兽研摘要
描述一只非隐睾伯恩山犬激素活性睾丸支持细胞瘤（SCT）的临床表现、诊断检查及成功结局。一只10岁未去势雄性犬因进行性脱毛、男性乳房发育和血尿就诊。诊断检查包括全血细胞计数、血清生化、雌二醇检测、腹部和睾丸超声检查、包皮细胞学以及双侧睾丸切除术后组织病理学检查。临床体征包括双侧对称性脱毛、色素沉着和下垂的包皮。实验室检查发现轻度非再生性贫血和严重高雌激素症（雌二醇：119 pg/mL）。包皮细胞学显示浅层上皮细胞占优势（> 80%），支持高雌激素症状态。超声检查发现左侧睾丸大型血管化肿块和前列腺囊性改变。组织病理学确诊为SCT。手术后，临床体征和实验室异常在9个月内完全消退。本病例强调，即使没有隐睾，SCT也应作为老年犬女性化综合征的鉴别诊断。它还突出表明包皮细胞学是一种快速、有效的微创工具，可用于高雌激素症的初步鉴定。
关键词：女性化综合征，高雌激素症，包皮细胞学，支持细胞瘤
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引言
睾丸支持细胞瘤（SCT）占犬诊断性睾丸肿瘤的14%–33%（Hayes and Pendergrass 1976; Hohšteter et al. 2014; Liao et al. 2009; Manuali et al. 2020）。与其他睾丸肿瘤一样，SCT最常见于隐睾，据报道患有腹股沟疝的犬肿瘤风险更高（Hayes et al. 1985）。通常，SCT是生长缓慢且无侵袭性的肿瘤，转移率低于10%（Subapriya et al. 2025）。与SCT相关的女性化综合征与高雌激素症有关，约57%的SCT患犬会出现该综合征（Mischke et al. 2002; Weaver 1983）。其特征为非瘙痒性、双侧对称性脱毛、色素沉着、男性乳房发育以及下垂、水肿的包皮（da Silva Flores et al. 2023; Fadok et al. 1986; Quartuccio et al. 2012）。尽管女性化综合征在隐睾病例中较为典型，这是由于滞留性腺的患病率和肿瘤转化率较高，但它也可在睾丸正常下降的犬中表现。雌激素诱导的骨髓毒性以骨髓发育不良为特征，也有与SCT相关的报道（Choi et al. 2008; Marshall 2018; Paepe et al. 2016; Post and Kilborn 1987; Sanpera et al. 2002; Sherding et al. 1981; Sontas et al. 2009; Withers et al. 2016）。在临床实践中，犬睾丸肿瘤的诊断方法包括体格检查、睾丸超声检查和组织学确认，而鉴别诊断包括其他原发性睾丸肿瘤，特别是间质细胞瘤和精原细胞瘤。
本报告描述了一例10岁雄性犬睾丸正常下降的睾丸SCT伴女性化综合征的临床病例。
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病例史
一只10岁6个月龄、未去势、非隐睾的雄性伯恩山犬，体重42.5 kg，因涉及腹部、腰部、胸部和肛周区域的双侧非瘙痒性脱毛，被转诊至萨萨里大学兽医教学医院进行临床评估。主人还报告了过去几个月内间歇性包皮血性分泌物和周期性出现的血尿，以及不愿爬楼梯和轻度嗜睡，他们将其归因于犬的年龄。未报告其他行为变化。该犬定期接种疫苗、常规驱虫和体外寄生虫治疗，饲喂商业干粮，可室内外活动。
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临床和实验室检查结果
体格检查显示一般健康参数正常，包括直肠温度38.1°C、脉搏率118次/分、呼吸频率19次/分、黏膜粉红湿润、毛细血管再充盈时间< 2秒、体况评分（BCS）为2/5。具体临床发现包括干燥、暗淡、变色、羊毛状被毛，伴有广泛对称性非瘙痒性脱毛（图1A）和色素沉着皮肤。包皮水肿且下垂（图1D），存在男性乳房发育（图1C），沿乳腺线和阴茎区域观察到丘疹，左侧睾丸大于右侧。该犬接受了血液和尿液分析、包皮细胞学和腹部超声检查。
[图：一只10岁伯恩山犬支持细胞瘤（SCT）的临床、大体和组织学发现。（A，B）C]
全血细胞计数显示轻度正细胞性、正色素性、非再生性贫血（表1）。血清生化分析显示天冬氨酸氨基转移酶轻度升高（AST 85 IU/L，参考区间[RIs] 17–52 IU/L），总蛋白浓度升高（TP 7.87 g/dL，RI 5.1–7.5 g/dL），由高球蛋白血症所致（GLOB 5.21 g/dL，RI 2.4–4.3 g/dL）。血清蛋白电泳显示白蛋白相对降低（ALB 38.2%，RI 45.5%–66.2%），β球蛋白（β-GLOB 26.5%，RI 12.8–23.7）和γ球蛋白（γ-GLOB 22.1%，RI 5.1%–17.8%）组分升高。此外，血清生化显示肌酸激酶升高（CPK 895 U/L）和高磷血症（11.6 mg/dL），阴离子间隙增大（34.0），而肾功能指标（尿素和肌酐）保持在正常参考区间内。主要血清生化和电泳结果总结于表2。
TABLE 1. Complete blood count (CBC) of the Bernese Mountain Dog at presentation.
