Introduction
Breast cancer is the most common malignancy in women worldwide. However, metastases to the breast from extramammary solid tumors are rare and account for only 0.2–0.9% of all breast malignancies [
1‐
3]. The most common primary tumors metastasizing to the breast vary depending on the specific patient population studied [
4], but malignant melanoma, lung carcinoma, ovarian carcinoma, gastrointestinal carcinoma, and sarcoma are repeatedly reported [
4‐
7].
Accurate diagnosis of metastatic tumors in the breast is crucial because their staging, treatment and prognosis are essentially different from primary breast tumors [
6]. One of the key morphological features for the diagnosis of metastatic tumors is their lack of an
in situ (intraductal and/or intralobular) carcinoma component [
3,
5,
7]. The presence of an
in situ component strongly supports the diagnosis of primary carcinoma. However, in this case report, we present a unique case of metastatic ovarian carcinoma spreading into mammary ducts, which mimicked an
in situ component of primary breast carcinoma.
Discussion
We present a unique case of ovarian carcinoma metastasizing to the breast and spreading into mammary ducts, which mimicked an
in situ component of primary breast carcinoma. One case report of metastatic pancreatic tumor in a child firstly confirmed this
in situ-mimicking growth pattern by immunohistochemistry [
8]. Two other reports briefly mentioned this growth pattern of metastatic tumors, but appropriate immunohistochemical stains to prove intraductal growth were not performed [
2,
9]. Thus, to our knowledge, this is the second case (and the first adult case) confirming the growth pattern by immunohistochemistry. This
in situ-mimicking growth pattern can be a potential pitfall for establishing a correct diagnosis of metastasis. The same growth pattern, aside from the metastatic tumor, was recently reported in a soft tissue tumor arising in the breast [
10].
Histologically correct and type-specific diagnosis of tumors metastasizing to the breast is vital to ensure appropriate management. However, because of their rarity, it is sometimes difficult for pathologists to make the accurate diagnosis. The following four points can be given as diagnostic clues for metastatic tumors [
2‐
5,
7,
11,
12]: (1) clinical history of extramammary malignancy, (2) unusual morphology for primary breast cancer, (3) absence of an
in situ component, and (4) lack of breast-related immunophenotype.
Clinical history of extramammary cancer is essential in making a diagnosis of metastasis to the breast [
3,
5,
11]. Almost all breast cancer cases that pathologists diagnose in daily practice are primary cancers. Thus, suspicion of metastatic tumors may sometimes be raised only after clinical history is provided. Comparison of mammary and extramammary tumors is important in this situation.
The diagnosis of metastatic tumors is easier when the tumor has an unusual appearance for a breast primary lesion or a typical morphology of its primary site of origin [
12]. Two-thirds of metastases to the breast have distinctive histological features, raising the possibility of the diagnosis [
3]. In remaining cases, however, the histological appearance is similar to a primary mammary tumor, and the clinical history and other information are important to establish the correct diagnosis for these cases.
The presence of an
in situ carcinoma component is pathognomonic of primary breast carcinoma. On the contrary, the absence of an
in situ component supports the diagnosis of a metastatic tumor to the breast [
3,
5,
7]. However,
in situ-like atypical ductal proliferations are reported in metastatic tumors in the breast, and pathologists should be careful not to regard this
in situ-like structure as true
in situ carcinoma and exclude the possibility of metastatic tumor. The
in situ-mimicking lesions in metastatic tumors can be classified into three types based on histogenesis: (a) lymphovascular emboli from metastatic tumors [
2,
11], (b) metastatic tumors spreading into existing mammary duct units [
2,
8,
9], and (c) true
in situ carcinoma or atypical ductal/lobular hyperplasia of breast origin coexisting with metastatic tumors [
9,
12]. The immunohistochemical panel mentioned below can be useful for the differential diagnosis (Table
2).
Table 2.
Immunohistochemical markers for the differential diagnosis of in situ-mimicking architectures in metastasis to the breast
Lymphovascular tumor emboli | (+) | (−) | (−) | (+) |
Intraductal spread by metastatic tumorsa | (+) | (−) | (+) | (−) |
Coexistence of true in situ carcinoma | (−) | (+) | (+) | (−) |
Immunohistochemistry plays a major role in the accurate diagnosis of metastatic tumor in the breast. A panel of breast-related markers (e.g., GATA3, mammaglobin, GCDFP15, and SOX10) is helpful to rule out a metastasis [
5]. In addition, a panel of extramammary organ/tumor-specific markers can be used to delineate the likely primary site of metastasis [
5]. In addition, myoepithelial markers (e.g. p63, cytokeratin 14, and calponin) and endothelial markers (e.g., podoplanin and CD31) may be useful for the differential diagnosis of
in situ-like architecture in the metastatic tumors [
4,
5,
11].
Serous carcinoma is the most common type of ovarian tumor metastasizing to the breast [
13]. Metastatic serous carcinoma can resemble invasive micropapillary carcinoma of the breast, and psammomatous calcifications can be seen in both [
3,
14,
15]. One study reported that approximately 24% of metastatic serous carcinomas in the breast were initially interpreted as primary carcinomas [
14]. In fact, invasive micropapillary carcinoma was originally designated “pseudopapillary (serous-like) carcinoma” because of its resemblance to serous carcinoma of Müllerian origin [
15]. A key morphological finding for the differential diagnosis may be the presence or absence of a fibrovascular core in the papillary/micropapillary structure. Invasive micropapillary carcinoma mainly shows micropapillary (pseudopapillary) architecture without fibrovascular cores [
15], while serous carcinoma often displays (macro-)papillary structure with fibrovascular cores in addition to their micropapillary architecture [
16]. A panel of breast-related and Müllerian duct/serous tumor-specific immunohistochemical markers (e.g. WT1 and PAX8) can be helpful in differentiating tumors of ovarian from breast origin. However, estrogen and progesterone receptors are not helpful because both tumors can be positive for these [
13].
In the present case, immunohistochemistry played a critical role in establishing an accurate diagnosis of the metastatic tumor and in elucidating the histogenesis of its in situ-mimicking architecture. Although the breast tumor was histologically similar to the previous ovarian carcinoma, invasive micropapillary carcinoma of breast origin could not be ruled out because the in situ-like component surrounded by myoepithelium was present. Based on the positive Müllerian/serous markers and negative breast-related markers, the breast tumor and the in situ-like component was diagnosed as metastatic serous carcinoma. The histogenesis of the in situ-like architecture could be due to spread of the metastatic tumor into existing mammary ducts, since myoepithelium around the in situ-like component was confirmed by myoepithelial immunomarkers.
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