Nipple adenoma in prepubescent boy：a case report and review

Nipple adenoma in prepubescent boy：a case report and review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Nipple adenoma in prepubescent boy：a case report and review Jianzhe Chen, Tian Xia, Xiaomei Chen, Ansi Yin, Jie Xiong, Zhicai Duan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4196794/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background：Nipple adenoma is a rare benign nipple tumor that is seldom seen in males and can be challenging to differentiate from Paget's disease. Case report：We report the case of a boy with nipple adenoma who was initially misdiagnosed with Syringocystadenoma papilliferum combined with a tubular apocrine adenoma. Six months post-diagnosis, a nipple-areolar resection was conducted, followed by a purse-string suture technique to restore and reshape the nipple's appearance. Histopathological examination confirmed the diagnosis of nipple adenoma. Conclusion：Nipple adenomas often prove difficult to alleviate without surgical intervention; surgical excision is deemed the gold standard for treatment. It is vital to establish a clear pathological diagnosis for nipple adenomas, as they are benign tumors, to prevent unnecessary overtreatment. Nipple adenoma Breast tumor Boy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Nipple adenoma（NA） is an uncommon benign epithelial tumor of the nipple, predominantly occurring in women during their fifth decade but with a broad age range (from 5 months to 89 years). It is exceptionally rare in males, with only one reported case in a boy. Although it is rare and benign, the lesion can clinically mimic Paget's disease or nipple squamous cell carcinoma, and histologically it can be confused with ductal carcinoma, potentially leading to unnecessary overtreatment. We report a case of nipple adenoma in a boy. CASE REPORT A 9-year-old boy presented to our hospital with a left nipple lump and bloody discharge persisting for over a year. Physical examination revealed a 1*0.5 cm firm lesion in the left nipple, with visible erythema, erosion, and a small amount of bloody discharge. The lesion was well-defined, and the right breast appeared normal (Fig.1) No enlarged lymph nodes were palpable in either axilla. Ultrasound suggested a 1.0 cm diameter mass beneath the left nipple with clear boundaries and visible punctate blood flow signals（Fig.2）. The biopsy indicated Syringocystadenoma papilliferum combined with a tubular apocrine adenoma （SCAP-TAA）, and the patient was advised to follow up for observation. Over the subsequent six months, the erosion adjacent to the left nipple worsened, failed to heal, intermittently discharged bright red blood, and was accompanied by occasional stabbing pain. The boy returned to our hospital, where a complete excision of the left nipple, areola, and subcutaneous tissue was performed, followed by purse-string suture to reshape and restore the nipple's appearance. Macroscopically, the lesion involved the nipple and areolar area with clear boundaries and a grayish-white cut surface, lacking a capsule (Fig.3); microscopically，epithelial proliferation involving large ducts, stroma and extending towards the epidermis，usual ductal hyperplasia with focal squamoid morphology，small tubules and florid usual ductal hyperplasia adjacent to keratin cysts(Fig.4); Immunohistochemistry indicates Estrogen receptor（ER）(+,15%), Progesterone receptor（PR）(+,5%), cytokeratin（CK5/6）(+), and P63(+) demonstrates the presence of myoepithelial cells(Fig.5). Histopathology confirms the diagnosis of NA, and the surgical margins are negative. DISCUSSION NA, also referred to as florid papillomatosis, erosive adenomatosis, superficial papillary adenomatosis, or papillomatosis of the nipple, was officially named "Nipple Adenoma" in the World Health Organization (WHO) 2012 classification of breast tumors. The WHO 2019 classification defines it as a benign epithelial lesion with lactiferous duct-like structures involving the nipple collecting ducts, surrounding stroma, and adjacent overlying epidermis. The first case of NA was reported in 1955 by David B. Jones, who termed it "Florid Papillomatosis of the Nipple Ducts" and suggested distinguishing it from Paget's disease [1]. The first case of nipple lesion in a boy was reported by Kou Fujisawa in 2018[2]. NA is more common in adult women and rare in men, with only a few cases reported in minors, almost all of which are girls. Clinical features