Primary Endodermal Sinus (Yolk Sac) Tumor of the Falciform Ligament ByJames
B. Atkinson,
Clarence
E. Foster III, Kevin P. Lally, Hat-t Isaacs, and Stuart E. Siegel
Los Angeles, California l Extragonadal yolk sac tumors (YSTs) are uncommon and YSTs of the liver are exceedingly rare, with only three reported cases in the literature. A case is described of primary YST of the falciform ligament extending into the left lobe of the liver in a 14-month-old boy. This is the first reported case of primary YST arising within the falciform ligament. The patient underwent an exploratory laparotomy after presenting with hemoperitoneum. An extremely friable and necrotic tumor was found extending from the falciform ligament into the liver. The tumor was debulked and the patient received 5 months of chemotherapy employing a modified Einhorn regimen. After a partial response to chemotherapy the patient had a second-look laparotomy, at which time a left hepatic lobectomy and en bloc resection of the falciform ligament was performed in order to remove residual tumor. At the present time the patient has no signs of metastases and is alive and well 2 years after his presentation. Copyright P 1992 by W.B. Saunders Company
platinum. 20 mgim’ intravenously (IV) daily for 5 days: VP-16, 75 mgim’ IV daily for 5 days; Vinblastine, 6 mgim’ IV on day 1 of each course; and Bleomycin. 15 U/m’ IV on day 1 of each course. Courses were repeated every 4 weeks. The patient received a total of five courses over a 4-month period. Five months after diagnosis, the patient underwent a second laparotomy. A left hepatic lobectomy and en bloc resection of the abdominal wall was performed to remove residual tumor with clear microscopic margins. The remaining peritoneal surfaces and the rest of the abdomen were free of tumor.
Pathological Findings Microscopic examination of the initial biopsy taken from the anterior surface of the liver during the first operation showed a
INDEX WORDS: Yolk sac tumor, falciform ligament; endodermal sinus tumor.
Y
OLK SAC tumors (YSTs) usually occur in the testes or ovaries and rarely in an extragonadal site. This germ cell tumor has been found in the central nervous system,’ anterior mediastinum,’ sacrococcygeal region,’ retroperitoneum,4 and the prostate.5 YST of the liver is exceedingly rare and, to our knowledge, there have been only three reported cases6-’ We report the first case of primary YST of the falciform ligament. CASE REPORT
A 14-month-old black boy was admitted for evaluation of increased abdominal girth, a right upper quadrant mass, and ascites. There was no history of trauma, bleeding abnormalities, jaundice or chronic anorexia. The patient was found to have a tensely distended, firm abdomen with a 7-cm mass in the right upper quadrant and both testes were normal. Abnormal laboratory values included a hematocrit of 23% and oc-fetoprotein of 76,000. Computed tomography scan showed free fluid and an anterior mass attached to the liver. At laparotomy a large friable mass was encountered invading the abdominal wall along the falciform ligament and extending into the anterior surface of the liver involving the medial and lateral segments of the left hepatic lobe. The tumor was debulked and tamponade of the raw surface was achieved by packing with hemostatic collagen and gelfoam. The peritoneal surface was noted to have multiple implants in the right upper quadrant, and large free-floating tumor clusters were removed from the peritoneal cavity. Postoperative ultrasound of the testes showed normal size and architecture. On the 7th postoperative day chemotherapy was begun using a modified Einhorn regimen consisting of cis-
JournalofPediafr;cSurgery,
Vol27,No
1 (January), 1992: pp 105.107
Fig 1. Microscopic section of the initial biopsy specimen showing an endodermal sinus tumor displaying papillary and reticular growth patterns. The small globules of intracellular material (arrows) stained positively for a-fetoprotein immunoperoxidase (H&E, original magnification x200).