| Parameter | Patient value | Reference interval | Status/note |
|---|---|---|---|
| Red blood cells (RBC) | 5.98 × 10 6 /μL | 5.90–8.70 | Normal |
| Haemoglobin (HGB) | 13.00 g/dL | 13.90–20.40 | Low |
| Haematocrit (HCT) | 40.50% | 43.20–63.20 | Low |
| Mean corpuscular volume (MCV) | 67.70 fL | 65.10–82.10 | Normal |
| Mean corpuscular HGB (MCH) | 21.70 pg | 21.40–25.60 | Normal |
| MCH concentration (MCHC) | 32.10 g/dL | 28.80–35.20 | Normal |
| Red cell distribution width (RDW) | 17.10% | 12.10–15.70 | High (Anisocytosis +++) |
| Reticulocytes | 65,182/μL (1.09%) | 11,504–147,178 | Non‐regenerative |
| White blood cells (WBC) | 11.35 × 10 3 /μL | 5.60–14.00 | Normal |
| Segmented neutrophils | 7673/μL (67.6%) | 3100–10,400 | Normal |
| Lymphocytes | 2145/μL (18.9%) | 1100–4300 | Normal |
| Monocytes | 885/μL (7.8%) | 100–900 | Normal |
| Eosinophils | 636/μL (5.6%) | 100–1200 | Normal |
| Basophils | 11/μL (0.1%) | 0–100 | Normal |
| Platelets (PLT) | 351 × 10 3 /μL | 110–475 | Normal (adequate) |
TABLE 2. Serum biochemistry profile of the Bernese Mountain Dog at presentation.
| Parameter | Patient value | Reference interval | Status/note |
|---|---|---|---|
| Creatine kinase (CPK) | 895 U/L | 35–200 | High |
| Aspartate aminotransferase (AST) | 85 U/L | 17–52 | High |
| Alanine aminotransferase (ALT) | 56 U/L | 19–76 | Normal |
| Alkaline phosphatase (ALP) | 67 U/L | 12–134 | Normal |
| Gamma‐glutamyl transferase (GGT) | 8 U/L | 2–9 | Normal |
| Total protein | 7.87 g/dL | 5.10–7.50 | High |
| Albumin | 2.66 g/dL | 2.40–3.70 | Normal |
| Globulins | 5.21 g/dL | 2.40–4.30 | High |
| Albumin/globulin ratio (A/G) | 0.51 | 0.60–1.30 | Low |
| Urea | 34 mg/dL | 18–50 | Normal |
| Creatinine | 1.12 mg/dL | 0.60–1.40 | Normal |
| Cholesterol | 233 mg/dL | 131–332 | Normal |
| Triglycerides | 39 mg/dL | 32–114 | Normal |
| Calcium | 10.1 mg/dL | 9.1–11.5 | Normal |
| Corrected calcium | 10.9 mg/dL | 9.9–12.1 | Normal |
| Phosphorus | 11.6 mg/dL | 2.5–5.5 | High |
| Calcium × phosphorus product | 125.9 | < 60.0 | High |
| Sodium | 149 mEq/L | 143–153 | Normal |
| Potassium | 5.5 mEq/L | 3.9–5.7 | Normal |
| Chloride | 103 mEq/L | 108–119 | Low |
| Bicarbonate HCO 3 − | 17.9 mEq/L | 17.0–24.0 | Normal |
| Anion gap | 34.0 | 15.0–25.0 | High |
| Iron (total) | 98 μg/dL | 80–214 | Normal |
血清雌二醇浓度为119.0 pg/mL，明显超过< 15 pg/mL的参考限值（Mischke et al. 2002）。
利什曼病酶联免疫吸附试验（ELISA）检测为阴性。血清胆固醇和甘油三酯浓度，以及基础皮质醇和尿皮质醇水平及甲状腺激素浓度均在实验室参考区间内。对自由采集尿样进行的尿液分析显示尿pH升高、血尿和蛋白尿，尿蛋白与肌酐比值为2.91。
按先前所述方法（Dreimanis et al. 2012）进行的包皮涂片细胞学检查显示细胞量高，以表层鳞状细胞为主（> 80%无核或核固缩）。副基底层细胞、中间层细胞和中性粒细胞罕见（图2）。
[图：包皮细胞学涂片显示细胞量高，以表层鳞状上皮细胞显著占优势（> 80%）]
腹部超声检查显示对称性前列腺增大，前列腺实质回声质地不均，并存在多个形态不规则的囊性结构，未从器官表面突出（图3）。左侧睾丸增大（约2.7 × 3.5 cm），回声质地不均、形态不规则且内部结构改变，彩色多普勒检查显示明显血管化（图4）。右侧睾丸形态、回声性和回声质地正常，但主观上体积减小（约2 × 1 cm）（图5）。观察到左侧髂内淋巴结增大（约4.1 cm × 1.4 cm）；淋巴结呈梭形，回声性正常。未检测到其他具有临床相关性的超声异常。
