi Nakamura,’ Jun Fujisawa2and
Hiroshi Matsukawa2
Depattments of‘ Pathology and ‘Surgery, Yokohama Minami Kyosai Hospital, and 3Depattmentof Pathology,
Yokohama City UniversitySchool of Medicine, Yokohama, Japan

Histiocytoid breast carcinoma (HBC) is a rare variant of
breast carcinoma and often causes a diagnostic dilemma
because of its histological similarities to some types of
breast cancer and benign lesions. To elucidate the
incidence of HBC and its biological properties, histological
specimens from 1010 breast cancer patients treated at
Yokohama Minami Kyosai Hospital between 1972 and 1996
were reviewed. Three cases of pure HBC and three cases of
combined HBC (two with pleomorphic lobular carcinoma
and one with apocrine ductal carcinoma) were found,
yielding an Incidenceof 0.3% for each. Two of the three pure
HBC cases contained foci of in situ lobular carcinoma.
Targetoid and Indian file invasive patterns, the features
characteristicof lobular carcinoma, were present Inall three
pure HBC cases and in two of the three combined HBC with
pleomorphlc lobular carcinoma. These results, together
with those of previous studies, suggestedthat the majority
of HBC are of lobular origin, although the apocrlne ductal
origin is also possible in a small number of HBC. Diastase-
resistant periodic acid-Schlff-positive granules and gran-
ular immunoreactivitles for gross cystic disease fluld
protein-15 (GCDFP-15) were characteristic of the hlstio-
cytold tumor cells in both the pure and combined HBC,
suggesting the apocrine differentiation of tumor cells. All
three pure HBC cases were in stage 1and were free of the
diseasefor up to 5 years and 1month after the lumpectomy.
Thus, the prognosis of HBC appears to be dependent on the
stage of the disease and may not always be poor, as
indicated by the original report mentioning a preferential
eyelid metastasis.
Key words: breast carcinoma, diagnostic criteria, differential
diagnosis, disease entity, GCDFP-I5, histiocytoid, pleomorphic
lobular carcinoma
~
Histiocytoid breast carcinoma (HBC) was first reported by
Hood et a/.’ in 1973 in eight patients with eyelid metastasis
and, since then, only about 30 cases have been reported in
the English and French Iiterature.l4 It was first introduced in
the textbook written byAzzopardilo as a rare variant of breast
carcinoma in 1979, and Tavassoli” in 1992 and Rosen’2 in
1997 also referred to this variant in their textbooks. We
reported the first Japanese case in 1996 and described, for
the first time, the electron microscopic and cytological
features of HBC.’ The occurrence of histiocytoid breast
carcinoma appears to be rare, but the precise incidence of
this tumor is not known, partly because of lack of definite
criteria for its histological diagnosis and also lack of wide
recognition of this tumor. In fact, several reported cases were
originally diagnosed as benign lesions.“ Accordingly, the
biological behavior has not yet been clarified, although Hood,
et a/. reported preferential metastasis to the eyelid.’ Most
cases were considered to be lobular in origin, but Eusebi et
al. recently proposed a ductal origin in a subset of their
cases? Thus, the histogenesis of HBC has not yet been
settled. The purposes of the present study were to clarify the
incidence of histiocytoid carcinoma among breast carcin-
omas, to investigate its histogenesis, and to establish its
diagnostic criteria.
CLINICAL SUMMARY
Hematoxylin-eosin (HE)-stained histological sections from
1010 patients with breast carcinoma who underwent surgery
at our hospital between 1972 and 1996 were reviewed with a

special reference to the histiocytoid appearance of tumor

Correspondence: Satoru Shimizu, MD, Department of Pathology,
Yokohama Minami Kyosai Hospital, 500 Mutsuuracho, Kanazawa-
ku, Yokohama 236,Japan. Email:<CAA82080@pop06.ODN.NE.JPr
Received 17 December 1997. Accepted for publication9 February
1998.
cells; that is, finely granular to vesicular cytoplasm and a
round to oval nucleus with a low nuclear to cytoplasmic ratio
(N: C ratio). We found three cases of lobular carcinoma
composed almost exclusively of histiucytoid tumor cells (pure
550 S. Shimizu eta/.