From the Divisions of Pediattic Swgev, Hemutology /Oncology. and Pathology, Departments of Surgery. Pathology. und Pediutrics. Children’s Hospital of Los Angeles and the IJni~wG~ of Southern California School of Medicine. Los Angeles. CA. Address reprint requests to James B. Atkinson, MD, Deparfment sf Surgery, Children’s Hospital of Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027. Copyright 8 1992 by W.B. Saunders Compatn 0022-3468/9212701-0030$03.00/O 105
106
ATKINSON ET AL
Table 1. Reported Cases of Endodermal Sinus Tumor of the Liver Age
Sex
Hart6
Investigators
18 mo
M
Originate in medial segment of left lobe, en-
Okamatsu et al’
27 mo
M
Left lobe, left diaphragm and left peritoneum
Location
of Tumor
Treatment
tire right lobe, extend into omentum
Survival
Extended right hepatectomy; chemother-
6.5 mo
apy: ACT-D, CYC, MTX XRTfor METS Left hepatic lobectomy; chemotherapy:
7mo
ACT-D, AMYC, CYC, 5FU, VIN; laparotomy X3, for METS; radiotherapy Natori et al*
29 yr
F
Right anterior segment, right diaphragm and right peritoneum, left lobe of liver
Atkinson et al
14 mo
M
Right hepatic lobectomy; chemotherapy:
5mo
ACT-D, VIN, CYC
Falciform ligament, left lobe and peritoneum anterior to liver
Exploratory laparotomy with debulking of tumor; chemotherapy:
>2 yr, alive and well
CIS, VP-16 velban,
ELEO; second exploratory laparotomy after chemotherapy,
left hepatic
lobec-
tomy Abbreviations:
ACT-D,
actinomycin-D;
CYC, cyclophosphamide;
MTX,
methotrexate;
XRT, radiation therapy;
METS,
metastases;
AMYC,
adriamycin; 5FU, 5-fluorouracil; VIN, vincristine; CIS, cisplatinum; VP-16, etoposide; velban, vinblastine; BLEO, bleomycin.
tumor composed of cells forming reticular and papillary patterns with perivascular endodermal sinus structures (Fig 1). The tumor cells were irregular and vacuolated containing cytoplasmic hyaline droplets that stained positively for a-fetoprotein immunoperoxidase. Mitoses were relatively common. The histological findings were diagnostic of endodermal sinus tumor (YST). The specimen obtained from the second operation 5 months later consisted of the left lobe of the liver, 9.5 x 7.5 x 3 cm, and attached to the abdominal wall. Grossly no tumor was identified but only a small amount of necrotic tissue was noted in the center of the specimen in the region of the falciform ligament. Microscopically, this necrotic tissue consisted of small foci of yolk sac stroma and essentially no viable tumor. The hepatic parenchyma and other lines of resection were free of tumor.
Follow-Up The patient’s course following secondary surgery was uncomplicated. He completed 6 full cycles of chemotherapy. The serum a-fetoprotein level decreased to 20,000 ng/mL immediately postoperatively, and remains < 20 ng/mL to the present time. The patient received 4 additional months of maintenance chemotherapy consisting of Vinblastine, 6 mg/m’ IV on day 1, and VP-16 75 mg/m’ IV daily for 5 days, repeated at 4-week intervals. Chemotherapy was discontinued 10 months after diagnosis. He is now off therapy with no clinical or radiologic evidence of disease for 14 months postcompletion of chemotherapy and 2 years since diagnosis. DISCUSSION
Endodermal sinus tumors (YSTs) were first described by Schiller in 1939.9 The histological appearance of the tumor reported here conforms to the classic description of yolk sac carcinoma described by Teilum” in 1959. The embryo forms the secondary or definitive yolk sac with clusters of germ cells in the endoderm at approximately the 13th day of development. It is proposed that YSTs develop from the germ cells found in the yolk sac. The germ cells migrate
into the gonadal ridge along the dorsal mesentery of the hind gut during the 6th week of gestation.” The most likely explanation for extragonadal germ cell tumors is that some germ cells become sequestered in extragonadal sites during this migration from the yolk sac to the gonadal ridge. The falciform ligament is derived from tissues adjacent to the yolk sac giving a possible explanation for the origin of YSTs in the falciform ligament as in this patient. Table 1 lists the three additional reported cases of the YST of the liver with the sex, age, location, treatment, and survival shown. The present case is unique in showing a disease-free survival greater than 2 years. The chemotherapy of germ cell tumors has greatly improved in the last 10 years. Einhorn introduced a triple chemotherapeutic regimen consisting of cisplatinum, vinblastine, and bleomycin in 1977.12This regimen has been refined in subsequent years. Logothetis et al have found cyclic chemotherapy with cyclophosphamide, adriamycin, cisplatinum, vinblastine, and bleomycin to be effective against extragonadal germ cell tumors.‘” The successful management of extragonadal germ cell tumors consists of early and accurate tissue diagnosis, application of an effective and vigorous chemotherapeutic regimen, and radical surgical extirpation subsequent to chemotherapy. The experience with this case suggests that the combination of aggressive surgical management coupled with intensive chemotherapy may produce an increased length of survival and potentially a cure in the face of advanced disease.
