On the Origin of Abdominal Venous Leiomyosarcomas: The Role of the Sex-Hormone Drainage Pathways

Abstract

Background: We hypothesized that abdominal venous leiomyosarcoma (AV-LMS) disproportionately originates in veins of the sex-hormone drainage pathway (SHDP). Our purpose was to classify the anatomical origin of AV-LMS in a large cohort using imaging and explore prognostic implications.

Methods: A retrospective review of imaging of all patients presenting with abdominal non-uterine LMS at a single tertiary oncology center was performed. Inclusion criteria were a biopsy-proven LMS of non-uterine abdominal/pelvic origin with pretreatment enhanced computed tomography (CT)/magnetic resonance imaging (MRI). Patients with uterine LMS or prior radiation were excluded. LMS site of origin was assigned by one expert radiologist and indeterminate sites were reviewed with a second external expert radiologist. Locations of inferior vena cava (IVC) tumors were subclassified based on a modification of prior literature. SHDP was defined as originating from ovarian/testicular vein, distal left renal vein, adrenal vein or mid-IVC (IIA).

Results: One hundred fifty-five (155) patients were included (92/152 (61%) female) with distant metastases found at presentation in 23/155 (14.8%). Most common organs of origins were veins (84/152, 55.3%), gastrointestinal (24, 15.8%), genital (11, 7.2%) and paratesticular/spermatic cord (11, 7.2%). For venous LMS, the adrenal (both sexes), mid-IVC (IVC IIA, females) and ovarian veins had the highest relative predilection for abdominal non-uterine LMS. Eighty-four (84/152, 55.3%) of tumors were SHDP. On multivariable analysis, both size and SHDP were significant predictors of distant metastases at presentation (P = 0.01), while sex, age, organ system/site and grade were not.

Conclusions: For both sexes, tumors arising from SHDP constitute the majority of AV-LMS and may impart a significantly lower risk of metastatic disease at presentation. Among veins, the adrenal veins had the highest predilection for LMS.

Keywords: Gonadal veins; Inferior vena cava; Leiomyosarcoma; Metastases; Ovarian vein; Pathogenesis sex-hormones; Pelvis; Retroperitoneum; Veins.

Figure 1

Illustration of designation of tumor origin in three different patients. (a) Left ovarian vein LMS. The left retroperitoneal tumor (asterisk) is located caudally to the left renal vein and laterally to the aorta. The left ovarian vein (arrow) extends into and from the tumor (not shown). (b) Right ovarian vein LMS. The right retroperitoneal tumor (asterisks) extends up the right ovarian vein (arrow) and into the IVC. (c) IVC IIA. The purely intravascular tumor (asterisks) lies within the right ovarian vein (arrow) and IVC, at and below the left renal vein. Because the tumor had a wider diameter in the IVC than in the ovarian vein, the former was designated as site of origin. IVC: inferior vena cava; LMS: leiomyosarcoma.

Figure 2

(a) IVC segments. The notation used is based on prior studies of IVC LMS with the following modifications: 1 - the cranial limit of IVC I was defined at the junction of the gonadal vein or either renal vein, whichever was more inferior; 2 - IVC II was divided into A and B segments with the hepatic margin as their boundary. (b) Sex-hormone drainage pathway (SHDP). The first and immediate second veins draining the hormone-producing organs were included as part of the drainage pathway. Anatomical annotations: I, IIA, IIB, III, IVC segments; 1 - common iliac vein, 2 - external iliac vein, 3 - right renal vein, 4 - medial left renal vein, 5 - lateral left renal vein, 6 - adrenal vein, 7 - ovarian vein. IVC: inferior vena cava; LMS: leiomyosarcoma.

Figure 3

Breakdown of derivation of the final population.

Figure 4

Normal anatomy (a: female; c: male) and proportional topographical (b: female; d: male) diagrams of selected retroperitoneal veins. The normal vessel lengths and diameter were drawn based on averages from 10 female/male patients in the study cohort. Proportional topographical diagrams are distortions of the anatomy normalized to one variable. For example, the cortical sensory homunculus is a proportional topographical diagram of the body distorted based on the size of the brain cortex supplying the various anatomical regions. These venous proportional topographical diagrams were obtained by altering the vessel diameter based on incidence per mm² and then normalized to IVC IIB segment. All altered vessels are therefore proportional to IVC IIB segment. Anatomical annotations: I, IIA, IIB, III, IVC segments; 1 - common iliac vein, 2 - external iliac vein, 3 - right renal vein, 4 - medial left renal vein, 5 - lateral left renal vein, 6 - adrenal vein, 7 - ovarian/testicular vein.