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doi:10.1111/jog.12292
J. Obstet. Gynaecol. Res. Vol. 40, No. 4: 1150–1153, April 2014
Massive perivillous fibrin deposition in the placenta and uterine metastasis of gastric adenocarcinoma during pregnancy Bada Jeong1, Jae-Yoon Shim1, Chong Jai Kim2, Hye-Sung Won1, Pil Ryang Lee1 and Ahm Kim1 Departments of 1Obstetrics and Gynecology and 2Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Abstract The prognosis of gastric cancer during pregnancy is unfavorable because of delayed diagnosis and advanced stage. We present a case of gastric carcinoma metastasized to the placenta and uterus during pregnancy. Pathological examination revealed a poorly differentiated adenocarcinoma of the stomach with lymph node metastasis. After counseling, the patient decided to terminate the pregnancy and begin immediate treatment for gastric cancer. Hysterectomy and subtotal hysterectomy were performed because medical termination of the pregnancy was unsuccessful. Pathological examination of the placenta and uterus revealed metastases of gastric adenocarcinoma. All the uterine vessels were packed with tumor cells and the myometrium showed extensive coagulative necrosis. Moreover, microscopic findings of the placenta were consistent with massive perivillous fibrin deposition. Our case clearly suggests that massive perivillous fibrin deposition in the placenta can be associated with malignancy during pregnancy and that uterine metastasis of maternal malignancy may result in myometrial dysfunction unresponsive to uterotonics. Key words: gastric cancer, metastasis, perivillous fibrin deposition, pregnancy.
Introduction Maternal malignancy during pregnancy is found in approximately 0.1% of pregnant women and gastric cancer accounts for less than 10% of all these malignancies.1 Previous studies show that the prognosis of gastric cancer during pregnancy is unfavorable because of a delayed diagnosis and an advanced stage of disease at the time of diagnosis.1 The delay in gastric cancer diagnosis is partly due to the unlikelihood of the disease in young female patients and also because cancer-related gastrointestinal symptoms are often mistaken as physiological symptoms of pregnancy.
Even when pregnancy-associated gastric cancer is diagnosed at an advanced stage, metastasis to the placenta and/or to the fetus is relatively rare,2–7 and there are no reports of uterine metastasis of gastric carcinoma during pregnancy. Furthermore, the detailed biological and functional consequences of placental or uterine metastasis remain to be elucidated. We present a case of gastric carcinoma metastasized to the placenta and uterus during pregnancy. This case shows that placental and uterine metastasis of malignancies can lead to serious uterine vascular and uteroplacental circulatory dysfunction. The unique pathological associations in this case provide valuable information in the context
Received: June 13 2013. Accepted: September 5 2013. Reprint request to: Dr Jae-Yoon Shim, Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Email: [email protected] Conflict of interest: The authors have no financial conflicts of interest.
1150
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Metastasis of gastric cancer during pregnancy
of the pathophysiology of placental and uterine dysfunction caused by metastasis.
Case Report A 37-year-old primigravida patient visited our tertiary centre at 21 weeks of gestation with complaints of epigastric pain. She suffered from anorexia and nausea for over 4 months associated with epigastric pain and lost 14 kg during the pregnancy. She had a history of primary infertility, and had undergone in vitro fertilization. A little ascites had been detected from early pregnancy, but it has been regarded as a complication of ovarian stimulation. She had never had a gastroscopy performed before pregnancy and she did not take any medications during pregnancy. Other past medical and family histories were unremarkable. Physical examination revealed marked abdominal distension and a palpable neck mass. Ultrasound examination demonstrated a singleton fetus appropriate for the gestational age of 21 weeks. Multiple right perihepatic masses and ascites were also found. Gastroscopy demonstrated a diffuse infiltrative lesion in the stomach. A biopsy of the neck mass was performed and pathological examination demonstrated a metastasis of poorly differentiated adenocarcinoma to the cervical lymph node. Metastatic adenocarcinoma was also found in the ascites. Computed tomography findings were compatible with peritoneal carcinomatosis, and metastasis to
