Primary Cutaneous Apocrine Adenocarcinoma of the Axilla in Klinefelter’s Syndrome: A Case Report PCAA in Klinefelter patient

Main Article Content

Nosakhare Ilerhunmwuwa
Kapilkumar Manvar
Richard Wu
Mathangi Chandramouli
Jen Chin Wang


primary cutaneous apocrine adenocarcinoma, immunohistochemistry, klinefelter syndrome


Background: Primary Cutaneous Apocrine Adenocarcinoma (PCAA) is a rare cutaneous malignancy that arises from areas rich in apocrine glands, particularly the axilla. There are less than 200 cases described in the literature. However, none has been reported in patients with Klinefelter syndrome, who are known to have an increased risk of breast cancer,

Case Presentation: We present a 66-year-old man with a significant family history of breast cancer who developed a right axillary mass initially thought to be hidradenitis suppurativa. On physical examination, he had bilateral gynecomastia. Laboratory workup was significant for hyper-gonadotrophic hypogonadism. Mammography showed bilateral gynecomastia with no radiologic evidence of malignancy in the breast, while magnetic resonance imaging of the breast revealed two suspicious masses seen in the right breast. Excision biopsy of the right axillary mass revealed a high-grade invasive adenocarcinoma involving the dermis and subcutis; the cells had prominent nucleoli vesicular chromatin pattern and voluminous eosinophilic cytoplasm consistent with primary cutaneous apocrine adenocarcinoma. Immunohistochemistry was positive for GATA-3, GCDFP-15, E-cadherin, ER Positive, PR negative, HER 2 by IHC 3 +, and androgen receptor-positive 100 %. Positron emission tomography showed mildly hypermetabolic asymmetric gynecomastia, right greater than left, but no abnormal hypermetabolic activity to suggest malignancy. Karyotype confirmed 47 XXY chromosomes which on. The patient underwent bilateral mastectomy due to his preference; excised breast tissue was negative for malignancy.

Conclusion: We presented the first case report of PCAA of axillary in Klinefelter syndrome. Awareness of this association and differentiation from breast carcinoma should be undertaken.


