Diseases of the liver and pancreas

Types of Germ Cell Tumors

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  Teratomas
  

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  Mature (Benign) Teratomas
  
• 
  Immature Malignant Teratomas
  
• 
  Monodermal or Specialized Teratomas
  

• 
  Dysgerminoma
  
• 
  Endodermal Sinus (Yolk Sac) Tumor
  
• 
  Choriocarcinoma
  

Germ Cell Tumor Classification

Dysgerminoma

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  Ovarian counterpart of the seminoma of the testis.
  
• 
  Similar to the latter, it is composed of large vesicular cells having a cleared cytoplasm, well-defined cell boundaries, and centrally placed regular nuclei.
  
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  Relatively uncommon tumors, the dysgerminomas account for about 2% of all ovarian cancers yet form about half of malignant germ cell tumors.
  
• 
  75% occur in the second and third decades.
  
• 
  Most of these tumors have no endocrine function.
  

• 
  Few produce elevated levels of chorionic gonadotropin
  
• 
  May have syncytiotrophoblastic giant cells on histologic examination
  
• 
  Tumors confined to the ovary have an excellent prognosis, with 5-year survival approaching 100%.
  
• 
  Dysgerminomas, like their testicular counterparts, are highly radiosensitive.
  

Morphology

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  Usually large, solid and bosselated with a smooth surface.
  
• 
  Cut surface is soft, fleshy and bulging with a homogeneous pink-tan color
  

Dysgerminoma

• 
  Note lobulation and uniform tan color with
  

foci of hemorrhage.

Histology

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  Sheets of monotonous rounded cells with central nuclei containing 1 to 2 prominent nucleoli, surrounded by fibrous stroma infiltrated with mature lymphocytes.
  
• 
  Occasional giant cells which stain positively with hCG may be seen.
  

• 
  There may be enough of these giant cells to produce clinically detectable hCG levels.
  

Dysgerminoma

• 
  Sheets of monotonous rounded cells with pale
  

cytoplasm and central nuclei. Lymphocytes

infiltrate the stroma.

Teratoma

• 
  A teratoma is a germ cell tumor that shows differentiation toward embryonic tissues.
  
• 
  They are usually composed of tissues from any, but usually all three germ (embryonic) layers and which are foreign to the ovary.
  
• 
  Subdivided into:
  

• 
  Mature
  
• 
  Immature
  
• 
  Monodermal
  

• 
  Unlike in the testis, the vast majority of ovarian germ cell tumors are benign mature cystic teratomas.
  

Mature teratomas

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  Are benign
  
• 
  May be solid or cystic.
  
• 
  Solid mature teratomas
  

• 
  Are uncommon
  
• 
  Always unilateral.
  

• 
  Mature cystic teratomas
  

• 
  25% of all ovarian tumors
  
• 
  33% of all benign ovarian tumors
  
• 
  Found mainly in young women between 20 and 30 years
  
• 
  Are usually unilateral
  
• 
  Also called dermoid cysts because 90% of the cysts are lined by mature epidermal tissue with underlying pilosebaceous structures.
  
• 
  Typically filled with sebaceous material and hair.
  
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  30% contain well-formed teeth in the wall.
  
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  Other tissues commonly seen include cartilage, bone, and respiratory epithelium
  

Mature cystic teratoma - gross

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  Containing hair and inspissated sebaceous material (lower right corner)
  

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  Note well-formed tooth (upper right corner)
  

Mature cystic teratoma – histology

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  showing keratinized squamous epithelium, and respiratory epithelium.
  

Immature teratomas

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  Composed totally or partially of immature or fetal tissues.
  
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  Found mainly in young pre-pubertal adolescents and young women < 20 years
  
• 
  ~ 20% of all malignant germ cell tumors
  

Immature teratoma – Gross Immature teratoma – Microscopic

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  Tumors are bulky with smooth external surfaces
  
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  Usually unilateral
  
• 
  Cut surface shows a solid or partly solid tumor
  

with areas of necrosis and hemorrhage.

• 
  There is a disorganized collection of tissues from the
  

three germ layers with at least part showing immature,

embryonic appearance.

