Case Reports
Squamous Metaplasia of the Breast
An Ultrastructural and Immunologic Evaluation
ROBERT L. REDDICK, M.D., J. CHARLES JENNETTE, M.D., AND FREDERIC B. ASKIN, M.D.
Squamous metaplasia in the breast is rare. This case of an intracystic papilloma of the breast with prominent squamous
change was found by electron microscopy and immunohistochemistry to contain evidence of squamous differentiation within
myoepithelial cells. The findings suggest that squamous metaplasia of the breast may result from myoepithelial cell differentiation in a manner analogous to the development of squamous
lesions in the cervix and salivary gland. The possible relationship
of this finding to the development of squamous lesions of the
breast is discussed. (Key words: Breast; Squamous metaplasia;
Myoepithelial cell) Am J Clin Pathol 1985; 84: 530-533
SQUAMOUS METAPLASIA and squamous cell carcinoma of the breast represent uncommon histopathologic
findings in breast lesions.'• 3 ' 6 ' 8 ' 314 Squamous metaplasia
was reported by Fisher and colleagues7 in only 3.6% of
1,000 cases of invasive breast carcinoma. Soderstrom and
Toikkanen 14 recently reported a single case of extensive
squamous metaplasia that was present in papillomatosis
of the breast. The recently described spindle cell carcinoma of the breast also may contain areas of squamous
metaplasia and squamous cell carcinoma.2'9
This study will report the ultrastructural and immunohistochemical findings in one case of florid squamous
metaplasia of the breast that was present within an intracystic papilloma and comment on the possible role of the
myoepithelial cell in the genesis of squamous transformation in breast tissue. These findings may give insight
into the development of squamous cell carcinoma and
mucoepidermoid carcinoma of the breast.
Report of a Case
The patient was a 37-year-old woman with a lesion in the right breast.
The mass had been present for 20 months. She was initially evaluated
Received October 16, 1984; received revised manuscript and accepted
for publication April 18, 1985.
Address reprint requests to Dr. Reddick: Brinkhous-Bullitt Building
228H, University of North Carolina School of Medicine, Chapel Hill,
North Carolina 27514.
Division of Surgical Pathology, University of North Carolina
School of Medicine, Division of Surgical Pathology,
Chapel Hill, North Carolina
at her local hospital. At that time, mammography was reported to show
the pattern offibrocysticdisease. She returned nine months later for
repeat examination and was found to have a 2-3-cm nodular density in
the upper outer quadrant of the right breast. Malignant change could
not be excluded. No further procedures were performed at that time.
Nine months later, xeromammography again showed a 2.5-3-cm welldefined breast mass with focal calcification at the periphery.
She was then referred to North Carolina Memorial Hospital for further
evaluation. On physical examination, she was found to have a firm but
movable 4 X 7 cm mass in the right breast just above the nipple. The
area was not tender, and there was no skin dimpling or nipple discharge.
There was no evidence of axillary or supraclavicular adenopathy. Aspiration cytology was performed. The cytologic findings consisted of
apocrine metaplasia, hyperplastic ductal epithelium, and foam cells consistent with a diagnosis offibrocysticdisease. The patient underwent
resection of the mass. On gross examination this was a 3.5 X 3.5 X 2
cm intracystic papilloma (Fig. 1).
Materials and Methods
Multiple sections of the resected lesion were taken immediately after resection for light and electron microscopy. Tissue for light microscopy was placed in 10% buffered formalin. Tissue for electron microscopy was minced
into small cubes and placed in 4% phosphate-buffered
formalin, pH 7.4. The samples for electron microscopy
were processed according to standard technics. Ten percent formalin-fixed tissues for light microscopy were
embedded in paraffin and stained initially with hematoxylin and eosin. Selected slides were stained with mucicarmine for evidence of mucin production.
Materials for immunohistochemical staining were derived from paraffin-embedded tissues. The slides were
stained by a peroxidase-anti-peroxidase immunoenzyme
method using commercially available kits for keratin,
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531
carcinoembryonic antigen (CEA), and human chorionic
gonadotropin (HCG). Positive and negative control sections stained appropriately.
Results
On light microscopy, an intracystic papillary lesion with
prominent areas of squamous metaplasia was present (Fig.
2). The entire lesion was surrounded by a dense fibrous
capsule. Most of the tumor consisted of solid areas of
squamous cells that had brightly eosinophilic cytoplasm
and evidence of intercytoplasmic interdigitations. The
nuclei were round to oval and often had a single prominent nucleolus. In some locations, keratohyaline granules
could be found. Glandular lumina containing mucinpositive material were admixed within these areas. In some
areas, definite metaplastic transitions could be found
within glands (Fig. 3). Within nonmetaplastic portions of
the glands, myoepithelial cells with clear nuclei could be
found. The remainder of the resected breast tissue showed
evidence of fibrocystic changes. Both epithelial and myoepithelial cells were clearly seen in these glands. Inflammatory cells were sparse.
