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Breast Cancer Metastasis in a Renal Carcinoma Pulmonary Metastasis: A Rare Example of Tumor-to-Tumor Metastasis

Breast Cancer Metastasis in a Renal Carcinoma Pulmonary Metastasis: A Rare Example of... Hindawi Case Reports in Oncological Medicine Volume 2021, Article ID 3054232, 6 pages https://doi.org/10.1155/2021/3054232 Case Report Breast Cancer Metastasis in a Renal Carcinoma Pulmonary Metastasis: A Rare Example of Tumor-to-Tumor Metastasis 1,2,3 4 5 6 7 Áurea Lima , Isa Peixoto , Susana Sarandão , Daniel Melo , Ângelo Rodrigues, and Helena Pereira Medical Oncology Service, Centro Hospitalar de Entre o Douro e Vouga, EPE, Unit of Santa Maria da Feira, R. Dr. Cândido Pinho 5, 4520-211 Santa Maria da Feira, Portugal Molecular Oncology and Viral Pathology Group, Research Center of Portuguese Institute of Oncology of Porto, Portuguese Institute of Oncology of Porto Francisco Gentil, EPE, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal CESPU, Institute for Research and Advanced Training in Health Sciences and Technologies, Cancer Research Group, R. Central da Gandra, 1317 Gandra, Portugal Medical Oncology Service, Centro Hospitalar Universitário do Porto, EPE, Largo Prof. Abel Salazar 4099-001 Porto, Portugal External Radiotherapy Service, Portuguese Institute of Oncology of Porto Francisco Gentil, EPE, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal Pathologic Anatomy Service, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro 4200-319 Porto, Portugal Pathologic Anatomy Service, Portuguese Institute of Oncology of Porto Francisco Gentil, EPE, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal Correspondence should be addressed to Áurea Lima; aurealimamd@gmail.com Received 12 April 2021; Accepted 1 June 2021; Published 23 June 2021 Academic Editor: Katsuhiro Tanaka Copyright © 2021 Áurea Lima et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The tumor-to-tumor metastasis phenomenon remains fairly uncommon, with fewer than 100 cases described to present time. Virtually any tumor can be a donor or a recipient neoplasm. Nevertheless, renal carcinomas have been implicated as the most common malignant tumors to harbor metastasis, while lung and breast tumors are the most frequent donors. This article reports an extremely rare case of a breast cancer metastasis in a lung metastasis of clear cell type renal cell carcinoma that met all Campbell and coworkers’ tumor-to-tumor metastasis criteria. Additionally, we present the literature case reports of breast cancer metastasis in renal cell carcinomas and try to discuss the mechanisms underlying its occurrence. Since this phenomenon identification will impact the therapeutic strategy and it is not easily detected by image, the anatomopathological study of any and all suspicious lesions is of crucial importance. To the best of our knowledge, this is the first report of a metastasis inside a metastasis. 1. Introduction with multiple synchronous or metachronous primary malig- nancies. The most common metastatic donor neoplasms are Tumor-to-tumor metastasis (TTM) is a term describing the lung and breast cancers, while meningioma is the most com- presence of two histologically distinct tumors at one location, mon recipient of metastasis among benign tumors and renal each with different morphologic and immunophenotypic cell carcinoma among malignant tumors [2]. Although the features [1]. It is an extremely rare phenomenon in patients lung is one of the organs most vulnerable to metastases, a 2 Case Reports in Oncological Medicine lung carcinoma is one of the rarest recipients of TTM [3]. Furthermore, the phenomenon of a metastasis in another metastasis is still a rarer event. Herein, we report a TTM case of a breast cancer metasta- sis in a pulmonary metastasis of clear cell type renal cell car- cinoma (ccRCC). This work has been approved by CHEDV’s Ethics Com- mittee, according to the Helsinki Declaration of the World Medical Association; also, the patient gave written informed consent to have her case used for this paper. 