产后女性外阴乳头状汗腺瘤1例报道并文献复习
Report of a Case of Vulvar Hidradenoma Papilliferum in a Postpartum Woman and Literature Review
DOI: 10.12677/acm.2025.151191, PDF, HTML, XML,   
作者: 段修杰:青岛大学青岛医学院,山东 青岛;蒋长青, 王 宁*:青岛大学附属医院妇科,山东 青岛
关键词: 乳头状汗腺瘤外阴产后女性Hidradenoma Papilliferum Vulvar Postpartum Woman
摘要: 目的:探讨外阴乳头状汗腺瘤的临床及病理学特征。方法:对1例产后外阴乳头状汗腺瘤患者的临床资料进行分析,并结合文献探讨乳头状汗腺瘤的临床及病理特征。结果:病人为32岁哺乳期女性,因“发现外阴肿物4月,增大半月余”入院,行外阴肿物切除术,术后病理诊断为外阴乳头状汗腺瘤。结论:产后外阴乳头状汗腺瘤是一种相对罕见的良性肿瘤,诊断需结合病史、术后病理形态学特征及免疫组织化学检查结果。
Abstract: Objective: To investigate the clinical and pathological features of vulvar hidradenoma papilliferum. Methods: The clinical data of one case of postpartum vulvar hidradenoma was analyzed, and the clinical and pathological features of vulvar hidradenoma were discussed in the literature. Results: The patient was a 32-year-old breast-feeding woman who was admitted to the hospital with a vulvar mass that had been found for 4 months and had increased in size for more than half a month. She underwent excision of the vulvar mass, and was diagnosed as a vulvar hidradenoma papilliferum on postoperative pathology. Conclusion: Postpartum vulvar hidradenoma papilliferum is a rare benign tumour, and the diagnosis should be based on the medical history, postoperative pathological features and immunohistochemical findings.
文章引用:段修杰, 蒋长青, 王宁. 产后女性外阴乳头状汗腺瘤1例报道并文献复习[J]. 临床医学进展, 2025, 15(1): 1429-1433. https://doi.org/10.12677/acm.2025.151191

1. 引言

乳头状汗腺瘤(hidradenoma papilliferum, HP)是一种少见的皮肤附属器良性肿瘤,以育龄期女性为主要发病人群,于哺乳期女性中发病罕见。因该肿瘤无特征性临床表现,易与其他疾病混淆,确诊依赖于术后病理检查。2023年9月,我科收治1例产后外阴乳头状汗腺瘤病人,本文对其临床资料进行分析,并结合相关文献进行复习,旨在提高对该病的认识及对其临床诊疗提供一定参考。

2. 病例资料

患者,女,32岁,因“发现外阴肿物4月,增大半月余”于2023-09-23就诊于青岛大学附属医院。患者4月前于孕晚期发现右侧外阴肿物,大小约1 cm,挤压时疼痛,偶有瘙痒,无接触性出血,肿物逐渐增大,患者未重视,未行诊治。产后哺乳期发现外阴肿物较前增大明显,并于产后半月出现肿物破溃出血,遂于我院妇科门诊就诊,行超声检查提示:右侧大阴唇见5.2 × 4.4 × 3.3 cm囊实性结节,形态规则,边界清,CDFI:内见较丰富点条状血流信号,RI:0.49。双侧腹股沟区未见明显有意义肿大淋巴结。考虑右侧大阴唇囊实性结节(见图1)。既往史:肾上腺嗜铬细胞瘤病史,已行手术治疗。手术史:2023-09-04于外院行剖宫产术。家族史:父母体健,否认家族中类似疾病史。妇科查体:右侧大阴唇肿物约6 × 5 cm,质硬,肿物包膜表面见两处菜花样肿物,直径均约1 cm,触血阳性(见图2)。阴道内褐色分泌物,宫颈少许糜烂,子宫前位,略大,质中,活动可,无压痛,双侧附件区未扪及明显异常。

