J Med Primatol doi:10.1111/jmp.12110
CASE REPORT
Mammary carcinoma in a male rhesus macaque (Macaca mulatta): histopathology and immunohistochemistry of ductal carcinoma in situ Bradley M. Roberts1, Kesara Chumpolkulwong1, Sujitra Tayamun1, Laksanee Inamnuay1, Anudep Rungsipipat2 & Eric D. Lombardini1 1 Divisions of Comparative Pathology and Veterinary Medical Research, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 2 Department of Veterinary Pathology, Chulalongkorn University, Bangkok, Thailand
Keywords Breast cancer – DCIS – male – mammary gland – neoplasia – non-human primate Correspondence Eric D. Lombardini, VMD, DACVP, DACVPM, Chief, Divisions of Comparative Pathology and Veterinary Medical Research, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand. Tel.: +662-696-4801; fax: +662-696-2838; e-mail: [email protected]
Abstract Background A mammary nodule was noted in a male rhesus macaque during physical examination. Methods and Results Histopathological and immunohistochemical analysis was performed. Ductal carcinoma in situ was confirmed. Conclusions To date, there are two reports of mammary carcinoma in male non-human primates, and none in the rhesus macaque.
Accepted February 20, 2014.
Introduction Mammary tumors in men account for less than one percent of all breast cancer diagnoses worldwide [11, 13]. Due to this rarity, almost all data concerning male breast cancer come from small, single-institutional studies, rather than from large clinical retrospective series as are conducted with female breast cancer. Because of the lack of epidemiological data, the behavior and optimal treatment for male breast cancer are not yet known [6]. Cases of male mammary neoplasia have been described in domestic animals, with frequent reports in cats and dogs [1, 14]. In laboratory species, mammary tumors have been observed in male rats, mice, and guinea pigs [16, 17]. While not noted with the same regularity as in these species, there are reports of mammary hyperplastic and neoplastic lesions in different species of female non-human primates [3, 20]. The veterinary literature only contains two cases of mammary carcinomas in male non-human primates.
The first describes a mammary adenocarcinoma diagnosed in a 16-year-old male squirrel monkey (Saimiri sciureus) [19]. The second case describes a ductal carcinoma in situ (DCIS) in a 23-year-old cynomolgus macaque (Macaca fascicularis) [20]. Case Report This study was conducted at the Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand. All animal care and procedures were approved by the AFRIMS Animal Care and Use Committee (IACUC). The AFRIMS macaque colony is accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC), International. The macaque was serologically negative for Simian retrovirus (SRV) types 1–5, Simian immunodeficiency virus (SIV) and Simian T-cell leukemia virus (STLV-1). This study describes the histopathological and immunohistochemical (IHC) characteristics of a
J Med Primatol 43 (2014) 213–216 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
213
Ductal carcinoma in situ in male rhesus macaque
Roberts et al.
spontaneous DCIS in a male rhesus macaque (Macaca mulatta). We believe this to be the first report of mammary carcinoma in a male rhesus macaque. A firm, round, 2.0-cm-diameter subcutaneous mass was identified in the right mammary gland of an 8-yearold adult male rhesus macaque during a routine physical examination in August 2009. No other clinical abnormalities were noted. The mass was surgically removed by excisional biopsy and placed in 10% neutral buffered formalin and embedded in paraffin for processing for histopathological and immunohistochemical (IHC) examination. All IHC was conducted in compliance with the purchased DAKO kits. No further treatment was required. Physical examinations over the subsequent 36 months were within normal limits, and the monkey is still alive. Histopathology Histopathological analysis confirmed solid-type DCIS (Fig. 1A, 1B). Expanding the mammary glandular tissue
(A)
(B)
(C)
(D)
(E)
214
(F)
