Advanced rectal cancer with multiorgan metastasis detected after single fetal death in twin pregnancy: a case report

Introduction

Detection of colorectal cancer (CRC) in pregnancy is even rarer, observed in approximately 1 in 13,000 deliveries (1). Recent research highlights an increasing trend toward CRC mortality rates in young adults in several nations, including the United States, Canada, Australia, and the United Kingdom (2). In recent years, as women increasingly give birth at an advanced age regardless of marital status, the incidence of malignant tumors during pregnancy has also increased (3). In a previous study, maternal cancer diagnosed during pregnancy was positively associated with fetal death (4). Therefore, early rectal cancer detection during pregnancy is crucial as it affects maternal and fetal prognoses. However, diagnosis can be challenging because digestive and systemic symptoms caused by rectal cancer often resemble the normal physiological changes occurring during pregnancy (1). Case reports of rectal cancer diagnosed following fetal death are extremely rare, and few mention the cause of fetal death. We report a case involving a twin pregnancy in which single fetal death served as a crucial clue for the detection of advanced CRC with multiorgan metastasis. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0011/rc).

Case presentation

A 36-year-old woman with a dichorionic twin pregnancy (gravida 3, para 0) conceived via in vitro fertilization, with a negative cell-free fetal DNA (cff DNA) test result. Her medical history included multiple uterine fibroids and constipation. Her family history included lung cancer and pancreatic cancer in her father and aunt, respectively.

The patient was referred to a local hospital with painful uterine contractions at 26 weeks and 3 days of gestation. Three days after initiating tocolysis with ritodrine, a nonstress test (NST) showed severely prolonged deceleration in one twin (Fetus I). She was transferred to Department of Obstetrics and Gynecology, The Jikei University School of Medicine because of a suspected non-reassuring fetal status (NRFS). Her body temperature was 36.6 ℃ with no fever. Blood tests showed mildly elevated inflammatory markers: white blood cells, 12,500/µL; C-reactive protein, 2.71 mg/dL; and D-dimer level, 14.4 µg/dL. Anemia was also noted, with a hemoglobin level of 9.6 g/dL. Vaginal examination revealed no bleeding or fluid leakage, and the Nugent score was negative. Transvaginal ultrasound measured a cervical length of 26.9 mm. Uterine contractions were controlled well by 50 µg/min ritodrine hydrochloride. Administration of 1 g ampicillin sodium every 6 hours was initiated due to suspected uterine fibroid infection, but there was no improvement in inflammatory markers. Given the elevated D-dimer level, a lower-extremity venous ultrasound was performed and ruled out deep vein thrombosis. Both fetuses showed appropriate growth with normal anatomy, amniotic fluid volume, and cord insertion; however, Fetus I demonstrated severe variable decelerations on NST (Figure 1). Therefore, we performed daily biophysical profile scoring and fetal Doppler studies, which revealed no abnormalities. The patient reported perceiving good fetal movements daily. However, following the morning examination on day 8 after admission, the patient reported decreased fetal movements. Repeat fetal ultrasonography confirmed intrauterine fetal death (IUFD) of Fetus I. Pelvic magnetic resonance imaging (MRI) was performed to investigate the fetal death and maternal inflammation. Multiple areas of hemorrhage and infarction were noted in the placentas of both fetuses. Therefore, placental dysfunction was considered the cause of IUFD in Fetus I. As Fetus II showed similar findings, the possibility of a similar outcome was considered. Additionally, multiple masses were observed in the maternal liver, raising the possibility of malignant tumor involvement (Figure 2A, images A1,A2). Bedside transabdominal ultrasonography revealed multiple liver masses with central necrosis, which raised the suspicion of metastatic liver cancer (Figure 2B). The patient and family received extensive counseling by gastroenterologists, surgeons, maternal-fetal medicine specialists, and social counselors. All management plans for pregnancy and additional investigations for suspected carcinoma were discussed. The patient agreed to undergo additional investigations. However, 2 days after the death of Fetus I, prolonged deceleration and irregular uterine contractions were observed for Fetus II (Figure 3). An emergency cesarean section was performed, and Fetus II weighing 1,169 g was delivered with Apgar scores of 8 (1 min) and 9 (5 min). He was admitted to the neonatal intensive care unit (NICU) for prematurity. Fetus I was stillborn, weighed 944 g, and showed no gross abnormalities. Products of conception testing showed a normal karyotype, and no autopsy was performed as per the family’s wishes. Histopathological examination of both placentas revealed multiple, extensive infarcts and hematomas, with no evident tumor metastases. There was no evidence of chorioamnionitis or abnormalities in the umbilical cords (Figure 4).

