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  Table of Contents    
CASE REPORT  
Year : 2014  |  Volume : 57  |  Issue : 4  |  Page : 611-613
Adenoid cystic carcinoma of the breast: Report of two cases with immunohistochemical profile of C-kit and MYB overexpression


1 Department of Pathology, Soonchunhyang University College of Medicine, Bucheon, Korea
2 Department of Surgery, Soonchunhyang University College of Medicine, Bucheon, Korea

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Date of Web Publication11-Oct-2014
 

   Abstract 

Adenoid cystic carcinoma (ACC) is a rare tumor with characteristic histologic features. Staining with basal markers for estrogen receptor, progesterone receptor, and HER2 usually shows negative results. Immunohistochemical analysis of C-kit and MYB overexpression of the ACC also has been reported. We report two cases of ACC of the breast with C-kit and MYB overexpression that clinically confirm these previously reported characteristics and suggest that further molecular study of the expression of these two proteins can lead to future therapeutic strategies.

Keywords: Adenoid cystic carcinoma, breast, C-kit, MYB, immunohistochemistry

How to cite this article:
Chin S, Kim Z. Adenoid cystic carcinoma of the breast: Report of two cases with immunohistochemical profile of C-kit and MYB overexpression . Indian J Pathol Microbiol 2014;57:611-3

How to cite this URL:
Chin S, Kim Z. Adenoid cystic carcinoma of the breast: Report of two cases with immunohistochemical profile of C-kit and MYB overexpression . Indian J Pathol Microbiol [serial online] 2014 [cited 2019 Dec 6];57:611-3. Available from: http://www.ijpmonline.org/text.asp?2014/57/4/611/142693



   Introduction Top


Adenoid cystic carcinoma (ACC) is a rare subtype of breast cancer, with an incidence of <0.1%. [1] Histologically, it resembles ACC of the salivary gland. The tumor comprises luminal epithelial cells and myoepithelial-like cells with tubular, cribriform, or solid architectural patterns. It generally lacks expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 [1] and frequently expresses basal markers such as epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK5/6), suggesting a basal-like phenotype of the tumor. [2] C-kit overexpression as well as MYB overexpression from frequent t(6;9)(q22-23;p23-24) translocation, which fuses the MYB oncogene to transcription factor NFIB, have been reported. [3],[4],[5] We present immunohistochemistry profiles of two cases of ACC of the breast with C-kit and MYB overexpression.


   Case report Top


Case 1

A 75-year-old woman without significant medical history who presented with a lump in her right breast. Ultrasonography showed a well-defined, lobulated mass (1.5 cm) in the upper-inner quadrant of the right breast and no axillary lymph node enlargement. Excisional biopsy specimen suggested fibroadenoma. The resected tumor measured 2 cm × 1.8 cm × 1 cm with lobulated borders and comprised basaloid and luminal epithelial cells exhibiting a cribriform and tubular growth pattern on microscopy [Figure 1]a. The tumor cells showed mild cytologic atypia of low-grade morphology. The tumor was categorized as grade I based on the three-tiered grading system. The resection margins were focally involved by the tumor. The patient was transferred to another hospital for further treatment.
Figure 1: (a) Case 1: The tumor shows cribriform and tubular pattern (H and E, ×100). (b) Case 2: Focal solid architecture is identified (H and E, ×100)

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Case 2

The second case is about a 49-year-old woman with a palpable mass of the left breast. Mammography and ultrasonography showed an irregular contour mass (3 cm). A needle biopsy specimen suggested ACC. The patient underwent skin-sparing mastectomy with sentinel lymph node biopsy. The resected tumor was a firm, lobulated, pink-tan mass measuring 4.5 cm × 2.5 cm × 2.2 cm; demonstrated an admixed cribriform, tubular-trabecular, and solid growth pattern; and comprised a typical biphasic cell population. The tumor revealed focal solid areas (Grade II). Neither perineural nor lymphovascular invasion was identified and all three sentinel lymph nodes and resection margins were free of tumor [Figure 1]b. The tumor was classified as stage IIa (pT2N0M0) carcinoma. The patient underwent six cycles of postoperative adjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide.

Both cases showed almost identical immunohistochemical features. The basaloid cells expressed smooth muscle actin and p63, revealing their myoepithelial differentiation [Figure 2]a. CK5/6 and EGFR were also predominantly stained in basaloid cells [Figure 2]b. Luminal epithelial cells expressed E-cadherin and CK7. Neither cell type expressed ER, PR, or HER2, indicating a basal-like phenotype [Figure 2]c and d.
Figure 2: (a) Small basaloid cells are highlighted by p63 (×200). (b) Cytokeratin 5/6 also predominantly stains basaloid cells (×200). (c) The tumor cells are negative for estrogen receptor (×200). (d) HER2 expression is not identified (×200)

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C-kit was expressed in both cases. Luminal cells of the tubular-trabecular and cribriform architectural pattern revealed consistent, strong membranous immunoreactivity to C-kit [Figure 3]a, but focal solid areas in case 2 showed a weak staining pattern in both epithelial and basaloid cells [Figure 3]b.