type, cases 1 to 3). two cases of pleomorphic lobular carci-
noma with focal histiocytoid features (combined type, refer-
ence case (RC) 1 and 2). and one case of apocrinecarcinoma
with focal histiocytoid features (combined type, RC 3). The
ctinicopathologicaldata of these six cases are summarized in
Table 1. These were all studied histochemically and immuno-
histochemically and, in the two cases of histiocytoid carci-
noma, an ultrastructural study was performed. For compari-
son, one case each of clear cell (glycogen-rich) carcinoma,
lipid-rich (lipid-secreting) carcinoma, signet ring cell carci-
noma of ductal origin, secretory (juvenile) carcinoma and
granular cell tumor was also histopathologically studied. For
light microscopic examination, the tissues were fixed in 10%
neutral formalin and embedded in paraffin. Sections of 4 pm
were stainedwith HE, periodic acid-Schiff (PAS) reactionwith
or without prior diastase digestion, and alcian blue (pH 2.5).
Lipid stainings with Sudan 111 were also carried out on frozen
sections in all three of the cases of pure histiocytoid carci-
noma. lmmunohistochemistry was performed by the avidin-
biotin peroxidase complex method for epithelial membrane
antigen (EMA, 1 : 100; DAKO, Glostrup, Denmark), cytok-
eratin (KL-1, 1 :200; Immunotech, Marseilles, France),
vimentin (1 : 50; DAKO), desmin (1 : 50; DAKO), S-100
protein (1 :200; DAKO), lactalbumin (1 : 100; DAKO), gross
cystic disease fluid protein-15 (GCDFP-15, 1 : 200; Signet
Laboratories, Dedham, MA, USA), c-erbB-2 oncogene
product (c-edS-2, pAb-I, 1 :30; Triton Diagnostics,
Alameda, CA, USA), p53 tumor suppressor gene protein
(p53, DO-7, 1 :100; Immunotech) and carcinoembryonic
antigen (CEA, 1 : 100; Kyowa Medex, Tokyo, Japan) and Ki-
67 (MIB-1, 1 : 1; Immunotech). For estrogen receptor (ER,
1D5,l :50; DAKO), sections were pretreatedby autoclave at
121"C for 15 min.
For electron microscopy, specimens were taken from
formalin-fixed tissues and post-fixed in 2.5% glutaraldehyde
and 1%osmium tetroxide. They were embedded in epoxy
resin, and ultrathin sections (80 nm in thickness) were
stained with uranyl acetate and lead citrate for observation
under electron microscope (JEOL2000, Tokyo, Japan).
PATHOLOGICAL FINDINGS
Histological findings of puretype histiocytoid breast
carcinoma
All three of the cases diagnosed as pure histiocytoid
carcinoma showed very similar histological and cytological
features. The tumors consisted of a diffuse infiltration of
large tumor cells with amphophilicfinely granular to vesicular
cytoplasm (Fig. 1). lntracytoplasmic luminae (ICL) were
seen, but rarely. The nuclei were round to oval with a single
small eosinophilic nucleolus, very fine chromatin pattern and
thin nuclear membrane. These cytological features were
similar to those of ordinary lobular carcinoma, but the size
of the nuclei was larger than that in ordinary lobular carci-
noma. Tumor cells having a smaller nucleus with condensed
chromatin were occasionally seen (Fig. 2). The nuclear
pleomorphismwas not obvious, and the mitotic figures were
less than one per several high-powerfields. Tumor cells were
separated from each other by hyalinous stroma producing a
scirrhous pattern, but also showed a focal, rather medullary
pattern with or without acinar structures. All three cases
showed invasion of the adipose tissue simulating chronic
fibrosing panniculitis, where the cancer cells were difficult to
recognize on HE-stained sections (Fig. 3a,b). The invasive
pattern was reminiscent of invasive lobular carcinoma with
targetoid and Indian file arrangements (Fig. 4a,b). Foci of in
situ lobular carcinoma and transitions from in situ to invasive
carcinoma were found in cases 1 and 3 (Fig. 5). Most tumor