入院后完善相关辅助检查,取外阴部分菜花样肿物送检,病理提示:外阴少许纤维囊壁样组织内见多量增生小腺体,伴急慢性炎细胞浸润,部分腺体呈双层上皮,部分腺体胞浆嗜酸,形态温和。倾向良性病变,不除外囊腺瘤或囊肿性病变可能。遂于2023-10-08行外阴肿物切除术,术中见:右侧大阴唇肿物约6 × 5 cm,质硬,肿物包膜表面见两处菜花样肿物,直径均约1 cm,触血阳性,见白色液体自菜花样肿物周围渗出。术后病理检查:肉眼观:带皮组织一件,大小4 × 4 × 2 cm,皮肤范围4 × 4 cm,皮肤表面带少许毛发,中央见两处破溃,直径0.8~0.9 cm。切开皮下见一灰红质软结节,大小4 × 3 × 2.5 cm,似有包膜,切面呈囊实性,局灶似有囊腔,内含灰红质脆内容物,基底及皮肤切缘涂墨。镜检提示:外阴肿物真皮内见较多腺样结构,部分呈乳头状生长,可见双层上皮,考虑来源汗腺的乳头状汗腺瘤(大小4 × 3 × 2.5 cm)伴浅溃疡形成,部分区域上皮增生活跃,可见少量核分裂像,部分区域上皮伴分泌性增生(不除外妊娠性改变),肿瘤未累及基底及皮肤四周切缘。免疫组化结果:S-100(+),GATA3(+),GCDFP-15 (少量+),P63 (肌上皮+),Ki-67 (热点区约20%),SM-MHC(+),ER (少量+),PR(−),PSA(−),CK7 (腺上皮+)。术后1月门诊复查外阴切口恢复良好。随访12个月无复发。

Figure 1. The ultrasonographic manifestations of vulvar papillary hidradenoma

1. 外阴乳头状汗腺瘤的超声表现

Figure 2. Post-operative sectional view of vulvar papillary hidradenoma

2. 外阴乳头状汗腺瘤术后剖视图

3. 讨论

乳头状汗腺瘤(HP),是由Worth于1878年首次描述的累及生殖器乳腺样腺体(Anogenital Mammary-Like Glands, AMLGs)的良性肿瘤[1] [2]。AMLGs是一种正常的皮肤附属器,组织学上界于小汗腺和大汗腺结构特征之间,主要位于肛门生殖器区域,目前被认为可能是在肛门生殖器区域发生的各种良性或恶性肿瘤的起源[2]。HP多累及肛门生殖器区域,也有耳部、眼睑、腹部、头皮、面部、胸部等部位的报道,这类发生于非肛门、生殖器区域的HP多被称为“异位汗腺瘤”[3]。HP多见于女性患者,男性患者报道少见,且男性患者的发病部位多位于颈肩部[4]

HP的临床表现无特异性,常表现为单发的、直径 ≤ 2 cm、质硬、界限清楚的类圆形结节[4] [5]。多发性HP约占HP患者的5%左右[6]。由于肿瘤生长缓慢,大部分患者无明显不适,仅少数患者可能出现瘤体破溃、出血、瘙痒及疼痛等症状。本例患者临床表现不同于既往文献报道,发生于哺乳期女性,在产后哺乳后出现肿瘤的迅速增大,肿瘤最大直径达4 cm,并出现破溃、瘙痒、出血等症状。

HP是一种良性病变,确诊依赖于手术病理检查。HP的皮肤镜检查结果可表现为:中央区域呈棕色/蓝色不规则结节,或无色素呈现,或整体呈灰蓝色均匀色素沉着,周边呈点状、不规则网状或细长毛细血管扩张,呈多形性血管模式,部分周边无任何血管模式[7]。免疫组化检测在乳头状汗腺瘤的诊断中具有重要意义,多数HP内层柱状细胞表达ER、PR、CK (AE1/AE3)、CK7、和EMA等,部分表达GCDFP-15,而外层肌上皮细胞则表达p63、actin、CD10、S-100和Calponin等[4]。既往研究表明约90%的HP中表达雌激素受体(ER),10%~90%表达孕激素受体(PR),并推测HP上皮细胞受卵巢产生的类固醇激素控制[8],在本例患者中,我们观察到ER少量阳性,PR表达缺失,这与先前报道的多数病例存在差异,考虑与妊娠期机体激素水平变化有关。研究表明,在妊娠期随着孕周增加,乳腺组织中ER、PR表达呈下降趋势[9];在妊娠及产后哺乳期女性乳腺肿瘤中,有ER、PR表达缺失情况出现[10],表明妊娠期及产后激素水平变化可能会导致妊娠期肿瘤的变化。Olecki等人[11]报道了1例肛门部位HP患者,在进行体外受精(In Vitro Fertilization, IVF)过程中出现了HP的增大,考虑HP受IVF中应用的外源性激素影响,但由于缺失该病例HP体积变化与各种激素应用的确切对应时间,仍需更多研究证实激素水平与HP的关系。在Hernández-Angeles报道的1例产后女性外阴HP中,肿瘤表现为产后的迅速增大,予手术切除后行病理检查,免疫组化结果提示肿瘤ER、PR表达均为阴性,研究者分析可能是由于妊娠期及哺乳期体内泌乳素水平升高,肿瘤细胞对泌乳素水平变化反应敏感,导致孕期及哺乳期HP患者出现瘤体短时间内迅速增大[12],但本例患者未进行泌乳素水平测定,目前也尚未有研究证实泌乳素与HP的关联性。Mcclain等人分析妊娠期激素水平或许会对HP产生组织学方面的变化[13]。鉴于妊娠期HP患者全球范围内罕见,以单例的病例报道为主,关于妊娠期激素水平变化与HP的发生发展的关系有待更多数据进行系统研究。

