Chapter12 Diseases of Genital System and Breast OBSERVATIONAL METHODS OF SPECIMEN The female reproductive system consists of the uterus, the ovaries and the uterine tubes. The male reproductive system consists of the testes, the epididymis, the prostate gland and the vas deferens. Uterus. The uterus is a hollow organ about the shape of an inverted pear composed of two distinct anatomic regions: the corpus and the cervix. It measures about 7.5 cm in length, 5 cm in breadth, 2.5 cm in thickness of its upper part, and weighs from 30 to 40g. The corpus is the major portion of the uterus, with the rounded region superior to the entrance of the uterine tubes, which is called the fundus. The cervix is a narrow cylindrical outlet which projects into the vagina inferiorly. There is an inverted cone-shaped cavity in the center of the uterus corpus, with the volume of 5ml. The wall of the uterus consists of three layers: the endometrium, the myometrium and the perimetrium. The endometrium undergoes cyclic changes of menstruation. The cervix is divided into the upper vaginal region and the vaginal region, the former mucosal lining of which is columnar epithelium and the latter squamous epithelium. It is important to observe the changes of the shape, size and the surface of uterus, and the thickness, neoplasm or bleeding on three layers of uterus. Observe if there are roughness, hemorrhage, erosion, and neoplasm or cyst formation on the cervix. Ovary. The ovaries are almonds shaped, gray colored, present either a smooth or a puckered uneven surface. Adult ovaries are each about 4 cm in length, 3 cm in width, and about 1 cm in thickness, and weigh from 5 to 6g. A layer of columnar cells covers the surface of the ovary. The condensed ovary shows a dull gray color on the cut surface, with corpus luteum occasionally. We should note the changes of the shape, size, the surface of the ovaries and the relationship with the fallopian tube. We should note whether there are masses, cysts or bleeding on the cut surface. Also note the substance contained in the cysts and the characteristics of the mass. Breast. The mammary gland consists of glands, fibrous connective tissue between the lobes and fat. The gland is composed of many lobes, within which are lobules and ducts lined by cubical and columnar epithelium respectively, surrounded by muscle epithelium. We must observe the changes of skin, papilla, such as peaud’orange, ulcer and retraction of the nipple. On the cut surface of a mamma we should note whether there is a mass or bleeding, necrosis and its confines, size, shape, location and texture. Testis. The olive-shaped, gray-colored adult testes weigh 20 to 30g, encapsulated in perimetrium. Deep to this is the tunica albuginea (white coat). The center of the testis is sponge-look, composed of coiled seminiferous tubules. We should note the size, shape, color and texture, as well as the masses on the surface. Prostate gland. The prostate gland is a yellowish-gray, soft organ about the size and shape of a chestnut, 4cm×3cm×2cm in volume and weighs 8 to 20g. It is composed of anterior, medium, posterior and two lateral lobes. Histologically, it is made up of glands, smooth muscle, fibrous tissue and blood vessels. We should note the size, shape, color and texture, as well as the masses on the surface. AIMS 1. To grasp the characteristics of squamous cell carcinoma of the cervix, and know the relationship of this tumor to the clinic. To understand the concept and the clinical significance of CIN. 2. To grasp the histological classification of breast cancer and their pathological characteristics. 3. To be acquainted with the pathological features of the gestational trophoblastic disease and their pathology-clinic relationship. 4. To understand the pathological features of ovarian cystadenoma 5. To understand the pathological characteristics of the seminoma, hyperplasia and the carcinoma of the prostate. 