the gallbladder, colon and bone were also found. There were no signs of sepsis immediately after ascites tapping. After counseling, the patient and her spouse decided to terminate the pregnancy and receive immediate treatment for gastric cancer. Termination of the pregnancy was initiated with laminaria and misoprostol but dilatation of the cervix did not progress after 3 days. On the fourth day, she was transferred to the intensive care unit because of hypotension, tachycardia, tachypnea and fever, which suggested septic shock. Hysterectomy was performed at 23 weeks of gestation because medical termination failed and sepsis developed. Multiple peritoneal seedings including uterine serosa were found. Subtotal hysterectomy was performed after delivery of a stillborn fetus to reduce tumor burden and to prevent further bleeding. She received supportive care but died 8 days later due to septic shock and disseminated intravascular coagulation. The placenta and uterus were submitted for pathological examination. Both of them revealed poorly differentiated metastatic adenocarcinoma of gastric origin. The placenta showed diffuse consolidation (Fig. 1a) and microscopic features showing extensive intervillous fibrin were consistent with those of massive perivillous fibrin deposition (MPFD) (Fig. 1b). Many of the uteroplacental vessels at the basal plate were plugged with mucin-producing carcinoma cells (Fig. 1c). Multiple leiomyomas were present in the
(a)
(b)
(c)
(d)
(e)
(f)
Figure 1 Gross and microscopic features of the placenta and uterus. (a) The placenta shows diffuse consolidation and (b) extensive intervillous fibrin, which is characteristic of massive perivillous fibrin deposition (hematoxylin–eosin [HE], original magnification ×40). (c) Many of the uteroplacental vessels in the basal plate are plugged with mucin-producing carcinoma cells (HE, ×40). (d) Multiple leiomyomas are present in the uterus and (e) all the uterine vessels in a leiomyoma are also packed with mucin-producing tumor cells (HE, ×100). (f) The myometrium as well as leiomyomas showed extensive coagulative necrosis due to compromised uterine circulation by tumor emboli (HE, ×40).
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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B. Jeong et al.
uterus (Fig. 1d) and all the intratumoral uterine vessels were also packed with mucin-producing tumor cells (Fig. 1e). The myometrium as well as leiomyomas showed extensive coagulative necrosis due to compromised uterine circulation by tumor emboli (Fig. 1f).
Discussion While gastric cancers are more common in the elderly population with a mean age of 60 years and a male-tofemale ratio of 1.7:1, those found in younger patients less than 40 years of age are predominantly found in females, with a poorly differentiated histology, and unfavorable prognosis.8,9 A recent study shows that gastric cancer associated with pregnancy is often diagnosed at a more advanced stage and consequently shows a poorer prognosis compared with age-matched control groups.1 Possible reasons for poorer prognosis include delayed diagnosis, limited therapeutic options, hormonal and biological alterations, and immunosuppression during pregnancy.10,11 In our case, the patient had suffered from gastrointestinal symptoms and weight loss but believed the symptoms were related to pregnancy. This led to a delayed diagnosis at an advanced stage of the disease. Going forward, gastroscopic examination should be performed in patients with atypical and severe gastric symptoms during pregnancy, especially after the first trimester, for earlier diagnosis. In addition, screening gastroscopy during pregnancy should be considered in high-risk patients: family history of gastric cancer, peptic ulcer history, immunosuppressive diseases, drug usage and cigarette smoking.11 Metastasis of maternal malignancy to the placenta or fetus is rare, and malignant melanoma is the most common cancer metastasizing to the placenta, followed by lung cancer, leukemia/lymphoma and breast cancer.12 Metastasis to the fetus is more uncommon than placental spread and there are two possible explanations for this. First, the placental trophoblast forms a maternal–fetal barrier to prevent cancer cell invasion across the chorionic villi.12 Second, the fetal immune system may destroy maternal cancer cells that manage to cross the trophoblast barrier.13 The true incidence of placental or fetal metastases is underestimated because pathological examination of the placenta or dead fetus is often not performed and placental involvement is often identified only microscopically without macroscopic evidence.12 Therefore, a thorough microscopic examination of the placenta is important in cases with maternal malignancy. In addition, autopsy of the fetus