HP病因尚不清楚,国外有文献报道HP多发于育龄期且性活跃阶段女性[14] [15],人乳头瘤病毒感染(HPV)被认为与部分HP患者的发病有关[16]。由于HPV仅在少数HP患者中被检测到,二者的相关性目前尚不明确。而Saliha等报道了一例无性生活史的外阴HP患者,一定程度上否认了HPV与HP发生相关的这类观点[17]

HP治疗以手术切除为首选。手术需保证完整切除瘤体,以防止复发。因HP无特异性临床表现,易与其他常见疾病混淆,如乳头状汗管囊腺瘤、乳头状汗管瘤、管状顶泌汗腺腺瘤或外阴恶性肿瘤等[4]。组织病理学检查可辅助鉴别诊断。HP患者通常预后良好,恶变罕见。但目前已有HP向导管原位癌、外阴腺鳞癌、汗腺癌等恶变的病例报道。外阴乳头状汗腺瘤如出现的破溃、出血、溢液及周围淋巴结肿大等症状,病理检查出现非典型核分裂象和坏死,需警惕HP恶变可能[18]。Pfarr等人还在部分HP患者中发现癌症相关基因的突变(如PIK3CA、AKT1、BRAF/APC/ERBB4等),认为癌症相关基因突变可能为HP的恶性转化奠定基础[19]

综上所述,发生于哺乳期女性的外阴乳头状汗腺瘤非常罕见,术前易误诊,应结合病史,对于哺乳期短期出现的外阴肿物的迅速增长,可考虑乳头状汗腺瘤可能,尽早发现并手术完整切除病变为治疗首选,结合病理学特征及免疫组织化学检查结果进行诊断。