of NA are variable; due to skin changes, it can be detected when small, with the most common clinical symptoms being nipple erosion, erythema, and nipple bleeding, followed by small nodules in the nipple-areolar area and nipple induration, which may also be accompanied by itching and pain [3]. NA is located beneath the nipple-areolar area, presenting as a small, round mass with clear boundaries from surrounding tissue, and a cut surface that is grayish-white or brownish-yellow, without a capsule. Epithelial hyperplasia with a partial or total obliteration of the lumen with intraductal papillary projections, presence of intraductal necrosis, and nipple may appear eroded and erythematous as glandular epithelium replaces squamous epithelium. Epithelial and myoepithelial cells are arranged in a double layer, and fibrosis or sclerosis of the stroma may cause glandular distortion, presenting a pseudo-infiltrative pattern, with squamous metaplasia and apocrine metaplasia, superficial keratin cysts, acanthosis, toker cell hyperplasia in the epidermis and multinucleated giant cells[4,5,6,7].According to the WHO classification of breast tumors, the 4 most common recognized histological subtypes of NA are: (1) adenosis type; (2) epithelial hyperplasia or papillomatosis type; (3) sclerosing papillomatosis or pseudo-infiltrating type; and (4) mixed type[8]. There is no consensus on the immunohistochemical profile of NA, especially regarding ER PR and HER2 status. Angel Fernandez-Flores suggested in his study that the immunophenotype of male NA is similar to that of females, with ER and PR being negative [9], but our study showed that the inner epithelial cells were ER and PR positive. In the outer myoepithelial cells, P63, smooth muscle myosin, calponin (SMA), and CK5/6 were positive, aiding in the differentiation from malignant tumors [5,6]. Jau-Yu Liau found activating PIK3CA mutations in 12/24 cases, KRAS in 1/24 cases, and BRAF mutations in 2/24 cases, dividing NA into (1) sclerosing adenomatous type and (2) epithelial hyperplasia pattern (UDH-like pattern). Sixty percent of adenomatous NA had mutations in PIK3CA, RAS, or BRAF (10/15). The mutation rate in adenomatous-like NA is higher than in usual-ductal-hyperplasia-like NA, but the difference is not statistically significant. Interestingly, concurrent PIK3CA and RAS mutations in breast cancer predict a higher histological grade, but in his study, tumors with combined PIK3CA and RAS mutations did not show atypical hyperplasia（ADH）features[10]. The study used Sanger technology instead of NGS ( Next-generation sequencing technology) and had a small sample size, so further exploration of the molecular cytology aspect of NA is needed. NA has a false-negative rate of about 33% in mammography due to the small size and superficial location of the mass [3]. Ultrasound lacks characteristics, presenting as a mass with or without cystic components and hypervascular on Doppler [11]. Nuclear magnetic resonance （MRI）shows mass enhancement but lacks features and is expensive, so it is not recommended 12 . Nipple biopsy confirmation and complete surgical excision remain the gold standard for the diagnosis and treatment of NA. However, with increased understanding of NA, new diagnostic tools such as dermatoscopy [13], fine-needle aspiration, and scrape cytology have been proposed. Traditional treatment is complete surgical excision. In our case, complete excision of the left nipple-areolar complex and subcutaneous tissue was performed, followed by purse-string suture to reshape the nipple and restore its appearance. As the pursuit of aesthetics and technological development continue, oncoplastic surgery, Mohs micrographic surgery, wedge resection technique, nipple split de-nucleation technique, and cryotherapy are gradually being applied in the treatment of NA [8]. Given the clinical non-specificity of NA, accurate differential diagnosis is essential to prevent unnecessary aggressive treatment. NA mainly needs to be distinguished from the following diseases: (1) Paget's disease, which, like NA, can manifest with eczematous changes in the nipple. However, Paget's disease is characterized by the presence of distinctive Paget cells throughout the epidermal layers, whereas Toker cells in NA are typically smaller. Paget's disease cells often exhibit nuclear pleomorphism and frequently test positive for HER2 and EMA [7]; (2) invasive ductal carcinoma, when NA presents a pseudo-infiltrative pattern, it may