REFERENCES 1. Stachura I, Mendelow H: Endodermal ing in the region of the pineal gland. Cancer 2. Gooneratne S, Keh P, Sreekanth S, et nal endodermal sinus (yolk sac) tumor in a 56:1430-1433,198s
sinus tumor originat45:2131-2137,198O al: Anterior mediastifemale infant. Cancer
3. Thiele J, Salvador C, Lee KD: Extragonadal endodermal sinus tumor (yolk sac tumor) of the pelvis. Cancer 27:391-396, 1971 4. Norgaard-Pedersen B, Albrechtser R, Teilum G: Serum a-foetoprotein as a marker for endodermal sinus tumor (yolk sac
ENDODERMAL SINUS TUMOR
tumor) or a vitelline component of teratocarcinoma. Acta Path01 Microbial Stand 83573-589, 1975 5. Benson RCJ, Segura JW, Carney JA: Primary yolk-sac (endodermal sinus) tumor of the prostate. Cancer 41:1395-1398,1978 6. Hart WR: Primary endodermal sinus (yolk sac) tumor of the liver. Cancer 35:1453-1458.1975 7. Okamatsu T, Nagai M, Lie U, et al: Yolk sac tumor of the liver, report of a case. Jpn J Pediatr Surg 12:821-826,198O 8. Natori T. Teshima S, Kikuchi Y, et al: Primary yolk sac tumor of the liver an autopsy case with ultrastructural and immunopathological studies. Acta Path01 Jpn 33:555-564, 1983 9. Teilum G: Mesonephroma ovarii (Schiller). Extraembryonic mesoblastoma of germ cell origin, ovary and testis. Acta Pathol Microbial Stand 27:249-261, 1950
107
10. Teilum G: Endodermal sinus tumors of the ovary and testis: comparative morphogenesis of the so-called mesonephroma ovarii (Schiller) and extraembryonic (yolk sac-allantoic) structures of the rat’s placenta. Cancer 12:1092-l 105, 1959 11. Altman AJ, Schwartz AD: Tumors of germ cell origin: Germinomas. embryonal carcinomas, extraembryonal tumors, and teratomas, in Malignant Diseases of Infancy, Childhood & Adolescence (ed 2). Philadelphia, PA, Saunders, 1983, chap 19 12. Einhorn LH, Donohue JP: Cis-diamminedichoroplatinum, vinblastine, bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 87:293-298, 1977 13. Logothetis CJ, Samuels ML, Trindade A, et al: The growing teratoma syndrome. Cancer 50:1629-1635. 1982
B. Atkinson,
Clarence
E. Foster III, Kevin P. Lally, Hat-t Isaacs, and Stuart E. Siegel
Los Angeles, California l Extragonadal yolk sac tumors (YSTs) are uncommon and YSTs of the liver are exceedingly rare, with only three reported cases in the literature. A case is described of primary YST of the falciform ligament extending into the left lobe of the liver in a 14-month-old boy. This is the first reported case of primary YST arising within the falciform ligament. The patient underwent an exploratory laparotomy after presenting with hemoperitoneum. An extremely friable and necrotic tumor was found extending from the falciform ligament into the liver. The tumor was debulked and the patient received 5 months of chemotherapy employing a modified Einhorn regimen. After a partial response to chemotherapy the patient had a second-look laparotomy, at which time a left hepatic lobectomy and en bloc resection of the falciform ligament was performed in order to remove residual tumor. At the present time the patient has no signs of metastases and is alive and well 2 years after his presentation. Copyright P 1992 by W.B. Saunders Company
platinum. 20 mgim’ intravenously (IV) daily for 5 days: VP-16, 75 mgim’ IV daily for 5 days; Vinblastine, 6 mgim’ IV on day 1 of each course; and Bleomycin. 15 U/m’ IV on day 1 of each course. Courses were repeated every 4 weeks. The patient received a total of five courses over a 4-month period. Five months after diagnosis, the patient underwent a second laparotomy. A left hepatic lobectomy and en bloc resection of the abdominal wall was performed to remove residual tumor with clear microscopic margins. The remaining peritoneal surfaces and the rest of the abdomen were free of tumor.
Pathological Findings Microscopic examination of the initial biopsy taken from the anterior surface of the liver during the first operation showed a
INDEX WORDS: Yolk sac tumor, falciform ligament; endodermal sinus tumor.