is a multilobular, pseudoencapsulated, circumscribed neoplasm composed of polygonal cells emerging from the glandular epithelium and occluding the glandular lumenae. The neoplastic cells are frequently arranged in islands, trabeculae and irregular glands with cellular piling, loss of both normal architecture and polarity, but without evidence of breach of the basement membrane. Neoplastic cells have distinct cell borders, a moderate amount of microvaculated amphophilic cytoplasm, round to oval nuclei with finely stippled chromatin and typically one prominent central nucleolus. There is mild to moderate anisocytosis and anisokaryosis. The mitotic rate is approximately three per high-powered field with occasional bizarre mitotic figures. There is frequent single cell necrosis and the neoplastic lobules, and affected glands are surrounded by loosely packed fibrosis admixed with edema. Adjacent glands often have hyperplastic epithelium characterized by epithelial piling and the formation of papillary projections, which obscure the glandular lumen. Multifocally, interspersed in the interstitium and fibrosis are small streams of lymphocytes
Fig. 1 Ductal carcinoma in situ, mammary gland, male rhesus macaque. (A) Multilobular pseudoencapsulated circumscribed neoplasm composed of polygonal cells emerging from the glandular epithelium and occluding the glandular lumenae (H&E, 4x). (B) Neoplastic cells have distinct cell borders, a moderate amount of microvaculated amphophilic cytoplasm, round to oval nuclei with finely stippled chromatin and typically one prominent central nucleolus. There is mild to moderate anisocytosis and anisokaryosis. (H&E, 40x). (C) Positive membranous and cytoplasmic staining for bcl-2 marker (IHC, 400x). (D) Positive nuclear staining for p53 marker (IHC, 400x). (E) Decreasing positivity for cytoplasmic staining CK19 marker within the neoplastic cells (IHC, 400x). (F) Weak positive membranous stain for E-cadherin marker (IHC, 400x). J Med Primatol 43 (2014) 213–216 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Ductal carcinoma in situ in male rhesus macaque
Roberts et al.
Table 1 Immunohistochemical characteristics of the ductal mammary gland carcinoma in situ from the current study and relevant immunohistochemical statistics of mammary carcinomas from published sources Percent of tissues staining positive from reported cases in the literature
Marker
Current study result
DCIS in female macaques [20]
Mammary carcinomas in macaques [20]
DCIS in female humans [9]
Mammary carcinomas in male humans [4, 6, 12]
ER PR bcl-2 p53 CK 19 EMA S100 Her2/neu E-cadherin
Negative Negative Positive Positive Positive1 Negative Negative Negative Positive
40% (2/5) 40% (2/5) – – – – – 40% (2/5) –
47% (7/15) 53% (8/15) – – – – – 40% (6/15) –
68% (111/163) 46% (75/163) 64% (105/163) 26% (42/163) 99% (162/163) 99% (162/163) 0% (0/163) 39% (64/163) 100% (163/163)
81% (1254/1548) 74% (952/1287) 94% (72/77) 21% (16/77) 91% (29/32) – – 34% (252/741) –
All Immunohistochemical markers were conducted in accordance with the instructions and methodology of the purchased kits from the Envision Polymer DAKOâ, Denmark. Markers: ER, estrogen receptor; PR, progesterone receptor; bcl-2, B-cell lymphoma 2; p53, tumor protein 53; CK19, cytokeratin 19; EMA, epithelial membrane antigen; Her2/neu, human epidermal growth factor receptor 2. 1 CK 19 was found to present positive; however, the positivity was found to be weaker within the neoplastic cells (Fig. 1E).