Table 1 Clinicopathologicaldata of three cases of histiocytoidbreast carcinoma and three reference cases (RC) with focal histiocytoid features
Original Age (years) Menopausal Pathological Outcome
Case diagnosis at operation state Location Size (cm) stage* Operation /duration
Case 1 Histiocytoid ca. 55 Post Right lower 1.2 X 1.I t l nOMO stage 1 Lumpectomy Disease free 2 years
outer 9 months
Case 2 Pleomorphic 41 Pre Right upper 1.7 x 1.5 t l nOMO stage 1 Lumpectomy Disease free 5 years
lobular ca. outer 1 month
Case 3 Histiocytoid ca. 77 Post Right upper 2.0 x 2.0 t l nOMO stage 1 Lumpectomy Disease free 1 year
6 months
RC 1 Pleomorphic 43 Pre Right upper 4.0 x 4.0 t2nOMO stage 1 Patey's Disease free 6 years
lobular ca. outer mastectomy 11 months
RC 2 Pleomorphic 47 Pre Right upper 7.0 X 5.5 t3n3M1 stage 4 Patey's Dead with disease
lobular ca. medial mastectomyt 2 months
RC3 Apocrineca. 60 Post Left areolar 5.0 x 4.0 t3nOMO stage 2 Patey's Disease free 3 years
mastectomy 5 months
'According to the classificationof the Japanese Breast Cancer Society?'
+After1 year of chemotherapy.
Cases 1-3, pure histimytoid carcinoma; RC 1 and 2, pleomorphic lobular carcinoma with focal histiocytoidfeatures; RC 3, apocrine carcinoma with
focal histiocytoidfeatures. ca,Carcinoma.

Figure 1 Diffuse infiltration of histiocytoid breast cancer cells (case
3). The nuclei are uniformly small and the cytoplasmic border is
indistinct. Note the intact tubulus.
Figure 3 Invasion of histiocytoid cancer cells in the adipose tissue. (a) Cancer cells are hardly recognized by the HE stain in this low-power
view (case 1). (b)lmmunostainingfor cytokeratin clearly demonstrates these cancer cells (the same site as a).
cells showed granular cytoplasmic positivity for PAS reaction
regardless of prior diastase digestion (Fig. 6). Apart from ICL,
alcian blue staining was only weakly positive in cases 1 and
2, and was diffusely positive in case 3. The lipid stainings
were negative overall, except for only a few cells with weak
positivity in case 1 (Table 2).
lmmunohistochemicalfindings for puretype
histiocytoid breast carcinoma
The tumor cells were positive for EMA and cytokeratins but
negative for vimentin and desmin. Gross cystic disease fluid
protein-15 was diffusely positive in the cytoplasm as granular
Histiocytoid breast carcinoma 551
Figure 2 High-power view of histiocytoid cells. The nuclei are
round to Ovalwith very fine a thin nuclear membrane and
a msinophilic
products in all three cases (Fig. 7). Lactalbumin was mostly
negative. Estrogen receptor was positive in case 2, in which
biochemical assays of ER (25 fmoWmg) and progesterone
receptor (PgR; 109 fmol/mg) were also positive. c-erbs2 was
negative in all cases, and p53 was weakly positive (less than
10%) only in case 3. Carcinoembryonic antigen was positive
in case 3 (Table 2).
Electron microscopicfindings for pure-type histiocytoid
breast carcinoma
The tumor cells were surrounded by densely packed collagen
fibers, and the junctional apparata were very poorly devel-
552 S.Shimizu eta/.

Figure 4 Cancer invasion similar to invasive lobular carcinoma. (a) Scirrhous invasion with Indian file arrangements (case 2). (b) Cancer
invasion around a small tubulus showing a targetoid pattern (case 3; cytokeratin).

Agum 5 An in situ focus suggesting a transition to invasive Figure 6 Granular cytoplasmic positivity for periodic acid-Schiff
histiocytoid carcinoma. (PAS) reaction in the histiocytoid cells (case 2; PAS after diastase
digestion).

Table 2 Results of histochemical and immunohistochemical stainings in three cases of histiocytoid breast carcinoma and three reference
cases (RC) with focal histiocytoid features
PAS D-PAS Alcian blue Lipid stain GCDFP-15 Lactalbumin ER Cvtokeratin CEA ~ 5 3 c-erbB-2 Ki-67 (%)
Case 1 + + + 10
Case 2 + + + 10
Case 3 + + + + + - 5
RC 1 H + + ND - 2 - 30
PL + + + ND - + - 30
RCPH + + + ND + + + 30
PL + + + ND + + + 40
RC3H * -c + ND 20
A + 2 ND 40
Cases 1-3, pure histiocytoidcarcinoma; RC 1 and RC 2, pleomorphic lobular carcinomawith focal histiocytoidfeatures; RC 3, apocrine carcinoma with
focal histiocytoid features; H,histiocytoid cells; PL. pleomorphic lobular carcinoma cells; A, apocrine carcinoma cells; D-PAS, diastase periodic acid-
Schiff; (+) diffusely positive; ( % ) focally positive; (-) negative; ND. not done; ER. estrogen receptor:CEA. carcinoembryonic antigen; GCDFP-15. gross
cystic disease fluid protein 15.
 Histiocytoid breast carcinoma 553

oped. The nuclei were round to oval with fine chromatin, a

thin nuclear membrane and a small round nucleolus (Fig.
8a), but cells with slightly irregular nuclei with coarsely con-
densate perinuclear chromatin were occasionally seen (Fig.
8b). The cytoplasm was abundant, but the organellas were
poorly developed with small numbers of mitochondria,
several lysosomes and Golgi apparatus. Membrane-bound
granules of diverse electron densities varying in size
(300 to 800 nm in diameter) were observed, and the rough
endoplasmic reticulum was scattered, often adjacent to these
granules or the Golgi apparatus. Glycogen granules were
scanty (Fig. 8a,b).