[图：前列腺纵切面（A）和横切面（B）的B型超声图像。器官 appears 增大，伴大的、i]
[图：左侧睾丸的B型（A）和彩色多普勒（B）超声图像。器官增大，边缘不规则]
[图：右侧睾丸纵切面B型超声图像（箭头），显示器官体积减小，保留正常]
对前列腺囊肿内液体进行了超声引导下抽吸，收集的样本随后送检进行细菌学培养。此外，对左侧髂内淋巴结进行了细针抽吸细胞学检查。细菌学培养为阴性，淋巴结细胞学结果与反应性淋巴样增生一致。
基于临床实验室和影像学诊断结果，怀疑单侧睾丸支持细胞瘤继发的女性化综合征，建议行睾丸切除术并进行组织病理学检查。
该犬术前给予右美托咪定（2 μg/kg；Sedastart 0.1% Ecuphar S.r.l.，米兰，意大利）、布托啡诺 0.2 mg/kg（Nargesic 1% ACME S.r.l.，雷焦艾米利亚，意大利）和马罗匹坦 1 mg/kg（Vetemex 1% Virbac S.r.l.，米兰，意大利）进行麻醉前给药。
使用丙泊酚 2 mg/kg 静脉注射（Proposure 1%，Merial Italia, S.p.a.，米兰，意大利）诱导麻醉，并以七氟烷（2%–2.2%；0.9–1 MAC）（SevoFlo Zoetis Belgium SA，新鲁汶，比利时）在氧气中维持麻醉。
实施了完全阴囊切除及双侧睾丸切除术。双侧睾丸及阴囊组织送组织学检查。
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病理学发现
大体检查发现，两侧睾丸在大小和质地方面存在显著差异（图1E）。左侧睾丸明显增大（27.1 mm × 35.2 mm），质地坚实、不规则，而右侧睾丸大小为 15.6 mm × 23.1 mm，质地规则。切开后，左侧睾丸肿物呈白色、外观均匀，并可见部分出血和局灶性坏死区域。右侧睾丸则外观正常。左侧睾丸的组织学检查显示，管状支持上皮细胞呈实性、多灶性和浸润性肿瘤性增生，符合支持细胞瘤（SCT）（图1F）。肿瘤细胞排列成索状、巢状及偶见的管状结构，由纤细的纤维血管间质支撑。可见中度细胞和核异型性，核分裂活性低（< 1个核分裂象/高倍视野）。此外，可见广泛凝固性坏死区域。肿瘤邻近的睾丸实质显示严重的生精萎缩，生精小管内精原细胞明显减少或缺失。右侧睾丸未见明显变化。
术后恢复顺利。在随后的几个月中，皮肤改变、男性乳腺发育、水肿和下垂的包皮逐渐消退，被毛完全重新生长，主人报告患犬活力增加，包皮出血消退。在5个月和9个月的随访中，该犬总体状况极佳，临床检查和实验室检查结果均正常（图1B）。主人报告偶有轻度漏尿。总体而言，结局良好，长期预后良好。
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讨论
本病例报告描述了一只未去势雄性犬左侧睾丸支持细胞瘤所致的女性化综合征。支持细胞瘤是激素活性肿瘤，起源于睾丸内的性腺间质组织，可产生雌激素和抑制素（Peters et al. 2000）。
尽管睾丸支持细胞瘤在隐睾犬中更为常见，但也可发生于阴囊内睾丸。对于睾丸正常下降的犬，年龄是主要危险因素，据报道腹腔内睾丸的平均年龄为7.8岁，腹股沟睾丸为8.8岁，阴囊内睾丸为11岁（Reif and Brodey 1969; Soto‐Heras et al. 2024）。这一考虑强调了将睾丸触诊纳入常规临床检查的重要性，尤其是在老年犬中，对于出现弥漫性皮肤改变的犬更为重要。
伯恩山犬未被列为睾丸肿瘤发病率最高的品种之一；然而，总体而言，纯种犬被诊断患有睾丸肿瘤的频率高于混种犬（Ngo et al. 2025）。
本病例中观察到的女性化综合征是一种公认的副肿瘤性病症，据报道见于24%–57%的支持细胞瘤患犬，由肿瘤功能性导致激素失衡所致（Lipowitz et al. 1973; Reif and Brodey 1969; Weaver 1983）。支持细胞瘤继发的高雌激素症是非炎症性脱发的已知原因。与高雌激素症相关的脱发是由于雌激素与雌激素受体α结合所致，该受体参与毛囊周期的调节。这种相互作用通过诱导毛囊提前进入退行期并延长休止期，从而破坏生长期–休止期转换，导致毛发生长受损（Hu et al. 2012）。女性化的其他体征，包括男性乳腺发育和下垂的包皮，在该病症中常被描述。而血尿和包皮出血报道较少，通常与潜在的前列腺疾病相关（Abalaka and Audu 2024; Pothiappan et al. 2025; Quartuccio et al. 2012; Spackman and Roth 1988）。在我们的临床病例中，前列腺的超声表现符合良性囊性前列腺增生。众所周知，在老年未去势雄性犬中，年龄相关的良性前列腺增生（BPH）常存在。然而，功能性支持细胞瘤继发的严重高雌激素症可显著改变雄激素与雌激素的平衡，诱导前列腺上皮鳞状化生、导管阻塞和液体积聚，从而加剧囊性实质改变（Spackman and Roth 1988）。
在本病例中，所发现的轻度正细胞性、正色素性、非再生性贫血被归因于已记录的高雌激素症。如文献报道，犬循环雌激素水平过高可诱导严重的骨髓毒性。该状况通常以短暂的白细胞增多和血小板增多阶段开始，随后进展为影响多系细胞的进行性骨髓发育不全或再生障碍（Sontas et al. 2009）。在本患者中，血清雌二醇浓度为119 pg/mL——约为生理上限的六至八倍——可能对红系活性产生了抑制作用。尽管雌激素诱导的骨髓毒性可进展为可能致命的泛血细胞减少，但及时诊断和手术切除肿瘤使随访期间血液学参数完全恢复正常。这证实，骨髓损伤若在早期被识别，一旦消除激素刺激源，可能是可逆的。
在本病例中，该状况的诊断基本上是临床性的，并得到血清雌激素水平的支持，尽管如既往研究报道，包皮细胞学和睾丸超声检查已被证明非常有用（Bigliardi et al. 2019; Cutler et al. 2022）。在健康犬中，年龄、体重和品种与特定阴道上皮细胞群体的患病率相关，而在雌激素水平未升高的情况下，表层细胞和角化细胞呈负相关（Vergou et al. 2023）。在患有睾丸肿块的犬中，包皮涂片中表层细胞超过20%与血清雌二醇浓度> 40 pmol/L显著相关（Dreimanis et al. 2012）。此外，患有脱毛症的犬包皮涂片中表层细胞数量显著增加。这种细胞成熟模式反映了明显的雌激素影响，支持女性化综合征的诊断。临床表现与睾酮/雌二醇比值降低密切相关，并且即使绝对雌二醇水平看似在生理范围内，也可能因肿瘤产生其他雌激素样物质而发生（Mischke et al. 2002）。在本病例中，未评估睾酮水平，因为已知雄性犬睾酮呈发作性和脉冲式分泌，导致显著的昼夜波动，限制了单次基础测量的诊断可靠性（DePalatis et al. 1978）。相反，功能性SCT的诊断得到显著升高的血清雌二醇水平、包皮细胞学和高雌激素症特征性体征的有力支持（Mischke et al. 2002）。包皮细胞学目前仅偶尔进行，主要用于评估炎症和肿瘤性状况。尽管需要进一步研究来评估纯角化细胞作为高雌激素症预测指标的可靠性，但本研究的主要目的是重新评估这一诊断方法，并强调在临床实践中进一步验证的必要性。最后，组织学确认和去势后临床症状及实验室异常的完全缓解进一步支持了诊断以及我们关于所观察临床症状的病因发病机制假设。