6. To understand the morphological features of chronic cervicitis, leiomyoma and endometrial carcinoma of uterus. CONTENTS Cervix disease Gross specimen Tissue section Chronic cervicitis Chronic cervicitis Squamous carcinoma Carcinoma in situ Invasive squamous carcinoma Tumor of the uterine corpus Tumor of ovary Gestational trophoblastic disease Male genital disease Tumor of the breast Endometrial adenocarcinoma Endometrial adenocarcinoma Leiomyoma Leiomyoma Serous cystadenoma Mucinous cystadenoma Serous cystadenoma Mucinous cystadenoma Teratoma Teratoma Hydatidiform mole Hydatidiform mole Invasive mole Invasive mole Choriocarcinoma Choriocarcinoma Hyperplasia of the prostate Hyperplasia of the prostate Carcinoma of the prostate Carcinoma of the prostate Seminoma Seminoma Fibroadenoma Fibroadenoma Breast carcinoma Invasive ductal carcinoma KEY POINTS OF SPECIMEN OBSERVATION 1. Diseases of the uterine cervix (ⅰ) Chronic cervicitis Basic pathologic changes (1) Gross morphology ◆ The mucosa of cervix show congestion, swelling, dark reddish with granules and erosions; ◆ Occasionally, the Nabothian cyst and cervical polyp in the cervix canal may be seen. (2) Histopathology ◆ There are massive lymphocytes infiltration and edema in the submucosa of cervix, accompanying with dilation and congestion of vessels; ◆ The overlying endocervical epithelium and gland undergoes epidermidalization (squamous metaplasia); ◆ Nabothian cyst and cervical inflammatory polyp may be observed. Specimen observation Case abstract: A married woman, aged 45, with multiple birth, had a chronic vaginal discharge and lower abdominal pain for 2 months. Gross specimen: (Fig. 12-01) Cervical mucosa congestion, swell, pale red with granules and erosions Tissue section: (Fig. 12-02a, b) Observe the changes of cervical epithelium, glands and the interstitial. (a)The slide shows chronic cervicitis at the squamo-columnar junction of the cervix accompanying with Naboth cyst. Lymphocytes infiltrate in the submucosa, accompanying with local hemorrhage. (b) squemous metaplasia of chornic cervitis. Questions: How does the disease develop after the cervical epidermidalization? (ⅱ) Cervical carcinoma Basic pathologic changes (1) Gross morphology ◆ In situ and early invasive carcinoma show red, granular-like or hypertrophy of the cervical mucosa. ◆ Invasive carcinoma includes the following types: cauliflower type, infiltrative type or erosion type. (2) Histopathology. ◆ Carcinoma in situ shows severe dysplasia and nuclear abnormalities, and is limited in the whole epithelium, and not invaded the basement membrane; ◆ The squamous cell carcinoma takes great proportion of invasive carcinoma, and the adenocarcinoma is less commonly; ◆ Early invasive carcinoma means small invasive foci which is less than 5 mm beyond the basal membrane. Specimen observation Case abstract: A 47-year-old married woman, with 2 adult children, complained of lower abdominal soreness, low back pain, and irregular menses of 1-year duration. In recent 3 months the irregular periods of bleeding had extended from 2 to 3 weeks and at times were accompanied with pain, most marked on the right side. Pelvic examination revealed an infected, boggy cervix with a spongy bleeding external os. Complete hysterectomy was performed. Gross specimen: (Fig. 12-03a, b, c) Observe the color, shape and the neoplasm of the cervix, and make classification. Tissue section: (Fig. 12-04a, b, c) Observe the histological features of the carcinoma in situ (a), early invasive (b) and invasive (c) squamous carcinoma. Tell the degree of differentation and analyze the processof development, as well as the clinical significance. 2. Tumor of the Uterine Corpus (ⅰ) Endometrial adenocarcinoma Basic pathologic changes (1) Gross morphology ◆ The uterus enlarged, and the endometrium thickens focally or diffusely. They may assume exophytic form of papillary, nodular or cauliflower-like mass, usually accompanying with hemorrhage and necrosis. Tumor tissue can invade the uterine wall. (2) Histopathology It shows anaplastic characteristics in glandular structures and cells. ◆ The normal structures of the endometrium are destroyed and replaced by neoplastic glandular tissues; ◆ The neoplastic gland is characterized by adenocarcinoma with well to poorly differentiated cells; ◆ Sometimes, the tumor invades into the myometrium. Specimen observation Case abstract: A 53-year-old married woman passed her menopause 3 years previously. During the past 2 months she suffered from painless uterine bleeding. Examination revealed an enlarged uterus. Curettage