Diseases of the liver and pancreas

Pouch of Douglas Pathology

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  Anterior to the rectum and posterior to the uterus; palpable with a rectal exam
  

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  Induration in a young woman: endometrial implants
  
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  Induration in elderly: seeding from primary ovarian cancer
  
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  Unclotted blood: ruptured ectopic
  
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  Pus: PID
  

Manifestations of Ovarian Disease

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  Infertility: caused by failure of ovulation
  
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  Menstrual irregularities: due to abnormal patterns of secretion of ovarian hormones
  
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  Ovarian Masses
  
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  Pelvic discomfort: very large masses
  
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  Pelvic pain
  

General Points - Ovary

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  Pregnancy is the MCC of a pelvic mass associated with amenorrhea
  
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  A functional ovarian cyst is the MC pelvic mass in menstruating reproductive-age women
  
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  Most childhood pelvic masses in females are either neoplastic or endocrine in origin
  

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  Originate from germ cells 80% of the time
  

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  During infancy, the MC adnexal mass is an ovarian cyst (relates to maternal estrogen); transient menses; regresses
  
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  In children <2, 40% of abdominal masses are renal in origin
  
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  The occurrence of new pelvic pain in a pre-menarchial girl or a postmenopausal woman is more often found associated with significant pathology
  

ID/CC A 20 year old Asian female visits her family doctor because of chronic, intermittent left lower quadrant pain.

HPI The pain is not accompanied by dyspareunia, menstrual irregularity, vaginal discharge, abdominal distention, nausea, vomiting, or diarrhea. It is not correlated with her menstrual periods

PE Left adnexal mass on bimanual exam; uterosacral ligaments normal; pouch of Douglas normal; McBurney’s point nontender; no evidence of ascites; remainder of exam normal

Labs Routine labs normal; CA-125 not elevated

Follicular Cyst of Ovary

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  Unruptured graafian follicles or follicles that have ruptured and immediately sealed
  
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  Filled with clear serous fluid and lined by a grey, glistening membrane
  
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  Unilocular without internal excrescences
  
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  Sometimes associated with hyperestrinism and endometrial hyperplasia
  
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  MOST COMMON OVERALL OVARIAN MASS
  

Follicular Cysts

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  Follicular cysts have smooth linings and are unilocular with no excrescences. The arrow is pointing to the single cell lining of a cyst
  

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  Large cysts are noted in both of these ovaries
  

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  Both of the ovaries from the specimen on the left have multiple follicular cysts; The cyst on the right has hemorrhaged.
  

ID/CC A 27 year old white female is admitted to the infertility clinic for evaluation of her inability to conceive; she also complains of dyspareunia and dysmenorrheal

HPI She is nulligravida. On directed history she admits to having rectal pain during menstruation; she also complains of having an abundant menstrual period (=menorrhagia or hypermenorrhea)

PE Bluish spots in posterior fornix on vaginal speculum exam; fixed tender bilateral ovarian masses palpable during menstruation on bimanual exam; induration in pouch of Douglas with multiple small nodules palpable through posterior fornix

Endometriosis

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  Ovary most common location
  
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  Produces Chocolate cysts
  

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  Multiple
  
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  Filled with dark-brown iron-containing fluid
  
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  Cysts lined by endometrial epithelium and stroma
  

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  A cyst of the ovary (endometrioma) is filled with dark blood (chocolate cyst).
  

