Potential predictors of the pathologic response after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer: a narrative review.

Background and Objective: Neoadjuvant chemoimmunotherapy (NACI) is the standard of care for patients with resectable non-small cell lung cancer (NSCLC). Although the pathological complete response (pCR) after NACI reportedly exceeds 20%, an optimal predictor of pCR is yet to be established. This review aims to examine the possible predictors of pCR after NACI. Methods: We identified research article published between 2018 and 2022 in English by the PubMed database. Fifty research studies were considered as relevant article, and were examined to edit information for this narrative review. Key Content and Findings: Recently, several studies have explored potential biomarkers for the pathological response after NACI. For example, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) imaging, tumor microenvironment (TME), genetic alternation such as circulating tumor DNA (ctDNA), and clinical markers such as neutrophil-to-lymphocyte ratio (NLR) and smoking signature were assessed in patients with resectable NSCLC to predict the pathological response after NACI. Based on the PET response criteria, the complete metabolic response (CMR) achieved a positive predictive value (PPV) of 71.4% for predicting pCR, and the decreasing rate of post-therapy maximum standardized uptake value (SUVmax) after NACI substantially correlated with the major pathological response (MPR). TME, as a significant marker for MPR in tumor specimens, was identified as an increase in CD8+ T cells and decrease in CD3+ T cells or Foxp3 T cells. Considering blood samples, TME comprised an increase in CD4+PD-1+ cells or natural killer cells and a decrease in CD3+CD56+CTLA4+ cells, total T cells, Th cells, myeloid-derived suppressor cells (MDSCs), or regulatory T cells. Although low pretreatment levels of ctDNA and undetectable ctDNA levels after NACI were markedly associated with survival, the relationship between ctDNA levels and pCR remains elusive. Moreover, the patients with a high baseline NLR had a low incidence of pCR. Heavy smoking (>40 pack-years) was favorable for predicting pathological response. Conclusions: A reduced rate of 18F-FDG uptake post-NACI and TME-related surface markers on lymphocytes could be optimal predictors for pCR. However, the role of these pCR predictors for NACI remains poorly validated, warranting further investigations. This review focuses on predictive biomarkers for pathological response after NACI in patients with resectable NSCLC.

Comment on Manole et al. Primary Pericardial Synovial Sarcoma: A Case Report and Literature Review. Diagnostics 2022, 12, 158.

With great interest, we read the article by Manole et al [...].

Case report: Characteristics and nature of primary cardiac synovial sarcoma.

Primary malignant cardiac tumors rarely occur, and cardiac synovial sarcoma (SS) is especially rare among such tumors. Herein, we present the case of a 35-year-old female with primary cardiac SS treated with surgery, chemotherapy, and radiotherapy. She presented with chest symptoms and underwent imaging examinations. A cardiac tumor was suspected, and an open biopsy was performed. The pathological findings suggested cardiac SS. Next, we performed a resection, and the tumors persisted at a macroscopic level. Immunohistochemistry was negative for SS18-SSX and positive for the SSX C-terminus and cytokeratin CAM5.2, a reduction of SMARCB1/INI1 was observed, and fluorescence in situ hybridization showed positive SS18 split staining. Owing to the FNCLCC grade 3 tumor and R2 margins, adjuvant chemotherapy with ifosfamide, doxorubicin, and radiotherapy was initiated, and the patient was diagnosed with cardiac SS. The differences in patients with cardiac SS compared with general SS include male predominance, larger tumor size, and poorer prognosis. Pathological findings of immunohistochemistry and fluorescence in situ hybridization were found to be more reliable than imaging findings for a correct diagnosis. Additionally, because incomplete resection is frequently performed, adjuvant therapy, including chemotherapy and radiation therapy, may be performed. The findings indicate that multiple therapies, including surgery, chemotherapy, and radiotherapy, are essential treatment strategies for improving the prognosis of patients with cardiac SS.

Pivotal role of IL-8 derived from the interaction between osteosarcoma and tumor-associated macrophages in osteosarcoma growth and metastasis via the FAK pathway.