Figure 1 Findings of a nonstress test performed at 26 weeks and 6 days of gestation (3 days after hospitalization). Severe variable deceleration is observed for Infant I. Uterine contractions are irregular. Black line: Fetus I; blue line: Fetus II.

Figure 2 Findings of pelvic magnetic resonance imaging (A) and transabdominal ultrasound (B) performed at 28 weeks and 1 day of gestation (9 days after hospitalization). (A1) True fast imaging with steady-state free precession reveals multiple areas of hemorrhage and infarction (×) in the placenta. (A2) Fat-suppressed T1-weighted three-dimensional volume imaging (FST-3D-vive) reveals multiple masses (→) within the maternal liver. (B) Multiple masses are observed in the liver. A hypoechoic area is noted at the center of the masses. 3D, three-dimensional; FST, fat-suppressed T1-weighted 3D volumetric interpolated breath-hold examination.

Figure 3 Findings of a nonstress test at 28 weeks and 2 days of gestation (10 days after hospitalization). Prolonged deceleration and irregular uterine contractions are observed for Fetus II.

Figure 4 Findings of histopathological examination of the placentas after emergency cesarean section. (A) Macroscopic placental findings: multiple, extensive infarcts and hematomas are observed in the placentas of both infants. (B) Hematoxylin and eosin stain; placental tissue from Fetus I (enlarged view of the red square area in A): histological appearance of a hematoma and yellowish-white nodules. a: a wide range of blood types are accepted. b: the infarct site is accompanied by neutrophil infiltration. c: the villi are small and mature, with chorangiosis, fibrin deposition around the villi, increased syncytiotrophoblast nodules, and blood stasis between the villi.

After delivery, we initiated a thorough investigation of the maternal tumors. Fecal occult blood was strongly positive, and tumor markers were elevated as follows: carcinoembryonic antigen, 14.3 ng/mL; alpha fetoprotein, 1,191 ng/mL; cancer antigen 19-9, 2,356 U/mL; and protein induced by vitamin K absence or antagonist-II, 25 mAU/mL. Contrast-enhanced computed tomography (CT) revealed findings suggestive of CRC and regional lymph node, liver, and lung metastases. Colonoscopy and biopsy confirmed the diagnosis of advanced CRC, type 3 adenocarcinoma. Overall, all examinations confirmed a final diagnosis of stage IV unresectable CRC (Figure 5). The diagnosis of CRC and the available treatment options were explained to the couple by a multidisciplinary team consisting of a gastroenterologist, a maternal-fetal medicine specialist, a midwife, and a certified oncology nurse. Chemotherapy was initiated 2 weeks after delivery. Infant II was discharged from NICU at 77 days of age with favorable progress. At 1 year and 10 months of age, the infant II showed normal physical, cognitive, and motor development. Three months after delivery, coagulation disorder and antiphospholipid antibody tests were conducted to investigate the cause of the stillbirth and yielded negative results. Twelve months after chemotherapy initiation, brain metastases were detected. Subsequently, the patient developed multiple cerebral infarctions and was diagnosed with Trousseau’s syndrome. Despite treatment, there was no improvement, and the patient died 13 months after delivery.

Figure 5 Diagnosis of advanced colorectal cancer with multiorgan metastasis after emergency cesarean section. (A) Chest, abdominal, and pelvic contrast-enhanced computed tomography images are shown. (A1) Findings suggestive of rectal cancer with wall thickening and serosal invasion are observed in the right rectum (red circle). Enlarged regional lymph nodes are also observed. (A2) Multiple masses are observed in the liver (→). (A3) Numerous nodules are noted within the lungs (red circle). (B) Colonoscopy showing advanced colorectal cancer, type 3 (ulcerative invasion). (C) Hematoxylin and eosin stain; histopathological examination of a biopsy specimen shows adenocarcinoma. On the basis of these findings, the patient was diagnosed with stage IV unresectable colorectal cancer.

