High-grade endometrial cancer presents with malignancy-associated disseminated intravascular coagulation: A case report

Highlights

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Abstract

Malignancy-associated DIC is uncommon and when it does occur, is often associated with hematologic malignancies rather than solid tumors. In this case, we describe an unusual case when a patient with advanced stage high-grade endometrial adenocarcinoma presented to care with vision loss and deep vein thrombosis, found to be in disseminated intravascular coagulation (DIC). The patient suffered many complications from her DIC, which was briefly managed with systemic therapy for her underlying malignancy but ultimately led to her death. DIC has been reported in the literature rarely for gynecologic malignancies, and never as presenting symptom for high-grade endometrial adenocarcinoma.

1. Introduction

Endometrial adenocarcinoma is rising in incidence with an estimated 67,880 new cases diagnosed in 2024 (Siegel et al., 2024). It is also the deadliest gynecologic malignancy, with an estimated 13,250 deaths in the United States this year and is the only gynecologic cancer where survival is decreasing (Siegel et al., 2024). High-grade endometrial adenocarcinoma often presents at an advanced stage compared to the more common, low-grade endometrioid endometrial cancer (Hamilton et al., 2021).

Disseminated intravascular coagulation (DIC) is defined as a hypercoagulable state due to systemic intravascular coagulation activation with simultaneous consumption of coagulation proteins. This state results in both deposition of intravascular platelets and fibrin with clot formation, while also causing bleeding due to consumption of these factors (Levi, 2019). Medical comorbidities that cause an inflammatory response and the release of coagulative factors can lead to DIC. DIC can be acute, associated with sudden illness such as sepsis or trauma, but may also be chronic and present in patients with malignancy (Sack et al., 1977, Siegal et al., 1978, Levi and Ten Cate, 1999).

The estimated incidence of DIC in solid tumors has been reported at 7 % but may approach 15 % in hematologic malignancies (Levi, 2019). Pancreatic, lung, prostate, and breast cancer were among the most common reported cases of DIC in solid tumors, while adenocarcinoma was the most common histology (Sack et al., 1977, Sallah et al., 2001 Sep). In this report, we present a rare case of DIC as a presenting symptom of high-grade endometrial adenocarcinoma. To our knowledge, this is the first such reported case in the literature.

2. Case report

This is a retrospective review of a patient with endometrial adenocarcinoma and malignancy-associated disseminated intravascular coagulation (DIC) treated at our institution. Relevant information from the case was obtained through the electronic medical record.

The patient was a 79-year-old female with post-menopausal bleeding and past medical history of polymyalgia rheumatica on steroids, Meniere’s disease, migraines, hyperlipidemia, and osteopenia, who presented to her rheumatologist with amaurosis fugax and concerns for giant cell arteritis. During this visit, she also reported left lower extremity edema concerning for deep vein thrombosis (DVT). The patient subsequently presented to the emergency department (ED) with lightheadedness after her lower extremity ultrasound confirmed a diagnosis of DVT. In the ED, she was found to have a segmental pulmonary embolus (PE). However, after being started on a heparin drip, she complained of right flank pain and was noted to have right flank ecchymosis. Anticoagulation was held, and flank CT showed right perirenal, retroperitoneal and intraperitoneal hemorrhage as well as distended endometrial canal and lymphadenopathy, concerning for malignancy. The patient then became hypotensive and was transferred to the intensive care unit (ICU) where she was resuscitated with massive transfusion protocol, given protamine, and stress-dose steroids. There was no active extravasation under fluoroscopy in interventional radiology to identify a source of bleeding at that time, but an IVC filter was placed. She remained stable following this and was discharged four days later without anticoagulation due to concern for bleeding. Inpatient gynecology consultants collected a Pap smear, but bedside endometrial biopsy (EMB) was unsuccessful given cervical stenosis.

The patient re-presented to the ED five days later with weakness, word-finding difficulty, and falls at home. She was found to have hemorrhagic shock secondary to DIC with bleeding into her right gluteus, as well as cerebral, splenic, and renal infarcts with a perinephric hematoma. She was resuscitated with close monitoring of D-dimer, fibrinogen, complete blood count, and INR, and Hematology was consulted. Her acute-on-chronic DIC was attributed to her possible underlying malignancy and hematologic workup for hypercoagulability or bleeding disorders was otherwise negative. After 5 days without further bleeding, the patient was started on a low-dose heparin drip. An enlarged left pelvic lymph node was biopsied by interventional radiology while the patient remained in the hospital for DIC management. Her pathology showed high-grade endometrial carcinoma with imaging consistent with at least 2009 stage IIIC1. CA 125 was elevated to 223. Gynecologic Oncology was consulted. While admitted, transition to prophylactic dosing of apixaban was attempted, but worsening of DIC was noted with increasing needs for cryoprecipitate and platelet transfusions. Therefore, she was transitioned back to a heparin drip. There was a similar response with worsening of DIC with attempted transition to prophylactic enoxaparin and thus was again placed back on heparin drip.

