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. Author manuscript; available in PMC: 2020 Aug 19.
Published in final edited form as: Turk Patoloji Derg. 2018;34(1):104–107. doi: 10.5146/tjpath.2014.01297

DEDIFFERENTIATED LIPOSARCOMA OF THE GASTROESOPHAGEAL JUNCTION

Gokce Askan 1, Pelin Bagci 1, Meera Hameed 2, Olca Basturk 2
PMCID: PMC7437155  NIHMSID: NIHMS1617791  PMID: 25690861

Abstract

Liposarcoma is one of the most common sarcomas in adults, but very rarely presents as a primary in the upper gastrointestinal system. Herein, we present a case of dedifferentiated liposarcoma of the gastroesophageal junction with morphologic evidence of both well-differentiated and dedifferentiated components as well as demonstration of MDM2 gene amplification by fluorescence in situ hybridization. We believe this is the first reported case of dedifferentiated liposarcoma of the gastroesophageal junction.

INTRODUCTION

Liposarcoma is one of the most common malignant soft tissue tumors in adults. Current World Health Organization (WHO) divides liposarcomas into four subtypes1, 2: The atypical lipomatous tumor/well differentiated liposarcoma (WDLPS) is the most common subtype and, along with dedifferentiated liposarcoma (DDLPS), commonly occur in the retroperitoneum3, 4, whereas the myxoid, and pleomorphic ones typically present in the extremities5.

In general, liposarcomas are extremely uncommon in the gastrointestinal tract6–13, especially at the gastroesophageal junction. We describe herein, the first case of DDLPS of the gastroesophageal junction. The diagnosis was based on morphology, MDM2 and CDK4 immunoexpression and fluorescence insitu hybridization analysis.

CASE REPORT

Seventy-one year old male patient with a history of long-term dysphagia underwent a wedge excision in 1996 for presumed benign gastroesophageal junction mass, as per history from the patient. In 2006, repeat endoscopy revealed a recurrent lesion and another partial excision was performed. Pathology materials of these excisions were not available for our evaluation.

The patient was regularly followed up and a 3–4 cm mass with ulceration was found in the cardia at upper endoscopy, performed in 2013. Biopsies were non-diagnostic. Endoscopic ultrasound revealed a 2,2 cm hypoechoic mass with superficial erosions at the gastroesophageal junction. It was thought to be arising from the mucosa and likely invading the superficial submucosa. The muscularis propria was intact. Fine needle aspiration (FNA) biopsy/cell block revealed a spindle cell neoplasm with nuclear pleomorphism and hyperchromasia. The neoplastic cells were positive for CD34, while negative for CD117 and DOG1, SMA, S100, and pan-cytokeratin. The morphologic and immunophenotypic findings were not sufficient for a definitive diagnosis; however sarcoma was favored. Axial oral-IV contrast enhanced CT revealed a solid mass in the gastroesophageal junction protruding into the lumen (Fig. 1). There was no definitive evidence of metastatic disease.

Figure 1:

Figure 1:

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Axial oral-IV contrast enhanced CT images showing a solid mass (arrow) in the gastrooeshaphageal junction protruding into the lumen.

The resection specimen consisted of a total gastrectomy with distal esophagus. There was a relatively well-circumscribed, submucosal lesion at the gastroesophageal junction measuring 3 cm in length, 2.5 cm in the width and 1.1 cm in the depth. Sectioning revealed tan-white, solid cut surface. Overlying mucosa was eroded but adjacent mucosa was unremarkable.