Cytological findings for pure-type histiocytoid breast

carcinoma
Figure 7 Most histiocytoid cells show granular cytoplasmic
positivity for gross cystic disease fluid protein (GCDFP)-15. Note a in all three pure-type HBC cases, the aspirates contained a
strongly positive cell also in the nest of in situ lobular carcinoma
(case 3; GCDFP-15).
few scattered tumor cells or sheet-like small-cell clusters
showing a histiocytoid appearance due to the rich and

Figure 8 Electron microscopicfeatures of histiocytoidcells of (a) case 1 and (b)case 3 showing many membrane-boundgranules of varying
electron density in the abundant cytoplasm. Most of them are similar to apocrine granules. The other organelles are poorly developed. The
nucleus in a has euchromatin. but those in b are rich in heterochromatin.which corresponds to the dark nuclei observed under light microscopy.
Bar = 2pm.
554 S. Shimizu era/.
Figure 9 Aspirates from the lesions of case 1 contain a few
histiocytoid cells as single cells or small cell clusters. These cells are
easily overlooked as benign cells unless the examiner is familiar with
the histiocytoid breast cancer variant.
granular pale cytoplasm and the low N : C ratio of the tumor
cells. lntracytoplasmic luminae were seldom seen. The cell
border was indistinct and occasionally shaggy. The nuclei
were located usually eccentrically and possessed either pale
or condensed chromatin. A single small nucleolus was visible
in each nucleus with a pale chromatin pattern (Fig. 9). The
aspirates also contained a few non-neoplastic duct epithelial
cells and small lymphocytes.
Findings for combined-type histiocytoid breast
carcinoma
In the three cases of combined HBC, the histological
appearance of the portion of histiocytoid cells was very
similar to that seen in the three cases of pure HBC. The
growth pattern was characterizedby scirrhous invasion. The
features of invasive lobular carcinoma with occasional
targetoid and Indian file arrangements were seen in two
cases of combined histiocytoid and pleomorphic lobular
carcinoma, but the other case of combined histiocytoid and
apocrine carcinoma lacked the targetoid pattern and typical
Indian file arrangements, even at the site with histiocytoid
features. In all of the combined cases, the portions of
invasion of the adipose tissue by histiocytoid cells were
similar to chronic fibrosing panniculitis. The appearance of
the cytoplasms was identical to that seen in the pure-type
HBC specimens. However, the nuclei of the histiocytoidcells
in the combined cases tended to be larger and more irregular
in shape than those of the pure-typecases. The PAS reaction
showed diastase-resistant granular positivity in the cyto-
plasm of the histiocytoid cancer cells, but was weaker in the
combined cases than in the pure-type cases. The portions of
pleomorphic lobular carcinoma showed diffuse and strong
positivity for the PAS reaction only in ICL, and those of
apocrine carcinoma tended to be only sporadic. Alcian blue
staining was positive in RC 2 and RC 3, but negative in RC 1.
Gross cystic disease fluid protein-15 was diffusely positive in
the cytoplasm of histiocytoid cancer cells in all three com-
bined cases. The portions of pleomorphic lobular carcinoma
histology in RC 1 and 2 showed irregular positivity for
GCDFP-15, while apocrine cancer cells in RC 3 were stained
very strongly. Estrogen receptor was positive in two cases
(RC 1 and RC 3). p53 was weakly positive in two cases (RC 1
and RC 2). Both c - e m - 2 and CEA were positive in one case
(RC 2; Table 2).
Other variants of breast carcinoma and benign lesions
mimicking histiocytoid breast carcinoma
Cases of both malignant and benign breast lesions
resembling histiocytoid carcinoma in HE specimens were
selected for the study of differential diagnosis. Clear cell
(glycogen-rich) carcinoma was easily differentiated by
abundant PAS-positive granules which were digested by
diastase pretreatment. The lipid-rich (secreting) carcinoma
and secretory (juvenile) carcinoma were negative for
GCDFP-15; this finding is very useful for the differential
diagnosis when the materialfor lipid staining is not available.
The signet ring cell carcinoma showed diffuse cytoplasmic
positivity for PAS reaction instead of the granular positivity
seen in the histiocytoidcarcinomas. The granular cell tumor,
xanthogranuloma and sclerosing mastitis could be differen-
tiated by negative immunostainings for epithelial markers
(cytokeratins and EMA), but they were also negative for
GCDFP-15. Thus, PAS reaction with or without prior diastase
digestion and immunohistochemistry for GCDFP-15 seemed
to be sufficient for the differentiation of every breast lesion
examined mimicking histiocytoidcarcinoma of the breast on
HE stain.
DISCUSSION
The tumor cells of HBC are characterized by fine granular to
vesicular cytoplasm and a round to oval nucleus with a low
N : C ratio, and should be differentiated from those of clear
cell (glycogen-rich) carcinoma, lipid-rich (secreting) carci-
noma and secretory carcinoma. Strong GCDFP-15, an estab-
lished apocrine marker,I3and diffuse diastase-resistant PAS
positivitieswere very useful for distinguishing HBC from these
tumor cells. The tumor cells of HBC also resemble reactive
histiocytes, particularly in the area of scirrhous invasion and
invasion of adipose tissue. In fact, several of the reported

