DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases.

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5') and centromeric (3') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category.

Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.

OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.

Chronic expanding hematoma of the liver: a case report and review of the literature.

Chronic expanding hematoma (CEH) is defined as a hematoma that grows slowly over a month or longer. CEH with a primary hepatic origin is extremely rare. An 85-year-old man presented with general malaise and low-grade fever. His medical history included hypertension and postoperative appendicitis, and he was taking oral aspirin. Computed tomography showed a 7-cm mass in liver S7 with calcification at the margin. On contrast-enhanced magnetic resonance imaging, the inside of the mass showed heterogeneous hyperintensity on T1-weighted images, mainly low intensity on T2-weighted images, and mild hyperintensity in some areas. Under the preoperative diagnosis of suspected CEH, hemorrhagic cyst, or hepatocellular carcinoma, S7 partial liver resection and cholecystectomy were performed. Histopathological findings showed that the mass was continuous with the liver and protruded extrahepatically, and was covered with a hard fibrous capsule. The capsule contained hematomas ranging from obsolete to relatively fresh, with no neoplastic lesions. He was diagnosed with CEH in the liver. This subcapsular hepatic hematoma was pathologically shown to be a CEH. Complete surgical resection was effective in treating this CEH in the liver.

A Case of Cystic Retroperitoneal Dedifferentiated Liposarcoma Diagnosed by Percutaneous Image-Guided Biopsy.

Introduction: Dedifferentiated liposarcoma (DDLP) was initially defined as a tumor containing differentiated liposarcoma and distinct regions of nonlipogenic spindle cell or pleomorphic sarcoma. Retroperitoneal liposarcomas feature a characteristic appearance with a predominantly fatty component, and cystic liposarcomas are rare. We describe a case of retroperitoneal DDLP predominantly consisting of multilocular cysts. Case Presentation: A 77-year-old man previously visited a doctor because an echo scan unexpectedly revealed an abdominal tumor. Contrast computed tomography (CT) disclosed a large multilocular cystic tumor spanning from the left upper abdomen to the retroperitoneum, and poorly marginated soft tissue structures were present around the abdominal aorta, inferior vena cava, pancreas, mesentery, and left kidney. CT also revealed a right lung mass. The soft tissue structures in the retroperitoneal cystic tumor and right lung mass were strongly enhanced on 2-deoxy-2-[fluorine-18] fluoro-d-glucose positron emission tomography, suggesting a malignant retroperitoneal tumor and lung metastasis. CT-guided percutaneous biopsy targeting the left perirenal soft tissue structure was performed, and the tumor was diagnosed as DDLP. Lung metastasis was present, and the retroperitoneal tumor surrounded multiple organs. Therefore, the tumor was not suitable for surgical resection but it was indicated for chemotherapy based on multidisciplinary discussion. Conclusion: We experienced a case of retroperitoneal cystic DDLP diagnosed by percutaneous image-guided biopsy and treated appropriately based on the pathological diagnosis.

Liver metastasis composed of pure squamous cell carcinoma component from pancreatic pure ductal adenocarcinoma: a case report.

BACKGROUND: Liver metastasis of pure squamous cell carcinoma (SCC) from pancreatic ductal adenocarcinoma has not been previously reported. CASE PRESENTATION: A 66-year-old man underwent a computed tomography scan 3 years after surgery for pancreatic head cancer, and the scan revealed a mass lesion in the right lobe of the liver. A liver tumor biopsy was performed, and SCC was diagnosed. Whole sections of the pancreatic head cancer were re-evaluated, but no areas of SCC-like differentiation were identified. Although the pathology differed between the pancreas and liver, metastasis of adenosquamous carcinoma was considered. Three courses of gemcitabine plus nab-paclitaxel were administered to treat the liver metastasis of pancreatic cancer, but no response was attained. Therefore, primary SCC of the liver was considered and hepatic resection was performed. The tumor had invaded the diaphragm, and S5/6 partial hepatic resection with right diaphragm resection was performed. Pathological examination showed pure SCC of the liver, which differed from the pancreatic cancer. KRAS mutations were evaluated in the pancreatic and liver tumor specimens, and Q61R mutation was identified in both specimens. This pure SCC of the liver was diagnosed as metastasis from pancreatic cancer not by histology but by genetic analysis. CONCLUSIONS: This is the first reported case of pure SCC liver metastasis from pancreatic cancer without a squamous cell component in the primary tumor. Evaluation of KRAS mutations in both specimens was useful for diagnosis.