• 
  Neuroepithelium (brain tissue) is the most common
  

immature element.

• 
  Seen here is primitive neuroepithelium with multiple neural tubes
  

• 
  High power view showing neural epithelium and neural tube.
  

Monodermal teratomas

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  Are teratomas that show unidirectional development to produce one tissue type.
  
• 
  Are rare
  

• 
  Most common are struma ovarii and carcinoid
  

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  Are always unilateral
  
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  Struma ovarii
  
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  Composed entirely of mature thyroid tissue.
  

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  There may be hyperfunction of the thyroid tissue to cause hyperthyroidism.
  

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  Ovarian carcinoid
  
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  Monodirectional differentiation toward argentaffin type cells
  
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  The tumor may be functional, producing 5-hydroxytrptamine (serotonin) and cause the carcinoid syndrome
  

Struma ovarii

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  Showing mature thyroid follicles containing colloid.
  

Endodermal sinus tumor (Yolk sac carcinoma)

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  A highly malignant and clinically aggressive neoplasm
  
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  Seen most frequently in young females particularly in the first three decades.
  
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  It is rare after 40 years and is perhaps, the most rapidly growing neoplasm that occurs at any site.
  
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  Is large, predominantly solid and shows extensive necrosis and hemorrhage.
  
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  Many have already spread beyond the ovary at time of surgery with bulky, friable tumor filling the pelvic cavity. Patients commonly present with abdominal pain resembling acute abdomen
  
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  The tumor displays multiple histologic patterns.
  
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  Presence of Schiller-Duval body
  

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  A glomerulus-like structure with central blood vessel surrounded by embryonal cells lying within a space also lined by embryonal cells.
  

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  Conspicuous intra and extra cellular hyaline globules of alpha-fetoprotein are seen.
  

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  AFP is secreted and appears in the blood as a biologic marker for the tumors used both for diagnosis and monitoring response to therapy
  

Endodermal sinus tumor (Yolk sac carcinoma)

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  Endodermal sinus tumor showing a Schiller-Duval body.
  

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  Pink globules of alpha-fetoprotein are present both intra- and extra-cellularly.
  

Choriocarcinoma

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  Majority of choriocarcinomas occurring in women arises within the uterus, placental in origin.
  
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  Arises much less commonly in the ovary from ovarian germ cells, unrelated to pregnancy and which differentiates into extra-embryonic (trophoblastic) tissue.
  
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  Usually unilateral, solid and hemorrhagic.
  
• 
  Clinically, the tumor behaves like the testicular form and has undergone wide hematogenous spread by the time of diagnosis.
  
• 
  The serum marker for choriocarcinoma is beta-HCG
  

• 
  used in diagnosis and to monitor response to treatment or tumor recurrence.
  

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  Unlike gestational choriocarcinoma, the ovarian tumor is resistant to methotrexate, used in treating the former.
  

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  There is often a marked response to newer forms of chemotherapy.
  

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  Histologically, it is composed of malignant cytotrophoblasts and intermediate trophoblasts surrounded by syncytiotrophoblasts.
  
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  Immunohistochemical staining shows production, or at least storage of hCG in syncytiotrophoblasts, but not in cytotrophoblasts.
  

Choriocarcinoma

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  Choriocarcinoma showing syncytiotrophoblasts (lower right corner) and cytotrophoblasts (upper left corner)
  

Sex Cord - Stromal Tumors

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  Account for about 3% of all ovarian tumors
  
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  Are derived from the gonadal (sex) cords and stroma
  
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  Thus tumors in this group may consist of ovarian stromal cells, theca cells, granulosa cells, Sertoli cells and Leydig cells either singly or in various combination.
  
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  Account for the substantial majority of the hormonally active neoplasms of the ovary
  
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  Neoplasms are either feminizing or virilizing
  
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  The cells from which they are derived normally secrete
  

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  estrogens (theca and granulosa cells), or ,
  
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  androgens (Leydig cells)
  

Granulosa-theca cell tumor

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  Composed almost entirely of granulosa cells or with varying proportions of theca cells.
  
