Colossal well-differentiated liposarcoma of the small bowel mesentery: A case report

Abstract

BACKGROUND

Well-differentiated small bowel mesenteric liposarcoma (LPS) is rare, with high malignancy, poor prognosis, and high preponderance to local recurrence.

CASE SUMMARY

Here we described a 71-year-old male, who complains of persistent abdominal distension for a month. The clinical manifestation is a huge abdominal mass occupying almost the entire abdomen. Physical examination indicated palpable massive mass in the abdomen, hard texture, indefinable boundary, poor mobility. The abdominal enhanced computed tomography at another hospital scan showed multiple abdominal masses originating from the small bowel mesentery. Abdominal and pelvic magnetic resonance imaging at our hospital showed multiple masses in the abdominal and pelvic cavities, indicating that the tumor originated from the mesentery or peritoneum. Results of exploratory laparotomy indicated that the tremendous mass primarily results from the mesentery of the small intestine, occupying the entire abdominal cavity in a polymorphic and lobulated shape. The patient underwent complete surgical resection of the tumor, and the weight of the tumor was approximately 11 kg. The histopathological examination of the resected specimens confirmed the diagnosis of well-differentiated LPS of the small bowel mesentery.

CONCLUSION

Completed surgical resection was cornerstone, and histopathological and molecular confirmations were crucial. The necessity of adjuvant therapy should be phrased as a potential consideration to improve patient’s survival time.

Key Words: Well-differentiated liposarcoma; Small bowel mesentery; Colossal liposarcoma; MDM2 gene amplification; Case report

Core Tip: Well-differentiated small bowel mesenteric liposarcoma (LPS) is rare, with high malignancy, poor prognosis, and high preponderance to local recurrence. The patient underwent complete surgical resection of the tumor, and the weight of the tumor was approximately 11 kg. Both histopathological and fluorescence in situ hybridization examination confirmed that MDM2 amplification, and the small intestine mesenteric well-differentiated LPS was accurate diagnosed.

INTRODUCTION

Liposarcomas (LPS) are rare malignant tumors of adipocytic differentiation, they are commonly found soft tissue sarcomas, but their occurrence in the small intestinal mesentery are extraordinarily rare. LPS are most detected in the soft tissues of the extremities and retroperitoneum, and less commonly in the mesentery, spermatic cord, mediastinum, head, and neck[1]. It presents as an abdominal enormous mass of indeterminate origin with vague abdominal distension; the size of the small bowel mesentery mass is approximately 25 cm × 23 cm × 15 cm. In general, small bowel mesenteric LPS occurs between 50 years and 70 years with a higher incidence in males.

Well-differentiated LPS (WDLPS) occurring in the mesentery of the small and large intestine is extremely uncommon. It usually presents as a large painless mass, which is incidentally found[2]. WDLPS/de-differentiated LPS (DDLPS) is a major subtype of LPS, and it accounts for approximately 40%-50% of all LPS, with an anatomical predilection for the retroperitoneum, and carrying the MDM2 and CDK4 genes[3]. MDM2 amplification can provide strong evidence for the correct diagnosis of WDLPS.

This case report aimed to present a rare case of a giant WDLPS, which originated from the small bowel mesentery treated successfully by complete surgical excision. The patient was a 71-year-old male who suffered from abdominal tremendous mass and was treated in Tongren City People’s Hospital in January 2025. Here the medical history, clinical symptoms, signs, laboratory results, imaging data, and histopathological examination results were reported. The patient was informed that the data from his case would be submitted for publication, and he agreed.

CASE PRESENTATION

Chief complaints

A 71-year-old male patient was presented to the hospital with primary complaint of "palpable abdominal mass for a month".

History of present illness

One month ago, the patient suddenly developed an abdominal mass without any obvious cause, the mass gradually enlarged. There were no symptoms such as fever, nausea, vomiting, hematemesis, black stools, cessation of anal defecation and exhaust. The patient initially visited another hospital and underwent abdominal ultrasound, it showed that a huge mass in the abdomen with unknown origin. Abdominal enhanced computed tomography (CT) examination at another hospital detected a large, solid abdominal mass that almost entirely occupied the abdominal cavity. The patient was not hospitalized in another hospital and ultimately chose to be hospitalized in our hospital for treatment.

