Primary IVC Leiomyosarcoma: A Case Series and Review of the Literature

Abstract

Leiomyosarcomas of the inferior vena cava (IVC) are the most common primary malignancy of the IVC; however, these lesions are extremely rare. These lesions are slow-growing, often asymptomatic and, present late in the disease course portending a poor prognosis. Surgical resection is considered the standard of care and only potential curative treatment. Progression free survival rates after surgical resection have been estimated to be 31.4% after five years and 7.4% after 10 years. To date, there have been a total of 418 cases documented within small and large single center institutional case series. Here, we present a case series from a single institution and a comprehensive literature review to investigate the presentation, treatment, and outcomes of this rare lesion. A surgically relevant designation of tumor location to include involvement of the renal veins is proposed.

Keywords

leiomyosarcoma inferior vena cava resection surgery clinical presentation primary venous malignancy

Introduction

Leiomyosarcomas of the inferior vena cava (IVC) are the most common primary malignancy of the IVC^1,2; however, these lesions are extremely rare^1,3-5 and account for around half of vascular leiomyosarcomas, which are 5% of all soft tissue leiomyosarcomas (15% of all soft tissue sarcomas).⁶ IVC leiomyosarcomas arise from endothelial smooth muscle cells of the intimal layer of the venous wall^4,7 and are slow-growing, often asymptomatic and, present late in the disease course^5,6,8-10 portending a poor prognosis.^1,3-5 If symptoms are noted, they are nonspecific, most often as flank pain or abdominal discomfort.² Treatment involves a multidisciplinary approach involving surgical and medical oncology, vascular surgery, and radiation oncology,⁵ with surgical resection being considered the standard of care and only potential curative treatment.^4,5,7 There are three main surgical techniques utilized, including IVC resection and ligation, IVC resection and grafting, and IVC partial resection and patch repair.^7,11 Progression free survival rates after surgical resection have been estimated to be 31.4% after five years and 7.4% after 10 years.^2,8 However, due to the rarity of these lesions, there are limited descriptions of clinical presentation and outcomes^4,5 making discrete prognosis unclear. To date, there have been a total of 418 cases documented within small and large single center institutional case series. Here, we present a case series from a single institution and a comprehensive literature review to investigate the presentation, treatment, and outcomes of this rare lesion and propose a standardized anatomic and surgical relevant based separation of lesions.

Case Series

Following IRB approval, a retrospective evaluation of all retroperitoneal IVC leiomyosarcomas diagnosed and/or treated at a single institution during the history of our institution was completed, with identified diagnoses ranging from 2008-2021. Overall, six patients were included in this review. The median age at diagnosis was 66.5 years (range 39-79); three patients were females and three were males (50%; Table 1). Four patients were black (66.67%) and two patients were white (33.33%). The mean BMI of the cohort was 24.81 (range 16.71-37.63); one patient was underweight (16.67%), three patients were normal weight (50%), one patient was overweight (16.67%), and one patient was obese (16.67%). Notable comorbidities were a history of smoking (33.33%), hypertension (66.67%), and hyperlipidemia (66.67%; Table 1).

Table 1.

Summary of the Demographics.

	n = 6
Age at Diagnosis
Median	66.5
Mean	62.67
Range	39-79
Sex
Female	3 (50%)
Males	3 (50%)
Race
Black	4 (66.67%)
White	2 (33.33%)
BMI
Mean	24.81
Range	16.71-37.63
Underweight	1 (16.67%)
Normal	3 (50%)
Overweight	1 (16.67%)
Obese	1 (16.67%)
Comorbidities
Smoking	2 (33.33%)
Hypertension	4 (66.67%)
Hyperlipidemia	4 (66.67%)
Atherosclerotic Heart disease	1 (16.67%)
Right Bundle Branch Block	1 (16.67%)
Diabetes mellitus	1 (16.67%)
Psychiatric	1 (16.67%)
Pulmonary Embolism	1 (16.67%)
IVC Thrombosis	1 (16.67%)
Hypothyroidism	1 (16.67%)
Gout	1 (16.67%)

