A pelvic cavity malignant solitary brous tumor with dedifferentiation and multifocal cytokeratin expression

Background: Solitary brous tumor is an uncommon mesenchymal neoplasm that originates from broblasts and occurs predominantly in the visceral pleura. Pelvic cavity small sized malignant solitary brous tumor is very rare; it is easily misjudged by surgeons as a benign lesion and resected by laparoscopic surgery. When accompanied by dedifferentiation, malignant solitary brous tumor is dicult to diagnose by pathologists. Here, we describe a challenging case. Case presentation: A 47-year-old man was accidentally found to have a pelvic mass for three months, with pain and distension for seven days. The mass was adhered and compressed to the ureter and bladder. The right side of the pelvic cavity had a palpable and substantial mass, with no obvious associated pain. With an assumed diagnosis of a benign tumor, the patient underwent laparoscopic surgery to resect the tumor. Histologically, spindle cell areas and dedifferentiated areas were observed. Immunohistochemical analysis of dedifferentiated regions revealed cytokeratin showed multifocal expression. Vimentin and CD34 were abnormal negative. This case was diagnosed as a MSFT with dedifferentiation. The patient was well after the operation, but, unfortunately, he had a recurrence one year later. Conclusion: Pelvic cavity malignant solitary brous tumor is a rare tumor that is in frequently dedifferentiated and exhibiting cytokeratin expression. The diagnosis of this type of tumor can be confusing, and it should be distinguished from Synovial Sarcoma, Liposarcoma, and other malignant tumors. The expression of cytokeratin and the absence of vimentin and CD34 are pitfalls to diagnosis. In this case, there was still a high degree of malignancy despite the small size of the tumor. Clinical-image-pathological multidisciplinary analysis has a great effect on diagnosis and therapy of diseases. This case is a cautionary tale for surgeons and pathologists.


Background
Solitary brous tumor (SFT) is an uncommon mesenchymal spindle cell tumor. SFT derives from broblasts and often occurs in the visceral pleura [1]. SFT can occur at any extrapleural area, such as head and neck, pelvic cavity, abdominal cavity, retroperitoneum, and surrounding soft tissue. The median age of SFT onset is between 40 and 60 [2]. Since 1931, when Klemperer and Rabin rst reported ve cases of solitary brous tumors that originated in the pleura, researchers and pathologists have gradually recognized solitary brous tumors as an independent tumor. Clinically, most patients present with slowgrowing painless masses, and the majority are found by coincidence. Tumors located in the pelvic cavity and abdomen may result in abdominal distension or following obstruction symptoms.
MSFT accompanied by dedifferentiation is a newly discovered, rare phenomenon. Our team diagnosed a case of MSFT in the pelvic cavity of a 46-year-old man. Microscopically, some tumor areas were associated with epithelioid differentiation. Some tumor regions presented dedifferentiation, and they were positive for cytokeratin expression and negative for vimentin and CD34; the absence of vimentin and CD34 creates di culty in diagnosis of SFT. This case was rare. Here we analyze and discuss the case, from its pathological and morphological changes, imaging manifestations, immunohistochemical assays, diagnosis, and prognosis.