2. Results Figure 1: Transverse section of a thorax CT scan presenting an 8 2.1. Patient History and Presentation. We present a 57-year- mm pulmonary nodule. old woman with a past medical history of stage IV ccRCC (pT3aR0cN0M1) diagnosed in August 2019. During diagno- sis and staging evaluation, she was observed to have a 12 mm suspicious lesion on the left kidney and a 20 mm nonsuspi- sented results raised the hypothesis of being a breast cancer cious solid nodule in the right adrenal; the multidisciplinary metastasis in a lung metastasis of ccRCC. team (MDT) decided left radical nephrectomy, performed in September 2019, plus clinical and imagological surveil- 2.3. Medical Management and Treatment. Concerning the lance of the right adrenal nodule. Follow-up exams revealed breast cancer, breast MDT proposed the patient, in Novem- an increment of 2 mm of the right adrenal nodule without ber 2020, for adjuvant radiotherapy plus hormone therapy new lesions; MDT decided histological evaluation of the with anastrozole and dual anti-HER2 therapy with trastuzu- lesion, which revealed a ccRCC metastasis. Since this was a mab/pertuzumab (the anatomopathological confirmation of unique metastasis, a right adrenalectomy was performed in the breast cancer metastasis in the lung metastasis of the February 2020. In March 2020, the patient referred to having ccRCC occurred later in December). As for the ccRCC, uro- a palpable nodule in the left breast. The auxiliary diagnostic logic MDT proposed the patient, in January 2021, to pazopa- tests carried out revealed a stage III invasive ductal carci- nib. An overview of patient clinical history and management noma (IDC) ER 100%, PgR negative, HER2 positive (FISH), is given in Figure 6. and Ki67 > 30%, initially managed with neoadjuvant chemo- therapy (CHT) with sequential anthracycline/taxane-based 3. Discussion regime combined with dual anti-HER2 blockade (trastuzu- mab/pertuzumab), followed by surgery (cT3N+/ypT2N1 Metastasis from one neoplasm (the donor) to another neo- (3/15)cM0). In November 2020, the follow-up CT scan plasm (the recipient) has been described in the literature (Figure 1) showed bilateral pulmonary nodules. for many years since Fried published the first documented case of bronchogenic carcinoma metastatic to a meningioma 2.2. Diagnostic Workup. The patient was asymptomatic, with in 1930 [4, 5]. In 1968, Campbell and coworkers proposed a Karnofsky performance status (KPS) score of 100. No pos- the following basic criteria for the diagnosis of TTM: (i) diag- itive findings were encountered in the anamnesis on physical nosis of more than one primary tumor; (ii) extravascular examination and/or other follow-up exams. PET/CT showed metastasis existence; (iii) confirmation that it has not resulted abnormal 18F-FDG uptake in the referred suspected pulmo- from direct contiguous spread nor from tumor cell emboliza- nary nodules, without other hypermetabolic changes that tion; and (iv) in the presence of generalized lymphatic or may suggest malignant involvement (Figure 2). hematological malignancy, exclusion of those tumors that Given the impossibility of performing needle biopsy, the metastasized to the lymphatic system [1]. During the decades patient was proposed and accepted for surgery. Three pulmo- that followed, some authors reported TTM phenomenon, nary nodules, located in the left lung (basal, cisural, and with the donor neoplasm arising from a variety of sites, upper lobe), were excised. Microscopic examination was per- including the breast. Although the lung is one of the rarest formed to all nodules. Cisural and upper lobe nodules corre- recipients of TTM [3], renal neoplasms, and particularly sponded to ccRCC metastasis without additional findings. ccRCC, are the most common tumor metastasis recipient. Microscopic examination (Figures 3 and 4) and immunohis- Additionally, there have been few cases previously reported tochemical study (Figure 5) of the basal nodule biopsy of metastatic breast cancer within ccRCC (Table 1). specimen revealed two distinct neoplasms. The following We reported an extremely rare case of breast cancer immunophenotype was observed: CD10+, vimentin+ (heter- metastasis in a lung metastasis of ccRCC that met all Camp- ogenous), MelanA-, inhibin-, CK7-, and ER-, and inside this, bell and coworkers’ TTM criteria. another distinct phenotype was observed: CD10-, vimentin-, Although the exact mechanism by which TTM occurs is MelanA-, inhibin-, CK7+ (few cells), ER+, PgR-, GCDFP15-, yet to be understood, two major theories have been described Cam5.2+, EMA+ (few cells), and CD56-. Therefore, the pre- to explain this