成人阴茎囊性淋巴管瘤1例

Cystic lymphangioma of the penis in an adult：A case report

摘要

淋巴管瘤是由淋巴系统发育异常所致的先天性脉管畸形，发病率约1/4000，多见于儿童，头颈部为好发部位，成人阴茎部位发病极为罕见，临床易误诊漏诊。本文报告 1 例成人阴茎囊性淋巴管瘤病例，患者 42 岁，因阴茎根部肿物 30 余年、近半年明显增大入院。查体于阴茎根部偏左侧触及约 7 cm×4 cm×5 cm 囊性肿物，透光试验阳性，双侧睾丸、附睾及精索未见异常。超声提示阴茎和阴囊交界区囊性无回声灶，边界清、形态不规则；磁共振成像显示阴茎根部多房囊性病变，范围约 5.6 cm×3.8 cm×6.3 cm ，影像学均支持囊性淋巴管瘤诊断。患者在硬膜外麻醉下行囊性肿物完整切除术，术中见肿物呈多房囊性，内含灰褐色液体；术后病理示囊壁内衬内皮细胞，免疫组织化学染色提示 CD31 阳性，确诊为囊性淋巴管瘤。基因检测提示体细胞 PIK3CA 基因 E545（GAG>GCG）杂合突变，与淋巴管瘤主要致病机制相符。淋巴管瘤主要与体细胞 PIK3CA 基因突变相关，突变可激活下游信号通路，促进淋巴内皮细胞异常增殖，进而形成囊性病变。临床表现以缓慢增大的无痛性囊性肿物为主，确诊依赖影像学与病理检查，需与腹股沟斜疝、鞘膜积液、精索静脉曲张等疾病鉴别。治疗以手术完整切除为首选，可有效降低复发；无法手术者可选择硬化治疗或西罗莫司、阿培利司等靶向药物。本例患者术后恢复良好，随访1个月无复发。成人阴茎囊性淋巴管瘤虽罕见，但具备典型临床、影像及病理特征，结合基因检测可明确诊断；早期完整切除预后良好，临床应加强对罕见部位淋巴管瘤的识别与规范处理。

Abstract

SUMMARY Lymphangioma is a congenital vascular malformation arising from aberrant lymphatic deve-lopment，with a reported incidence of approximately 1 in 4000.The condition predominates in the pedia- tric population，with the head and neck representing the most frequently affected anatomical regions.By contrast，scrotal lymphangioma in adults is exceedingly rare and remains highly susceptible to misdiagno- sis or diagnostic omission in clinical settings.Here，we report a case of cystic lymphangioma of the penis in a 42 -year-old male who presented with a mass at the penile root persisting for over 30 years，with marked enlargement over the preceding six months.Physical examination revealed a cystic mass measuring approximately 7 cm×4 cm×5 cm on the left aspect of the penile root，with a positive transil-lumination sign.Bilateral testes，epididymides，and spermatic cords were unremarkable.Ultrasonography demonstrated an irregular cystic anechoic lesion at the penoscrotal junction with well-defined margins. Magnetic resonance imaging（MRI）revealed a multilocular cystic lesion at the scrotal root measuring approximately 5.6 cm × 3.8 cm × 6.3 cm.Both imaging modalities were consistent with cystic lymphangio- ma.The patient underwent complete surgical resection under epidural anesthesia.Intraoperatively，the mass was confirmed to be multilocular and contained taupe-colored fluid.Histopathological analysis re- vealed endothelial cell lining of the cyst wall，and immunohistochemical staining was positive for CD31， establishing the definitive diagnosis of cystic lymphangioma.Genomic profiling identified a somatic heterozygous missense mutation in the PIK3CA gene at codon E545（GAG>GCG），consistent with the established pathogenic mechanism underlying lymphangioma.Mechanistically，somatic PIK3CA mutations activate downstream signaling cascades，driving aberrant proliferation of lymphatic endothelial cells and culminating in cystic lesion formation.Clinically，lymphangioma typically manifests as a painless，slowly enlarging cystic mass.Definitive diagnosis relies on integrated imaging and histopathological evaluation， with differential diagnoses encompassing indirect inguinal hernia，hydrocele，and varicocele.Complete surgical resection remains the first-line therapeutic strategy and is associated with a substantially reduced recurrence rate.For patients deemed ineligible for surgery，sclerotherapy or molecularly targeted agents， including sirolimus and alpelisib，represent viable alternatives.The patient achieved an uneventful post-operative recovery with no evidence of recurrence at one-month follow-up.Although adult scrotal cystic lymphangioma is a rare clinical entity，it exhibits characteristic clinical，radiological，and pathological features that，in conjunction with molecular genetic analysis，enable accurate diagnosis.Early complete resection confers a favorable prognosis.Heightened clinical awareness and standardized management of lymphangioma at atypical anatomical sites are warranted.