History of past illness

The patient had no history of any diseases, family history of hereditary diseases, digestive diseases, hepatitis, tuberculosis, typhoid fever, smoking, alcohol consumption, or drug abuse.

Personal and family history

The patient had no personal or family history of tumours.

Physical examination

A clinical examination revealed a temperature of 36.7 °C, respiratory rate of 20 breaths per minute, pulse rate of 78 beats per minute, and blood pressure level of 145/98 mmHg. His height is 165 cm, weight is 69 kg, body mass index is 26.08 kg/m². Abdominal physical examination revealed abdominal distention (frog belly). The mass occupied the entire abdominal cavity, located in the midaxillary line on both sides, up to the xiphoid process and down to the pubic symphysis region (Figure 1A). The mass was approximately 40 cm × 30 cm in size, and the abdominal circumference was 109 cm (Figure 1B). The liver and the spleen were not palpable, and percuss demonstrated a drum-like sound around the umbilicus. In addition, no tenderness and rebound were observed. The shifting dullness was negative, and bowel sounds were normal on auscultation. The other systems were also normal. No palpable lymph nodes were found in the cervical, axillary, or inguinal regions.

Figure 1 Abdominal physical examination preoperatively. A: The patient had obvious abdominal distension (frog-belly); B: The measured abdominal girth was 109 centimeters.

Laboratory examinations

The routine blood results, cancer antigen 19-9, carcinoembryonic antigen, alpha fetoprotein, liver function tests, and renal function were normal. The patient was negative for hepatitis B, syphilis, and human immunodeficiency virus. The electrocardiogram was also normal.

Imaging examinations

Abdominal ultrasound at another hospital manifested an abdominal giant mass in the abdomen in which the origin is unknown. CT scan of the chest at our hospital indicated that no lesions of metastasis were found. Abdominal enhanced CT examination at another hospital detected a large, solid abdominal mass that almost entirely occupied the abdominal cavity. Abdominal and pelvic magnetic resonance imaging at our hospital was completed, which showed that multiple round masses were found in the abdominal cavity with an envelope. The mass originated from the mesentery. It was also well circumscribed, lobulated, heterogeneous, and compartmentalized, with a maximum size of 25 cm × 23 cm × 15 cm (Figure 2). The mass removed intraoperatively was isolated, with a maximum size of 25 cm × 23 cm × 15 cm, and all masses were approximately 11 kg in weight (Figure 3A). The mass cut surface was soft, with a white-to-yellow color (Figure 3B). The histopathological examination of the specimens revealed that the tumor composed of atypical cells. In the focal areas, WDLPS was observed. Immunohistochemistry staining showed that the leucocyte antigen was positive on MDM2, S-100, P53, P16, Vim, and Ki-67 (3%) tumor cells and negative on EMA and CK-pan (Figure 4). Given these findings, the case was reported as WDLPS. Fluorescence in situ hybridization revealed MDM2 gene amplification in neoplastic cells. Thus, the definitive diagnosis was atypical lipomatous tumor (ALT) or WDLPS (Figure 4).

Figure 2 Abdominal and pelvic magnetic resonance imaging scan indicated that multiple round masses were found in the abdominal cavity with an envelope, and occupy the entire abdominal cavity, which originated from the small bowel mesentery. Tremendous masses, well circumscribed, lobulated, heterogeneous mass, compartmentalized, with a maximum size of 25 cm × 23 cm × 15 cm (mark with orange lines). A: Coronal position; B: Sagittal position; C: Transverse position T2 weighted image; D: Transverse position T1 weighted image.

Figure 3 Resected specimen, macroscopic findings. A: The heterogeneous and multifocal masses found during laparotomy, all masses approximately 11 kg in weight; B: The mass cut surface was soft, white to yellow and without necrotic, without invasion into the mucosal surface of the small intestine.