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结论
总之，本病例支持将SCT纳入老年未去势雄性犬的主要鉴别诊断，这些犬表现为弥漫性皮肤病变、女性化体征或血液学异常，无论品种或是否存在隐睾。该病发生于一只睾丸正常下降的伯恩山犬，进一步强调了老年患者全面体格检查的重要性，包括仔细的阴囊触诊和睾丸超声检查。
该犬观察到的临床和实验室发现与肿瘤相关的高雌激素症一致，后者促成了所观察到的临床症状。去势后血液学参数正常化和临床症状完全缓解进一步支持了激素失衡与全身表现之间的关联。
在本特定病例中，包皮细胞学作为一种有趣的观察性发现，反映了 underlying 高雌激素症。然而，由于该观察仅限于单例病例报告，包皮细胞学的临床效用仍属初步。虽然表层或角化细胞比例增加可能在激素检测和影像学之外提供支持性背景，但严格需要广泛、对照的前瞻性研究来评估其敏感性、特异性和真实诊断价值。
总体而言，早期识别和及时手术干预似乎对于防止进展为泛血细胞减少等严重并发症并确保良好的长期预后至关重要，如随访期间完全临床康复和毛发完全再生所证明。
作者贡献
Ariu Federica：概念构思、调查研究、撰写——初稿、项目管理与监督。Burrai Giovanni Pietro：形式分析（细胞学和组织学）与撰写——审阅和编辑。Cubeddu Francesca：调查研究（麻醉）与资源提供。Masala Gerolamo：方法学（外科手术）与调查研究。Moalli Marzia：调查研究（临床诊断）、可视化与撰写——审阅和编辑。Antuofermo Elisabetta：参与数据解读及稿件起草与修订。Corda Francesca：调查研究（超声检查）与撰写——审阅和编辑。Pinna Parpaglia Maria Luisa：验证、撰写——审阅和编辑与监督。Corda Andrea：概念构思、调查研究（超声检查）、监督与撰写——审阅和编辑。
资金
作者无需报告任何事项。
伦理声明
本研究按照高标准的兽医诊疗规范开展。犬主已就临床操作及本病例报告的发表提供书面知情同意。本研究经萨萨里大学伦理委员会批准，批件编号28277，日期为2026年3月10日。
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致谢
开放获取出版由萨萨里大学（Universita degli Studi di Sassari）提供支持，系Wiley‐CRUI‐CARE协议的一部分。
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参考文献
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关联数据
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查看英文原文▾
ABSTRACT
To describe the clinical presentation, diagnostic workup and successful outcome of a hormonally active testicular Sertoli cell tumour (SCT) in a non‐cryptorchid Bernese Mountain Dog. A 10‐year‐old intact male dog was evaluated with a history of progressive alopecia, gynaecomastia and haematuria. Diagnostic investigations included complete blood count, serum biochemistry, oestradiol assay, abdominal and testicular ultrasonography, preputial cytology and histopathological examination following bilateral orchiectomy. Clinical signs included bilaterally symmetrical alopecia, hyperpigmentation and a pendulous prepuce. Laboratory findings revealed mild non‐regenerative anaemia and severe hyperestrogenism (oestradiol: 119 pg/mL). Preputial cytology showed a predominance of superficial epithelial cells (> 80%), supporting the state of hyperestrogenism. Ultrasonography identified a large, vascularized left testicular mass and cystic prostatic changes. Histopathology confirmed an SCT. Following surgery, clinical signs and laboratory abnormalities resolved completely within 9 months. This case emphasizes that SCTs should be a differential diagnosis for feminization syndrome in older dogs even without cryptorchidism. It also highlights preputial cytology as a rapid and effective minimally invasive tool for the preliminary identification of hyperestrogenism.