All patients in our cohort were symptomatic: 33% reported abdominal fullness or bloating (n = 2), 50% had abdominal pain (n = 3), 66.67% noted flank or back pain (n = 4), 33.33% presented with lower extremity swelling (n = 2). Other symptoms noted were shortness of breath (16.67%), nausea (16.67%), and other nonspecific symptoms (33.33%). Past medical histories included abdominal surgery (50%; n = 3) and a previous malignancy (33.33%; n = 2). One previous malignancy was a leiomyosarcoma and one was breast cancer.

Symptoms warranted imaging; all patients had CT CAP which revealed extraluminal masses (Figure 1(A) and (B)). Histology from biopsy or resection revealed spindle cells arranged in fascicles, atypia, mitotic figures, and necrosis (Figure 2(A)–(C)). When staining was completed, vimentin, smooth muscle actin (SMA), and desmin were positive (Figure 2(B)). Negative stains included S100, CD117, Bcl2, CD34, and DOG1. Genetic testing on one sample noted with mutations in CBLC, TP53, EP300, FLT1, and PI3KR2; all abnormalities were associated with an aggressive neoplasm and/or poor prognosis.

Lymph nodes were resected in 33.33% of patients (n = 2); one incidental lymph node resected was positive for sarcoma by local extension, while one other patient had two retroperitoneal lymph nodes resected, both showing no sign of malignancy (data not shown).

The mean tumor size was 8.38 cm (range 3.6-14.5; Table 2) at its greatest diameter. Tumor location was documented in relation to renal veins: half of the tumors arose inferior to the renal veins (n = 3), half were at the level of the renal veins or directly involved the renal vein (n = 3). Of those three arising at the renal veins, 33.3% involved the right renal vein (n = 1), 33.3% involved the left renal vein (n = 1); one was nonspecified. Of those three arising inferior to the renal veins, one involved the IVC inferior to the right renal vein, one involved the IVC inferior to both the right and left renal veins, and one was nonspecified (data not shown). Three lesions were FNCLCC grade 3 (high-grade; 50%), and three were FNCLCC grade 2 (intermediate grade; 50%; Table 2).

Table 2.

Treatments and Outcomes.

Patient	Tumor Size (cm)	Tumor Location^a	FNCLCC Tumor Grade	Surgical Technique^b	Resection	Neoadjuvant/Adjuvant Chemo	Recurrence site	Time to Recurrence	OS
1	8.4	RV	3	PRP	R1	N	Liver	30 mo	Alive
2	3.6	RV	3	CRR	R1	Y^c	Liver, lung	26 mo^d	Alive
3	7	BRV	3	CRN	R1	N	Local	9 mo	12 mo
4	7.8	BRV	2	PRP	R1	N	none	-	24 mo
5	9	RV	2	CRN	R1	N	none	-	72 mo
6	14.5	BRV	2	PRP	R1	N	none	-	Alive

^aLocations include at the level of the renal veins (RV) or below the level of the renal veins (BRV); no tumors were located above the renal vein.

^bSurgical techniques included PRP = Partial resection with patch; CRR = complete resection with reconstruction; CRN = complete resection with no reconstruction; Various surgical techniques were employed based on location and size. The one complete resection with venous reconstruction used polytetrafluoroethylene tube grafting (PTFE). Two of the partial resections with patches used bovine pericardial patches, and one used a right gonadal vein patch angioplasty.

^cOne patient received neoadjuvant chemotherapy of gemcitabine and docetaxel before their resection. Following resection, this one patient was referred to radiation oncology and underwent external beam radiation therapy in adjuvant fashion and also had chemotherapy but did not do well on it and went on a 4 week treatment break due to Doxyrubicin side effects of fatigue, weight loss, skin rash, and red palms of the hand. A recurrence was then noted. The patient rebegan chemotherapy and has since transferred institutions.

