女性生殖系统和乳腺疾病 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 女性生殖系统和乳腺疾病The Female Genital System

and Breast

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

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 I

CIN II

CIN III

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

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

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• 12-14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 <20y or >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

Choriocarcinoma

Choriocarcinoma

Choriocarcinoma (metastasis to vagina )

Choriocarcinoma (metastasis to lung )

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 influencesGeographic factors VariesAge Increase after 30yFamily history First-degree relative with BC 1.2-3.0

Menstrual history Age at menarche<12y 1.3 Age at menopause>55y 1.5-2.0

Pregnancy First live birth 25-29yo 1.5 First live birth >30yo 1.9 First live birth >35yo 2.0-3.0 Nulliparous 3.0

Factors Relative risk

Well-Established influencesBenign breast disease Proliferative disease 1.9 Proliferative disease with atypical hyperplasia 4.4 Lobular carcinoma in situ 6.9-12.0

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

粉刺癌

粉刺癌

DCIS, cribriform type

DCIS, cribriform type

DCIS, cribriform type

DCIS, cribriform type

DCIS, papillary type

DCIS, papillary type

DCIS, solid 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

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