Clear cell sarcoma metastasizing to the pancreas

Abstract

In this editorial based on a case report, we delve into a seldom-seen occurrence of clear cell sarcoma featuring pancreatic metastasis in a 47-year-old male patient. Recognized for its typical tendency to metastasize to the lungs, bones, and brain, clear cell sarcoma rarely extends its reach to the pancreas. Despite the initial absence of discernible abnormalities during the patient's physical examination, the manifestation of abdominal pain prompted further investigation. Subsequent abdominal computed tomography brought to light the presence of a pancreatic tumor, culminating in the definitive diagnosis of clear cell sarcoma with pancreatic metastasis. The successful management of this atypical presentation involved a series of surgical interventions, including distal pancreatectomy and splenectomy. This report not only sheds light on the infrequent manifestation of clear cell sarcoma within the pancreas but also underscores the pivotal role of vigilant postoperative follow-up in addressing this rare sarcoma. The emphasis on postoperative care serves as a crucial aspect of the broader narrative, acknowledging the need for ongoing monitoring and management to ensure a comprehensive and successful treatment trajectory for patients with this unique presentation of clear cell sarcoma.

Key Words: Clear cell sarcoma; Pancreatic metastasis; Soft tissue sarcoma; Surgical interventions; Postoperative follow-up

Core Tip: This editorial elucidates a rare case of clear cell sarcoma (CCS) with pancreatic metastasis, emphasizing the unusual presentation of this soft-tissue sarcoma. The case highlights the diagnostic challenges, successful surgical interventions, and the paramount importance of meticulous postoperative follow-up for optimal patient management. Clinicians and oncologists are urged to consider pancreatic involvement in CCS, fostering heightened awareness and early detection. The reported case contributes valuable insights into refining treatment strategies for CCS, encouraging a comprehensive approach that integrates timely diagnosis, surgical intervention, and vigilant postoperative care.

INTRODUCTION

Pancreatic ductal adenocarcinoma accounts for a significant majority, approximately 90%, of all pancreatic neoplasms, featuring a spectrum of subtypes such as acinar carcinoma, pancreaticoblastoma, and neuroendocrine tumors[1]. The diagnosis of pancreatic cancer is often complicated by the prevalence of nonspecific symptoms, leading to a delayed identification at advanced stages where curative surgery poses greater challenges.

Undifferentiated pleomorphic sarcoma, previously designated as malignant fibrous histiocytoma, stands out as the prevailing form of soft tissue sarcoma. Typically manifesting in the limbs, trunk, and retroperitoneal tissues, its occurrence within digestive organs remains infrequent[2]. In contrast, primary pancreatic clear cell carcinomas, characterized by a predominant composition of clear tumor cells, are exceptionally rare in clinical observations, adding to the uniqueness of this malignancy within the pancreatic landscape.

Clear cell sarcoma (CCS) stands out as an uncommon tumor with a predilection for developing in the deep soft tissues of the lower extremity, often in close proximity to tendons, fascia, or aponeuroses. This malignancy predominantly affects adolescents and young adults, characterized by a significant proclivity for regional or distant metastases. The elusive origins of this tumor have been a subject of prolonged debate, contributing to the complexity of understanding its pathogenesis.

CCS adds a layer of complexity to the spectrum of rare soft tissue tumors, sparking intricate debates in classification due to its unique combination of clinical, pathologic, and molecular traits. This neoplasm shares characteristics with both melanoma and sarcoma, contributing to the ongoing discourse surrounding its classification within the broader landscape of soft tissue malignancies. Notably, the rarity of CCS within the gastrointestinal tract adds to its overall clinical uncommonness.

The historical trajectory of CCS recognition traces back to Enzinger's initial description in 1965, where it was identified as a distinctive form of soft tissue sarcoma. Over the years, multiple lines of evidence have emerged, suggesting a potential for melanocytic differentiation[3]. In 1983, Chung and Enzinger proposed a name change to "melanoma of soft parts," hinting at a potential origin from migrated neural crest cells capable of melanin synthesis[4]. This shift in nomenclature reflects the evolving understanding of CCS and its intricate relationship with melanocytic elements. The journey of CCS, from its first characterization by Enzinger to subsequent refinements in nomenclature proposed by Chung and Enzinger, showcases the ongoing evolution in our comprehension of this unique soft tissue tumor.

The distinctive characteristics of CCS are often highlighted by its immunoreactivity for melanoma markers such as HMB45 and the presence of melanosomes, both confirmed through meticulous ultrastructural analysis[5,6].The pathogenesis of CCS is intricately linked to its origin from neural spinal cells, a process marked by the EWSR1-ATF1 gene fusion resulting from t(12;22) (q13;q12) translocation[7,8]. This translocation event gives rise to a chimeric protein, wherein the C-terminal of EWS, encompassing an RNA binding domain, is replaced by the functional bZIP DNA-binding and dimerization domain of ATF1, a transcription factor typically under the regulation of cAMP[9,10].

The molecular underpinnings of CCS underscore its complexity and distinctive nature within the realm of soft tissue tumors. The fusion of EWSR1 and ATF1 not only provides insight into the cellular origin but also contributes to the unique characteristics observed in CCS. This fusion event plays a pivotal role in the tumorigenic process, shaping the phenotype and behavior of CCS.