^dRecurrences were synchronous.

Neoadjuvant therapy was received by only one patient; all patients underwent resection. Surgical techniques were noted (Table 2): complete resection with no reconstruction (33.3%; n = 2), complete resection with reconstruction (16.67%; n = 1), partial resections with patches (50%; n = 3). All resections were R1 (Table 2). Additional organ resection was required in 66.67% of cases (n = 4); no notable post-op complications or mortality occurred. After all surgeries, patients were placed on Lovenox or Eliquis for 30 days.

Post-operative treatment was received by one patient and included chemotherapy and radiation (Table 2). There were no cases of post-operative iliac vein or infra-inguinal acute venous thrombosis. Recurrences occurred in 50% of patients (n = 3; Table 2). The mean overall survival time for the entire cohort was 57.5 months post operation (range 12-179; data not shown); for those that succumbed to their disease, mean survival was 36 months (range 12-72; Table 2). To date, 50% of the cohort has survived the disease (mean survival 79 months; range 27-129).

Discussion

Primary leiomyosarcoma of the IVC is exceedingly rare, with our institutional case series among few ever recorded (Table 3). Our mean age is consistent with literature, being in the 5^th-6^th decade of life.^2,5,8 While most studies noted typically female cases,^{1,2,5,8,10,12} our cohort was 50% male, consistent with only one other published report⁷; the female predominance has been associated with hormonal influence on growth and proliferation.⁶ Only one other study noted race associations with IVC leiomyosarcomas: a predominance in white patients⁴; however, four out of the six patients in our cohort were black, contrasting to the demographic of our area.¹³

Table 3.

Comprehensive Case Series.

Institution	# Cases	Author	Year
International registry	218	Mingoli⁸	?-1996
Mayo Clinic	13	Dzsinich¹⁸	1957-1990
UCLA Medical Center	14	Hines⁹	1978-1997
University of Marseille Medical School	14	Hardwigsen¹⁹	1992-1998
Memorial Sloan Kettering	25	Hollenbeck¹¹	1982-2002
Pitié-Salpêtrière University Hospital	22	Kieffer²	1979-2004
Wake Forest University School of Medicine	8	Dew¹⁷	1984-2004
Brigham and Women’s Hospital/Dana-Farber Cancer Institute	20	Ito¹⁰	1990-2006
Armed Forces of Pathology	40	Laskin¹²	1976-2008
Hospital of the University of Pennsylvania	6	Wachtel⁷	2005-2013
Stanford Hospital	16	Zhou⁵	2002-2020
Northwestern Memorial Hospital	8	Joung⁴	2009-2020
University of New Mexico	3	Alkhalili²⁰	2012-2014
Clinical Center of Serbia	5	Lazar¹	2014-2021
Prisma Health Hospital	6	Bartholomew	2008-2021
Total # cases	418

Although IVC leiomyosarcomas could be asymptomatic and may be diagnosed incidentally,⁶ our patients all presented with some symptoms or discomfort. The most common clinical presentation reported involved flank pain or abdominal discomfort.^2,10,11 This is consistent with our findings, with four of the six patients having flank pain (66.67%) and three patients having abdominal discomfort (50%). Lower extremity edema was another symptom (33.33%), also reported.^2,10 These nonspecific symptoms in addition to the slow-growing tumor progression may result in a delay of diagnosis and subsequent treatment. Especially with the reported predominance of female cases, diagnostic delay could be exacerbated by the various differentials for abdominal complaints in women.⁶

