Normal Lab Values

Week 16: Breast & Female Reproductive System

Suggested readings from
Robbins 8th ed.
Female Genital Tract: pp. 1005-1064

Pathology of the Breast: pp. 1065-1096

Cases for Week 16

Micro cases for Week 16

Review Items for Week 16: Breast Pathology

Review Items for Week 16: Female Reproductive System

 

Pathology Case Descriptions

CASE NUMBER 199
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Clinical History: A 34-year-old woman discovered a mass in her breast. Mammogram revealed microcalcifications. A mastectomy was perfomed.

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(Summary of Gross Findings - click here)
There is inflammation and dimpling of the areola. The cut surface of the resected breast tissue reveals a 3 x 3 x 2 cm firm mass with stellate borders. The center of the mass is firm, scirrhous and white because of the desmoplasia. There are areas of yellowish necrosis in the portions of neoplasm infiltrating into the surrounding breast. Such tumors appear very firm and non-mobile on physical exam.
(Summary of Microscopic Findings - click here)
The virtual image was derived from a breast biopsy on another patient and shows both intraductal carcinoma with a comedo pattern of necrosis and invasive infiltrating ductal carcinoma. Ductal carcinomas range from well-differentiated tumors characterized by good duct formation to poorly-differentiated tumors. This one is composed of infiltrating glands and sheets of pleomorphic cells which infiltrate into the adjacent breast tissue. This infiltrating ductal carcinoma of breast at low magnification appears to radiate from a central area of desmoplasia. This collagenous component gives the neoplasm a hard "scirrhous" consistency that is palpable on physical examination or breast self-examination. Such an invasive carcinoma may be fixed to underlying chest wall, making it non-mobile. Also note the nerve which is invaded by tumor. It would also be important for treatment and prognosis to determine if the tumor cells were estrogen and progesterone receptor positive.
(Review Normal Histology - click here)
Norm No. 19 Female breast
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The female breast is a secretory organ that produces milk during lactation. Breast tissue that is not stimulated to lactate consists of resting apocrine cells arranged in nests and small ductules which are lined by cuboidal epithelium. The secretory units are separated from one another by loose connective tissue.

 

199-1. What is the MOST LIKELY diagnosis?

  1. Medullary carcinoma
  2. Lobular carcinoma
  3. Infiltrating ductal carcinoma
  4. Lymphoma
  5. Adenoid cystic carcinoma

ANSWER


199-2. The following are elements used in the staging of this tumor:

  1. Degree of tubule formation
  2. Amount of nuclear pleomorphism
  3. Mitotic rate
  4. ALL of the above
  5. NONE of the above

ANSWER


199-3. The following are elements used in the grading of this tumor:

  1. The size of the tumor
  2. How many axillary lymph nodes contain metastatic tumor
  3. Distant metastases to lung and/or brain
  4. ALL of the above
  5. NONE of the above

ANSWER

 

199-4. What are some of the major risk factors for breast cancer?

ANSWER

 

199-5. The following features are poor prognostic markers in breast cancer EXCEPT?

  1. Tumor stage
  2. Tubular carcinoma histological type
  3. Invasion of chest wall
  4. Negative estrogen and progesterone receptors by immunohistochemistry
  5. Lymphovascular invasion

ANSWER

 

199-6. Concerning BRCA1 and BRCA2 genes, which of the following is FALSE?

  1. Mutations in either account for about 25% of familial breast cancers.
  2. Mutated BRCA1 is also associated with 20-40% higher risk of ovarian cancer.
  3. BRCA1 mutation is common in sporadic breast cancer.
  4. Hypermethylation of BRCA1 is common in breast cancers of medullary and mucinous types.

ANSWER

 

 

 

CASE NUMBER 233
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Clinical History: This 23-year-old white female was found to have a cervical lesion three months previous to this admission. A biopsy revealed carcinoma of the cervix. The uterus was removed. Preoperative radiation therapy is common today.

