Liposarcoma with lymph node spread - Springer Link

Review Eur Surg (2015) 47:94–100 DOI 10.1007/s10353-015-0314-z

Liposarcoma with lymph node spread: a case presentation and a systematic review of the literature I.B. Correia de Sá · J. Carvalho · R. Silva · P. Ferreira · L. Matos-Lima · A. Taveira-Gomes

Received: 7 April 2013 / Accepted: 7 April 2015 / Published online: 7 May 2015 © Springer-Verlag Wien 2015

Summary Background Liposarcomas are neoplasms of mesodermic origin derived from adipose tissue. Metastases at the time of initial presentation are uncommon, and the spread to regional nodes is extremely infrequent. The aim of this work is to present a rare case of a giant liposarcoma, presenting with regional lymph node extension, and composed of three different histological subtypes and present a systematic review of all the cases described in the literature of liposarcoma with lymphatic extension. Methods A 71-year-old woman presented with a giant retroperitoneal liposarcoma with lymph node invasion. Excision of the tumor en bloc with right radical nephrectomy and lymphadenectomy was performed. Histological analysis revealed a mixed-type liposarcoma consisting of well-differentiated, myxoid, and pleomorphic components, and lymph node involvement. A systematic review of the literature of the cases of liposarcoma with lymph node involvement was performed. I.B. Correia de Sá, MD () · J. Carvalho, MD Department of Plastic and Reconstructive Surgery, Hospital de S. João, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal e-mail: [email protected] I. Correia de Sá, MD · A. Taveira-Gomes, MD, PhD Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal R. Silva, MD Departement of Pathological Anatomy, Hospital de S. João, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal P. Ferreira, MD · L. Matos-Lima, MD · A. Taveira-Gomes, MD, PhD Department of General Surgery, Hospital de S. João, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

Results This is the first description of a retroperitoneal liposarcoma with lymphatic involvement. There are only seven articles, including 9 patients, in literature describing lymph node invasion of liposarcomas. The majority are dedifferentiated liposarcomas. Conclusions Giant retroperitoneal liposarcomas with mixed histological pattern and lymph node invasion are rare presentation in the literature and associated with a poor prognosis. The available data are spare, and our understanding of these tumors is limited, with no known effective therapy. Keywords Liposarcoma · Sarcoma · Lymph · Node · Metastasis

Introduction Soft tissue sarcomas are uncommon tumors that represent only 1–1.5 % of all adult human cancers [1]. The histological subtype, liposarcoma, is a rare histological form, accounting for approximately 10–15 % of the soft tissue sarcomas [2]. Although only 15 % of the soft tissue sarcomas are located in the retroperitoneum [1, 3], the majority of those found in that location are liposarcomas [3–7]. Liposarcomas are neoplasms of mesodermic origin derived from adipose tissue, and are currently classified into five groups: myxoid liposarcomas, well-differentiated liposarcomas, round-cell liposarcomas (poorly differentiated myxoid liposarcomas), pleomorphic liposarcomas, and dedifferentiated liposarcomas [8]. The clinical characteristics [8] and the prognosis [9–11] are closely related to the histological type, and they occur most commonly in the extremities (52 %), retroperitoneum (19 %), and inguinal region (12 %) [12], although their overall anatomical distribution is widespread [13].

94 Liposarcoma with lymph node spread: a case presentation and a systematic review of the literature

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Retroperitoneal liposarcoma with mixed histological pattern is a rare clinical entity [14–16]. It is difficult to detect liposarcomas early in retroperitoneal location because symptoms are late and nonspecific, so it can grow slowly in the retroperitoneal space, reaching a considerable size before being diagnosed. There are remarkable descriptions in literature of liposarcomas weighing up to 46.9 kg [17]. Despite that, metastases at the time of initial presentation are uncommon [18], and the spread to regional nodes is extremely infrequent [19], as those tumors, like other, in general spread by direct, local extension or hematogenous routes [18]. On the other hand, the exact amount of retroperitoneal liposarcomas that spread by lymphatic route is not known, as the majority of the systematic reviews include other types of soft tissue tumors that are known to have higher rates of lymph node involvement, as synovial sarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma, and angiosarcoma [20]. The main goal of this article is to describe a rare presentation of a giant liposarcoma, presenting with regional lymph node spread, and composed of three different histological subtypes and present a systematic review of all the cases described in the literature of liposarcomas with lymphatic extension.