Other institutions utilized both abdominal ultrasound and CT as first method of noninvasive imaging techniques²; however, CT has been reported to be as the method of choice since ultrasound is nonspecific.⁶ Imaging preference at our institution for all patients was CTs of the abdomen and chest. On radiologic examination, most IVC leiomyosarcomas are extraluminal.⁶ Interestingly, while all six of our patients demonstrated extraluminal tumors (Figure 1(A) and (B)), 33% also had lower extremity swelling, reported to be a hallmark of intraluminal tumors.² This could be accounted for due to size and duration of outer tumor compression into the luminal space. Published tumor sizes range in from 2-80 cm,⁶ with the mean tumor size of our cohort 8.38 cm in the greatest dimension (range 3.6-14.5), similar to other published data.¹²

Pathogenesis for this tumor can be challenging. Besides the characteristic spindle cell morphology, immunohistochemistry can be helpful for a definitive diagnosis when the morphology is uncertain; positive staining for desmin, α-SMA, and CD34 are diagnostically important.¹⁴

Little is understood about the etiology of vascular leiomyosarcomas, and the karyotyping is complex, with significant heterogeneity and multiple genes being implicated in its pathogenesis.⁶ However, anomalies in tP53 is reported to have been found in every case of IVC leiomyosarcoma,⁶ reinforcing tumor profiling from one patient which demonstrated TP53 mutations. Regardless, as clinical presentation and imaging are nonspecific, pathology remains the gold standard for diagnosis of leiomyosarcoma.⁶

Our patient cohort demonstrated IVC leiomyosarcomas evenly dispersed between below the renal veins (50%) and at the level of the renal veins (50%); no cases were above the renal veins. Other literature designates these regions as inferior, middle, and upper segments, roughly landmarked, respectively, by the common iliac veins to renal veins, renal veins to hepatic veins, and between hepatic vein and supradiaphragmatic IVC to the right atrium.⁴ This designation does not account for the surgical relevance of involvement of the renal veins. A surgically relevant diagram is proposed in Figure 3. Tumors located above the renal veins are more surgically complex to resect due to the vital blood supply to other organs. However, in relation to the established designation, our cohort follows the typical pattern of middle segment, next to inferior segment, with the upper segment being least common.^2,4,10

Controversy still exists regarding the optimal management of the IVC after tumor resection. Resection with ligation, patches, and IVC reconstruction have been utilized and it has been noted that vascular reconstruction is not always mandatory.¹⁴ The various surgical techniques utilized in our cohort depended on the location and size of each tumor. For exposure to the IVC, all surgeries mobilized the right colon medially and performed an extended Kocher to the ligament of Treitz.

While using a bovine patch with partial resection has been reported, for one patient in our group, a partial resection and vein patch angioplasty was completed with the right gonadal vein, as the vascular surgeon described the vein to be an ample size and viability for patch repair. To our knowledge, this has not been described before for this specific lesion and procedure. Interestingly, this patient has the longest overall survival of 176 months, almost 15 years, post initial surgical resection and patch repair. This outcome may warrant further investigation into the efficacy of this patch repair method and any correlation to long-term survival.

While reports have indicated achievement of an R0 resection,^7,12 all six of our patients had a R1 resection; however, only 50% had progression of disease with one local, one metastasis to the liver, and one to both the lung and liver. The surgical resection technique was different for each patient: a complete resection with ligation, a complete resection with venous reconstruction via PTFE and a partial resection with a bovine pericardial patch, respectively. Bovine patch and PTFE grafts are commonly used^4,7,10; Dacron graft,¹ reimplantation of renal vein into replacement grafts,¹⁰ saphenous vein patch,⁷ and aortic homograft⁷ have also been reported.

Non-surgical treatments for leiomyosarcomas have utilized neoadjuvant and adjuvant chemotherapy regimens^2,5; only one of our patients underwent neoadjuvant therapy prior to their resection (16.67%), similar to another report.⁴ This patient also underwent adjuvant chemotherapy, most likely due to the metastatic spread of their disease. Interestingly, as chemotherapy for IVC leiomyosarcomas is recommended, 83% of our cohort opted for no further treatment following resection. It must be noted, however, there was one patient with unclear history from other institutions that was prescribed a chemotherapy regimen, but refused treatment until appearing at our institution several years later, at which point a plan for resection was initiated.

