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In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases.

Chondroblastoma (CB) is histologically characterized by oval to polygonal-shaped mononuclear neoplastic cells, multinucleated osteoclastic giant cells, and eosinophilic matrix with occasional calcification. Genetically, the majority of CBs harbor H3F3B p.K36M mutation. Despite the historical nomenclature, it has been reported that the matrix of CB is similar to osteoid rather than true cartilage; however, it remains unclear whether neoplastic cells in CB have the potential for osteoblastic differentiation. To clarify this issue, we immunohistochemically examined the expression of osteogenic and chondrogenic markers (SATB2, RUNX2, p63, and SOX9) as well as H3K36M mutant protein in 33 cases of CB. All 33 cases of CB were positive for H3K36M, while SATB2, RUNX2, p63, and SOX9 were expressed in 30/33 (91%), 33/33 (100%), 29/33 (88%), and 31/32 (97%) CB cases, respectively. Our immunohistochemical results suggest that neoplastic cells in CB frequently express both osteogenic and chondrogenic markers and may have an intermediate feature of osteoblastic and chondroblastic nature.

AimsLiposarcoma is a malignant soft tissue tumour with adipocytic differentiation. Dedifferentiated liposarcoma (DDLS) and myxoid liposarcoma (MLS) are classified as high-grade liposarcomas. Lipid droplet-associated protein (also known as perilipin 1 (PLIN1)) is the predominant perilipin and has utility as a specific marker of adipogenic differentiation. Adipose differentiation-related protein (also known as adipophilin (ADRP)) is ubiquitously expressed in a range of tissues. High ADRP expression is reportedly a poor prognostic factor in several cancer types. However, no previous studies have examined the association between PLIN1 or ADRP expression and prognosis in sarcoma. This study therefore aimed to evaluate the association between PLIN1 or ADRP expression and prognosis in liposarcoma.MethodsIn total, 97 primary resection specimens (53 MLS and 44 DDLS) were examined in this study. PLIN1 and ADRP expression was evaluated by immunohistochemistry. Survival analyses were performed for MLS and DDLS.ResultsOf the 53 MLS specimens, 15 (28.3%) exhibited high PLIN1 expression. PLIN1 expression was not observed in DDLS specimens. High PLIN1 expression was significantly associated with increased disease-free survival (DFS) among patients with MLS (p=0.045). Distinct ADRP expression was observed in 13 of 53 (24.5%) MLS specimens and 5 of 44 (11.4%) DDLS specimens. High ADRP expression was associated with shorter overall survival (OS) in MLS (p=0.042) and DFS and shorter OS in DDLS (p=0.024 and pConclusionsPLIN1 and ADRP expression is associated with poor prognosis in high-grade liposarcoma.

Chondrosarcoma is the second most common primary malignant bone tumor, which produces cartilaginous matrix without neoplastic osteoid or bone formation. The histological grade in the WHO Classification of Soft Tissue and Bone (2020 edition) is the most important factor in predicting the clinical outcome of conventional chondrosarcoma, but the lack of clarity in its detailed definition is occasionally problematic. Here, we reviewed conventional chondrosarcoma cases and validated the significance of histological findings. Moreover, we proposed a new scoring system of conventional chondrosarcoma.Clinicopathological features of 60 cases of conventional chondrosarcoma and 21 cases of dedifferentiated chondrosarcoma were reviewed.Moderate to severe nuclear atypia was correlated with distant metastasis. Moderate and severe nuclear atypia, high cellularity, and1 % myxoid change were correlated with adverse overall survival. On the other hand, cases with mild nuclear atypia showed no tumor-related death and no metastases. Based on the above results, we proposed a new scoring system based on nuclear atypia (mild: 0, moderate: +1, severe: +2), cellularity (no and mildly increased cellularity: 0, moderately and diffusely increased cellularity: +1), necrosis [(-): 0, (+): + 1], and chondromyxoid area [(-): 0, (+): + 1]. Each grade was defined as follows: cases with only mild nuclear atypia as grade 1, cases with total score 1-3 excluding mild nuclear atypia as grade 2, and cases with total score 4 or 5 as grade 3. There were 18 cases (30 %) of grade 1 including 5 cases (28 %) of local recurrence, but no metastasis or tumor-related death; 26 cases (43 %) of grade 2 including 2 cases (8 %) of local recurrence, 3 cases (12 %) of metastasis, and 1 case (4 %) of tumor-related death; and 16 cases (27 %) of grade 3 including 4 cases (25 %) of local recurrence, 6 cases (38 %) of metastasis, and 5 cases (31 %) of tumor-related death. There was no statistically significant association between the histological findings and dedifferentiation.From this study, we propose a new histological scoring system for the grading of conventional chondrosarcoma, based on nuclear atypia, cellularity, necrosis, and myxoid change. Using this system, conventional chondrosarcoma may be clearly classified into three grades: grade 1, non-metastasizing; grade 2, metastasizing but rarely life-threatening; and grade 3, frequently metastasizing and life-threatening.

Dedifferentiated liposarcoma (DDLS) has varying histopathological features, but their significance for the biological behaviour of this disease has not been fully clarified. The aim of this study was to elucidate the prognostic factors for DDLS by clinicopathologically reviewing a large case series.We clinicopathologically reviewed 123 cases of primary de-novo DDLS without preoperative treatment, including 81 in the internal trunk (internal DDLS) and 42 in peripheral sites (peripheral DDLS). Univariate and multivariate analyses of their features were also performed for all cases, the internal DDLS group, and the peripheral DDLS group. The results showed that, in all three groups, distant metastasis was significantly associated with shorter overall survival (OS) (univariate analysis, P 0.0001, P = 0.0011, and P = 0.0101, respectively), whereas local recurrence showed no significant effect on prognosis. Histopathologically, a high mitotic count and the presence of round tumour cells were significantly associated with shorter OS in multivariate analysis of the internal DDLS group [respectively: P = 0.0022, hazard ratio (HR) 4.39, 95% confidence interval (CI) 1.71-11.28; and P = 0.0014, HR 7.19, 95% CI 2.14-24.16]. In the peripheral DDLS group, necrosis and high-grade histological components were significantly associated with shorter OS (univariate analysis, P = 0.0068 and P = 0.0174, respectively).The presence of round tumour cells may be one of the histological factors associated with a worse prognosis of DDLS patients, as previous studies indicated. This study also suggests that distant metastasis may be predictive of prognosis for both internal and peripheral DDLS, rather than local recurrence.

Synovial sarcoma (SS) is a malignant soft tissue neoplasm harboring SS18-SSX fusion gene and is histologically characterized by spindle cells and epithelial components. Some investigations have demonstrated that desmoplastic reaction (DR) is an independent prognostic factor of cancers. However, it remains unknown whether DR is of predictive value for the prognosis of synovial sarcoma patients. Here, we reviewed the clinical and histological findings of 88 patients with SS. We defined DR as hyalinized collagenous structures and classified the degree of DR as follows: none, mild, moderate, and severe. Overall, 23 SS cases (24%) showed moderate or severe DR histologically. Statistically, the cases with moderate or severe degree of DR showed poorer prognosis than those with no or mild DR (local recurrence: P = 0.0059, distant metastasis: P = 0.0002, tumor death: P = 0.0382). The findings of the study suggest that the DR of synovial sarcoma could be an important prognostic factor.