be confused with Invasive ductal carcinoma（IDC）, but NA has a double layer of epithelial and myoepithelial cells, while breast cancer lacks myoepithelium and shows marked cellular atypia, common mitotic figures, and tumor nest formation, with immunohistochemical markers P63,CK5/6 helping to differentiate; (3) syringomatous tumor, which feature ducts of teardrop, comma, and branching shapes, and exhibit infiltrative growth with desmoplastic stroma. These tumors may show perineural invasion but do not involve the epidermis; (4) SCAP-TAA, as NA can be associated with apocrine metaplasia, Our initial biopsy mistakenly identified the condition as SCAP-TAA, which presents as cystic invaginations of the infundibular epithelium projecting into the dermis, covered by a double cell layer; the innermost layer is composed of columnar cells with decapitation secretion, and the outermost layer is composed of cuboidal cells with papillary projections, with immunohistochemical positivity for carcinoembryonic antigen(CEA) and epithelial membrane antigen（EMA）helping to differentiate[14]. Since NA is a benign proliferative process, complete excision is curative. However, as reported by Jones, M.W., and F.A. Tavassoli in 1995, five women with NA were found to have coexisting IDC or Ductal Carcinoma In Situ (DCIS) [15]. The relationship between NA and breast cancer remains undefined. Consequently, it is advisable for patients with NA to undergo long-term follow-up and observation post-treatment to detect any potential development of breast cancer or NA recurrence. Conclusion In summary, we report a rare case of nipple adenoma in a prepubescent boy. In males, the nipple-areolar complex is smaller, which limits the options of method for preserving the nipple shape as in female patients, where techniques such as the nipple split de-nucleation technique can be considered, performed by purse-string suture to reshape and restore the nipple's appearance in our case. Therefore, neoplastic changes occurring in the nipples of prepubescent male children should raise the suspicion of nipple adenoma. Abbreviations NA: nipple adenoma; SCAP-TAA: Syringocystadenoma papilliferum combined with a tubular apocrine adenoma; H&E: hematoxylin and eosin; ER: estrogen receptor; PR: progesterone receptor; SMA: smooth muscle myosin; CK5/6: cytokeratin; WHO: World Health Organization; MRI: magnetic resonance imaging; HER2: human epidermal growth factor receptor 2; ADH: atypical hyperplasia; NGS: next-generation sequencing technology; EMA: epithelial membrane antigen; CEA: carcinoembryonic antigen. Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the Clinical Trial Ethics Committee of the Southwest Medical University Affiliated Hospital. The publication of this case report and any accompanying images has been approved by the patient with written informed consent. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing financial interests. Authors’ contributions Jianzhe Chen was responsible for the collection of materials and the writing of the manuscript; Tian Xia provided pathological materials; Xiaomei Chen provided ultrasound materials; Ansi Yin，Jie Xiong and Zhicai Duan were in charge of collecting all human materials; Huaiquan Zuo* and Guangrui Pan* designed the research.This manuscript was read and approved the submission by all coauthors. Acknowledgments The authors would like to thank the Multidisciplinary Team (MDT) of the Department of Breast Surgery at Southwest Medical University for the assistance. Funding The authors declare no any funding. Data availability statement The authors will supply the relevant data in response to reasonable requests. References Jones DB. Florid papillomatosis of the nipple ducts. Cancer. 1955;8(2):315-9. Fujisawa K, Kato M, Kono T, Utsunomiya H, Watanabe A, Watanabe S. Nipple adenoma in a 2-year-old boy. Pediatr Dermatol. 2018;35(3):e184-e5. Fujii T, Yajima R, Morita H, Yamaguchi S, Tsutsumi S, Asao T, Kuwano H. Adenoma of the nipple projecting out of the nipple: curative resection without excision of the nipple. World J Surg Oncol. 