声 明

该病例报道已获得病人的知情同意。

NOTES

*通讯作者。

参考文献

[1] Baker, G.M., Selim, M.A. and Hoang, M.P. (2013) Vulvar Adnexal Lesions: A 32-Year, Single-Institution Review from Massachusetts General Hospital. Archives of Pathology & Laboratory Medicine, 137, 1237-1246.
https://doi.org/10.5858/arpa.2012-0434-oa
[2] Grabczynska, S.A., Toh, C.T., Francis, N., Costello, C. and Bunker, C.B. (2001) Rosai-Dorfman Disease Complicated by Autoimmune Haemolytic Anaemia: Case Report and Review of a Multisystem Disease with Cutaneous Infiltrates. British Journal of Dermatology, 145, 323-326.
https://doi.org/10.1046/j.1365-2133.2001.04325.x
[3] Foucar, E., Rosai, J. and Dorfman, R. (1990) Sinus Histiocytosis with Massive Lymphadenopathy (Rosai-Dorfman Disease): Review of the Entity. Seminars in Diagnostic Pathology, 7, 19-73.
[4] 展瑞, 赵光明, 钱振华, 等. 乳头状汗腺瘤10例临床病理分析[J]. 诊断病理学杂志, 2016, 23(12): 902-904+908.
[5] Spindler, L., Pommaret, E., Moyal Barracco, M., Fathallah, N., Plantier, F., Duchatelle, V., et al. (2019) Les hidradénomes papillifères de l’anus ressemblent à ceux de la vulve: Étude de 14 cas. Annales de Dermatologie et de Vénéréologie, 146, 537-541.
https://doi.org/10.1016/j.annder.2019.04.020
[6] El-Khoury, J., Renald, M., Plantier, F., Avril, M. and Moyal-Barracco, M. (2016) Vulvar Hidradenoma Papilliferum (HP) Is Located on the Sites of Mammary-Like Anogenital Glands (MLAGS): Analysis of the Photographs of 52 Tumors. Journal of the American Academy of Dermatology, 75, 380-384.
https://doi.org/10.1016/j.jaad.2016.01.034
[7] Konstantinova, A.M., Michal, M., Kacerovska, D., Spagnolo, D.V., Stewart, C.J., Kutzner, H., et al. (2016) Hidradenoma Papilliferum: A Clinicopathologic Study of 264 Tumors from 261 Patients, with Emphasis on Mammary-Type Alterations. The American Journal of Dermatopathology, 38, 598-607.
https://doi.org/10.1097/dad.0000000000000495
[8] Offidani, A. and Campanati, A. (1999) Papillary Hidradenoma: Immunohistochemical Analysis of Steroid Receptor Profile with a Focus on Apocrine Differentiation. Journal of Clinical Pathology, 52, 829-832.
https://doi.org/10.1136/jcp.52.11.829
[9] Taylor, D., Pearce, C.L., Hovanessian-Larsen, L., Downey, S., Spicer, D.V., Bartow, S., et al. (2009) Progesterone and Estrogen Receptors in Pregnant and Premenopausal Non-Pregnant Normal Human Breast. Breast Cancer Research and Treatment, 118, 161-168.
https://doi.org/10.1007/s10549-009-0322-4
[10] Jahanbin, B. and Soleimani, V. (2020) Histology of Pregnancy-Associated Breast Cancer. In: Advances in Experimental Medicine and Biology, Springer, 81-86.
https://doi.org/10.1007/978-3-030-41596-9_10
[11] Olecki, E.J. and Scow, J.S. (2021) Hidradeonoma Papilliferum of the Anus: A Case Report about the Relationship between Neoplasms of the Mammary-Like-Glands and Hormones. Cureus, 13, e13061.
https://doi.org/10.7759/cureus.13061
[12] Hernández-Angeles, C., Nadal, A. and Castelo-Branco, C. (2017) Hidradenoma Papilliferum of the Vulva in a Postpartum Woman: A Case Report. Journal of Obstetrics and Gynaecology, 37, 683-684.
https://doi.org/10.1080/01443615.2017.1284186
[13] McClain, C.M., Deavers, M.T., Sauls, C.D. and Diwan, A.H. (2015) Hidradenoma Papilliferum Associated with Pregnancy: A Case Report. Journal of Cutaneous Pathology, 42, 983-986.
https://doi.org/10.1111/cup.12586
[14] McGauran, M.F.G., Manolitsas, T., Tawfik, B., Joshi, D. and Lamont, J.M. (2021) Poroid Hidradenocarcinoma and Atypical Hidradenoma Papilliferum of the Vulva—Two Cases. Gynecologic Oncology Reports, 38, Article 100886.
https://doi.org/10.1016/j.gore.2021.100886
[15] Theodosiou, G., Zafeiriadou, V., Papageorgiou, M. and Mandekou-Lefaki, I. (2016) An Unusual Lesion in the Right Place. Dermatology Practical & Conceptual, 6, 7-9.
https://doi.org/10.5826/dpc.0603a03
[16] Kazakov, D.V., Mikyskova, I., Kutzner, H., Simpson, R.H.W., Hes, O., Mukensnabl, P., et al. (2005) Hidradenoma Papilliferum with Oxyphilic Metaplasia. The American Journal of Dermatopathology, 27, 102-110.
https://doi.org/10.1097/01.dad.0000154400.45465.a7
[17] Sağnıç, S., Ay, S.S., Tuncer, H.A., Doğan, S. and Şimşek, T. (2023) Hidradenoma Papilliferum of the Perineum; A Rare Tumour in a Rare Location. Journal of Obstetrics and Gynaecology, 43, Article 2186781.
https://doi.org/10.1080/01443615.2023.2186781
[18] MacNeill, K.N., Riddell, R.H. and Ghazarian, D. (2005) Perianal Apocrine Adenocarcinoma Arising in a Benign Apocrine Adenoma; First Case Report and Review of the Literature. Journal of Clinical Pathology, 58, 217-219.
https://doi.org/10.1136/jcp.2004.021394
[19] Pfarr, N., Sinn, H., Klauschen, F., Flechtenmacher, C., Bockmayr, M., Ridinger, K., et al. (2015) Mutations in Genes Encoding PI3K-AKT and MAPK Signaling Define Anogenital Papillary Hidradenoma. Genes, Chromosomes and Cancer, 55, 113-119.
https://doi.org/10.1002/gcc.22315