女性生殖系统和乳腺疾病 The Female Genital System and Breast女性生殖系统和乳腺疾病 第十三章

子宫颈疾病  慢性宫颈炎 Chronic cervicitis  宫颈上皮内瘤变 Cervical intraepithelial Neoplasia (CIN) 宫颈上皮不典型增生 Cervical epithelial dysplasia 宫颈原位癌 Carcinoma in situ  宫颈癌 Cervical carcinoma

Normal cervix

宫颈炎 阴道（粘液）脓性分泌物 感染性 – 沙眼衣原体 (40% of cases) – 真菌类 – 淋球菌 – 单纯疱疹 II 型 – 人类乳头瘤状病毒 HPV 非感染性

Nabothian cyst at 5 o'clock

宫颈肿瘤  癌前病变  CIN （组织学）  SIL （脱落细胞学）  浸润型癌

CIN I ： Mild dysplasia CIN II ： Moderate dysplasia CIN III : Severe dysplasia and CIS Cytologic smears  SIL low-grade: CINI or flat condylomas  SIL high-grade: CINII or CINIII ，癌

Cervical conization

PAP smear

A normal Pap smear picture

LSIL

HSIL

Normal cervical squamous epithelium

CIN I

CIN II

CIN III

Carcinoma in situ (glands involved)

It is important to emphasize that most (perhaps all) invasive cervical squamous cell carcinoma arise from precursor epithilial changes referred to as CIN. However, not all cases of CIN progress to invasive cancer, and indeed many persist without change or even regress.

CINI Regression 50-60% Persistence 30% Progression to CIN III 20% Progression to invasive cancer 1-5% CINIII Regression 33% Progression 6-74%

流行病学 CIN 高峰年龄 30y ，癌高峰年龄 50y Risk factors –Early age at first intercourse –Multiple sexual partners –A male partner with multiple previous sexual partners –Persistent infection by “High-risk” HPV –Others

The Death of Eva Peron Eva Peron ("Evita"), wife of Argentina's left-wing dictator Juan Peron, died in January 1952 of cervical cancer.

宫颈癌 75-90% 鳞癌 腺癌和腺鳞癌 小细胞癌 <5% 20% 糜烂型 外生菜花型 内生浸润型 溃疡型  "Microinvasive carcinoma"

Squamous cells carcinoma

Immunostaining for keratin

Spreading

临床表现 Pap smear 有助于早期诊断 未能早期诊断者 – 不规则阴道流血 – 白带增多，伴有异味 – 性交痛，排便困难 – 扩散引起的症状 晚期患者化疗有效

宫颈癌分期 (FIGO,1985) 0 Preinvasive carcinoma Ⅰ Carcinoma strictly confined to the cervix Ⅱ Carcinoma that extends beyond the cervix, but does not extend into the pelvic wall Ⅲ Carcinoma that has extended into the pelvic sidewall Ⅳ Carcinoma that has extended beyond the true pelvis or has clinically involved the mucosa of the bladder and/or rectum

五年生存率 Stage 0 100% Stage I 90% Stage II 82% Stage III 35% Stage IV 10%

滋养层细胞疾病 Gestational trophoblastic disease  Hydatidiform mole  Invasive mole  Choriocarcinoma HCG↑

Implantation of the Placenta 5 days after fertilization

6 days after fertilization

12 days after fertilization

a third- trimester placenta with baby

葡萄胎 Hydatidiform mole

Big uterus with mole

葡萄胎 Hydatidiform Mole 一堆水肿甚至囊性扩张的绒毛 美国 1/ 1000 次妊娠 ，中国发病率更高 分为完全性和不完全性葡萄胎

完全性葡萄胎 complete mole  No associated baby  The villi are uniformly swollen  All the chromosomes from father (46XX,46XY)

部分性葡萄胎 Partial mole  May have a non-viable baby  Unevenly swollen villi  69XXX, 69XXY

Partial mole

临床表现 周发现子宫过大就诊，超声可早期 诊断 5 个月出血流产 hCG 升高 清宫后 –80-90% remains benign –10% complete mole become invasive –2-3% give rise to choriocarcinoma

侵袭性葡萄胎 Invasive mole  不发生转移  绒毛可栓塞至肺和脑

绒毛膜癌 Choriocarcinoma Aggressive 起源于绒毛上皮细胞或全能干细胞 1:2000 Age 40y History –50% of case follow a complete mole –25% arise after an abortion –Remainder after a normal pregnancy

患者，女， 24 岁，农民，孕 3 产 1+2 。 主诉：流产 1 年多，阴道不规则流血，痰中带血 3 月， 头痛 1 月，呕吐 3 天。 现病史： 1 年前，因停经 5 月后自然流产，流出物似 “ 烂肉一堆 ” ，未见胎儿成份，当时未清宫，以后月经 正常。 3 月前开始阴道不规则流血，时多时少， 1 月前 阴道掉出鹅蛋大之腥臭 “ 肉块 ” ，同时有咳嗽，痰中带 血，头昏头痛。近 3 日来，头昏头痛加重，并出现剧 烈呕吐。去某院妇科门诊求治，在检查中病人突然头 痛、呕吐、昏迷，四肢小抽搐，急诊入院。 病例讨论