For IVC leiomyosarcomas, no standard overall survival rate is reported. Literature historically compares to the 1996 international registry demonstrating malignancy-free survival rates after surgical resection to be 31.4% after five years and 7.4% after 10 years.^2,15 Other studies describe five year survival rates ranging from 31 to 62%.^16,17 For those that succumbed to the disease, our survival rates compare to the literature, with five year survival of 33.33% (n = 2) and 10 year survival of 16.67% (n = 1). Interestingly, as of this report, three patients are still alive. The survival of our patients with IVC leiomyosarcoma is evidence of a well-coordinated treatment approach. However, other means to promote longer term survival have yet to be developed.

Conclusion

Primary IVC leiomyosarcomas are rare and, while long-term survival is possible, prognosis is poor. Symptoms are nonspecific and patients often present late in disease course. Although vascular tumors prove to be surgically difficult and complex, radical resection is still the standard of care. Various surgical techniques can be employed based on sarcoma location, size, and complexity, and for surgical resection relevance, categorizing IVC leiomyosarcomas based on location relative to renal veins rather than previously demarcated segments has been proposed. Earlier diagnosis is essential; however currently symptoms and imaging are the primary means of identification. Outcomes may be improved by tumor genetic analyses and the identification of targetable mutations for adjunct therapy. Overall, successful patient care contains a collaborative effort consisting of listening to patient complaints, performing early CT CAP for nonspecific symptoms, having skilled oncologic and vascular surgeons, and maintaining appropriate follow-up to detect potential recurrence early.^21-25

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical Statement

ORCID iD

Christine M. G. Schammel

Data availability statement

Data will be available upon reasonable request*.

References

Lazar

Stefan

Marko

, et al. Case series of the inferior vena cava primary leiomyosarcoma treatment. J Surg Case Rep. 2024;2024(6):rjad546. doi:10.1093/jscr/rjad546

Kieffer

Alaoui

Piette

Cacoub

Chiche

. Leiomyosarcoma of the inferior vena cava: experience in 22 cases. Ann Surg. 2006;244(2):289-295. doi:10.1097/01.sla.0000229964.71743.db

Fujita

Takahashi

Kanzaki

, et al. Primary leiomyosarcoma in the inferior vena cava extended to the right atrium: a case report and review of the literature. Case Rep Oncol. 2016;9(3):599-609. Erratum in: Case Rep Oncol. 2017 Feb 2;10(1):153. doi. 10.1159/000455977. doi:10.1159/000450598

Joung

Nooromid

Eskandari

Wayne

. Surgical approach, management, and oncologic outcomes of primary leiomyosarcoma of the inferior vena cava: an institutional case series. J Surg Oncol. 2020;122(7):1348-1355. doi:10.1002/jso.26163

Zhou

Javadi

Charville

, et al. Surgical resection of leiomyosarcoma of the inferior vena cava: a case series and literature review. Surg Oncol. 2021;39:101670. doi:10.1016/j.suronc.2021.101670

Gama

Almeida

Oliveira

Casanova

. When Vessels and sarcomas Combine: a review of the inferior vena cava leiomyosarcoma. J Vasc Dis. 2024;3:34-48.

Wachtel

Jackson

Bartlett

, et al. Resection of primary leiomyosarcoma of the inferior vena cava (IVC) with reconstruction: a case series and review of the literature. J Surg Oncol. 2015;111(3):328-333. doi:10.1002/jso.23798

Mingoli

Cavallaro

Sapienza

Di Marzo

Feldhaus

Cavallari

. International registry of inferior vena cava leiomyosarcoma: analysis of a world series on 218 patients. Anticancer Res. 1996;16(5B):3201-3205.

Hines

Nelson

Quinones-Baldrich

Eilber

. Leiomyosarcoma of the inferior vena cava: prognosis and comparison with leiomyosarcoma of other anatomic sites. Cancer. 1999;85(5):1077-1083.