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(Summary of Gross Findings - click here)
The entire external cervix showed a large, gray-pink, fungating lesion, 5.5 cm in size. It extended into the internal cervical canal and also involved one of the obturator lymph nodes.
(Summary of Microscopic Findings - click here)
The external cervix shows fibrosis and acute and chronic inflammatory infiltration. A portion of the cervical mucosa is infiltrated with squamous cell carcinoma. The tumor cells are pleomorphic and bizarre and frequently form giant cells. Strands and nests of the tumor cells are seen in the cervical stroma. Marked acute and chronic inflammation is present in association with the tumor.
(Review Normal Histology - click here)
Slide 249 (cervix, H&E) WebScope ImageScope
UCSF slide 405 (cervix, trichrome) WebScope ImageScope

The uterine cervix shown in slide 249 is continuous with both the body of the uterus and the upper portion of the vagina. Note that the wall has considerable smooth muscle and much dense connective tissue. Note also the number of collagen fibers in the stroma.

The mucosa is lined by a tall columnar mucus-secreting epithelium in its uterine portion, but note the abrupt change to stratified squamous epithelium at its vaginal face. This stratocolumnar junction which should be readily identifiable in both slide 249 [example] and UCSF slide 405 [example] is frequently the site of pre-neoplastic and neoplastic (cervical cancer) changes. The mucosa is thrown into deep irregular folds known as plicae palmitae (palmate folds). During the majority of the uterine cycle these glands secrete a highly viscous mucus forming a barrier to microorganisms, while at mid-cycle (ovulation) the mucus becomes more hydrated, which facilitates sperm entry. Blockage of the openings of the cervical mucosal glands frequently results in the accumulation of secretory products within the glands, leading to the formation of dilated Nabothian cysts which may be seen in USCF slide 304 [example]. These cysts are generally benign; however, they can become clinically relevant should they become enlarged enough to cause obstruction of the cervical canal.

 

What is the MOST LIKELY diagnosis?

ANSWER

 

233-1. Which of the following statements about this tumor is/are true?

  1. It may present at any age of life from second decade onwards
  2. Related to HPV infection
  3. Fungating tumor in the cervix
  4. 95% of squamous cell carcinomas are large cell
  5. ALL of the above
  6. NONE of the above

ANSWER

 

 

 

CASE NUMBER 70
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Clinical history: This 60-year-old female presented to her physician with a complaint of post menopausal bleeding. A hysterectomy was performed.

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(Summary of Gross Findings - click here)
The surgical specimen was an enlarged uterus, distorted by multiple firm, grayish-white nodes and nodules (myomata). Within the endometrial cavity was a pedunculated grayish-red mass with smooth surfaces, measuring about 2.5 x 1 cm, lying in the long axis of the uterus.
(Summary of Microscopic Findings - click here)
A pedunculated, endometrial polyp arises from the endometrial surface. It is composed of distorted endometrial glands of various sizes, some of which show cystic dilatation. The glands are lined by one or more rows of cells with uniform oval or round nuclei and scanty, eosinophilic cytoplasm. The lumina contain a small amount of mucoid secretions. The surrounding stroma shows slight diffuse, lymphocytic infiltration. The endometrium adjacent to the polyp shows pressure atrophy and focal hemorrhages. Located submucosally and within the myometrium are two small leiomyomas.
(Review Normal Histology - click here)
Norm No. 21 Uterus
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The uterus is a reproductive organ, capable of enormous growth during pregnancy. It is composed of an inner endometrium which supports the placenta during pregnancy. The glandular endometrium undergoes monthly cycles in response to endocrine influence. It undergoes proliferation and then a secretory phase when it is capable of supporting a fertilized ovum. It is subsequently shed during menstruation. The endometrial here is proliferative. If you look carefully you can see mitotic figures in the endometrial glands. Note the regular spacing and orderly array of the endometrial glands. Beneath the endometrium is the myometrium which is composed of smooth muscle cells.

 

What is the MOST LIKELY diagnosis?

