Metastatic Cervicomedullary Lesion in the Postpartum Period: A Case-Based Review of CNS Metastases in Pregnancy and Postpartum Period

Abstract

Central nervous system (CNS) metastases in pregnancy are exceedingly rare but represent a complex and life-threatening condition requiring prompt diagnosis and a multidisciplinary approach. This report highlights a rare case of cervicomedullary junction metastasis in a postpartum patient, exploring diagnostic challenges and management strategies. A 32-year-old woman, postcesarean section, presented with progressive quadriparesis and dysphagia, weeks after delivery. Initial symptoms of neck pain during pregnancy resolved postpartum but rapidly worsened, leading to diagnostic uncertainty. Contrast-enhanced MRI revealed a cervicomedullary lesion. Given the rarity of cervicomedullary metastases and the overlapping presentation with pregnancy-related neurological conditions, there was a delay in identifying the underlying malignancy. CNS metastases in pregnancy are most commonly linked to breast cancer, melanoma, and gestational trophoblastic disease (GTD), with choriocarcinoma being particularly aggressive. However, nongestational metastases, such as in our case, are significantly underreported. Pregnancy-related physiological changes, including immune modulation and hormonal influences, may accelerate tumor progression, complicating the clinical picture. Our patient's presentation of quadriparesis and bulbar dysfunction was initially confused with other pregnancy-related conditions, highlighting the importance of maintaining a high index of suspicion for neurological compromise in pregnant and postpartum women. Early diagnostic imaging with contrast-enhanced MRI is critical for timely intervention. Management of CNS metastases in pregnancy poses unique challenges due to concerns regarding maternal and fetal health. Surgical decompression was performed for our patient due to rapid neurological decline. For surgically inaccessible lesions, stereotactic radiosurgery (SRS) offers a viable alternative, with minimal extracranial radiation exposure. Whole-brain radiotherapy (WBRT) and chemotherapy, while effective, are typically reserved for cases of multiple metastases or systemic disease. Obstetric considerations, such as timing of delivery, are also paramount, with early cesarean section often necessary in cases of severe neurological compromise. CNS metastases in pregnancy are rare but require rapid diagnosis and a tailored treatment approach. Early recognition of symptoms, timely imaging, and surgical intervention are essential to improving patient outcomes. Nongestational metastases remain underreported, and further research is needed to refine management guidelines, incorporating advanced imaging and molecular profiling. Our case underscores the importance of considering CNS metastasis in the differential diagnosis of postpartum patients with neurological symptoms, particularly in cases with cervicomedullary junction involvement.

Keywords

central nervous system metastases - cervicomedullary junction metastasis - postnatal neurological deficits

Introduction

Metastatic tumors involving the central nervous system (CNS) during pregnancy and the postpartum period are exceedingly rare, presenting unique diagnostic and therapeutic challenges. Among these, lesions located at the cervicomedullary junction are particularly uncommon and can lead to rapidly progressive neurological deterioration. These cases often signify advanced-stage systemic malignancy and are associated with a poor prognosis. Due to their rarity, there is limited guidance on optimal diagnostic and therapeutic approaches, making management complex and highly individualized.

The rarity of CNS metastases in the peripartum period may be attributed to physiological changes during pregnancy, including immunosuppression, increased vascular permeability, and hormonal influences that may affect tumor progression and metastatic spread. The most commonly reported CNS metastases in pregnancy are associated with gestational trophoblastic disease (GTD), particularly choriocarcinoma, followed by breast cancer and melanoma. However, nongestational CNS metastases remain underreported, leading to potential delays in diagnosis and treatment.

In this case-based review, we present a postpartum patient with a rare cervicomedullary metastatic lesion, followed by an analysis of similar cases reported in the literature. We discuss the diagnostic challenges, differential considerations, and evolving treatment strategies, including the role of surgery, systemic therapy, and stereotactic radiosurgery (SRS) such as gamma knife (GK) radiosurgery. By integrating insights from recent studies, we aim to provide a comprehensive overview of current management approaches for CNS metastases in pregnant and postpartum patients, emphasizing the need for a multidisciplinary strategy to optimize outcomes.

Case Presentation

A 33-year-old female patient presented to our facility with a history of progressively worsening neurological symptoms. Her symptoms began during the third trimester of pregnancy at 33 weeks of gestation when she first experienced severe neck pain and tingling sensations around the neck and bilateral shoulders. These symptoms resolved after 2 days of analgesic treatment. However, after 4 days, she experienced a recurrence of similar symptoms, prompting her to visit the obstetrics department. Routine obstetric examination revealed intrauterine death of the fetus with an unidentifiable cause. The patient was induced with injectable oxytocin and delivered to the fetus vaginally. Following delivery, her symptoms improved significantly within hours and she remained asymptomatic for the next 3 days.

