adenomyoepithelioma of the breast misdiagnosed as invasive ductal

INTRODUCTION

Myoepithelial cells are normally present inthe breast localized between epithelial cells andthe basal lamina of secretory elements of the

mammary duct system (1,2). Tumors derivedfrom these cells have been described in skin, sa-livary glands, breast and lungs (1,2). Adenom-yoepithelioma (AME) of the breast is a rare le-sion, and usually affects adult female patients(1,2). Rare cases have been described in males(3,4). It usually presents as a palpable nodule,ranging from 0.5 cm to 7 cm at its greatest di-ameter (1,2). AME has a bicellular pattern con-sisting of epithelial and myoepithelial cells,

ABSTRACT

The consultation material of total mastectomy and axil-lary lymph node dissection specimens taken from a 34-year-old female with a previous diagnosis of invasiveductal carcinoma was evaluated. Microscopic examina-tion of the 6,5 cm well-circumscribed tumor revealedrounded tubules lined by both epithelial and myoepit-helial cells in a myxomatous stroma. Obvious smoothmuscle differentiation and area of fibroadenoma werealso noted. Immunohistochemically, myoepithelial cellsand cells with smooth muscle differentiation exhibitedvimentin and smooth muscle actin. Myoepithelial cellswere also reactive for S100 protein and epithelial mem-brane antigen. Luminal epithelial cells revealed positivereaction for epithelial membrane antigen and pan-cyto-keratin (AE1/AE3), but displayed only focal stainingwith carcinoembryonic antigen. Based on these findingsa final diagnosis of adenomyoepithelioma was made.Differential diagnosis of adenomyoepithelioma from itsmalignant counterpart and invasive ductal carcinomamay occasionally be challenging. Moreover, althoughconsidered an indolent neoplasm but with a potentialrisk for recurrence and sometimes metastasis, adenom-yoepithelioma of the breast requires long-term follow-up.

Key words: Adenomyoepithelioma, breast, benign, ma-lign

ÖZET

Bir baflka merkezde invaziv duktal karsinom tan›s› alan34 yafl›ndaki kad›n hastan›n total mastektomi ve aksil-ler lenf nodu diseksiyonunu içeren konsültasyon mater-yali de¤erlendirilmifltir. Mastektomi materyalinde sap-tanan 6,5 cm boyutundaki düzgün s›n›rl› kitlenin mik-roskobik incelemesinde, mikzoid stromada epiteliyal vemyoepiteliyal hücreler ile döfleli tübül yap›lar› izlenmifl,belirgin düz kas diferansiyasyonu ve bir alanda fibro-adenom oda¤› dikkati çekmifltir. ‹mmünhistokimyasalolarak, myoepiteliyal ve düz kas diferansiyasyonu izle-nen hücrelerde vimentin ve düz kas aktini ile, miyoepi-teliyal hücrelerde ise S100 proteini ve epitelyal mem-brane antijeni ile reaksiyon belirlenmifltir. Lüminal epi-telyal hücrelerde epitelyal membran antijeni, pan-sito-keratin (AE1/AE3) ve fokal olarak karsinoembriyonikantijen ile reaksiyon gözlenmifltir. Olguya adenomiyo-epiteliyoma tan›s› verilmifltir. Adenomiyoepiteliyomay›,malign eflde¤eri ve invaziv duktal karsinomdan ay›rt et-mek zor olabilir. Ayr›ca, benign bir tümör oldu¤u düflü-nülse de, rekürrens ve nadiren metastaz yapabilme ka-pasitesinden dolay›, olgular uzun süre takip edilmeli-dir.

Anahtar sözcükler: Adenomiyoepiteliyoma, meme, be-nign, malign

Adenomyoepithelioma of the breast misdiagnosed as invasive ductal carcinoma

‹nvaziv duktal karsinom olarak hatal› tan› alan memenin adenomiyoepiteliyomas›

Sibel BEKTAfi, Burak BAHADIR, Banu DO⁄AN GÜN, Sacide ÇOLAK, fiükrü O¤uz ÖZDAMAR

Department of Pathology, Zonguldak Karaelmas University, Faculty of Medicine, ZONGULDAK

This case report was presented during 2nd Inter-Congress of theEuropean Society of Pathology in Ioannina, Greece at 23-27 May2006, as a poster presentation.