ANSWER

 

70-1. Which of the following is FALSE of this pathology?

  1. Composed of hyperplastic endometrium with cystic glands
  2. May respond to effect of estrogen
  3. Associated with thiazide treatment
  4. Commonly present with bleeding
  5. Stromal cells are clonal and show rearrangements of 6p21
  6. ALL of the above statements are false regarding this type of pathology.
  7. NONE of the above statements are false regarding this type of pathology.

ANSWER

 

70-2. Which of the following statements about endometrial hyperplasia is/are TRUE?

  1. It is characterized by a decrease in glandular to stromal ratio.
  2. It is linked to prolonged progesterone stimulation of the endometrium.
  3. p53 inactivation is seen in 63% of premalignant endometrial hyperplasia and 50-80% of endometrial carcinomas.
  4. Complex atypical hyperplasia features crowded glands with cell stratification, nuclear enlargement and frequent mitoses.
  5. Low grade (simple non-atypical) endometrial hyperplasia is associated with luteal phase insufficiency.
  6. ALL of the above
  7. NONE of the above

ANSWER

 

 

CASE NUMBER 220
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Clinical History: This was a 58 year-old-female whose uterus was removed for uterine prolapse and urinary incontinence.

Image Gallery:

(Summary of Gross Findings - click here)
The uterus was slightly enlarged, and contained many gray firm circumscribed nodules 0.5 cm - 2 cm in size. These nodules bulged out of the cut surface. Most of them were located intramurally, but there were some are located in the sub mucosal or the subserosal areas.
(Summary of Microscopic Findings - click here)
The tumor nodules are composed of interlacing bundles of cells, which have long spindle nuclei and pink fibrillary cytoplasm. These cells resemble the smooth muscle cells of the myometrium. Portions of the tumor tissue have become pink hyalinized masses in which only a few cells are present. These tumor nodules do not have a definite capsule, though their outlines are rather distinct. A small number of vessels are present within the tumor.
(Review Normal Histology - click here)
Norm No. 21 Uterus
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The uterus is a reproductive organ, capable of enormous growth during pregnancy. It is composed of an inner endometrium which supports the placenta during pregnancy. The glandular endometrium undergoes monthly cycles in response to endocrine influence. It undergoes proliferation and then a secretory phase when it is capable of supporting a fertilized ovum. It is subsequently shed during menstruation. The endometrial here is proliferative. If you look carefully you can see mitotic figures in the endometrial glands. Note the regular spacing and orderly array of the endometrial glands. Beneath the endometrium is the myometrium which is composed of smooth muscle cells.

 

220-1. This tumor in the uterus arises from:

  1. endometrial stromal cells
  2. smooth muscle
  3. endometrial cells
  4. nervous tissue
  5. fibroblasts

ANSWER

 

220-2. The diagnosis is:

  1. uterine adenomyosis
  2. endometrial adenosarcoma
  3. endometrial stromal sarcoma
  4. uterine leiomyoma
  5. uterine schwannoma

ANSWER

 

220-3. In the pathologic assessment of this sort of pathology:

  1. Nuclear atypia and giant cells are not compatible with a benign tumor.
  2. The distinction between leiomyosarcoma and leiomyoma is based on nuclear atypia, mitotic index and necrosis.
  3. Malignant transformation of a leiomyoma is common.
  4. Subserosal leiomyoma is the most likely cause of menorrhagia.

ANSWER

 

 

 

CASE NUMBER 123 (micro case 6)
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Clinical History: A 25-year-old woman had pelvic pain, fever, and vaginal discharge for 3 weeks. On physical examination, she has lower abdominal adnexal tenderness and a painful, swollen left knee.  Laboratory studies show WBC count of 11,875/mm3 with 68% segmented neutrophils, 8% bands, 18% lymphocytes, and 6% monocytes.

