Diana Žilovič1,2,3, Dovilė Čerkauskaitė 4, Kotryna Kvitkovskaja4, Rūta Čiurlienė3
1 Institute of Biosciences, Life Sciences Center, Vilnius University, Saulėtekio Avenue 7, LT-10222 Vilnius, Lithuania;
2 Laboratory of Clinical Oncology, National Cancer Institute, Santariškių 1, LT-08406 Vilnius Lithuania;
3 Oncogynecology Department, National Cancer Institute, Santariškių 1, LT-08406 Vilnius Lithuania;
4 Lithuanian University of Health Sciences, Faculty of Medicine, Vilnius Lithuania;
Abstract
Uterine leiomyoma is a very frequent pathology, which affects up to 30% of female population over the age of 35. Although leiomyomas are benign tumors there are some unusual locations and growth patterns of how they can develop and progress. Intravenous leiomyomatosis is one of the extra uterine types of leiomyoma, which is described as intralumenal growth of smooth muscle into either venous or lymphatic vessels outside the limits of myoma. Intravenous leiomyomatosis is a rare benign tumor, but despite its benign histological features, invasion of large vessels and cardiac extension can occur and be fatal (1-3). We present a case of 46-year-old woman who was histologically diagnosed with uterine leiomyoma after vaginal hysterectomy. The aim of the study is to investigate all possible treatments of the intravenous leiomyomatosis and determine the further follow-up
Keywords: intravenous leiomyomatosis, uterine leimyoma.
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Medical Sciences 2021 Vol. 9 (1), p. 226-230
Intravenous leiomyomatosis. Case report
Diana Žilovič
1,2,3
, Dovilė Čerkauskaitė
4
, Kotryna Kvitkovskaja
4
, Rūta Čiurlienė
3
.
1
Institute of Biosciences, Life Sciences Center, Vilnius University, Saulėtekio Avenue 7, LT-10222 Vilnius,
Lithuania;
2
Laboratory of Clinical Oncology, National Cancer Institute, Santariškių 1, LT-08406 Vilnius Lithuania;
3
Oncogynecology Department, National Cancer Institute, Santariškių 1, LT-08406 Vilnius Lithuania;
4
Lithuanian University of Health Sciences, Faculty of Medicine, Vilnius Lithuania;
Abstract
Uterine leiomyoma is a very frequent pathology, which affects up to 30% of female population over the age of
35. Although leiomyomas are benign tumors there are some unusual locations and growth patterns of how they
can develop and progress. Intravenous leiomyomatosis is one of the extra uterine types of leiomyoma, which is
described as intralumenal growth of smooth muscle into either venous or lymphatic vessels outside the limits of
myoma. Intravenous leiomyomatosis is a rare benign tumor, but despite its benign histological features, invasion
of large vessels and cardiac extension can occur and be fatal (1-3). We present a case of 46-year-old woman
who was histologically diagnosed with uterine leiomyoma after vaginal hysterectomy. The aim of the study is to
investigate all possible treatments of the intravenous leiomyomatosis and determine the further follow-up.
Keywords: intravenous leiomyomatosis, uterine leimyoma.
Journal of Medical Sciences. Jan 30, 2021 - Volume 9 | Issue 1. Electronic - ISSN: 2345-0592
227
Introduction
Uterine leiomyomas is a very frequent pathology,
which affects 20% to 30% of female population over
the age of 35. Leiomyomas are benign tumors and
mainly located in the uterus, but there are some
unusual locations and growth patterns of how they can
develop and progress (1-3). Group of extra uterine
types of leiomyoma consists of: benign metastasizing
leiomyoma, disseminated peritoneal leiomyomatosis,
parasite leiomyoma (located in the broad
ligament/retroperitoneal space) and intravenous
leiomyomatosis. Intravenous leiomyomatosis (IVL) is
described as a smooth muscle cell tumor that grows
within the venous channels without invading them.
The etiology of IVL revolves around two major
hypotheses: first one suggesting that tumor arises from
the uterine vein walls, while the second proposes that
the uterine leiomyoma is a primary tumor with
intravascular projections into an adjacent venous
channel (4-7). IVL was first described by Birch-
Hirschfeld in 1896 in an then in 1907 Dursk et al.
described the first case of IVL with intra-cardiac
extension (8). Although it is a very rare condition with
less than 300 case reports in English literature, it can
be easily overlooked due to the risk of sudden death
caused by total outflow tract obstruction (8, 9).