2014;12:91. Wang C, Wang X, Ma R. Diagnosis and surgical treatment of nipple adenoma. ANZ J Surg. 2015;85(6):444-7. M DIB, Cantile M, Collina F, D'Aiuto M, Liguori G, R DEC, Botti G. Adenoma of the nipple: A clinicopathological report of 13 cases. Oncol Lett. 2014;7(6):1839-42. Tuveri M, Calo PG, Mocci C, Nicolosi A. Florid papillomatosis of the male nipple. Am J Surg. 2010;200(3):e39-40. Dillon DA, Lester SC. Lesions of the Nipple. Surg Pathol Clin. 2009;2(2):391-412. Spohn GP, Trotter SC, Tozbikian G, Povoski SP. Nipple adenoma in a female patient presenting with persistent erythema of the right nipple skin: case report, review of the literature, clinical implications, and relevancy to health care providers who evaluate and treat patients with dermatologic conditions of the breast skin. BMC Dermatol. 2016;16(1):4. Fernandez-Flores A, Suarez-Penaranda JM. Immunophenotype of nipple adenoma in a male patient. Appl Immunohistochem Mol Morphol. 2011;19(2):190-4. Liau JY, Lee YH, Tsai JH, Yuan CT, Chu CY, Hong JB, Sheen YS. Frequent PIK3CA activating mutations in nipple adenomas. Histopathology. 2017;70(2):195-202. Li M, Du J, Wang LJ, Li Z, Chen X. A Case of Nipple Adenoma Detected by Sonography. Chin Med J (Engl). 2016;129(19):2386-7. Matsubayashi RN, Adachi A, Yasumori K, Muranaka T, Ikejiri K, Yahara T, Takeshita M. Adenoma of the nipple: correlation of magnetic resonance imaging findings with histologic features. J Comput Assist Tomogr. 2006;30(1):148-50. Ansari MS, Taghizadeh Fazli J, Ehsani A. Dermoscopy of nipple adenoma. Clin Case Rep. 2020;8(12):3254-6. Leda L, Lins M, Leite E, Cardoso AEC, Houly RLS. Syringocystadenoma papilliferum combined with a tubular apocrine adenoma. An Bras Dermatol. 2017;92(5):721-3. Jones MW, Tavassoli FA. Coexistence of nipple duct adenoma and breast carcinoma: a clinicopathologic study of five cases and review of the literature. Mod Pathol. 1995;8(6):633-6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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It is exceptionally rare in males, with only one reported case in a boy. Although it is rare and benign, the lesion can clinically mimic Paget\u0026apos;s disease or nipple squamous cell carcinoma, and histologically it can be confused with ductal carcinoma, potentially leading to unnecessary overtreatment. We report a case of nipple adenoma in a boy.\u003c/p\u003e"},{"header":"CASE REPORT","content":"\u003cp\u003eA 9-year-old boy presented to our hospital with a left nipple lump and bloody discharge persisting for over a year. Physical examination revealed a 1*0.5 cm firm lesion in the left nipple, with visible erythema, erosion, and a small amount of bloody discharge. The lesion was well-defined, and the right breast appeared normal (Fig.1) No enlarged lymph nodes were palpable in either axilla. Ultrasound suggested a 1.0 cm diameter mass beneath the left nipple with clear boundaries and visible punctate blood flow signals（Fig.2）. The biopsy indicated Syringocystadenoma papilliferum combined with a tubular apocrine adenoma （SCAP-TAA）, and the patient was advised to follow up for observation. Over the subsequent six months, the erosion adjacent to the left nipple worsened, failed to heal, intermittently discharged bright red blood, and was accompanied by occasional stabbing pain. The boy returned to our hospital, where a complete excision of the left nipple, areola, and subcutaneous tissue was performed, followed by purse-string suture to reshape and restore the nipple\u0026apos;s appearance. Macroscopically, the lesion involved the nipple and areolar area with clear boundaries and a grayish-white cut surface, lacking a capsule (Fig.3); microscopically，epithelial proliferation involving large ducts, stroma and extending towards the epidermis，usual ductal hyperplasia with focal squamoid morphology，small tubules and florid usual ductal hyperplasia adjacent to keratin cysts(Fig.4); Immunohistochemistry indicates Estrogen receptor（ER）(+,15%), Progesterone receptor（PR）(+,5%), cytokeratin（CK5/6）(+), and P63(+) demonstrates the presence of myoepithelial cells(Fig.5). Histopathology confirms the diagnosis of NA, and the surgical margins are negative.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eNA, also referred to as florid papillomatosis, erosive adenomatosis, superficial papillary adenomatosis, or papillomatosis of the nipple, was officially named \u0026quot;Nipple Adenoma\u0026quot; in the World Health Organization (WHO) 2012 classification of breast tumors. The WHO 2019 classification defines it as a benign epithelial lesion with lactiferous duct-like structures involving the nipple collecting ducts, surrounding stroma, and adjacent overlying epidermis. The first case of NA was reported in 1955 by David B. Jones, who termed it \u0026quot;Florid Papillomatosis of the Nipple Ducts\u0026quot; and suggested distinguishing it from