1152
and close follow-up of babies are indicated once placental metastasis is confirmed. Massive perivillous fibrin deposition of the placenta is characterized by pathological accumulation of fibrinoid extracellular matrix materials that surrounds the placental villi.14 It can result in spontaneous abortion, preterm delivery, fetal death and fetal growth restriction.15 The etiology is unknown, and yet the entity has been linked to a variety of pathologies including maternal hypertension/pre-eclampsia, autoimmune diseases, inherited or acquired coagulopathy, and infection. We suggest that maternal metastatic cancer may be a possible etiologic factor for the development of MPFD. In this case, many of the uteroplacental vessels and all the uterine vessels were packed with tumor cells, which resulted in extensive necrosis of the myometrium and MPFD. From the pathophysiological aspect, the presence of MPFD strongly suggested that stagnation of intervillous circulation by tumor cells played a role in the development of this unique pathological alteration of the placenta. It is noteworthy that pre-eclampsia and maternal thrombophilia can be associated with MPFD, and both conditions would lead to compromised intervillous maternal blood circulation.16,17 Therefore, placental metastasis and tumor emboli in uterine vessels in our case may have resulted in an analogous situation with pre-eclampsia and maternal thrombophilia in the context of placental perfusion. Alternatively, it is also possible that tumor cells in the intervillous space are producing fibrin.18 Metastases to the uterus from extragenital malignancy are also rare. The published work indicates that the most common primary tumors are breast, colon, stomach and pancreas.19 Usually, disease is widespread at the time of diagnosis with poor prognosis.20 To our knowledge, this is the first case showing uterine metastasis of gastric cancer during pregnancy. The low incidence of uterine metastasis, together with the insufficiency or lack of pathological examinations of the uterus, may explain why this type of metastasis has been underestimated. In the present case, all the uterine vessels were packed with mucin-producing tumor cells and the myometrium as well as leiomyomas showed extensive coagulative necrosis. This explains why the myometrium was unresponsive to the uterotonic drugs: the myometrial blood supply compromised by disseminated intravascular tumor emboli caused medical termination to fail. Extensive coagulative necrosis of the myometrium resulted in the absence of a functional myometrial reservoir and the myometrium was unable to respond to any uterotonic drugs.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Metastasis of gastric cancer during pregnancy
In conclusion, the overall clinical consequences of our case underscore the importance of screening for underlying malignancies in pregnant women whose clinical courses are atypical. Gastroscopy needs to be considered in pregnant women suffering from severe gastrointestinal symptoms. Our case also clearly suggests that MPFD in the placenta may be associated with malignancy during pregnancy and that uterine metastasis of maternal malignancy may result in myometrial dysfunction.
References 1. Lee HJ, Lee IK, Kim JW, Lee KU, Choe KJ, Yang HK. Clinical characteristics of gastric cancer associated with pregnancy. Dig Surg 2009; 26: 31–36. 2. Miller K, Zawislak A, Gannon C, Millar D, Loughrey MB. Maternal gastric adenocarcinoma with placental metastases: What is the fetal risk? Pediatr Dev Pathol 2012; 15: 237–239. 3. Baker AM, Haeri S, Shafer A, Moldenhauer JS. Maternal gastric carcinoma metastatic to the placenta. Eur J Obstet Gynecol Reprod Biol 2010; 153: 225–226. 4. Bender S. Placental metastases in malignant disease complicated by pregnancy with a report of 2 cases. Br Med J 1950; 1: 980–981. 5. Lee MS, Kim SH, Lee JH et al. A case of placental metastasis from advanced gastric carcinoma. J Korean Cancer Assoc 1998; 30: 608–612. 6. Lee HS, Kim Y, Kim CJ, Chi JG. Placental metastais of maternal gastric adenocarcinoma: A case report. Korean J Pathol 1999; 33: 214–216. 7. Khatib F, Shaya M, Samueloff A. Gastric carcinoma with metastasis to the placenta and amniotic fluid: Case report and review of the literature. Eur J Obstet Gynecol Reprod Biol 2003; 107: 208–209. 8. Kath R, Fiehler J, Schneider CP, Hoffken K. Gastric cancer in very young adults: Apropos four patients and a review of the literature. J Cancer Res Clin Oncol 2000; 126: 233–237.
