“Wnt/β-catenin-activated Ewing's sarcoma with metastasis to pancreas:” A rare case report

Shilpa Kapoor; Trupti Patel; Kanwalpreet Kaur; Priti Trivedi

doi:10.4103/aort.aort_17_22

CASE REPORT

Year : 2022 | Volume : 2 | Issue : 2 | Page : 101-103

“Wnt/β-catenin-activated Ewing's sarcoma with metastasis to pancreas:” A rare case report

Shilpa Kapoor, Trupti Patel, Kanwalpreet Kaur, Priti Trivedi
Department of Oncopathology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India

Date of Submission	29-May-2022
Date of Decision	22-Jun-2022
Date of Acceptance	23-Jun-2022
Date of Web Publication	18-Nov-2022

Correspondence Address:
Dr. Shilpa Kapoor
Department of Oncopathology, Room 412, First Floor, New Cancer Building, Gujarat Cancer and Research Institute, Ahmedabad - 380 016, Gujarat
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aort.aort_17_22

Abstract

Ewing's sarcoma (ES) family of tumors are aggressive tumors with high metastatic potential. Various unusual sites of metastasis have been reported, with pancreas being one of the exceptional sites. Herein, we report a case of a 21-year-old biopsied for a pancreatic mass and its histopathological evaluation revealed infiltration by a malignant small round cell tumor. Given that the patient was under treatment for ES of the right iliac bone an immunohistochemistry panel applied showed CD99, FLI-1 positivity proving it to be a metastasis. Furthermore, β-catenin put on clinical suspicion of solid pseudopapillary neoplasm was positive. Recent evidence suggest that elevated β-catenin expression is associated with poor outcomes, signifying Wnt/β-catenin signaling pathway contributes to disease progression. We not only report an uncommon metastasis of ES to the pancreas with four other cases reported so far but we also attempt to analyze probable correlation of β-catenin to disease advancement and its prognostic implication.

Keywords: Ewing's sarcoma, metastasis, Wnt/β-catenin signaling

How to cite this article:
Kapoor S, Patel T, Kaur K, Trivedi P. “Wnt/β-catenin-activated Ewing's sarcoma with metastasis to pancreas:” A rare case report. Ann Oncol Res Ther 2022;2:101-3

How to cite this URL:
Kapoor S, Patel T, Kaur K, Trivedi P. “Wnt/β-catenin-activated Ewing's sarcoma with metastasis to pancreas:” A rare case report. Ann Oncol Res Ther [serial online] 2022 [cited 2023 Mar 25];2:101-3. Available from: http://www.aort.info/text.asp?2022/2/2/101/361490

Introduction

Ewing's sarcoma (ES) family of tumors comprises 5%–10% of all primary bone and soft-tissue tumors. The prognosis of patients presenting with metastasis at the time of initial diagnosis is dismal despite aggressive therapies given.^[1] Usual sites of metastasis are lungs and bones but cases with metastasis to the stomach, bowel, ovary, and brain have also been reported. ES metastasis to pancreas is extremely rare with only four other cases reported in literature till date.^[2] Mechanisms underlying disease development and progression remain poorly known but recent studies have shown that elevated Wnt/β-catenin expression is associated with worse clinical outcomes.^[3] Herein, we are enriching the literature with another case of ES metastasis to the pancreas in a 21-year-old male highlighting the role of β-catenin signaling pathway through immunohistochemistry (IHC).

