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Case Report Breast metastases from renal cell carcinoma in a male patient: a rare case and review of the literature

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Case Report

Breast metastases from renal cell carcinoma in a male

patient: a rare case and review of the literature

Cheng-Qian Yu1, Bruce D Jr Leckey2, Endi Wang2, Shuai Shen1, Lian-He Yang3, Liang Wang3, Juan-Han Yu3,

Xu-Yong Lin3, Xu-Hong Tao3, Shuang Ma1

1Department of Neurology, Shengjing Hospital of China Medical University, Shenyang 110022, Liao Ning, China; 2Department of Pathology, Duke University Medical Center 2301 Erwin Rd, Durham 27710, NC; 3Department of Pathology, First Affiliated Hospital of China Medical University and College of Basic Medical Sciences, Shenyang 110013, Liao Ning, China

Received September 3, 2017; Accepted March 12, 2018; Epub June 15, 2018; Published June 30, 2018

Abstract: Metastases to the breast from extra-mammary tumors are uncommon. Renal cell carcinoma (RCC) is considered to be an unusual source of such metastases, especially for a male, with only three previously reported cases. Here, we report a 40-year-old Asian male post nephrectomy for RCC diagnosed three years prior who pre-sented with a breast mass. Ultrasound evaluation of the breast mass revealed a solid lesion that was concern-ing for malignancy. Given the relatively recent history of renal cell carcinoma, the possibility of a metastasis was considered. However, the extremely low incidence of RCC metastasis to the breast would lead pathologists and

clinicians to consider a primary tumor such as male breast cancer as the first differential diagnosis. Ultimately, the

histopathological evaluation showed that the neoplastic cells showed clear cell carcinoma features. Immunohisto-chemistry (IHC) showed that the neoplastic cells were positive for cytokeratin (CK), CD10, vimentin, and epithelial membrane antigen (EMA), but were negative for estrogen receptor (ER), progesterone receptor (PR), and GATA-3. Based on the medical history, morphology, and IHC study, the diagnosis of RCC metastatic to the breast was estab-lished. Due to the extremely low incidence of metastatic RCC to the breast, the risk of misdiagnosis is high and has the potential to negatively impact patient management. Here, we review the clinical, pathological, and prognostic information of RCC metastasis to the breast. When a male with a history of RCC presents with a suspicious breast mass, metastatic carcinoma should be taken into consideration, and pathologic examination is the most useful tool

for the definitive diagnosis.

Keywords: Breast, renal cell carcinoma, histological, metastatic carcinoma, treatment

Introduction

Renal cell carcinoma (RCC) accounts for 2-3% of adult tumors, representing 90% of renal ma- lignancies and is the most lethal neoplasm of the urologic system [1, 2]. Lung, lymph-node, bone, and liver present as the most common metastatic sites [3-6]. Metastases to the br- east from extra-mammary malignancies are rare, particularly in males [7, 8]. Most frequent-ly, these metastases are observed in mela- noma, lymphoma, and leukemia, while metas-tasis from RCC is considered as an uncommon source [9]. Here we report a 40-year-old Asian male, with an isolated metastasis to the br- east occurring three years after undergoing a nephrectomy for RCC. To our knowledge, there are only twenty-seven cases of RCC metastatic

to the breast reported previously, and this is the third reported case in a male. Due to the extremely low incidence of the metastatic RCC to the breast, it is easily overlooked in favor of more likely diagnoses which may severely impact both treatment and prognosis.

Case presentation

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Materials and methods

Ultrasound examination was performed to eval-uate the mass. H&E staining was performed using the resected tissues according to the standard protocol. Immunohistochemistry was-performed using the SP kit (Maixin Biote- chnology, Fuzhou, Fujian, China) according to the manufacturer’s protocol. Thesections were

[image:2.612.91.523.72.215.2]

Moreover, it showed that the nodule contained rich blood flow (Figure 1B), classifying the lesion as BI-RADS 4C. Both the radiologist and clinician became suspicious of this lesion. However, it was felt that this mass more likely represented a primary breast malignancy given that the incidence of metastatic RCC to the breast is so low. The patient opted to have the mass removed, which was completed under

Figure 1. Ultrasound shows a solid mass measuring 1.23 × 0.97 × 1.17 cm3 at 8 o’clock, 4 cm from the left nipple,

with a circumscribed border and regular shape. The mass is identified with a white arrow (A). Color Doppler flow imaging (CDFI) shows the mass contains rich blood flow (B).