was performed, and pathologic diagnosis is uterine adenocarcinoma. A total hysterectomy, with bilateral salpingo-oophorectomy, was performed. Gross specimen: (Fig. 12-05a, b) Observe the thickness of endometrium, color, shape, the neoplasm and its invasion of the cervix, and explain the clinical manifestation. Tissue section: (Fig.12-06a, b) Observe the histological features of the carcinoma, and identify the degree of cellular differentiation. (ⅱ) Leiomyoma of uterus Basic pathologic changes (1)Gross morphology ◆ Leiomyoma usually occurs single or multiple, round, varying in diameter, embedded within the myometrium or be subserosal or lie directly beneath the endometrium. ◆ Leiomyomas are sharply circumscribed, firm, gray-white masses, with a characteristically whorled cut surface. They may show cystic changes or muciod degeneration or hyline degeneration. (2) Histopathology ◆ The tumors are characterized by whirling bundles of uniform spindle cells, in which the nuclei are elongated and have blunt ends. The cytoplasm is abundant, eosinophilic, and fibrilar. Specimen observation Gross specimen: (Fig. 12-07) Observe the numbers, location, shape, color and boundary of the leiomyoma. Tissue section: Reference to Chapter 6. 3. Gestational trophoblastic disease (ⅰ) Hydatidiform mole Basic pathologic changes (1) Gross morphology ◆ The mole appears as friable mass of thin-walled, grape-like swollen chorionic villi, with translucent cystic structures varying in diameters of 0.1 to 1.0 cm; ◆ The villi of the complete mole are obviously abnormal, whereas, in partial moles, the villous edema involves only a proportion of villi. Accompaning with fetus or auxiliary organs. (2) Histopathology The hydatidiform mole has large avascular villi and areas of trophoblastic proliferation ◆ The chorionic villi show hydropic swelling; ◆ Absence of vascularization of villi; the central of the villi is a loose, myxomatous, edematous stroma. ◆ The surface trophoblasts, both cytotrophoblast and syncytiotrophoblast are hyperplasia. Specimen observation Case abstract: A 33-year-old married woman, in the 5th month of pregnancy, was hospitalized for severe uterine hemorrhage. Examination showed the uterus to be the size of a 4-to-5-months’ pregnancy. The cervical os was soft. The fetal heart beat could not be heard. The patient was in shock, and the blood pressure was 70/30mmHg. She discharged several large blood clots in fist size, followed by a mass of grapelike clusters of soft vascular myxomatous tissue. The HCG level of blood was very high. A curettage was performed, and much mole tissue was found. Gross specimen: (Fig. 12-08 a,b) Observe the shape of the chorionic villi, and observe the fetus and auxiliary organs. (a) the complete mole. (b) the partial mole. Tissue section: (Fig.12-09) Observe the size, stromal vessels and proliferation of trophoblast. (ⅱ) Invasive mole Basic pathologic changes (1) Gross morphology ◆Chorionic villi invade into the myometrium, usually accompanying with the focal hemorrhage and necrosis. (2) Histopathology ◆ Swollen chorionic villi invade the myometrium. ◆ The epithelium of the villi are markedly hyperplastic and atypical. Specimen observation Gross specimen: (Fig. 12-10) Observe the shape, size of the villi, and observe whether there are mole, hemorrhage and necrosis. Questions: What are the similarities and differences between invasive mole and hydatidiform mole, and what are their biological behavioral features? (ⅲ) Choriocarcinoma Basic pathologic changes (1)Gross morphology ◆ Choriocarcinoma appears usually as a bulky hemorrhagic mass invading the uterine wall. The uterus is irregularly enlarged, and with some purple-blue nodes on the surface usually; There are some gore-like substances in the cavity of the uterus and invading the wall on the cut surface. (2) Histopathology ◆ The tumor is composed of obviously atypical hyperplasia of cytotrophoblasts syncytiotrophoblasts, arranged in nests and cords. ◆ There are no stroma and vessels in the tumor. Chorionic villi are not formed, accompanying with masses of hemorrhage. ◆ The tumor invades the uterine wall. Specimen observation Case abstract: A 24-year-old married woman had her first pregnancy 5 years ago, which was terminated by curettage