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This 42-year-old woman had a pelvic mass discovered during her annual physical exam. A 15.0 cm right ovarian tumor was removed at surgery. The cut surface of the tumor was tan, markedly hemorrhagic and multicystic. There were no discernible papillary excrescences. Immunohistochemical stains performed on representative tumor sections showed: a-fetoprotein +, PLAP +, β-HCG –, CK7 –, EMA –, AE1/AE3 +.
Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2009, case 36, and is yolk sac tumor.
Criteria for Diagnosis and Comments:
This is a yolk sac tumor (YST) which is the second most common ovarian malignant germ cell neoplasm; only dysgerminoma is more frequent. YSTs are most frequent in adolescents and young adults (mean age of 19 years); it is very rarely seen beyond the age of 40 years of age. They may occur in a pure form or as a component of a mixed malignant germ cell tumor. Rare examples of YST have been reported in association with an endometrioid or mucinous ovarian tumor in older patients. Many patients present with abdominal pain and/or a large abdominal or pelvic mass. The serum a-fetoprotein (AFP) is almost always elevated preoperatively. However, serum AFP may also be elevated in other tumors seen in young women, i.e., embryonal carcinoma and Sertoli-Leydig cell tumor, although not at the very high levels commonly seen with YST.
Yolk sac tumors are typically very large, averaging 15.0 cm in greatest dimension. They are well encapsulated with smooth external surface; the cut surface is yellow to gray, soft and friable. Cysts are common, but only rarely are they entirely cystic. Gross evidence of other germ cell neoplasms (especially a dermoid cyst) may also be present in up to 15% of cases. They are almost never bilateral; however, a dermoid cyst may be seen in the contralateral ovary in 10% of cases.
YSTs may have several different histologic patterns. These frequently coexist in various combinations, but only a few usually predominate. Proper tissue sampling may be a critical issue in order to make diagnosis. The reticular pattern is one of the most characteristic patterns as seen in this case; this is formed by a loose myxoid stroma and a meshwork of microcystic spaces lined by clear and commonly flattened epithelial cells. The nuclei are hyperchromatic, irregular, contain prominent nucleoli and they are smaller than the nuclei of embryonal carcinoma. Mitoses are frequent. The reticular pattern may merge with a microcystic or even a macrocystic pattern also seen in this case. Many of the cells have cytoplasmic eosinophilic globules or smaller eosinophilic granules that are PAS positive and diastase resistant. Schiller-Duval bodies are among the most distinctive histologic features and are considered diagnostic of YST. They consist of papillae with a connective tissue core and a single central blood vessel covered with primitive columnar cells. The papillae lie in a space lined by cuboidal or flattened cells. These are most commonly focal, but when prominent the tumor is termed "endodermal sinus tumor."
There are other less common variants. These may predominate over other patterns and could be the source of confusion for those unaware of the full spectrum. The polyvesicular vitelline pattern is formed by cysts lined by columnar, cuboidal or flattened in a dense and of spindle cell stroma. A solid yolk sac tumor is composed of polygonal cells with clear cytoplasm and many times abundant hyaline globules. A yolk sac tumor with accumulations of large amounts of extracellular basement membrane material is termed parietal yolk sac tumor. A glandular variant of yolk sac tumor is composed of numerous endodermal type glands which may show intestinal or the pseudo-glandular phase of embryonal lung. A yolk sac tumor with a hepatoid pattern has large polygonal cells with abundant eosinophilic cytoplasm and may resemble hepatocellular carcinoma.
Clear cell carcinoma of the ovary may have a prominent edematous appearance similar to a reticular pattern of yolk sac tumor. Additionally, they may have numerous oxyphilic cells and therefore may be confused with a hepatoid YST. Other distinct yolk sac patterns are not seen in clear cell carcinoma. Clear cell carcinoma tends to have a more prominent tubular pattern and papillary fronds lined by clear or hobnail cells The patients with clear cell carcinoma are usually older than those with yolk sac tumor and serum AFP is not elevated. Appropriate tissue sampling can usually clarify the proper diagnosis. Immunohistochemistry can be of assistance in this differential diagnosis. Although YST is usually positive for AFP this may only be focal positivity and YST may be AFP negative in 10 – 20% of cases. Additionally, clear cell carcinoma may also be focally immunoreactive for AFP. Therefore, AFP should not be relied upon to make this differential diagnosis without the support of other immunostains and/or morphologic features. YST is CK7 –, EMA –, Leu-M1 weak+; while clear cell carcinoma is CK7 +, EMA +, Leu-M1 strong +.
The glandular variant of YST may be mistaken for an endometrioid adenocarcinoma especially in an older patient. Endometrioid adenocarcinoma are CK 7 +, EMA + and AFP –, whereas YST is CK7 –, EMA – and AFP +.
Dysgerminoma may be mistaken for solid variant of yolk sac tumor. Important morphologic features help distinguish these two tumors most of the time. The cells of dysgerminoma are more uniform than those seen in YST and dysgerminoma usually lacks a microcystic appearance. In addition, dysgerminoma characteristically has stroma with lymphocytes and granulomatous reaction. Immunostains may be helpful in making this distinction: dysgerminoma is AFP –, AE1/AE3 – and OCT4 + while YST is AFP +, AE1/AE3 +, OCT4 –.
Embryonal carcinoma rarely involves the ovary. However, this may also be confused with YST because they are closely related. Embryonal carcinoma generally does not have the distinctive patterns seen in yolk sac tumor, and it is composed of larger and more pleomorphic cells. Embryonal carcinoma is OCT4 + and YST is OCT4 –.
YST is a rapidly growing neoplasm. One third of patients present with extra ovarian spread to peritoneum and/or retroperitoneal lymph nodes. Survival rates were very poor prior to chemotherapy. However, survival rates of 80% in stage I disease and 50% in higher stage tumors have been achieved since the advent of chemotherapy.