Gastrointestinal clear cell sarcoma (GI CCS) is recognized for its aggressive behavior, showcasing a high incidence of both local (lymph node) and distant metastasis, with the liver being the most frequently affected site. This aggressive nature underscores the clinical challenges associated with GI CCS, emphasizing the importance of early detection and comprehensive management strategies in addressing its metastatic potential. The unique molecular and clinical features of CCS contribute to its status as a distinctive entity within the broader spectrum of soft tissue sarcomas. Approximately 50% of reported cases presented with lymph node metastasis at the time of diagnosis, and some cases showed metastases to the liver[11].

Within this editorial, the focal point is the article titled ‘Metastatic clear cell sarcoma of the pancreas: A rare case report,’ penned by Liu et al[12] and published in the World Journal of Clinical Cases. This report distinguishes itself by adeptly illuminating the intricacies associated with a rare presentation of an already uncommon disease entity.

The significance of this case report lies in its ability to shed light on the challenges posed by the atypical manifestation of CCS in the pancreas, specifically addressing the complexities of metastatic occurrences. Diagnosing CCS within the gastrointestinal (GI) tract, as exemplified by the pancreatic manifestation explored in the case report, poses a notable challenge. This challenge arises from the inconsistent expression of melanocytic markers, a characteristic feature of CCS, and the atypical site of presentation within the GI tract. The multifaceted diagnostic approach advocated in the article underscores the need for a comprehensive and thorough examination to navigate the complexities associated with identifying and characterizing CCS in uncommon anatomical locations.

CASE REPORT

Clinical Presentation: The patient's medical odyssey commenced with the persistence of abdominal pain and diarrhea for an extended period of over half a month. Initial examinations, including thorough physical and laboratory tests, failed to reveal any alarming signs. However, the application of advanced imaging techniques, specifically computed tomography and magnetic resonance imaging (MRI), brought to light a singular lesion located in the pancreatic tail. This particular presentation underscores the diagnostic challenges associated with the rarity of CCS metastasis to the pancreas.

Diagnostic Dilemma: The preoperative diagnostic phase did not conclusively rule out the potential recurrence of CCS, especially given the patient's pertinent medical history. This underscores the intricate nature of diagnosing rare metastatic cases and emphasizes the critical role of comprehensive evaluations in informing and guiding treatment decisions. The nuances of this diagnostic dilemma highlight the need for a meticulous and multi-faceted approach in navigating the complexities associated with uncommon disease presentations, ultimately contributing to more informed and effective patient care.

Treatment Strategy: The patient underwent a comprehensive surgical intervention, which encompassed a distal pancreatectomy and splenectomy. This meticulous procedure involved the precise ligation of various pancreatic arteries, freeing the pancreas, and excising the tumor. The outcome proved to be a highly successful surgery, with no discernible evidence of residual tumors noted in the pancreatic margins or spleen.

Follow-up and Recovery: In the postoperative phase, the patient exhibited a remarkably smooth recovery, devoid of any complications. Notably, during the 6-month follow-up period, the patient remained asymptomatic and opted to forego additional therapeutic interventions or examinations. This case contributes a distinctive dimension to the limited existing literature on metastatic CCS in the pancreas. The success of the surgical intervention and the patient's uneventful recovery underscore the paramount importance of tailored approaches in managing such rare occurrences. It accentuates the necessity for the ongoing exploration of effective treatment modalities and underscores the critical role of vigilant postoperative follow-up in ensuring the patient's long-term well-being.

CLINICAL IMPLICATION

The clinical implications of metastatic CCS of the pancreas are underscored by its rarity and challenging management. Typically affecting the lower extremities, CCS is infrequently observed in the pancreas. Clinical manifestations include abdominal pain, intestinal obstruction, anaemia, nausea, and vomiting. Current management relies on surgery as the standard treatment, emphasizing the importance of clean tumor margins. Preoperative imaging, particularly MRI, aids in surgical planning.

Despite surgery being the primary approach, CCS has a poor prognosis, and postoperative treatments like chemotherapy and radiotherapy show limited effectiveness. Targeted therapy or immunotherapy holds potential, but conclusive clinical trials are lacking. Long-term follow-up is crucial due to the high likelihood of recurrence or metastasis, significantly reducing the 5-year survival rate in advanced stages. Early detection through postoperative monitoring is vital, yet the patient's resistance to follow-ups in this case led to delayed treatment. This highlights the importance of patient compliance and regular surveillance for effective disease management and improved outcomes.

CONCLUSION

In conclusion, metastatic CCS of the pancreas poses a clinical challenge due to its rarity and complex management. Originating from neural spinal cells with specific genetic characteristics, CCS primarily affects the lower extremities but sporadically appears in the pancreas, leading to diverse clinical manifestations. The predominant treatment remains surgery, emphasizing the necessity of achieving clean tumor margins, supported by preoperative imaging assessments such as MRI.

Overall, the prognosis for CCS is bleak, and conventional postoperative interventions like chemotherapy and radiotherapy demonstrate limited efficacy. While targeted therapy or immunotherapy holds promise, definitive clinical trials are lacking. The condition's high recurrence and metastasis rates underscore the importance of long-term follow-up, as delayed detection significantly impacts the already compromised 5-year survival rate in advanced stages. Patient compliance with regular surveillance is paramount, as demonstrated in the presented case, where resistance to follow-ups led to delayed treatment. This emphasizes the critical role of postoperative management in CCSLGT to enhance early detection, inform timely interventions, and ultimately improve patient outcomes.