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(Summary of Lab & Gross Findings - click here)
The tubes were markedly distended and thickened with adhesions between the fimbriated end and the ovaries. On sectioning, pus exuded from the lumen. Neisseria gonnorheae requires chocolate agar for culture. Thayer-Martin agar contains antibiotics that suppress growth of other organisms and allow the growth of N. gonnorheae. The organisms aresmall gram negative cocci in pairs.
(Summary of Microscopic Findings - click here)
The villi of the uterine tube are plump and edematous, with marked dilation and congestion of capillaries. The mucosa is heavily infiltrated by polymorphonuclear leukocytes, which have broken through foci of necrotic mucosa, producing the purulent exudate. Besides this acute phase, there are chronic features evidenced by plasma cell, lymphocytic and macrophage infiltration and fibroblastic proliferation. The muscular layers are edematous and infiltrated by acute and chronic inflammatory cells. This probably represents gonorrheal infection, the mucosa being predominantly involved, in contrast to other pyogenic infections which more frequently involve the outer layers and relatively spare the mucosa.
(Review Normal Histology - click here)
Norm No. 20 Uterine (fallopian) tube (aka oviduct)
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The fallopian tube is lined by ciliated columnar epithelium that aid in transport of the ovum to the uterus. The epithelium is arranged in fronds that project into the lumen. The wall consists of smooth muscle and connective tissue.

 

What is the MOST LIKELY diagnosis?

ANSWER

 

123-1. What is a likely complication of this disease?

  1. Ectopic pregnancy
  2. Infertility
  3. Tubo-ovarian abscess
  4. ALL of the above

ANSWER

 

123-2. What organisms are most likely to cause this disease?

  1. Bacteria
  2. Viruses
  3. Fungi
  4. Parasites

ANSWER

 

123-3. Which of the following statement about this disease is FALSE?

  1. It is usually associated with endometriosis
  2. May be complicated by strictures and infertility
  3. May also involve the adjacent ovary
  4. May result in a hydrosalpinx
  5. May be complicated by septicemia
  6. ALL of the above statements are false regarding this disease.
  7. NONE of the above statements are false regarding this disease.

ANSWER

 

123-4. The following organisms are commonly responsible for pelvic inflammatory disease EXCEPT:

  1. Gonococci
  2. Chlamydia
  3. Aspergillus
  4. Streptococcus
  5. Staphylococcus

ANSWER

 

 

 

CASE NUMBER 116
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Clinical History: This 50-year-female complained of lower abdominal pressure. A mass was palpated on pelvic examination.

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(Summary of Gross Findings - click here)
A hysterectomy and salpingoophorectomy was performed. The uterus is grossly normal. One ovary is markedly enlarged and replaced by multiloculated cysts. When the cysts are opened they are found to be filled with thick mucinous material.
(Summary of Microscopic Findings - click here)
The cysts are complex and lined by benign mucin secreting epithelium.
(Review Normal Histology - click here)
Norm No. 4 Ovary
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Ovary tissue consists of stoma which is composed of elongated stromal cells. Within the stoma are oocytes in various stages of development. Most of the oocytes have not been stimulated to mature. These resting oocytes have very large nuclei with prominent nucleoli. There are corpora albicantia in a bland stroma.  The Corpus Luteum of Pregnancy is composed of granulosa cells with abundant foamy cytoplasm. The granulosa cells are arranged in complex folds.

 

What is the MOST LIKELY diagnosis?

ANSWER

 

116-1. This type of ovarian tumor:

  1. Arises from the ovarian germ cells
  2. Shows prominent proliferation of the fibrous stroma
  3. Tends to occur in middle adult life and rarely after menopause
  4. Is associated with Meigs syndrome
  5. May result in precocious puberty

ANSWER

 

116-2. Which of the following statements about ovarian mucinous tumors of borderline malignancy is/are TRUE?