The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.

Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

Prognostic scores for patients with salivary adenoid cystic carcinoma without lymph node metastasis.

Adenoid cystic carcinoma (AdCC) of salivary gland grows relatively slowly, but occasionally develops distant metastasis. Although cervical lymph node metastasis (LNM) has been reported as a strong prognostic factor, most of AdCC do not have LNM. In this study, we investigated the prognostic factors to predict disease free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS) for 175 patients surgically treated for AdCC without LNM, and developed prognostic score (PS) determined as number of positive prognostic factors. The following emerged as significant prognostic factors: positive surgical margin in DFS, pT3/4 and positive surgical margin in DMFS, and positive surgical margin and high-histological grade in OS. 10-year DFS rates were 56.4% in PS0, and 19.1% in PS1 (p < 0.0001). 10-year DMFS rates were 86.3% in PS0, 56.4% in PS1, and 30.7% in PS2 (p < 0.0001). 10-year OS rates were 100% in PS0, 73.3% in PS1, and 38.8% in PS2 (p < 0.0001).

Secondary Peripheral Dedifferentiated Chondrosarcoma: A Case Report with Special Emphasis on the Radiology/Pathology Correlation.

CASE: In a 54-year-old man, imaging findings suggested a malignant bone tumor having 2 distinct components of the left ilium. Histopathologically, the resected tumor was diagnosed as dedifferentiated chondrosarcoma (CS) arising in secondary peripheral CS. CONCLUSION: Dedifferentiated CS consists of a high-grade noncartilaginous sarcoma adjacent to a preexisting low-grade CS, among which the peripheral type is extremely rare. Because the bimorphic imaging findings reflected the dedifferentiated area and the CS area, they were considered useful for diagnosis. In addition, the dedifferentiated area was localized to the tumor's edge, suggesting that the dedifferentiation originated from the cartilage cap.

Prognostic impact of noninvasive areas in resected pathological stage IA lung adenocarcinoma.

MAIN PROBLEMS: In non-small-cell lung cancer, ground-glass opacity on computed tomography imaging reflects pathological noninvasiveness and is a favorable prognostic factor. However, the significance of pathological noninvasive areas (NIAs) has not been fully revealed. In this study, we aimed to elucidate the prognostic impact of NIAs on lung adenocarcinoma. METHODS: We analyzed 402 patients with pathological stage (p-Stage) IA lung adenocarcinoma who underwent surgery in 2013-2016 at two institutions and examined the association of the presence of NIAs with clinicopathological factors and prognosis. Furthermore, after using propensity-score matching to adjust for clinicopathological factors, such as age, sex, smoking history, pathological invasive area size, pathological T factor (p-T), p-Stage, and histological subtype (lepidic predominant adenocarcinoma [LPA] or non-LPA), the prognostic impact of NIAs was evaluated. RESULTS: Patients were divided into NIA-present (N = 231) and NIA-absent (N = 171) groups. Multivariable analysis showed that NIA-present was strongly associated with earlier p-T, earlier p-Stage, LPA, and epidermal growth factor receptor mutation. Kaplan-Meier survival analysis showed that the NIA-present group displayed a better prognosis than the NIA-absent group in disease-free survival (DFS) and overall survival (OS) (5-year DFS 94.6% vs. 87.2%, 5-year OS 97.2% vs. 91.1%). However, after adjusting for clinicopathological factors by propensity score matching, no significant differences in prognosis were identified between the NIA-present and NIA-absent groups (5-year DFS 92.4% vs 89.6%, 5-year OS 95.6% vs 94.3%). CONCLUSIONS: Our current study suggests that the prognostic impact of the presence of NIAs on lung adenocarcinoma is due to differences in clinicopathological factors.