and plasma cells. There is no evidence of lymphatic or circulatory invasion in the sample provided. Theoretically, by definition, DCIS is a pre-invasive, non-infiltrating lesion with little potential for lymph node or other organ metastasis [2, 10] and as such, surgical excision in humans is associated with 15-year survival rates of approximately 96%, free from distant metastases [15]. While all histological variants of mammary neoplasia have been identified in men [5, 8], DCIS is reported much less frequently than other types, with a prevalence rate of only 5–10% [5]. In women, DCIS is the most common subtype of non-invasive female breast cancer [18]. Immunohistochemistry The IHC statistics from relevant publications on mammary carcinoma and results from the current study are reported in Table 1. In this case, the tissues were negative for both estrogen receptor (ER) and progesterone receptor (PR). In men, neoplastic mammary tissues are generally immunoreactive for sex steroid antibodies (ER: 81%; PR: 74% [6]). However, there was a decrease in positive staining for sex steroids in women (ER: 68%; PR: 46% [9]) and in female macaques (ER: 40%; PR: 40% [20]) diagnosed specifically with DCIS. While rare, there have been reports of human male mammary tumors, which were negative for both ER and PR [7]. The rhesus neoplasm was immunoreactive for the oncoproteins B-cell lymphoma 2 (bcl-2) and p53, as well as for E-cadherin (Fig. 1C, 1D, 1F). In human neoplastic tissues, bcl-2 immunoreactivity is reported
in 94% of human male breast cancer cases; however, only 21% are positive for p53 [12]. 100% of tissues from women with DCIS were E-cadherin immunoreactive [9]. This tumor stained positive for cytokeratin 19 (CK 19), which correlates with the 91% immunoreactivity noted in human male breast cancer cases [4]. There was decreased positivity within the neoplastic cells in this instance in comparison with adjacent hyperplastic or normal epithelium (Fig. 1E). The neoplasm in this case was negative for human epidermal growth factor receptor 2 (HER2/neu), S100 protein and epithelial membrane antigen (EMA). HER2/neu has been found to be negative in 66% of mammary neoplasia in men [6]. Similar statistics are found in mammary carcinomas in female macaques [20] and DCIS in women [9] (Table 1). Comparable with our results, it is reported that 0% of human DCIS are positive for S-100 protein, dissimilarly; however, 99% were immunoreactive for EMA [9]. Conclusion There have only been two prior reports of carcinoma in the mammary glands of male non-human primates [19, 20], neither of which described the immunohistochemical features of the tumors, and there are no descriptions in the literature in the rhesus macaque (Macaca mulatta). The description and investigation of this rare finding contributes to the knowledge base of mammary carcinomas in the male rhesus macaque and adds to the extremely limited data available in male non-human primates in general.
J Med Primatol 43 (2014) 213–216 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
215
Ductal carcinoma in situ in male rhesus macaque
Roberts et al.
Conflict of interests
Funding
E. D. Lombardini is a Lieutenant Colonel in the US Army. The opinions or assertions herein are those of the authors and do not necessarily reflect the view of the Department of the Army or The Department of Defense.
No funding information is required.
References 1 Bearss JJ, Schulman FY, Carter D: Histologic, immunohistochemical, and clinical features of 27 mammary tumors in 18 male dogs. Vet Pathol 2012; 49:602–7. 2 Boler DE, Cabioglu N, Ince U, Esen G, Uras C: Sentinel lymph node biopsy in pure DCIS: is it necessary? ISRN Surg 2012; 2012:394095. 3 Choi JH, Yoon BI, Kim JH, Shin NS, Kwon SW, Lee KW, Kim DY: Mammary gland adenocarcinoma in a mandrill (Mandrillus sphinix). J Vet Med Sci 2001; 63:1233–5. 4 Ciocca V, Bombonati A, Gatalica Z, Di Pasquale M, Milos A, RuizOrrico A, Dreher D, Folch N, Monzon F, Santeusanio G, Perou CM, Bernard PS, Palazzo JP: Cytokeratin profiles of male breast cancers. Histopathology 2006; 4:365–70. 5 Fentiman IS, Fourquet A, Hortobagyi GN: Male breast cancer. Lancet 2006; 367:595–604. 6 Korde LA, Zujewski JA, Kamin L, Giordano S, Domchek S, Anderson WF, Bartlett JM, Gelmon K, Nahleh Z, Bergh J, Cutuli B, Pruneri G, McCaskill-Stevens W, Gralow J, Hortobagyi G, Cardoso F: Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol 2010; 28:2114–22. 7 Kornegoor R, Verschuur-Maes AH, Buerger H, Hogenes MC, De Bruin PC, Oudejans JJ, Van der Groep P, Hinrichs B, Van Diest PJ: Molecular subtyping of male breast cancer by immunohistochemistry. Mod Pathol 2012; 25:398–404.