Materials and methods Case presentation A 71-year-old woman presented 14 times at the emergency department of S. João Hospital, in Oporto, for a 2-year period, with complaints of lumbar pain on the right side and thoracic pain. She did not have any other symptoms or any signs on physical examination. As she was previously (6 months before her first appearance in the emergency room) submitted to cardiac surgery for coronary bypass, and had a history of peptic ulcer disease, she was discharged from the hospital after complete cardiac evaluation. As she had persisting symptoms, a thoracic computed tomography (CT) was performed, and reveled a giant retroperitoneal tumor (at least 148 × 137 mm), with a large fatty component but

also a nodular solid area (soft tissue appearance), that was compressing and displacing anteriorly the inferior vena cava, and that was suggestive of being a liposarcoma. Routine blood examinations did not reveal abnormal values. She was immediately referred to our General Surgery Department. A thoracic–abdominal–pelvic CT was performed for better characterization of the tumor, which revealed the giant retroperitoneal mass previously described, 163 × 151 × 211 mm in size, displacing the right kidney anteriorly, without hydronephrosis, and two other lesions, one 59 × 43 × 63 mm in size, compressing the inferior vena cava and the left renal vein and other 57 × 21 mm in size, located anteriorly to the right kidney, with soft tissue appearance and a calcification component, both suggestive of metastatic disease (Fig. 1). Excision of the tumor en bloc with right radical nephrectomy was performed via a right subcostal incision extended to the left (Fig. 2). A giant bulky lipomatous mass surrounded by a thin capsule but nonuniform colored (white-yellow to red), with hemorrhagic areas, was found arising from the right perinephric area. The tumor measuring 32 × 23 × 15 cm and weighing 3217 g was totally excised (Fig. 3a), whereas right radical nephrectomy was necessary as the lesion involved the right kidney and adrenal gland (Fig. 3b). The nodular mass located posteriorly to the inferior vena cava was also removed, measuring 7.5 × 6.3 × 4.2 cm and weighing 101 g (Fig. 3a). The operation took 4 h and 15 min, and no blood transfusion was required. There were no complications in the postoperative period, and the patient was discharged home on day 9. At macroscopic examination of cut sections of the tumor, it was possible to observe three distinct areas (Fig. 3c). Histological analysis revealed a mixed-type liposarcoma consisting of well-differentiated lipoma-like, myxoid and pleomorphic components (Fig. 4). In addition, the myxoid component included an area of central ossification (Fig. 4b). The other mass removed was suggestive of lymph node involvement, as it comprises two components: cells from the tumor and lymphocytes, disposed in a germinal center. The kidney specimen had no evidence of tumor invasion. A microscopically positive margin (R1) was obtained.

Fig. 1 Computed tomographic images of the tumor (a) and lymph node (b)

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Liposarcoma with lymph node spread: a case presentation and a systematic review of the literature

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Fig. 3 Tumor (32 × 23 × 15 cm, 3217 g) and lymph node (7.5 × 6.3 × 4.2 cm, 101 g) (a), right kidney involved by the tumor (b), and cut section of the tumor (c)

Fig. 4 Microscopy images (100 ×) of the well-differentiated (a), myxoid including an area of central ossification (b) and pleomorphic (c) subtypes

The patient underwent chemotherapy. However, a CT performed 6 months after surgery revealed a recurrence of the tumor, located in her abdomen.

Systematic review A systematic review of the cases described in the literature of retroperitoneal liposarcomas with lymph node involvement was also performed. Relevant studies published until September 2011 were searched in PubMed databases using the following MeSH keywords: Liposarcoma AND metastasis; Liposarcoma AND lymph node. One author screened titles and abstracts for potential eli-

gibility and the full texts for final eligibility. We extracted the data using a standardized data collection form to record study design and methodological characteristics, patient characteristics, interventions, outcomes, and missing outcome data (Table 1).

Results Case presentation There were no complications in the postoperative period, and the patient was discharged home at day 9.


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Table 1 Characteristics of the studies included in the systematic analysis—liposarcoma with lymph node metastasis described in literature Study (authors, year, reference)

Study design

Number of patients (PLN/ total)

Sex

Age (years)

Location of primary tumor

Location of lymph node

Size of tumor

Histological subtype

Time for metastasis presentation from tumor diagnosis

Outcome

Treatment

Mazeron and Suit, 1987 [19]a

Retrospective cohort study

1/14

–

–

–

–

–

–

–

–

–

Geethamani et al., 2010 [21]a

Case report

1/1

Feminine

65

Upper back

Axilla

–

Dedifferentiated

0

–

–

Gaakeer et al., 1988 [22]a


1/64

–

–

Extremities

–

–

–

–

Death

–

Gritli et al., 2010 [23]


1/15

–

–

Head and neck

Cervical

–

–

–

–

–

Schofer et al., 2009 [24]

Case report

1/1

Masculine

41

Forearm

Axilla

140 × 10 × 60 mm

Dedifferentiated

0

Free of disease for 3 months

Tumour and axillary lymph resection + RT

Fiore et al., 2007 [25]


2/329

–

–

–

–

–

Myxoid liposarcoma/ round-cell liposarcoma

Recurrent

–

–

Ghadimi et al., 2011 [26]


2/277

–

–

–

Hilar/?

