Case Report
Long-Term Survival of a Patient with Uterine Leiomyosarcoma Treated With Repeated Metastasectomies: A Case Report
Attila Zaránd1*, Valéria Jósa2, Tamás Vass1 and Zsolt Baranyai1
11st Clinic of Surgery, Semmelweis University, Budapest, Hungary
2‘Flór Ferenc’ Hospital, Kistarcsa, Hungary
*Corresponding author: Attila Zaránd, 1st Clinic of Surgery, Semmelweis University, Üllői út 78, H-1082 Budapest, Hungary
Published: 30 Nov, 2016
Cite this article as: Zaránd A, Jósa V, Vass T, Baranyai Z.
Long-Term Survival of a Patient with
Uterine Leiomyosarcoma Treated With
Repeated Metastasectomies: A Case
Report. Ann Clin Case Rep. 2016; 1:
1193.
Abstract
Uterine leiomyosarcomas are uncommon malignancies characterized by early recurrence and
metastasis. The authors report the case of a female patient, who has undergone total extirpation of
the uterus for leiomyosarcoma, followed by further ten metastasectomies performed in two body
cavities. The patient died 23 years after her initial surgery.
According to the available literature, neither postoperative adjuvant chemotherapy, nor irradiation
has proven successful for the treatment of leiomyosarcoma. In particular, neither of these procedures
can halt the propagation and the metastatic spread of the tumor, as well as both fail to improve
survival. Lately, repeated surgical resections and metastasectomies have proven the most effective
therapeutic interventions, as these might improve survival. It appears that the location of metastases
(i.e. pulmonary vs. extrapulmonary) is unimportant-what matters is to remove them.
Keywords: Uterine leiomyosarcoma; Multiple resections; Oophorectomy; Pulmonary metastasis; Survival
Introduction
Leiomyosarcoma of the uterus is a particularly rare tumor accounting for only one percent
of uterine malignancies. Its annual incidence is reported at 0.64 case per 100,000 women [1].
Its etiology is currently unknown, and appears to be unrelated to pregnancy or childbirth. Most
patients are diagnosed in the fifth decade of life. In the vast majority of cases, the tumor involves
the uterine fundus and/or the cervix [2,3]. Leiomyosarcomas tend to be subclinical. Often, clinical manifestations occur only when the tumor exerts pressure on adjacent blood vessels and nerves,
or dislocates neighboring organs. The leading symptoms include bleeding, hemorrhagic diathesis,
and more or less severe lower abdominal pain. Leiomyosarcomas are usually diagnosed ‘by chance’
– that is, during the histological evaluation of the surgical specimens of removed uterine fibroids.
The prognosis of uterine leiomyosarcoma is poor – 5-year survival is 50 to 65 percent after the
complete resection of Stage I and II tumors [2-4]. In 30 to 35% of cases, malignancy has already
spread beyond the uterus by the time of diagnosis [5]. Nearly 80% of the recurrences occur outside
the pelvis [3,6]. In more than 70% of patients with a leiomyosarcoma confined to the uterus, and in all cases with an extrauterine tumor, surgical resection is followed by recurrence within 8 to 16 months on average [2,3,6].
Case Presentation
1. In 1986, at the age of 41 years, the female patient underwent surgery for a pelvic mass
of 4 cm diameter. The lesion was contiguous with the uterine portion of the cervix, and filled the
uterovesical pouch. Total uterine extirpation was performed by the abdominal route. The final
histopathological diagnosis was leiomyosarcoma and therefore, the patient was re-laparotomized
and the uterine appendages removed. Subsequently, the patient underwent pelvic telecobalt
radiation therapy.
2. A symptom-free period of nine years followed and then, in 1995, chest imaging detected
an asymptomatic metastasis of 2 cm diameter in the third segment of the right lung. Atypical
resection of the right upper pulmonary lobe was performed (Figure 1).
3. In 1997, a metastatic lymph node of 3 cm diameter was
removed from the left para-aortic region. The patient was symptomfree;
doxorubicin chemotherapy was administered after the operation.
4. In 1998, follow-up evaluation detected a retroperitoneal
lymph node metastasis, which was then removed.
5. In 1999, round shadows (of 7 to 8 mm diameter each) were
observed in the second, sixth, and tenth segments of the left lung.
