Case 5 -
Sclerosed Papilloma and Usual Hyperplasia Without Atypia
Jean F. Simpson, Vanderbilt Univ Med Ctr, Nashville, TN
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A 56 year-old woman underwent an excisional biopsy for a breast mass. One year
before, she had been diagnosed with high grade ductal carcinoma in situ in the ipsilateral breast. The
current specimen was described as having a gritty cut surface. Pathological/Microscopic Findings and any
Immunohistochemical or Other Studies: Histologic examination shows a vaguely nodular and irregular
proliferation of epithelium associated with a densely sclerotic central area. The central sclerotic area
contains entrapped epithelial nests, cords, and glandular structures. Larger epithelial nests are
present at the periphery. Closer examination shows an epithelial proliferation characterized by cellular
variability, nuclear overlap, and central secretions. In areas, the epithelial proliferation has an
intimate association with fibrotic stroma. Smaller nests and glandular structures are arranged in
roughly parallel arrays, encircling the sclerotic center, and not infiltrating into fat.
Case 5 - Figure 1
On low power, there is a nodular density with irregular placed epithelial nests and small glands.
Case 5 - Figure 2
Closer view of irregular glands in an infiltrative patter, as well as an expanded space with marked epithelial proliferation
Case 5 - Figure 3
Higher magnification view of the epithelial proliferation, including central secreted material
Case 5 - Figure 4
Compressed epithelial clusters and glands are present at the periphery of a fibrotic center. Note fibrovascular core associated with epithelial proliferation at the bottom right of the image
Case 5 - Figure 5
The epithelial cords and glandular structures are entrapped by the sclerotic center of the lesion
Case 5 - Figure 6
The epithelial proliferation is associated with a predominantly fibrous core
Case 5 - Figure 7
Entrapped glands maintain a parallel arrangement within the fibrous stroma
The differential diagnosis includes invasive carcinoma of no special type or with tubular features,
in association with ductal carcinoma in situ; radial scar or complex sclerosing lesion, and sclerotic
papilloma associated with usual hyperplasia.
Sclerosed Papilloma and Usual Hyperplasia Without Atypia
The key to recognizing the benign nature of this process is the lower power arrangement of entrapped
epithelial nests and small glands within a central sclerotic stroma. These glands are present in a
roughly parallel arrangement without infiltration into adjacent fat. The overall configuration is
lobulocentric, composed of a confluence of several adjacent lobular units. Within the center of this
lesion, as well as at the 4:00 o'clock position (and shown in image 6) is residual papilloma, an
important clue to recognizing the lesion as benign. The epithelial proliferation (image 3) shows nuclear
variability, cellular overlap, and central secretions (not necrosis), features of ordinary hyperplasia.
The most important differential diagnosis is invasive carcinoma.
Review of the Literature/Treatment Options (if applicable):
Sclerosed papillomas, also known as ductal adenomas when the sclerosing process creates
numerous small glandular structures)
 can mimic invasive carcinoma both
radiographically and histologically. Radiograpically, the central sclerotic center
is similar to a radial scar and may result in a nodular density or even spiculations on
imaging studies. The most important diagnostic consideration histologically is the
recognition that small glandular structures are entrapped in fibrous stroma, and
not infiltrating as in invasive carcinoma. Absence of irregularly placed glandular
structures in fat is a helpful feature in arriving at the correct diagnosis. The
low power configuration of sclerosing lesions is key to recognizing their
benignity. A careful search of the lesion usually reveals some remnant of an intraductal
papilloma, which lends assurance to a benign process. Often a
myoepithelial layer may be recognized at higher magnification, but the absence of these on
hematoxylin and eosin should not be used solely as evidence of malignancy.
Immunohistochemical studies have used a number of antibodies to highlight myoepithelial cells
with varying specificity and sensitivity, and these include smooth muscle actin,
calponin, smooth muscle myosin heavy chain, p63,CD10, cytokeratin 5/6 and p75
presence may be helpful, but occasionally in sclerotic lesions they may be reduced
in number or staining intensity
Moreover if the lesion has been previously
biopsied using a needle, MEC may not be well preserved due to disruption and reaction to the
procedure. The etiology of sclerosis in papillary lesions is
unknown, but may represent a reparative reaction following infarction of
fibrovascular cores. Often sclerotic papillomas are a component of complex sclerosing lesions
. Papillary lesions are usually not diagnostically
difficult, however the following scenerios may be challenging. Epithelial
proliferations within the papillary lesion may raise the possibility of atypical
ductal hyperplasia or even ductal carcinoma in situ, and this distinction may be
difficult on core biopsy. A prudent approach is to construct the pathology report in a
manner to guide the treating physician to excise the lesion for full
characterization. Another setting that may be challenging is examination of an excision
specimen containing a papillary lesion following needle biopsy. Displacement of
epithelium from the previous procedure can mimic invasion, but the presence of hemosiderin,
granulation tissue, and a linear array of displaced glands is useful in recognizing
this mimicker of invasion. Diagnostic and management issues of papillary lesions on
core biopsy as well as excision have been reviewed . A rare
but important consequence of sclerotic papillomas is the development of a low-grade
metaplastic spindle cell carcinoma . These metaplastic spindle cell carcinomas
may be misinterpreted as reactive stromal myofibroblastic proliferations. The correct
diagnosis requires recognizing increased numbers of plump, spindled cells which
express cytokeratins and p63 . It is not uncommon for the correct diagnosis to be reached
only after one or more recurrence .
Sclerosed papilloma of the breast may mimic invasive carcinoma, but recognizing the lobulocentric
nature of the lesion is key to achieving the correct diagnosis. Immunohistochemical studies highlighting
myoepithelial cells may be a useful adjunct in this setting.
- Azzopardi JG, Salm R. Ductal adenoma of the breast: a lesion which can mimic carcinoma. J Pathology 144:15-23; 1984.
- Moritani S, Kushima R, Sugihara H,Bamba M, Kobayashi TK, Hattori T. Availability of CD10 immunohistochemistry as a marker of breast myoepithelial cells on paraffin sections. Mod Pathol 15:397–405; 2002.
- Collins LC, Schnitt SJ. Papillary lesions of the breast: selected diagnostic and management issues. Histopathology 52:20-9; 2008.
- Werling RW, Hwang H, Yaziji H, Gown AM. Immunohistochemical distinction of invasive from noninvasive breast lesions: a comparative study of p63 versus calponin and smooth muscle myosin heavy chain. Am J Surg Pathol 27:82-90; 2003.
- Hilson JB, Schnitt SJ, Collins LC. Phenotypic alterations in myoepithelial cells associated with benign sclerosing lesions of the breast. Am J Surg Pathol 34:896-900; 2010.
- Hilson JB, Schnitt SJ, Collins LC. Phenotypic alterations in ductal carcinoma in situ-associated myoepithelial cells: biologic and diagnostic implications. Am J Surg Pathol 33:227-32; 2009.
- Sanders ME, Page DL, Simpson JF, Schuyler PA, Dale Plummer W, Dupont WD. Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies. Cancer 106:1453-61; 2006.
- Gobbi H, Simpson JF, Jensen RA, Olson SJ, Page DL. Metaplastic spindle cell breast tumors arising within papillomas, complex sclerosing lesions, and nipple adenomas. Mod Pathol 16:893-901; 2003.