Keywords: feminization syndrome, hyperestrogenism, preputial cytology, Sertoli cell tumour
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Introduction
Testicular Sertoli cell tumours (SCTs) accounted for 14%–33% of diagnosed testicular tumours in dogs (Hayes and Pendergrass 1976; Hohšteter et al. 2014; Liao et al. 2009; Manuali et al. 2020). Like other testicular tumours, SCTs are most common in cryptorchid testes, and dogs with inguinal hernias are reported to have a higher tumour risk (Hayes et al. 1985). Usually, SCTs are slow‐growing and non‐invasive tumours with a metastasis rate of less than 10% (Subapriya et al. 2025). The feminizing syndrome associated with SCT is linked to hyperestrogenism and develops in approximately 57% of dogs with SCTs (Mischke et al. 2002; Weaver 1983). It is characterized by non‐pruritic, bilaterally symmetrical alopecia, hyperpigmentation, gynaecomastia and a pendulous, oedematous prepuce (da Silva Flores et al. 2023; Fadok et al. 1986; Quartuccio et al. 2012). Although feminization syndrome is classical in cryptorchid cases due to the higher prevalence and neoplastic transformation rate of retained gonads, it can also manifest in dogs with normally descended testes. Oestrogen‐induced myelotoxicity, characterized by bone marrow hypoplasia, has also been reported in association with SCTs (Choi et al. 2008; Marshall 2018; Paepe et al. 2016; Post and Kilborn 1987; Sanpera et al. 2002; Sherding et al. 1981; Sontas et al. 2009; Withers et al. 2016). In clinical practice, the diagnostic approach to canine testicular tumours involves physical examination, testicular ultrasonography and histological confirmation, while differential diagnosis includes other primary testicular neoplasms, particularly leydigomas and seminomas.
This report describes a clinical case of testicular SCT associated with feminization syndrome in a 10‐year‐old male dog with normally descended testes.
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Case History
A 10‐year, 6‐month‐old, intact, non‐cryptorchid, male Bernese Mountain Dog, weighing 42.5 kg, was referred to the Veterinary Teaching Hospital of the University of Sassari for clinical evaluation because of bilateral, non‐pruritic alopecia involving the abdomen, lumbar region, thorax and perianal area. The owners also reported intermittent preputial haemorrhagic discharge and haematuria occurring periodically over the previous few months, as well as reluctance to climb stairs and mild lethargy, which they attributed to the dog's age. No other behavioural changes were reported. The dog was regularly vaccinated, routinely dewormed and treated for ectoparasites, fed a commercial dry diet and had indoor and outdoor access.
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Clinical and Laboratory Findings
Physical examination revealed normal general health parameters, including a rectal temperature of 38.1°C, pulse rate of 118 bpm, respiratory rate of 19 breaths/min and pink, moist mucous membranes with a capillary refill time < 2 s and a body condition score (BCS) of 2/5. Specific clinical findings included a dry, dull, discoloured, woolly‐type hair coat with extensive symmetrical, non‐pruritic alopecia (Figure 1A) and hyperpigmented skin. The prepuce was oedematous and pendulous (Figure 1D), gynaecomastia (Figure 1C) was present, papules were observed along the mammary line and penile region, and the left testicle was larger than the right. The dog underwent blood and urine analysis, preputial cytology and abdominal ultrasonography.
[图：Clinical, gross and histological findings of a Sertoli cell tumour (SCT) in a 10‐year‐old Bernese Mountain Dog. (A, B) C]
Complete blood count revealed a mild normocytic, normochromic, non‐regenerative anaemia (Table 1). Serum biochemical analysis showed a mild increase in aspartate aminotransferase (AST 85 IU/L, reference intervals [RIs] 17–52 IU/L) and increased total protein concentration (TP 7.87 g/dL, RI 5.1–7.5 g/dL) due to hyperglobulinemia (GLOB 5.21 g/dL, RI 2.4–4.3 g/dL). Serum protein electrophoresis revealed a relative decrease in albumin (ALB 38.2%, RI 45.5%–66.2%), increased beta (β‐GLOB 26.5%, RI 12.8–23.7) and gamma globulin (γ‐GLOB 22.1%, RI 5.1%–17.8%) fractions. In addition, serum biochemistry revealed an elevation in creatine kinase (CPK 895 U/L) and hyperphosphatemia (11.6 mg/dL) with an increased anion gap (34.0), while renal function parameters (urea and creatinine) remained within normal RIs. The main serum biochemical and electrophoretic findings are summarized in Table 2.