体格检查 : 神志不清，脉搏 90 次 /min ，呼吸 16 次 /min ，血压 129/90mmHg ，心肺（－），肝脾未扪 清，子宫底在耻骨联合上 4 指，外阴水肿，阴道前 后壁有 4 个紫红色结节，小者直径为 0.5cm ，最大 者直径 5cm ，掉出阴道之外。子宫 2 月孕大，前位， 活动，双附件（－），入院后 1 小时，呼吸骤停， 抢救无效死亡。 实验室检查：入院前 20 天，胸部 X 线照片见双肺有 结节状影。查血：血红蛋白 38g/L ，白细胞 15.3×109/L ，嗜中性粒细胞 0.86 ，淋巴细胞 0.13 ， 大单核细胞 0.01 ，尿妊娠试验（ + ）。

尸检摘要 : 子宫长大如拳头，表面有黄豆大结节 数个，子宫底右侧有 5cm×5cm×6cm 大包块，表 面有坏死，溃烂，切面呈紫红色，边界不清， 已侵及肌层和浆膜，阴道前壁有 4 个大小不等的 紫红色结节（同前），子宫旁有数个蚕豆大小 的结节，双附件（－）。双肺内可扪及多个黄 豆大小的硬结节，切面为深紫红色，中心有坏 死；双侧胸膜脏壁层有局灶性纤维性粘连。脑 重 1230 克，左顶颞部硬膜下有血块约 10cm×6cm×0.6cm ，左侧脑室后角有核桃大小 紫红色结节，右额极也有 3cm×2.5cm 之紫红色 结节。有明显小脑扁桃体疝形成。

Choriocarcinoma

Choriocarcinoma (metastasis to vagina )

Choriocarcinoma (metastasis to lung )

临床表现 阴道流血伴 hCG 显著升高 早期血道转移至肺 (50%) ， 阴道 (30- 40%) ， 脑，肝，肾 Chemotherapy saves almost all cases

乳腺癌 Breast carcinoma 212,920 new case, 40,940 death (USA, 2006) 全球发病率增高 发病机制 Pathogenesis – 遗传 Genetic change – 激素 Hormonal influence – 环境 Environmental factors

Factors Relative risk Well-Established influences Geographic factors Varies Age Increase after 30y Family history First-degree relative with BC Menstrual history Age at menarche<12y 1.3 Age at menopause>55y Pregnancy First live birth 25-29yo 1.5 First live birth >30yo 1.9 First live birth >35yo Nulliparous 3.0

Factors Relative risk Well-Established influences Benign breast disease Proliferative disease 1.9 Proliferative disease with atypical hyperplasia 4.4 Lobular carcinoma in situ Less Well-Established influences Exogenous estrogens Oral contraceptives Obesity High-fat diet Alcohol consumption Cigarette smoking

乳腺癌类型 原位癌 Non-invasive –Ductal carcinoma in situ (DCIS) –Lobular carcinoma in situ (LCIS) 浸润性癌 Invasive (infiltrating) – Invasive ductal carcinoma ( 硬癌 ) –Invasive lobular carcinoma –Medullary carcinoma –Colloid carcinoma –Tubular carcinoma –Other types

Normal resting breast

Normal pregnant lady’s breast

导管内原位癌 DCIS 常伴坏死和钙化 ( 乳腺摄片 ) 97% long term survival 1/2 low-grade DCIS (left alone) turns invasive at the same site (Cancer 103: 2481, 2005). Architectural patterns of DCIS – 粉刺癌 Comedo subtype –Solid, cribriform, papillary

Van Nuys grading-and-treatment scheme for non-infiltrating ductal carcinoma: (Lancet 345: 1154, 1995) 1: No necrosis (lumpectomy, skip the radiation) 2: Necrosis but no ugly nuclei (lumpectomy, maybe radiation) 3: Ugly nuclei (lumpectomy-radiation or mastectomy)

粉刺癌

DCIS, cribriform type

DCIS, papillary type

DCIS, solid type

Paget disease of the nipple

A distinctive proliferation of tame- looking cells filling the ductules of one or more lobules Signet-ring cells are common The lobules are expanded but not distorted Does not form masses Usually bilateral 1/3 turns invasive 小叶原位癌 LCIS

LCIS

浸润型导管癌 Invasive ductal carcinoma All carcinimas that cannot be subclassified into one of the specialized types described below. (NST) Some arise in the lobules 70-80% 浸润性乳腺癌为浸导 大部分为硬癌