cases of histiocytoidcarcinomawere originally misdiagnosed
as chronic sclerosing inflammati~n,'-~ the late stage of chronic
periductal mastitis," xanthogranulomatous lesions,' or gran-
ular cell tumor.' The immunohistochemistry using cytoker-
atins and EMA was essential to the differentiation between
HBC and these benign lesions, but they were also differenti-
ated by negative staining for GCDFP-15.
As for the differentiation phenotype of histiocytoid tumor
cells, apocrine metaplasia has been considered. In 1980,
Mossler et a/. noted a pale granular cytoplasmic change
(histiocytoidchange) in apocrine ~arcinorna.'~ A histiocytoid
breast carcinoma case reported by Eisenberg et a/.4and two
cases described by Walford and Velden' were designated as
apocrine variants of lobular carcinoma. Eusebi eta/. recently
examined thirteen cases and demonstrated the apocrine
characteristics immunohistochemically as well as by in situ
hybridization and northern blotting for GCDFP-15.5 All of
the reported cases studied by immunohistochemistry for
GCDFP-15 expression were found to be p ~ s i t i v e ~as ~ ~ . ~cells
were the three cases reported here. Granular positivity for
GCDFP-15 was characteristic in our cases. The electron
microscopic study of our two cases (cases 1 and 3)showed
intracytoplasmic membrane-bound granules similar to
apocrine g r a n ~ l e s . ' ~ ~ ' ~ ~ ' ~ ~ ' ~
Most of the above authors postulated a lobular origin of
HBC. Filotico et a/L6 Walford and Velden,g Remadi and
Chappuis' and the present authors7described the presence
of in situ lobular carcinoma foci with a transition from in sit0
lesion to invasive histiocytoid carcinoma. Since Dixon et a/.'6 cellular and histological appearances similar to those of
introduced a pleomorphic lobular carcinoma as a subtype of
invasive lobular carcinoma in 1982, histiocytoid carcinoma
has been regarded as closely related to or identical to
pleomorphic lobular carcinoma." To the contrary, Eusebi et
a/. in 1995 reported, in addition to four cases of lobular origin,
nine cases of ductal origin including two cases of mixed
ductal and lobular origin and one case of intraductal
carcinoma composed of histiocytoid tumor c e k 5 They
collected their cases based on the granular to foamy
appearance of tumor cell cytoplasm. They demonstrated
apocrine differentiation in all of the cases and designated
them as a specific group of apocrine carcinoma of both ductal
and lobular origins. The pure ductal features of histiocytoid diagnosis or misinterpreting the hi~todiagnosis.6.~
carcinoma among their cases were unique findings, because
histiocytoid carcinoma had been regarded as a variant of
invasive lobular carcinoma (especially the pleomorphic type)
with apocrine metaplasia prior to publication of their article.
Therefore, the diagnostic criteria of histiocytoid carcinoma
must now be settled again in order to test whether histiocytoid
carcinoma stands as a distinct variant of metaplastic breast
carcinoma, a variant of apocrine carcinoma, or a variant of
invasive lobular carcinoma.
In the present study, we histopathologically examined
three cases of pure histiocytoid carcinoma of lobular origin
Histiocytoid breast carcinoma 555
and three combined cases (two pleomorphic lobular carcino-
mas and one apocrine carcinoma) with focal histiocytoid
features. The common histological characteristics of these
tumors were: (i) histiocytoid appearance of the tumor cells
on HE staining; (ii) diastase-resistant granular cytoplasmic
positivity for PAS reaction; and (iii) diffusegranular cytoplas-
mic positivity for GCDFP-15. We thus propose the above
three findings as the diagnostic criteria for histiocytoid carci-
noma, regardless of its origin (ductal or lobular) and whether
the tumor is invasive or not. Combined cases like our refer-
ence cases should be classified into the basic histological
types with the additional comment of focal histiocytoid fea-