TABLE 1. Complete blood count (CBC) of the Bernese Mountain Dog at presentation.
| Parameter | Patient value | Reference interval | Status/note |
|---|---|---|---|
| Red blood cells (RBC) | 5.98 × 10 6 /μL | 5.90–8.70 | Normal |
| Haemoglobin (HGB) | 13.00 g/dL | 13.90–20.40 | Low |
| Haematocrit (HCT) | 40.50% | 43.20–63.20 | Low |
| Mean corpuscular volume (MCV) | 67.70 fL | 65.10–82.10 | Normal |
| Mean corpuscular HGB (MCH) | 21.70 pg | 21.40–25.60 | Normal |
| MCH concentration (MCHC) | 32.10 g/dL | 28.80–35.20 | Normal |
| Red cell distribution width (RDW) | 17.10% | 12.10–15.70 | High (Anisocytosis +++) |
| Reticulocytes | 65,182/μL (1.09%) | 11,504–147,178 | Non‐regenerative |
| White blood cells (WBC) | 11.35 × 10 3 /μL | 5.60–14.00 | Normal |
| Segmented neutrophils | 7673/μL (67.6%) | 3100–10,400 | Normal |
| Lymphocytes | 2145/μL (18.9%) | 1100–4300 | Normal |
| Monocytes | 885/μL (7.8%) | 100–900 | Normal |
| Eosinophils | 636/μL (5.6%) | 100–1200 | Normal |
| Basophils | 11/μL (0.1%) | 0–100 | Normal |
| Platelets (PLT) | 351 × 10 3 /μL | 110–475 | Normal (adequate) |
TABLE 2. Serum biochemistry profile of the Bernese Mountain Dog at presentation.
| Parameter | Patient value | Reference interval | Status/note |
|---|---|---|---|
| Creatine kinase (CPK) | 895 U/L | 35–200 | High |
| Aspartate aminotransferase (AST) | 85 U/L | 17–52 | High |
| Alanine aminotransferase (ALT) | 56 U/L | 19–76 | Normal |
| Alkaline phosphatase (ALP) | 67 U/L | 12–134 | Normal |
| Gamma‐glutamyl transferase (GGT) | 8 U/L | 2–9 | Normal |
| Total protein | 7.87 g/dL | 5.10–7.50 | High |
| Albumin | 2.66 g/dL | 2.40–3.70 | Normal |
| Globulins | 5.21 g/dL | 2.40–4.30 | High |
| Albumin/globulin ratio (A/G) | 0.51 | 0.60–1.30 | Low |
| Urea | 34 mg/dL | 18–50 | Normal |
| Creatinine | 1.12 mg/dL | 0.60–1.40 | Normal |
| Cholesterol | 233 mg/dL | 131–332 | Normal |
| Triglycerides | 39 mg/dL | 32–114 | Normal |
| Calcium | 10.1 mg/dL | 9.1–11.5 | Normal |
| Corrected calcium | 10.9 mg/dL | 9.9–12.1 | Normal |
| Phosphorus | 11.6 mg/dL | 2.5–5.5 | High |
| Calcium × phosphorus product | 125.9 | < 60.0 | High |
| Sodium | 149 mEq/L | 143–153 | Normal |
| Potassium | 5.5 mEq/L | 3.9–5.7 | Normal |
| Chloride | 103 mEq/L | 108–119 | Low |
| Bicarbonate HCO 3 − | 17.9 mEq/L | 17.0–24.0 | Normal |
| Anion gap | 34.0 | 15.0–25.0 | High |
| Iron (total) | 98 μg/dL | 80–214 | Normal |
The serum oestradiol concentration was 119.0 pg/mL, markedly exceeding the reference limit of < 15 pg/mL (Mischke et al. 2002).
The enzyme‐linked immunosorbent assay (ELISA) test for leishmaniosis was negative. Serum cholesterol and triglyceride concentrations, as well as basal and urinary cortisol levels and thyroid hormone concentrations, were within laboratory RIs. Urinalysis performed on a free‐catch urine sample revealed increased urine pH, haematuria and proteinuria with a urine protein‐to‐creatinine ratio of 2.91.
Cytological examination of the preputial smear, performed as previously described (Dreimanis et al. 2012), showed high cellularity characterized predominantly by superficial squamous cells (> 80% anucleated or pyknotic). Parabasal cells, intermediate cells and neutrophils were rarely observed (Figure 2).
[图：Preputial cytology smear showing high cellularity with a marked predominance (> 80%) of superficial squamous epitheli]
Abdominal ultrasonography revealed symmetrical prostatomegaly, with a heterogeneous prostatic parenchymal echotexture and the presence of multiple irregularly shaped cystic structures that did not protrude from the organ surface (Figure 3). The left testicle was enlarged (approximately 2.7 × 3.5 cm) and showed a heterogeneous echotexture, irregular shape and altered internal architecture, with marked vascularization on colour Doppler examination (Figure 4). The right testicle had a normal shape, echogenicity and echotexture, but was subjectively reduced in size (approximately 2 × 1 cm) (Figure 5). Left medial iliac lymphadenomegaly was observed (approximately 4.1 cm × 1.4 cm); the lymph node had a fusiform shape and normal echogenicity. No other clinically relevant ultrasonographic abnormalities were detected.