Corresponding Author: Sibel Bektas, M.D. Department ofPathology, Zonguldak Karaelmas University, Faculty ofMedicine, 67600, Kozlu, Zonguldak

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Turkish Journal of Pathology 2007;23(2):116-120

which are regularly distributed in the tubularstructures, based on peculiar histological and ul-trastructural features of the lesion. AME is con-sidered to be a benign or a low grade malignantlesion, and carcinoma arising in an AME of thebreast is a rare entity (1,2,5). The morphologicappearance of this tumor varies, leading to erro-neous diagnoses of other types of benign oreven malignant lesions. The tumor has a poten-tial for local recurrence, therefore, wide excisi-on is recommended for proper diagnosis and tre-atment (1,2,6). We report a case of adenomyo-epithelioma in the breast formerly diagnosed asan invasive ductal carcinoma.

CASE REPORT

The consultation material containing totalmastectomy and axillary lymph node dissectionspecimens from a 34-year-old female which hadbeen previously diagnosed as invasive ductalcarcinoma was reevaluated. Gross examinationrevealed a well-circumscribed, mobile and yel-lowish, solid nodule, measuring 6.5x6x4 cm insize (Figure 1). Histopathologically, the tumorwas well demarcated from the surrounding bre-ast tissue through a thin fibrous capsule. The tu-mor was composed of rounded tubules lined byboth epithelial and myoepithelial cells within amyxomatous stroma (Figure 2). Obvious smo-oth muscle differentiation and area of fibroade-

nomatous lesions were also noted (Figure 3 and4). Prominent myoepithelial hyperplasia resul-ting in obliteration of some of the tubular lu-mens was present in areas with rounded tubules.

Figure 1. Gross appearance of the tumor; well-circumscribedtumor surrounded by a thin capsule.

Figure 2. Irregular small glandular structures (HE x200).

Figure 3. Prominent smooth muscle differentiation (HE x200).

Figure 4. Fibroadenomatous area within the adenomyoepithe-lioma (HE x100).

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The epithelial cells had flattened or cuboidalconfiguration with pink cytoplasm. They werelocated toward the center of the glands, some of

which displayed apocrine metaplasia. The myo-epithelial cells were round or polygonal withclear or eosinophilic cytoplasm. Occasional so-lid areas exclusively composed of myoepithelialcells were also found. Epithelial cells had mini-mal cytologic atypia, but the myoepithelial cellshad neither cytologic atypia nor pleomorphism.The mitotic index was less than three in 10 highpower fields (HPFs) for both elements. Apocri-ne metaplasia and myoepithelial cell proliferati-on involving the ducts were seen within the sur-rounding breast tissue. Immunostaining wasperformed using antibodies against epithelialand myoepithelial markers, including pan-cyto-keratin (AE1/AE3), epithelial membrane anti-gen (EMA) (Figure 5), carcinoembryonic anti-gen (CEA), vimentin, smooth muscle actin(SMA) (Figure 6), S100 protein, estrogen recep-tor (ER) (Figure 7), progesterone receptor (PR)and Ki-67. Table 1 summarizes the immunohis-tochemical findings. The Ki-67 labeling indexfor epithelial and myoepithelial cells were 0.007and 0.012. The axillary lymph nodes were freeof tumor. A final diagnosis of adenomyoepithe-lioma was made. The patient has been well wit-hout any recurrences or metastases in 22 monthsof follow-up.

Figure 5. Strong staining for EMA in the epithelial andmyoepithelial cells (B-SA, DAB x200).

Figure 6. SMA decorated the outer myoepithelial layer (B-SA,DAB x200).

Figure 7. Estrogen receptor expression in the inner epitheliallayer (B-SA, DAB x400).

Table 1. Adenomyoepithelioma of the breast; immunohisto-chemical findings.

Antibody

Pan-cytokeratin(AE1/AE3)EMACEAVimentinSMAS100 proteinERPR

Inner Cells

Positive

PositivePositiveNegativeNegativeNegativePositivePositive

Outer Cells

Negative

PositiveNegativePositivePositivePositiveNegativeNegative

Cells withSmooth MuscleDifferentiation

Negative

NegativeNegativePositivePositiveNegativeNegativeNegative

EMA: Epithelial membrane antigen, CEA: Carcinoembryonic an-tigen, SMA: Smooth muscle actin, ER: Estrogen receptor, PR:Progesterone receptor.