at the third month of pregnancy because of incomplete abortion. The second pregnancy occurred 2 years ago and terminated in a normal full-term infant. The last suspected pregnancy was accompanied with intermittent bleeding for 3 months. At the end of this time the uterus was enlarged to the size of a 6-months' pregnancy, and HCG level was high; however, ultrasound examination showed no fetal parts. In the fourth month the patient dischargeed a benign hydatidiform mole, with decidual tissue, and curettage was performed. One month later the patient had a severe hemorrhage. A panhysterectomy was performed. Gross specimen: (Fig. 12-11) Observe the shape, color, size and invasion of the tumor in the cavity of the uterus. Observe the differences between invasive mole and endometrial adenocarcinoma. Tissue section: (Fig.12-12) Observe the shape, arrangement, invision of the carcinoma cells, and observe if there are villi? Choriocarcinoma shows clear cytotrophoblastic cells with central nuclei and light stained cytoplasm and syncytiotrophoblastic cells with multiple dark nuclei embbedded in eosinophilic cytoplasm. Questions: 1) What is the relationship between choriocarcinoma and hydatidiform mole, and what are the differences of other carcinomas? What are the metastasis patterns? 2) What clinical manifestation does the patient have, and which examinations should be done? 4. Tumor of ovary (ⅰ) Cystadenoma of ovary Basic pathologic changes (1)Gross morphology ◆ The tumors are usually spherical or ovoid cystic structure; ◆ Serous tumors are usually monolocular cyst, filled with clear serous fluid. There are papilla in the cystic cavities; ◆Mucinous tumors are usually multilocular cyst with smooth inner wall, filled with mucinous contents; ◆Exuberant papillations, abundant the solid areas with hemorrhage or necrosis, and more prominent subserosal or serosal nodularity or papillation suggested the lesion were borderline or malignant; (2) Histopathology Serous tumors are characterized by cubical or columnar epithelium, with ◆ red-stained plasma; Mucinous tumors are characterized by tall columnar epithelium, with boundary ◆ pale-stained mucous plasma; ◆ Complex papillations, atypical epithelium and infiltration of the tumor into the stroma suggested the lesion were borderline or malignant. Specimen observation Case abstract: A 35-year-old married woman suffered progressive enlargement of the lower abdomen for the past year, accompanying with intermittent pain. The menstrual periods remained regular. Pelvic examination revealed a large tender tumor mass about 8cm in diameter in the region of the right ovary. Bilateral salpingo-oophorectomy and total hysterectomy were performed. Gross specimen: (Fig. 12-13a, b) Observe the locular cysts of the tumor, and observe the contents and papillae inside, and observe if there are solid areas. The gross specimen shows an opened cystic growth. The cyst wall has a smooth glistening surface. (a) The inner wall of the cyst contains numerous papillary excrescences with relative dense fibrous stalks. It’s borderline serous papillary cystadenoma. (b) It’s mucinous multicellular cystadenoma. Tissue section: (Fig. 12-14a, b) Observe the shape, plasma stain, papillary branches and exuberance of the lining epithelium, and determine its type. (a) These excrescences are covered by low columnar epithelial cells with conspicuous nuclei and irregularly shaped cytoplasm. A, benign; B, borderline; C, malignant. (b) covered with columnar epithelium, there is deep blue mucus in cytoplasma and cavity. A, benign; B, borderline; C, malignant. (ⅱ) Teratoma Basic pathologic changes (1)Gross morphology ◆ Ovarian teratomas are usually mature and immature teratoma. ◆ The mature type is usually with cystic structure, with smooth inner wall. These tumors characteristically contain hair and sebaceous material and teeth in the cavity of cyst. ◆ The immature type is usually solid, with focal cystic formation. The solid area is gray or yellowish-gray, fragile, accompanying with hemorrhage and necrosis. (2) Histopathology The mature type contains elements of skin, fat, brain, thyroid, respiratory ◆ epithelium derived from all three germ cell layers. There are various amounts of immature tissue differentiating