Microscopic sections revealed a multinodular neoplasm at the gastroesophageal junction, predominantly located within submucosa and focally extending to the surface epithelium (Fig. 2). The tumor was cellular and was predominantly composed of pleomorphic and spindle cells (Fig. 3), associated with polymorphic inflammatory infiltrate including neutrophils, eosinophils, lymphocytes, and plasma cells. Some of the cells had cytoplasmic vacuoles/bubbly cytoplasm. The mitotic count was up to 15/50 HPF. Differential diagnoses included GIST, leiomyosarcoma, schwannoma, malignant melanoma and less likely sarcomatoid carcinoma. Performed immunohistochemical stains revealed that the tumor cells are negative for CD117, DOG1, CD34, SMA, Desmin, S-100, HMB45, SOX10 as well as AE1/AE3, CAM5.2, and CK18, arguing against these differential diagnoses. At this point additional sampling was done and revealed a small component composed of adipose tissue with fibrous septae containing atypical hyperchromatic stromal cells and scattered lipoblasts (Fig. 4), suggesting DDLPS as the likely diagnosis. Second round immunohistochemical stains revealed that the tumor cells were indeed positive for MDM2 (Fig. 5A), and CDK4, supporting the diagnosis of DDLPS. In order to confirm the diagnosis, fluorescence insitu hybridization was performed and MDM2 gene (12q15) amplification was detected (Fig. 5B).

Figure 2:

Figure 2:

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A multinodular spindle cell tumor at the gastroesophageal junction (x40, H&E).

Figure 3:

Figure 3:

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The dedifferentiated component is predominantly composed of highly pleomorphic spindle cells with nuclear hyperchromasia (x100, x400, H&E).

Figure 4:

Figure 4:

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Atypical lipomatous tumor/well differentiated liposarcoma component is characterized by adipose tissue with fibrous septae containing atypical hyperchromatic stromal cells.

Figure 5A:

Figure 5A:

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Tumor cells show diffuse nuclear labeling with MDM2 antibody (x 200, anti-MDM2).

Figure 5B:

Figure 5B:

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Fluorescence in situ hybridization analysis show amplification of the MDM2 gene(Green - CEP 12 and red - MDM2).

The patient is alive with no evidence of disease 4 months after the resection.

DISCUSSION

Per its first description by Evans14, dedifferentiated liposarcoma (DDLPS) is defined as a combination of atypical lipomatous tumor/well-differentiated liposarcoma (WDLPS) and high grade non-lipogenic sarcoma-like component, such as undifferentiated high-grade pleomorphic sarcoma (i.e. malignant fibrous histiocytoma), fibrosarcoma, or myxofibrosarcoma. It occurs in late adult life (sixth to seventh decades) with an equal distribution between males and females1. The most common location is the retroperitoneum.

DDLPS can occur de novo (90%) or about 10% occur as recurrence from a preexisting WDLPS (10%)15. If it is arising from a preexisting WDLPS, dedifferentiation develops in 20% of the first local recurrences and 44% of the second local recurrences5. Although we could not evaluate the previous pathology materials, the history of recurrent lesions at the gastroesophageal junction suggests preexisting WDLPS in our patient.

CT imaging have been described as the best way to confirm the adipose component in these tumors16, 17, and FNA/tru-cut biopsy seems to be the best way to confirm the diagnosis of sarcoma18, and the tissue obtained by biopsy may even be used for the molecular tests.

The histologic diagnosis is usually based on the identification of WDLPS areas, which was very limited as in our case. In such cases, immunopositivity for CDK4 and MDM2 and detection of amplification of MDM2 and CDK4 genes is diagnostically helpful. Although MDM2 and CDK4 immunohistochemical staining alone is sufficient for the accurate diagnosis in the appropriate context19, 20, they are not 100% specific and sensitive. Therefore, FISH, quantitative PCR, and/or CGH may be essential in cases with diagnostic difficulties21, 22.

To our knowledge, this is the first DDLPS of the gastroesophageal junction and there are only two primary DDLPS of the esophagus have been reported in the English literature23, 24. Both patients are elderly males presented with progressive dysphagia, weight loss, and large masses, measuring up to 10 cm, one protruding into the lumen. In one of these cases, the tumor was also predominantly located in the mucosa and submucosa, as seen in our case.

DDLPS appear to have a better prognosis (especially in terms of metastatic potential) than other high-grade sarcomas. However, careful long term follow up is recommended as approximately 40% of DDLPS will recur locally, 17% will metastasize and 28% of patients will ultimately die of disease1. Surgery is still the best choice of treatment for DDLPS and it is important to remove the tumor entirely4. Targeted chemotherapeutic agents and radiation therapy are being investigated25.