[图：B‐mode images of the prostate in longitudinal (A) and transverse (B) sections. The organ appears enlarged, with large, i]
[图：B‐mode (A) and colour Doppler (B) ultrasound images of the left testicle. The organ is enlarged, with irregular margins ]
[图：B‐mode image of a longitudinal section of the right testicle (arrows), showing a reduced‐size organ with preserved norma]
Ultrasound‐guided aspiration of the fluid contained within the prostatic cysts was performed, and the collected samples were subsequently submitted for bacteriological culture. In addition, fine‐needle aspiration cytology of the left medial iliac lymph node was performed. Bacteriological culture was negative, and lymph node cytology was consistent with reactive lymphoid hyperplasia.
Based on clinical laboratory and imaging diagnostic findings, feminization syndrome secondary to a unilateral testicular SCT was suspected, and orchiectomy with histopathological examination was recommended.
The dog was premedicated with medetomidine (2 μg/kg; Sedastart 0.1% Ecuphar S.r.l., Milano, Italy), butorphanol 0.2 mg/kg (Nargesic 1% ACME S.r.l., Reggio Emilia, Italy) and maropitant 1 mg/kg (Vetemex 1% Virbac S.r.l., Milano, Italy).
Anaesthesia was induced with propofol IV 2 mg/kg (Proposure 1%, Merial Italia, S.p.a., Milan, Italy) and maintained with sevoflurane (2%–2.2%; 0.9–1 MAC) (SevoFlo Zoetis Belgium SA, Louvain‐la‐Neuve, Belgium) in oxygen.
A complete scrotal ablation with bilateral orchiectomy was performed. Both testes and the scrotal tissue were submitted for histological examination.
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Pathological Findings
On gross examination, a marked difference in the size and consistency of the testes was noted (Figure 1E). The left testicle appeared significantly enlarged (27.1 mm × 35.2 mm) and had a firm, irregular consistency, unlike the right testicle, which measured 15.6 mm × 23.1 mm and had a regular consistency. On incision, the mass of the left testicle showed a whitish colour and a homogeneous appearance, with some areas of haemorrhage and focal necrosis. The right testicle, however, appeared normal. Histological examination of the left testicle revealed a solid, multifocal and infiltrating neoplastic proliferation of tubular supporting epithelial cells, consistent with an SCT (Figure 1F). The neoplastic cells were arranged in cords, nests and occasional tubular structures, supported by a fine fibrovascular stroma. Moderate cellular and nuclear atypia was observed, with low mitotic activity (< 1 mitosis per high‐power field). Furthermore, extensive areas of coagulative necrosis were identified. The testicular parenchyma adjacent to the tumour showed severe germinal atrophy, with a marked reduction or absence of spermatogonia in the seminiferous tubules. The right testicle showed no significant changes.
Postoperative recovery was uneventful. Over the following months, cutaneous alterations, gynaecomastia, oedema and pendulous prepuce progressively resolved with complete coat regrowth, and the owners reported increased vitality and resolution of preputial bleeding. At 5‐ and 9‐month follow‐ups, the dog was in excellent general condition, with normal clinical examination and laboratory findings (Figure 1B). Occasional mild urinary leakage was reported by the owner. Overall, the outcome was favourable with a good long‐term prognosis.
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Discussion
This case report describes feminization syndrome in an intact male dog with a left testicular SCT. SCTs are hormonally active tumours that originate from gonadostromal tissue within the testes and produce oestrogens and inhibin (Peters et al. 2000).
Although testicular SCTs are more common in cryptorchid dogs, they can also occur in scrotal testes. In dogs with normally descended testes, age is a major risk factor, with reported mean ages of 7.8 years for abdominal, 8.8 years for inguinal and 11 years for scrotal testes (Reif and Brodey 1969; Soto‐Heras et al. 2024). This consideration highlights the importance of including testicular palpation as part of the routine clinical examination, especially in older dogs, and even more so in those presenting with diffuse cutaneous changes.
The Bernese Mountain Dog is not listed among the breeds with the highest incidence of testicular tumours; however, purebred dogs overall are more frequently diagnosed with testicular tumours than mixed‐breed dogs (Ngo et al. 2025).
The feminization syndrome observed in this case is a well‐recognized paraneoplastic condition, reported in 24%–57% of dogs with SCTs, and results from hormonal imbalance due to tumour functionality (Lipowitz et al. 1973; Reif and Brodey 1969; Weaver 1983). Hyperestrogenism secondary to SCTs is a well‐known cause of non‐inflammatory alopecia. The alopecia associated with hyperestrogenism results from oestrogen binding to oestrogen receptor α, which is involved in regulation of the hair follicle cycle. This interaction disrupts the anagen–telogen transition by inducing premature catagen and prolonging the telogen phase, leading to impaired hair growth (Hu et al. 2012). Additional signs of feminization, including gynaecomastia and a pendulous prepuce, are commonly described in this condition. Whereas haematuria and preputial blood discharge have been reported less frequently and are usually associated with underlying prostatic disease (Abalaka and Audu 2024; Pothiappan et al. 2025; Quartuccio et al. 2012; Spackman and Roth 1988). In our clinical case, the ultrasonographic appearance of the prostate was consistent with benign cystic prostatic hyperplasia. It is well recognized that in an older intact male dog, age‐related benign prostatic hyperplasia (BPH) is commonly present. However, severe hyperestrogenism secondary to a functional SCT can markedly alter the androgen‐to‐oestrogen balance, inducing squamous metaplasia of the prostatic epithelium, ductal occlusion and fluid accumulation, thereby exacerbating cystic parenchymal changes (Spackman and Roth 1988).