The prognosis of osteosarcoma (OS) has remained stagnant over the past two decades, requiring the exploration of new therapeutic targets. Cytokines, arising from tumor-associated macrophages (TAMs), a major component of the tumor microenvironment (TME), have garnered attention owing to their impact on tumor growth, invasion, metastasis, and resistance to chemotherapy. Nonetheless, the precise functional role of TAMs in OS progression requires further investigation. In this study, we investigated the interaction between OS and TAMs, as well as the contribution of TAM-produced cytokines to OS advancement. TAMs were observed to be more prevalent in lung metastases compared with that in primary tumors, suggesting their potential support for OS progression. To simulate the TME, OS and TAMs were co-cultured, and the cytokines resulting from this co-culture could stimulate OS proliferation, migration, and invasion. A detailed investigation of cytokines in the co-culture conditioned medium (CM) revealed a substantial increase in IL-8, establishing it as a pivotal cytokine in the process of enhancing OS proliferation, migration, and invasion through the focal adhesion kinase (FAK) pathway. In an in vivo model, co-culture CM promoted OS proliferation and lung metastasis, effects that were mitigated by anti-IL-8 antibodies. Collectively, IL-8, generated within the TME formed by OS and TAMs, accelerates OS proliferation and metastasis via the FAK pathway, thereby positioning IL-8 as a potential novel therapeutic target in OS.

Follicular adenoma with a papillary architecture originating from an ectopic thyroid gland: a case report.

BACKGROUND: Follicular adenomas with papillary architecture are rare tumors of thyroid origin and are composed of completely encapsulated follicular cells with a papillary architecture lacking the nuclear characteristics of papillary carcinoma. Herein, we present a case of follicular adenoma with papillary architecture originating from an ectopic thyroid gland, diagnosed from a mass in the submandibular region. CASE PRESENTATION: A 70-year-old woman was referred to our hospital with the chief complaint of a painless left submandibular mass that had been present for one year. The patient underwent left submandibular dissection for therapy and diagnosis. Microscopically, papillary lesions with fibrovascular cores were observed in the interior, and the epithelial cells were cylindrical in shape with eosinophilic cytoplasm, round or oval nuclei, with no pathological features, leading to a diagnosis of papillary carcinoma or follicular carcinoma. The mass was diagnosed as a follicular thyroid adenoma with papillary architecture. This is the first report of a follicular adenoma with a papillary architecture originating from an ectopic thyroid gland. CONCLUSION: This experience suggests that follicular adenoma should be included in the differential diagnosis of ectopic thyroid tumors.

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.

Clinical significance of antinuclear antibody as prognostic marker for first-line pembrolizumab in advanced non-small cell lung cancer.

BACKGROUND: The relationship between antinuclear antibody (ANA) and the efficacy of programmed death-1 (PD-1) blockade remains controversial. Here, we investigated the prognostic significance of ANA titer in patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab monotherapy as the first-line treatment, compared with that of platinum-based chemotherapy with PD-1 blockade. METHODS: Our clinical data based on the ANA titer (1:80) were retrospectively reviewed for patients with advanced NSCLC, who were treated with first-line pembrolizumab monotherapy and platinum-based chemotherapy with PD-1 blockade. Immunohistochemical staining for tumor-infiltrating lymphocytes such as CD4, CD8 and Foxp3 was performed. RESULTS: Among 106 patients treated with pembrolizumab, 19 (17.9%) tested high for ANA. Progression-free survival (PFS) and overall survival (OS) were significantly better in patients with high ANA than in those with low ANA, and high ANA was identified as an independent prognostic predictor, particularly in the subgroup with programmed death ligand-1 (PD-L1) ≥ 50%. However, no statistically significant difference in PFS and OS based on the ANA titer was observed in 59 patients treated with combinational chemotherapy and immunotherapy. High numbers of intratumoral Foxp3 and stromal CD8 were significantly associated with low ANA. CONCLUSIONS: Assessment of preexisting ANA titers was useful to prognose PD-1 blockade as a first-line setting, particularly for the PD-L1 ≥ 50% subgroup, but not in the case of combined immunotherapy and chemotherapy.

A Rare Clinical Presentation With a Difficult Imaging Diagnosis of an Intra-articular Clear Cell Sarcoma of the Knee.