Ethical consideration

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Informed consent was obtained from the patient’s family for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

To our best knowledge, this is the first reported case in which advanced rectal cancer with multiorgan metastases was detected after single fetal death in a twin pregnancy. This case highlights the difficulty in diagnosing CRC during pregnancy as well as the significant impact of malignancy and hypercoagulable state induced by pregnancy on placental circulation. In addition to digestive symptoms caused by CRC, several symptoms commonly seen in malignant tumors, such as fatigue and anemia, are similar to the physiological changes occurring during pregnancy (5). Consequently, CRC is often diagnosed postpartum (6,7). In this case, subjective symptoms were scarce, and useful information for determining the treatment plan was first obtained from an ultrasound test and MRI performed after the death of Fetus I. Common tests for CRC diagnosis include fecal occult blood testing, blood tumor marker testing, digital rectal examination, imaging tests, and colonoscopy. These tests can be reasonable options for CRC diagnosis during pregnancy. In addition, surveillance for anemia even if patients report no visible blood in their feces would be helpful, as moderate to severe anemia detected in pregnancy would correlate with intestinal bleeding (8). In the present case, IUFD in Fetus I was the key trigger for initiating surveillance, and subsequent MRI identified multiple tumors in the maternal liver. Although it may be difficult to perform contrast-enhanced CT to investigate inflammation in afebrile pregnant women, plain CT or MRI with surveillance for anemia might be highly beneficial. Proactive testing should be pursued, even for pregnant women, if necessary. In recent years, the potential of using cell-free DNA (cfDNA) for detecting malignant tumors in pregnant women has garnered significant attention. In a previous study, pregnant or postpartum patients who underwent cfDNA sequencing during their routine obstetrical care, from 12 different facilities in North America, were screened for cancer. In that study, 48.6% of participants who underwent unusual or nonreportable clinical cfDNA-sequencing results had an occult cancer (9). Although this case underwent NIPT, data could not be traced, because the test was performed at a non-certified facility. As observed in this case, even with few subjective symptoms, progressive malignant tumors might be present. Developing screening methods for malignant tumors, including cfDNA, holds potentials for improving maternal and fetal prognosis through early diagnosis and therapeutic intervention for managing malignant tumor complications in pregnant women.

A study from 1973 to 2012 by Lu et al. calculated stillbirth rates among approximately 4 million infants born to mothers diagnosed with malignant tumors during pregnancy or within 1 year postpartum in Sweden. The stillbirth rate was 2.5 times higher for pregnancies complicated by malignant tumors than for those without tumor complications (3,4). However, this report did not address factors contributing to fetal death. Furthermore, there are no large-scale investigations of the causes of IUFD in patients with malignant tumors diagnosed during pregnancy. At the case report level, reported factors for fetal death in pregnancies complicated by malignancy include tumor metastasis to the placenta, chemotherapy during pregnancy, and poor maternal nutritional status (10,11). Patient with cancer exhibit enhanced coagulation owing to tumor cell-mediated activation of the coagulation cascade, leading to thrombosis (12,13). In this case, multiple infarcts were observed in the placenta, suggesting fetal death due to placental dysfunction. Although placental dysfunction is not routinely emphasized in pregnancies complicated by malignant tumors, acute NRFS due to placental dysfunction may be an important clue suggesting the presence of advanced maternal malignancy.

The American College of Obstetricians and Gynecologists recommend that when malignancy is diagnosed during pregnancy, surgery should not be delayed regardless of gestational age (14). When surgery is not indicated, chemotherapy or radiation therapy during pregnancy may be an option. These choices must be discussed thoroughly with the patient and their family to confirm their wishes. Treatment options, including continuation of pregnancy, must be selected, and the timing of treatment initiation and delivery must be determined. Currently, there are no detailed treatment guidelines for pregnant women with CRC. Given the highly complex clinical and ethical context of cancer-complicated pregnancy, Linkeviciute et al. proposed a comprehensive framework to guide healthcare professionals in ethical decision-making (15). We managed this case in accordance with the ethical checklist outlined in their study. Clinicians should proactively anticipate and address potential ethical issues. Further research with multidisciplinary collaboration and treatment information is required to develop evidence-based protocols that address the healthcare needs of this population.

