Primary Broad Ligament Leiomyosarcoma: a Rare Case Report with Review of Literature

Introduction

Leiomyosarcoma (LMS) constitutes approximately 10% of all soft tissue sarcoma [1]. In the gynecological tract, LMS most commonly occurs in the uterus [2]. Broad ligament LMS is very rare with less than 30 cases reported in English literature. Gardner et al. proposed the definition of tumor of broad ligament as “Tumors occurring on or in the broad ligament and completely separated from and in no way connected with either the uterus or the ovary” [3]. LMS has a varied prognosis but in general is aggressive with 5-year survival of 25–76% [4]. We hereby report a rare case of this malignant tumor in a premenopausal female.

Case Report

A 40-year old premenopausal female with 2 living children presented with symptoms of dull abdominal pain and abdominal distension of 7 months duration. There was no significant gynecological or past medical history. There were no complaints of menorrhagia, metrorrhagia, or dysmenorrhoea. General physical examination revealed a vague ill-defined, non-tender lump palpable in the left side of the lower abdomen. All her hematological and biochemical parameters were within normal limits. An ultrasound examination of the abdomen and pelvis showed a heterogeneous hypoechoic mass 11.59*8.77*8.03 cm in the left adnexa and pouch of Douglas. The uterus was normoechoic with normal thickness of endometrium and displayed anteriorly. MRI pelvis revealed an abdomino-pelvic mass with lobulated margins and prominent central necrosis/cystic areas (20*15 cm) arising from the left adnexa and extending upwards into the abdominal cavity (Fig. 1). The serum CA-125, CEA, CA19.9, and LDH were within normal limits. She underwent exploratory laparotomy. Intraoperatively, there was a 20*20 cm multilobulated mass arising from the left broad ligament. The mass was separate from the uterus and left ovary. Bilateral ovaries, fallopian tubes, uterus, and urinary bladder were normal. She underwent left broad ligament mass excision, total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), and peritoneal wash cytology. The cut section of the mass showed areas of hemorrhage and whirling. The cut surface of the uterus and both ovaries were unremarkable. Microscopic examination of the mass showed a malignant spindle cell tumor with nuclear and cellular pleomorphism along with the areas of coagulative necrosis. The tumor cells had pleomorphic, vesicular coarse chromatin with conspicuous nucleoli. Mitosis was brisk at about 12–15/10 HPFs. There were interspersed areas of necrosis (Fig. 2). Sections from both ovaries and uterus were unremarkable. The uterus shows secretory endometrium and chronic cervicitis. Peritoneal washing was within normal limit.

Fig. 1.

MRI showing the large mass in pelvis

Fig. 2.

A- Low magnification showing a malignant mesenchymal tumor demonstrating smooth muscle differentiation with interlacing bundles and fascicles of pleomorphic spindle cells intersecting at right angles. B and C- Higher magnification illustrating differentiated smooth muscles cells with some nuclear atypia, blunt ended nuclei with eosinophilic cytoplasm. Occasional cells have perinuclear vacuoles and atypical mitotic figures

Immunohistochemistry (IHC) studies showed the tumor cells to be positive for smooth muscle actin (Fig. 3), desmin (Fig. 4), and vimentin. The ki67 index was high (Fig. 5). The cells were negative for PanCK, CD117, S-100, and CD68. Based on these morphological and IHC analyses, a diagnosis of primary LMS of left Broad Ligament—Grade II (intermediate) as per FNCLCC (French Federation of Cancer Centers Sarcoma Group) grading system was made.

Fig. 3.

The tumor are diffusely immunopositive (Cytoplasmic) for smooth muscle actin (SMA)

Fig. 4.

The tumors are diffusely immunopositive (Cytoplasmic) for Desmin

Fig. 5.

