FINAL DIAGNOSIS: Yolk sac tumor arising in association with mature cystic teratoma (dermoid cyst).
DISCUSSION:
Yolk sac tumor (also known as endodermal sinus tumor) of the ovary is a malignant germ cell neoplasm. It often occurs in pure form but is also frequently found as a component of mixed malignant germ cell tumors. Yolk sac tumor occurs at a median age of 18 years and is nearly as common as dysgerminoma in young patients. A typical presentation is abdominal pain and a large, unilateral, rapidly growing pelvic mass. In about 10% of patients, rupture or torsion of the tumor occurs. Greatly increased serum levels of ¦Á-fetoprotein (> 1000 ng/ml) are consistently found in patients with yolk sac tumor, whether pure or as a component of a mixed germ cell tumor; other ovarian tumors (i.e., immature teratoma, Sertoli-Leydig cell tumor) may also be associated with increased ¦Á-fetoprotein, but usually at lower levels than those seen in patients with yolk sac tumor.
At gross evaluation, yolk sac tumors are large (average diameter 15 cm) and encapsulated with a smooth, glistening external surface. Characteristically, the sectioned surface is solid and cystic with soft, gray-to-yellow tissue and areas of hemorrhage and necrosis. A concomitant benign mature teratoma (dermoid cyst) is frequently seen.
The most common ("typical") pattern consists of papillary projections, each of which contains a central blood vessel, surrounded by a thick layer of basement membrane material, and then covered by a layer of embryonic epithelial cells with clear or eosinophilic cytoplasm; this structure is referred to as a Schiller-Duval body. Another frequently encountered feature is hyaline globules, which are eosinophilic, PAS-positive, diastase-resistant globules.
Yolk sac tumors display a variety of histologic patterns. Most will contain areas of the typical pattern, but tumors consisting purely of a histologic variant have been reported. Recognition of other patterns is important, because the differential diagnosis varies between patterns, and some patterns are reported to be more resistant to chemotherapy. Some of these patterns and their differential diagnoses are listed in the table below.
Histologic Variant |
Microscopic Description |
Differential Diagnosis |
|
|
|
Typical |
See above |
Clear cell adenocarcinoma |
Polyvesicular-vitelline |
Multiple small cysts lined by flattened, cuboidal, or columnar cells, separated by loose, edematous mesenchyme (honeycomb appearance)
Tends to occur in pure form
|
Juvenile granulosa cell tumor |
Solid |
Solid sheets of polygonal cells with eosinophilic to clear cytoplasm, distinct cell borders, and no nuclear overlapping
|
Dysgerminoma Embryonal carcinoma Clear cell adenocarcinoma
|
Glandular |
Prominent subnuclear or apical vacuolization, similar to secretory endometrium
Tends to occur in pure form
More resistant to chemotherapy |
Endometrioid adenocarcinoma Metastatic endometrial adenocarcinoma Malignant mixed mullerian tumor (MMMT) |
Hepatoid |
Large, uniform, eosinophilic granular cells with round, centrally-located nuclei distinct borders, arranged in cords or trabeculae with sinusoidal spaces
Rare, tends to occur in pure form
More resistant to chemotherapy |
Metastatic hepatocellular carcinoma Tumors with tumors with eosinophilic cytoplasm (steroid cell tumor, endometrioid and clear cell adenocarcinoma with oxyphilic change, metastatic melanoma)
|
Yolk sac tumors are typically diffusely positive with immunohistochemical stains for ¦Á-fetoprotein (AFP) placental alkaline phosphatase (PLAP), ¦Á-1 antitrypsin, and cytokeratin. Epithelial membrane antigen (EMA) and human chorionic gonadotropin (hCG) are usually negative. The hyaline globules are positive for PAS-D and negative for ¦Á-1 antitrypsin. Finally, the thick basement membrane material within papillary structures is positive for laminin and type IV collagen. The combination of the morphologic findings (Schiller-Duval bodies, hyaline globules) and positivity for AFP and cytokeratin are useful in separating yolk sac tumor from other entities in the differential diagnosis.
REFERENCES:
Contributed by J. Manuel Zarandona, M.D., and Mamatha Chivukula, M.D.