Conclusions

One of the factors leading to the diagnosis of maternal malignancy was IUFD. In cases of advanced cancer during pregnancy, attention must also be paid to fetal-placental function. In pregnant women, when IUFD occurs accompanied by unexplained maternal inflammatory response elevation and coagulation activation, thorough investigation for malignant tumors is necessary.

Acknowledgments

We would like to thank the members of the Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, for their guidance and cooperation. We also thank the patient and the family members for granting permission to use the patient’s clinical information in this article. Finally, during the preparation of this work the authors used Editage for English language editing. After using this tool, the authors have reviewed and edited the content as needed and take full responsibility for the content of the published article.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0011/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0011/prf

Funding: This study was supported by The Jikei University School of Medicine, Department of Obstetrics and Gynecology.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0011/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Informed consent was obtained from the patient’s family for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Khodaverdi S, Kord Valeshabad A, Khodaverdi M. A Case of Colorectal Cancer during Pregnancy: A Brief Review of the Literature. Case Rep Obstet Gynecol 2013;2013:626393. [Crossref] [PubMed]
2. Sinicrope FA. Increasing Incidence of Early-Onset Colorectal Cancer. N Engl J Med 2022;386:1547-58. [Crossref] [PubMed]
3. Walters B, Midwinter I, Chew-Graham CA, et al. Pregnancy-Associated Cancer: A Systematic Review and Meta-Analysis. Mayo Clin Proc Innov Qual Outcomes 2024;8:188-99. [Crossref] [PubMed]
4. Lu D, Ludvigsson JF, Smedby KE, et al. Maternal Cancer During Pregnancy and Risks of Stillbirth and Infant Mortality. J Clin Oncol 2017;35:1522-9. [Crossref] [PubMed]
5. Dahling MT, Xing G, Cress R, et al. Pregnancy-associated colon and rectal cancer: perinatal and cancer outcomes. J Matern Fetal Neonatal Med 2009;22:204-11. [Crossref] [PubMed]
6. Yang H, Han X. Colorectal cancer in pregnancy: a case report and literature review. J Gastrointest Oncol 2021;12:885-91. [Crossref] [PubMed]
7. Galante A, Cerbone M, Mannavola F, et al. Diagnostic, Management, and Neonatal Outcomes of Colorectal Cancer during Pregnancy: Two Case Reports, Systematic Review of Literature and Metanalysis. Diagnostics (Basel) 2024;14:559. [Crossref] [PubMed]
8. Oka K, Hasegawa A, Mikuni H, et al. Recurrent severe anemia associated with a jejunal arteriovenous malformation in pregnancy: A case report. Case Rep Womens Health 2023;40:e00559. [Crossref] [PubMed]
9. Turriff AE, Annunziata CM, Malayeri AA, et al. Prenatal cfDNA Sequencing and Incidental Detection of Maternal Cancer. N Engl J Med 2024;391:2123-32. [Crossref] [PubMed]
10. Framarino-dei-Malatesta M, Perrone G, Giancotti A, et al. Epirubicin: a new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature. BMC Cancer 2015;15:951.
11. Niu C, Zhang J, Sun M, et al. Maternal and perinatal outcomes of pregnant patients with colorectal cancer: a population-based study. J Cancer Res Clin Oncol 2023;149:14159-67. [Crossref] [PubMed]
12. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015;12:464-74. [Crossref] [PubMed]
13. Hutten BA, Prins MH, Gent M, et al. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 2000;18:3078-83. [Crossref] [PubMed]
14. ACOG Committee Opinion No. 775: Nonobstetric Surgery During Pregnancy. Obstet Gynecol 2019;133:e285-6. [Crossref] [PubMed]
15. Linkeviciute A, Canario R, Peccatori FA, et al. Caring for Pregnant Patients with Cancer: A Framework for Ethical and Patient-Centred Care. Cancers (Basel) 2024;16:455. [Crossref] [PubMed]