Case Presentation
The 46-year-old male patient came to our hospital due to an "accidentally found pelvic mass for three months, with pain and distension for 7 days". The physical examination did not show swelling or tenderness in the kidney and ureteral areas. The right side of the pelvic cavity had a palpable and substantial mass, with no obvious associated pain. Ultrasonography suggested a hypoechoic mass on the right side of the right lower abdominal bladder with unclear boundary, irregular shape, and uneven internal echo. Color doppler ow imaging showed a spot color blood ow signal that could be seen inside the mass. Pelvic Computed Tomography showed the mass shadow on the right side of the pelvic cavity, and the size was approximately 3.8cmX3.5 cm with uneven and obvious enhancement, and continuous enhancement. The adjacent ureter basin was compressed, ureter and renal pelvis above the mass were dilated, and hydronephrosis was observed ( Figure. 1a and b).
With an assumed diagnosis of a benign tumor, the patient underwent laparoscopic surgery to resect the pelvic tumor and replant the right ureteral and bladder. An elliptical tumor was found on the right side of the bladder during the operation; the tumor was adhered to the bladder wall and the right ureter. The tumor had an abundant blood supply. The surgeons had di culty separating the ureter and bladder wall from the mass because of an unclear boundary between the right ureter and the tumor. In addition, the bladder wall was adhered to the tumor; thus, a small part of the ureter and bladder wall was removed.
Gross examination showed grayish-yellow and grayish-white fragments measuring 40 mm x 40 mm x 10 mm. Microscopically, mature adipocytes and ber cells and microcystic changes were observed in the center of the tumor, with sparse arrangement ( Figure.  SFT is a type of mesenchymal spindle cell tumor, with complex and diversi ed histological morphology. Morphologically, benign SFT, highly malignant sarcoma, and dedifferentiated components can occur simultaneously in MSFT. Dedifferentiated manifestations were various, such as poorly differentiated epithelioid cells or small round cells, accompanied by heterogeneous differentiation (usually manifested as the presence of osteosarcoma, rhabdomyosarcoma and liposarcoma components), neuroendocrine differentiation and squamous differentiation [6][7][8][9][10].Although most tumors exhibit classic spindle cell morphology, they may also be associated with myxoid/microcystic change, epithelioid morphology, lipomatous differentiation, and interstitial giant cell [11]. Due to the lack of speci c morphological manifestations, liposarcoma, brosarcoma, myo broblast sarcoma, pleomorphic undifferentiated sarcoma, leiomyosarcoma, and malignant peripheral schwannomas were the differential diagnosis of MSFT. Therefore, diagnosis of SFT relies heavily on immunohistochemistry. SFT speci cally expresses CD34, BCL-2, and CD99 to different degrees. In MSFT, various dedifferentiated morphologies are seen besides classical spindle cell morphology, and CD34 expression can be absent. [12] Monoclonal STAT6 immunohistochemical staining has high sensitivity and speci city to SFT, and it was particularly useful in the diagnosis of di cult SFT cases [13]. STAT6 nuclear positive expression is a reliable diagnostic indicator for SFT that is negative for CD34 expression [14]. But STAT-6 was not expressed frequently in some MSFT dedifferentiated regions [15].The high expression of Ki-67 index and the strong staining of BCL-2 also have implications for identi cation of benign and malignant tumors [16]. Over expression of IGF2 has a certain signi cance for the diagnosis of malignant isolated brous tumors [17]. Ouladan et al. con rmed that STAT6 and ALDH1 (cytoplasmic expression) were the most sensitive and speci c markers in the differential diagnosis of SFT [18].
Besides immunohistochemical expression, recent genetic studies have great signi cance in the diagnosis of soft tissue tumors. Vivero et al. showed that the GRIA2 gene was highly expressed in SFT, and GRIA2 could be used as a marker for SFT diagnosis [19]. Moreover, a NAB-STAT6 gene fusion has been found in SFTs. CD34 negative-MSFTs can be diagnosed clearly with the combined expression of STAT6 and the NAB2-STAT6 gene fusion [20]. However, some STAT6-positive cases lacked the NAB2-STAT6 gene fusion. Some cases were reported to have a NAB2ex4-STAT6ex2 fusion but were negative for STAT6 immunohistochemistry [21]. Therefore, the diagnosis of MSFT should be based on immunohistochemistry of CD34, STAT-6, ALDH1, BCL-2, CD99, and detection of a NAB2-STAT6 gene fusion.
Malignant solitary brous tumors with by dedifferentiated expression tend to predict lower differentiation and worse prognosis. In a study of 10 MSFT patients with high-grade sarcomatoid growth patterns, seven patients died of the disease [11]. In another study of eight patients of MSFT with dedifferentiated features, four patients had distant metastasis, and three patients had metastasis and died within three years. Thus, MSFT with features of dedifferentiation is more aggressive, whereas a positive surgical margin and tumor size greater than 10 cm suggests lower survival and higher recurrence metastasis rate. Hypercellularity, atypia of tumor cells, size of tumors, mitotic rate, epithelioid morphology, hemorrhage and necrosis were adverse prognostic factors of SFT, and tumors with less nuclear division were not prone to metastasis [22]. In this case, there was still a high degree of malignancy despite a small size of the tumor. For the patient described in this case, the recurrence of the tumor after surgery suggested that MSFT with dedifferentiation had a higher degree of malignancy.
Most surgeons rely on imaging; however, MSFT diagnosis is unreliable by imaging alone. [23] Surgery is the main treatment for MSFT. Patients with malignant tumors or tumors that invade adjacent structures should undergo an entire resection with wide margins of adjacent tissue. [24] MSFT patients can also achieve a better therapeutic outcome by appropriate adjuvant radiotherapy and chemotherapy according to the size, degree of malignancy, and metastasis status of the tumor. However, in the treatment of MSFT with dedifferentiation, application of an angiogenesis inhibitor, pazotinib, was more effective than the traditional treatment [25]. Pazotinib as a choice for advanced solitary brous tumor. [26] Conclusion A patient will have a better prognosis if the benign or malignant lesion is accurately evaluated by aspiration biopsy before the surgery. Then, surgeons can select an appropriate method instead of blindly opting for laparoscopic surgery. Therefore, surgeons should pay more attention to preoperative pathological assessment. Clinical-image-histopathological multidisciplinary analysis has a great effect on diagnosis and therapy of diseases.

Declarations
Ultrasonography suggested a hypoechoic mass on the right side of the right lower abdominal bladder with unclear boundary, irregular shape, uneven internal echo, and visible color blood ow signals (a) Computed Tomography showed that the mass shadow on the right side of the pelvic cavity, and it pressed on the bladder and ureter (b).