DDLPS of the upper gastrointestinal system is rare but should be considered in the differential diagnosis of any poorly or undifferentiated sarcoma, and extensive sampling may be required for accurate diagnosis. We believe that our case represents the first report of DDLPS of the gastroesophageal junction with both well differentiated liposarcoma and dedifferentiated sarcoma components, as well as confirmation with molecular analysis.

ACKNOWLEDGMENTS

The authors thank Allyne Manzo and Lorraine Biedrzycki for assistance with the figures.

REFERENCES

  • 1.Goldblum JR, Folpe AL, and SW W eds., Enzinger and Weiss’s Soft Tissue Tumors. 6 edn Philadelphia: Elsevier, 2014. [Google Scholar]
  • 2.Fletcher CDM, Bridge JA, Hogendoorn PCW, and F. M, eds., Who Classification of Tumours of Soft Tissue and Bone. ed. by Bosman FT, Jaffe ES, Lakhani SR and H O 4 edn, World Health Organization Classification of Tumours Lyon: International Agency for Research on Cancer, 2013. [Google Scholar]
  • 3.Singer S, Antonescu CR, Riedel E, and MF B, ‘Histologic Subtype and Margin of Resection Predict Pattern of Recurrence and Survival for Retroperitoneal Liposarcoma’. Ann Surg. 2003; 238 (3): 358–70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Choi Y, Kim Y, and Jin S, ‘Primary Liposarcoma of the Ascending Colon: A Rare Case of Mixed Type Presenting as Hemoperitoneum Combined with Other Type of Retroperitoneal Liposarcoma’. BMC Cancer. 2010; 10 (1): 239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Dalal KM, Kattan MW, Antonescu CR, Brennan MF, and S S, ‘Subtype Specific Prognostic Nomogram for Patients with Primary Liposarcoma of the Retroperitoneum, Extremity, or Trunk’. Ann Surg. 2006; 244 (3): 381–91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Okabayashi T, Shima Y, Iwata J, et al. , ‘Primary Liposarcoma of the Duodenum: A First Case Presentation’. Internal Medicine. 2013; 52 (24): 2753–57. [DOI] [PubMed] [Google Scholar]
  • 7.Bostanoğlu A, Yıldız B, Kulaçoğlu S, and F A, ‘Primary Liposarcoma of the Stomach’. Turk J Gastroenterol. 2013; 24 (2): 167–9. [DOI] [PubMed] [Google Scholar]
  • 8.Sui X, Li Y, Zhao H, and Wang J, ‘Giant Liposarcoma of the Esophagus with Li-Fraumeni-Like Syndrome’. European Journal of Cardio-Thoracic Surgery. 2011; 40 (5): 1253–55. [DOI] [PubMed] [Google Scholar]
  • 9.HOHF RP, ENGEL KL, and NJ C, ‘Liposarcoma of the Stomach’. Ann Surg. 1955; 142 (6): 1029–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Laky D, and T S, ‘Gastric Liposarcoma. A Case Report’. Pathol Res Pract. 1986; 181 (1): 112–7. [DOI] [PubMed] [Google Scholar]
  • 11.López-Negrete L, Luyando L, Sala J, et al. , ‘Liposarcoma of the Stomach’. Abdominal Imaging. 1997; 22 (4): 373–75. [DOI] [PubMed] [Google Scholar]
  • 12.Michiels A, Hubens G, Ruppert M, Balliu L, and W V, ‘Giant Liposarcoma of the Stomach Involving the Mediastinum.’. Acta Chir Belg. 2007; 107 (4): 468–71. [DOI] [PubMed] [Google Scholar]
  • 13.Smith MA, Kluck E, Jagannath S, and Yang SC, ‘Giant Multi-Polypoid Liposarcoma of the Esophagus: An Atypical Presentation’. The Annals of Thoracic Surgery. 2010; 89 (2): 610–12. [DOI] [PubMed] [Google Scholar]