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  Granulosa-theca cell tumors the most common estrogenic ovarian neoplasm.
  

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  Tumors with a prominent theca cell component are almost always hormonally active
  
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  75% of pure granulosa cell tumors are functional
  

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  Virtually always unilateral
  
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  The tumors exist in an adult and juvenile forms.
  

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  Adult form occurs mainly in postmenopausal women
  
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  Juvenile type occurs in the first two decades.
  

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  Functioning tumors in prepubertal girls may cause precocious sexual development.
  
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  In adults, they are associated with endometrial hyperplasia and carcinoma.
  

Granulosa-theca cell tumor

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  Gross-The tumors vary in size from small incidental findings to very large, focally cystic to entirely solid masses.
  
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  Gross-Cut surface shows yellow and white areas with focal hemorrhages, which may be massive.
  

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  Histologically-
  
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  These tumors have very diverse appearances.
  
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  The most well-known pattern consists of monotonous islands of granulosa cells with "coffee-bean" nuclei
  
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  Containing small punched out spaces lined by granulosa cells giving a follicle-like appearance called Call-Exner bodies
  

Fibroma-Thecoma

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  Tumors arising in the ovarian stroma that are composed of either
  

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  Fibroblasts (fibromas), or,
  
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  Plump spindle cells with lipid droplets (thecomas)
  
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  Mixture of these cells (fibroma-thecomas)
  

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  Fibroma-thecomas of the ovary are unilateral in about 90% of cases
  
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  Usually are solid, spherical or slightly lobulated, encapsulated, hard, gray-white masses covered by glistening, intact ovarian serosa
  
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  Histologically, they are composed of well-differentiated fibroblasts with a more or less scant collagenous connective tissue interspersed between the cells.
  

Fibromas

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  Are the commonest ovarian stromal tumors.
  
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  Pure forms are nonfunctioning
  
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  Usually occur in middle-aged, perimenopausal women as unilateral, fibrous solid growths, with a hard, gray to white, whorled cut surface.
  
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  Frequently extensively calcified and difficult to cut.
  

Composed of well-differentiated fibroblasts in a collagenous stroma.

Thecoma

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  Pure theca cell tumors also occur, although rare.
  
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  Are functional tumors producing estrogen and occur in postmenopausal women.
  
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  Cause menstrual irregularities and breast enlargement.
  
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  Endometrial hyperplasia or carcinoma may develop.
  
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  Thecomas vary in size from small, impalpable tumors to large, rubbery, solid tumors, usually 5 to 10 cm in diameter and vary in color from yellow to orange depending on the amount of lipid content.
  
• 
  Are virtually never malignant.
  

Thecoma

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  Solid tumor with variegated yellow - orange appearance due to lipid content
  

• 
  Composed of sheets of round to oval cells with pale cytoplasm containing lipid.
  

Sertoli-Leydig Cell Tumors (Androblastoma)

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  Extremely rare (<1% of ovarian neoplasms)
  
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  Unilateral
  
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  Presence of cells resembling the Sertoli and Leydig cells of the testis.
  
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  Predominantly in young women with mean age in the mid-twenties.
  
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  Commonly androgenic
  
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  May cause defeminization of women manifested as breast atrophy, amenorrhea, and loss of hair and hip fat.
  
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  This may progress to virilization with hirsutism, male distribution of hair, hypertrophy of clitoris and deepening of the voice.
  
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  Microscopically, well-differentiated tumors contain tubules composed of Sertoli cells surrounded by a stroma filled with Leydig cells, mimicking the architecture of the testis.
  

Sertoli-Leydig Cell Tumors (Androblastoma)

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  Gross-Vary in size from microscopic to very large, forming yellow to tan lobulated masses.
  
• 
  Areas of hemorrhage and necrosis are present in some tumors
  
• 
  Microscopically-Tubules lined by Sertoli cells and sheet of Leydig cells (upper right corner).
  
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  Microscopically-Homogeneous, eosinophilic, rod-shaped structures - Reinke’s crystals may be seen in some of the Leydig cells (Repeat Picture see also-Brenner Tumor, Female Genital Tract pg 35)
  

Metastatic Ovarian Tumors

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  The ovary may be the site of metastatic tumor.
  