tures. In addition, the term 'histiocytoid' should not be used to
describe breast cancers verified to be other than histiocytoid
carcinoma, such as clear cell carcinoma or lipid-secreting
carcinoma.i8 Differential diagnoses from all breast lesions
resembling histiocytoid carcinoma are possible and not
difficult when these criteria are applied. However, histiocytoid
~ ' ~ as well as the cancer cells of basic histology in
pleomorphic lobular carcinoma (RC 1 and RC 2) and
apocrine carcinoma (RC 3)showed stain characteristics very
similar to those of pure histiocytoid carcinoma, although the
intensity was weaker than that of the pure type. This may
indicate the close relationship of histiocytoid carcinoma to
both pleomorphic lobular carcinoma and apocrine carcinoma.
Hence, we propose that histiocytoid breast carcinoma is
basically a variant of pleomorphic lobular carcinoma with
apocrine metaplasia, and that apocrine carcinoma may show
histiocytoidcarcinoma of lobular origin.
The incidence of HBC has not yet been established, but
may be higher than hitherto estimated from the reported
case numbers. In fact, our present study revealed as many
as three cases among 1010 operated breast cancers at our
hospital (0.3%).
The aspiration cytology of HBC is characterized by a
paucity of cancer cells and benign-looking cytology, and is,
therefore, quite difficult to correctly diagnose. The scirrhous
invasive pattern of HBC may reflect the small number of
aspirated cancer cells. It should be stressed that this variant
must be kept in mind to avoid overlooking it in the cyto-
The prognosis of HBC has been considered poor since
Hood ef a/.' reported eyelid metastasis in all eight cases
examined, as well as in a case reported by Dabski et aL3 In
addition, Allenby and Chowdhuty2 reported an autopsy case
with systemic cancer metastasis. The prognosis of pleomor-
phic lobular carcinoma is also regarded as poor compared
to classical lobular car~ i noma.' ~Given ~ that histiocytoid
carcinoma is a variant of pleomorphc lobular carcinoma, the
poor prognosis may, thus, be accurate. However, the prog-
nosis of apocrine carcinoma is still controversial, reportedto
be both equa12'.p and p00P.~' compared to the ordinary
556 S. Shimizu et al.
invasive ductal carcinomas. The three cases of pure histio-
cytoid carcinoma presented here were in stage 1 without
metastasis at surgery, and are recurrence free to date,
although the follow-up period may be short. The pathological
prognostic factors for breast cancer in these three cases
were relatively similar, with a few exceptions. The pathologi-
cal grade of these cases according to Bloom and Richard-
son's criteria was intermediatewith moderate nuclear grade,
low mitotic activity and a dissociated cellular pattern.=
Estrogen receptor and PgR were positive in one case (case
2): the c-erbl32 and p53 immunostainings, the positivity of
which is considered to relate to poor prognosis in breast
cancer,%were negative except for p53 in case 3. The Ki-67
labeling indexes of the pure histiocytoid carcinomas were
lower than those of the combined cases. and the labeling
index of the histiocytoidcells in the combinedcases tendedto
be lower than the cancer cells showing the features of
pleomorphic lobular or apocrine carcinoma. Thus, the
prognosis of histiocytoid carcinoma will not always be poor
and may depend mainly on the stage, as with ordinary breast
carcinomas. We suggest that the three criteria described
above are the proper diagnostic criteria of histiocytoid breast
carcinoma, and we propose that HBC be established as
a distinct variant of breast carcinoma, in order to avoid
misdiagnosis.
ACKNOWLEDGMENTS
The authors thank Professor Hitoshi Kitamura, Yokohama
City University School of Medicine, for reviewing this manu-
script, and Hiroki lmai for his excellent technical assistance
and secretarial help.
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