Figure 2. Histopathological findings show that the tumor nodule is well cir

-cumscribed (A and B), magnification 40 × and 100 ×, respectively. The tumor

cells were arranged in acini or small nests, with clear or acidophilic

cyto-plasm (C), magnification 200 ×. Nucleoli could be seen in rare cells, identi

-fied with a black arrow 400 × (D).

incubated overnight at 4°C with the followingprimary an- tibodies: CK (1:100, Dako, Carpinteria, CA), vimentin (1: 200, Dako), CD10 (1:200, Da- ko), ER (1:100, Dako) PR (1: 100, Dako), GATA-3 (1:200, Dako) and EMA (1:100, Dako). This study was prospectively performed and approvedby the institutional Ethics Com- mittees of China MedicalUni- versity and conducted in accordance with the ethical-guidelines of the Declaration of Helsinki. Written informed-consent was obtained from the patient for the publication and accompanying images.

Result

Currently, an ultrasound exa- mination showed a solid mass measuring 1.23 × 0.97 × 1.17 cm3 with a regular margin at

[image:2.612.90.377.275.551.2]
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local anesthesia. Gross examination revealed a white to pink, circumscribed, 1.3 × 1.2 × 1.2 cm3 mass. H&E and immunohistochemistry

(IHC) staining was subsequently performed. Microscopically, the tumor was well circum-scribed (Figure 2A), with a nest or gland-like architecture (Figure 2B) and small to medium size tumor cells with clear or eosinophilic cyto-plasm showed atypical nuclei on low magnifica-tion (Figure 2C). Nucleoli were occasionally observed in some tumor cells on high magnifi-cation (Figure 2D). IHC showed that the tumor cells were strongly positive for CK, CD10, vimentin, and EMA (Figure 3), but negative for ER, PR, and GATA-3. Based on the medical his-tory, morphology, and IHC, the diagnosis of metastatic RCC to the breast was confirmed (Furhman grade I).

Discussion

Breast is an uncommon site for metastatic dis-ease, especially RCC, with only twenty-seven cases previously reported. Among these, there are fifteen cases of breast metastases discov-ered years after nephrectomy. In twelve of these cases, including two male patients, the initial presenting symptom was that of a

palpa-metastasis. The prognosis is more favorable with a better functional status and single ver-sus multiple metastases, disease-free survival from the first nephrectomy being greater than one year and having a low grade RCC [10]. According to the results of follow-up, those who develop secondary symptoms after nephrecto-my in a short period tend to have a poor prog-nosis. Compared to the incidence of metastatic disease to the breast, primary breast malignan-cy is much more common, and clinicians will usually favor this as the top differential. So in this case, male breast carcinoma is the most important differential diagnosis.

[image:3.612.88.379.72.342.2]

During initial consultation, detailed examina-tion should be performed to confirm whether the patient has any underlying malignant tumor. At present, fine needle aspiration cytology (FNAC) is the most usual method for breast lesion diagnosis, but it may increase the possi-bility of false negative rates for the vascular network that characterizes metastases from RCC [13]. Histopathologic examination is the most important tool in evaluating the differen-tial diagnosis. Neoplastic cells from a malig-nant tumor will most often have a different mor-phology and immunohistochemical profile from

Figure 3. Immunohistochemistry findings show that the tumor cells were strongly positive for CD10 (A), CK (B), EMA (C) and vimentin (D). Magnifica

-tion 100 ×, Magnifica-tion 400 × in the lower right corner with black square.