9. Sakamoto K, Kanda T, Ohashi M et al. Management of patients with pregnancy-associated gastric cancer in Japan: A mini-review. Int J Clin Oncol 2009; 14: 392–396. 10. Ueo H, Matsuoka H, Tamura S, Sato K, Tsunematsu Y, Kato T. Prognosis in gastric cancer associated with pregnancy. World J Surg 1991; 15: 293–297. discussion 298. 11. Jaspers VK, Gillessen A, Quakernack K. Gastric cancer in pregnancy: Do pregnancy, age or female sex alter the prognosis? Case reports and review. Eur J Obstet Gynecol Reprod Biol 1999; 87: 13–22. 12. Al-Adnani M, Kiho L, Scheimberg I. Maternal pancreatic carcinoma metastatic to the placenta: A case report and literature review. Pediatr Dev Pathol 2007; 10: 61–65. 13. van der Velden VH, Willemse MJ, Mulder MF et al. Clearance of maternal leukaemic cells in a neonate. Br J Haematol 2001; 114: 104–106. 14. Uxa R, Baczyk D, Kingdom JC, Viero S, Casper R, Keating S. Genetic polymorphisms in the fibrinolytic system of placentas with massive perivillous fibrin deposition. Placenta 2010; 31: 499–505. 15. Griffin AC, Strauss AW, Bennett MJ, Ernst LM. Mutations in long-chain 3-hydroxyacyl coenzyme a dehydrogenase are associated with placental maternal floor infarction/massive perivillous fibrin deposition. Pediatr Dev Pathol 2012; 15: 368– 374. 16. Kanfer A, Bruch JF, Nguyen G et al. Increased placental antifibrinolytic potential and fibrin deposits in pregnancyinduced hypertension and preeclampsia. Lab Invest 1996; 74: 253–258. 17. Gogia N, Machin GA. Maternal thrombophilias are associated with specific placental lesions. Pediatr Dev Pathol 2008; 11: 424–429. 18. Salgado R, Benoy I, Weytjens R et al. Arterio-venous gradients of IL-6, plasma and serum VEGF and d-dimers in human cancer. Br J Cancer 2002; 87: 1437–1444. 19. Tsoi D, Buck M, Hammond I, White J. Gastric adenocarcinoma presenting as uterine metastasis – a case report. Gynecol Oncol 2005; 97: 932–934. 20. Kumar NB, Hart WR. Metastases to the uterine corpus from extragenital cancers. A clinicopathologic study of 63 cases. Cancer 1982; 50: 2163–2169.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
1153
doi:10.1111/jog.12292
J. Obstet. Gynaecol. Res. Vol. 40, No. 4: 1150–1153, April 2014
Massive perivillous fibrin deposition in the placenta and uterine metastasis of gastric adenocarcinoma during pregnancy Bada Jeong1, Jae-Yoon Shim1, Chong Jai Kim2, Hye-Sung Won1, Pil Ryang Lee1 and Ahm Kim1 Departments of 1Obstetrics and Gynecology and 2Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Abstract The prognosis of gastric cancer during pregnancy is unfavorable because of delayed diagnosis and advanced stage. We present a case of gastric carcinoma metastasized to the placenta and uterus during pregnancy. Pathological examination revealed a poorly differentiated adenocarcinoma of the stomach with lymph node metastasis. After counseling, the patient decided to terminate the pregnancy and begin immediate treatment for gastric cancer. Hysterectomy and subtotal hysterectomy were performed because medical termination of the pregnancy was unsuccessful. Pathological examination of the placenta and uterus revealed metastases of gastric adenocarcinoma. All the uterine vessels were packed with tumor cells and the myometrium showed extensive coagulative necrosis. Moreover, microscopic findings of the placenta were consistent with massive perivillous fibrin deposition. Our case clearly suggests that massive perivillous fibrin deposition in the placenta can be associated with malignancy during pregnancy and that uterine metastasis of maternal malignancy may result in myometrial dysfunction unresponsive to uterotonics. Key words: gastric cancer, metastasis, perivillous fibrin deposition, pregnancy.
Introduction Maternal malignancy during pregnancy is found in approximately 0.1% of pregnant women and gastric cancer accounts for less than 10% of all these malignancies.1 Previous studies show that the prognosis of gastric cancer during pregnancy is unfavorable because of a delayed diagnosis and an advanced stage of disease at the time of diagnosis.1 The delay in gastric cancer diagnosis is partly due to the unlikelihood of the disease in young female patients and also because cancer-related gastrointestinal symptoms are often mistaken as physiological symptoms of pregnancy.