Figure 4 Pathological examination results. Histopathological examination showed hematoxylin and eosin stains (× 40). Microscopic examination of the mesenteric mass showing variably sized lipoblasts with vacuolated cytoplasm, central hyperchromatic nuclei and nuclear scalloping. Histopathologic features of well-differentiated liposarcoma. A-F: Immunohistochemical stain is positive for the neoplastic cells. Positive: MDM2 (A), S-100 (B), P16 (C), Vim (D), Ki-67 (3%; E), and p53 (F); G and H: Immunohistochemical stain is negative [CK-pan (G) and EMA (H)]; I and J: Fluorescence in situ hybridization showed that MDM2 gene amplification is further confirmed (red signals represent MDM2; green signals represent chromosome 12 centromeres; magnification: × 400).

MULTIDISCIPLINARY EXPERT CONSULTATION

We organized a multidisciplinary team discussion preoperatively, the patient was preliminarily diagnosed with abdominal giant mass based on the physical examination and imaging report, and drew up an accurate surgical plan.

FINAL DIAGNOSIS

The final diagnosis was colossal WDLPS of the small bowel mesentery.

TREATMENT

The patient’s family should be fully informed of the relevant surgical risks, and they should sign the surgical consent form preoperatively. After improving the relevant preoperative preparation, the entire abdominal heterogeneous mass was excised successfully on January 24, 2025. The whole surgery lasted for 2 hours, blood loss was approximately 50 mL, without blood transfusion and intraoperative complications.

OUTCOME AND FOLLOW-UP

The patient died 2 months after discharge, and the specific cause of death is unknown.

DISCUSSION

LPS frequently develop from fat, muscles, and other connective tissues of mesenchymal origin and are a rare class of extremely aggressive cancers, which often fatal disease due to their higher recurrence, poor prognosis, higher and significant mortality rate among the patients[4].

The World Health Organization classification of soft tissue and bone tumors recognizes four major LPS subtypes: (1) ALP/WDLPS; (2) DDLPS; (3) Myxoid LPS; and (4) Pleomorphic LPS[5]. These four main subgroups are characterized by distinctive morphologies, unique genetic findings, and distinct clinical behavior. Accurate classification requires the integration of morphological, immunohistochemical, and (in selected situations) genetic findings, which are essential for providing patients with the best available treatments[6].

The clinical symptoms of intra-abdominal LPS are mainly painless palpable masses, which are presented with inherent characteristics in relation to deep localization and expansive growth. Clinically, the tumors tend to present with abdominal swelling and an increase in abdominal girth. Occasionally, symptoms occur because of displacement of nerves and vessels or compression of adjacent organs and structures. Signs and symptoms of bowel obstruction are rarely observed. Thes findings are a testament to the clinically silent nature of these tumors, which can be present without significant symptoms for long periods of time because they are often “pushing” tumors rather than tumors that invade into adjacent structures[7]. Notably, the tumor size of the present case was also exceptionally large (25 cm × 23 cm × 15 cm), and the patient had complained about palpable abdominal mass and abdominal distension.

Genetically, WDLPS is a genetically distinct group of lesions, represented by the presence of a unique ring and enormous marker chromosomes. WDLPS have molecular genetics consisting of ring chromosomes and giant markers (12q13-15), and molecular genetics: Amplification of MDM2, CDK4, and HMGA2[8]. Accordingly, molecular or immunohistochemical techniques can be used to detect the amplification of HMGA2, MDM2, and CDK4 (as well as overexpression of corresponding proteins) in ALT/WDLPS, which can be a helpful for diagnostic and therapeutic instrument[9-11]. In WDLPS, MDM2 is the most studied of among genomic aberrations. In comparison with WDLPS, DDLPS includes supererogatory genetic abnormalities, primarily co-amplifications of 1p32 and 6q23, that increase the rate of recurrence and metastasis[2].

