Undifferentiated pleomorphic sarcoma (UPS) is a rare malignant mesenchymal tumor with a poor prognosis. It mainly occurs in the extremities, trunk, head and neck, and retroperitoneum regions. Owing to the lack of specific clinical manifestations and imaging features, UPS diagnosis mainly depends on pathological and immunohistochemical examinations for exclusive diagnosis. Here we report an extremely rare case of high-grade UPS in the common bile duct (CBD). There are limited available data on such cases.

A 70-year-old woman was admitted to our department with yellow eyes and urine accompanied by upper abdominal distending pain for 2 wk. Her laboratory data suggested significantly elevated hepatorenal function levels. The imaging data revealed calculous cholecystitis, intrahepatic and extrahepatic bile duct dilation with extrahepatic bile duct calculi, and a space-occupying lesion at the distal CBD. After endoscopic biliary stenting and symptomatic support therapy, CBD exploration and biopsy were performed. The frozen section indicated malignant spindle cell tumor of the CBD mass, and further radical pancreaticoduodenectomy was performed. Finally, the neoplasm was diagnosed as a high-grade UPS combined with the light-microscopic morphology and immunohistochemical results.

This extremely rare case highlighted the need for increasing physicians' vigilance, reducing the odds of misdiagnosis, and providing appropriate treatment strategies.

Undifferentiated pleomorphic sarcoma (UPS), also known as malignant fibrous histiocytoma (MFH)[1], is a rare malignant mesenchymal tumor with a mixed pattern of fibroblast and histiocyte growth. MFH was divided into five histological subtypes, namely, storiform-pleomorphic, myxoid, giant-cell, inflammatory, and angiomatoid MFH[2]. In 2002, the World Health Organization (WHO) classified myxoid and angiomatoid MFH into myofibroblast-like and uncertain differentiated tumors, respectively[3]. The redefined MFH includes three histological subtypes. The first subtype is Storiform-pleomorphic MFH, also known as high-grade UPS, which was the most common subtype. The typical microstructure of the tumor cells is that they have obvious atypia, predominantly characterized by a combination of storiform and pleomorphic areas. Cells within the storiform area have spindle-shaped or circular morphology. The second subtype is the giant-cell MFH, also known as UPS with giant cells. Its typical microstructure includes a large number of multinucleated giant cells, mostly osteoclast-like. The third subtype is the inflammatory MFH, also known as UPS with obvious inflammation. This subtype is rare and its characteristic microstructure includes spindle cells and xanthoma cells accompanied by inflammatory cells infiltration. According to the 2013 WHO classification of soft tissue tumors (STT), the term MFH was removed and substituted with UPS, categorized as undifferentiated/unclassified soft tissue sarcoma (STS)[4].

UPS mainly occurs in elderly individuals, men are slightly dominant, usually involves the extremities and trunk[5], head and neck[6,7], and retroperitoneum regions[8]. Owing to the complexity of its clinical manifestations and histopathological features, the diagnosis of this condition have presented significant challenges. Here we report an extremely rare case of high-grade UPS in the common bile duct (CBD). For all we know, this is the first reported case of UPS in the CBD.

According to these clinical manifestations and radiographic findings, the patient's primary diagnosis was STT of the distal CBD, with minor diagnoses of intrahepatic and extrahepatic bile duct dilation with extrahepatic bile duct calculi, obstructive jaundice, calculous cholecystitis, hepatorenal dysfunction, hypertension, and diabetes.

Owing to hepatorenal insufficiency, the initial treatment for the patient involved endoscopic biliary stent implantation to alleviate jaundice (Figure 2), followed by adjunctive hepatorenal protection treatment. After the hepatorenal functions were significantly improved, the patient underwent an exploration and biopsy of the CBD, and the frozen section indicated that the neoplasm at the distal CBD was spindle malignant cell tumor. Therefore, further radical pancreaticoduodenectomy was performed.

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Figure 2 Endoscopic retrograde cholangiopancreatography was recommended and a biliary plastic stent was implanted for alleviating jaundice. A: Endoscopic retrograde cholangiopancreatography revealed a space-occupying lesion of the distal common bile duct; B: Endoscopic biliary plastic stent implantation.

The patient experienced a smooth recovery, with the exception of mild pancreatic leakage and an incisional infection. In situ, the neoplasm was located in the distal CBD, measuring approximately 2.2 cm × 1.8 cm in size, and exhibited clear boundaries (Figure 3). Microscopically, the neoplastic cells presented a spindle-shaped or pleomorphic morphology, arranged in sarciniform structure. They exhibited deeply stained nuclei, singular nuclei with evidence of nuclear division, abundant cytoplasm, and scattered infiltration of inflammatory cells (Figure 4). Immunohistochemically, the cytoplasm of the neoplasm cells was diffuse positive for Vimentin (Figure 5A), partially positive for SMA and CD34 (Figure 5B and C), and scattered positive for CK (AE1/AE3) and EMA (Figure 5D and E). The nuclei of the neoplastic cells were positive for H3K27Me3 (Figure 5F). The cytoplasm and nuclei of the tumor cells were positive for S-100 (Figure 5G). The proportion of Ki-67-positive cells was 60% (Figure 5H). However, the neoplastic cells were negative for CK7, Desmin, and CD117 (Figure 5I-K). Based on these histopathologic features, the neoplasm was eventually diagnosed as a high-grade UPS. The patient refused to undergo follow-up treatment and died 22 months later due to tumor recurrence and metastasis.

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Figure 3 In situ, the neoplasm was located in the distal common bile duct, measuring approximately 2.2 cm × 1.8 cm in size, and exhibited clear boundaries.