Even when pregnancy-associated gastric cancer is diagnosed at an advanced stage, metastasis to the placenta and/or to the fetus is relatively rare,2–7 and there are no reports of uterine metastasis of gastric carcinoma during pregnancy. Furthermore, the detailed biological and functional consequences of placental or uterine metastasis remain to be elucidated. We present a case of gastric carcinoma metastasized to the placenta and uterus during pregnancy. This case shows that placental and uterine metastasis of malignancies can lead to serious uterine vascular and uteroplacental circulatory dysfunction. The unique pathological associations in this case provide valuable information in the context
Received: June 13 2013. Accepted: September 5 2013. Reprint request to: Dr Jae-Yoon Shim, Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Email: [email protected] Conflict of interest: The authors have no financial conflicts of interest.
1150
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Metastasis of gastric cancer during pregnancy
of the pathophysiology of placental and uterine dysfunction caused by metastasis.
Case Report A 37-year-old primigravida patient visited our tertiary centre at 21 weeks of gestation with complaints of epigastric pain. She suffered from anorexia and nausea for over 4 months associated with epigastric pain and lost 14 kg during the pregnancy. She had a history of primary infertility, and had undergone in vitro fertilization. A little ascites had been detected from early pregnancy, but it has been regarded as a complication of ovarian stimulation. She had never had a gastroscopy performed before pregnancy and she did not take any medications during pregnancy. Other past medical and family histories were unremarkable. Physical examination revealed marked abdominal distension and a palpable neck mass. Ultrasound examination demonstrated a singleton fetus appropriate for the gestational age of 21 weeks. Multiple right perihepatic masses and ascites were also found. Gastroscopy demonstrated a diffuse infiltrative lesion in the stomach. A biopsy of the neck mass was performed and pathological examination demonstrated a metastasis of poorly differentiated adenocarcinoma to the cervical lymph node. Metastatic adenocarcinoma was also found in the ascites. Computed tomography findings were compatible with peritoneal carcinomatosis, and metastasis to
the gallbladder, colon and bone were also found. There were no signs of sepsis immediately after ascites tapping. After counseling, the patient and her spouse decided to terminate the pregnancy and receive immediate treatment for gastric cancer. Termination of the pregnancy was initiated with laminaria and misoprostol but dilatation of the cervix did not progress after 3 days. On the fourth day, she was transferred to the intensive care unit because of hypotension, tachycardia, tachypnea and fever, which suggested septic shock. Hysterectomy was performed at 23 weeks of gestation because medical termination failed and sepsis developed. Multiple peritoneal seedings including uterine serosa were found. Subtotal hysterectomy was performed after delivery of a stillborn fetus to reduce tumor burden and to prevent further bleeding. She received supportive care but died 8 days later due to septic shock and disseminated intravascular coagulation. The placenta and uterus were submitted for pathological examination. Both of them revealed poorly differentiated metastatic adenocarcinoma of gastric origin. The placenta showed diffuse consolidation (Fig. 1a) and microscopic features showing extensive intervillous fibrin were consistent with those of massive perivillous fibrin deposition (MPFD) (Fig. 1b). Many of the uteroplacental vessels at the basal plate were plugged with mucin-producing carcinoma cells (Fig. 1c). Multiple leiomyomas were present in the
(a)
(b)
(c)
(d)
(e)
(f)
Figure 1 Gross and microscopic features of the placenta and uterus. (a) The placenta shows diffuse consolidation and (b) extensive intervillous fibrin, which is characteristic of massive perivillous fibrin deposition (hematoxylin–eosin [HE], original magnification ×40). (c) Many of the uteroplacental vessels in the basal plate are plugged with mucin-producing carcinoma cells (HE, ×40). (d) Multiple leiomyomas are present in the uterus and (e) all the uterine vessels in a leiomyoma are also packed with mucin-producing tumor cells (HE, ×100). (f) The myometrium as well as leiomyomas showed extensive coagulative necrosis due to compromised uterine circulation by tumor emboli (HE, ×40).
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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B. Jeong et al.
uterus (Fig. 1d) and all the intratumoral uterine vessels were also packed with mucin-producing tumor cells (Fig. 1e). The myometrium as well as leiomyomas showed extensive coagulative necrosis due to compromised uterine circulation by tumor emboli (Fig. 1f).
