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| CASE REPORT |
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| Year : 2019 | Volume
: 8
| Issue : 2 | Page : 129-133 |
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Adenomyoepithelioma of the breast misdiagnosed as metaplastic carcinoma in a 64-year-old female: A case report and review of literature
IF Ezejiofor1, GU Chianakwana2, CO Ukah1, ME Onwukamuche1, OA Egwuonwu2, CC Ogbu1, CC Okoli1
1 Department of Histopathology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria
2 Department of Surgery, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria
| Date of Submission | 01-Mar-2018 |
| Date of Acceptance | 11-May-2018 |
| Date of Web Publication | 30-Jul-2019 |
Correspondence Address:
Dr. I F Ezejiofor
Department of Histopathology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State
Nigeria
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/JDRNTRUHS.JDRNTRUHS_18_18
Adenomyoepithelioma (AME) of the breast is a benign and indolent biphasic rare neoplasm characterized by dual proliferation of glandular and myoepithelial elements, which have propensity for local recurrences and malignant transformations. AME tumors are easily recognized in an excised biopsy, but it is more difficult to make a definitive diagnosis with core needle or limited biopsy because of morphologic heterogeneity. In these biopsies, diagnosis may be mistaken for invasive carcinoma most probably metaplastic carcinoma/carcinosarcoma or invasive ductal carcinoma. This article aims to highlight the diagnostic challenge of AME on core nipple biopsy or challenges encounter in inadequate sampling of the lesion, its recurrence potential, and rarity of this neoplasm in literature. We report a case of AME in the breast formerly diagnosed as an invasive ductal and metaplastic carcinoma on limited biopsies at different times and in different hospitals.
Keywords: Adenomyoepithelioma, core needle biopsy, invasive ductal carcinoma, local recurrence, metaplastic carcinoma
How to cite this article:
Ezejiofor I F, Chianakwana G U, Ukah C O, Onwukamuche M E, Egwuonwu O A, Ogbu C C, Okoli C C. Adenomyoepithelioma of the breast misdiagnosed as metaplastic carcinoma in a 64-year-old female: A case report and review of literature. J NTR Univ Health Sci 2019;8:129-33 |
How to cite this URL:
Ezejiofor I F, Chianakwana G U, Ukah C O, Onwukamuche M E, Egwuonwu O A, Ogbu C C, Okoli C C. Adenomyoepithelioma of the breast misdiagnosed as metaplastic carcinoma in a 64-year-old female: A case report and review of literature. J NTR Univ Health Sci [serial online] 2019 [cited 2023 Mar 22];8:129-33. Available from: https://www.jdrntruhs.org/text.asp?2019/8/2/129/263631 |
| Introduction | |  |
Adenomyoepithelioma (AME) was first described by Hamperl in 1970.[1] Myoepithelial cells are present in the normal mammary duct system and are often prominent in benign lesions, such as usual ductal hyperplasia, sclerosing adenosis, and intraductal papilloma.[1] It's present at the interface between the epithelial and stromal compartments and attached closely to the luminal cells by desmosomes and to the basement membrane by hemidesmosomes.[2] Tumors derived from these cells are seen in the skin, salivary glands, breast, and lungs.[3] AME of the breast is rare, and affects all ages of female but usually adult female between ages 20 and 90 years with mean age at 60 years.[2],[4] Rare cases have been described in males.[2],[4] The etiology is unknown but is considered a variant of intraductal papilloma.[4] It morphologically presents as a firm well circumscribed rounded to lobulated mass, ranging from 0.5 cm to 7 cm at its greatest diameter with occasional satellite nodule whereas recurrent tumors may have irregular borders and ranged from 2 cm to 6 cm.[5],[6] Histologically, AME may dispose as tubular, lobular, papillary, spindle, or mixed patterns with epithelial cells showing hyperchromatic nuclei and eosinophilic cytoplasm whereas myoepithelial cells display spindle, polygonal shaped, or clear cytoplasm.[2] The morphologic appearance of this tumor varies, leading to erroneous diagnoses of other types of benign or even malignant lesions.[7] In recurred cases or cases with malignant outcome, tumors have atypical features such as increased mitotic activity, cytologic atypia, with nuclear pleomorphism, prominent nucleoli, hyperchromasia, and necrosis leading to missed diagnoses.[5] Immunostaining for epithelial and myoepithelial markers are necessary for accurate diagnosis.