phenomenon [12–15]. The first one, the Case Reports in Oncological Medicine 3 Figure 2: PET/CT images showing an increased metabolic activity in the pulmonary suspected lesion. metabolic theory, argues that metastatic tumor cells would preferentially grow in microenvironments with abundant micronutrients, while the second one, the mechanical/ana- tomic theory, proposes that tumor metastasis is mainly determined by hemodynamic factors of the vascular and lymphatic system, as these factors are most important for successful delivery of metastatic tumor cells. The ccRCC is highly vascularized due to the inactivation of the von Hippel Lindau tumor suppressor gene, which increases hypoxia- inducible factor, leading to increased vascular endothelial Figure 3: Microscopic examination of the basal nodule biopsy growth factor [16]. This, in addition to the fact that kidneys specimen (H&E, 40x). Pulmonary parenchyma (upper left corner) receive approximately 20% of the cardiac output, makes with involvement of epithelial cells with the clear cytoplasm and ccRCC a hemodynamically favorable recipient, from a mech- well-defined cell membrane, interspersed within a highly anistic perspective [17]. Moreover, and from a metabolic vascularized stroma, compatible with ccRCC. Inside this, a distinct standpoint, ccRCC has increased glycogen and lipid content, population cells, arranged in nests, with a more eosinophilic which may account for its favorable microenvironment [18]. cytoplasm is identified, corresponding to the breast carcinoma. With this in mind, it is easy to understand why renal cell car- cinoma, and in particular ccRCC, is such a frequent recipient of TTM. Awareness of the TTM phenomenon is important to avoid an incorrect diagnosis and to select the appropriate treatment when unusual malignancies are encountered. In this case, due to their distinct biological behavior, there is not a single effective treatment for both HER2+ breast and ccRC metastatic cancers. Therefore, and since this patient has a good KPS score, both neoplasms were addressed sepa- rately. The change of the breast cancer stage led to the alter- ation of the anti-HER2 treatment strategy, with the initiation of dual blockade, as indicated by Cleopatra trial results for HER2+ metastatic disease [19]. Concerning the ccRCC treat- ment, our patient was in the International Metastatic Renal Cell Carcinoma Database Consortium (IMRCCDC) favor- able risk group. The results of Keynote 426 and of Check- Mate 9ER trials support the use of pembrolizumab plus Figure 4: Microscopic examination of the basal nodule biopsy axitinib or nivolumab plus cabozantinib, respectively, as the specimen with a high-power field showing the two neoplastic first-line treatment in metastatic disease for all IMRCCDC components (H&E, 400x). Note the two mitotic figures on the risk groups, being the preferred choices in the favorable risk breast cancer component. group, but neither of them are reimbursed by the Portuguese 4 Case Reports in Oncological Medicine (a) (b) (c) Figure 5: Immunohistochemical stains. (a) (Cam5.2, 200x) Both neoplasms are positive for cytokeratins, confirming an epithelial origin of the two neoplastic populations. (b) (CD10, 200x) Strong and diffuse positivity for CD10, characteristic of ccRCC. Highlight the antibody’s negativity in the breast carcinoma cell population. (c) (ER, 200x) Strong and nuclear positivity for the antibody directed to ER in breast carcinoma cells. Highlight the antibody’s negativity in the ccRCC component. Stage IV ccRCC Diagnosis Stage III IDC (unique metastasis at contralateral adrenal) Lung metastasectomy: breast cancer Radical Le mastectomy Adrenal metastasectomy Surgery metastasis in pulmonary metastasis of ccRCC nephrectomy with ALD Neoadjuvant treatment Systemic with AC followed by Pazopanib therapy Anastrozol+T+P D+T+P Chest wall and regional Radiation nodal irradiation (EBRT) 08-09/2019 02/2020 03/2020 10/2020 11/2020 12/2020 01/2021 Figure 6: Overview of the patient clinical history and management. Table 1: Clinical cases of breast carcinoma to renal cell carcinoma tumor-to-tumor metastasis described in the literature. Gender Age (years) Donor histology Receipt histology Location Reference Female 79 Invasive ductal carcinoma Clear cell renal cell carcinoma Right kidney [6] Female 62 Invasive ductal carcinoma Clear cell renal cell