Polycystic Ovarian Disease

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  Bilateral
  
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  Multiple follicular cysts (lack of FSH leads to atresia of follicles)
  
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  Absence of corpora lutea
  
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  Hyperplastic ovarian stroma-low FSH and high LH (ratio > 3/1)
  

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  FSH is not increased with LH, probably because of the synergistic negative feedback of chronically elevated estrogen levels and normal follicular inhibin
  
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  Increased LH stimulates the ovary to produce testosterone and 17-ketosteroids (androgens leading to hirsutism); increased adipose aromatizes androgens to estrogens (endometrial hyperplasia/cancer)
  

Polycystic Ovarian Syndrome:

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  Oligomenorrhea, Amenorrhea, infertility, virilism (Stein-Leventhal syndrome) and obesity
  
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  Excess androgens-hirsutism
  
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  Elevated estrogens- endometrial hyperplasia and menorrhagia
  
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  Increased risk of endometrial CA
  
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  Insulin resistance and hyperinsulinism-caused by obesity
  

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  SHBG is decreased with excess androgens and insulin increase leading to increase in free testosterone
  

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  Acanthosis nigricans is a marker for insulin resistance in hirsute women
  

Treatment:

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  Birth control pills or clomiphene if patient wants to become pregnant
  

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  Note the hirsuitism and obesity. The section of ovary on the right shows a hyperplastic stroma and multiple follicular cysts
  

Surface Coelomic Epithelium Derived Tumors

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  Clear Cell Carcinoma
  
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  Serous Tumors
  
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  Mucinous Tumors
  
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  Endometrioid Tumor
  
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  Brenner Tumor
  
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  Undifferentiated
  

Sex-Cord-Stromal Cell Derived Tumors

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  Granulosa-Theca Cell Tumors
  
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  Thecoma-Fibromas
  
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  Sertoli-Leydig Cell Tumors (Androblastomas)
  
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  Sex Cord Tumor with Annular Tubules
  
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  Steroid (Lipid) Cell Tumors
  

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  Stromal luteomas
  
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  Hilum cell tumors
  

Germ Cell Derived Ovarian Tumors

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  Teratoma (Cystic and Immature)
  
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  Dysgerminoma
  
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  Yolk Sac tumor
  
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  Embryonal Cell carcinoma
  
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  Choriocarcinoma
  

Facts Regarding Ovarian Tumors

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  80-90% of ovarian neoplasms are benign
  
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  Most common overall benign tumor and most common benign surface derived tumor: serous cystadenoma; second is Brenner’s tumor
  
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  Most ovarian tumors are in 20-45 year olds
  
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  High mortality rate in ovarian cancer due to late clinical presentation
  
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  Risk factors for cancer
  

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  nulliparity
  
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  family history
  

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  Fixed, irregular nodular adnexal mass with cul-de-sac nodularity or a palpable post-menopausal ovary should be considered malignant until ruled otherwise
  

Facts Regarding Ovarian Neoplasms

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  MC gynecologic malignancy=endometrial CA of uterus
  
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  Second MC gynecologic malignancy=ovary
  
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  Third MC gynecologic malignancy=cervix
  
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  30% of adnexal masses in women >50 are malignant
  
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  Most ovarian tumors arise from surface epithelium (65%)
  
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  SURFACE EPITHELIAL DERIVED TUMORS REPRESENT 94% OF MALIGNANT TUMORS OF THE OVARY
  
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  The MC pelvic mass in postmenopausal women is a leiomyoma of uterus
  
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  Ca 125 is the tumor marker for surface epithelial derived tumors of ovary; CEA is associated with mucinous cystadenoma (borderline) and cystadenocarcinoma
  

Serous cystadenoma-Benign

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  20% bilateral
  
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  75% of serous tumors are benign or borderline
  
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  20-50 years of age
  
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  Unilocular or multilocular with lining epithelium resembling fallopian tube-no papillary structures or epithelial thickening
  
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  Most common overall benign tumor
  

Serous Cystadenoma

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  The lining of cysts in a serous cystadenoma resembles fallopian tube epithelium. It is a single cell layer.
  