MDM2 is a proto-oncogene which is involved in cell cycle regulation, approximately 7% of all human malignancies and one-third of all types of sarcomas involve MDM2 amplification, although the amplification rates are significantly higher in WDLPS and DDLPS. MDM2 is an E3 ubiquitin protein ligase whose expression products binds to the transcription activation domain of p53, and it is involved in the transcription inhibition of p53, while MDM2 blocks the p53 transactivation domain, targeting p53 for degradation, potentially leading to tumor cell death[12,13]. A typical class of MDM2 antagonists was specifically designed to obstruct the interaction between MDM2 and p53[14,15]. However, further research is needed to optimize the translation of MDM2 inhibitors into the clinical setting. Notably, no other carcinomatous component was recognized after pathological examination, whereas a lipoma-like WDLPS component was identified in our case. Combining immunohistochemical staining and MDM2 amplification in this case, the diagnosis of WDLPS was more appropriate.

Given the rarity of small bowel mesenteric LPS, the possibility of secondary DDLPS should be excluded, and molecular genetic validation and examinations must be performed to exclude metastasis to confirm whether it is of primary retroperitoneal origin. However, the patient did not have a history of LPS, and imaging examinations did not reveal any evidence of other tumor other than the small bowel. Consequently, further researches on a larger scale are needed to reveal whether LPS has unique characteristics in the small intestine mesentery.

WDLPS arises at similar frequency in the retroperitoneum and limbs. Morphological variants of WDLPS tend to exhibit anatomical tropism, which can be helpful diagnostically. Moreover, the difference in MDM2 amplification between tumor and adipose tissue exterior the small bowel mesentery demonstrated that the tumor stemmed from the small bowel mesentery, and confirmed the accurate diagnosis of WDLPS.

WDLPS is a low-grade tumor characterized by malignant adipocytes, slow-growing masses with no metastatic potential, and is insensitive to radiation and chemotherapy, may recur locally after surgery[4,16]. Resection of all macroscopic disease without obligate resection of nearby structures is referred to as limited (or “marginal”) resection. In order to preserve the functional state of the small intestine as much as possible, the option of extended resection should not be considered. In a systematic review of ALT/WDLPS, lymph node resection is not indicated because these tumors do not spread to the lymph nodes, and local recurrence rates following marginal compared with wide resection were 11% vs 3% respectively[17]. Whereas DDLPS, round cell, and pleomorphic LPS are aggressive high-grade tumors with metastatic potential[18], particularly located in the retroperitoneum compared with the extremity and trunk wall. The early symptoms of these diseases are nonspecific, manifest as abdominal masses when they enlarge sizes and may cause pressure symptoms or lower limb edema[19]. Nevertheless, the current case exhibited peculiar low-grade WDLPS morphological features.

At present, without validated guidelines have been established for the treatment of mesenteric LPS. Regardless of the type of LPS, provided that there is no organ infiltration or distant metastasis, surgical excision is the recommended preferred treatment of mesenteric LPS, widespread resection of the negative margin (R0) is the standard surgical method, but it is more challenging for large mesenteric tumors. It is worth noting that avoid damaging the intraoperative mesenteric blood vessels of the small intestine to prevent ischemic necrosis of the small intestine, without grievous vice-damages and complications occurred. In this case, preoperative multidisciplinary discussion was organized, formulated precise surgical plans for patients.

Clinically, the potential morbidity must be taken into account, while adhering to oncological principles (e.g., not severely damaging the integrity of the tumor), with the goal of at least complete resection. Surgery should remove as much of the tumour and surrounding adipose tissue as possible, or else the remaining adipose tissue could be a cause of recurrence. If the adjacent tissues and organs were invaded, the surrounding infiltrating tissues and organs should be removed to obtain a good prognosis. Regular follow-up and long-term monitoring of the surgical site are recommended for assessment of the local condition. However, regardless of the degree of the resection, the integrity of surgical resection is an independent prognostic factors of local recurrence and overall survival[20].

Due to the large size of the tumor, unclear defined disease scope, and its location in the pivotal structures of the small intestine mesentery, surgical resection becomes technically challenging. Textbook outcomes are complicated measures aimed at determining the gold standard surgical outcomes for complicated tumor resection, which include direct or alternative indicators of perioperative duration, technical proficiency, intraoperative complications, and short-term morbidity rate and mortality[21].