Y
OLK SAC tumors (YSTs) usually occur in the testes or ovaries and rarely in an extragonadal site. This germ cell tumor has been found in the central nervous system,’ anterior mediastinum,’ sacrococcygeal region,’ retroperitoneum,4 and the prostate.5 YST of the liver is exceedingly rare and, to our knowledge, there have been only three reported cases6-’ We report the first case of primary YST of the falciform ligament. CASE REPORT
A 14-month-old black boy was admitted for evaluation of increased abdominal girth, a right upper quadrant mass, and ascites. There was no history of trauma, bleeding abnormalities, jaundice or chronic anorexia. The patient was found to have a tensely distended, firm abdomen with a 7-cm mass in the right upper quadrant and both testes were normal. Abnormal laboratory values included a hematocrit of 23% and oc-fetoprotein of 76,000. Computed tomography scan showed free fluid and an anterior mass attached to the liver. At laparotomy a large friable mass was encountered invading the abdominal wall along the falciform ligament and extending into the anterior surface of the liver involving the medial and lateral segments of the left hepatic lobe. The tumor was debulked and tamponade of the raw surface was achieved by packing with hemostatic collagen and gelfoam. The peritoneal surface was noted to have multiple implants in the right upper quadrant, and large free-floating tumor clusters were removed from the peritoneal cavity. Postoperative ultrasound of the testes showed normal size and architecture. On the 7th postoperative day chemotherapy was begun using a modified Einhorn regimen consisting of cis-
JournalofPediafr;cSurgery,
Vol27,No
1 (January), 1992: pp 105.107
Fig 1. Microscopic section of the initial biopsy specimen showing an endodermal sinus tumor displaying papillary and reticular growth patterns. The small globules of intracellular material (arrows) stained positively for a-fetoprotein immunoperoxidase (H&E, original magnification x200).
From the Divisions of Pediattic Swgev, Hemutology /Oncology. and Pathology, Departments of Surgery. Pathology. und Pediutrics. Children’s Hospital of Los Angeles and the IJni~wG~ of Southern California School of Medicine. Los Angeles. CA. Address reprint requests to James B. Atkinson, MD, Deparfment sf Surgery, Children’s Hospital of Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027. Copyright 8 1992 by W.B. Saunders Compatn 0022-3468/9212701-0030$03.00/O 105
106
ATKINSON ET AL
Table 1. Reported Cases of Endodermal Sinus Tumor of the Liver Age
Sex
Hart6
Investigators
18 mo
M
Originate in medial segment of left lobe, en-
Okamatsu et al’
27 mo
M
Left lobe, left diaphragm and left peritoneum
Location
of Tumor
Treatment
tire right lobe, extend into omentum
Survival
Extended right hepatectomy; chemother-
6.5 mo
apy: ACT-D, CYC, MTX XRTfor METS Left hepatic lobectomy; chemotherapy:
7mo
ACT-D, AMYC, CYC, 5FU, VIN; laparotomy X3, for METS; radiotherapy Natori et al*
29 yr
F
Right anterior segment, right diaphragm and right peritoneum, left lobe of liver
Atkinson et al
14 mo
M
Right hepatic lobectomy; chemotherapy:
5mo
ACT-D, VIN, CYC
Falciform ligament, left lobe and peritoneum anterior to liver
Exploratory laparotomy with debulking of tumor; chemotherapy:
>2 yr, alive and well
CIS, VP-16 velban,
ELEO; second exploratory laparotomy after chemotherapy,
left hepatic
lobec-
tomy Abbreviations:
ACT-D,
actinomycin-D;
CYC, cyclophosphamide;
MTX,
methotrexate;
XRT, radiation therapy;
METS,
metastases;
AMYC,
adriamycin; 5FU, 5-fluorouracil; VIN, vincristine; CIS, cisplatinum; VP-16, etoposide; velban, vinblastine; BLEO, bleomycin.
tumor composed of cells forming reticular and papillary patterns with perivascular endodermal sinus structures (Fig 1). The tumor cells were irregular and vacuolated containing cytoplasmic hyaline droplets that stained positively for a-fetoprotein immunoperoxidase. Mitoses were relatively common. The histological findings were diagnostic of endodermal sinus tumor (YST). The specimen obtained from the second operation 5 months later consisted of the left lobe of the liver, 9.5 x 7.5 x 3 cm, and attached to the abdominal wall. Grossly no tumor was identified but only a small amount of necrotic tissue was noted in the center of the specimen in the region of the falciform ligament. Microscopically, this necrotic tissue consisted of small foci of yolk sac stroma and essentially no viable tumor. The hepatic parenchyma and other lines of resection were free of tumor.