ID/CC A 56 year old white nulliparous woman is referred for evaluation of pelvic mass found on routine physical

HPI She reports increased frequency of micturition and irregular periods until they ceased three years previously. She has a history of breast cancer in the distant past.
PE Large cystic mass the size of a grapefruit in right pelvis that can be felt above the pubis symphysis
Labs CA-125 levels elevated
Serous Cystadenocarcinoma

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  40% of all cancers of ovary
  
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  MC malignant primary ovarian tumor
  
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  66% bilateral
  
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  Psammoma bodies-see on x-ray
  
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  Stratification >3 cell layers; nuclear atypia; stromal invasion; hemorrhage and necrosis; solid areas
  

Serous Cystadenocarcinoma

A,B. These tumors have solid areas and the cyst lining is stratified with >3 cell layers. Nuclear atypia is

noted; Psammoma bodies are present

C. Another example of a malignant serous tumor with psammoma bodies

Mucinous Cystadenoma

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  These tumors reach the largest sizes of all ovarian tumors.
  
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Mucinous Cystadenoma

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  The lining of the cysts resembles endocervical mucosa. It will be a single cell layer. The cysts are filled with sticky, gelatinous fluid
  

Mucinous Cystadenocarcinoma

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  20% bilateral
  
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  Solid areas with atypia and no connective tissue supports or cribriform pattern, stratification ( > 4 cell layers), necrosis, glandular structures
  
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  Pseudomyxoma peritonei-may cause bowel obstruction; most common associated with pseudomyxoma peritonei
  
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  Also due to CA of Gastrointestinal tract and appendix)
  

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  Associated with CEA production
  

Mucinous Cystadenocarcinoma

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  The patient on the left has pseudomyxoma peritonii with massive ascites. Malignant serous tumors have solid areas and complex lining to the cystic spaces with a cribriform appearance
  

Endometrioid Tumors

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  20% of malignant ovarian tumors
  
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  Most are malignant; greatest association of ovarian tumors with endometriosis
  
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  40% bilateral
  
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  Composed of glands resembling endometrial glands
  
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  15-33% accompany carcinoma of endometrium
  
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  40-50% 5-year survival-Best of surface epithelial derived tumors
  

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  mimics the endometrial glands and stroma best prognosis of all of the surface derived ovarian tumors
  

Clear Cell Adenocarcinoma

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  May occur in association with endometriosis or endometrioid CA of ovary
  
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  Resembles clear cell CA of endometrium (A histologic variant of endometrial CA)
  
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  Solid or Cystic-large cells with clear abundant cytoplasm; the cells lining the cysts are called hobnail cells
  

Another example of clear cell carcinoma. Note the “hob-nail” cells lining the cysts on the right
Brenner Tumor of Ovary

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  Adenofibroma-composed of nests of epithelial cells which resemble transitional cells of the urinary bladder (Walthard’s rests) + fibrous stroma
  
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  Benign
  
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  90% unilateral
  

Note the presence of “Walthard Rests” resembling transitional epithelium. These are diagnostic features of the Brenner tumor

Germ cell tumors of ovary

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  15-20% of all ovarian tumors
  
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  Most are benign cystic teratomas
  
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  Composed of cells derived from oocytes
  

Teratoma-Mature (Benign)

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  Also called Dermoid Cysts; originate from a single germ cell after its first meiotic division
  
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  Young women (age 20-40)
  
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  Contain ectoderm, endoderm, and mesoderm
  
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  Often are calcified usually bone or tooth formation; most cysts are unilocular and lined by skin tissue
  
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  10-15% bilateral; risk is undergoing torsion
  
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  If malignant component-squamous cell carcinoma
  

ovarian cystic teratomas

Benign Cystic Teratoma

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  Gross of a teratoma on left; on right, CNS tissue, pigmented retina, and sebaceous glands
  

Immature Malignant Teratomas

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  Component tissue resembles fetal tissue
  
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  Mean age=18
  
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  Solid tumors; 3rd most common malignant ovarian germ cell tumor
  
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  Grading of tumor based on amount of tumor tissue that is immature neuroepithelium
  

Note the presence of immature neuroepithelium

Specialized Teratomas

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  Struma ovarii
  

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  Unilateral
  
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  Mature thyroid tissue which may produce hyperthyroidism
  

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  Carcinoid tumor
  

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  Unilateral
  
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  May produce carcinoid syndrome
  