Immune Checkpoint Inhibitors for Nasopharyngeal Carcinoma in a Real-world Setting in Japan.

BACKGROUND/AIM: The advent of immune checkpoint inhibitor (ICI) treatment has transformed the treatment of recurrent or metastatic head and neck cancer; however, nasopharyngeal carcinoma (NPC) has not been included in major phase III trials. The clinical outcomes of ICI for NPC in real-world practice remain to be fully elucidated. PATIENTS AND METHODS: We retrospectively reviewed 23 patients with recurrent or metastatic NPC treated with nivolumab or pembrolizumab at 6 institutions from April 2017 to July 2021 and investigated the correlation of clinicopathological factors and immune-related adverse events with the effects of ICI therapy and the prognosis. RESULTS: The objective response rate was 39.1% and the disease control rate was 78.3%. The median progression-free survival was 16.8 months and overall survival has not been reached. As with other treatment procedures, the efficacy and the prognosis tended to be better in EBER-positive cases than in EBER-negative cases. The rate of significant immune-related adverse events that necessitated discontinuation of treatment was only 4.3%. CONCLUSION: ICI monotherapy (e.g., nivolumab and pembrolizumab) was effective and tolerable for NPC in a real-world setting.

Comparative analyses of tumour immune microenvironment between collecting duct carcinoma and fumarate hydratase-deficient renal cell carcinoma.

AIMS: Collecting duct carcinoma (CDC) and fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) have similar histological morphologies and both show a poor prognosis. Programmed death ligand 1 (PD-L1) inhibitor has been approved for the treatment of RCC. However, tumour-infiltrating neutrophils stimulated by interleukin-8 (IL-8) interfere with PD-L1 inhibitors. Here, we retrospectively analysed PD-L1 and IL-8 expression, and examined its relationship with infiltrating immune cells. METHODS: Nine cases of CDC and seven cases of FH-deficient RCC were selected. We defined PD-L1 and IL-8 expression by the Tumour Proportion Score and Combined Positive Score (CPS). We counted the numbers of CD8+, CXCR2+, CD11b+, CD66b+ and CD33+ immune cells located in the tumour components. RESULTS: A number of CXCR2+ (p=0.0058), CD11b+ (p=0.0070) and CD66b+ (p=0.0067) immune cells infiltrating into CDC were significantly higher than those infiltrating into FH-deficient RCC. In CDC, PD-L1 expression was correlated with a high density of CD8+ lymphocytes (p=0.0389), but was not in FH-deficient RCC (p=0.6985). IL-8 CPS was significantly higher in CDC than in FH-deficient RCC (p=0.0069). In addition, among the CDC cases, IL-8 CPS showed significant positive correlations with CXCR2+, CD11b+ and CD66b+ immune cell densities (p=0.0250, p=0.0104 and p=0.0374, respectively), whereas FH-deficient RCC showed no significant correlations between IL-8 CPS and immune cell densities. CONCLUSIONS: Our results suggest the difference of each tumour microenvironment between CDC and FH-deficient RCC, and IL-8 is a potential therapeutic target for treating CDC, but not FH-deficient RCC.

A new scoring system for the grading of conventional chondrosarcoma: Its clinicopathological significance.

BACKGROUND: 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. MATERIAL AND METHODS: Clinicopathological features of 60 cases of conventional chondrosarcoma and 21 cases of dedifferentiated chondrosarcoma were reviewed. RESULTS: Moderate to severe nuclear atypia was correlated with distant metastasis. Moderate and severe nuclear atypia, high cellularity, and >1 % 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. CONCLUSION: 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.