Follow-Up The patient’s course following secondary surgery was uncomplicated. He completed 6 full cycles of chemotherapy. The serum a-fetoprotein level decreased to 20,000 ng/mL immediately postoperatively, and remains < 20 ng/mL to the present time. The patient received 4 additional months of maintenance chemotherapy consisting of Vinblastine, 6 mg/m’ IV on day 1, and VP-16 75 mg/m’ IV daily for 5 days, repeated at 4-week intervals. Chemotherapy was discontinued 10 months after diagnosis. He is now off therapy with no clinical or radiologic evidence of disease for 14 months postcompletion of chemotherapy and 2 years since diagnosis. DISCUSSION
Endodermal sinus tumors (YSTs) were first described by Schiller in 1939.9 The histological appearance of the tumor reported here conforms to the classic description of yolk sac carcinoma described by Teilum” in 1959. The embryo forms the secondary or definitive yolk sac with clusters of germ cells in the endoderm at approximately the 13th day of development. It is proposed that YSTs develop from the germ cells found in the yolk sac. The germ cells migrate
into the gonadal ridge along the dorsal mesentery of the hind gut during the 6th week of gestation.” The most likely explanation for extragonadal germ cell tumors is that some germ cells become sequestered in extragonadal sites during this migration from the yolk sac to the gonadal ridge. The falciform ligament is derived from tissues adjacent to the yolk sac giving a possible explanation for the origin of YSTs in the falciform ligament as in this patient. Table 1 lists the three additional reported cases of the YST of the liver with the sex, age, location, treatment, and survival shown. The present case is unique in showing a disease-free survival greater than 2 years. The chemotherapy of germ cell tumors has greatly improved in the last 10 years. Einhorn introduced a triple chemotherapeutic regimen consisting of cisplatinum, vinblastine, and bleomycin in 1977.12This regimen has been refined in subsequent years. Logothetis et al have found cyclic chemotherapy with cyclophosphamide, adriamycin, cisplatinum, vinblastine, and bleomycin to be effective against extragonadal germ cell tumors.‘” The successful management of extragonadal germ cell tumors consists of early and accurate tissue diagnosis, application of an effective and vigorous chemotherapeutic regimen, and radical surgical extirpation subsequent to chemotherapy. The experience with this case suggests that the combination of aggressive surgical management coupled with intensive chemotherapy may produce an increased length of survival and potentially a cure in the face of advanced disease.
REFERENCES 1. Stachura I, Mendelow H: Endodermal ing in the region of the pineal gland. Cancer 2. Gooneratne S, Keh P, Sreekanth S, et nal endodermal sinus (yolk sac) tumor in a 56:1430-1433,198s
sinus tumor originat45:2131-2137,198O al: Anterior mediastifemale infant. Cancer
3. Thiele J, Salvador C, Lee KD: Extragonadal endodermal sinus tumor (yolk sac tumor) of the pelvis. Cancer 27:391-396, 1971 4. Norgaard-Pedersen B, Albrechtser R, Teilum G: Serum a-foetoprotein as a marker for endodermal sinus tumor (yolk sac
ENDODERMAL SINUS TUMOR
tumor) or a vitelline component of teratocarcinoma. Acta Path01 Microbial Stand 83573-589, 1975 5. Benson RCJ, Segura JW, Carney JA: Primary yolk-sac (endodermal sinus) tumor of the prostate. Cancer 41:1395-1398,1978 6. Hart WR: Primary endodermal sinus (yolk sac) tumor of the liver. Cancer 35:1453-1458.1975 7. Okamatsu T, Nagai M, Lie U, et al: Yolk sac tumor of the liver, report of a case. Jpn J Pediatr Surg 12:821-826,198O 8. Natori T. Teshima S, Kikuchi Y, et al: Primary yolk sac tumor of the liver an autopsy case with ultrastructural and immunopathological studies. Acta Path01 Jpn 33:555-564, 1983 9. Teilum G: Mesonephroma ovarii (Schiller). Extraembryonic mesoblastoma of germ cell origin, ovary and testis. Acta Pathol Microbial Stand 27:249-261, 1950
107
10. Teilum G: Endodermal sinus tumors of the ovary and testis: comparative morphogenesis of the so-called mesonephroma ovarii (Schiller) and extraembryonic (yolk sac-allantoic) structures of the rat’s placenta. Cancer 12:1092-l 105, 1959 11. Altman AJ, Schwartz AD: Tumors of germ cell origin: Germinomas. embryonal carcinomas, extraembryonal tumors, and teratomas, in Malignant Diseases of Infancy, Childhood & Adolescence (ed 2). Philadelphia, PA, Saunders, 1983, chap 19 12. Einhorn LH, Donohue JP: Cis-diamminedichoroplatinum, vinblastine, bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 87:293-298, 1977 13. Logothetis CJ, Samuels ML, Trindade A, et al: The growing teratoma syndrome. Cancer 50:1629-1635. 1982