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  Distinguish from metastatic carcinoid to ovary=bilateral; AGGRESSIVE
  

Struma ovarii (thyroid tissue) on the left

Carcinoid tumor on the right

Dysgerminomas of Ovary

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  2% ovarian cancers
  
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  50% of malignant germ cell tumors; most common malignant germ cell tumor
  
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  75% occur in 2nd and 3rd decade
  
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  Unilateral-80-90%
  
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  Large anaplastic cells with prominent nucleoli + benign lymphoid stroma
  
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  Usually no endocrine function; few produce hCG; LDH elevated
  
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  Radiosensitive; now being treated with cisplatin
  
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  Associated with Turner’s syndrome
  

A,B. Dysgerminomas are solid tan tumors; microscopically, they are composed of nests of germ cells with

lymphocytes in the stroma

C. High magnification showing the nests of germ cells and lymphocytes in the stroma.

Endodermal Sinus (Yolk Sac Tumor)

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  Second MC malignant germ cell tumor; rare
  
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  Alpha-fetoprotein is tumor marker
  
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  Also produces Alpha-1-antitrypsin
  
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  Glomerular like structures composed of a central blood vessel enveloped by germ cells (Schiller-Duval body)
  
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  Patients are children or young women (in age group under 20 years, yolk sac tumors are as common as dysgerminoma) who present with abdominal pain and a rapidly expanding pelvic mass
  
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  Unilateral
  

A.Yolk sac tumors resemble primitive lung tissue.

B.A Schiller-Duval body is seen on the far right (blood vessel surrounded by germ cells)

C.A Schiller-Duval Body on the left

D.The slide on the right show eosinophilic droplets of alpha-fetoprotein

Embryonal Carcinoma

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  Unilateral; young patients
  
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  Present with an abdominal mass
  
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  Positive pregnancy test due to ß-hCG; tumor also produced alpha-fetoprotein (only tumor producing both)
  
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  A pluripotential stem cell tumor capable of differentiating along different pathways
  

Choriocarcinoma

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  Nongestational primary choriocarcinoma of the ovary is rare and malignant
  

Sex Cord-Stromal Tumors

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  Tumors derived from ovarian stroma which is derived from the sex cords of the embryonic gonad
  
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  Counterpart tumors in males
  
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  May be associated with Peutz-Jegher syndrome
  

Granulosa-Theca Cell Tumor

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  5% of all ovarian tumors
  
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  2/3 occur in post-menopausal women
  
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  Present with endometrial hyperplasia, cystic disease of breast, endometrial carcinoma
  
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  Also occur in young girls
  
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  Precocious sexual development
  
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  Excess estrogen
  
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  Call-Exner body-central cystic cavity filled with eosinophilic fluid surrounded by granulosa cells resembling a follicle
  

These tumors are typically hormone-producing

A microscopic marker is the Call-Exner body(a cluster of tumor cells resembling a graffian follicle of the ovary
Granulosa-Theca Cell tumor

Call-Exner Body on the left

Granulosa cells with bean-shaped nuclei

Thecoma-Fibromas

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  90% unilateral
  
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  Fibroblasts (fibromas)(no estrogen) or plump spindle cells with lipid droplets (thecomas)-produce estrogen
  
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  Fibromas are the MC sex-cord stromal tumor-frequently calcify
  
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  Thecoma: 80% of patients are postmenopausal; less common than granulosa cell tumors
  
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  Present with pain and pelvic mass
  
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  Meig’s syndrome: Hydrothorax (right side) + ovarian tumor (fibroma) + ascites
  
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  Associated with basal cell nevus syndrome
  

The yellow-staining portions of the tumor are the hormone positive areas. This can be demonstrated by lipid stains of the tumor (note the red areas)

Ovarian Fibromas

Bilateral Ovarian Fibromas

Note the massive enlargement of both ovaries by fibromas. The arrow indicates the uterus
Sertoli-Leydig Cell Tumors (Androblastoma or Arrhenoblastoma)