Case Report

A 21-year-old male patient found to have an ill-defined 59 mm × 68 mm sized heterogeneously enhancing mass in the distal pancreas [Figure 1]a was biopsied for the same. Its histopathological examination revealed cores of tissue [Figure 2]a composed of fairly monotonous tumor cells with individual cell showing high nucleocytoplasmic ratio, round nuclei, fine chromatin, inconspicuous nucleoli, and scant cytoplasm [Figure 2]b. A fragment of pancreatic tissue was identified infiltrated by tumor cells [Figure 2]c. Occasional mitosis was evident. First impression was a malignant round cell tumor. On looking back into the history it was found that the patient had been diagnosed with a case of ES of right iliac bone with concurrent lung metastasis 3 years back. He was initially treated with chemotherapy (vincristine, doxorubicin, and ifosfamide) followed by radiotherapy. Residual mass was followed thereafter with radiology [Figure 1]b, but he did not achieve remission at primary site though lung metastasis showed complete resolution. On routine follow-up, he was incidentally found to have a pancreatic mass on computed tomography (CT) scan and its histomorphology was comparable with the morphology of initial iliac bone biopsy [Figure 2]d. Working on the rare possibility of ES metastasis to pancreas, any other differentials including lymphomas, neuroendocrine neoplasms, and solid pseudopapillary neoplasm (SPEN) were considered while planning an IHC panel. The panel included CD99, FLI-1, LCA, vimentin, synaptophysin, and β-catenin. IHC performed showed positivity for vimentin, CD99 [Figure 3]a, FLI-1 [Figure 3]b, β–catenin while being negative for synaptophysin, LCA. This not only consolidated diagnosis of ES metastasis to the pancreas but also revealed nuclear β-catenin positivity [Figure 3]c. This was compared with β-catenin expression on the iliac bone biopsy which was negative [Figure 3]d. On follow-up after 4 months, the patient is on cyclophosphamide with topotecan and is being planned for surgery.

Figure 1: (a) CT scan showing a soft-tissue density in distal pancreas, (b) CT scan of Ill-defined sclerotic lesion in the right iliac bone with no soft-tissue component. CT: Computed tomography

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Figure 2: (a) Cores of tissue obtained from pancreatic biopsy (H and E, ×4), (b) Tumor tissue showing cells with small round cell morphology (H and E, ×400), (c) Tumor cells infiltrating into pancreatic tissue (H and E, ×400), (d) Histomorphology of tumor from initial iliac bone biopsy (H and E, ×400)

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Figure 3: (a) IHC for CD99 positive in tumor tissue, (b) IHC for FL-1 positive in tumor tissue, (c) β-catenin IHC shows strong nuclear positivity in tumor from pancreatic biopsy (d) β-catenin IHC showing only cytoplasmic positivity in tumor from iliac bone biopsy. IHC: Immunohistochemistry

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Discussion

We report an uncommon case of pancreatic metastasis from a primary osseous ES in a patient who did not completely respond to the therapy despite aggressive treatment. Four other case studies reported in literature demonstrate the development of pancreatic metastasis as early as 8 months to as late as 2½ years after initial diagnosis. Our patient developed pancreatic metastasis after 3 years which is a while longer compared to other cases reported. Metastasis to such rare sites even after years of treatment should be kept in mind if clinically or radiologically suspicious and a biopsy is advised. The multimodality approach including imaging, biopsy, and IHC greatly helps in patient management. Differentials were excluded based on histomorphology and IHC results. SPEN which is a low-grade pancreatic neoplasm affecting young with distinct female preponderance was considered because of atypical clinical presentation. Individual nuclear β-catenin positivity without synaptophysin and favorable morphology not only excluded SPEN as a diagnosis but also provides evidence that high Wnt/β-catenin activity can be associated with disease progression and emerging drug resistance. Positive expression of β-catenin at the metastatic site in contrast to expression at primary biopsy indicates a phenotypic switch of Wnt/β-catenin in a certain population of tumor cells, all contribute to disease progression and relapse. It has been hypothesized through transcriptomic data analysis that β-catenin-activated tumor cells alter tumor microenvironment and promote angiogenic switch.^[4] We demonstrated the expression of WNT/β-catenin signaling pathway via IHC which can help us to predict tumor behavior in advance. Targeting of Wnt/β-catenin axis for focused therapy remains a challenge because of intrinsic difficulties directed toward transcriptional networks. Nevertheless, target therapy in these tumors can be a worthy endeavor therefore we recommend more such studies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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2.	Polimera H, Moku P, Abusharar SP, Vasekar M, Chintanaboina J. Metastasis of Ewing sarcoma to the pancreas: Case report and literature review. Case Rep Oncol Med 2020;2020:7075048.
3.	Pedersen EA, Menon R, Bailey KM, Thomas DG, Van Noord RA, Tran J, et al. Activation of Wnt/β-Catenin in Ewing sarcoma cells antagonizes EWS/ETS function and promotes phenotypic transition to more metastatic cell states. Cancer Res 2016;76:5040-53.
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