216
8 Meguerditchian AN, Falardeau M, Martin G: Male breast carcinoma. Can J Surg 2002; 45:296–302. 9 Mejinen P, Peterse JL, Antonini N, Rutgers E, van der Vijver MJ: Immunohistochemical categorisation of ductal carcinoma in situ of the breast. Br J Cancer 2008; 98:137–42. 10 Misdorp W, Else RW, Hellmen E, Lipscomb TP: Hisological Classification of Mammary Tumors of the Dog and the Cat.Washington DC: Armed Forces Institute of Pathology in cooperation with the American Registry of Pathology and The World Health Organization Collaborating Center for Worldwide Reference on Comparative Oncology, 1999. 11 Ottini L, Palli D, Rizzo S, Federico M, Bazan V, Russo A: Male breast cancer. Crit Rev Oncol Hematol 2010; 73:141–55. 12 Rayson D, Erlichman C, Suman VJ, Roche PC, Wold LE, Ingle JN, Donohue JH: Molecular markers in male breast carcinoma. Cancer 1998; 83:1947–55. 13 Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 2012; 62:10–29. 14 Skorupski KA, Overley B, Shofer FS, Goldschmidt MH, Miller CA, Sorenmo KU: Clinical characteristics of mammary carcinoma in male cats. J Vet Intern Med 2005; 19:52–5. 15 Solin LJ, Kurtz J, Fourquet A, Amalric R, Recht A, Bornstein BA, Kuske R, Taylor M, Barrett W, Fowble B, Haffty B, Schultz DJ, Yeh IT, McCormick B, McNeese M: Fifteen-year results of breast-conserving surgery and
16
17
18
19
20
definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast. J Clin Oncol 1996; 14:754–63. Squire R, Goodman D, Valerio M, Fredrickson T, Strandberg J, Levitt M, Lingeman C, Harshbarger J, Dawe C: Tumors. Male reproductive system. In: Pathology of Laboratory Animals. Benirschke, Garner & Jones (eds). New York: SpringerVerlag, 1978; 1213–25. Suarez-Bonnet A, Martin de Las Mulas J, Millan MY, Herraez P, Rodriguez F, Espinosa de los Monteros A: Morphological and immunohistochemical characterization of spontaneous mammary gland tumors in the guinea pig (Cavia porcellus). Vet Pathol 2010; 47:298–305. Trentham-Dietz A, Sprague B, Alagoz O, Reaidi P, Rosenberg M, Gangnon R, Stout N: The impact of detection and treatment of carcinoma in situ on breast cancer mortality. Cancer Epidemiol Biomarkers Prev 2011; 20:720–720. Waggie KS, Tolwani RJ, Lyons DM: Mammary adenocarcinoma in a male squirrel monkey (Saimiri sciureus). Vet Pathol 2000; 37: 505–7. Wood CE, Usborne AL, Starost MF, Tarara RP, Hill LR, Wilkinson LM, Geisinger KR, Feiste EA, Cline JM: Hyperplastic and neoplastic lesions of the mammary gland in macaques. Vet Pathol 2006; 43:471–83.
J Med Primatol 43 (2014) 213–216 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
CASE REPORT
Mammary carcinoma in a male rhesus macaque (Macaca mulatta): histopathology and immunohistochemistry of ductal carcinoma in situ Bradley M. Roberts1, Kesara Chumpolkulwong1, Sujitra Tayamun1, Laksanee Inamnuay1, Anudep Rungsipipat2 & Eric D. Lombardini1 1 Divisions of Comparative Pathology and Veterinary Medical Research, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 2 Department of Veterinary Pathology, Chulalongkorn University, Bangkok, Thailand
Keywords Breast cancer – DCIS – male – mammary gland – neoplasia – non-human primate Correspondence Eric D. Lombardini, VMD, DACVP, DACVPM, Chief, Divisions of Comparative Pathology and Veterinary Medical Research, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand. Tel.: +662-696-4801; fax: +662-696-2838; e-mail: [email protected]
Abstract Background A mammary nodule was noted in a male rhesus macaque during physical examination. Methods and Results Histopathological and immunohistochemical analysis was performed. Ductal carcinoma in situ was confirmed. Conclusions To date, there are two reports of mammary carcinoma in male non-human primates, and none in the rhesus macaque.
Accepted February 20, 2014.
Introduction Mammary tumors in men account for less than one percent of all breast cancer diagnoses worldwide [11, 13]. Due to this rarity, almost all data concerning male breast cancer come from small, single-institutional studies, rather than from large clinical retrospective series as are conducted with female breast cancer. Because of the lack of epidemiological data, the behavior and optimal treatment for male breast cancer are not yet known [6]. Cases of male mammary neoplasia have been described in domestic animals, with frequent reports in cats and dogs [1, 14]. In laboratory species, mammary tumors have been observed in male rats, mice, and guinea pigs [16, 17]. While not noted with the same regularity as in these species, there are reports of mammary hyperplastic and neoplastic lesions in different species of female non-human primates [3, 20]. The veterinary literature only contains two cases of mammary carcinomas in male non-human primates.