Paget\u0026apos;s disease [1]. The first case of nipple lesion in a boy was reported by Kou Fujisawa in 2018[2]. NA is more common in adult women and rare in men, with only a few cases reported in minors, almost all of which are girls. Clinical features of NA are variable; due to skin changes, it can be detected when small, with the most common clinical symptoms being nipple erosion, erythema, and nipple bleeding, followed by small nodules in the nipple-areolar area and nipple induration, which may also be accompanied by itching and pain [3]. NA is located beneath the nipple-areolar area, presenting as a small, round mass with clear boundaries from surrounding tissue, and a cut surface that is grayish-white or brownish-yellow, without a capsule. Epithelial hyperplasia with a partial or total obliteration of the lumen with intraductal papillary projections, presence of intraductal necrosis, and nipple may appear eroded and erythematous as glandular epithelium replaces squamous epithelium. Epithelial and myoepithelial cells are arranged in a double layer, and fibrosis or sclerosis of the stroma may cause glandular distortion, presenting a pseudo-infiltrative pattern, with squamous metaplasia and apocrine metaplasia, superficial keratin cysts, acanthosis, toker cell hyperplasia in the epidermis and multinucleated giant cells[4,5,6,7].According to the WHO classification of breast tumors, the 4 most common recognized histological subtypes of NA are: (1) adenosis type; (2) epithelial hyperplasia or papillomatosis type; (3) sclerosing papillomatosis or pseudo-infiltrating type; and (4) mixed type[8].\u003c/p\u003e\n\u003cp\u003eThere is no consensus on the immunohistochemical profile of NA, especially regarding ER PR and HER2 status. Angel Fernandez-Flores suggested in his study that the immunophenotype of male NA is similar to that of females, with ER and PR being negative [9], but our study showed that the inner epithelial cells were ER and PR positive. In the outer myoepithelial cells, P63, smooth muscle myosin, calponin (SMA), and CK5/6 were positive, aiding in the differentiation from malignant tumors [5,6]. Jau-Yu Liau found activating PIK3CA mutations in 12/24 cases, KRAS in 1/24 cases, and BRAF mutations in 2/24 cases, dividing NA into (1) sclerosing adenomatous type and (2) epithelial hyperplasia pattern (UDH-like pattern). Sixty percent of adenomatous NA had mutations in PIK3CA, RAS, or BRAF (10/15). The mutation rate in adenomatous-like NA is higher than in usual-ductal-hyperplasia-like NA, but the difference is not statistically significant. Interestingly, concurrent PIK3CA and RAS mutations in breast cancer predict a higher histological grade, but in his study, tumors with combined PIK3CA and RAS mutations did not show atypical hyperplasia（ADH）features[10]. The study used Sanger technology instead of NGS\u0026nbsp;(\u003cem\u003eNext-generation sequencing\u003c/em\u003e technology) and had a small sample size, so further exploration of the molecular cytology aspect of NA is needed.\u003c/p\u003e\n\u003cp\u003eNA has a false-negative rate of about 33% in mammography due to the small size and superficial location of the mass [3]. Ultrasound lacks characteristics, presenting as a mass with or without cystic components and hypervascular on Doppler [11]. Nuclear magnetic resonance （MRI）shows mass enhancement but lacks features and is expensive, so it is not recommended\u003cstrong\u003e\u003csup\u003e12\u003c/sup\u003e\u003c/strong\u003e. Nipple biopsy confirmation and complete surgical excision remain the gold standard for the diagnosis and treatment of NA. However, with increased understanding of NA, new diagnostic tools such as dermatoscopy [13], fine-needle aspiration, and scrape cytology have been proposed. Traditional treatment is complete surgical excision. In our case, complete excision of the left nipple-areolar complex and subcutaneous tissue was performed, followed by purse-string suture to reshape the nipple and restore its appearance. As the pursuit of aesthetics and technological development continue, oncoplastic surgery, Mohs micrographic surgery, wedge resection technique, nipple split de-nucleation technique, and cryotherapy are gradually being applied in the treatment of NA [8].