Showing high ki67 proliferative index

Post-operative recovery was uneventful, and a repeat thoraco-abdomino-pelvic CT scan did not show any residual disease. Because of an intermediate grade LMS with no residual disease, the patient received 6 cycles single-agent doxorubicin adjuvant chemotherapy for six cycles followed by adjuvant pelvic external beam radiotherapy 50.4 Gy in 28 fractions over five and half weeks. The patient is on regular follow-up and is clinico-radiologically disease free for the last 2 years.

Discussion

Primary LMS originating in the broad ligament is a rare neoplasm. This tumor occurs commonly in postmenopausal women, and only few cases in younger age group have been reported. The clinical manifestations of the cases are nonspecific including abdominal pain, distension, nausea, constipation, and malaise [5–31]. As there are very few case reports of primary broad ligament LMS, the histological diagnostic and grading criteria, and the staging and management used are similar to uterine LMS. The microscopic diagnosis of LMS has evolved gradually over the years. Presently, the diagnosis of LMS relies on the presence of three criteria: coagulative tumor cell necrosis, cytologic atypia, and mitotic activity. Zaloudek and Hendrickson proposed that the presence of coagulative necrosis itself is enough for the diagnosis of LMS [32]. In the absence of cell necrosis, the diagnosis of LMS needs to diffuse moderate to severe cellular atypia and more than 10 mitoses/10 HPFs [33]. Various authors have refined and redefined the diagnostic criteria that have been used for years and have made attempts to correlate these findings with clinical outcome. The systems used for grading of soft tissue sarcomas are the NCI (National Cancer Institute) and FNCLCC systems. We used the FNCLCC grading system which is based on a score obtained by evaluating three parameters: tumor differentiation, mitotic rate (0–9, 10–19, and > 20 mitoses/10 HPFs), and the amount of tumor necrosis (< 50% tumor necrosis and > 50% tumor necrosis). According to both these systems, LMS is classified as low, intermediate, and high grade. The present case was classified as intermediate grade LMS.

There is a wide variation in the management practices of this uncommon tumor, but initial treatment is usually excision of mass, total abdominal hysterectomy, and bilateral salpingo-oophorectomy as depicted in Table 1. Pelvic lymph node dissection is debatable and has not been consistently shown to improve survival in uterine LMS [4, 34]. Our patient did not undergo lymph node dissection keeping in mind lack of evidence and risk of lymphedema [35]. The role of adjuvant chemotherapy and/or radiotherapy is usually extrapolated from that of uterine LMS. The results of adjuvant radiotherapy in the treatment of uterine LMS are conflicting with some studies showing improvement in local control [36], while others are not showing any impact [37]. These studies have been either retrospective in nature or underpowered prospective studies due to the rarity of the disease. Keeping in mind the local failure rates of 30–40% [38] in different studies, we delivered adjuvant radiotherapy to the pelvis. Data on adjuvant chemotherapy is also conflicting. There is presently no completed randomized adequately powered study on uterine LMS to determine the role of adjuvant chemotherapy. Some studies have shown small improvements in disease-free survival with chemotherapy. Our patient received adjuvant chemotherapy with a single-agent doxorubicin as this drug is well tolerated and been shown to have good response rates in metastatic LMS [39].

Table 1.