carcinoma Right kidney [7] Female 71 Invasive ductal carcinoma Clear cell renal cell carcinoma Right kidney [8] Female 74 Invasive ductal carcinoma Chromophobe renal cell carcinoma Right kidney [9] Female 43 Invasive ductal carcinoma Clear cell renal cell carcinoma Left kidney [10] Female 57 Invasive lobular carcinoma Clear cell renal cell carcinoma Right kidney [11] Medicines and Heath Care Products Authority (INFARMED), We report this case for its rarity. To date, literature which justify the option of pazopanib administration for this reported only six cases of metastasis of breast cancer in renal case therapeutic strategy (noninferior to sunitinib in the cell carcinomas. Nevertheless, and to the best of our knowl- COMPARZ trial with better quality of life) [20–22]. edge, this is the first report of a metastasis inside a metastasis. Case Reports in Oncological Medicine 5 [6] I. C. Lakovschek, ,E. Petru, M. J. Pollheimer, M. Ratschek, Abbreviations H. Augustin, and V. Bjelic-Radisic, “A rare case of cancer- AC: Doxorubicin and cyclophosphamide to-cancer metastasis: breast cancer to renal cell cancer : case ALD: Axillary lymph node dissection report and review of literature,” Wiener Medizinische Wochenschrift (1946), vol. 169, no. 13-14, pp. 350–353, ccRCC: Clear cell type renal cell carcinoma CHT: Chemotherapy CT: Computed tomography [7] M. G. Moller, T. Gribbin, S. Ebrom, G. Padula, and T. L. Fitz- gerald, “Breast cancer metastatic to renal cell carcinoma,” Sur- D: Docetaxel gery, vol. 139, no. 4, pp. 577–579, 2006. EBRT: External beam radiation therapy [8] M. Urdiales-Viedma, R. J. Luque, F. Valle, and S. Martos- ER: Estrogen receptor Padilla, “Clear cell renal cell carcinoma metastasized by a 18F-FDG: 18-F-Fluoro-2-deoxyglucose breast ductal carcinoma,” Archivos Españoles de Urología, FISH: Fluorescence in situ hybridization vol. 69, no. 4, pp. 197–201, 2016. H&E: Hematoxylin and eosin [9] W. Toro-Zambrano, Á. Gómez-Durán, A. F. Conde-Martin, HER2: Human epidermal growth factor receptor 2 C. Mayoral-Guisado, A. Ruiz-Guerrero, and A. Rubio- IDC: Invasive ductal carcinoma Fernández, “From tumour to tumour: metastasis of invasive IMRCCDC: International Metastatic Renal Cell Carcinoma ductal breast carcinoma to chromophobe renal cell carci- Database Consortium noma,” Revista Española de Patología, vol. 50, no. 1, pp. 58– KPS: Karnofsky performance status 63, 2017. MDT: Multidisciplinary team [10] Z. Huo, Y. Gao, Z. Yu, W. Zuo, and Y. Zhang, “Metastasis of P: Pertuzumab breast cancer to renal cancer: report of a rare case,” Interna- PET/CT: Positron emission computed tomography tional Journal of Clinical and Experimental Pathology, vol. 8, PgR: Progesterone receptor no. 11, pp. 15417–15421, 2015. T: Trastuzumab [11] D. Ashman, G. Quiroga-Garza, and D. Lee, “Rare presentation TTM: Tumor-to-tumor metastasis. of metastatic lobular breast carcinoma involving clear cell renal cell carcinoma,” Case Reports in Oncological Medicine, vol. 2020, Article ID 5315178, 5 pages, 2020. Conflicts of Interest [12] S. Paget, “The distribution of secondary growths in cancer of The authors declare no competing interests. the breast. 1889,” Cancer Metastasis Reviews, vol. 8, no. 2, pp. 98–101, 1989. [13] H. Peinado, H. Zhang, I. R. Matei et al., “Pre-metastatic niches: Authors’ Contributions organ-specific homes for metastases,” Nature Reviews. Cancer, H.P. was responsible for the case management. H.P., A.L., vol. 17, no. 5, pp. 302–317, 2017. I.P., and S.S. contributed to the case review. D.M. and A.R. [14] I. J. Fidler and G. Poste, “The “seed and soil” hypothesis revis- conducted the pathological review. A.L. and I.P. were the ited,” The Lancet Oncology, vol. 9, no. 8, p. 808, 2008. principal writers of the manuscript. A.L., I.P., S.S., and H.P. [15] N. Diseases, “A treatise on tumours. By James Ewing, A.M., edited and provided valuable insight into the preparation of M.D., Sc.D., Professor of Pathology at Cornell University Med- the paper. All authors approved the final paper. Áurea Lima ical College, N.Y.; Pathologist to the Memorial Hospital. Third edition. Royal 8vo. Pp. 1127, with 546 illustrations. 