Two additional, one-centimeter large masses were described in the
sixth and tenth segments of the right lung. Bilateral pulmonary
metastasectomy was performed through transverse sternotomy, and
altogether seven metastases were removed.
6. In 2000, a CT-scan depicted a pelvic soft-tissue mass of 25
mm diameter, located above the aortic bifurcation and in front of the
inferior vena cava. Follow-up CT-scans confirmed the propagation of
the lesion and by 2002, it had grown to a size of 40 mm and therefore,
it was excised through the retroperitoneal approach.
7. In 2005, MRI revealed a 5.5 × 3.5 cm large mass, located
below the level of the aortic bifurcation, among the intestines. Two
additional masses of 3.4 × 2.3 cm and 3 × 2 cm size were identified
in the left para-iliacal region. Again, all these lesions were removed
surgically (Figure 2).
8. Still in 2005, a pelvic lesion of 10 × 7 cm size was detected
left to the urinary bladder; it caused an indentation of the wall of the latter. The lesion, located on the pelvic surface of the sacrum, was extirpated (Figure 3).
9. In 2006, the PET/CT-scan showed a 51-mm mass in the left
half of the pelvis, next to the acetabulum, along with another 58-mm
lesion. A third lesion of 28 mm size and exhibiting minimal FDGenhancement
was detected in the corresponding location on the right
side. According to the literature, leiomyosarcoma is an intensely
FDG-avid malignancy. Therefore, the negligible FDG-enhancement
seen in this case might have reflected the well-differentiated/slowly
progressive nature of the tumor. All these lesions were removed.
10. In 2007, CT imaging performed on the asymptomatic
patient showed three metastases, which were then removed. One
subcutaneous lesion of 5×5×5 cm size was located in the right
subcostal region. Another, 15 × 15 × 15 cm large mass was detected at
the bifurcation of the left common iliac artery. Finally, a third tumor
of 4 × 4 × 4 cm dimension was identified under the junction of the left
iliac vein and the inferior vena cava.
11. The last operation was performed in January 2009 for a
lesion discovered by chance during the follow-up evaluation of the
asymptomatic patient. On this occasion, a mass of 4 × 3 × 3 cm size,
located at the thoracic-diaphragmatic border, was removed from the
splenic region.
In May 2009, a follow-up CT-scan confirmed multiple pulmonary
metastases; however, further surgical intervention was no longer
possible. In December 2009, the patient died from acute renal failure at
the age of 64 years. It can thus be concluded that follow-up treatment
comprised multiple excisions of small, easy-to-remove lesions,
which were detected at the follow-up visits scheduled every year at
the outset, and every six months after 2005. The patient recovered
without serious complications after these operations; abdominal wall
reconstruction for hernia was necessary on two occasions.
The presence of metastatic leiomyosarcoma has been confirmed
pathologically in all surgical specimens obtained during the above
operations. The histological appearance of the tumor tissue was
suggestive of low malignancy; mitotic cells were seen in moderate
numbers, without any tissue necrosis.
Immunohistochemistry staining was positive for vimentin and
for smooth muscle actin after the ninth, as well as for vimentin and desmin after the last operation. Histopathology evaluation did not detect vascular invasion in any of the surgical specimens obtained during the ten procedures performed for metastatic spread.
Figure 1
Figure 1
Lung metastasis identified in the right upper pulmonary lobe
(arrow) on the chest x-ray film.
Figure 2
Figure 3
Discussion
Uterine leiomyosarcoma is a rare disorder and hence, only meager
information is available in the literature to develop an appropriate
management strategy.
The current (NCCN 2015) guidelines recommend hysterectomy
with bilateral salpingo-oophorectomy for leiomyosarcoma confined
to the uterus, as confirmed by preoperative diagnostic evaluation. The
surgical management of advanced disease or of extrauterine organ
involvement should be individualized. Surgery is the treatment of
choice for resectable disease (e.g. local propagation, metastatic spread,
or symptomatic disease). Leitao et al. [7] found that while prolonging
progression-free survival, surgical cytoreduction has no impact on
overall survival. According to two additional studies, preservation
of the ovaries does not influence patient survival either [2,3]. On
the other hand, there is evidence that oophorectomy might have a
negative effect on survival [8]. A recent study of 1396 female patients
established that oophorectomy alone does not influence survival [9].
The need for para-aortic lymph node dissection is controversial.