关键词

阴茎 / 囊性淋巴管瘤 / 淋巴管畸形

Key words

Penis / Cystic lymphangioma / Lymphatic malformation

参考文献

[1] 中华医学会整形外科分会血管瘤脉管畸形学组, 林晓曦. 血管瘤与脉管畸形诊疗指南(2024版)[J]. 组织工程与重建外科, 2024, 20(1):1-50.

[2] Karkkainen MJ, Haiko P, Sainio K, et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic ves- sels from embryonic veins[J]. Nat Immunol, 2004, 5(1): 74 - 80.

[3] Hägerling R, Pollmann C, Andreas M, et al. A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy[J]. EMBO J, 2013, 32(5):629-644.

[4] Petrova TV, Karpanen T, Norrmén C, et al. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis[J]. Nat Med, 2004, 10(9): 974 - 981.

[5] Martin-Almedina S, Martinez-Corral I, Holdhus R, et al. EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic- related hydrops fetalis[J]. J Clin Invest, 2016, 126(8): 3080 - 3088.

[6] Zhang G, Brady J, Liang WC, et al. EphB4 forward signalling regulates lymphatic valve development[J]. Nat Commun, 2015, 6 : 6625.

[7] Mäkinen T, Adams RH, Bailey J, et al. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature[J]. Genes Dev, 2005, 19(3):397-410.

[8] Mäkinen T, Boon LM, Vikkula M, et al. Lymphatic malforma- tions:Genetics,mechanisms and therapeutic strategies[J]. Circ Res, 2021, 129(1):136-154.

[9] Kunimoto K, Yamamoto Y, Jinnin M. ISSVA classification of vas- cular anomalies and molecular biology[J]. Int J Mol Sci, 2022, 23(4): 2358.

[10] Luks VL, Kamitaki N, Vivero MP, et al. Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA[J]. J Pediatr, 2015, 166 (4): 1048 - 1054.

[11] Osborn AJ, Dickie P, Neilson DE, et al. Activating PIK3CA alleles and lymphangiogenic phenotype of lymphatic endothelial cells isolated from lymphatic malformations[J]. Hum Mol Genet, 2015, 24(4):926-938.

[12] Janardhan HP, Saheera S, Jung R, et al. Vascular and lymphatic malformations:Perspectives from human and vertebrate studies[J]. Circ Res, 2021, 129(1):131-135.

[13] Elluru RG, Balakrishnan K, Padua HM. Lymphatic malforma- tions:Diagnosis and management[J]. Semin Pediatr Surg, 2014, 23(4):178-185.

[14] Rodriguez-Laguna L, Agra N, Ibañez K, et al. Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly[J]. J Exp Med, 2019, 216(2):407-418.

[15] Martinez-Corral I, Zhang Y, Petkova M, et al. Blockade of VEGF-C signaling inhibits lymphatic malformations driven by oncogenic PIK3CA mutation[J]. Nat Commun, 2020, 11: 2869.

[16] Churchill P, Otal D, Pemberton J, et al. Sclerotherapy for lym- phatic malformations in children:A scoping review[J]. J Pediatr Surg, 2011, 46(5):912-922.

[17] Ghaffarpour N, Petrini B, Svensson L, et al. Patients with lym- phatic malformations who receive the immunostimulant OK-432 experience excellent long-term outcomes[J]. Acta Paediatr, 2015, 104(11):1169-1173.