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One of the most aggressive forms of kidney cancer is renal cell carcinoma (RCC) with sarcomatoid changes and rhabdoid features (S/R). Adenosine produced via CD73 binds to adenosine 2 A receptor (A2AR) and suppress antitumor immunity. Here, we attempted to analyze the expression of CD73/A2AR in S/R RCC and examined its relationships with other immune microenvironments and prognostic effect. Sixty cases of S/R RCC were selected. CD73/A2AR expression levels were graded in the tumor cells or infiltrating immune cells on a score of 0-3 and divided into low (0 or 1) or high (2 or 3) groups. PD-L1 results were defined by the tumor proportion score (TPS). We counted the numbers of CD8 + , FOXP3 + , CD68 + , and CD163 + immune cells. The rates of CD73/A2AR expression in epithelial component (23.3% and 15.0%) were lower than those in high-grade component (70.0% and 45.0%). CD73/A2AR were significantly correlated to high numbers of regulatory Tcells and macrophages of M2 subtype (CD73: P = 0.0059 and 0.0002; A2AR: P = 0.0002 and 0.018, respectively). Multivariate analysis showed that CD73/A2AR expressions were independent markers of unfavorable prognosis in S/R RCCs (P = 0.0204 and 0.0116, respectively). In RCC, the S/R component had higher expressions of CD73/A2AR than the epithelial component, and CD73/A2AR were independent prognostic factors. Compared with other RCCs, S/R RCCs are more effective at blocking adenosine signaling and CD73/A2AR inhibitors are expected to enhance the therapeutic efficacy and improve the prognosis of immune checkpoint inhibitor therapies., Competing Interests: Conflicts of interest All authors declare that have no conflicts of interest to disclose., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

It is possible that PRCCs may still contain a variety of unknown histologic subtypes. Some PRCCs express high expression of TFE3 protein without TFE3 gene rearrangement, but no reports have investigated the significance of this. Here we attempted to examine clinicopathological and molecular significance of the TFE3-immunopositive PRCC. We reviewed the histology and immunohistochemistry in 58 PRCCs. TFE3 immunoexpression was recognized in 7 cases. Because TFE3 immunostaining shows false-positive, to ensure the integrity of TFE3 immunostaining, the immunostaining was performed under strict control of internal controls and western blotting was performed on 2 positive cases and 5 negative cases, and differences in protein expression between two groups were confirmed. Significant immunohistochemical expressions of autophagy/lysosome proteins were observed in TFE3-positive group. No TFE3 gene arrangement was detected in all positive cases by fluorescence in situ hybridization. Whole-exome sequencing was performed on 6 TFE3-positive and 2 TFE3-negative cases. Gain of chromosome 7 was found in five of 6 TFE3-positive cases (83%). TFE3-positive group was correlated significantly with higher pTstage, cNstage, WHO/ISUP nuclear grade, and decreased OS. TFE3-immunopositive PRCC group had a poorer prognosis than TFE3-negative PRCC group and showed correlation with expressions of autophagy/lysosome proteins, suggesting that enhancement of autophagy/lysosome function drives an environment of energy metabolism that is favorable for cancer. It is necessary to recognize that there is TFE3-immunopositive group without TFE3 gene rearrangement within PRCC. Because of its aggressive biological behaviour, TFE3 can act as a biomarker in PRCC; moreover, autophagy-inhibiting drugs may have therapeutic effects on TFE3-immunopositive PRCC., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

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., Competing Interests: Conflicts of interest The authors declare that there are no conflicts of interest to disclose., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

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., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Aim: Amyloidosis is a systemic or localized disease of protein deposition characterized by amorphous eosinophilic morphology and positivity of Congo Red staining. The typing of amyloidosis is becoming increasingly important because therapeutic agents for each amyloidosis type have been developed. Herein, the authors review the autopsy cases at an institution to reveal the putative Japanese characteristics of each amyloidosis type and evaluate the clinicopathological significance of each type., Materials and Methods: A total of 131 autopsy cases of systemic and localized amyloidosis were retrieved for classification by immunohistochemistry. Immunohistochemistry for transthyretin, amyloid A (AA), immunoglobulin light-chain kappa and lambda, and β2-microglobulin was performed for all cases., Results: The 131 amyloidosis cases were classified as follows: 71 cases (54.2%) of transthyretin amyloidosis, 32 cases (24.4%) of AA amyloidosis, 8 cases (6.1%) of light-chain amyloidosis, and 5 cases (3.8%) of β2-microglobulin amyloidosis, along with 15 equivocal cases (11.5%). All cases showed myocardial involvement of amyloidosis. Histopathologically, the transthyretin type was significantly associated with the interstitial and nodular patterns, and with the absence of the perivascular and endocardial patterns. The AA type was significantly associated with the perivascular and endocardial patterns, and with the absence of the nodular pattern., Conclusion: The authors revealed the putative characteristics of cardiac amyloidosis in Japan by using autopsy cases. About 90% of amyloidosis cases were successfully classified using only commercially available antibodies., (Copyright © 2021 Elsevier GmbH. All rights reserved.)