The first describes a mammary adenocarcinoma diagnosed in a 16-year-old male squirrel monkey (Saimiri sciureus) [19]. The second case describes a ductal carcinoma in situ (DCIS) in a 23-year-old cynomolgus macaque (Macaca fascicularis) [20]. Case Report This study was conducted at the Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand. All animal care and procedures were approved by the AFRIMS Animal Care and Use Committee (IACUC). The AFRIMS macaque colony is accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC), International. The macaque was serologically negative for Simian retrovirus (SRV) types 1–5, Simian immunodeficiency virus (SIV) and Simian T-cell leukemia virus (STLV-1). This study describes the histopathological and immunohistochemical (IHC) characteristics of a
J Med Primatol 43 (2014) 213–216 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
213
Ductal carcinoma in situ in male rhesus macaque
Roberts et al.
spontaneous DCIS in a male rhesus macaque (Macaca mulatta). We believe this to be the first report of mammary carcinoma in a male rhesus macaque. A firm, round, 2.0-cm-diameter subcutaneous mass was identified in the right mammary gland of an 8-yearold adult male rhesus macaque during a routine physical examination in August 2009. No other clinical abnormalities were noted. The mass was surgically removed by excisional biopsy and placed in 10% neutral buffered formalin and embedded in paraffin for processing for histopathological and immunohistochemical (IHC) examination. All IHC was conducted in compliance with the purchased DAKO kits. No further treatment was required. Physical examinations over the subsequent 36 months were within normal limits, and the monkey is still alive. Histopathology Histopathological analysis confirmed solid-type DCIS (Fig. 1A, 1B). Expanding the mammary glandular tissue
(A)
(B)
(C)
(D)
(E)
214
(F)
is a multilobular, pseudoencapsulated, circumscribed neoplasm composed of polygonal cells emerging from the glandular epithelium and occluding the glandular lumenae. The neoplastic cells are frequently arranged in islands, trabeculae and irregular glands with cellular piling, loss of both normal architecture and polarity, but without evidence of breach of the basement membrane. Neoplastic cells have distinct cell borders, a moderate amount of microvaculated amphophilic cytoplasm, round to oval nuclei with finely stippled chromatin and typically one prominent central nucleolus. There is mild to moderate anisocytosis and anisokaryosis. The mitotic rate is approximately three per high-powered field with occasional bizarre mitotic figures. There is frequent single cell necrosis and the neoplastic lobules, and affected glands are surrounded by loosely packed fibrosis admixed with edema. Adjacent glands often have hyperplastic epithelium characterized by epithelial piling and the formation of papillary projections, which obscure the glandular lumen. Multifocally, interspersed in the interstitium and fibrosis are small streams of lymphocytes
Fig. 1 Ductal carcinoma in situ, mammary gland, male rhesus macaque. (A) Multilobular pseudoencapsulated circumscribed neoplasm composed of polygonal cells emerging from the glandular epithelium and occluding the glandular lumenae (H&E, 4x). (B) Neoplastic cells have distinct cell borders, a moderate amount of microvaculated amphophilic cytoplasm, round to oval nuclei with finely stippled chromatin and typically one prominent central nucleolus. There is mild to moderate anisocytosis and anisokaryosis. (H&E, 40x). (C) Positive membranous and cytoplasmic staining for bcl-2 marker (IHC, 400x). (D) Positive nuclear staining for p53 marker (IHC, 400x). (E) Decreasing positivity for cytoplasmic staining CK19 marker within the neoplastic cells (IHC, 400x). (F) Weak positive membranous stain for E-cadherin marker (IHC, 400x). J Med Primatol 43 (2014) 213–216 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Ductal carcinoma in situ in male rhesus macaque
Roberts et al.
Table 1 Immunohistochemical characteristics of the ductal mammary gland carcinoma in situ from the current study and relevant immunohistochemical statistics of mammary carcinomas from published sources Percent of tissues staining positive from reported cases in the literature
Marker
Current study result
DCIS in female macaques [20]
Mammary carcinomas in macaques [20]
DCIS in female humans [9]
Mammary carcinomas in male humans [4, 6, 12]
ER PR bcl-2 p53 CK 19 EMA S100 Her2/neu E-cadherin
Negative Negative Positive Positive Positive1 Negative Negative Negative Positive
40% (2/5) 40% (2/5) – – – – – 40% (2/5) –
47% (7/15) 53% (8/15) – – – – – 40% (6/15) –
68% (111/163) 46% (75/163) 64% (105/163) 26% (42/163) 99% (162/163) 99% (162/163) 0% (0/163) 39% (64/163) 100% (163/163)
81% (1254/1548) 74% (952/1287) 94% (72/77) 21% (16/77) 91% (29/32) – – 34% (252/741) –
All Immunohistochemical markers were conducted in accordance with the instructions and methodology of the purchased kits from the Envision Polymer DAKOâ, Denmark. Markers: ER, estrogen receptor; PR, progesterone receptor; bcl-2, B-cell lymphoma 2; p53, tumor protein 53; CK19, cytokeratin 19; EMA, epithelial membrane antigen; Her2/neu, human epidermal growth factor receptor 2. 1 CK 19 was found to present positive; however, the positivity was found to be weaker within the neoplastic cells (Fig. 1E).