–

Dedifferentiated

–

–

–

PLN positive lymph node, RT radiotherapy a Only abstract available

An abdominal mass, measuring 55 × 22 × 50 mm, located between the liver and the inferior vena cava was revealed in a follow-up CT, 6 months after surgery.

node metastases was reported to have origin from a retroperitoneal liposarcoma. The results are summarized in Table 1.

Systematic review

Discussion

Our initial search yielded 645 literature citations. Of those, we excluded 638 cases based on the following reasons: abstract or full text not available, duplicated titles, no English, Spanish, or Portuguese language, other histological subtypes of sarcoma (not liposarcoma subtype), mixed information where it was not possible to understand what histological subtype was responsible for lymph node involvement, and satellite lesions presented in retroperitoneal space not clearly being lymph nodal metastasis but multicentric primary lesions instead. Finally, only seven articles, including nine patients, were retrieved for analysis (Table 1) [19, 21–26]. Three studies were from Europe, two from North America, one from North Africa, and one from Asia. Overall, five studies were retrospective cohort studies, and two were case reports. Four of the tumors originating from lymph node metastasis were dedifferentiated liposarcomas, one myxoid liposarcoma, one round-cell liposarcoma, and three of unknown histological subtype. None of the lymph

In our case report, we present a patient with a giant liposarcoma located on the retroperitoneum, with lymphatic spread to two lymph nodes at initial presentation, and with a mixed histological subtype consisting of three different components (well differentiated, myxoid, and pleomorphic)—both extremely rare presentations in the literature. It was not possible to find on histological images an unequivocal fibrous capsule or a marginal sinus, fundamental characteristics to identify a lymphatic ganglion. Yet, both microscopy and CT images of satellite lesion were strongly suggestive of lymph node metastatic disease. Histological analyses revealed a mass composed of cells from the tumor and lymphocytes, disposed in a germinal center, and the CT image revealed a nodular mass measuring 59 × 43 × 63 mm with soft tissue appearance and no lipomatous component (as observed in the primary tumor). Taken together, these data strongly suggest lymph node spread. This is, as far as we know, the

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first case reported in the literature with lymphatic spread of a liposarcoma located in the retroperitoneal space. Mixed-type liposarcomas are exceedingly rare [14–16], founded in approximately 4 % of all liposarcoma cases [14], and when present, usually only comprise two different components. Our case presented with three different components: well differentiated, myxoid, and pleomorphic. The pleomorphic subtype is also known to be very rare in this location [9]. The histological subtype has an important prognostic value: dedifferentiation histology, accounting for approximately 20 % of all liposarcomas, is considered a high-grade marker and has been associated with worse prognosis [27]. Singer et al. [9] reported that dedifferentiated histological subtype was associated with a 6-fold increased risk of death and 15-fold increased risk of distant recurrence compared with well-differentiated tumors. Pleomorphic liposarcomas have high metastatic potential, accounting for the decreased rate of survival [9], and are also considered as high-grade tumors. One the other hand, well-differentiated liposarcomas are classified as low-grade tumors, as they are relatively slow-growing tumors, imposing mass effects on adjacent anatomic structures [27]; they may recur locally, but metastatic potential is low. Overall 5-year survival for well-differentiated subtypes is 90 %, while 5-year survival for pleomorphic subtypes is only 30–50 % and for dedifferentiated and myxoid/round-cell subtypes is 75 % and 60–90 %, respectively [9]. In our patient, the prognosis of the pleomorphic component fares worse than its welldifferentiated and myxoid counterparts. Retroperitoneal location is also a negative prognostic factor [28]. The tumor is often large (> 10 cm) at the time of diagnosis, as the retroperitoneum provides a sizeable potential space allowing significant growth prior to development of symptoms [9]. An aggressive attempt at complete surgical resection is the type of treatment that has the most favorable prognosis in patients with retroperitoneal liposarcomas [2–5, 7, 29–32]. Incomplete resection has no positive impact on survival compared with no resection at all [5], and there is no definitive evidence that postoperative radiotherapy or chemotherapy would modify the clinical course of the disease [33]. In our case, although a more aggressive approach was tried, removing not only the tumor but also the lymph nodes involved, it was not possible to accomplish complete surgical resection of liposarcoma, with margins involved microscopically (R1). The patient was referred to an Oncologic Center, where she underwent chemotherapy. The prognosis for this patient was poor, as she presented a giant liposarcoma, weighing 3217 g, located in the retroperitoneal space, with an aggressive pleomorphic component, involved surgical margins, and lymph node spread, all characteristics that are related with a poor outcome [9, 28, 34]. This systematic review summarizes the available data in the literature about lymphatic spread of liposarcomas. Lymph node metastasis is considered an infrequent event in the natural history of soft tissue sarcomas and