1928. Phil- and Isa Peixoto contributed equally to this work. adelphia and London: W. B. Saunders Co. Ltd. 63s. net,” Brit- ish Journal of Surgery, vol. 16, 2005. References [16] X. Na, G. Wu, C. K. Ryan, S. R. Schoen, P. A. di’santagnese, and E. M. Messing, “Overproduction of vascular endothelial [1] L. V. Campbell Jr., E. Gilbert, C. R. Chamberlain Jr., and A. L. growth factor related to von Hippel-Lindau tumor suppressor Watne, “Metastases of cancer to cancer,” Cancer, vol. 22, no. 3, gene mutations and hypoxia-inducible factor-1α expression in pp. 635–643, 1968. renal cell carcinomas,” The Journal of Urology, vol. 170, no. 2, [2] K. Honma, K. Hara, and T. Sawai, “Tumour-to-tumour metas- pp. 588–592, 2003. tasis. A report of two unusual autopsy cases,” Virchows Archiv [17] D. P. Kaufman, H. Basit, and S. J. Knohl, Physiology, Glomeru- A Pathological Anatomy and Histopathology, vol. 416, no. 2, lar Filtration Rate, StatPearls Publishing, Treasure Island, FL, pp. 153–157, 1989. USA, 2020. [3] F. Piacentini, G. Rossi, C. Casali, A. Cadioli, E. Barbieri, and [18] J. H. Pinthus, K. F. Whelan, D. Gallino, J. P. Lu, and V. Guarneri, “Primary pulmonary cancer colliding with meta- N. Rothschild, “Metabolic features of clear-cell renal cell static breast carcinoma: hitherto unreported cases of cancer- carcinoma: mechanisms and clinical implications,” Cana- to-cancer metastasis focusing on clinical implications,” Lung dian Urological Association Journal, vol. 5, no. 4, pp. 274– Cancer, vol. 74, no. 1, pp. 145–148, 2011. 282, 2011. [4] B. M. Fried, “Metastatic inoculation of a meningioma by can- [19] S. M. Swain, J. Baselga, S. B. Kim et al., “Pertuzumab, trastuzu- cer cells from a bronchiogenic carcinoma,” The American mab, and docetaxel in HER2-positive metastatic breast can- journal of pathology, vol. 6, 1930. cer,” The New England Journal of Medicine, vol. 372, no. 8, [5] C. Petraki, ,M. Vaslamatzis, T. Argyrakos et al., “Tumor to pp. 724–734, 2015. tumor metastasis: report of two cases and review of the litera- ture,” International Journal of Surgical Pathology, vol. 11, [20] B. I. Rini, E. R. Plimack, V. Stus et al., “Pembrolizumab plus no. 2, pp. 127–135, 2003. axitinib versus sunitinib for advanced renal-cell carcinoma,” 6 Case Reports in Oncological Medicine The New England Journal of Medicine, vol. 380, no. 12, pp. 1116–1127, 2019. [21] T. K. Choueiri, T. Powles, M. Burotto et al., “Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carci- noma,” The New England Journal of Medicine, vol. 384, no. 9, pp. 829–841, 2021. [22] R. J. Motzer, T. E. Hutson, D. Cella et al., “Pazopanib versus sunitinib in metastatic renal-cell carcinoma,” The New England Journal of Medicine, vol. 369, no. 8, pp. 722–731, http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Breast Cancer Metastasis in a Renal Carcinoma Pulmonary Metastasis: A Rare Example of Tumor-to-Tumor Metastasis

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Copyright © 2021 Áurea Lima et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Case Reports in Oncological Medicine Volume 2021, Article ID 3054232, 6 pages https://doi.org/10.1155/2021/3054232 Case Report Breast Cancer Metastasis in a Renal Carcinoma Pulmonary Metastasis: A Rare Example of Tumor-to-Tumor Metastasis 1,2,3 4 5 6 7 Áurea Lima , Isa Peixoto , Susana Sarandão , Daniel Melo , Ângelo Rodrigues, and Helena Pereira Medical Oncology Service, Centro Hospitalar de Entre o Douro e Vouga, EPE, Unit of Santa Maria da Feira, R. Dr. Cândido Pinho 5, 4520-211 Santa Maria da Feira, Portugal Molecular Oncology and Viral Pathology Group, Research Center of Portuguese Institute of Oncology of Porto, Portuguese Institute of Oncology of Porto Francisco Gentil, EPE, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal CESPU, Institute for Research and Advanced Training in Health Sciences and Technologies, Cancer Research Group, R. Central da Gandra, 1317 Gandra, Portugal Medical Oncology Service, Centro Hospitalar Universitário do Porto, EPE, Largo Prof. Abel Salazar 4099-001 Porto, Portugal External Radiotherapy Service, Portuguese Institute of Oncology of Porto Francisco Gentil, EPE, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal Pathologic Anatomy Service, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro 4200-319 Porto, Portugal Pathologic Anatomy Service, Portuguese Institute of Oncology of Porto Francisco Gentil, EPE, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal Correspondence should be addressed to Áurea Lima; aurealimamd@gmail.com Received 12 April 2021; Accepted 1 June 2021; Published 23 June 2021 