Molecular features evaluation of metastatic foci as the basis for metastatic breast cancer treatment personalization. Is there a place of CDK4/6-inhibitors in late-line therapy after chemotherapeutic regimens?

The problem of metastatic breast cancer treatment is linked with clonal selection both in the process of tumor evolution and under the influence of previous treatment. The analysis of metastatic niche microenvironment and the molecular genetic features become essential for treatment individualization. Studies demonstrate hormonal expression and epidermal growth factor receptor (HER2neu) discordance between the primary tumor and the metastatic focus. The advantages of combined hormone therapy (CНT) with CDK4/6 inhibitors were revealed in comparison with hormone therapy (НT) with survival rates benefits in the 1st and 2nd lines of НT, as well as after the 1st line of chemotherapy in clinical trials. However, there are lack of data on patients with multiple lines of chemotherapy. In the present retrospective study, more than half of the patients were treated palliative chemotherapy before administration of CDK4/6 inhibitors. Main metastatic foci represented luminal types after biopsy, however, loss of progesterone receptor expression was noted with the initial luminal A-subtype. At the time of the data cut-off, most patients have a longterm clinical effect, improvement conditions and reduction of pain, including the cases of late line CHT setting after chemotherapeutic regimens. Taking into account the heterogeneity of metastatic breast cancer, clonal selection and phenotype discordance there is the crucial need for molecular and genetic characteristics of the metastatic process. At the same time it is possible to consider the appointment of combined hormone therapy with CDK4/6 inhibitors as additional option for late-line treatment of the disseminated process. Prospective studies on combined hormonal therapy with CDK4/6 inhibitors in metastatic breast cancer in late lines of therapy with proven HR+HER2neu-negative receptor status of the metastatic focus are strongly recommended.

Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification

BackgroundPrimary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC). Currently, anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has become an important treatment for NSCLC. Anti-human PD-1 monoclonal antibodies, such as nivolumab, significantly prolong the survival time of patients with advanced lung adenocarcinoma and lung squamous cell carcinoma. However, there are few reports on the therapeutic effect, drug resistance mechanism, and strategies to overcome resistance to anti-PD-1/PD-L1 treatment in advanced pulmonary LELC. We report the case of a patient with advanced pulmonary LELC harboring fibroblast growth factor receptor (FGFR)3 gene amplification that showed resistance to nivolumab. After treatment with anlotinib, a multi-targeted small-molecule tyrosine kinase inhibitor, the patient’s resistance to nivolumab was reversed. She achieved long-term disease remission with a combination of anlotinib and nivolumab treatment.Case PresentationA 68-year-old woman was diagnosed with stage IVA pulmonary LELC. After multiple-line chemotherapy, her disease progressed. Since the PD-L1 expression rate of the patient was 90%, nivolumab was administered. However, the therapeutic effect of nivolumab was not ideal; the disease continued to progress, and a new cervical lymph node metastasis appeared. FGFR3 gene amplification was detected in lymph node metastasis. Based on this gene abnormality, we added anlotinib to the treatment. After two cycles of anlotinib and nivolumab, the metastatic focus of the patient was significantly reduced. The patient continued to receive this combined treatment and achieved remission for more than 15 months.ConclusionPulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.

Acute posteromedial papillary muscle rupture secondary to aortic valve endocarditis: a case report

Background Acute papillary muscle rupture due to infective involvement has been recognized as a complication of infective endocarditis. However, there is very limited literature describing the rupture of the posteromedial papillary muscle in primary aortic valve endocarditis without aortic root abscess. This report highlights the etiology of the papillary muscle rupture in the setting of primary aortic valve endocarditis and the importance of a multidisciplinary approach. Case summary An 81-year-old man without any heart failure symptoms presented with fever and loss of vision in his left eye. Initial echocardiography revealed moderate aortic valve regurgitation due to a perforated right coronary cusp without aortic root abscess, and his blood cultures were positive for Group G Streptococci. During adequate antibiotic therapy, he developed acute severe mitral regurgitation secondary to posteromedial papillary muscle rupture. Following emergent aortic and mitral valve replacement using bioprosthetic valves, he made excellent progress on a 6-week course of intravenous antibiotics. Discussion The echocardiography and the histological findings suggested that the main cause of papillary muscle rupture was most likely a metastatic focus of infection from the aortic valve via a regurgitant jet. Successful treatment of this fatal complication includes early diagnosis and prompt surgical intervention by a multidisciplinary approach.