Given that the underlying cause of her DIC was attributed to her malignancy, decision was made to start treatment while inpatient with IV carboplatin AUC 5 and weekly paclitaxel at 60 mg/m2. Over time, the patient was uptitrated on her heparin drip to full therapeutic anticoagulation. The patient was then transitioned to therapeutic enoxaparin and found stable for discharge on hospital day 25. She was transitioned to q 3-week paclitaxel 135 mg/m2 with carboplatin AUC 5 for cycle 2 and received a total of 6 cycles with disease improvement noted on CT imaging after cycle 3 and again after cycle 6. Notably, the patient did not have further dose reductions or treatment delays. At completion of chemotherapy, the patient had no measurable disease. Discussion was had with the patient regarding next steps after her chemotherapy including offering radiation or surveillance. Surgery was not recommended due to medical comorbidities, persistent thrombus burden with associated surgical risks, and overall performance status (ECOG 1). The patient and her family opted for disease surveillance.

The patient required admission during her cancer treatment for COVID-19 pneumonia and Clostridium perfringens bacteremia, which was treated with dexamethasone and Remdesivir, and Ampicillin/Sulbactam, respectively. During this admission she was treated with therapeutic apixaban.

Three months after her admission for COVID and 19 months after initial presentation in DIC, she presented with a right multifocal middle cerebral artery (MCA) ischemic stroke, DIC, and was transitioned inpatient to a therapeutic heparin drip. During this admission, the patient had an acute change in mental status, likely secondary to hemorrhagic transformation of her ischemic stroke. Given her goals, she was transitioned to comfort care and died three days after admission.

3. Discussion

Although case reports of ovarian cancer and DIC have been reported, cases of high-grade endometrial cancer presenting with DIC have yet to be reported (Sack et al., 1977, Sallah et al., 2001 Sep). The underlying pathophysiology of malignancy-induced DIC is not fully understood but may be attributed to expression of tissue factor by tumor cells which binds with Factor VIIa to activate the coagulation cascade. Alternative hypotheses suggest the release of pro-inflammatory cytokines trigger DIC or that cancer cells cause underlying endothelial dysfunction (Levi, 2019). For mucin-producing malignancies, it is thought that mucin interacts with P-selectin and L-selectin, leading to aggregation of platelets and coagulation (Wahrenbrock et al., 2003).

The treatment of DIC is primarily supportive care and aimed at addressing the underlying cause (Sohal et al., 2020, Feinstein, 2015). Given the underlying cause in this case was the patient’s high-grade endometrial adenocarcinoma, the patient was started on systemic treatment with carboplatin and paclitaxel. The patient did require dose-reduction of carboplatin and paclitaxel based on her age and comorbidities but was able to tolerate 6 cycles of treatment with complete response on CT imaging. Although not required in our case, in case reports of DIC and lung cancer, patients have been treated with Erlotinib or Amivantamab when thrombocytopenia limited the ability to receive chemotherapy (Ahmad and Tanvetyanon, 2023, Kim et al., 2018). Anti-neoplastics with less bone-marrow suppression may be required in other situations of malignancy-associated DIC.

Unfortunately, our patient did ultimately die from complications of her DIC. In a review, thrombotic microangiopathic complications may lead to mortality rates as high as 20–30 % (Levi, 2019). The early identification and treatment of DIC and the underlying malignancy may help to reduce morbidity and mortality. Furthermore, clinicians should consider malignancy as a cause for DIC in patients without other underlying etiologies. In summation, we describe a case of DIC as the presenting symptom of advanced high-grade endometrial cancer.

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

CRediT authorship contribution statement

Jennifer Hansen: Writing – review & editing, Writing – original draft, Investigation, Conceptualization. Andreea Dinicu: Writing – review & editing, Writing – original draft, Investigation, Conceptualization. Johanna Kelley: Writing – review & editing, Writing – original draft, Investigation, Conceptualization. Lindsey Beffa: Writing – review & editing, Writing – original draft, Supervision, Investigation, Conceptualization.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.