Academic Editor: Katsuhiro Tanaka Copyright © 2021 Áurea Lima et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The tumor-to-tumor metastasis phenomenon remains fairly uncommon, with fewer than 100 cases described to present time. Virtually any tumor can be a donor or a recipient neoplasm. Nevertheless, renal carcinomas have been implicated as the most common malignant tumors to harbor metastasis, while lung and breast tumors are the most frequent donors. This article reports an extremely rare case of a breast cancer metastasis in a lung metastasis of clear cell type renal cell carcinoma that met all Campbell and coworkers’ tumor-to-tumor metastasis criteria. Additionally, we present the literature case reports of breast cancer metastasis in renal cell carcinomas and try to discuss the mechanisms underlying its occurrence. Since this phenomenon identification will impact the therapeutic strategy and it is not easily detected by image, the anatomopathological study of any and all suspicious lesions is of crucial importance. To the best of our knowledge, this is the first report of a metastasis inside a metastasis. 1. Introduction with multiple synchronous or metachronous primary malig- nancies. The most common metastatic donor neoplasms are Tumor-to-tumor metastasis (TTM) is a term describing the lung and breast cancers, while meningioma is the most com- presence of two histologically distinct tumors at one location, mon recipient of metastasis among benign tumors and renal each with different morphologic and immunophenotypic cell carcinoma among malignant tumors [2]. Although the features [1]. It is an extremely rare phenomenon in patients lung is one of the organs most vulnerable to metastases, a 2 Case Reports in Oncological Medicine lung carcinoma is one of the rarest recipients of TTM [3]. Furthermore, the phenomenon of a metastasis in another metastasis is still a rarer event. Herein, we report a TTM case of a breast cancer metasta- sis in a pulmonary metastasis of clear cell type renal cell car- cinoma (ccRCC). This work has been approved by CHEDV’s Ethics Com- mittee, according to the Helsinki Declaration of the World Medical Association; also, the patient gave written informed consent to have her case used for this paper. 2. Results Figure 1: Transverse section of a thorax CT scan presenting an 8 2.1. Patient History and Presentation. We present a 57-year- mm pulmonary nodule. old woman with a past medical history of stage IV ccRCC (pT3aR0cN0M1) diagnosed in August 2019. During diagno- sis and staging evaluation, she was observed to have a 12 mm suspicious lesion on the left kidney and a 20 mm nonsuspi- sented results raised the hypothesis of being a breast cancer cious solid nodule in the right adrenal; the multidisciplinary metastasis in a lung metastasis of ccRCC. team (MDT) decided left radical nephrectomy, performed in September 2019, plus clinical and imagological surveil- 2.3. Medical Management and Treatment. Concerning the lance of the right adrenal nodule. Follow-up exams revealed breast cancer, breast MDT proposed the patient, in Novem- an increment of 2 mm of the right adrenal nodule without ber 2020, for adjuvant radiotherapy plus hormone therapy new lesions; MDT decided histological evaluation of the with anastrozole and dual anti-HER2 therapy with trastuzu- lesion, which revealed a ccRCC metastasis. Since this was a mab/pertuzumab (the anatomopathological confirmation of unique metastasis, a right adrenalectomy was performed in the breast cancer metastasis in the lung metastasis of the February 2020. In March 2020, the patient referred to having ccRCC occurred later in December). As for the ccRCC, uro- a palpable nodule in the left breast. The auxiliary diagnostic logic MDT proposed the patient, in January 2021, to pazopa- tests carried out revealed a stage III invasive ductal carci- nib. An overview of patient clinical history and management noma (IDC) ER 100%, PgR negative, HER2 positive (FISH), is given in Figure 6. and Ki67 > 30%, initially managed with neoadjuvant chemo- therapy (CHT) with sequential anthracycline/taxane-based 3. Discussion regime combined with dual anti-HER2 blockade (trastuzu- mab/pertuzumab), followed by surgery (cT3N+/ypT2N1 Metastasis from one neoplasm (the donor) to another neo- (3/15)cM0). In November 2020, the follow-up CT scan plasm (the recipient) has