toward nerve, bone, ◆ cartilage and others. Specimen observation Case abstract: A 36-year-old married woman with 3 children had pain in the lower abdomen and vaginal bleeding of 13-days duration. She was admitted with a tentative diagnosis of tubal pregnancy, because such a complication of gestation had occurred 11 years ago. Left salpingo-oophorectomy and hysterectomy were performed. Gross specimen: (Fig. 12-15a,b) Observe the cystic wall and the components inside, and inditify the layers they are original. Observe whether it is mature or immature type. Tissue section: (Fig.12-16a,b): (a) Microscopic examination revealed epidermis with underlying sebaceous glands and mucous glands, cartilage and respiratory epithelium. It’s mature teratoma. (b) primary neural tube can be seen. It’s immature teratoma. 5. Male genital disease (ⅰ) Hyperplasia of the prostate Basic pathologic changes (1) Gross morphology ◆ The prostatic lobes are enlarged and nodular with increasing weight, and the cut surface of the enlarged prostate shows multiple circumscribed solid nodules and cysts, giving the apperance of gray or yellowish-gray and rubbery. (2)Histopathology ◆ Histological examination reveals two components: hyperplasia of both glands and of stroma (smooth muscle and fibrous tissue). Specimen observation Gross specimen: (Fig. 12-17) Describe by self-observation. Tissue section: (Fig. 12-18a,b) The acini are lined by columnar epithelium with numberous infoldings. The muscular stroma is abnormally abundant. (ⅱ) Carcinoma of the prostate Basic pathologic changes (1) Gross morphology The prostate is enlarged, with gray nodes and firm texture on the cut surface. ◆ Small yellowish focuses of necrosis and vague borderline may been seen. (2) Histopathology Most are adenocarcinoma, usually well differentiated, forming acini, tubules or ◆ a cribriform pattern, invading the fibrous stroma. Specimen observation Gross specimen: (Fig.12-19) To observe the differences among the tumor, the hyperplasia and the surrounding prostate tissue. Tissue section: (Fig.12-20) To observe the differences between the tumor and the surrounding prostate tissue, especially the differentiations and the invasions. (ⅲ) Seminoma Specimen observation Gross specimen: (Fig. 12-21a,b). The testis is enlarged by a homogenous firm white solid tumor, which can replace all or part of the body of the testis. A rim of residual testis may be compressed at one edge of the tumor. Tissue section: (Fig.12-22) The tumor display solid nests between randomly scattered, thin, fibrovascular septa, infiltrated by lymphocytes. The tumor cells are well differentiated uniform polygonal cells with distinct cell membranes, clear cytoplasm, and the nuclei show limited plemorphism and coarse granular chromatin. 6. Tumor of the breast (ⅰ) Fibroadenoma of breast Basic pathologic changes (1) Gross morphology Fibroadenomas are gray, spherical, firm and well circumscribed with a lobulated ◆ appearance on the cut surface, and range in size from 1-4cm in diameter. The surrounding breast tissue can be compressed. (2) Histopathology ◆ Fibroadenomas show duct-like structures or elongated and thinned ductular structure associated with overgrown connective tissue masses. Specimen observation Gross specimen: (Fig. 12-23a,b) Describe by self-observation Tissue section: (Fig.12-24a,b) Describe by self-observation. (ⅱ) Breast carcinoma (Invasive ductal carcinoma) Basic pathologic changes (1)Gross morphology ◆ The carcinomas vary in size from less than 1cm in diameter to over 8cm, white, fragile or soft on the cut surface, and are not clearly defined with the surrounded tissue. The skin shows peaud’orange, and the nipple may be retracted. (2) Histopathology ◆ Tumor cells are arranged in scattered solid nests, cords and gland-like structures; ◆ The tumor cells are fairly uniform, obviously atypical, with various amount of stroma and lymphocytes infiltration. ◆ There are prominent fibrous tissue and few tumor cell in scirrhous tumors. While the medullary tumors are very cellular with little stroma. Specimen observation Case abstract: A woman of 54, 3 years past her menopause, had noted a painless mass in tile upper hemisphere of the right breast for the past 9 months. Examination revealed a mass, 