The accurate diagnosis of WDLPS demands an experienced pathologist and applies immunohistochemistry and cytogenetics. Distinguishing WDLPS from DDLPS is necessary to determine the region of DDLPS for differential diagnosis. In addition, pathologist need to differentiate other conditions from these diseases such as lipoma, fibrosarcoma, fibroadenoma, lymphoma, and so on. If difficult diagnosis is encountered, senior pathologists should be consulted, and genetic testing can be performed if necessary.

The amplification of MDM2 and CDK4 is the main molecular feature of WDLPS and DDLPS. For these cases arising from rare diseases, postoperative histological inspection and molecular detection can be valuable for making a correct diagnosis. Immunohistochemical and fluorescence in situ hybridization analysis of this case revealed that high amplification of the MDM2 gene strongly supported the diagnosis of the small intestinal mesenteric LPS. However, CDK4 molecular detection was not carried out in the pathology department of our hospital.

Given the rarity of this disease, different LPS subtypes have varying clinical features and sensitivities to treatment regimens, and thus necessitate a tailored and specific approaches to their management. There are no guidelines are available regarding adjuvant therapy, chemotherapy and radiotherapy are still being controversial, which make the development of clear protocols a substantial challenge. However, targeting MDM2 is a promising treatment strategy, as evidenced by the increasing number of MDM2 inhibitors entering the clinic. Additional clinical investigation is needed to further elucidate the role of MDM2 inhibitors in the treatment of human cancers[22].

At present, scholars focus is on defining sarcomas based on their histologic subtype, molecular profile and genetic alterations, instead of their anatomic origins, which will facilitate the development of novel therapies, such as these that involve MDM2 and CDK4/6 inhibitors. Well-differentiated subtypes are characterized by recurrent amplifications within chromosome 12, which resulting in the overexpression of disease-driving genes that have been the focus of therapeutic targeting. Although some histologic variants demonstrate indolent behavior with a low metastatic risk, others are highly aggressive, and require prompt intervention and multimodal treatment. Systemic therapies, including chemotherapy, radiotherapy, and immunotherapy, are increasingly being explored in neoadjuvant and adjuvant settings, which can reduce the risk of local recurrence[23].

Anatomical position is a significant prognostic factor for LPS, and retroperitoneal LPS ecumenically exhibits a poor clinical manifestation[24]. Tumor grading, subtype, surgical complete resection, metastasis, and tumor size are associated with the prognosis for LPS[25].

Despite the patient did not receive postoperative radiotherapy or chemotherapy on account of personal selection, but close and regular follow-up ensured prompt management of any tumor progression. It is worth noting that MDM2 amplification in this type of tumor is beneficial for patients to provide opportunities to benefit from targeted therapy. MDM2 is a paramount driver gene for ALT/WDLPS/DDLPS and even if it is remained in clinical trial stages, which expected to become an effective treatment option, especially for patients with disease recurrence or tumor metastasis[26].

However, after the patient was discharged, we conducted close follow-up via phone two months later. We learned that the patient had passed away, but the specific cause of death is unknown. We didn't know whether it was due to pulmonary embolism, cerebral hemorrhage, acute myocardial infarction, or sudden cardiac death, but the patient's family didn't disclose whether the patient died from accidental accident. Therefore, we can’t estimate whether the tumor had recurred after learned that the patient didn’t follow the doctor's advice to visit the oncology department for any adjuvant therapy postoperatively. We wanted to determine the cause of the patient's death, but the patient's family didn't provide specific information about the death of patient.

In clinical practice, when an abdominal mass is associated with a radiographical mass lesion, especially the mass is derived from the small bowel mesentery or retroperitoneal, LPS should be considered in differential diagnosis. In addition, more experts can provide diagnosis and treatment suggestions for mesenteric LPS and reach an expert consensus.

CONCLUSION

In conclusion, complete surgical resection remains the primary curative treatment for colossal mesenteric WDLPS. Histopathological examination supplemented by MDM2 amplification analysis is crucial for a definitive diagnosis. The role of adjuvant therapy in this specific scenario remains unclear and requires further investigation. Despite successful resection, close postoperative monitoring is essential, acknowledging that patient comorbidities and compliance with follow-up significantly impact on overall outcomes.