1. Agarwal S, Krishnamurthy K. StatPearls. StatPearls Publishing; Treasure Island (FL): May 8, 2022. Histology, Skin.
2. Nawrocki S, Cha J. The etiology, diagnosis, and management of hyperhidrosis: A comprehensive review: Etiology and clinical work-up. J Am Acad Dermatol. 2019;81(3):657-666. doi: 10.1016/j.jaad.2018.12.071.
3. Fulton EH, Kaley JR, Gardner JM. Skin Adnexal Tumors in Plain Language: A Practical Approach for the General Surgical Pathologist. Arch Pathol Lab Med. 2019;143(7):832-851. doi: 10.5858/arpa.2018-0189-RA.
4. Morabito A, Bevilacqua P, Vitale S, Fanelli M, Gattuso D, Gasparini G. Clinical Management of a Recurrent Apocrine Gland Carcinoma of the Scalp: Efficacy of a Chemotherapy Schedule with Methotrexate and Bleomycin. Tumori Journal. 2000;86(6):472-474. doi: 10.1177/030089160008600608
5. Horn RC. Malignant papillary cystadenoma of sweat glands with metastases to the regional lymph nodes. Surgery 1944; 16:348-55.
6. Hollowell KL, Agle SC, Zervos EE, Fitzgerald TL. Cutaneous apocrine adenocarcinoma: defining epidemiology, outcomes, and optimal therapy for a rare neoplasm. J Surg Oncol. 2012; 105:415-419. doi: 10.1002/jso.22023.
7. Robson A, Lazar AJ, Ben Nagi J, Hanby A, Grayson W, Feinmesser M, et al. Primary cutaneous apocrine carcinoma: a clinicopathologic analysis of 24 cases. Am J Surg Pathol. 2008;32(5):682-90. doi: 10.1097/PAS.0b013e3181590ba4.
8. Bonouvrie K, van der Werff Ten Bosch J, van den Akker M. Klinefelter syndrome and germ cell tumors: a review of the literature. Int J Pediatr Endocrinol. 2020; 2020:18. doi: 10.1186/s13633-020-00088-0.
9. Mies R, Fischer H, Pfeiff B, Winkelmann W, Würz H. Klinefelter's syndrome and Breast cancer. Andrologia. 1982;14(4):317-21. doi: 10.1111/j.1439-0272.1982.tb02268.x.
10. Crabtree M, Cheng D, Jeon C, Munteanu A, Vadehra K, Chiu R, et al. Primary cutaneous apocrine carcinoma in a 50-year old male, Human Pathology Reports, Volume 26, 2021, 300560, ISSN 2772-736X, doi: 10.1016/j.hpr.2021.300560.
11. Brown Z, Riesco-Martinez M, Petrella T. Treatment of primary cutaneous apocrine carcinoma of the scalp - case and review of the literature. Global Dermatology. 2016. 3. 356-360. doi: 10.15761/GOD.1000188.
12. Choi JH, Oh HM, Kim KS, Choi YD, Joo SP, Hwang WJ, et al. Primary cutaneous apocrine carcinoma of the scalp: Two case reports and literature review. Medicine (Baltimore). 2022; 11;101(6):e28808. doi: 10.1097/MD.0000000000028808.
13. Shintaku M, Tsuta K, Yoshida H, Tsubura A, Nakashima Y, Noda K. Apocrine adenocarcinoma of the eyelid with aggressive biological behavior: report of a case. Pathol Int. 2002;52(2):169-73. doi: 10.1046/j.1440-1827.2002.01323.x.
14. Seong M., Kim EK., Han K, Seol H, Kim H, Nohet W. Primary apocrine sweat gland carcinomas of the axilla: a report of two cases and a review of the literature. World J Surg Onc 13, 59 (2015). doi: 10.1186/s12957-015-0473-1.
15. Murphy GP, Elder DE. Non-melanocytic tumors of the skin. Atlas of tumor Pathology, 1991, third series. Vol I, pp 61-153. Armed Forces Institute of Pathology, Washington DC.
16. Groscurth P (2002) Anatomy of sweat glands. Curr Probl Dermatol 30:1–9.
17. Beier K, Ginez I, Schaller H. Localization of steroid hormone receptors in the apocrine sweat glands of the human axilla. Histochem Cell Biol. 2005;123(1):61-5. doi 10.1007/s00418-004-0736-3.
18. Paties C, Taccagni GL, Papotti M, Valente G, Zangrandi A, Aloi F. Apocrine carcinoma of the skin. A clinicopathologic, immunocytochemical, and ultrastructural study. Cancer 1993;71:375-81.
19. Fernandez-Flores A. A Modern Approach to Differential Diagnosis Between Cutaneous Apocrine Carcinoma and Metastasis From Breast Carcinoma. Am J Dermatopathol. 2016 Feb;38(2):162-4. doi: 10.1097/DAD.0000000000000302.
20. Piris A, Peng Y, Boussahmain C, Essary LR, Gudewicz TM, Hoang MP. Cutaneous and mammary apocrine carcinomas have different immunoprofiles. Hum Pathol. 2014;45(2):320-6. doi 10.1016/j.humpath.2013.09.007.
21. Wick MR, Ockner DM, Mills SE, Ritter JH, Swanson PE. Homologous carcinomas of the breasts, skin, and salivary glands. A histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat gland carcinoma, and salivary duct carcinoma. Am J Clin Pathol 1998; 109: 75–84.
22. Misago N, Shinoda Y, Okawa T, Aoki S, Toda S, Koike K, Narisawa Y. Histiocytoid and signet-ring cell carcinoma of the axilla: a type of cutaneous apocrine carcinoma equivalent to histiocytoid lobular carcinoma of the breast? Clin Exp Dermatol. 2011 Dec;36(8):874-7. doi: 10.1111/j.1365-2230.2011.04106.x.
23. Otsuka M, Yamasaki O, Kaji T, Shien T, Iwatsuki K. Metastatic cutaneous apocrine adenocarcinoma treated with a combination of pertuzumab-based targeted therapy and taxane chemotherapy: a case report. JAMA Dermatol. 2016;152(1):111-113. doi: 10.1001/jamadermatol.2015.2507.
24. Furudate S, Fujimura T, Tsukada A, Sato Y, Hidaka T, Tanita K, et al. Successful Treatment of Advanced Primary Cutaneous Apocrine Carcinoma on the Scrotum with Systemic Chemotherapy and Radiotherapy Followed by Denosumab. Case Rep Oncol. 2017 Jan 16;10(1):52-56. doi 10.1159/000455091.
25. Hidaka T, Fujimura T, Watabe A, Hashimoto A, Haga T, Onami K, Mizuashi M, Aiba S. Successful treatment of HER-2-positive metastatic apocrine carcinoma of the skin with lapatinib and capecitabine. Acta Derm Venereol. 2012 ;92(6):654-5. doi 10.2340/00015555-1354.
26. Ogata D, Kiyohara Y, Yoshikawa S, Kasami M. Treatment strategy for cutaneous apocrine carcinoma. J Clin Oncol. 2014;19:712-715.
27. Rogatsch M, Schmid J, Lax S, Uranitsch M, Schmid-Zalaudek K, Giuffrida R, Zalaudek I. Metastatic cutaneous apocrine adenocarcinoma responsive to the programmed cell death protein 1 inhibitor pembrolizumab. Eur J Cancer. 2018; 90:146-148. doi: 10.1016/j.ejca.2017.11.008.
28. Theriault RL, Carlson RW, Allred C, Anderson BO, Burstein HJ, et al.; National Comprehensive Cancer Network. Breast cancer, version 3.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2013;11(7):753-760.
29. Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, et al. Translational Breast Cancer Research Consortium (TBCRC 011). Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer Res. 2013 Oct 1;19(19):5505-12. doi 10.1158/1078-0432.CCR-12-3327.
30. Bonnefoi H, Grellety T, Tredan O, Saghatchian M, Dalenc F, Mailliez A, et al. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor-positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 2016;27(5):812-8. doi: 10.1093/annonc/mdw067.
31. Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, et al. Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer. J Clin Oncol. 2018. 20;36(9):884-890. doi: 10.1200/JCO.2016.71.3495.
32. Robson A, Lazar AJ, Ben Nagi J, Hanby A, Grayson W, Feinmesser M, et al. Primary cutaneous apocrine carcinoma: a clinicopathologic analysis of 24 cases. Am J Surg Pathol. 2008 ;32(5):682-90. doi: 10.1097/PAS.0b013e3181590ba4.
33. Collette F, Hamoir M, Van Eeckhout P, D'Abadie P, Duprez T, Schmitz S, Machiels JP. Metastatic cutaneous apocrine adenocarcinoma successfully treated with a systemic anti-androgen therapy-A case report. Clin Case Rep. 2020 Oct 30;8(12):3472-3478. doi: 10.1002/ccr3.3434.
34. Cardoso JC, Calonje E. Malignant sweat gland tumors: An update. Histopathology. 2015; 67:589-606.
35. Prasad V, Kao WH, Kao GF. Cutaneous adnexal carcinoma with apocrine differentiation. Cutis. 2016;98: E16-E19.

Article Statistics :Views : 95 | Downloads : 34 : 2