ABSTRACT: Clear cell sarcoma, a highly aggressive cell sarcoma with melanotic differentiation, typically occurs in the tendon and aponeuroses of the lower extremities and rarely develops in the intra-articular region. Herein, we present an extremely rare case of clear cell sarcoma originating from the intra-articular knee and suspected as benign tumors due to the benign-looking findings on MRI and PET/CT. The image results in our case were completely consistent with a tenosynovial giant cell tumor, resulting in the misdiagnosis. For differential diagnosis, especially malignant melanoma, histopathology, including IHC and FISH, was indispensable.

Case Report: Angiomatoid fibrous histiocytoma in the hand: a rare clinical presentation and diagnostic challenge.

Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of mesenchymal origin occurring in young adults. Based on its clinical course, it is said to have an intermediate potential. We present a case of a 59-year-old woman with AFH in the hand that was difficult to diagnose. A benign soft tissue tumor was suspected on magnetic resonance imaging, and its size and open biopsy suggested nodular fasciitis or inflammatory myofibroblastic tumor. A diagnosis of AFH was eventually made based on the analysis of the resected specimens. The characteristic findings of histopathology and immunohistochemistry in this case were relatively poor, so fluorescence in situ hybridization contributed to making the correct diagnosis. Considering its prognosis, careful follow-up was decided upon without additional surgery. Our case is a challenging one because of its atypical presentation and inconclusive imaging and histopathological findings.

Synovial chondromatosis: Rare involvement of metacarpophalangeal joint and diagnostic challenges in MR imaging.

Synovial chondromatosis (SC) is a rare benign tumor of the cartilaginous tissue that frequently affects large joints intra-articularly. Characteristic imaging findings were reported for the diagnosis of SC. Herein, we report a case of SC of the metacarpophalangeal joint with atypical MRI findings. Considering the clinical presentation, erosion, absence of calcification on X-ray and CT, and low intensity on short tau inversion recovery (STIR), tenosynovial giant cell tumor was the initially diagnosis. However, histopathological findings revealed SC with fibrosis, which was confirmed using Elastica Van Gieson (EVG) staining. In general, low intensity on STIR in SC indicate calcification; however, it can also represent fibrosis in SC. In this case, the diagnosis of SC using MRI was limited highlighting the importance of histopathological findings for an accurate diagnosis of SC.

Indolent Multinodular Synovial Sarcoma of Peripheral Nerves Mimicking Schwannoma: A Case Report and Literature Review.

BACKGROUND/AIM: Most cases of synovial sarcoma (SS) are aggressive and large-sized; only few show indolent behavior, having a small size. Nerves are rare sites of SS occurrence. An atypical case of SS can lead to its misdiagnosis as a benign tumor and delay its treatment. CASE REPORT: Here, we report a case of primary SS of indolent multinodular synovial sarcoma of peripheral nerves. Considering the clinical and imaging findings at the first visit, we suspected a benign tumor and continued careful follow-up. Three years later, marginal resection was performed and SS was suspected. We then performed an additional wide resection using a free flap. Histopathologically, the proximal tumor showed a diffuse proliferation of spindle cells without pleomorphism, whereas the distal tumor showed a similar histology with more hypercellularity. Additional wide-resection specimens showed remnant tumors derived from the peripheral nerve. Immunohistochemistry (IHC) showed positive staining for SS18:SSX and SSX in both tumors and fluorescence in situ hybridization showed positive staining for the SS18 split in both tumors. Finally, SS of the peripheral nerve was diagnosed. Owing to FNCLCC grade 2 tumor and tumor size, adjuvant chemotherapy was not performed. CONCLUSION: In cases of SS or other sarcomas with atypical clinical courses, with imaging findings mimicking benign tumors, we recommend marginal resection along with pathological examination for correct diagnosis.

A Case of Bile Duct Mixed Neuroendocrine-nonendocrine Neoplasm with a Complete Response to Chemoradiotherapy.

The incidence of neuroendocrine carcinomas arising from the bile duct is low, and that of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) is even lower; therefore, there is no standard treatment for MiNENs. Choosing the appropriate treatment in clinical practice is difficult. We herein report a case of unresectable extrahepatic bile duct MiNEN in a 66-year-old man who received curative chemoradiotherapy and achieved a complete response, remaining recurrence-free for 2.5 years. We consider the findings of this case to be valuable in selecting a treatment strategy for unresectable bile duct MiNENs.