10.

Ito

Hornick

Bertagnolli

, et al. Leiomyosarcoma of the inferior vena cava: survival after aggressive management. Ann Surg Oncol. 2007;14(12):3534-3541. doi:10.1245/s10434-007-9552-z

11.

Hollenbeck

Grobmyer

Kent

Brennan

. Surgical treatment and outcomes of patients with primary inferior vena cava leiomyosarcoma. J Am Coll Surg. 2003;197(4):575-579. doi:10.1016/S1072-7515(03)00433-2

12.

Laskin

Fanburg-Smith

Burke

Kraszewska

Fetsch

Miettinen

. Leiomyosarcoma of the inferior vena cava: clinicopathologic study of 40 cases. Am J Surg Pathol. 2010;34(6):873-881. doi:10.1097/PAS.0b013e3181ddf569

13.

www.census.gov/quickfacts/fact/table/greenvillecitysouthcarolina/PST045223; accessed 4/7/25

14.

Rusu

Gorbatâi

Szatmari

, et al. Leiomyosarcoma of the inferior vena cava. Our experience and a review of the literature. Rom J Morphol Embryol. 2020;61(1):227-233. doi:10.47162/RJME.61.1.25

15.

Mingoli

Feldhaus

Cavallaro

Stipa

. Leiomyosarcoma of the inferior vena cava: analysis and search of world literature on 141 patients and report of three new cases. J Vasc Surg. 1991;14(5):688-699. doi:10.1067/mva.1991.30426

16.

Roland

Boland

Demicco

, et al. Clinical observations and molecular variables of primary vascular leiomyosarcoma. JAMA Surg. 2016;151(4):347-354. doi:10.1001/jamasurg.2015.4205

17.

Dew

Hansen

Hammon

McCoy

Levine

Shen

. Leiomyosarcoma of the inferior vena cava: surgical management and clinical results. Am Surg. 2005;71(6):497-501. doi:10.1177/000313480507100609

18.

Dzsinich

Gloviczki

van Heerden

, et al. Primary venous leiomyosarcoma: a rare but lethal disease. J Vasc Surg. 1992;15(4):595-603.

19.

Hardwigsen

Baqué

Crespy

Moutardier

Delpero

Le Treut

. Resection of the inferior vena cava for neoplasms with or without prosthetic replacement: a 14-patient series. Ann Surg. 2001;233(2):242-249. doi:10.1097/00000658-200102000-00014

20.

Alkhalili

Greenbaum

Langsfeld

, et al. Leiomyosarcoma of the inferior vena cava: a case series and review of the literature. Ann Vasc Surg. 2016;33:245-251. doi:10.1016/j.avsg.2015.10.016

21.

Guo

Meng

. A world-wide systematic review of the primary leiomyosarcoma of inferior vena cava. Asian J Surg. 2023;46(12):5983-5984. 1015-9584. doi:10.1016/j.asjsur.2023.09.018

22.

Wang

Menias

Elsherif

Segaran

Ganeshan

. Current update on IVC leiomyosarcoma. Abdom Radiol (NY). 2021;46(11):5284-5296. doi:10.1007/s00261-021-03256-9

23.

De Luca

Gurrado

Marzullo

, et al. Fainting as an unusual presentation of a large inferior vena cava leiomyosarcoma. Phlebology. 2015;30(7):492-495. doi:10.1177/0268355514535928

24.

Ben

Yakoubi

Kacem

Sebai

Daghfous

Kacem

. Inferior vena cava resection for a leiomyosarcoma: a case report. Int J Surg Case Rep. 2023;106:108304. doi:10.1016/j.ijscr.2023.108304

25.

Mandava

Koppula

Kandati

Reddy

Abubacker

. Primary leiomyosarcoma of Suprahepatic inferior vena cava with Metastases. Indian J Nucl Med. 2024;39(1):63-65. doi:10.4103/ijnm.ijnm_130_23