Case presentation
A 46-year-old woman presented with heavy and
irregular bleeding from the uterus lasting for around 12
months. She was previously treated with hormonal
intrauterine device (IUD) although no effect was
achieved. On further evaluation, pelvic ultrasound was
performed and showed myoma on the posterior wall of
the uterus, about 4 cm. ( Described as type 3 according
to the International Federation of Gynecology and
Obstetrics classification )(10). Transvaginal
hysterectomy without salpingo-oophorectomy was
performed. Upon revision, smooth, 6 week-sized-
uterus was found and 4,0 cm 3
rd
type myoma on
posterior wall was seen, adnexal masses were intact.
Patient was referred to National Cancer Institute of
Vilnius for further evaluation and treatment, as
histological findings showed leiomyoma, most likely
sarcoma. Thoracic, abdominal and pelvic computed
tomography (CT) was performed and showed no signs
of metastases. Histological specimens were re-
examined and conclusion of histology and
immunohistochemical staining was IVL. Mitotic
activity was low (3/10 high-power fields).
Immunohistochemical staining showed that 100% of
the cells had positive (+++) desmin (DES) cytoplasmic
reaction, 80% of the cells had positive (+++) smooth
muscle actin (SMA) reaction, >95% of the cells
expressed positive (++/+++) estrogen receptors, 100%
of the cells expressed positive (+++) progesterone
receptors. CD10 receptors were negative (-),
MYOD1/MYOG receptors were negative (-), there was
positive (+++) D240 endothelial cytoplasmic reaction,
positive (+++) CD34 endothelial cytoplasmic reaction,
KI67 proliferative activity <3%. As the tumor is
hormone-dependent, medical multidisciplinary team
agreed on necessity of bilateral salpingo-
oophorectomy, however - patient refused any further
surgical treatment. Hormonal therapy with
gonadotropin-releasing hormone agonists (GnRH
agonists) and follow up after 3 months was
recommended.
Discussion
The clinical presentation IVL usually depends on the
extension and size of the tumor. Usually, it affects
premenopausal women, they may experience pelvic,
abdominal or cardiac symptoms (9-10). Various non-
specific symptoms including dyspnea, edema of lower
extremities, palpitation, fatigue and ascites can appear
(9-11). Chest tightness and palpitation were considered
to be results of impaired heart pumping function
caused by tumor obstacles in the heart chambers.
Lower extremities swelling was related to tumor-
induced blood reflux occlusion in the inferior vena
cava. Other rare manifestations of IVL with inferior
vena cava extension (IVCE) or intracardiac extension
(ICE) include stroke, pulmonary embolism, heart
failure, and Budd-Chiari syndrome (12,13). Serious
complications, like syncopal episodes, cardiogenic
shock or even sudden cardiac death, have also been
reported. In some cases IVL can be asymptomatic and
usually first symptoms can be associated with uterine
myomas, which include abnormal uterine bleeding and
lower abdominal tenderness (9-11).
When to suspect?
Early diagnosis of IVL is very difficult, as patients
may have only symptoms of fibroids or even be
asymptomatic, despite extensive intravenous
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228
extension. The presence of tumor extension within the
venous system would be difficult to define
intraoperatively, unless the patient has undergone some
pre-operative imaging. Patients who have large fibroid
with unusual features or extensions into the pelvic side
walls should be under close supervision. The condition
should also be suspected if there are other cardiac or
venous compression symptoms. In our case, diagnosis
was not suspected preoperatively and confirmed only
on histological examination of the uterus. IVL can be
suspected during surgery, when fibroids seem to
extend beyond the uterus into the broad ligaments or
show extensions into vascular systems.
