Clinical presentation of brain metastases from endometrial carcinoma: A case series

Abstract

Brain metastases from endometrial carcinoma are rare, however they do occur, and they are associated with an especially poor prognosis. There is evidence demonstrating improved outcomes with early diagnosis and subsequent multimodal treatment. This study therefore aims to review cases of brain metastases from endometrial carcinoma with specific focus on clinical presentation and disease history. This retrospective case series evaluated all cases of brain metastases from endometrial carcinoma at a single institution over a seven-year period. A medical records search was performed using ICD codes for endometrial cancer, brain lesions and brain imaging. Analysis of patient and disease characteristics was performed with descriptive statistics. Twelve cases were identified. The majority of cases had intermediate or high-grade histology (97.7%), advanced stage disease (58.3%), and at least one prior disease recurrence (66.7%). Eleven of 12 cases (91.7%) had lung metastases diagnosed prior to brain metastases. All 12 cases had neurologic signs and symptoms present at time of brain metastases diagnosis; 14 different types of neurologic deficits were noted. Headache was the most common neurologic symptom (5/12, 41.7%), followed by focal weakness (3/12, 25.0%) and aphasia (3/12, 25.0%). In conclusion, clinical presentation at time of diagnosis of brain metastases consistently includes neurologic signs and symptoms with persistent headache being the most common. Endometrial cancer patients that present with new neurologic complaints or exam findings should be evaluated for brain metastases.

Clinical characteristics of CNS metastases from primary gynecologic cancers

“…A total of 22 patients in our cohort had endometrial primaries with only 4 patients (17%) displaying the usual grade 1 or 2 endometrioid histologies. The disproportionately high percentage of type II endometrial cancers in the population with brain metastasis (83% in this cohort vs 20–30% in general population) is not unexpected due to the known aggressiveness of these histologies, and is consistent with existing literature (Moroney et al, 2019, Uccella et al, 2016). Furthermore, on a molecular level, there are marked differences in surface protein expression, such as mutation load of cadherin proteins, which increases the risk of intercellular cohesion loss and potentially downstream hematogenous spread (Liu, 2007).…”

“…Several mechanisms of spread have been postulated regarding CNS and brain metastases, including direct hematogenous seeding, retrograde lymphatic spread, and direct invasion secondary to bony involvement (Kumar et al, 2003). Neoplasms of gynecologic origin rarely involve the CNS as most tumors spread or recur via direct extension, transcoelomic dissemination, or by locoregional lymphatic channels, with incidence rates reported at 0.5–1% for uterine, ovarian, and cervical cancers (Ratner et al, 2019, Moroney et al, 2019, Kim et al, 2018). Typically, gynecologic cancers exhibiting hematogenous spread are associated with advanced stage or widely disseminated disease, particularly to the lungs.…”

Brain Metastases from Uterine Cervical and Endometrial Cancer

“…Approximately 70% of the patients who developed BMs from EC had advanced-stage disease (stage III, 37.2% and stage IV, 31.2%) at the time of diagnosis. The histologic type was available in 391 patients [ 6 , 28 , 31 , 37 , 53 , 59 , 62 , 66 , 67 , 74 , 75 , 81 , 87 , 88 , 90 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 106 , 107 , 108 , 109 , 110 , 112 , 113 , 114 , 115 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 131 ], of whom 319 (81.5%) had adenocarcinomas and 74 (18.9%) had unfavorable cancer types, such as carcinosarcoma, leiomyosarcoma, small-cell carcinoma, and undifferentiated carcinoma. BM was...…”

“…BM was more likely to occur in patients with carcinosarcoma and undifferentiated histological type than in the general population of patients with primary endometrial lesion [ 6 ]. Among the 192 patients for whom the histological grade was known, 74.5% had high-grade (Grade 3) disease [ 6 , 20 , 31 , 37 , 81 , 90 , 93 , 94 , 95 , 96 , 98 , 100 , 101 , 102 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 112 , 113 , 114 , 117 , 118 , 121 , 122 , 123 , 124 , 125 , 126 , 128 , 131 ], including 27 cases of serous adenocarcinoma and 5 cases of clear cell adenocarcinoma.…”

“…Around 2010, a substantial decrease in the number of patients with a single BM was observed (68.0% vs. 42.1%), and this was observed for other solid tumors, as described earlier in the CC section. Data on the site of BMs, that is, whether the metastasis was supratentorial (cerebrum) or infratentorial (cerebellum) or both, were available for 195 patients [ 20 , 28 , 31 , 49 , 55 , 72 , 75 , 87 , 88 , 90 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 112 , 113 , 114 , 117 , 118 , 119 , 120 , 121 , 122 , 124 , 125 , 126 , 127 , 128 , 131 ]. Most of the BMs were located in the supratentorial region (cerebrum; 143/195 (73.3%) patients); in 50/195 (25.6%) and 12/195 (6.2%) patients, the BMs were in the infratentorial region (cerebellum) and in both sites, respectively.…”