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that of a primary breast carcinoma. As in our case presentation, the tumor cells showed clear cell features which would lead the pathol-ogist to consider a diagnosis of RCC. IHC also plays an important role, and in our case the tumor cells were positive for CK, CD10, vimen-tin, and EMA, and were negative for ER, PR, and GATA-3. The treatment of metastatic RCC and primary carcinoma of the male breast is quite different. The principle treatment for male breast carcinoma is a modified radical mastec-tomy. Based on the high rate of expression of estrogen and progesterone receptors (80-90%), endocrine therapy is utilized and is extremely effective in improving the prognosis, especially in patients with advanced disease [21]. Previous studies have shown that adju-vant radiotherapy and chemotherapy are effec-tive in improving prognosis, but in some cases of older male patients, radiotherapy could cause severe cardiovascular and lung injury which leads to a worse clinical result [22]. Chemotherapy could be performed for patients with endocrine therapy resistance or positive lymph node status [23]. Due to the limited amount of the cases of solitary RCC metastasis to the breast, no standard treatment plan has been widely accepted. Lumpectomy is the main treatment, whether adjuvant radiotherapy and chemotherapy is necessary still needs further study. However, breast involvement may be a signal of rapid widespread dissemination of the neoplasm, and in that situation, the cancer

cells are usually not sensitive to classical che-motherapy and radiotherapy. Targeted therapy against vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) are more effective in improving progno-sis in that setting [24].

Conclusion

Establishing the correct diagnosis is crucial due to the differences in treatment and prognosis of male breast carcinoma and RCC metastatic to the breast. The correct diagnosis will aid the clinicians in choosing the most suitable medi-cal plan for the patient and will hopefully trans-late to better patient outcomes. The possibility of metastatic carcinoma should not be ruled out for a lesion that does not show the typical characteristics of breast cancer.

Acknowledgements

[image:4.612.88.525.96.307.2]

This study was supported by the National Natural Science Foundation ofChina (No. 813- 01930 to LH Yang, No. 81372497 to HT Xu, No. 81301837 to JH Yu, Grant No. 81401885 to XY Lin, No. 81302192 to L Wang), General project of Education Department of Liaoning Province (No. L2015595 to LH Yang), and Program for Liaoning Excellent Talents in University (No. LR2015067 to HT Xu), Students’ Innovation and Entrepreneurship Training Program (No. 201610159000036 to LH Yang).

Table 1. The clinical features and prognosis of patients with RCC metastasis to breast after nephrec-tomy

NO. Source Age (yr) Sex Tumor Type Fuhrman grade interva l (yr) Follow-upRecurrence

1 A. Botticelli, et [10] 60 F CCC II 4 NM

2 Mervat Mahrous, et [5] 58 F CCC II 5 Died at 14 months

3 S Ganapathi, et [11] 88 F CCC NM 4 At 1 and 6 months, no evidence of recurrence

4 Ahmed Alzaraa, et [8] 81 F NM NM 6 NM

5 H Hairulfaizi, et [6] 67 F CCC NM 5 NM

6 Mark E O’Donnell, et [12] 63 F NM NM 4 Died at 3 yrs

7 McLauglin SA, et [9] 76 F CCC II 12 At 3 months, no evidence of recurrence

8 G. Falco, et [13] 70 F CCC NM 9 NM

9 Svetana Bortnik [14] 57 F CCC III 2.8 At 2 yrs, no evidence of recurrence

10 Mauro Gacci [15] 82 F CCC II 3 Died at 7 months

11 Marlena Pursner [16] 14 F NM III 1 NM

12 Lucia Vassalli [17] 72 F NM II 9 At 1 yr, no evidence of recurrence

13 Neeta Pathe [18] 64 F CCC II 10 At 4 months, no evidence of recurrence

14 A. Forte [19] 71 F CCC NM 6 NM

15 Tai-Di Chen [20] 74 F NM III 3 NM

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Disclosure of conflict of interest

None

Address correspondence to: Shuang Ma, Depart- ment of Neurology, Shengjing Hospital of China Medical University, Shenyang 110022, Liao Ning, China. Tel: 86-18940258288; E-mail: cos360@163. com

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Figure

Figure 1. Ultrasound shows a solid mass measuring 1.23 × 0.97 × 1.17 cmwith a circumscribed border and regular shape
Figure 3. Immunohistochemistry findings show that the tumor cells were strongly positive for CD10 (A), CK (B), EMA (C) and vimentin (D)
Table 1. The clinical features and prognosis of patients with RCC metastasis to breast after nephrec-tomy

References

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