\u003c/p\u003e\n\u003cp\u003eGiven the clinical non-specificity of NA, accurate differential diagnosis is essential to prevent unnecessary aggressive treatment. NA mainly needs to be distinguished from the following diseases: (1) Paget\u0026apos;s disease, which, like NA, can manifest with eczematous changes in the nipple. However, Paget\u0026apos;s disease is characterized by the presence of distinctive Paget cells throughout the epidermal layers, whereas Toker cells in NA are typically smaller. Paget\u0026apos;s disease cells often exhibit nuclear pleomorphism and frequently test positive for HER2 and EMA\u0026nbsp;[7]; (2) invasive ductal carcinoma, when NA presents a pseudo-infiltrative pattern, it may be confused with Invasive ductal carcinoma（IDC）, but NA has a double layer of epithelial and myoepithelial cells, while breast cancer lacks myoepithelium and shows marked cellular atypia, common mitotic figures, and tumor nest formation, with immunohistochemical markers P63,CK5/6 helping to differentiate; (3) syringomatous tumor, which feature ducts of teardrop, comma, and branching shapes, and exhibit infiltrative growth with desmoplastic stroma. These tumors may show perineural invasion but do not involve the epidermis; (4) SCAP-TAA, as NA can be associated with apocrine metaplasia, Our initial biopsy mistakenly identified the condition as SCAP-TAA, which presents as cystic invaginations of the infundibular epithelium projecting into the dermis, covered by a double cell layer; the innermost layer is composed of columnar cells with decapitation secretion, and the outermost layer is composed of cuboidal cells with papillary projections, with immunohistochemical positivity for carcinoembryonic antigen(CEA) and epithelial membrane antigen（EMA）helping to differentiate[14].\u003c/p\u003e\n\u003cp\u003eSince NA is a benign proliferative process, complete excision is curative. However, as reported by Jones, M.W., and F.A. Tavassoli in 1995, five women with NA were found to have coexisting IDC or Ductal Carcinoma In Situ (DCIS) [15]. The relationship between NA and breast cancer remains undefined. Consequently, it is advisable for patients with NA to undergo long-term follow-up and observation post-treatment to detect any potential development of breast cancer or NA recurrence.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, we report a rare case of nipple adenoma in a prepubescent boy. In males, the nipple-areolar complex is smaller, which limits the options of method for preserving the nipple shape as in female patients, where techniques such as the nipple split de-nucleation technique can be considered, performed by purse-string suture to reshape and restore the nipple\u0026apos;s appearance in our case. Therefore, neoplastic changes occurring in the nipples of prepubescent male children should raise the suspicion of nipple adenoma.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNA: nipple adenoma; SCAP-TAA: Syringocystadenoma papilliferum combined with a tubular apocrine adenoma; H\u0026amp;E: hematoxylin and eosin; ER: estrogen receptor; PR: progesterone receptor; SMA: smooth muscle myosin; CK5/6: cytokeratin; WHO: World Health Organization; MRI: magnetic resonance imaging; HER2: human epidermal growth factor receptor 2; ADH: atypical hyperplasia; NGS: next-generation sequencing technology; EMA: epithelial membrane antigen; CEA: carcinoembryonic antigen.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the Clinical Trial Ethics Committee of the Southwest Medical University Affiliated Hospital. The publication of this case report and any accompanying images has been approved by the patient with written informed consent. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing financial interests.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eJianzhe Chen was responsible for the collection of materials and the writing of the manuscript; Tian Xia provided pathological materials; Xiaomei Chen provided ultrasound materials; Ansi Yin，Jie Xiong and Zhicai Duan were in charge of collecting all human materials; Huaiquan Zuo* and Guangrui Pan* designed the research.This manuscript was read and approved the submission by all coauthors.\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the Multidisciplinary Team (MDT) of the Department of Breast Surgery at Southwest Medical University for the assistance.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe authors declare no any funding.\u003c/p\u003e\n\u003cp\u003eData availability statement\u003c/p\u003e\n\u003cp\u003eThe authors will supply the relevant data in response to reasonable requests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJones DB. Florid papillomatosis of the nipple ducts. Cancer. 