Undifferentiated embryonal sarcoma of the liver occurring in an adolescent: a case report with genomic analysis.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant mesenchymal tumor that usually occurs in children and is rarely diagnosed in adults. CASE PRESENTATION: The case was a female in her late 20s who presented with a huge liver mass found upon the examination of fever. Imaging analysis showed a well-defined mass measuring 9 cm in the largest dimension in the right posterior segment of the liver. The patient underwent right hemi-hepatectomy. Histopathological studies revealed that the circumscribed tumor was composed of a proliferation of atypical epithelioid to spindle-shaped cells with pleomorphic nuclei arranged in haphazard pattern. Histopathological features observed in immunohistochemical analyses confirmed a final diagnosis of UESL. Genome analysis using FoundationOne CDx revealed 11 somatic mutations including TP53 (R196*) and STK11 (F354L). Adjuvant chemotherapy with ifosfamide and etoposide was performed, and the case has been followed up without recurrence for 1 year after hepatectomy. CONCLUSIONS: A UESL should be considered in the differential diagnosis of large and well-defined solid liver lesions. Although the prognosis of UESL is extremely unfavorable, aggressive surgical resection with adjuvant chemotherapy and genomic analysis may be helpful for ensuring long-term survival.

Frequency and clinical features of deficient mismatch repair in ovarian clear cell and endometrioid carcinoma.

OBJECTIVE: To clarify the frequency of deficient mismatch repair (dMMR) in Japanese ovarian cancer patients, we examined microsatellite instability (MSI) status and immunohistochemistry (IHC) subtypes, including endometrioid carcinoma (EMC), clear cell carcinoma (CCC), or a mixture of both (Mix). METHODS: We registered 390 patients who were diagnosed with EMC/CCC/Mix between 2006 and 2015 and treated at seven participating facilities. For 339 patients confirmed eligible by the Central Pathological Review Board, MSI, IHC, and MutL homolog 1 methylation analyses were conducted. The tissues of patients with Lynch syndrome (LS)-related cancer histories, such as colorectal and endometrial cancer, were also investigated. RESULTS: MSI-high (MSI-H) status was observed in 2/217 CCC (0.9%), 10/115 EMC (8.7%), and 1/4 Mix (25%). Additionally, loss of MMR protein expression (LoE-MMR) was observed in 5/219 (2.3%), 16/115 (14.0%), and 1/4 (25%) patients with CCC, EMC, and Mix, respectively. Both MSI-H and LoE-MMR were found significantly more often in EMC (p<0.001). The median (range) ages of patients with MMR expression and LoE-MMR were 54 (30-90) and 46 (22-76) (p=0.002), respectively. In the multivariate analysis, advanced stage and histological type were identified as prognostic factors. CONCLUSION: The dMMR rate for EMC/CCC was similar to that reported in Western countries. In Japan, it is assumed that the dMMR frequency is higher because of the increased proportion of CCC.

Neuroectodermal Rosettes in Immature Teratomas Are Not the Counterpart of Embryonal Tumours With Multilayered Rosettes.

BACKGROUND/AIM: Immature teratomas (IMT) are malignant germ cell tumours composed of immature embryonal tissue, mostly neuroectodermal tubules and rosettes. Meanwhile, embryonal tumours with multilayered rosettes (ETMR) are aggressive central nervous system tumours composed of neurocyte proliferation with rosette formation. The histopathological appearance of rosette formation in ETMR is the same as that in IMT. Recently, 19q13.42 amplification was reported as a specific genetic marker of ETMR. The aim of this study was to compare ETMR with IMT from histological, immunohistochemical and genetic perspectives. MATERIALS AND METHODS: We retrospectively analysed tumour samples from 48 patients with IMT and 1 patient with ETMR. We performed fluorescence in situ hybridization (FISH) analysis, which revealed amplification of the 19q13.42 locus in the ETMR case. In addition, immunohistochemical analyses of LIN28A, ß-catenin and p53 were performed. RESULTS: In FISH analysis all 48 cases of IMT showed diploidy. By immunohistochemical analysis, LIN28A expression was observed in 54% of IMT cases (25/48 cases) and in the ETMR case. Nuclear staining of ß-catenin was observed in 33% of IMT cases (16/48 cases). Meanwhile, aberrant expression of p53 was not identified in IMT nor ETMR cases. CONCLUSION: Genetic changes associated with IMT differ from those in ETMR, but LIN28A protein immunohistochemical expression, which is specific for ETMR, can be a biomarker for the immature neuroepithelial component in IMT.