On the fourth day postpartum, the patient began experiencing severe neck pain radiating to both shoulder joints and the upper back. This was soon followed by weakness in her left upper limb, which gradually progressed to involve the left lower limb, right upper limb, and right lower limb over the next 4 days. The patient also developed difficulty swallowing and was unable to tolerate solid food. At this point, she was admitted to a local hospital where she was managed conservatively. Over the following days, the weakness continued to progress, leading to quadriparesis. She presented to our facility with complete quadriplegia, with power in all four limbs recorded as 0/5, and severe hypotonia. Reflexes were absent in all four limbs, and bilateral plantar responses were mute. Cranial nerve examination revealed a central uvula, but gag reflexes were impaired bilaterally.

Upon presentation to our institution, the patient was started on RT feeds, DVT pumps were applied bilaterally, and steroids were initiated. A contrast-enhanced MRI ([Fig. 1]) of the brain and cervical spine was performed, revealing a well-defined, T1 hypointense, homogeneously enhancing intra-axial lesion at the cervicomedullary junction, measuring 1.5 cm × 1.6 cm × 1.4 cm. The lesion caused expansion of the brainstem at the cervicomedullary junction, with adjacent medullary and posterior pons involvement and central T2/FLAIR hyperintensity indicative of perilesional edema. ASL and T2^* perfusion imaging showed homogenously increased cerebral blood flow within the lesion. Based on the clinical–radiological findings, the decision was made to proceed with surgical intervention.

Fig. 1 A well-defined T1 hypointense, homogeneously enhancing (A–C), T2/FLAIR hyperintense (D, E), intra-axial lesion, measuring 1.5 cm × 1.6 cm × 1.4 cm, is seen involving the brainstem at the cervicomedullary junction, causing its expansion. The adjacent medulla, posterior aspect of the pons, and cervical cord (up to C5/6 level) show central T2/FLAIR hyper-intensity (s/o perilesional edema). ASL and T2^* perfusion shows homogeneously increased cerebral blood flow within the lesion (F).

The patient underwent a midline suboccipital craniectomy and C1 laminectomy to excise the lesion. A 5-mm posterior medullary incision was made for the tumor removal. Intraoperatively, a greyish–white, soft, moderately vascular tumor was found and aspirated using a CUSA ([Fig. 2]). Frozen section analysis suggested carcinomatous characteristics, with a possibility of choriocarcinoma or metastasis. The patient was given an intraoperative methylprednisolone infusion, which was continued until postoperative day 1. The patient was extubated on day 1 after surgery, but her power remained 0/5 in the postoperative period. Steroids were gradually tapered off.

Fig. 2 Intraoperative photographs show C1 arch removal and suboccipital laminectomy (A), durotomy (B), posterior medullotomy (C), and tumor aspiration using CUSA (D, E). Histopathological images show a cellular tumor arranged in small islands, cords, and a glandular pattern with moderate pleomorphism, increased mitosis, and areas of necrosis in a fibroblastic background (F), CK7 positivity (G), CK19 positivity (H), and a raised Ki67 labeling index (I).

Histopathological analysis ([Fig. 2]) revealed diffusely infiltrative tumor cells arranged in sheets and glandular patterns, with moderate pleomorphism, increased mitotic activity, and areas of necrosis within a fibroblastic background. Immunohistochemical staining showed positivity for CK7 and CK19, but negativity for CK20, TTF1, GATA3, PAX8, Beta HCG, HepPar, p-40, SALL-4, and WTI, with a Ki67 labeling index of approximately 80 to 90%. These features were suggestive of metastatic carcinoma, most likely originating from the upper gastrointestinal or female genital tract.

Beta-HCG levels were within normal limits, and a CT scan of the neck, thorax, abdomen, and pelvis failed to identify any primary carcinoma. Due to financial constraints, a PET scan could not be performed. The patient was discharged in stable condition with no improvement in her neurological status and was referred to a cancer facility for further workup and management. Unfortunately, she passed away from her illness a month after discharge.

Discussion

Metastatic involvement of the CNS during pregnancy and the postpartum period is exceptionally rare, presenting unique diagnostic and therapeutic challenges. The presence of a metastatic lesion at the cervicomedullary junction, as seen in our index case, is even more unusual. These lesions often signify advanced systemic malignancy and are associated with a poor prognosis due to limited treatment options, diagnostic delays, and physiological constraints imposed by pregnancy.

