Endodermal sinus tumor
Synonyms and keywords: Endodermal sinus tumor(EST), yolk sac tumor.

# Overview
Endodermal sinus tumor was first discovered by Dr. Gunner Telium, a Danish pathologist, in 1959. The hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor has been associated with the development of endodermal sinus tumor. Endodermal sinus tumor is a rare type of malignant ovarian tumor that occurs in the second decade of life. On gross pathology, a solid gray-white with gelatinous, myxoid, or mucoid appearance, necrosis, cystic changes, and hemorrhage are characteristic findings of endodermal sinus tumor. On microscopic histopathological analysis, Schiller-Duval bodies is a characteristic finding of endodermal sinus tumor. Endodermal sinus tumor must be differentiated from other diseases that cause pelvic mass, such as Stein-Leventhal syndrome, and seminoma. In 2015, the incidence of endodermal sinus tumor is estimated to less than 1/100,000 case per year in U.S. Endodermal sinus tumor may be classified according to histology groups.The diagnosis of endodermal sinus tumor is made based on the imaging (U/S and MRI) and alpha fetoprotein (AFP) tumor marker greater than 100 ng/ml. Endodermal sinus tumor have a bimodal distribution more commonly observed among young and adult population. The symptoms of endodermal sinus tumor include the followings: abdominal distention, acute/sub acute abdominal pain. Endodermal sinus tumor is treated with surgery depending on the tumor marker and imaging as well as fertility desired.The medical therapy for endodermal sinus tumor is chemotherapy such as bleomycin, etoposide, and cisplatin for 3 to 4 cycles for 21 days.

# Historical Perspective
- Endodermal sinus tumor was first discovered by Dr. Gunner Telium, a Danish pathologist in 1959.

# Classification
- Endodermal sinus tumor may be classified according to histology into 10 groups:
- Reticular
- Endodermal sinus-like
- Microcystic
- Papillary
- Solid
- Glandular
- Alveolar
- Polyvesicular vitelline
- Enteric
- Hepatoid

# Pathophysiology
- The hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor has been associated with the development of endodermal sinus tumor.
- Ovarian endodermal sinus tumor may be result of differentiation of primitive malignant germ cell components of vitelline structures.
- On gross pathology, encaptulated, firm, smooth, round, globular, solid gray-white with a gelatinous, myxoid, or mucoid appearance, necrosis, cystic changes, and hemorrhage are characteristic findings of endodermal sinus tumor.
- On microscopic histopathological analysis, Schiller-Duval bodies (invaginated papillary structures with central vessel) is a characteristic finding of endodermal sinus tumor. The tumors are composed of irregular space lined by flattened to cuboidal cells and recticular stroma.

# Causes
- There are no established causes for endodermal sinus tumor.

# Differentiating Endodermal sinus tumor from Other Diseases
Endodermal sinus tumor must be differentiated from other diseases that cause pelvic mass, abdominal pain and abdominal distention such as:
- Stein-Leventhal syndrome
- Ovary teratoma
- Tubal pregnancy
- Ovary adenocarcinoma
- Tubo-ovarian abscess
- Seminoma
- For more information on endodermal sinus tumor differential diagnosis, click here.
- Also, you can find more information by clicking here.

# Epidemiology and Demographics
- In 2015, the incidence of endodermal sinus tumor is estimated to less than 1/100,000 case per year in U.S.

## Age
- Endodermal sinus tumor have a bimodal distribution more commonly observed among young and adult population
- Pure yolk sac tumor (endodermal sinus tumor) affects mostly children of less 2 years old.

## Gender
- Endodermal sinus tumor affects men and women equally.

## Race
- There is no racial predilection for endodermal sinus tumor.

# Natural History, Complications and Prognosis
- Endodermal sinus tumor has a poor prognosis in adult.
- Endodermal sinus tumor has a favorable prognosis in children.
- Endodermal sinus tumor is the most common malignant germ cell tumor in children.
- If left untreated, endodermal sinus tumor quickly metastasizes in other parts of the body such as the brain.
- Endodermal sinus tumor can be found in the ovaries or testicles including the chest, abdomen, and the brain.
- Ovarian endodermal sinus tumor metastasizes quiclky into the intraabdominal area compared to testicular endodermal sinus tumor.

# Diagnosis

## Diagnostic criteria
- The diagnosis of endodermal sinus tumor is made based on the imaging and alpha fetoprotein (AFP) tumor marker greater than 100 ng/ml.

## Symptoms
- Endodermal sinus tumor is usually asymptomatic.
- Most children and young adults with endodermal sinus tumor have stage I.
- Symptoms of endodermal sinus tumor may include the following: 
- Abdominal distention
- Acute/subacute abdominal pain

## Physical Examination
- Patients with endodermal sinus tumor usually appear normal.
- Physical examination may be remarkable for:
- Abdominal distention
- Abdominal tenderness
- Adnexal mass
- Testicular mass

## Laboratory Findings
- An elevated concentration of serum alpha fetoprotein is a diagnostic of endodermal sinus tumor.
- SALL4 (sal-like protein 4) is positive in endodermal sinus tumor.
- AFP is very important for diagnosis, disease monitoring and early metastasis.

## Imaging Findings
- On MRI, endodermal sinus tumor is characterized by areas of haemorrhage and necrosis.
- Ultrasound shows solid and cystic mass.

## Other Diagnostic Studies
- Endodermal sinus tumor may also be diagnosed using biopsy and measurement of  GATA-4, a transcription factor.

# Treatment
- Endodermal sinus tumor is treated with surgery depending on the tumor marker and imaging as well as fertility desired.
- For positive tumor markers and imaging, fertility desired
Treat with fertility-sapring surgery and comprehensive staging.
- Treat with fertility-sapring surgery and comprehensive staging.
- For positive tumor markers and imaging, fertility not desired
Treat with completion staging surgery with possible tumor reductive surgery or chemotherapy
- Treat with completion staging surgery with possible tumor reductive surgery or chemotherapy
- For negative imaging and positive or negative tumor markers
Treat with chemotherapy
- Treat with chemotherapy

## Medical Therapy
- The medical therapy for endodermal sinus tumor is chemotherapy such as bleomycin, etoposide, and cisplatin for 3 to 4 cycles for 21 days depending on the stage..

## Surgery
- Surgery is the mode of treatment for endodermal sinus tumor with adjuvant chemotherapy:

## Stage I endodermal sinus tumor
- Unilateral salpingo-oophorectomy with adjuvant chemotherapy
- Unilateral salpingo-oophorectomy followed by observation

## Stage II endodermal sinus tumor
- Unilateral salpingo-oophorectomy with adjuvant chemotherapy
- Second-look laparotomy

## Stage III endodermal sinus tumor
- Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy, with or without neoadjuvant chemotherapy
- Unilateral salpingo-oophorectomy with adjuvant chemotherapy, with or without neoadjuvant chemotherapy
- Second-look laparotomy

## Stage IV endodermal sinus tumor
- Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy with or without neoadjuvant chemotherapy
- Unilateral salpingo-oophorectomy with adjuvant chemotherapy with or without neoadjuvant chemotherapy

## Prevention
- There are no primary preventive measures available for endodermal sinus tumor.

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