Approach for reclassification of collecting duct carcinoma and comparative histopathological analysis with SMARCB1/INI1-deficient renal cell carcinoma and fumarate hydratase-deficient renal cell carcinoma.

Collecting duct carcinoma (CDC) is a rare subset of high-grade renal cell carcinoma (RCC). To diagnose CDC, it is necessary to rule out other renal tumors including renal medullary carcinoma and fumarate hydratase (FH)-deficient RCC. However, there is overlap in the morphology of these three tumors, which all have poor outcomes. There is also still a need to sufficiently examine the therapeutic strategies for each of these tumors. In this study, we retrospectively reclassified invasive/infiltrating high-grade RCC and investigated its pathological features. We reviewed 18 cases previously diagnosed as "CDC," "FH-deficient RCC," and "unclassified RCC," which were reclassified as SMARCB1/INI1-deficient RCC, FH-deficient RCC, and CDC by SMARCB1/INI1, FH, and 2SC immunohistochemistry (IHC) and FH gene mutational status. As the result, 18 cases were reclassified into 2 cases of SMARCB1/INI1-deficient RCC, 7 cases of FH-deficient RCC, and 9 cases of CDC. The morphological features of each group overlapped, and no specific immunohistochemical expression except for SMARCB1/INI1, FH, and 2SC was detected. These results suggest that invasive/infiltrating high-grade RCC should be diagnosed by the combination of immunohistochemistry and molecular biological technique.

Serum immunoglobulin G as a discriminator of infection in follicular lymphoma patients undergoing chemotherapy with bendamustine in combination with rituximab.

OBJECTIVES: Chemotherapy, including bendamustine, usually causes lymphocytopaenia and hypogammaglobulinaemia as side effects in patients with haematological malignancies. Therefore, the possibility has been considered that these immunological adverse events induced by bendamustine may lead to infectious diseases. However, lymphocytopaenia and/or hypogammaglobulinaemia have not yet been shown to have a statistically significant association with infection in cancer patients who receive bendamustine. METHODS: We retrospectively studied 27 patients with relapsed or refractory indolent follicular lymphoma who were treated with bendamustine and rituximab (BR). In order to elucidate relationships between immune-related laboratory parameters (i.e. peripheral blood leukocyte, neutrophil, lymphocyte and immunoglobulin G [IgG]) and infectious events, receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. RESULTS: Infectious diseases occurred in 11 patients (11/27, 41%), including 3 (3/27, 11%) with severe diseases. The area under the ROC curve (AUC) showed that the lowest IgG level during and after BR discriminated infectious events (cut-off value, 603 mg/dL) with 81.8% sensitivity and 68.8% specificity (AUC, 0.76; 95% CI, 0.52-0.90). Furthermore, a multivariate regression analysis revealed that the minimal serum IgG value during and after BR therapy was the only variable that was significantly associated with infection (odds ratio, 8.29; 95% CI, 1.19-57.62; p value, 0.03). CONCLUSION: Serum IgG ≤603 mg/dL during and after BR therapy was independently associated with an increased risk of infection. The monitoring of serum IgG during chemotherapy may help to predict the development of infection in blood cancer patients undergoing chemotherapy with bendamustine in combination with rituximab.

Cytoreductive Nephrectomy After Combination of Nivolumab Plus Ipilimumab for Mucinous Tubular and Spindle Cell Carcinoma of the Kidney With Bone Metastases: A Case Report.