Despite the rarity, the incidence of CNS metastases during pregnancy may be underreported due to a combination of factors, including physiological changes masking early symptoms, diagnostic hesitancy due to fetal safety concerns, and prioritization of obstetric care over maternal oncological assessment. The physiological adaptations during pregnancy—including immune modulation, increased vascular permeability, and elevated hormone levels—may contribute to metastatic tumor progression and dissemination.[1]

Several case series have documented brain metastases in pregnancy, but nongestational CNS metastases, like the one in our case, remain significantly underreported.[1] [2] The most common primary malignancies associated with brain metastases in pregnant patients include breast cancer, melanoma, and GTD, particularly choriocarcinoma.[2] [3] [4] Our case adds to the limited literature by highlighting the diagnostic complexity and management dilemmas associated with cervicomedullary metastases in a postpartum patient of unknown primary origin.

Epidemiology and Primary Sources of CNS Metastases in Pregnancy

Brain metastases occur in 20 to 40% of all cancer patients but their incidence during pregnancy remains significantly lower, given that pregnancy is not a high-risk state for primary malignancies.[5] A prospective review by Verheecke et al documented 27 cases of intracranial tumors diagnosed during pregnancy, including both primary brain tumors and metastases.[1] The study highlighted that 30% of cases required neurosurgery, 26% received radiotherapy, and chemotherapy was administered in 11% of cases during pregnancy.

1. GTD and choriocarcinoma: GTD, particularly choriocarcinoma, is the most aggressive and neurotropic malignancy affecting pregnant and postpartum patients.[6] Song et al reported a case of postpartum choriocarcinoma with brain metastases (stage IV, risk score 16), which was successfully treated with multi-agent chemotherapy and whole-brain radiotherapy (WBRT).[3] The Xiao et al study on 109 patients with GTD-related brain metastases found that aggressive multi-agent chemotherapy combined with intrathecal methotrexate significantly improved survival outcomes.[4]

2. Breast cancer: The most common non-GTD source, apart from GTD, breast cancer is the most frequent nongestational primary malignancy leading to CNS metastases in pregnant women. Sharma et al reported that, prior to their study, only three cases of breast cancer metastasizing to the brain during pregnancy had been documented.[2] Their case involved a 35-year-old woman with recurrent breast cancer metastasizing to the frontal lobe, requiring repeated craniotomies, chemotherapy adjustments, and WBRT.

3. Other sources and unknown primary: Other documented sources of CNS metastases in pregnant women include melanoma and lung cancer.[5] In 15% of cases, the primary tumor remains unknown, as in our index case.[5] In such cases, PET-CT imaging is invaluable in identifying the primary source, but financial constraints may limit its availability, as seen in our patient.

Clinical Presentation and Diagnostic Challenges

Symptomatology and Delays in Diagnosis

Symptoms of CNS metastases in pregnant and postpartum patients vary based on tumor location and burden but frequently include:

• Headache (due to increased intracranial pressure)

• Seizures (indicative of cortical irritation or hemorrhagic metastases)

• Visual disturbances and cognitive dysfunction

• Hemiparesis and ataxia (common with supratentorial and cerebellar lesions)

• Bulbar dysfunction and respiratory compromise (as seen in cervicomedullary junction lesions like our case)

In our index case, the patient developed progressive quadriparesis and dysphagia, a presentation that overlaps with pregnancy-related neurological conditions such as Guillain–Barré syndrome, postpartum demyelination, and eclampsia. This atypical symptomatology led to diagnostic uncertainty and delayed imaging, emphasizing the need for early MRI in pregnant patients with neurological symptoms.[7]

Role of MRI in Diagnosis

Contrast-enhanced MRI is the gold standard for CNS metastase diagnosis, but concerns regarding fetal safety often lead to delayed imaging.[5] Rodrigues et al emphasized that MRI should not be postponed when neurological symptoms arise, particularly when rapid deterioration is noted.[7]

Treatment Considerations in Pregnancy and Postpartum

Surgical Considerations

For patients with significant mass effects or rapid neurological decline, surgical decompression is the preferred approach, as in our case.[8] However, anesthetic and perioperative risks must be carefully balanced in pregnant patients.[9] Tewari et al recommended that pregnant patients with unstable neurological symptoms should undergo cesarean section in the early third trimester, followed by immediate neurosurgical decompression.[8]