Reported cases of broad ligament Leiomyosarcoma

No	Author	Year	Age (Years)	Diameter (cm)	Preop diagnosis	Mitoses (per 10 hpf)	Surgery	Adjuvant therapy	Status
1	Ahmed F et al. [5]	2019	62	28	Uterine sarcoma	NA	TAH + BSO + Resection of mass	RT	NED at 6 months
2	Chaichian et al. [6]	2016	55		Retroperitoneal tumor	NA	TAH + BSO + OM + PLN + PAND	RT, CT	NED >9 months
3	Nishat et al. [7]	2015	58		Ovarian cancer	5	BSO + OM + PLN + PAND	–
4	Devika Gupta et al. [8]	2015	41	10.3	Adnexal tumor	12–14	TAH + BSO	CT	AWD 2 months
5	Makihara et al. [9]	2014	61	18	Ovarian cancer BLLMS	NA	Resection (?) of broad ligament LMS		NA
6	Akhavan A [10]	2013	60	10	?	10	TAH + BSO	RT	Metastases to abdominal wall 5 years
7	Kolusari et al. [11]	2009	35	18	pelvic mass	> 20	TAH + BSO	CT + RT	NED > 12 month
							+OM
							+PLN + PAND
8	Duhan et al. [12]	2009	45	24	NA	> 10	Resection+BSO	CT	NED > 15 months 5
9	Papachat zopoulos et al. [13]	2009	38	20	fibroid	> 10	TAH + BSO	–	DOD 8 months
10	Bouraoui S et al. [14]	2008	45	NA	Broad ligament leiomyo sarcoma	NA	resection	CT	NED >15 months
11	Falconi et al. [15]	2006	52	NA	NA	NA	TAH + BSO	NA	AWD 117 months
12	R Murialdo et al. [16]	2005	53	?	Broad ligament leiomyosarcoma	<10	TAH + BSO	None	NED 13 months
13	Ben Amara et al. [17]	2005	49	23	ovarian cancer	7	TAH + BSO + OM	–	DOD 5 month
14	El-Idrissi & Fadli [18]	2004	52	12.5	NA	NA	TAH + BSO	–	DOD 3 months
15	Kir et al. [19]	2003	35	17	NA	15–20	TAH + BSO + PLN	–	NA
16	Shah et al. [20]	2003	87	20	ovarian cancer	30–40	TAH + BSO + OM	–	DOD 2 M
17	Agarwal et al. [21]	2003	55	14	NA	>10	TAH + BSO	CT	NED > 12 months
18	Pekin et al. [22]	2000	56	11	ovarian tumor	14	TAH + BSO	–	NED > 25 months
19	Cheng et al. [23]	1995	59	7	NA	> 10	TAH + BSO	–	NED > 12 months
20	Lee et al. [24]	1991	65	16. 4	fibroid	> 10	STH + BSO	CT	AWD > 26 months
21	Lee et al. [24]	1991	36	35	ovarian cancer	> 10	TAH + BSO	CT	AWD > 33 months
22	Shimm & McDonough et al. [25]	1987	31	9	NA	8	Resection	RT	AWD 30 months
23	Herbold et al. [26]	1983	73	15	NA	21	TAH + BSO	–	DOD 1 month
24	Raj-Kumar [27]	1982	70	10	NA	< 10	Resection	–	NED > 24 months
25	DiDomenico et al. [28]	1982	48	11	NA	10.5	TAH + BSO	–	NED > 21 months
26	Weed & Podger [29]	1976	50	11	NA	NA	TAH + BSO	–	DOD 19 months
27	Ullman & Roumell [30]	1973	50	11	NA	NA	TAH + BSO		NA
28	Lowel & Karsh [31]	1968	50	11	NA	0–4	TAH + BSO	–	NED > 12 months

^*NED: No evidence of disease; DOD: Died of disease; AWD: Alive with disease; TAH: Total abdominal hysterectomy; BSO: Bilateral salpingo-oopherectomy; STH: Sub-total hysterectomy; OM: Omentectomy; PLN: Pelvic lymph node dissection; PAND: Para-aortic node dissection

Data on uterine LMS shows that among those patients who recur, > 65% fail at distant sites like the lungs, abdomen, and liver [38]. Close follow-up is therefore necessary. We followed up our patient with 3 monthly imaging including CT of thorax, abdomen, and pelvis for the first 18 months followed by 6 monthly imaging. The patient is at present on regular follow up with no evidence of recurrence.

Conclusion

Broad ligament LMS is rare. Complete surgical resection with TAH and BSO followed by adjuvant chemotherapy and radiotherapy should be considered in treatment.

Compliance with Ethical Standards

Disclosure of Potential Conflicts of Interest

The authors have no conflict of interest.

Disclosures

The authors have nothing to disclose.

Informed Consent

Obtained from participant in the presence of two neutral witnesses.