| Case Report | | |
A 64-year-old moderately obsessed female with body mass index of 36.1%, P1+ 0 Nigerian of Igbo tribe, 10 years postmenopausal who presented to the surgical outpatient department with a history of recurrent right breast swelling of 4 years duration. The swelling was initially noticed as small lump but progressively increased in size. There was no prior history of trauma, nor associated ulceration, pain, skin change, or nipple discharge. There were also no associated axillary or neck swelling and no positive family history, no weight loss, chronic cough nor back pain noted. She had initial lumpectomy in a private hospital with histology report suggestive of invasive ductal carcinoma and was placed on chemotherapy but she defaulted because of associated complications (hair loss and generalized hyperpigmentation). She represented a year later in the same hospital with surgical site dehiscence and bloody discharge and was placed on 10 months course of chemotherapy that was followed up with tamoxifen. The patient symptoms however resurfaced a year later and was referred to NAUTH for expert management. On examination, she was mildly pale, not in any distress, the respiratory rate was 28 cycles/min, pulse rate was 96 beats/min, blood pressure was 120/80 mmHg. The breast examination showed asymmetry of right and left breasts. There was a healed incision scar in the right lower quadrant and an oval-shaped lump measuring 7 cm × 7 cm, smooth surface, hard in consistency, not tender, no differential warmth, not attached to overlying, or underlying structures. Impression of recurrent breast lump query malignant breast disease was made. Investigation showed normal values of E/U/Cr, marginal decreased value of pack cell volume (PCV) of 0.312 (0.370–0.470), low hemoglobin of 101 g/L (110–150), Hemoglobin AA (Hb AA) genotype and negative RVS status. FBC and platelet showed normal morphology: Marginally reduced WBC count of 3.67 × 109/L (4.00–10.00), as well as low RBC of 3.14 × 1012/L (3.50–5.00) with normal value of platelet count of 149 × 109/L (100–300). Abdominopelvic scan showed fatty liver with normal spleen and uterus no metastasis present. Chest x-ray shows no abnormality. She had histology on trucut biopsy sample and metaplastic carcinoma with squamous differentiation was entertained and subsequently had modified right radical mastectomy. Tumor was submitted to the histopathology department for further analysis and diagnosis. She was discharged on satisfactory condition 19th day postsurgery and is currently on follow-up.
Gross examination at the histopathology department, revealed a mastectomy specimen with an attached ellipsoidal skin and an intact nipple-areolar complex as well as three axillary lymph nodes embedded in fibrofatty tissue. The breast measures 17.5 × 16.5 × 6.0 cm and weighs 650 g. There is a palpable peri-areolar mass [Figure 1]b, measuring 5.0 cm in widest dimension. Serial sectioning reveals a well circumscribed tumor with necrotic center, soft to firm in consistency and surrounded by thin capsule [Figure 1]a and [Figure 1]b. | Figure 1: (a) Shows a well circumscribed peri-areolar tumour mass with necrotic centre. (b) shows a well circumscribed tumour mass measuring 4 x 4 cm and surrounded by thin capsule with central area of necrosis
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Microscopic sections of the mastectomy specimen show a well circumscribed encapsulated mixed tumor composed of nests and sheets of epithelial and myoepithelial cells exhibiting mild cytologic atypia [Figure 2]a. The myoepithelial cells have vacuolated/clear cytoplasm with vesicular nuclei whereas the epithelial cells have hyperchromatic nuclei and are disposed in tubules rimmed by myoepithelial cells within a chondromyxoid stroma [Figure 2]b. There is a central area of extensive necrosis within the tumor. The margins of the tumor are well encapsulated and free of tumor infiltrate; however, the tumor harbors 8–12 mitotic figures per high power field in both components [Figure 2]c. All the three lymph nodes harvested showed expanded sinusoids replete with histocytes. Overall features are those of adenomyoepithelioma lobular variant with sinus histiocytosis of the lymph nodes. | Figure 2: (a) A well circumscribed encapsulated (double arrows) benign mixed tumour composed of nests, sheets and tubules of epithelial and myoepithelial cells with extensive area of central necrosis (single arrow). (b) Higher magnification showing dual proliferation of cells composed of glandular (an arrow) and myoepithelial component (double arrows). (c) Photomicrograph showing myoepithelial cells with clear cytoplasm on a chondromyxoid background
