Case 5 -

Sclerosed Papilloma and Usual Hyperplasia Without Atypia Jean F. Simpson, Vanderbilt Univ Med Ctr, Nashville, TN

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Clinical History 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 Differential Diagnoses: 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. Final Diagnosis: Sclerosed Papilloma and Usual Hyperplasia Without Atypia Case Discussion: 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) [1] 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 [2, 3, 4]. Their presence may be helpful, but occasionally in sclerotic lesions they may be reduced in number or staining intensity [5, 6]. 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 [7]. 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 [3]. A rare but important consequence of sclerotic papillomas is the development of a low-grade metaplastic spindle cell carcinoma [8]. 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 [8]. It is not uncommon for the correct diagnosis to be reached only after one or more recurrence [8]. Conclusion(s): 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. References: 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.