1955;8(2):315-9.\u003c/li\u003e\n\u003cli\u003eFujisawa K, Kato M, Kono T, Utsunomiya H, Watanabe A, Watanabe S. Nipple adenoma in a 2-year-old boy. Pediatr Dermatol. 2018;35(3):e184-e5.\u003c/li\u003e\n\u003cli\u003eFujii T, Yajima R, Morita H, Yamaguchi S, Tsutsumi S, Asao T, Kuwano H. Adenoma of the nipple projecting out of the nipple: curative resection without excision of the nipple. World J Surg Oncol. 2014;12:91.\u003c/li\u003e\n\u003cli\u003eWang C, Wang X, Ma R. Diagnosis and surgical treatment of nipple adenoma. ANZ J Surg. 2015;85(6):444-7.\u003c/li\u003e\n\u003cli\u003eM DIB, Cantile M, Collina F, D\u0026apos;Aiuto M, Liguori G, R DEC, Botti G. Adenoma of the nipple: A clinicopathological report of 13 cases. Oncol Lett. 2014;7(6):1839-42.\u003c/li\u003e\n\u003cli\u003eTuveri M, Calo PG, Mocci C, Nicolosi A. Florid papillomatosis of the male nipple. Am J Surg. 2010;200(3):e39-40.\u003c/li\u003e\n\u003cli\u003eDillon DA, Lester SC. Lesions of the Nipple. Surg Pathol Clin. 2009;2(2):391-412.\u003c/li\u003e\n\u003cli\u003eSpohn GP, Trotter SC, Tozbikian G, Povoski SP. Nipple adenoma in a female patient presenting with persistent erythema of the right nipple skin: case report, review of the literature, clinical implications, and relevancy to health care providers who evaluate and treat patients with dermatologic conditions of the breast skin. BMC Dermatol. 2016;16(1):4.\u003c/li\u003e\n\u003cli\u003eFernandez-Flores A, Suarez-Penaranda JM. Immunophenotype of nipple adenoma in a male patient. Appl Immunohistochem Mol Morphol. 2011;19(2):190-4.\u003c/li\u003e\n\u003cli\u003eLiau JY, Lee YH, Tsai JH, Yuan CT, Chu CY, Hong JB, Sheen YS. Frequent PIK3CA activating mutations in nipple adenomas. Histopathology. 2017;70(2):195-202.\u003c/li\u003e\n\u003cli\u003eLi M, Du J, Wang LJ, Li Z, Chen X. A Case of Nipple Adenoma Detected by Sonography. Chin Med J (Engl). 2016;129(19):2386-7.\u003c/li\u003e\n\u003cli\u003eMatsubayashi RN, Adachi A, Yasumori K, Muranaka T, Ikejiri K, Yahara T, Takeshita M. Adenoma of the nipple: correlation of magnetic resonance imaging findings with histologic features. J Comput Assist Tomogr. 2006;30(1):148-50.\u003c/li\u003e\n\u003cli\u003eAnsari MS, Taghizadeh Fazli J, Ehsani A. Dermoscopy of nipple adenoma. Clin Case Rep. 2020;8(12):3254-6.\u003c/li\u003e\n\u003cli\u003eLeda L, Lins M, Leite E, Cardoso AEC, Houly RLS. Syringocystadenoma papilliferum combined with a tubular apocrine adenoma. An Bras Dermatol. 2017;92(5):721-3.\u003c/li\u003e\n\u003cli\u003eJones MW, Tavassoli FA. Coexistence of nipple duct adenoma and breast carcinoma: a clinicopathologic study of five cases and review of the literature. Mod Pathol. 1995;8(6):633-6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Nipple adenoma, Breast tumor, Boy","lastPublishedDoi":"10.21203/rs.3.rs-4196794/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4196794/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground：Nipple adenoma is a rare benign nipple tumor that is seldom seen in males and can be challenging to differentiate from Paget's disease.\u003c/p\u003e\n\u003cp\u003eCase report：We report the case of a boy with nipple adenoma who was initially misdiagnosed with Syringocystadenoma papilliferum combined with a tubular apocrine adenoma. Six months post-diagnosis, a nipple-areolar resection was conducted, followed by a purse-string suture technique to restore and reshape the nipple's appearance. Histopathological examination confirmed the diagnosis of nipple adenoma.\u003c/p\u003e\n\u003cp\u003eConclusion：Nipple adenomas often prove difficult to alleviate without surgical intervention; surgical excision is deemed the gold standard for treatment. It is vital to establish a clear pathological diagnosis for nipple adenomas, as they are benign tumors, to prevent unnecessary overtreatment.\u003c/p\u003e","manuscriptTitle":"Nipple adenoma in prepubescent boy：a case report and review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-12 18:27:22","doi":"10.21203/rs.3.rs-4196794/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ee28db5d-6ab5-4871-bfee-1a6226ce181e","owner":[],"postedDate":"April 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-27T15:58:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-12 18:27:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4196794","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4196794","identity":"rs-4196794","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}