  1. Associated with Peutz Jeghers syndrome
  2. Commonly show calcifications (psammoma bodies)
  3. Nests of transitional cells are frequently seen
  4. Are associated with Schiller-Duval bodies
  5. Bilateral tumors are often associated with a mucinous neoplasm of the appendix
  6. ALL of the above
  7. NONE of the above

ANSWER

 

 

Micro Cases

Micro Case 15

Clinical history: A 35-year-old man with HIV complains that he has had a "bad" taste in his mouth and discoloration of his tongue for the past 6 weeks.

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(Summary of Gross and Lab Findings - click here)
There are areas of adherent, yellow-tan, circumscribed plaque on the oropharynx and the tongue. This plaque can be scraped off as a pseudomembrane to show an under­lying granular, erythematous base. The material is composed of organisms and inflammatory debris. Gram stained smear shows yeast with pseudohyphae. Culture shows pearly colonies typical of yeast. Germ tube test is positive. Invasive infections may occur in immunocomprised individuals. Pseudohyphae may be seen in tissue section with PAS stain.

 

m15-1. What is the MOST LIKELY diagnosis?

ANSWER

 

 

BREAST PATHOLOGY Review Items

Key Vocabulary Terms (click here to search any additional terms on Stedman's Online Medical Dictionary)

adenosis Indian filing
blue dome cyst  inflammatory carcinoma
comedocarcinoma intraductal papilloma
cribriform pattern microcalcification
fibrocystic change peau d’orange
gynecomastia scirrhous

LEARNING OBJECTIVES

Absolutely critical information you must know to practice medicine is in bold font.
Important information that will be needed for routine patient care is in regular font.
Information about less common diseases that you may encounter in clinical practice and that will probably appear on examinations is in italics

  1. Describe the hormonally-induced morphologic changes which occur in the female breast during the following stages:
    • neonatal
    • pubertal
    • menstrual
    • gestational
    • lactational
    • postmenopausal

  2. Discuss the clinical and pathologic features of the following reactive breast conditions:
  3. Discuss silicone breast implants, in terms of:
    • morphologic changes in adjacent breast
    • known epidemiologic relationships with autoimmune disease

  4. Compare and contrast fibroadenoma and phyllodes tumor in terms of:
    • incidence
    • clinical presentation
    • morphology
    • clinical features and prognosis

  5. Discuss fibrocystic change of the breast in terms of:
    • age predilection
    • incidence
    • etiology
    • clinical presentation
    • general morphology
    • mammographic appearance
    • relationship to carcinoma of the breast

  6. Compare and contrast the clinical and pathologic features of the following morphologic manifestations of fibrocystic change of the breast:
  7. Compare and contrast the clinical and pathologic features of the following:
  8. Discuss female mammary carcinoma in terms of:
    • genetics
    • risk factors
    • incidence
    • etiology
    • pathogenesis
    • clinical presentation
    • gross morphology
    • patterns of spread
    • methods of diagnosis
    • clinical course
      • staging
      • prognostic indicators
    • treatment options
    • survival rates

  9. Compare and contrast the clinical and pathologic features of the following types of invasive mammary carcinoma:
  10. Discuss the indications for as well as sensitivity and specificity of the following diagnostic procedures for evaluating breast masses:
    • self-examination
    • mammography
    • fine needle aspiration cytology

  11. List the most common causes of breast mass in females during the following ages:
    • under 35 years of age
    • 35-50 years of age
    • over 50 years of age

  12. Compare and contrast the following diseases of the male breast:

 

FEMALE GENITAL SYSTEM Review Items

Key Vocabulary Terms (click here to search any additional terms on Stedman's Online Medical Dictionary)