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| Discussion | | |
AME is a relatively rare benign or a low grade malignant lesion. Since 1970, only four comprehensive studies are in literatures others are case reports.[5] In Nigeria, Nwachokor et al. of Central hospital Warri in delta state in the South-South Nigeria reported only three cases of AME of 133 cases of benign breast lesions in children and adolescence.[8] There has been no reported case of AME in Southeast Nigeria following extensive search in PubMed, MEDLINE, and Google scholar. The index case is the first case from the Southeast Nigeria. Because of the morphologic heterogeneity of this tumor, misinterpretation on a needle biopsy may occur with tumor being misdiagnosed as metaplastic carcinoma, clear cell carcinoma and invasive ductal carcinoma. Sibel et al. of Department of Pathology in Zonguldak Karaelmas University reported AME of the breast in a 34-year-old female misdiagnosed as invasive ductal carcinoma and had total mastectomy with axillary lymph node dissection.[9] Catena et al. in St Orsola Malpighi University Italy also reported C5 carcinoma on fine needle aspiration cytology on a 42-year-old female with right breast mass whose histology and immunostain confirmed AME.[10] In the index case inadequate sampling of the first lumpectomy specimen as well as lack of insight due to rarity of the tumor, and limited tissue on the subsequent core biopsy also led to misdiagnosed report received as invasive ductal carcinoma and metaplastic carcinoma, respectively.
AME has variable locations but is usually present in the peripheral portions of the breast and can be centrally located or near the areola [4] as seen in this index case [Figure 1]a. Patient with AME may also present with nipple discharge, pain, or tenderness to palpation, which were the cardinal signs and symptoms seen in this index case.[2] World Health Organisation (WHO) divides AME into benign AME and AME with carcinoma.[2] Several variants of AME exist ranging from tubular, spindle, lobular, papillary, and mixed.[2] AME tumors with infiltrative border, metastatic potential, brisk mitotic activity, and marked or severe cytologic atypia are referred to as malignant AME (mAME).[2]
Although most tumors have been benign, local recurrences, malignant transformations, and metastases have been reported.[2],[4] Local recurrences have occurred 8 months to 5 years after initial excision.[3],[5] In recurred AME tumors, the cells are more bizarre than the original tumor as seen in this index case that display cytologic atypia in both components. Different histological types behave differently both in clinical presentation and follow-up. Some literatures reported that tubular variants and some lobular variants with high mitotic activity are particularly prone to local recurrence AME tumors.[4] Tavossoli et al. also reported that tubular variants are the most recurred AME especially those with extension into the adjacent normal ducts but in contrast the recurred tubular lesions lacked an aggressive morphologic appearance or noticeable mitotic activity as lobular variant.[5] Recurred lobular variant AME displayed cytologic atypia, increased mitotic activity with 8/10 high-power fields as seen in the index case (unlike original tumor that displays 3/10 high-power fields).[5] Cytologic atypia and mitotic rates were found to be variable in other reported studies.[7] Benign appearing tumors rarely metastasize and if metastasis occur it shows hematogenous spread to lung brain, or jaws and not lymphatic spread.[11] Lymph node involvement is unusual and is mainly by extension.[2],[11]
The hallmark of diagnosis of AME tumor is histologic recognition of biphasic cellular elements and the overall architecture of the tumor in combination with immunohistochemistry.
Immunohistochemical stain of AME exhibit diffuse positive reaction to epithelial cells with antibodies to cytokeratins (CK-AE1/3), CAM 5.2, or CK7, EMA whereas myoepithelial cells show strong reaction to p63, smooth muscle myosin heavy chains, CK5/6, CD10, calponin, actin, and S100.[2],[4] McLaren et al. reported that p63 produced the best results with consistent, intense nuclear staining.[12] Proliferative indices of Ki-67 immunostaining are present in both compartments of the tumor but may be higher in the myoepithelial cells than it is in the ductal cells.