Areas selected for electron microscopy contained admixtures of both normal and metaplastic tissues. In some
areas, typical myoepithelial cells were present. These cells
contained longitudinally arranged cytoplasmic microfilaments. Focal dense condensations were present at intervals along the filaments. These cells were bordered by a
single or reduplicated basement membrane. Cells with
features of myoepithelial cells that contained keratin fibrils
occasionally were present (Fig. 4). Other myoepithelial
cells showed total loss of the filamentous arrangements
normally present within the cytoplasm. A basement
membrane was present adjacent to these cells in some
areas. The overlying glandular epithelium could easily be
distinguished from the myoepithelial cells and did not
contain cytoplasmic tonofilaments. The nuclei of the epithelial cells were oval to spindle shaped and had finely
granular nuclear chromatin. A prominent nucleolus was
present in most nuclei. The cytoplasm contained lysosomes, occasional small fat droplets, and nondilated profiles of rough endoplasmic reticulum. Occasional cells had
prominent glycogen granules. These epithelial cells were
joined by well-formed desmosomes to the myoepithelial
cells and to adjacent epithelial cells. The luminal surface
of the epithelial cells were bordered by thin, short microvilli.
Immunohistochemical staining for keratin demonstrated strong positivity in solid areas of squamous metaplasia. Within a few small glands away from the intracystic
papilloma, definite staining of the basal layer of cells could
be seen. In these glands, the epithelial cells adjacent to
the lumen did not stain for keratin. This pattern of basal
FIG. 1. The gross appearance of the resected lesion was that of a cystic
mass surrounded by a dense capsule. Hematoxylin and eosin (X165).
cell staining was present not only in small glands but aiso
in cystically dilated glands (Fig. 5). The epithelial cells
lining the lumens of these glands did not stain for keratin,
however. Immunohistochemical staining for CEA showed
focal luminal positivity in a few areas. Staining for HCG
was negative.
Discussion
Breast lesions with evidence of squamous differentiation
are reportedly rare but have been described in association
with infarction, 614 with fibroadenoma,13 as spindle cell
lesions with evidence of squamous differentiation on light
and electron microscopy2,9 or as typical squamous cell
carcinomas.'- 38 In addition, tumors with the histologic
pattern of mucoepidermoid carcinomas also have been
described. 810 " In all of these studies, little attention has
been paid to the cell of origin. In most studies the lesions
have been considered to be derived from acinar epithelial
cells with little attention paid to an origin in either the
myoepithelial or ductal epithelial cell. Lesions of the breast
diagnosed as myoeipheliomas also have been described.515
In these lesions, the proliferating cell is considered to be
the myoepithelial cell. Erlandson and associates have
shown that myoepithelial cells in these lesions may show
evidence of squamous metaplasia.
The histologic findings obtained in this study are in
agreement with previous descriptions of squamous differentiation in papillary lesions of the breast.14 This study
utilized a combination of electron microscopic and immunohistochemical studies and has shown that meta-
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REDDICK, JENNETTE, AND ASKIN
A.J.C.P. • October 1985
Vol. 84 • No. 4
CASE REPORTS
533
FlG. 2 (upper, left). Low-power magnification showing prominent squamous change. Dilated acinar structures
are also present. Hematoxylin and eosin (XI65).
FIG. 3 (upper, right). A focal area of squamous metaplasia is present within a gland. Keratohyaline granules are present
in the solid area of metaplasia (arrow). Hematoxylin and eosin (X350).
FIG. 4 (lower, left). Myoepithelial cell with both myoepithelial features (arrows) and bundles of tonofilaments (arrow heads) (XI 1,360).
FlG. 5 (lower, right). Immunohistochemical staining for keratin showing positive staining for basal cells and
not luminal epithelial cells (arrows). Immunoperoxidase staining (X260).
plastic squamous change in the breast initially involved
the myoepithelial cell. In no areas did we find evidence
of prominent squamous differentiation of ductal epithelial
cells without concomitant changes in the myoepithelial
layer. The ultrastructural morphology of the myoepithelial
cells in this case are similar to those described by Erlandson and Rosen.5 In our case, as demonstrated by electron
microscopy, the myoepithelial cell cytoplasm contained
numerous tonofilaments. Basal lamina was variably present adjacent to these cells. On histochemical staining,
keratin was prominent in basally placed cells of the acini.
Toth15 described one case of benign myoepithelioma of
the breast. In that case and ours, the lesion was associated
with intraductal papillomatosis. Further, in our case
myoepithelial cells not present within the cystic lesion
also stained with antibodies to keratin.
Mucoepidermoid carcinoma of the breast has been described in several reports.8,'°'" As reported by Fisher and
colleagues,8 these tumors represent approximately 0.2%
of all breast carcinomas. The tumors described in that
report contained benign-appearing squamous epithelium
and tubuloductal or glandular structures. Mucin production was demonstrated in those tumors. Support for the
concept that metaplastic transformation may originate
from myoepithelial cells is supported by recent studies of
mucoepidermoid tumors of the salivary gland4 and cervix.12 In mucoepidermoid tumors of the salivary gland,
the squamoid elements were thought to arise from metaplastic transformation of myoepithelial cells or from cells
within intercalated ducts and in the cervix from totipotential reserve cells with the capacity to differentiate into
either squamous or mucin-producing columnar cells. The
results obtained from these studies and thefindingsin this
report may suggest an etiologic role for the myoepithelial
cell in the formation of squamous metaplasia, spindle cell
carcinomas, mucoepidermoid tumors, and typical squamous cell carcinomas of the breast. Thefindingsreported
in this study would suggest that squamous changes in the
breast initially begins within the myoepithelial cell layer
with progression that eventually involves the entire acinus.
The results further suggest that the process of squamous
change in the breast results from mechanisms similar to
those that result in metaplastic changes in other locations.
Further studies of the type reported here would help to
clarify the mechanism of squamous metaplasia in the
breast.
References
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