been described in the literature (Figure 1) showed bilateral pulmonary nodules. for many years since Fried published the first documented case of bronchogenic carcinoma metastatic to a meningioma 2.2. Diagnostic Workup. The patient was asymptomatic, with in 1930 [4, 5]. In 1968, Campbell and coworkers proposed a Karnofsky performance status (KPS) score of 100. No pos- the following basic criteria for the diagnosis of TTM: (i) diag- itive findings were encountered in the anamnesis on physical nosis of more than one primary tumor; (ii) extravascular examination and/or other follow-up exams. PET/CT showed metastasis existence; (iii) confirmation that it has not resulted abnormal 18F-FDG uptake in the referred suspected pulmo- from direct contiguous spread nor from tumor cell emboliza- nary nodules, without other hypermetabolic changes that tion; and (iv) in the presence of generalized lymphatic or may suggest malignant involvement (Figure 2). hematological malignancy, exclusion of those tumors that Given the impossibility of performing needle biopsy, the metastasized to the lymphatic system [1]. During the decades patient was proposed and accepted for surgery. Three pulmo- that followed, some authors reported TTM phenomenon, nary nodules, located in the left lung (basal, cisural, and with the donor neoplasm arising from a variety of sites, upper lobe), were excised. Microscopic examination was per- including the breast. Although the lung is one of the rarest formed to all nodules. Cisural and upper lobe nodules corre- recipients of TTM [3], renal neoplasms, and particularly sponded to ccRCC metastasis without additional findings. ccRCC, are the most common tumor metastasis recipient. Microscopic examination (Figures 3 and 4) and immunohis- Additionally, there have been few cases previously reported tochemical study (Figure 5) of the basal nodule biopsy of metastatic breast cancer within ccRCC (Table 1). specimen revealed two distinct neoplasms. The following We reported an extremely rare case of breast cancer immunophenotype was observed: CD10+, vimentin+ (heter- metastasis in a lung metastasis of ccRCC that met all Camp- ogenous), MelanA-, inhibin-, CK7-, and ER-, and inside this, bell and coworkers’ TTM criteria. another distinct phenotype was observed: CD10-, vimentin-, Although the exact mechanism by which TTM occurs is MelanA-, inhibin-, CK7+ (few cells), ER+, PgR-, GCDFP15-, yet to be understood, two major theories have been described Cam5.2+, EMA+ (few cells), and CD56-. Therefore, the pre- to explain this phenomenon [12–15]. The first one, the Case Reports in Oncological Medicine 3 Figure 2: PET/CT images showing an increased metabolic activity in the pulmonary suspected lesion. metabolic theory, argues that metastatic tumor cells would preferentially grow in microenvironments with abundant micronutrients, while the second one, the mechanical/ana- tomic theory, proposes that tumor metastasis is mainly determined by hemodynamic factors of the vascular and lymphatic system, as these factors are most important for successful delivery of metastatic tumor cells. The ccRCC is highly vascularized due to the inactivation of the von Hippel Lindau tumor suppressor gene, which increases hypoxia- inducible factor, leading to increased vascular endothelial Figure 3: Microscopic examination of the basal nodule biopsy growth factor [16]. This, in addition to the fact that kidneys specimen (H&E, 40x). Pulmonary parenchyma (upper left corner) receive approximately 20% of the cardiac output, makes with involvement of epithelial cells with the clear cytoplasm and ccRCC a hemodynamically favorable recipient, from a mech- well-defined cell membrane, interspersed within a highly anistic perspective [17]. Moreover, and from a metabolic vascularized stroma, compatible with ccRCC. Inside this, a distinct standpoint, ccRCC has increased glycogen and lipid content, population cells, arranged in nests, with a more eosinophilic which may account for its favorable microenvironment [18]. cytoplasm is identified, corresponding to the breast carcinoma. With this in mind, it is easy to understand why renal cell car- cinoma, and in particular ccRCC, is such a frequent recipient of TTM. Awareness of the TTM phenomenon is important to avoid an incorrect diagnosis and to select the appropriate treatment when unusual malignancies are encountered. In