Objective:To investigate the clinicopathological features, immunophenotypes, and molecular characteristics of PRRX1-rearranged fibroblastic tumor and to discuss their differential diagnoses.Methods:Four cases of PRRX1-rearranged fibroblastic tumor retrieved from Anning First People′s Hospital and Fudan University Shanghai Cancer Center and their clinicopathological features, immunophenotypes and molecular profiles were analyzed. The literature was reviewed.Results:All 4 cases occurred in adult women with an age of 34(27,41) years. Three tumors occurred in the low extremities and 1 in the trunk. The patients presented with a slowly growing mass or swelling, accompanied by pain in 1 patient. Three tumors were located in the subcutis, and 1 tumor in the intermuscular space. The duration lasted for 6 months to 1 year. Tumor ranged in size from 4.0 to 15.8 cm (mean 7.3 cm). At lower power, the tumors were well circumscribed, showing a multinodular architecture. They were composed of bland ovoid to short spindled cells arranged irregularly with interstitial ropey collagen fibers, and set in a fibrous to fibromyxoid matrix with a close resemblance to low-grade fibromyxoid sarcoma. However, all 4 tumors showed negative staining for MUC4. Two tumors were focally positive for S-100 and SOX10. Apart from vimentin, they were all negative for other immunohistochemical stains including SMA, desmin, CD34, STAT6 and β-catenin. The expression of H3K27Me3 was retained. The proliferative index measured by Ki-67 was less than 5%. RNA-sequencing analysis identified PRRX1::NCOA1 fusions in 3 cases, and PRRX1::KMT2D fusion in 1 case. Subsequent FISH study confirmed NCOA1 rearrangement in 3 cases harboring NCOA1 rearrangement. On follow-up (1-14 months), no patient developed either local recurrence or distant metastasis.Conclusions:PRRX1-rearranged fibroblastic tumor is a novel entity of soft tissue tumor that has a predilection for the trunk and extremities, characterized by PRRX1 gene rearrangement and benign clinical course. Familiarity with its clinicopathological features is helpful in the distinction from low-grade fibromyxoid sarcoma and other spindle cell tumors with overlapping features.

Objective:To investigate the clinicopathological features, immunophenotypes, and molecular characteristics of PRRX1-rearranged fibroblastic tumor and to discuss their differential diagnoses.Methods:Four cases of PRRX1-rearranged fibroblastic tumor retrieved from Anning First People′s Hospital and Fudan University Shanghai Cancer Center and their clinicopathological features, immunophenotypes and molecular profiles were analyzed. The literature was reviewed.Results:All 4 cases occurred in adult women with an age of 34(27,41) years. Three tumors occurred in the low extremities and 1 in the trunk. The patients presented with a slowly growing mass or swelling, accompanied by pain in 1 patient. Three tumors were located in the subcutis, and 1 tumor in the intermuscular space. The duration lasted for 6 months to 1 year. Tumor ranged in size from 4.0 to 15.8 cm (mean 7.3 cm). At lower power, the tumors were well circumscribed, showing a multinodular architecture. They were composed of bland ovoid to short spindled cells arranged irregularly with interstitial ropey collagen fibers, and set in a fibrous to fibromyxoid matrix with a close resemblance to low-grade fibromyxoid sarcoma. However, all 4 tumors showed negative staining for MUC4. Two tumors were focally positive for S-100 and SOX10. Apart from vimentin, they were all negative for other immunohistochemical stains including SMA, desmin, CD34, STAT6 and β-catenin. The expression of H3K27Me3 was retained. The proliferative index measured by Ki-67 was less than 5%. RNA-sequencing analysis identified PRRX1::NCOA1 fusions in 3 cases, and PRRX1::KMT2D fusion in 1 case. Subsequent FISH study confirmed NCOA1 rearrangement in 3 cases harboring NCOA1 rearrangement. On follow-up (1-14 months), no patient developed either local recurrence or distant metastasis.Conclusions:PRRX1-rearranged fibroblastic tumor is a novel entity of soft tissue tumor that has a predilection for the trunk and extremities, characterized by PRRX1 gene rearrangement and benign clinical course. Familiarity with its clinicopathological features is helpful in the distinction from low-grade fibromyxoid sarcoma and other spindle cell tumors with overlapping features.