4 cm in diameter, with dimpling and orange-peel appearance in the overlying skin. When the arms were raised, the right breast retracted to the chest wall, and tile right nipple was 2 cm higher than the left. An enlarged lymph node was palpated in the right axilla. A radical mastectomy was performed. Gross specimen: (Fig. 12-25a,b) Observe the skin, nipple and the size, border, color and texture of the tumor. Tissue section: (Fig. 12-26a,b,c) To note the arrangement, shape, proportion to the stroma of the tumor cells, together with the infiltration of lymphocytes and invasion in surrounded tissue. Questions: What are the differences between fibroadenoma and breast carcinoma? What factors are related to the prognosis of breast carcinoma? CASE DISCUSSION Case One Case abstract: A 32-year-old married woman, who has three pregnancies history, had irregular vaginal bleeding for 7 months. Six years ago she had right salpingo-oophorectomy for ectopic tubal pregnancy. Abnormal exudation and chronic cervicitis showed 7 months ago, followed by aggravated vaginal discharge. Pelvic examination disclosed a deep erosion of 1cm in diameter on the posterior lip of tile cervical os, which bled when touched. Surgical removal of the uterus was performed. Gross examination: (Fig. 12-27) Describe by self-observation: Microscopy examination: (Fig. 12-28) Describe by self-observation: Discussion: 1) Suggest a diagnosis based on the appearances in the photograph, giving your reasons 2) Analyze the pathogenesis, development and prognosis of the disease. Case two Case abstract: A 47-year-old woman had a hydatidiform mole removal from the uterus by curettage 4 months previously. Vaginal hemorrhage occurred about twice monthly. Urinary HCG tests were done at intervals of 6 weeks, 2 months and 4 months. The latest one was positive and was preceded by a profuse vaginal hemorrhage. On admission the patient was in shock, anemic, with hemoglobin of 9g, and blood pressure of 65/30mmHg. Pelvic examination revealed moderate enlargement of the uterus. A panhysterectomy was performed following multiple transfusions. The patient was well 3 years after the operation. Gross examination: (Fig. 12-29) Describe and observe by yourself: Microscopy examination: (Fig. 12-30a, b) Describe and observe by yourself: Discussion: 1) Suggest a diagnosis based on the appearances in the photograph, giving your reasons. 2) Why a panhysterectomy must be performed? What should be paid attention to after operation? Case three Case abstract: A 34-year-old married woman who had normal menstruations until 6 months previously, when she noted profuse hemorrhage at intervals varying from 14 days to 3 weeks. Examination revealed lower abdominal tenderness and a large boggy uterus. Curettage revealed malignant cells, and the panhysterectomy was performed. Gross examination: (Fig. 12-31) Describe by self-observation: Microscopy examination: (Fig. 12-32a,b) Describe by self-observation: Discussion: Suggest a diagnosis and give your reasons. Case four Case abstract: A 65-year-old woman noticed a mass in the upper outer zone of the right breast one year ago. In the past 6 weeks the tumor enlarged rapidly. Examination revealed an indurated irregular mass, 4 cm in diameter, with poor-mobility, in the upper outer quadrant of the right breast. The nipple was slightly retracted, and there was suggestive dimpling of the overlying skin. A hard enlarged lymph node was felt in the right axilla. Mammectomy was performed. Gross examination: (Fig. 12-33) Describe by self-observation: Microscopy examination: (Fig. 12-34) Describe by self-observation: Discussion: Suggest a diagnosis and give your reasons. PRACTICE REPORT 1. Illustrate the histological morphology of choriocarcinoma and invasive ductal carcinoma. 2. Describe the gross morphology of breast carcinoma; describe the gross and histological morphology of the invasive mole; describe the pathological features of teratoma. QUESTIONS FOR REVIEW 1. Will all the cervical carcinoma in situ develop into the invasive carcinoma? How to treat the cervical carcinoma in situ in clinical practice? 2. Can we make a diagnosis of invasive mole only by examination of specimen from curettage? Give your reasons. (Shandong University Li Jinsong)