Discussion

This patient was diagnosed in 2007 with stage IIB infiltrating ductal carcinoma of the right breast. He underwent a right-sided mastectomy with lymph node dissection. The pathology at that time revealed a 2.5 cm lesion with marked stromal invasion, and one out of nine (1/9) lymph nodes showed a 5 mm focus of carcinoma without extranodal extension. The patient underwent four cycles of Adriamycin-based chemotherapy followed by four cycles of Taxol. Subsequent chemotherapy was not given due to the patient’s development of severe neuropathic effects shortly after initiation of Taxol chemotherapy, resulting in hospitalization. Despite the fact that the patient’s tumor was ER positive, he was ineligible to receive tamoxifen due to a coagulation disorder. Immunohistochemical stains performed on the current specimen reveal that the tumor cells are strongly positive for ER (80%), PR (50%), and GATA-3 (Figures 7-9), thus confirming the diagnosis of metastatic adenocarcinoma consistent with breast origin.

It should be noted at this point that, although more U.S. cytology laboratories are increasingly performing immunohistochemistry (IHC), there is currently no standardized approach to validating IHC use on cytology specimens. In fact, a recent CAP survey showed that more than seventeen different fixation and processing platforms have been utilized when performing IHC on cytology specimens. The only platform that proved problematic for performing IHC was using air-dried preparations for HER-2. Otherwise, no significant systemic problems were detected for any particular platform or antibody.4 Nevertheless, current ASCO/CAP guidelines recommend that ER, PR, and HER-2 testing be performed preferably on formalin-fixed preparations. ER and PR should be considered positive only if >1% of cells show nuclear positivity (intensity of staining must also be reported)5, and HER-2 should be considered positive if >10% of the tumor cells shows strong, circumferential membranous staining on IHC or a HER-2/CEP17 of 2.0 or greater on fluorescent in-situ hybridization.6 For the current case study, we were able to perform IHC on a formalin-fixed cell block as well as compare it to the patient’s previous resection specimen, with the staining results for both cases being similar. With regard to GATA-3, studies have shown that GATA-3 plays a very integral role in breast luminal cell differentiation. As such, it is particularly useful in diagnosing metastatic breast carcinoma, especially triple-negative, sarcomatoid, or metaplastic carcinomas that lack ER and/or PR positivity.7  The same holds true when using GATA-3 on fine-needle aspirates, with one study by Liu et al showing that 88% of primary breast carcinomas and 82% of metastatic breast carcinomas on FNA stained positively with GATA-3.8

Male breast cancer is a very uncommon occurrence, accounting for only 1% of all breast cancers.8-10  For 2016, The American Cancer Society estimates that approximately 2600 cases of male breast cancer will be diagnosed in the United States, with 440 resulting in death.9  Most of the risk factors for male breast cancer are essentially the same as those identified in women and include increasing age, a family history of breast cancer (particularly of first degree relatives), obesity, exogenous estrogen exposure, and irradiation.8-9  Some risk factors unique to men include having liver disease, undescended testes, testicular dysfunction due to Klinefelter’s syndrome, and working in high-heat environments, such as steel mills. Having mutations in the BRCA2 gene, and, to a lesser extent the BRCA1 gene, has also been linked to a higher risk of developing male breast cancer, although not to the same degree as in women.8,11  Whether gynecomastia is a clear risk factor for the development of breast cancer in men remains unclear. Although it has been suggested that such an association exists, it must be remembered that gynecomastia can also be found in healthy male patients.

In men, breast cancer most commonly presents as a palpable subareolar mass, 2-3 cm in size, with or without nipple discharge. While the pathology of breast carcinoma in men is very similar to that in women, there are some key differences. The most common histologic type of breast cancer identified in men is ductal carcinoma, with only a very small percentage of all breast cancers in men being of the lobular type. Cancers of the male breast are also more likely to be estrogen receptor and progesterone receptor positive.8,12

As in women, the current standard of care for male breast cancer is to perform a modified radical mastectomy with axillary lymph node dissection.8,10  Performing an axillary lymph node dissection is of utmost importance because, in the absence of distant metastases, axillary lymph node status is the most important prognostic factor that influences long-term survival in both male and female breast cancer patients. In patients with no nodal involvement, the 10-year survival rate approaches 70-80%. This rate decreased to 35-40% with 1-3 involved nodes and to 10-15% with more than 10 involved nodes. As such, about half of all men with breast cancer are found to have lymph node involvement at the time of diagnosis. Distant spread to the lungs, brain, bones, and liver is also common. Although aromatase inhibitors have been used in the treatment of male breast cancer, tamoxifen remains the agent of choice in estrogen receptor positive cancers.10,13  While it is true that men often present at a much later stage than women, it has been shown that, when matched stage for stage, men have a similar prognosis to women.8,14

Studies have shown FNA to be an excellent means of appropriately triaging breast lesions.15,16 Nevertheless, there are at least two important limitations that should be considered before making a diagnosis of IDC. One limitation is that scirrhous carcinoma, a subtype of IDC, is associated with extensive fibrosis; this, in turn, can lead to sampling issues and thus, a false-negative diagnosis. In these cases, a tissue biopsy is required for a definitive diagnosis. Another limitation is that FNA cannot be used to reliably differentiate between DCIS and IDC, both of which are virtually identical on cytologic preparations. One must also consider that the differential diagnosis for IDC includes other entities which can rarely result in a false-positive diagnosis. As outlined in Table 1 below, these include fibroadenoma, phyllodes tumor, proliferative fibrocystic changes, and pregnancy or lactational changes. This is especially true because all of these lesions can be associated with hypercellularity, prominent nucleoli, and numerous isolated and/or naked cells. However, the presence of stromal fragments and bipolar cells in pairs are much more commonly seen in fibroadenomas than in ductal carcinomas. While marked nuclear atypia can be seen in phyllodes tumors, stromal fragments with spindled cell atypia are not seen in ductal carcinomas. The use of immunostains, such as SMA and p63, to identify myoepithelial cells can also prove helpful in these instances. The changes of pregnancy and lactation can also resemble those of carcinoma, but the lack of pronounced nuclear pleomorphism, hyperchromasia, and coarsely granular chromatin all favor a benign diagnosis.1,2

Table 1:  Differential Diagnosis for Infiltrating Ductal Carcinoma
Ductal carcinoma-in-situ

Scirrhous carcinoma

Fibroadenoma

Phyllodes tumor

Proliferative fibrocystic changes

Pregnancy/lactational changes