Based on the resource poor setting and unavailability of these immunostains, we use only three most important immunostains: p63, Pan-cytokeratin (CK) or EMA, and Ki-67 although EMA is preferred due to its sole reaction to epithelia cells unlike Pan-CK that show strong epithelial cell stain and weak myoepithelial reaction. The tumour shows diffuse strong membranous epithelial stain with EMA [Figure 3]a whereas both components (myoepithelial cells & epithelial cells) show 30% and 50% positive reaction to Ki-67 respectively. [Figure 3]b, The tumour cells also show strong positive nuclear stain of myoepithelial cells to p63 [Figure 3]c, [Figure 3]d, [Figure 3]e and diffuse strong positive reaction for Pan-CK [Figure 3]f. Some mimics of AME include majorly intraductal papilloma but others are nipple adenoma, tubular adenoma, myoid harmatoma, and pleomorphic adenoma that can be distinguished using morphology and immunostains. | Figure 3: (a) EMA x10 Obj Immunostain showing strong positive membranous stain on epithelial cells while the myoepithelial components show negative reaction. (b) Ki67x20 Obj postive stain showing nuclear positivity for epithelial component. (c) p63 Stain showing strong postivity for myoepithelial component x10 Obj with internal control showing basal cell postive stain. (d) (a) p63 Stain showing myoepithelial positive stain while the epithelial components are negative (IHC X10 Obj). (e) Higher magnification showing myoepithelial positive stain with p63 while the epithelial components are negative (IHC x20 Obj). (f) Pan-cytokeratin Stain showing strong positive stain on epithelial component but weak stains on myoepithelial cells (IHC X10 Obj)
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Treatment modalities of AME considered the potential local recurrence rate of this tumor and recommend wide excision for proper diagnosis and treatment and also requires long-term follow-up. Based on needle core biopsy misdiagnosis, thrice local recurred lesion in this index case and high mitotic figure a more aggressive surgery of simple right mastectomy with axillary clearance was done as reported by Sibel et al.[9] But with knowledge of this tumor axillary nodes should not have been removed to avoid complications such as lymphedema.
In conclusion, AME is a rare benign breast tumor with biphasic elements that may be misinterpreted in limited biopsy and inadequate samples. The recognition of dual components in combination with immunostains will aid in diagnosis. Knowledge of expected biological behaviors is important in guiding the most appropriate management protocol.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Hamperl H. The myothelia (myoepithelial cells): Normal state; regressive changes; hyperplasia; tumors. Curr Top Pathol 1970;53:161-220.  |
| 2. | Adenomyoepithelioma and adenomyoepithelioma with carcinoma. In: SunilLR, Ian OE, Stuart JS, Puay HT, MarcJ Van de Vijver, editors. World Health Organization Classification of Tumours of the Breast. 4 th ed. IARC Press; 2012. pp 122-3. |
| 3. | Tavassoli FA. Miscellaneous Lesions. In Tavassoli FA (ed). Pathology of the Breast. 2 nd ed. Norwalk, Appleton& Lange, 1992. 595-609. |
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| 5. | Tavassoli FA. Myoepithelial lesions of the breast: Myoepitheliosis, adenomyoepithelioma, and myoepithelial carcinoma. Am J Surg Pathol 1991;15:554-68. |
| 6. | Loose JH, Patchefsky AS, Hollander IJ, Lavin LS, Cooper HS, Katz SM. Adenomyoepithelioma of the breast: A spectrum of biologic behavior. Am J Surg Pathol 1992;16:868-76. |
| 7. | Rosen PP. Adenomyoepithelioma of the breast. Hum Pathol 1987;18:1232-7. |
| 8. | Nwachokor F, Igbe AP, Forae GD. Histopathological review of breast tumours in children and adolescents in Delta State Nigeria. Afr J Paediatr Surg 2013;10:65-7. [Full text] |
| 9. | Bektas S, Bahadir B, Gun BD, Colak S, Özdamar ŞO. Adenomyoepithelioma of the breast misdiagnosed as invasive ductal carcinoma. Turk J Pathol 2007;23:116. |
| 10. | Catena F, Santini D, Di Saverio S, Ansaloni L, Taffurelli M. Adenomyoepithelioma of the breast: An intricate diagnostic problem. Breast Care 2008;3:125-7. |
| 11. | Howlett DC, Mason CH, Biswas S, Sangle PD, Rubin G, Allan SM. Adenomyoepithelioma of the breast: Spectrum of disease with associated imaging and pathology. Am J Roentgenol 2003;180:799-803. |
| 12. | McLaren BK, Smith J, Schuyler PA, Dupont WD, Page DL. Adenomyoepithelioma: Clinical, histologic, and immunohistologic evaluation of a series of related lesions. Am J Surg Pathol 2005;29:1294-9. |
[Figure 1], [Figure 2], [Figure 3]
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