A. Introduction

1. Constitute 25% of all ovarian tumors
2. In adults, these are nearly all benign
   1. Tend to have more differentiated tumor cells, usually benign cystic (mature) teratoma
   2. Malignancies, when they arise, appear from transformation of benign tumor
3. In children and young adults, they are primarily malignant
   1. Tend to be solid lesions with immature cell types
   2. Most are Endodermal Sinus tumor and Immature Teratoma
4. Germ cell neoplasms are the most common ovarian tumors of children (60%)
5. Lines of Differentiation (Normal Cell ±> Neoplasm)
   1. Oogonia ±> Dysgerminoma
   2. Embryonic Tissues ±> Teratoma
   3. Endoderm ±> Yolk Sac CA (Endodermal Sinus Tumor)
   4. Placental Villi ±> Choriocarcinoma

B. Dysgerminoma

1. Ovarian counterpart of testicular seminoma; ie. Neoplasm of primordial germ cells
2. In women under 20 years of age, responsible for up to 10% of ovarian cancers
3. Histology
   1. Nests of monotonously arranged primordial germ cells
   2. Cells have clear cytoplasm with glycogen and irregularly flattened central nuclei
   3. Fibrous septa containing lymphocytes are found
4. Radiotherapy is highly effective, with 5 year survival rate for stage I ~100%

C. Mature Teratoma

1. Most common (25% of) germ cell tumor, also called dermoid cyst
2. Peak incidence is in women 20-30 years old
3. Pathogenesis
   1. Develops by parthenogenesis
   2. Haploid germ cells autofertilize leading to diploid tumor cells, 46XX
4. Histology
   1. Cystic tumor
   2. >90% contain skin, sebaceous glands, and hair follicles
   3. Other tissue types such as teeth are seen less frequently
5. About 1% of these tumors undergo malignant transformation
   1. Usually to squamous cell carcinomas
   2. Mainly in older women

D. Immature Teratoma

1. Tumor in the ovary is comprised of solid embryonal tissue
2. Account for 20% of malignant tumors of women under 20 years of age
3. Often differentiates towards nerves (neuroepithelial), glands, and other tissues
4. Only a small percentage of the tumors are low grade (0-1); these have good prognosis
5. The majority are higher grade spread quickly and recur, but are sensitive to chemotherapy

E. Yolk Sac Carcinoma (Endodermal Sinus Tumor)

1. Highly malignant tumor of women <30 years old
2. Secretes alpha-fetoprotein (AFP) and can monitor this
3. Extremely sensitive to chemotherapy
4. Schiller-Duval Body

F. Sex Cord Stromal Tumors

1. Arise from cells from gonadal stroma; ~10% of all ovarian cancers.
2. Range from benign to low grade malignant
3. Differentiation towards female (granulosa / theca) or male (Sertoli / Leydig)
4. Account for most of the clinically functional ovarian tumors
   1. Hyperestrogenism (female hormones)
   2. Hyperandrogenism (male hormones)
   3. Precocious puberty is usual result

G. Granulosa Cell Tumor

1. This is a feminizing tumor
   1. Estrogen secretion by tumor (75%)
   2. May lead to endometrial hyperplasia and cancer
   3. Precocious puberty is also seen
2. Large tumors, focally cystic to solid; may be hemorrhagic
3. Microfollicular patterns, cells surround a central space = Call-Exner Bodies
4. Cells are typically coffee-bean shaped
5. Tumors do not usually recur (5% recurrence)

H. Sertoli-Leydig Cell Tumor

1. Androgen Secretion: hirsutism, amenorrhea, clitoromegaly, deep voice
2. Rare tumor, most common in young women of child-bearing age
3. Grossly, tumor is yellow/tan and unilateral
4. Three differentiation grades (well to poorly) and a fourth type with heterologous elements
5. Poorly differentiated tumors can recur or metastasize
6. Characteristic large Leydig cells

I. Chemotherapy [2]

1. For selected cases with high metastatic potenital or invasion
2. Bleomycin + etoposide + cisplatin
3. Alternative: vincrstine + dactinomycin + cisplatin
4. Alternative: carboplatin or cisplatin + etoposide

References

1. Williams SD. 1998. Semin Oncol. 25(3):407
2. Drugs of Choice for Cancer Chemotherapy. 2000. Med Let. 42(1087):83