adenomyosis dysgerminoma malignant mixed Müllerian tumor (MMMT)
adenosis dysmenorrhea Meigs syndrome
atypical endometrial hyperplasia dysplasia  menometrorrhagia (MMR)
borderline ovarian tumor (BOT) embryonal carcinoma menorrhagia
Brenner tumor endodermal sinus tumor metrorrhagia
Call-Exner body endometriosis microinvasive carcinoma
carcinoma in situ (CIS) fibroma nabothian cyst
carcinosarcoma flat condyloma Pap smear
cervical intraepithelial neoplasia (CIN) follicular cyst pelvic inflammatory disease (PID)
chocolate cyst gonadoblastoma pseudomyxoma peritonei
choriocarcinoma granulosa cell tumor pyosalpinx
colposcopy hematosalpinx sarcoma botryoides
condyloma acuminatum HPV Schiller-Duval body
condyloma latum HSV Sertoli-Leydig cell tumor
cone biopsy hydrosalpinx squamous intraepithelial lesion (SIL)
curettage koilocytosis teratoma
cystadenocarcinoma Krukenberg tumor thecoma
cystadenofibroma leukoplakia vaginal intraepithelial neoplasia (VAIN)
cystadenoma low malignant potential (LMP) vulvar intraepithelial neoplasia (VIN) 
dysfunctional uterine bleeding (DUB) luteal cyst  

LEARNING OBJECTIVES

Absolutely critical information you must know to practice medicine is in bold font.
Important information that will be needed for routine patient care is in regular font.
Information about less common diseases that you may encounter in clinical practice and that will probably appear on examinations is in italics

  1. Describe the following congenital anomalies and their embryologic bases:
  2. List the common microorganisms which cause:
  3. Discuss the clinical and pathologic features of the following vulvar lesions:
  4. Compare and contrast trichomonal and monilial vaginitis, in terms of:
    • predisposing factors
    • etiology
    • pathogenesis
    • symptoms
    • methods of detection

  5. Compare and contrast the clinical and pathologic features of :
  6. Define discuss general features of extramammary Paget disease, in terms of:
    • clinical presentation
    • morphology
    • associated malignancies
    • clinical course

  7. Discuss vaginal adenosis and vaginal adenocarcinoma, in terms of
    • epidemiology
    • etiology
    • pathogenesis
    • morphology
    • clinical significance

  8. Compare and contrast the clinical and pathologic features of cervical lesions:
  9. Discuss the screening and diagnostic procedures for cervical cancer in terms of methodology, indications, and utilization.

  10. Discuss cervicovaginal cytology, in terms of:
    • technique of obtaining specimen
    • utility in diagnosis of inflammatory conditions
    • types and significance of abnormalities
    • utility in diagnosis of CIN of cervix, carcinoma of cervix and carcinoma of endometrium

  11. Outline the morphologic effects of oral contraceptive agents (oral contraceptive pills, OCP's) on the endometrium, in relation to mode of action and possible adverse complications.

  12. Compare and contrast endometriosis and adenomyosis in terms of:
    • incidence
    • clinical presentation
    • pathogenesis
    • morphology
    • organs involved
    • complications

  13. Discuss the clinical and pathologic features of the following endometrial processes:
  14. Discuss endometrial carcinoma in terms of:
    • incidence
    • age distribution
    • risk factors
    • clinical presentation
    • epidemiology
    • predisposing factors
    • pathogenesis
    • morphology including common types
    • methods of detection
    • grading and staging
    • prognosis

  15. Compare and contrast the clinical and pathologic features of:
  16. List the conditions which result in non-neoplastic enlargement or cysts of the ovary.

  17. Discuss polycystic ovarian disease in terms of clinical presentation and morphology.

  18. Compare and contrast the clinical and pathologic features of ovarian neoplasms:
    • surface epithelial tumors
      • benign
      • borderline
      • malignant
    • sex cord-stromal tumors
    • germ cell tumors
    • metastatic malignancy to ovary

  19. Compare and contrast ovarian vs. placental (gestational) choriocarcinoma, in terms of:
    • cell of origin
    • pathogenesis
    • morphology
    • clinical features
    • treatment and prognosis

  20. List the most common primary malignant tumors which metastasize to the ovary.

  21. List and differentiate among clinical etiologies of:
    • pelvic pain in reproductive age group
    • vaginal bleeding in reproductive age group
    • vaginal bleeding in post-menopausal age group
    • vulvar lesions in older women

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