this case, due to their distinct biological behavior, there is not a single effective treatment for both HER2+ breast and ccRC metastatic cancers. Therefore, and since this patient has a good KPS score, both neoplasms were addressed sepa- rately. The change of the breast cancer stage led to the alter- ation of the anti-HER2 treatment strategy, with the initiation of dual blockade, as indicated by Cleopatra trial results for HER2+ metastatic disease [19]. Concerning the ccRCC treat- ment, our patient was in the International Metastatic Renal Cell Carcinoma Database Consortium (IMRCCDC) favor- able risk group. The results of Keynote 426 and of Check- Mate 9ER trials support the use of pembrolizumab plus Figure 4: Microscopic examination of the basal nodule biopsy axitinib or nivolumab plus cabozantinib, respectively, as the specimen with a high-power field showing the two neoplastic first-line treatment in metastatic disease for all IMRCCDC components (H&E, 400x). Note the two mitotic figures on the risk groups, being the preferred choices in the favorable risk breast cancer component. group, but neither of them are reimbursed by the Portuguese 4 Case Reports in Oncological Medicine (a) (b) (c) Figure 5: Immunohistochemical stains. (a) (Cam5.2, 200x) Both neoplasms are positive for cytokeratins, confirming an epithelial origin of the two neoplastic populations. (b) (CD10, 200x) Strong and diffuse positivity for CD10, characteristic of ccRCC. Highlight the antibody’s negativity in the breast carcinoma cell population. (c) (ER, 200x) Strong and nuclear positivity for the antibody directed to ER in breast carcinoma cells. Highlight the antibody’s negativity in the ccRCC component. Stage IV ccRCC Diagnosis Stage III IDC (unique metastasis at contralateral adrenal) Lung metastasectomy: breast cancer Radical Le mastectomy Adrenal metastasectomy Surgery metastasis in pulmonary metastasis of ccRCC nephrectomy with ALD Neoadjuvant treatment Systemic with AC followed by Pazopanib therapy Anastrozol+T+P D+T+P Chest wall and regional Radiation nodal irradiation (EBRT) 08-09/2019 02/2020 03/2020 10/2020 11/2020 12/2020 01/2021 Figure 6: Overview of the patient clinical history and management. Table 1: Clinical cases of breast carcinoma to renal cell carcinoma tumor-to-tumor metastasis described in the literature. Gender Age (years) Donor histology Receipt histology Location Reference Female 79 Invasive ductal carcinoma Clear cell renal cell carcinoma Right kidney [6] Female 62 Invasive ductal carcinoma Clear cell renal cell carcinoma Right kidney [7] Female 71 Invasive ductal carcinoma Clear cell renal cell carcinoma Right kidney [8] Female 74 Invasive ductal carcinoma Chromophobe renal cell carcinoma Right kidney [9] Female 43 Invasive ductal carcinoma Clear cell renal cell carcinoma Left kidney [10] Female 57 Invasive lobular carcinoma Clear cell renal cell carcinoma Right kidney [11] Medicines and Heath Care Products Authority (INFARMED), We report this case for its rarity. To date, literature which justify the option of pazopanib administration for this reported only six cases of metastasis of breast cancer in renal case therapeutic strategy (noninferior to sunitinib in the cell carcinomas. Nevertheless, and to the best of our knowl- COMPARZ trial with better quality of life) [20–22]. edge, this is the first report of a metastasis inside a metastasis. Case Reports in Oncological Medicine 5 [6] I. C. Lakovschek, ,E. Petru, M. J. Pollheimer, M. Ratschek, Abbreviations H. Augustin, and V. Bjelic-Radisic, “A rare case of cancer- AC: Doxorubicin and cyclophosphamide to-cancer metastasis: breast cancer to renal cell cancer : case ALD: Axillary lymph node dissection report and review of literature,” Wiener Medizinische Wochenschrift (1946), vol. 169, no. 13-14, pp. 350–353, ccRCC: Clear cell type renal cell carcinoma CHT: Chemotherapy CT: Computed tomography [7] M. G. Moller, T. Gribbin, S. Ebrom, G. Padula, and T. L. Fitz- gerald, “Breast cancer metastatic to renal cell carcinoma,” Sur- D: Docetaxel gery, vol. 139, no. 4, pp. 577–579, 2006. EBRT: External beam radiation therapy [8] M. Urdiales-Viedma, R. J. Luque, F. Valle, and S. 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Case Reports in Oncological MedicineHindawi Publishing Corporation

Published: Jun 23, 2021

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