In leiomyosarcoma, the incidence of lymph node metastases is 6.6
to 9.1%, and these lesions are usually accompanied by metastases to
additional extrauterine locations [3,6,9,10]. As lymphadenectomy
does not improve patient survival [9,11], this intervention is not
recommended in the absence of lymphadenopathy or extrauterine
metastases.
Leiomyosarcoma recurs in 45 to 73% of cases; the initial recurrence
occurs within 18 months on average [8]. In many instances, patient
survival is long despite the presence of metastases, whereas recurrence
is aggressive in others. Overall, recurrence is influenced by the extent
of primary spread, tumor grade, and tumor rupture [8].
Several studies have identified doxorubicin and iphosphamide as
the most effective chemotherapeutic agents [12-14]. Add-on cisplatin
[15], or paclitaxel [16] prolongs both progression-free and overall
survival. However, the latest guidelines recommend watchful waiting
in early (Stage I/II) leiomyosarcoma of the uterine corpus, whereas
adjuvant chemotherapy (gemcitabine + docetaxel followed by
doxorubicin) is recommended for advanced (III to IV) stages of the
disease [17]. Some patients might respond to endocrine therapy [18].
The retrospective analysis of the SEER database found that
adjuvant radiotherapy does not prolong patient survival [19].
Another study of 3000 patients established that although it reduced
the recurrence rate, radiotherapy had no impact on survival [20].
Therefore, this modality may be considered, in the first place, as
definitive or palliative therapy for advanced stages, or as an individual
treatment option.
Because of the limited oncological treatment modalities available
for patients with metastases, data on the outcomes of surgical
treatment are relatively abundant. The removal of pulmonary
leiomyosarcoma metastases prolongs survival [21,22,23]. In their
series of 21 patients treated with lung resection, McCormack &
Martini reported 27% 5-year survival [21]. Levenback et al. [22] studied a heterogenous population of 45 patients with uterine
sarcoma and found 43% 5-year, and 35% 10-year survival following
the removal of isolated pulmonary metastases. According to Leitao [7], this intervention achieved a 71% 2-year survival rate. This is a
remarkable result, considering that these patients usually receive
only chemotherapy and survive for 7 to 15 months on average. In
particular, survival was 60 months in patients who underwent
thoracotomy later than 60 months after hysterectomy, whereas those
thoracotomized within 60 months survived only for 31 to 32 months.
The comparison in terms of the presence of intra- vs. extrathoracic
metastasis did not reveal any significant difference in patient survival
[24]. Billigsley found longer survival in non-surgical patients,
compared with – at least in part – resectable pulmonary metastases.
According to this comparison, survival was much better when the
pulmonary metastases could be removed completely [25].
Survival is dependent on several factors. Giuntoli et al. [8]
followed-up 208 patients with leiomyosarcoma for 24 years. They
found that survival was longer (4.9 years on average), when the
tumor was discovered in an earlier stage, at a younger age (<51
years), and at a size less than 5 cm upon detection. According to their
multivariate analysis, only the type of surgery (i.e. complete vs. partial
removal of the lesion; the occurrence vs. the lack of tumor rupture
before or during surgery) influenced survival [8]. As shown by the
univariate analysis undertaken by Leito et al. [24]. longer time (>12
months) to the first recurrence, and complete tumor removal were
associated with longer survival. Possibly, early recurrence indicates
persistent rather than recurrent disease. Pautier analyzed data on 78
leiomyosarcomas identified amongst 157 uterine sarcoma cases, and
found that only staging information correlated with tumor recurrence
and patient survival [26]. Sagae emphasized that complete tumor
removal is the most important prognostic factor [27].
Conclusion
The surgical treatment of leiomyosarcoma should consist of hysterectomy with bilateral salpingo-oophorectomy. As shown by literature data, adjuvant therapy is not necessarily effective in reducing the propagation and metastatic spread of the tumor, or in prolonging patient survival. Therefore, surgical removal remains the mainstay of therapy. The lesion must always be removed, regardless of its location (i.e. pulmonary or extrapulmonary). This conclusion is exemplified by the case described in the foregoing. In the lack of an effective, non-invasive, and curative treatment modality, surgical resection should be offered to all patients with recurrent, resectable leiomyosarcoma, as the repeated removal of recurrent tumors may improve survival.
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