and plasma cells. There is no evidence of lymphatic or circulatory invasion in the sample provided. Theoretically, by definition, DCIS is a pre-invasive, non-infiltrating lesion with little potential for lymph node or other organ metastasis [2, 10] and as such, surgical excision in humans is associated with 15-year survival rates of approximately 96%, free from distant metastases [15]. While all histological variants of mammary neoplasia have been identified in men [5, 8], DCIS is reported much less frequently than other types, with a prevalence rate of only 5–10% [5]. In women, DCIS is the most common subtype of non-invasive female breast cancer [18]. Immunohistochemistry The IHC statistics from relevant publications on mammary carcinoma and results from the current study are reported in Table 1. In this case, the tissues were negative for both estrogen receptor (ER) and progesterone receptor (PR). In men, neoplastic mammary tissues are generally immunoreactive for sex steroid antibodies (ER: 81%; PR: 74% [6]). However, there was a decrease in positive staining for sex steroids in women (ER: 68%; PR: 46% [9]) and in female macaques (ER: 40%; PR: 40% [20]) diagnosed specifically with DCIS. While rare, there have been reports of human male mammary tumors, which were negative for both ER and PR [7]. The rhesus neoplasm was immunoreactive for the oncoproteins B-cell lymphoma 2 (bcl-2) and p53, as well as for E-cadherin (Fig. 1C, 1D, 1F). In human neoplastic tissues, bcl-2 immunoreactivity is reported
in 94% of human male breast cancer cases; however, only 21% are positive for p53 [12]. 100% of tissues from women with DCIS were E-cadherin immunoreactive [9]. This tumor stained positive for cytokeratin 19 (CK 19), which correlates with the 91% immunoreactivity noted in human male breast cancer cases [4]. There was decreased positivity within the neoplastic cells in this instance in comparison with adjacent hyperplastic or normal epithelium (Fig. 1E). The neoplasm in this case was negative for human epidermal growth factor receptor 2 (HER2/neu), S100 protein and epithelial membrane antigen (EMA). HER2/neu has been found to be negative in 66% of mammary neoplasia in men [6]. Similar statistics are found in mammary carcinomas in female macaques [20] and DCIS in women [9] (Table 1). Comparable with our results, it is reported that 0% of human DCIS are positive for S-100 protein, dissimilarly; however, 99% were immunoreactive for EMA [9]. Conclusion There have only been two prior reports of carcinoma in the mammary glands of male non-human primates [19, 20], neither of which described the immunohistochemical features of the tumors, and there are no descriptions in the literature in the rhesus macaque (Macaca mulatta). The description and investigation of this rare finding contributes to the knowledge base of mammary carcinomas in the male rhesus macaque and adds to the extremely limited data available in male non-human primates in general.
J Med Primatol 43 (2014) 213–216 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
215
Ductal carcinoma in situ in male rhesus macaque
Roberts et al.
Conflict of interests
Funding
E. D. Lombardini is a Lieutenant Colonel in the US Army. The opinions or assertions herein are those of the authors and do not necessarily reflect the view of the Department of the Army or The Department of Defense.
No funding information is required.