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Figure 4 Pathological examination findings. The tumor cells were spindle-shaped or pleomorphic, arranged in sarciniform structure, with deeply stained nuclei, singular nuclei and nuclear division, abundant cytoplasm, and scattered inflammatory cells infiltration. A: Hematoxylin & eosin (H&E) staining, magnification: 100 ×; B: H&E staining, magnification: 200 ×.

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Figure 5 Immunohistochemical examination findings. A: The tissue was diffusively positive for Vimentin; B: The tissue was partially positive for SMA; C: The tissue was partially positive for CD34; D: The tissue was scatteredly positive for CK (AE1/AE3); E: The tissue was scatteredly positive for EMA; F: The tissue was partially positive for H3K27Me3; G: The tissue was partially positive for S-100; H: Ki-67 was approximately 60%; I: The tissue was negative for CK7; J: The tissue was negative for Desmin; K: The tissue was negative for CD117.

The etiology and pathogenesis of UPS remain unclear, but it may be secondary to ionizing radiation, inflammation, surgical trauma, smoking or other cancers[9-12]. Recently, with the advancement of molecular gene technology, some studies have suggested that TP53, RB1, PTEN, and ATRX may play an important role in UPS tumorigenesis[13,14]. In addition to common sites, UPS has also been reported in the liver, pancreas, small intestine, spleen and even the gallbladder in a small amount[15-19]. However, it occurring in the CBD is extremely rare.

UPS lacks special clinical manifestations and imaging characteristics. The diagnosis depends on the differentiation of cell morphology under the microscope and the application of immunohistochemistry. Microscopically, UPS presents as a mixture of spindle-shaped and pleomorphic cells, which can be arranged in a storiform or sarciniform pattern[20,21]. Nuclear division is easily observable, and the presentation may be accompanied by various histiocytic and inflammatory cell infiltrations[21,22]. Immunohistochemically, UPS showed no characteristic markers, most of which expressed Vimentin and CD86[21,23], but not HMB45[18]. P53 Overexpression or Rb1 deficiency was common in UPS[24]. In our case, the tumor cells were spindle-shaped or pleomorphic, arranged in sarciniform structure, with deeply stained nuclei, singular nuclei and nuclear division, abundant cytoplasm, and scattered inflammatory cells infiltration. Vimentin exhibited diffuse positivity, while SMA, CD34, H3K27Me3, and S-100 showed partial positivity. CK (AE1/AE3) and EMA showed scattered positivity, whereas CK7, Desmin, and CD117 were negative. The Ki-67 proliferation index 60%.

UPS should to be distinguished from other well-classified STS. For example, myxiod liposarcoma is composed of vacuolar lipoblast cells with myxiod mesenchyme, slender plexiform capillary structure, and S-100 is often expressed[25]. Additionally, pleomorphic liposarcoma is characterized by a bizarre giant lipoblast and often expresses S-100[26]. Moreover, pleomorphic rhabdomyosarcoma is composed of large pleomorphic rhabdomyoblast, cytoplasmic stripes may be observed, and Desmin exhibited diffuse positive, MyoD1 exhibited positive[27]. Furthermore, in pleomorphic leiomyosarcoma cases, classic leiomyosarcoma areas are commonly observed, and the tumor cells express at least one antigen that symbolizes smooth muscle differentiation, such as SMA, Desmin, and h-caldesmon[28]. Finally, in cases of dedifferentiated liposarcoma morphologically indistinguishable from UPS, we need to look for highly differentiated liposarcoma components. If such components are not identified, the inclusion of the MDM2 fluorescence in situ hybridization (FISH) test is warranted. If the FISH tests show MDM2 gene amplification, dedifferentiated liposarcoma should be considered[29]. Therefore, based on microscopic cytological morphology and immunohistochemical analysis, our case was diagnosed as a high-grade UPS. In recent years, Zhou et al[30] have showed that neurofibromin 1 and its related miRNAs, including hsa-miRNA-34a-5p and hsa-miRNA-199a-3p, may be novel biomarkers for the diagnosis of UPS[30].

The UPS treatment mainly consists of early surgical complete resection and postoperative adjuvant radiotherapy. Doxorubicin and/or ifosfamide first-line chemotherapy can be used for patients with UPS who cannot undergo resection or present metastasis[31]. However, the overall efficacy of this treatment approach is not satisfactory. Although the anti-angiogenic small-molecule targeted drug pazopanib was approved by the United States Food and Drug Administration in April 2012 for second-line treatment in patients with advanced STS (excluding liposarcoma and gastrointestinal stromal tumor) and has shown some efficacy and tolerability, there are no a standard guideline[32,33]. Recent immune checkpoint inhibitors (ICIs) have been identified as a treatment for many solid cancers. However, there is limited evidence on the efficacy of ICIs in UPS, mainly comprising small studies[34,35]. Currently, no ICIs are approved for STS treatment. In our case, the patient underwent radical surgical resection, but refused to undergo subsequent treatment, such as radiotherapy and chemotherapy, and eventually died of tumor recurrence and metastasis, with an overall survival period of 22 months.

UPS in CBD is extremely rare. Recognition of this type of neoplasm in the CBD is of great significance for increasing physicians' vigilance, reducing the odds of misdiagnosis, and providing appropriate treatment strategies to improve the prognosis of patients.

We wish to acknowledge Quan Zhou (Department of Pathology, The Second Affiliated Hospital of Jiaxing University, Jiaxing) for his support in pathology of this case, and Xin Wang (Department of Radiology, The Second Affiliated Hospital of Jiaxing University, Jiaxing) for her interpretations in radiology of this case.