• 
  About 3% of malignant tumors in the ovary are metastatic.
  
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  The most common primary site is the breast followed by the large intestine, stomach, and other genital tract organs.
  
• 
  Most metastastases from the breast are microscopic.
  
• 
  Metastases from the colon produce large ovaries, which may mimic primary ovarian tumor.
  
• 
  Krukenberg tumor is applied to the uniform enlargement of the ovaries (usually bilaterally) due to diffuse infiltration of the ovarian stroma by metastatic signet-ring cell carcinoma.
  

• 
  The commonest primary site is the stomach followed by the colon
  

Diseases Of The Female Genital Tract

• 
  Normal
  

• 
  Embryology
  
• 
  Anatomy
  
• 
  Endometrial Histology and Menstrual Cycle
  

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  Pathology
  

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  Female Genital Infections
  
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  Vulva
  
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  Vagina
  
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  Cervix
  
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  Body of Uterus and Endometrium
  
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  Fallopian Tubes
  
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  Ovaries
  

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  Gestational and Placental Disorders
  

Female Genital Infections

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  A large variety of organisms can infect the female genital tract
  
• 
  Common, may cause significant discomfort with no serious sequelae:
  

• 
  Candida infections
  
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  Trichomoniasis
  
• 
  Gardnerella
  

• 
  Major causes of female infertility
  

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  Gonorrhea
  
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  Chlamydia
  

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  Implicated in spontaneous abortions
  

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  Mycoplasma infections
  

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  Pathogenesis of vulvar and cervical cancer
  

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  Viruses, principally the human papillomaviruses
  

Infections Confined to Lower Genital Tract

Herpes simplex infection

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  Is common
  
• 
  Lesions begin 3 to 7 days after sexual relations
  
• 
  Lesions heal spontaneously in 1-3 weeks
  
• 
  Involves the vulva, vagina, and cervix
  
• 
  Vulva:
  
• 
  Painful red papules > vesicles > coalescent ulcers
  

• 
  Contains numerous virus particles
  

• 
  High transmission rate during active infection
  

• 
  Cervix and Vagina:
  
• 
  Severe leukorrhea (genital discharge)
  
• 
  Systemic symptoms, such as fever, malaise, and tender inguinal lymph nodes
  
• 
  Gravest consequence: Transmission to the neonate during birth
  
• 
  Highest risk infection is active during delivery and particularly if it is a primary (initial) infection in the mother
  

Mycotic and yeast (Candida) infections

• 
  Are common
  
• 
  Diabetes mellitus, oral contraceptives, and pregnancy may enhance the development of infection
  
• 
  Manifests as
  

• 
  Small white surface patches
  
• 
  Leukorrhea
  
• 
  Pruritus
  

• 
  Trichomonas vaginalis, a large, flagellated ovoid protozoan
  
• 
  May occur at any age
  
• 
  Seen in ~15% of women in STD clinic
  
• 
  Purulent vaginal discharge and discomfort
  
• 
  Vaginal and cervical mucosa has a characteristic fiery red appearance, called “strawberry cervix.”
  
• 
  Diagnosis: Finding the organism in wet mounts of the lesions
  

Pelvic Inflammatory Disease (PID)

• 
  PID is a common disorder characterized by pelvic pain, adnexal tenderness, fever, and vaginal discharge
  
• 
  Results from infection by one or more of the following groups of organisms:
  
• 
  Gonococcus, chlamydia, and enteric bacteria
  
• 
  Gonococcal inflammation begins usually in Bartholin’s and other vestibular glands or periurethral glands
  
• 
  Cervix involvement is common and frequently asymptomatic
  
• 
  From any of these loci, the organisms may spread upward to involve the tubes and tubo-ovarian region. The adult vagina is remarkably resistant to gonococcus, but in the child, presumably because of a more delicate lining mucosa, vulvovaginitis may develop.
  
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  The nongonococcal bacterial infections that follow induced abortion, dilatation and curettage of the uterus, and other surgical procedures on the female genital tract are thought to spread from the uterus upward through the lymphatics or venous channels rather than on the mucosal surfaces. These infections therefore tend to produce less mucosal involvement but more reaction within the deeper layers.
  