MYB was also expressed in both cases. Contrary to C-kit, its expression was confined to the basaloid cells. The nuclear staining pattern showed moderately to strong immunoreactivity in a tubular-trabecular and cribriform architectural pattern [Figure 4]a. In solid areas, MYB was weakly stained [Figure 4]b.
Figure 3: (a) Luminal epithelial cells of cribriform and tubular pattern show strong C-kit expression (×200). (b) Solid nests of tumor show weak C-kit immunoreactivity in both basaloid cells and epithelial cells (×200)

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Figure 4: (a) MYB reveals strong nuclear staining pattern in basaloid cells of cribriform and tubular architecture (×200). (b) Weak stain of MYB in solid pattern (×200)

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   Discussion Top


Adenoid cystic carcinoma of the breast is a rare, slow-growing neoplasm that affects older women (median age, 60 years). [1] It arises as a subareolar lesion, but nipple discharge is unusual. Most patients with ACC have a breast mass at first presentation. Contrary to its salivary gland counterpart, ACC of the breast shows a favorable prognosis. [3] Lymph node involvement and distant metastasis are uncommon. [1]

Adenoid cystic carcinoma tumors show epithelial and myoepithelial-like cells forming cribriform, tubular-trabecular, or solid architectural patterns. The tumor is graded as I, II, or III based on the proportion of a solid element, which correlates with prognosis. [6] The myoepithelial-like cells lining the cribriform spaces occasionally contain basement membrane-like materials that can be myxoid or mucinous. Because cribriform architecture is the most commonly observed pattern in ACC of the breast, the major differential diagnosis for ACC includes breast carcinoma showing cribriform pattern, such as cribriform carcinoma. Cribriform carcinoma comprises only epithelial cells and no basement membrane-like materials in the spaces and usually expresses ER and PR, whereas ACC of the breast usually does not express ER, PR, and HER2 and tends to express CK5/6 or EGFR. Immunohistochemically, ACC is categorized as a basal-like subtype of breast carcinoma, which is supported by microarray-based gene expression profiling studies. [2]

C-kit, a transmembrane tyrosine kinase receptor protein encoded by the proto-oncogene KIT, is highly expressed in ACC of the salivary gland (89-100%) and breast (83-100%). [3],[4],[7] C-kit overexpression is well-established in gastrointestinal stromal tumor and melanoma, which harbor the KIT mutation. Unlike those tumors, though, KIT mutation in ACC is very rare, and the precise mechanism for C-kit overexpression is still unknown. [8] ACCs with C-kit overexpression without mutation show no response to treatment with tyrosine kinase inhibitor. [9] Despite its weak therapeutic significance, immunohistochemical detection of C-kit overexpression is useful in the differential diagnosis of ACC because other invasive carcinomas of the breast usually do not express C-kit. [3],[4]

Analogous to its salivary gland counterpart, ACC of the breast also has t(6;9)(q22-23;p23-24) translocation, causing MYB-NFIB fusion. [5] In the salivary gland, MYB-NFIB fusion induces the loss of several microRNAs that negatively regulate MYB expression, leading to MYB overexpression as shown by nuclear staining. [5] The present cases also showed strong nuclear staining for MYB, revealing its overexpression. MYB may play a key role in the molecular pathogenesis of ACC and is expected to be a candidate therapeutic target. [5]

In summary, we report two cases of ACC of the breast, a rare tumor known to be a basal-like subtype of breast carcinoma with overexpression of C-kit and MYB protein. Further molecular studies of these overexpressed proteins may lead to future therapeutic strategies.


   Acknowledgement Top


This work was partly supported by the Soonchunhyang University Research Fund.

 
   References Top

1.
Kulkarni N, Pezzi CM, Greif JM, Suzanne Klimberg V, Bailey L, Korourian S, et al. Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base. Ann Surg Oncol 2013;20:2236-41.  Back to cited text no. 1
    
2.
Vranic S, Bender R, Palazzo J, Gatalica Z. A review of adenoid cystic carcinoma of the breast with emphasis on its molecular and genetic characteristics. Hum Pathol 2013;44:301-9.  Back to cited text no. 2
    
3.
Azoulay S, Laé M, Fréneaux P, Merle S, Al Ghuzlan A, Chnecker C, et al. KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome. Mod Pathol 2005;18:1623-31.  Back to cited text no. 3
    
4.
Crisi GM, Marconi SA, Makari-Judson G, Goulart RA. Expression of c-kit in adenoid cystic carcinoma of the breast. Am J Clin Pathol 2005;124:733-9.  Back to cited text no. 4
    
5.
Persson M, Andrén Y, Mark J, Horlings HM, Persson F, Stenman G. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci U S A 2009;106:18740-4.  Back to cited text no. 5
    
6.
Ro JY, Silva EG, Gallager HS. Adenoid cystic carcinoma of the breast. Hum Pathol 1987;18:1276-81.  Back to cited text no. 6
    
7.
Freier K, Flechtenmacher C, Walch A, Devens F, Mühling J, Lichter P, et al. Differential KIT expression in histological subtypes of adenoid cystic carcinoma (ACC) of the salivary gland. Oral Oncol 2005;41:934-9.  Back to cited text no. 7
    
8.
Moskaluk CA, Frierson HF Jr, El-Naggar AK, Futreal PA. C-kit gene mutations in adenoid cystic carcinoma are rare. Mod Pathol 2010;23:905-6.  Back to cited text no. 8
[PUBMED]    
9.
Pfeffer MR, Talmi Y, Catane R, Symon Z, Yosepovitch A, Levitt M. A phase II study of Imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands. Oral Oncol 2007;43:33-6.  Back to cited text no. 9
    

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Correspondence Address:
Susie Chin
Department of Pathology, Soonchunhyang University College of Medicine, 170 Jomaru-ro, Wonmi-gu, Bucheon 420-767
Korea
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.142693

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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