Glandular Areas

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DISCUSSION

Adenomyoepithelioma (AME) of the bre-ast is an uncommon disorder characterized bythe simultaneous proliferation of ductal epitheli-um and myoepithelial cells (1,2,6). The occur-rence of AME in the breast was first describedand illustrated by Hamperl in 1970 (7). Bult etal. (8) has reported 125 adenomyoepitheliomasup to year 2001 in the literature including be-nign and malign cases in their review article.Afterwards 78 additional adenomyoepitheliomacases were reported in the literature. Histogene-sis of this tumor has been remained unclear, butit has been suggested that AME derives frommyoepithelial overgrowth from long-standingadenosis, fibroadenoma, or other benign breastlesions (6). Tavassoli (2) proposed a classifica-tion system of myoepithelial lesions of the bre-ast, dividing them into three types as myoepithe-liosis, adenomyoepithelioma and malignantmyoepithelioma. AME is subdivided into foursubtypes as spindle cell, tubular, lobulated andcarcinoma arising in adenomyoepithelioma.Combinations of growth patterns sometimesexist (1,2,9). Presented case has been classifiedas a tubular subtype. These different histologi-cal types behave differently both in clinical pre-sentation and follow-up (1,2,9). Tubular vari-ants and some lobuler tumors with high mitoticactivity are particularly prone to local recurren-ce (2).

The majority of AMEs is grossly well cir-cumscribed and they can even be encapsulated.However, AMEs may have lobulated, somewhatirregular appearance which may grossly mimicmalignancy (10). The typical histologic appe-arance of an AME consists of acinar structurescomposed of an inner layer of epithelial cellswith eosinophilic cytoplasm and a prominentperipheral layer of myoepithelial cells with cle-ar cytoplasm (1,2). Minimal pleomorphism andlow mitotic rate (usually less than 3 mitotic fi-gures per 10 HPFs), as noted in this case, maybe seen in both elements (11). Moreover, focal

apocrine, squamous, mucinous, sebaceous oreven chondroid and oseeous metaplasia may beencountered (1,2,9,12). Coexistent areas of fib-roadenoma in this case support the hypothesisthat myoepithelial overgrowth from benign bre-ast lesions give rise to AME, and as might beexpected smooth muscle differentiation may beencountered. Immunohistochemically, consis-tent with the current case, myoepithelial cellsexhibit positive reactions for SMA, smoothmuscle myosin, vimentin, EMA, cytokeratin 14,S100 protein, calponin and p63, while the lumi-nal epithelial cells are strongly positive for cyto-keratin, EMA and CEA. Contrary to normalmyoepithelial cells, luminal cells possess recep-tors for ovarian steroid hormones and activelycycle in response to hormonal levels, howevertheir growth regulation is largely unknown(1,2,11-14). On the other hand, AME’s resemb-lance to usual ductal carcinoma -not uncom-monly and as noted in the current case- and dif-ferentiation from its malignant counterparts arethe most challenging issues complicating the di-agnosis. In these circumstances, careful exami-nation for myoepithelial differentiation verifiedby immunohistochemistry may be helpful.

AME is regarded as either a benign or alow-grade malignant lesion. The biologic beha-vior of AME still remains uncertain. In fact thepresence of two-cell lineages alone is of no helpin differentiating benign from malignant AME.Although high mitotic activity, cellular pleo-morphism, high cellularity, necrosis, reactivestromal response (desmoplasia) and infiltrating(rather than pushing) borders (if present), aresuggestive of a malignant behaviour, quite oftensome malignant AMEs have only one of theabove characteristic features (1,2,6,12,15,16).Malignant change may involve only one cellularelement, more often epithelial component ratherthan the myoepithelial component (1,2). Severalcases with local recurrences and distant metasta-ses to lung, liver, brain, bone, thyroid, chest walland lymph nodes have been reported (6,8,13,17-19).

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In conclusion, AME is an unusual breastneoplasm mostly with a benign course, but has apotential for local recurrence, and may simulatemalignant lesions. Furthermore, malignantchange of one or both cellular components mayalso occur. Therefore, it should be considered inthe differential diagnosis of solid lesions of thebreast and complete excision is necessary foraccurate diagnosis and treatment of this unusualbreast lesion with long term follow-up.

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16. Dorpe JV, De Pauw A, Moerman P. Adenoid cysticcarcinoma arising in an adenomyoepithelioma of thebreast. Virchows Arch 1998;432:119-122.

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18. Takahashi II, Tashiro H, Wakasugi K, Onohara T, Nis-hizaki T, Ishikawa T, et al. Malignant adenomyoepit-helioma of the breast: a case with distant metastases.Breast Cancer 1999;6:73-77.

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adenomyoepithelioma of the breast misdiagnosed as invasive ductal

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