References 1 Bearss JJ, Schulman FY, Carter D: Histologic, immunohistochemical, and clinical features of 27 mammary tumors in 18 male dogs. Vet Pathol 2012; 49:602–7. 2 Boler DE, Cabioglu N, Ince U, Esen G, Uras C: Sentinel lymph node biopsy in pure DCIS: is it necessary? ISRN Surg 2012; 2012:394095. 3 Choi JH, Yoon BI, Kim JH, Shin NS, Kwon SW, Lee KW, Kim DY: Mammary gland adenocarcinoma in a mandrill (Mandrillus sphinix). J Vet Med Sci 2001; 63:1233–5. 4 Ciocca V, Bombonati A, Gatalica Z, Di Pasquale M, Milos A, RuizOrrico A, Dreher D, Folch N, Monzon F, Santeusanio G, Perou CM, Bernard PS, Palazzo JP: Cytokeratin profiles of male breast cancers. Histopathology 2006; 4:365–70. 5 Fentiman IS, Fourquet A, Hortobagyi GN: Male breast cancer. Lancet 2006; 367:595–604. 6 Korde LA, Zujewski JA, Kamin L, Giordano S, Domchek S, Anderson WF, Bartlett JM, Gelmon K, Nahleh Z, Bergh J, Cutuli B, Pruneri G, McCaskill-Stevens W, Gralow J, Hortobagyi G, Cardoso F: Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol 2010; 28:2114–22. 7 Kornegoor R, Verschuur-Maes AH, Buerger H, Hogenes MC, De Bruin PC, Oudejans JJ, Van der Groep P, Hinrichs B, Van Diest PJ: Molecular subtyping of male breast cancer by immunohistochemistry. Mod Pathol 2012; 25:398–404.
216
8 Meguerditchian AN, Falardeau M, Martin G: Male breast carcinoma. Can J Surg 2002; 45:296–302. 9 Mejinen P, Peterse JL, Antonini N, Rutgers E, van der Vijver MJ: Immunohistochemical categorisation of ductal carcinoma in situ of the breast. Br J Cancer 2008; 98:137–42. 10 Misdorp W, Else RW, Hellmen E, Lipscomb TP: Hisological Classification of Mammary Tumors of the Dog and the Cat.Washington DC: Armed Forces Institute of Pathology in cooperation with the American Registry of Pathology and The World Health Organization Collaborating Center for Worldwide Reference on Comparative Oncology, 1999. 11 Ottini L, Palli D, Rizzo S, Federico M, Bazan V, Russo A: Male breast cancer. Crit Rev Oncol Hematol 2010; 73:141–55. 12 Rayson D, Erlichman C, Suman VJ, Roche PC, Wold LE, Ingle JN, Donohue JH: Molecular markers in male breast carcinoma. Cancer 1998; 83:1947–55. 13 Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 2012; 62:10–29. 14 Skorupski KA, Overley B, Shofer FS, Goldschmidt MH, Miller CA, Sorenmo KU: Clinical characteristics of mammary carcinoma in male cats. J Vet Intern Med 2005; 19:52–5. 15 Solin LJ, Kurtz J, Fourquet A, Amalric R, Recht A, Bornstein BA, Kuske R, Taylor M, Barrett W, Fowble B, Haffty B, Schultz DJ, Yeh IT, McCormick B, McNeese M: Fifteen-year results of breast-conserving surgery and
16
17
18
19
20
definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast. J Clin Oncol 1996; 14:754–63. Squire R, Goodman D, Valerio M, Fredrickson T, Strandberg J, Levitt M, Lingeman C, Harshbarger J, Dawe C: Tumors. Male reproductive system. In: Pathology of Laboratory Animals. Benirschke, Garner & Jones (eds). New York: SpringerVerlag, 1978; 1213–25. Suarez-Bonnet A, Martin de Las Mulas J, Millan MY, Herraez P, Rodriguez F, Espinosa de los Monteros A: Morphological and immunohistochemical characterization of spontaneous mammary gland tumors in the guinea pig (Cavia porcellus). Vet Pathol 2010; 47:298–305. Trentham-Dietz A, Sprague B, Alagoz O, Reaidi P, Rosenberg M, Gangnon R, Stout N: The impact of detection and treatment of carcinoma in situ on breast cancer mortality. Cancer Epidemiol Biomarkers Prev 2011; 20:720–720. Waggie KS, Tolwani RJ, Lyons DM: Mammary adenocarcinoma in a male squirrel monkey (Saimiri sciureus). Vet Pathol 2000; 37: 505–7. Wood CE, Usborne AL, Starost MF, Tarara RP, Hill LR, Wilkinson LM, Geisinger KR, Feiste EA, Cline JM: Hyperplastic and neoplastic lesions of the mammary gland in macaques. Vet Pathol 2006; 43:471–83.
J Med Primatol 43 (2014) 213–216 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