To reduce the chance of missed diagnosis of IVL,
women between 40 and 60 years old, with a history of
hysterectomy due to fibroids with symptoms of chest
tightness, hernia, and lower extremity edema have to
be examined (4, 5). Examinations for such patients
include CT or MRI, echocardiography, and if
necessary, CT pulmonary angiography, PET/CT, or
PET/MRI (14,15). Echocardiography can be used to
identify atrial occupancy and mobility (floating or
adhesion), assess the size of the cardiac chambers and
function of the tricuspid valve and overall heart, and
provide a diagnosis (14). Echocardiography usually
reveals a right atrial mass with caval involvement, and
an intravascular and intra-atrial mass not attached to
the endothelial surface of endocardium, but instead
freely mobile within the IVC and right-sided cardiac
chambers. These masses are typically long and
serpentine, and they can resemble “walking-stick
heads” or “snakeheads”(11).
Staging.
IVL is categorized into 4 stages reflecting tumor
progression before the surgery:
• Stage I: tumor penetrates the uterine venous wall, but
is confined to the pelvic cavity.
• Stage II- tumors extends into the abdominal cavity, but
does not reach renal vein.
• Stage III- tumor reaches renal vein and IVC, and
extends into right atrium but does not reach pulmonary
arteries.
• Stage IV- tumor reaches pulmonary arteries and/or
lung metastases are observed (5).
Treatment
Radical surgical approach remains „the gold standard“
and includes complete tumor excision, total
hysterectomy and bilateral salpingo-oophorectomy
with total resection of the IVL extensions, when it is
technically feasible (16-18). Radical parametrectomy
and intravenous tumor resection may be necessary (3).
To prevent tumor migration ligation of the ovarian
arteries and veins at high position is recommended. For
patient in whom the tumor cannot be removed
completely, ligation of the proximal vascular end of
the tumor is recommended to prevent tumor thrombus
entering the inferior vena cava (14). To achieve a
successful operation for complex IVL cases, a
multidisciplinary team meeting with gynecologist,
oncologist, anesthesiologist, general surgeon, vascular
surgeon and cardiothoracic surgeon is mandatory for
optimal surgical planning. Steps taken should depend
on a patient’s symptoms, previous operative history, as
well as the tumor’s extension (6). If the patient is
ineligible for one stage surgery because of poor
clinical condition, due to cardiac and pulmonary
comorbidities, a two-stage operation may be favorable
(6).
Given the fact that estrogen and progesterone receptors
are present in myoma and its intravenous extension,
bilateral salpingo-oophorectomy is essential and
exogenous estrogens must be avoided to prevent
subsequent growth of microscopic or unresected foci
of IVL (3). Tamoxifen, gonadotropin-releasing
hormone agonists, medroxyprogesterone and other
drugs are used postoperatively due to their
antiestrogenic effects to control possible residual
tumors or preoperatively, to inhibit tumor growth and
reduce tumor volume (14,16). Hormone therapy may
also be used for poor surgical candidates. Individuals
who refuse surgery or for non-castration cases (3,11).
Ma et al. showed outcomes of patients treated
surgically for IVL. Recurrence was reported in only 4
of 76 cases of IVL, all of whom opted for total surgery.
Removal of both ovaries is necessary for inhibiting
tumor growth and avoiding recurrence (3,17).
Literature review showed that complete tumor excision
with total hysterectomy and bilateral salpingo-
oophorectomy had lower recurrence rates (7,6%)
compared to patients treated with preservation of
adnexes (25%) and patients treated with simple
myomectomy (75%) (3,5,6).
Monitoring and follow up
The true recurrence of completely resected
leiomyomatosis is unknown, but regrowth of the tumor
has been documented in up to 30% of patients, from 7
months to 15 years after primary surgery (3). Therefore
due to late, but serious clinical manifestation, long
term monitoring after hysterectomy is recommended
(16). Predisposing factor of recurrence may be young
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age, size of the initial tumor and multiparity. Post-
surgery, patients need to be followed up every 6
months. At each follow up appointment, chest and
abdominal CT scan or MRI with MRI venography,
pelvic ultrasound and echocardiography is necessary
(5).
Conclusions: IVL is rare, benign disease with a
spectrum of clinical presentations, which imitates
malignant tumors regarding its patterns of growth and
extension. Also, IVL has a tendency for recurrence,
especially when complete resection of the tumor is not
performed. Radical surgery is main treatment, which
can be combined with neoadjuvant hormonal therapy
to counter estrogenic stimulatory effects. Long-term
follow-up of patients is recommended.
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