Stereotactic Radiosurgery versus Whole-Brain Radiotherapy

Gamma knife (GK) SRS is emerging as a viable alternative for patients with surgically inaccessible metastases. Soon et al described the successful use of GK SRS in a pregnant patient with cerebellar metastasis, demonstrating minimal extracranial radiation exposure.[10] Studies by Soffietti et al confirm that SRS achieves comparable outcomes to surgery for lesions ≤3.5 cm, making it a preferred modality for select cases.[5]

WBRT remains an option for multiple metastases but carries significant neurotoxicity risks. Stelzer et al emphasized that WBRT should be reserved for patients with poor surgical candidacy or multiple lesions.[11]

Chemotherapy Considerations

Chemotherapy use during pregnancy depends on gestational age and tumor type. For GTD-related metastases, systemic chemotherapy is the mainstay.[4] [12] For non-GTD cases, chemotherapy is generally deferred until postpartum unless the tumor burden requires immediate intervention.[7] [9]

Prognostic Factors and Future Directions

Prognosis in CNS metastases during pregnancy remains poor, with median survival <6 months in non-GTD cases.[11] Factors associated with better survival include:

• Younger age

• Single metastasis

• Controlled primary tumor

• Absence of extracranial metastases[5]

The evolving role of molecular biomarkers may aid in early detection and risk stratification, optimizing surveillance strategies.[11] Future research should focus on refining treatment guidelines for CNS metastases in pregnancy, integrating targeted therapy, immunotherapy, and advanced imaging techniques.

Conclusion

CNS metastases during pregnancy and the postpartum period remain a diagnostic and therapeutic challenge. Our case highlights the need for early imaging, aggressive intervention, and multidisciplinary management. SRS is emerging as a promising treatment modality, particularly in cases where surgery is not feasible. Further studies are needed to establish standardized guidelines and improve maternal–fetal outcomes.

Conflict of Interest

None declared.

• References

• 1 Verheecke M, Halaska MJ, Lok CA. et al; ESGO Task Force ‘Cancer in Pregnancy’. Primary brain tumours, meningiomas and brain metastases in pregnancy: report on 27 cases and review of literature. Eur J Cancer 2014; 50 (08) 1462-1471
• 2 Sharma A, Nguyen HS, Lozen A, Sharma A, Mueller W. Brain metastases from breast cancer during pregnancy. Surg Neurol Int 2016; 7 (Suppl. 23) S603-S606
• 3 Song L, Li Q, Yin R, Wang D. Choriocarcinoma with brain metastasis after term pregnancy: a case report. Medicine (Baltimore) 2018; 97 (42) e12904
• 4 Xiao C, Yang J, Zhao J. et al. Management and prognosis of patients with brain metastasis from gestational trophoblastic neoplasia: a 24-year experience in Peking Union Medical College Hospital. BMC Cancer 2015; 15 (01) 318
• 5 Soffietti R, Rudā R, Mutani R. Management of brain metastases. J Neurol 2002; 249 (10) 1357-1369
• 6 Lima LL, Parente RCM, Maestá I. et al. Clinical and radiological correlations in patients with gestational trophoblastic disease. Radiol Bras 2016; 49 (04) 241-250
• 7 Rodrigues AJ, Waldrop AR, Suharwardy S. et al. Management of brain tumors presenting in pregnancy: a case series and systematic review. Am J Obstet Gynecol MFM 2021; 3 (01) 100256
• 8 Tewari KS, Cappuccini F, Asrat T. et al. Obstetric emergencies precipitated by malignant brain tumors. Am J Obstet Gynecol 2000; 182 (05) 1215-1221
• 9 Chaudhary K, Mehra S, Saxena K, Wadhwa B, Sikri H. Emergency cesarean delivery in a parturient with intracranial tumor: anesthesiologist's challenge. MAMC J Med Sci 2018; 4 (03) 145
• 10 Soon B, Ismail F, Nik Ezzamudden M. et al. Experience of gamma knife radiosurgery for treatment of brain metastases in pregnancy with literature review. J Radiosurg SBRT 2024; 9 (02) 171-175
• 11 Stelzer KJ. Epidemiology and prognosis of brain metastases. Surg Neurol Int 2013; 4 (Suppl. 04) S192-S202
• 12 Altintaş A, Vardar MA. Central nervous system involvement in gestational trophoblastic neoplasia. Eur J Gynaecol Oncol 2001; 22 (02) 154-156

Publikationsverlauf

Artikel online veröffentlicht:
29. Mai 2025