BACKGROUND/AIM: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma and generally considered a low-grade renal epithelial neoplasm. However, MTSCC with distant metastases often shows a poor prognosis. This is the first reported case of cytoreductive nephrectomy after nivolumab plus ipilimumab combination treatment. CASE REPORT: A 26-year-old man had a 72-mm tumor at the left kidney with multiple osteolytic bone metastases. A biopsy of the renal tumor and bone metastases resulted in the diagnosis of MTSCC of the kidney with bone metastases. After nivolumab plus ipilimumab combined treatment, he underwent cytoreductive nephrectomy. The excised specimen showed higher PD-L1 expression in the spindle components than in the tubular components, but CD4- and CD8-positve T-cells showed greater infiltration in the tubular components than the spindle components. CONCLUSION: Combination immunotherapy of nivolumab and ipilimumab may be an effective treatment option for metastatic MTSCC of the kidney.

An Analysis of 20 Cases of Radiation-Associated Sarcoma, Including 4 Cases Treated by Carbon Ion Radiotherapy.

INTRODUCTION: Radiation-associated sarcoma (RAS) is one of the most life-threatening complications associated with the treatment of malignant neoplasms. Because all RAS patients have a history of radiotherapy, there have been no effective treatment options when RAS is not completely resected. METHODS: We retrospectively reviewed 20 RAS patients, including 4 unresectable cases treated by carbon ion radiotherapy (CIRT). RESULTS: The primary diseases targeted by radiotherapy included malignant lymphoma (n = 4), cervical cancer (n = 3), pharyngeal cancer (n = 3), breast cancer (n = 2), lung cancer (n = 1), rectal cancer (n = 1), maxillary cancer (n = 1), synovial sarcoma (n = 1), and benign neoplasms (n = 4). The histological diagnoses of RAS included osteosarcoma (n = 8), leiomyosarcoma (n = 3), undifferentiated pleomorphic sarcoma (n = 3), rhabdomyosarcoma (n = 1), angiosarcoma (n = 1), malignant peripheral nerve sheath tumor (n = 1), spindle cell sarcoma NOS (n = 1), and sarcoma not further specified (n = 2). The median survival time from the diagnosis of RAS was 26 months. Eleven patients underwent surgery. Five of these patients achieved a continuous disease free (CDF) status or showed no evidence disease. Four patients underwent CIRT. One of these patients with leiomyosarcoma achieved a CDF status, and the other patient with osteosarcoma achieved a partial response. On the other hand, 2 patients experienced grade 3 toxicities that required surgical treatment. CONCLUSION: RAS originates from various types of diseases that are treated by radiotherapy and shows diverse pathological features. Complete resection achieves a good prognosis. CIRT can be an effective and feasible option for unresectable RAS.

Impact of serum vitamin D on the response and prognosis in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Several studies have recently reported that the relationships between serum vitamin D and the prognosis or the pathological response to neoadjuvant chemotherapy (NAC) in breast cancer. However, there are no data regarding the clinical impacts of the vitamin D in Japanese breast cancer patients so far. PATIENTS AND METHODS: In the present study, a total of 250 patients with clinical Stage I-III primary breast cancer who were treated with NAC and subsequently underwent definitive surgery were included. Serum 25-hydroxvitamin D (25(OH)D) levels were evaluated using blood samples obtained before NAC. RESULTS: The serum 25(OH)D was positively associated with age, and the serum 25(OH)D was significantly higher in postmenopausal women than that in pre/peri-menopausal women. Serum 25(OH)D level was not associated with the achievement of pathological complete response (pCR) in this cohort. The low 25(OH)D levels were significantly associated with shorter time to distant recurrence (TTDR). According to the univariate analysis, high clinical stage before NAC (cStage III) and low serum 25(OH)D level were significantly associated with the shorter TTDR, and pCR was significantly associated with the longer TTDR. According to a multivariate analysis, low serum 25(OH)D level were independent poor prognostic factors for TTDR. CONCLUSIONS: The low 25(OH)D levels were significantly associated with poorer prognosis in Japanese women with operable breast cancer patients treated with NAC.