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  Peak age: 2nd and 3rd decade
  
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  Virilizing tumors-excess androgens
  
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  Rarely produce estrogens
  
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  Benign
  
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  These tumors typically produce androgens
  

Sex Cord Tumor with Annular Tubules (SCTAT)

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  33% of cases are associated with Peutz-Jeghers syndrome
  
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  Features are intermediate between a granulosa cell tumor and a Sertoli cell tumor
  

Hilar Cell (Steroid) Tumors

(Leydig Cell Tumors)

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  Benign
  
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  Secrete androgens
  
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  Unilateral
  
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  Contain large, lipid filled cells and rod-like crystals called REINKE CRYSTALLOIDS
  
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  A characteristic microscopic feature of the hilar cell tumor is the Reinke crystalloid.
  

Gonadoblastoma
Ovarian Tumors of Dysgenetic Gonads

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  Combination of a germ cell tumor plus a sex-cord stromal tumor
  
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  Occurs with gonadal dysgenesis-usually Turner’s syndrome with a Y chromosome; all patients are genotypic males with a Y chromosome
  
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  80% are phenotypic females
  
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  50% have associated dysgerminoma
  
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  May calcify
  
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  Benign
  

Characteristic features of gonadoblastoma. Note the glandular spaces on the left and right and the calcifications on the right (arrow)

Ovarian Tumors that may Calcify

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  Fibromas
  
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  Cystic Mature Teratomas
  
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  Gonadoblastomas
  
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  Serous Epithelial Tumors with Psammoma bodies
  

Metastatic Tumors to Ovary

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  Breast Cancer MC
  
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  Carcinoma of stomach (signet ring type)
  
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  Krukenberg tumors-metastatic mucin-producing adenocarcinomas-usually gastric-but may be from other sites
  
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  Colon carcinoma: may be microscopically confused with endometrioid carcinoma
  
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  Burkitt’s lymphoma may involve ovary
  
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Metastatic Adenocarcinoma to Ovary

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  Note the nests of malignant cells within mucin lakes on the left; the slide on the right shows signet ring cells from stomach producing a Krukenberg tumor
  

Female Genital Tumors

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  The only primary tumors of the female genital tract that are associated with ascites are derived from the ovary!!
  

Placental Pathology



Spontaneous Abortion

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  A pregnancy that terminates usually before the 22nd week of gestation (before the fetus is capable of extrauterine life)
  
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  45% of fertilized ova are aborted
  
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  Majority of errors are in maternal gametogenesis
  
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  Causes include:
  
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  problems with the ovum or fetus (50% have trisomy 16; hydatidiform mole, neural tube defects)
  
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  infection early in pregnancy
  
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  mechanical factors affecting the uterus
  
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  endocrine factors or immunologic factors
  
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  Patients present with vaginal bleeding and lower abdominal pain
  

Placenta accreta

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  Attachment of the placenta directly to the myometrium; decidual layer is defective
  
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  Placenta does not separate easily after delivery causing significant bleeding problems
  
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  MC presenting sign is bleeding in the 3rd trimester
  
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  Uterine rupture in 15%
  
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  Due to scars (Asherman’s syndrome) from previous C-sections or endometrial inflammation; loss of decidua basalis
  

Placenta Previa

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  Implantation over or close to the cervical os
  
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  Presents with PAINLESS bleeding
  
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  Most common cause of antepartum hemorrhage
  

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  Predisposing factors include maternal age, parity, anatomic uterine abnormalities, and previous uterine surgery
  

Abruptio Placenta

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  A significant complication of preeclampsia
  

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  Due to a premature separation of the placenta with a resultant retroplacental clot
  
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  Patient presents with PAINFUL, vaginal bleeding
  
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  Hematomas involving 1/3 or more of the maternal surface can result in fetal death
  
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  Associated with maternal hypertension or cocaine abuse
  

Abruptio Placenta

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  Note the large amount of retroplacental hemorrhage in both specimens