  • 14.HL E, ‘Liposarcoma: A Study of 55 Cases with a Reassessment of Its Classification’. Am J Surg Pathol. 1979; 3 (6): 507–23. [DOI] [PubMed] [Google Scholar]
  • 15.Henricks WH, Chu YC, Goldblum JR, and SW W, ‘Dedifferentiated Liposarcoma: A Clinicopathological Analysis of 155 Cases with a Proposal for an Expanded Definition of Dedifferentiation’. Am J Surg Pathol. 1997; 21 (3): 271–81. [DOI] [PubMed] [Google Scholar]
  • 16.Ferrozzi F, Tognini G, Marchesi G, Spaggiari E, and P. P, ‘Gastric Tumors with Fatty Components. Ct Findings and Differential Diagnosis’. Radiol Med. 2000; 100 (5): 343–7. [PubMed] [Google Scholar]
  • 17.Ferrozzi F, Tognini G, Bova D, and P. P, ‘Lipomatous Tumors of the Stomach: Ct Findings and Differential Diagnosis’. J Comput Assist Tomogr. 2000; 24 (6): 854–8. [DOI] [PubMed] [Google Scholar]
  • 18.Takahashi Y, Irisawa A, Bhutani MS, et al. , ‘Two Cases of Retroperitoneal Liposarcoma Diagnosed Using Endoscopic Ultrasound-Guided Fine-Needle Aspiration (Eus-Fna)’. Diagnostic and Therapeutic Endoscopy. 2009; ( [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Binh MB, Sastre-Garau X, Guillou L, et al. , ‘Mdm2 and Cdk4 Immunostainings Are Useful Adjuncts in Diagnosing Well-Differentiated and Dedifferentiated Liposarcoma Subtypes: A Comparative Analysis of 559 Soft Tissue Neoplasms with Genetic Data’. Am J Surg Pathol. 2005; 29 (10): 1340–7. [DOI] [PubMed] [Google Scholar]
  • 20.Neuville A, Ranchère-Vince D, Dei Tos AP, et al. , ‘Impact of Molecular Analysis on the Final Sarcoma Diagnosis: A Study on 763 Cases Collected During a European Epidemiological Study’. Am J Surg Pathol. 2013; 37 (8): 1259–68. [DOI] [PubMed] [Google Scholar]
  • 21.Hostein I, Pelmus M, Aurias A, et al. , ‘Evaluation of Mdm2 and Cdk4 Amplification by Real-Time Pcr on Paraffin Wax-Embedded Material: A Potential Tool for the Diagnosis of Atypical Lipomatous Tumours/Well-Differentiated Liposarcomas’. J Pathol. 2004; 202 (1): 95–102. [DOI] [PubMed] [Google Scholar]
  • 22.Sirvent N, Coindre JM, Maire G, et al. , ‘Detection of Mdm2-Cdk4 Amplification by Fluorescence in Situ Hybridization in 200 Paraffin-Embedded Tumor Samples: Utility in Diagnosing Adipocytic Lesions and Comparison with Immunohistochemistry and Real-Time Pcr’. Am J Surg Pathol. 2007; 31 (10): 1476–89. [DOI] [PubMed] [Google Scholar]
  • 23.Watkin E, Devouassoux-Shisheboran M, Pedeutour F, et al. , ‘A First Reported Case of Dedifferentiated Liposarcoma of the Esophagus with Molecular Diagnosis’. Journal of Gastrointestinal Cancer. 2011; 42 (1): 65–67. [DOI] [PubMed] [Google Scholar]
  • 24.Torres-Mora J, Moyer A, Topazian M, et al. , ‘Dedifferentiated Liposarcoma Arising in an Esophageal Polyp: A Case Report’. Case Reports in Gastrointestinal Medicine. 2012; 2012: 3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Radaelli S, Stacchiotti S, Casali PG, and Gronchi A, ‘Emerging Therapies for Adult Soft Tissue Sarcoma’. Expert Rev Anticancer Ther. 2014; 14 (6): 689–704. [DOI] [PubMed] [Google Scholar]

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