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Immune checkpoint inhibitor (ICI)-related myocarditis has been reported to appear in the early phase after ICI initiation. Herein, we report the case of a 78-year-old man with non-small cell lung cancer. Pembrolizumab was introduced as first-line therapy. After 9 months, second-line therapy, including bevacizumab, was initiated. After another 7 months, echocardiography showed diffuse left ventricular dysfunction. Based on the histopathologic examination of the myocardium, the patient was diagnosed with ICI-related myocarditis. Initiation of prednisolone therapy improved cardiac function. This case of late-onset ICI-related myocarditis illustrates that endomyocardial biopsy can be useful in the differential diagnosis of cancer-related left ventricular dysfunction. Résumé: Il a été rapporté qu’une myocardite pouvait survenir peu après l’instauration d’un traitement par des inhibiteurs des points de contrôle immunitaire (ICI). Nous présentons le cas d’un homme de 78 ans atteint d’un cancer du poumon non à petites cellules. Le pembrolizumab a été administré comme traitement de première intention. Neuf mois plus tard, un traitement de deuxième intention par le bévacizumab a été instauré. Après sept autres mois, l’échocardiographie a montré une dysfonction ventriculaire gauche diffuse. À la suite des résultats de l’examen histopathologique du myocarde, une myocardite liée aux ICI a été diagnostiquée. L’instauration d’un traitement par la prednisolone a amélioré la fonction cardiaque du patient. Ce cas de myocardite tardive liée aux ICI montre l’utilité éventuelle de la biopsie de l’endomyocarde dans le diagnostic différentiel d’une dysfonction ventriculaire gauche liée au cancer.

Liver metastasis is not uncommon in various malignant tumors. Most of liver metastases present as discrete masses. However, liver metastases can appear as diffuse infiltrating neoplasms. Infiltration of malignant cells can provoke hepatic fibrosis, which mimics cirrhosis. Progress of diffuse type of liver metastasis remains unclear because of its difficulty in diagnosis or aggressive nature. In this report, we describe a 27-year-old woman with diffuse type of liver metastasis from renal cell carcinoma. The present case showed atypical findings of clinical images on liver examinations, which was histologically diagnosed as a focally spared region in diffuse type of liver metastasis by needle biopsy. Liver fibrosis was not observed in the biopsy specimen. Our case report suggests that liver biopsy is essential for diagnosis of diffuse type of liver metastasis, and the spared region can be observed in the metastatic process of the diffuse type.

Adenosquamous carcinoma of the sinonasal tract is extremely rare. We report a case of such tumor in a 66-year-old Japanese male who presented with a 3.0-cm tumor in the maxillary sinus. The tumor mass filled the maxillary sinus, and part of the maxillary sinus floor was destroyed. Histological analysis showed that tumor cells with a marked atypia and pleomorphism with a high nuclear-cytoplasm ratio infiltrated beneath the mucosa. The tumor formed invasive nests and cribriform structures, and these structures were partially accompanied by marked necrosis. Additionally, tendency toward keratinization and peripheral palisading were present in the nests, and neoplastic cells showed varying cellular morphology including clear cells, where immunohistochemically positive staining for p63, p40 and CK5/6 was observed. While, immunoreactivity for these markers was absent in some of cribriform structures and solid nests, as well as areas showing fine nesting and cells surrounding glandular lumina. p16 was negative throughout the tumor, while p53 positive staining was detected throughout the tumor. CDX2 expression was observed in some solid nests. The tumor could be termed adenosquamous carcinoma, and also simultaneously considered to be essentially an adenocarcinoma derived from the ciliated epithelium of the maxillary sinus mucosa gradually increasing nuclear atypia with partial squamous metaplasia. The morphological transition was more clearly recognized in the p53 immunostaining. The patient died of disease two years after the primary surgery. This tumor is considered a histological type that can be fatal, and clinical attention is especially required when such a tumor encountered.

SCLC transformation in EGFR-mutated lung adenocarcinoma is one of the major phenotypic changes that is observed during the resistance to EGFR tyrosine kinase inhibitors. However, the mechanism of this transformation remains unclear. In this study, we found a small de novo SCLC component in surgically resected specimens of EGFR-mutated lung adenocarcinoma before EGFR tyrosine kinase inhibitor treatment. By using laser microdissection and whole-exome sequencing, TP53 loss of heterozygosity was found to be possibly involved in SCLC transformation.

A SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rapidly progressing subtype of lung cancer with a poor prognosis and causes early postoperative recurrence among operable patients. In this study, we present a case of SMARCA4-UT with vertebral and chest wall invasion that successfully underwent conversion surgery after treatment with atezolizumab in combination with bevacizumab, paclitaxel, and carboplatin. The surgical specimen comprised SMARCA4-deficient and SMARCA2-positive adenocarcinoma, confirming intratumor heterogeneity. Gene panel analysis revealed no substantial differences in mutant gene profiles among tumors and no differences in SMARCA2 mutations. Furthermore, no recurrence occurred for 9 months after surgery. Thus, this case illustrates the possibility of multidisciplinary treatment including neoadjuvant therapy with immunotherapy and conversion surgery for SMARCA4-UT.

Recent studies demonstrated that homologous repair deficiency (HRD) score is a useful marker for response to poly (ADP-ribose) polymerase inhibitors or platinum-based chemotherapy. We determined HRD scores and elucidated the clinicopathologic characteristics of HRD-high tumors and their response to non-platinum-based chemotherapy. Primary breast cancer patients (n = 120) were pre-operatively treated with paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC). Germline and somatic homologous recombination related gene mutations (gHRRm and sHRRm, respectively) and HRD scores were analyzed using whole exome sequencing (WES) in tumor tissues obtained before chemotherapy. Of 120 tumors, 30 were determined to be HRD-high tumors, significantly associated with high Ki-67 (P = 0.014), ER negativity (P = 0.007), and PR negativity (P = 0.021). Triple-negative cancers showed significantly higher HRD scores than the luminal, luminal-HER2, and HER2 subtypes (P = 0.023, 0.016, and 0.033, respectively). HRD scores were significantly higher in tumors with gHRRm than in those with sHRRm (P = 0.002) or wild-type HRR genes (P = 1.44e-4), but no significant difference was found in HRD scores between tumors with sHRRm and wild-type HRR genes (P = 0.206). HRD-high tumors had significantly (P = 0.003) higher pCR rates and higher near-pCR rates (P = 0.049) compared with those of the HRD-low tumors in all tumors and the luminal subtype, respectively. HRD-high tumors were associated with aggressive phenotypes and gHRRm, but not sHRRm. Our findings suggested that HRD scores might be useful in predicting response to P-FEC in the luminal subtype.