• 
  Morphology
  
• 
  The complications of PID include (1) peritonitis; (2) intestinal obstruction owing to adhesions between the small bowel and the pelvic organs; (3) bacteremia, which may produce endocarditis, meningitis, and suppurative arthritis; and (4) infertility, one of the most commonly feared consequences of long-standing chronic PID. In the early stages, gonococcal infections are readily controlled with antibiotics, although regrettably penicillin-resistant strains have emerged. When the infection becomes walled off in suppurative tubes or tubo-ovarian abscesses, it is difficult to achieve a sufficient level of antibiotic within the centers of such suppuration to control these infections effectively. Postabortion and postpartum PIDs are also amenable to antibiotics but are far more difficult to control than the gonococcal infections. Sometimes it becomes necessary to remove the organs surgically.
  

• 
  With the gonococcus, approximately 2 to 7 days after inoculation of the organism, inflammatory changes appear in the affected glands. Wherever it occurs, gonococcal disease is characterized by an acute suppurative reaction with inflammation largely confined to the superficial mucosa and underlying submucosa. Smears of the inflammatory exudate should disclose the intracellular gram-negative diplococcus, but absolute confirmation requires culture. If spread occurs, the endometrium is usually spared, for obscure reasons. Once within the tubes, an acute suppurative salpingitis ensues. The tubal serosa becomes hyperemic and layered with fibrin, the tubal fimbriae are similarly involved, and the lumen fills with purulent exudate that may leak out of the fimbriated end. Over days or weeks, the fimbriae may seal or become plastered against the ovary to create a salpingo-oophoritis. Collections of pus within the ovary and tube (tubo-ovarian abscesses) or tubal lumen (pyosalpinx) may occur. Adhesions of the tubal plica may produce gland-like spaces (follicular salpingitis). In the course of time, the infecting organisms may disappear, the pus undergoing proteolysis to a thin, serous fluid, to produce a hydrosalpinx or hydrosalpinx follicularis.
  
• 
  PID caused by staphylococci, streptococci, and the other puerperal invaders tends to have less exudation within the lumina of the tube and less involvement of the mucosa, with a greater inflammatory response within the deeper layers. The infection tends to spread throughout the wall to involve the serosa and may often track into the broad ligaments, pelvic structures, and peritoneum. Bacteremia is a more frequent complication of streptococcal or staphylococcal PID than of gonococcal infections.
  

VULVA

• 
  Vulva is prone to skin infections because it is constantly exposed to secretions and moisture
  
• 
  Nonspecific vulvitis is particularly likely to occur in blood dyscrasias, uremia, diabetes mellitus, malnutrition, and avitaminoses
  
• 
  Diseases:
  

• 
  Bartholin’s Cyst
  
• 
  Vestibular Adenitis
  
• 
  Vulvar Dystrophy
  
• 
  Tumors
  

Bartholin’s Cyst

• 
  Acute infection of Bartholin’s gland produces
  

• 
  Acute inflammation of the gland (adenitis)
  
• 
  May result in a Bartholin’s abscess
  

• 
  Bartholin’s cysts
  
• 
  Common
  
• 
  Occur at all ages
  
• 
  Result from obstruction of Bartholin’s duct, usually by a preceding infection
  
• 
  Can be up to 3 to 5 cm in diameter.
  
• 
  Cyst is lined by either the transitional epithelium of the normal duct or squamous metaplasia
  
• 
  Produce pain and local discomfort
  
• 
  Treatment: Excised or opened permanently (marsupialization)
  

Vestibular Adenitis

• 
  Vulvar vestibule:
  

• 
  Located in the posterior introitus at the entrance to the vagina
  
• 
  Contains small glands in the submucosa (vestibular glands)
  

• 
  Vestibular adenitis:
  
• 
  Inflammation of vestibular glands
  
• 
  Is associated with a chronic, recurrent, and exquisitely painful condition
  
• 
  Treatment: Surgical removal of the inflamed mucosa