is associated with poor outcome [35]. This is probably the reason for the majority of the systematic reviews and retrospective cohort studies present in the literature describing the metastatic spread of soft tissue sarcomas to include other histological subtypes that are known to have higher rates of lymph node involvement, as synovial sarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma, and angiosarcoma [20]. The exact extent of lymph node invasion of liposarcomas is unknown, making the study of their natural history difficult. There is no consensus about the prognosis and treatment of clinically evident lymph node metastasis, making it a difficult decision for the physician who finds an individual with this rare condition [19, 22, 36]. In our systematic review, we could only find seven studies [19, 21–26] describing nine individuals with liposarcoma and lymph node involvement, comprising five retrospective cohort studies and two case reports. The available information in each study is incomplete, making it difficult to estimate the exact percentage of lymphatic spread. The prognosis and ideal treatment are also impossible to assess with the information reported. In four patients (over five described), the histological subtype associated with this condition is dedifferentiated liposarcoma. This allows us to figure that dedifferentiated liposarcomas are the histological subtype more associated with lymphatic spread, as it was already stated to be the one more prone for distant metastasis [28], spreading by hematogenous routes. The percentage of lymphatic spread in the retrospective cohort studies was very heterogeneous, as was the studied population in each one. Only the studies by Mazeron et al. [19] and Gaakeer et al. [22] included, as one of primary objectives, the quantification of lymph node metastasis in soft tissue sarcomas, and described in those series of cases an incidence of lymph node metastasis in liposarcoma of 7.14 % [19] and 1.56 % [22], respectively. However, in both studies, the total number of patients with liposarcoma is very low (14 and 64, respectively), which may cause an overestimation of those with lymphatic metastasis. On the other hand, in the study by Gaakeer et al. [22], the population studied are those affected with liposarcomas located in the extremities, and the incidence of 1.56 % of lymph node metastasis can only represent those affected with liposarcomas in that anatomical location. For those articles [19, 22], we only assessed the abstract, and we could not review other important information. For the other two studies, those with the largest number of patients studied, Fiore et al. [25] and Ghadimi et al. [26] with 329 and 277 individuals affected with liposarcomas, the incidence of lymphatic node spread was 0.608 and 0.722 %, respectively. However, in the study by Fiore et al. [25], the population studied included those with myxoid liposarcoma and round-cell histological subtype, and in the study by Ghadimi et al. [26], those affected with the dedifferentiated histological subtype, known to have a worse prognosis than well-differentiated liposarcomas, and, in case of the dedifferentiated subtype, also a high metastatic potential [9]. This obviously is causing a selec-


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tion bias. We can only accomplish that the incidence for lymph node metastatic disease is approximately 0.608 % for the myxoid liposarcoma and round-cell histological subtype [25] and 0.722 % for dedifferentiated histological subtype [26]. We can also say that the probability for those tumors to have a lymphatic spread is higher in the extremities, as the incidence of lymph nodes affected in the study by Gaakeer et al. [22], i.e., 1.56 %, is higher, when compared with the tumors located in other anatomical regions [25, 26]. However, more studies need to be conducted to accomplish the importance of lymph node invasion and to define a better approach for these tumors. In conclusion, we report a rare case of a giant retroperitoneal liposarcoma with mixed histological pattern and lymph node invasion, both rare presentations in the literature, and associated with a poor prognostic. A systematic review of the literature revealed that this is the first liposarcoma in the retroperitoneal space with lymphatic spread reported. The data available are few, and more studies should be done to assess the incidence of this condition and the management for this pattern of dissemination. Acknowledgments The authors thank Pinheiro-Torres, MD, from the Department of Cardiothoracic Surgery, Hospital de S. João, Porto, Portugal, who kindly had referenced the patient to our Department of General Surgery. Disclosure There are no financial disclosures to be made with this article. Conflict of interest The authors declare that there is no conflict of interest.

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