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Fine-needle aspiration of metastatic renal cell carcinoma to a male breast: A rare initial presentation

Sir, 
 
Breast metastasis from extramammary tumors is extremely uncommon and accounts for only 3% of all breast masses.[1,2] Reported primary malignant tumors that spread to the breast include melanoma, ovarian, thyroid, pulmonary, hepatic and rarely renal cell carcinoma.[3,4,5,6] Clinical symptoms at presentation are unreliable to distinguish between a primary breast carcinoma and a metastatic tumor to the breast. Prompt diagnosis of a metastatic tumor is imperative to prevent an unnecessary lumpectomy or mastectomy as well as to render appropriate management for what may be an occult primary tumor. We herewith report an interesting case of a de novo male breast mass that demonstrated atypical cytological features suspicious for malignancy on fine-needle aspiration (FNA), which initiated an excisional biopsy, revealing a metastasis from what was determined to be an occult renal cell carcinoma. On literature search, all the reported cases of metastatic renal cell carcinoma to the breast were in females, except one in which metastasis was noted in the skin of the male breast.[7] The present case describe the first report of clear cell renal cell metastasis in the male breast parenchyma with no skin involvement. 
 
A 57-year-old male presented for a 1.3 cm palpable right breast mass, which was detected by self-examination. There were no associated overlying skin lesions. He denied having nipple discharge, pain, or any other masses. Ultrasonography of the right breast revealed a 1.3 cm solid non-specific mass at the 12:00 position of intermediate suspicion (ACR BIRADS Category: 4). There were no associated microcalcifications. FNA of the mass (two direct smears stained with the Papanicolaou stain) demonstrated moderately cellular smears of epithelioid to spindled cells arranged in three-dimensional clusters as well as two-dimensional sheets of cells with vague papillary configurations. A few singly dispersed cells were also noted. The cells demonstrated a low nuclear to cytoplasmic ratio, clear/vacuolated cytoplasm and regular to convoluted nuclear membranes, inconspicuous nucleoli, and rare intra-nuclear pseudo-inclusion. Some of the cellular groups demonstrated a fine capillary meshwork. The background was clean with no evidence of necrosis [Figure ​[Figure1a1a–c]. The FNA was performed in a physician's office, so no on-site pathological evaluation was done; neither additional material for a cellblock preparation was provided. The differential diagnosis included a primary breast carcinoma or metastasis from an unknown primary such as clear cell renal cell carcinoma, pulmonary adenocarcinoma and clear cell “sugar” tumor of the lung, epithelioid hemagioendothelioma, adrenal cortical carcinoma or melanoma. Due to limited available material, further work-up by immunohistochemical stains could not be performed. A diagnosis of atypical cytological features suspicious for malignancy was rendered with a recommendation for a repeat FNA with a cellblock preparation or a biopsy of the mass. 
 
 
 
Figure 1 
 
(a) Moderately cellular smear demonstrates three-dimensional clusters of epithelioid to spindled cells in vague papillary configuration with occasional singly dispersed cells (Papanicolaou, ×100). (b) Two-dimensional sheets of epithelioid cells ... 
 
 
 
At 1 week later, the patient underwent a right breast lumpectomy, which revealed fatty breast parenchyma with a circumscribed mass. Histological sections of the mass demonstrated a low-grade clear cell carcinoma [Figure 1d]. There were no mitoses or areas of necrosis. Immunohistochemical stains revealed that the tumor cells were positive for PAN-cytokeratin (CK), CK7, CD10 and PAX-8, and negative for CK20, TTF-1, ER and PR. A diagnosis of metastatic renal cell carcinoma, clear cell type was rendered. Subsequently, an abdomen computed tomography scan demonstrated an 8.6 cm peripherally enhancing mass involving the upper pole of the right kidney. At 1 month later, a right nephrectomy demonstrated a clear cell renal cell carcinoma (10.1 cm) with tumor extending into the perinephric fat and in the segmental branch of the renal vein (pT3aNxM1). No other sites of metastasis from the renal carcinoma were found radiologically. The patient has been on regular follow-up for the past 3 years with no recurrence or evidence of other metastases. 
 
Renal cell carcinoma is also known as “the internist's tumor” because of bizarre and unpredictable initial presentations. Breast metastasis from renal cell carcinoma is rare with 16 cases reported in the literature including 7 cases presenting as the initial sign of metastatic disease.[8] In the majority, the breast masses were noted 1-18 years status post-nephrectomy of renal cell carcinoma of clear cell type.[9] The metachronous metastases have been found to carry a better prognosis than the synchronous metastasis.[10] Of the 16 cases reported, 15 have been described in women and in one man a palpable metastatic lesion was noted in the skin of the breast.[7] The present report is the first case of clear cell renal cell carcinoma metastasis appearing initially as a breast mass in a male breast without skin involvement. 
 
Differentiation of primary breast cancer from secondary metastasis is very important because of differences in treatment and prognosis. Breast involvement may be a signal of rapid widespread dissemination of the neoplasm with a crude survival rate of only 10.9 months reported before, but occasionally long-term survival may also occur.[11] Breast radiology does not seem to always helpful but features such as microcalcifications and spiculations are not usually seen in metastatic extramammary breast tumors when compared to the primary breast carcinoma. Extramammary tumors do not involve the ducts and thus nipple retraction, skin dimpling, and nipple discharge are rare as is the regional lymph node involvement. No microcalcifications or skin changes were seen in our case, but in the absence of a cell-block preparation and the unusual cytomorphology prompted us to consider the other differential diagnosis besides primary breast carcinoma and to recommend a biopsy for a definitive diagnosis. 
 
In summary, this case highlights that rare metastasis from an extramammary site such as kidney can occur and can be the initial presenting sign. This report is the first case of clear cell renal metastasis presenting initially as a breast mass in a male breast without skin involvement. A cell-block preparation for performing immunohistochemical studies in addition to both Diff Quik and Papanicolaou stains on FNA specimens can aid in the differentiation of primary breast carcinoma from metastasis.