Discussion While gastric cancers are more common in the elderly population with a mean age of 60 years and a male-tofemale ratio of 1.7:1, those found in younger patients less than 40 years of age are predominantly found in females, with a poorly differentiated histology, and unfavorable prognosis.8,9 A recent study shows that gastric cancer associated with pregnancy is often diagnosed at a more advanced stage and consequently shows a poorer prognosis compared with age-matched control groups.1 Possible reasons for poorer prognosis include delayed diagnosis, limited therapeutic options, hormonal and biological alterations, and immunosuppression during pregnancy.10,11 In our case, the patient had suffered from gastrointestinal symptoms and weight loss but believed the symptoms were related to pregnancy. This led to a delayed diagnosis at an advanced stage of the disease. Going forward, gastroscopic examination should be performed in patients with atypical and severe gastric symptoms during pregnancy, especially after the first trimester, for earlier diagnosis. In addition, screening gastroscopy during pregnancy should be considered in high-risk patients: family history of gastric cancer, peptic ulcer history, immunosuppressive diseases, drug usage and cigarette smoking.11 Metastasis of maternal malignancy to the placenta or fetus is rare, and malignant melanoma is the most common cancer metastasizing to the placenta, followed by lung cancer, leukemia/lymphoma and breast cancer.12 Metastasis to the fetus is more uncommon than placental spread and there are two possible explanations for this. First, the placental trophoblast forms a maternal–fetal barrier to prevent cancer cell invasion across the chorionic villi.12 Second, the fetal immune system may destroy maternal cancer cells that manage to cross the trophoblast barrier.13 The true incidence of placental or fetal metastases is underestimated because pathological examination of the placenta or dead fetus is often not performed and placental involvement is often identified only microscopically without macroscopic evidence.12 Therefore, a thorough microscopic examination of the placenta is important in cases with maternal malignancy. In addition, autopsy of the fetus
1152
and close follow-up of babies are indicated once placental metastasis is confirmed. Massive perivillous fibrin deposition of the placenta is characterized by pathological accumulation of fibrinoid extracellular matrix materials that surrounds the placental villi.14 It can result in spontaneous abortion, preterm delivery, fetal death and fetal growth restriction.15 The etiology is unknown, and yet the entity has been linked to a variety of pathologies including maternal hypertension/pre-eclampsia, autoimmune diseases, inherited or acquired coagulopathy, and infection. We suggest that maternal metastatic cancer may be a possible etiologic factor for the development of MPFD. In this case, many of the uteroplacental vessels and all the uterine vessels were packed with tumor cells, which resulted in extensive necrosis of the myometrium and MPFD. From the pathophysiological aspect, the presence of MPFD strongly suggested that stagnation of intervillous circulation by tumor cells played a role in the development of this unique pathological alteration of the placenta. It is noteworthy that pre-eclampsia and maternal thrombophilia can be associated with MPFD, and both conditions would lead to compromised intervillous maternal blood circulation.16,17 Therefore, placental metastasis and tumor emboli in uterine vessels in our case may have resulted in an analogous situation with pre-eclampsia and maternal thrombophilia in the context of placental perfusion. Alternatively, it is also possible that tumor cells in the intervillous space are producing fibrin.18 Metastases to the uterus from extragenital malignancy are also rare. The published work indicates that the most common primary tumors are breast, colon, stomach and pancreas.19 Usually, disease is widespread at the time of diagnosis with poor prognosis.20 To our knowledge, this is the first case showing uterine metastasis of gastric cancer during pregnancy. The low incidence of uterine metastasis, together with the insufficiency or lack of pathological examinations of the uterus, may explain why this type of metastasis has been underestimated. In the present case, all the uterine vessels were packed with mucin-producing tumor cells and the myometrium as well as leiomyomas showed extensive coagulative necrosis. This explains why the myometrium was unresponsive to the uterotonic drugs: the myometrial blood supply compromised by disseminated intravascular tumor emboli caused medical termination to fail. Extensive coagulative necrosis of the myometrium resulted in the absence of a functional myometrial reservoir and the myometrium was unable to respond to any uterotonic drugs.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Metastasis of gastric cancer during pregnancy
In conclusion, the overall clinical consequences of our case underscore the importance of screening for underlying malignancies in pregnant women whose clinical courses are atypical. Gastroscopy needs to be considered in pregnant women suffering from severe gastrointestinal symptoms. Our case also clearly suggests that MPFD in the placenta may be associated with malignancy during pregnancy and that uterine metastasis of maternal malignancy may result in myometrial dysfunction.