In the present case, the mild normocytic, normochromic, non‐regenerative anaemia identified was attributed to the documented hyperestrogenism. As reported in the literature, excessive levels of circulating oestrogens in dogs can induce severe myelotoxicity. This condition typically begins with a transient phase of leucocytosis and thrombocytosis, followed by progressive bone marrow hypoplasia or aplasia affecting multiple cell lines (Sontas et al. 2009). In our patient, the serum oestradiol concentration of 119 pg/mL—approximately six to eight times the physiological upper limit—could have exerted a suppressive effect on erythroid activity. Although oestrogen‐induced myelotoxicity can progress to potentially fatal pancytopenia, the timely diagnosis and surgical removal of the neoplasm led to the complete normalization of haematological parameters during the follow‐up period. This confirms that marrow damage, when identified early, may be reversible once the source of hormonal stimulation is eliminated.
In our case, the diagnosis of this condition was essentially clinical and supported by oestrogen serum levels, although preputial cytology and testicular ultrasonography have proven to be very useful, as reported in previous studies (Bigliardi et al. 2019; Cutler et al. 2022). In healthy dogs, age, body weight and breed are associated with specific vaginal epithelial cell population prevalences, while superficial and cornified cells show a negative correlation in the absence of elevated oestrogen levels (Vergou et al. 2023). In dogs with testicular masses, the presence of more than 20% superficial cells in preputial smears was significantly associated with a serum oestradiol concentration > 40 pmol/L (Dreimanis et al. 2012). In addition, the number of superficial cells was significantly increased in preputial smears from dogs with alopecia. This pattern of cellular maturation reflects a pronounced estrogenic influence, supporting a diagnosis of feminization syndrome. The clinical manifestations are strongly linked to a decreased testosterone/oestradiol ratio, and may occur even when absolute oestradiol levels appear within the physiological range due to the production of other oestrogen‐like substances by the tumour (Mischke et al. 2002). In the present case, testosterone levels were not evaluated due to the known episodic and pulsatile secretion of testosterone in male dogs, which results in marked diurnal fluctuations and limits the diagnostic reliability of a single basal measurement (DePalatis et al. 1978). Instead, the diagnosis of functional SCT was robustly supported by the markedly elevated serum oestradiol levels, preputial cytology and characteristic signs of hyperestrogenism (Mischke et al. 2002). Preputial cytology is currently performed only occasionally, mainly for the evaluation of inflammatory and neoplastic conditions. Although further studies are required to assess the reliability of exclusively cornified cells as predictors of hyperestrogenism, the primary aim of the present study was to re‐evaluate this diagnostic approach and highlight the need for its further validation in clinical practice. Finally, histological confirmation and the complete resolution of clinical signs and laboratory abnormalities after castration further supported the diagnosis and our etiopathogenetic hypotheses regarding the observed clinical signs.
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Conclusion
In conclusion, this case supports the inclusion of SCTs among the primary differential diagnoses in older intact male dogs presenting with diffuse dermatological changes, signs of feminization or haematological abnormalities, regardless of breed or the presence of cryptorchidism. The occurrence in a Bernese Mountain Dog with normally descended testes further emphasizes the importance of thorough physical examination in geriatric patients, including careful scrotal palpation and testicular ultrasonography.
The clinical and laboratory findings observed in this dog are consistent with tumour‐associated hyperestrogenism, which contributed to the clinical signs observed. The normalization of haematological parameters and complete resolution of clinical signs following orchiectomy further support the association between hormonal imbalance and systemic manifestations.
In this specific case, preputial cytology served as an interesting observational finding that mirrored the underlying hyperestrogenism. However, as this observation is limited to a single case report, the clinical utility of preputial cytology remains preliminary. While an increased proportion of superficial or cornified cells may offer supportive context alongside hormonal assays and imaging, extensive, controlled prospective studies are strictly required to evaluate its sensitivity, specificity and true diagnostic value.
Overall, early recognition and timely surgical intervention appear crucial to prevent progression towards severe complications such as pancytopenia and to ensure an excellent long‐term prognosis, as demonstrated by complete clinical recovery and full hair regrowth during follow‐up.
Author Contributions
Ariu Federica: conceptualization, investigation, writing – original draft, project administration and supervision. Burrai Giovanni Pietro: formal analysis (cytological and histological) and writing – review and editing. Cubeddu Francesca: investigation (anaesthesia) and resources. Masala Gerolamo: methodology (surgery) and investigation. Moalli Marzia: investigation (clinical diagnostic), visualization and writing – review and editing. Antuofermo Elisabetta: contributed to data interpretation and manuscript drafting and revision. Corda Francesca: investigation (ultrasonography) and writing – review and editing. Pinna Parpaglia Maria Luisa: validation, writing – review and editing and supervision. Corda Andrea: conceptualization, investigation (ultrasonography), supervision and writing – review and editing.
Funding
The authors have nothing to report.
Ethics Statement
This study was conducted in accordance with high standards of veterinary care. The owner of the dog provided written informed consent for the clinical procedures and the publication of this case report. Approved by the Ethics Committee of the University of Sassari, protocol no. 28277 of 10 March 2026.
Conflicts of Interest
The authors declare no conflicts of interest.
Acknowledgements
Open access publishing facilitated by Universita degli Studi di Sassari, as part of the Wiley ‐ CRUI‐CARE agreement.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
References
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Associated Data
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.