References 1. Lee HJ, Lee IK, Kim JW, Lee KU, Choe KJ, Yang HK. Clinical characteristics of gastric cancer associated with pregnancy. Dig Surg 2009; 26: 31–36. 2. Miller K, Zawislak A, Gannon C, Millar D, Loughrey MB. Maternal gastric adenocarcinoma with placental metastases: What is the fetal risk? Pediatr Dev Pathol 2012; 15: 237–239. 3. Baker AM, Haeri S, Shafer A, Moldenhauer JS. Maternal gastric carcinoma metastatic to the placenta. Eur J Obstet Gynecol Reprod Biol 2010; 153: 225–226. 4. Bender S. Placental metastases in malignant disease complicated by pregnancy with a report of 2 cases. Br Med J 1950; 1: 980–981. 5. Lee MS, Kim SH, Lee JH et al. A case of placental metastasis from advanced gastric carcinoma. J Korean Cancer Assoc 1998; 30: 608–612. 6. Lee HS, Kim Y, Kim CJ, Chi JG. Placental metastais of maternal gastric adenocarcinoma: A case report. Korean J Pathol 1999; 33: 214–216. 7. Khatib F, Shaya M, Samueloff A. Gastric carcinoma with metastasis to the placenta and amniotic fluid: Case report and review of the literature. Eur J Obstet Gynecol Reprod Biol 2003; 107: 208–209. 8. Kath R, Fiehler J, Schneider CP, Hoffken K. Gastric cancer in very young adults: Apropos four patients and a review of the literature. J Cancer Res Clin Oncol 2000; 126: 233–237.
9. Sakamoto K, Kanda T, Ohashi M et al. Management of patients with pregnancy-associated gastric cancer in Japan: A mini-review. Int J Clin Oncol 2009; 14: 392–396. 10. Ueo H, Matsuoka H, Tamura S, Sato K, Tsunematsu Y, Kato T. Prognosis in gastric cancer associated with pregnancy. World J Surg 1991; 15: 293–297. discussion 298. 11. Jaspers VK, Gillessen A, Quakernack K. Gastric cancer in pregnancy: Do pregnancy, age or female sex alter the prognosis? Case reports and review. Eur J Obstet Gynecol Reprod Biol 1999; 87: 13–22. 12. Al-Adnani M, Kiho L, Scheimberg I. Maternal pancreatic carcinoma metastatic to the placenta: A case report and literature review. Pediatr Dev Pathol 2007; 10: 61–65. 13. van der Velden VH, Willemse MJ, Mulder MF et al. Clearance of maternal leukaemic cells in a neonate. Br J Haematol 2001; 114: 104–106. 14. Uxa R, Baczyk D, Kingdom JC, Viero S, Casper R, Keating S. Genetic polymorphisms in the fibrinolytic system of placentas with massive perivillous fibrin deposition. Placenta 2010; 31: 499–505. 15. Griffin AC, Strauss AW, Bennett MJ, Ernst LM. Mutations in long-chain 3-hydroxyacyl coenzyme a dehydrogenase are associated with placental maternal floor infarction/massive perivillous fibrin deposition. Pediatr Dev Pathol 2012; 15: 368– 374. 16. Kanfer A, Bruch JF, Nguyen G et al. Increased placental antifibrinolytic potential and fibrin deposits in pregnancyinduced hypertension and preeclampsia. Lab Invest 1996; 74: 253–258. 17. Gogia N, Machin GA. Maternal thrombophilias are associated with specific placental lesions. Pediatr Dev Pathol 2008; 11: 424–429. 18. Salgado R, Benoy I, Weytjens R et al. Arterio-venous gradients of IL-6, plasma and serum VEGF and d-dimers in human cancer. Br J Cancer 2002; 87: 1437–1444. 19. Tsoi D, Buck M, Hammond I, White J. Gastric adenocarcinoma presenting as uterine metastasis – a case report. Gynecol Oncol 2005; 97: 932–934. 20. Kumar NB, Hart WR. Metastases to the uterine corpus from extragenital cancers. A clinicopathologic study of 63 cases. Cancer 1982; 50: 2163–2169.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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