[68Ga] Ga-DOTA-FAPI-04 And [18F] FDG PET / CT For Diagnosis of Metastatic Lesions In Patients With Recurrent Papillary Thyroid Carcinoma

Context: PET CT imaging methods based on fibroblast activation protein inhibitors (FAPIs) have recently demonstrated promising clinical results. Objective: We aimed to evaluate the use of 68Ga-FAPI PET / CT and 18FDG PET / CT imaging techniques to detect the metastatic foci in recurrent papillary thyroid carcinoma.Design and Patients: This is a prospective study. Patients who were diagnosed with papillary thyroid carcinoma, achieved biochemical recovery after the first operation and having recurrence for papillary thyroid carcinoma on the follow up were included in the study. [68Ga] Ga-DOTA-FAPI-04 and [18F] FDG PET / CT were performed for comparative purpose and detection of recurrence localization.Results: [18F] FDG PET / CT detected the metastatic foci in 21 of 29 patients (72.4%), [68Ga] Ga-DOTA-FAPI-04 was able to detect the metastatic foci in 25 of 29 patients (86.2%). When the two imaging techniques were used together, the metastatic foci in 27 of the 29 patients could be detected (93.1%.). Also between the [18F] FDG PET / CT SUVmax values and [68Ga] Ga-DOTA-FAPI-04 SUVmax values, a statistical significance was found in favor of 68Ga-FAPI PET (p = 0,002).Conclusion: In conclusion, 68Ga-FAPI PET imaging technique can be used as an alternative method to detect the metastatic focus or foci in patients with recurrent papillary thyroid carcinoma. It can also increase the chance of metastatic focus or foci detection when used in conjunction with the 18 FDG PET.

BRAF V600E and lymph node metastases in papillary thyroid cancer

Objective To evaluate the relationship between the BRAF V600E mutation in lymph node metastasis (LNM) and its invasive characteristics in papillary thyroid cancer (PTC). Material and methods A total of 373 PTC patients were enrolled in this study conducted at Zhujiang Hospital of Southern Medical University between January 2017 and December 2018. PTCs with cervical lymph node metastases were verified pathohistologically, and primary tumors and LNM were examined for the BRAF V600E mutation. Patients were excluded from the study if the BRAF V600E mutation was examined only in primary tumors or only in LNM. Results Of the 373 patients examined, BRAF V600E mutation frequency in primary tumors was slightly higher than in LNM (81.5% vs 78.0%, P = 0.000), the intra-class correlation coefficient (ICC) was 0.865 (95% CI 0.835–0.890). The BRAF V600E mutation in both primary tumor and LNM negatively correlated with the size of the largest metastatic focus of LNM (Odds ratio, OR = 0.297, 95% CI 0.143–0.616, P = 0.001; OR = 0.242, 95% CI 0.119–0.492, P = 0.000, respectively). There was no relationship between BRAF V600E mutation in LNM and the number, extranodal extension or stage of LNM (P > 0.05). Conclusion The BRAF V600E mutation in LNM may not be related to the invasive characteristics of LNM in PTC.

The value and practical utility of intraoperative touch imprint cytology of sentinel lymph node(s) in patients with breast cancer: A retrospective cytology-histology correlation study

Objective: Intraoperative evaluation of sentinel lymph nodes (SLNs) for patients with breast cancer is widely performed with frozen section (FS), cytology, or a combination of both. Touch imprint cytology (TIC) reportedly has an equivalent sensitivity to FS. We studied its diagnostic utility to detect SLN metastases. Materials and Methods: Cases of 367 patients with breast cancer who underwent intraoperative valuation of SLNs (507 LNs) were evaluated. All FS and corresponding TIC slides of SLNs of each case were reviewed microscopically for the presence of metastases of any size. If present, the metastatic focus was measured on the FS. Results: Of these 507 SLNs, 82 LNs (16.2%) from 69 women were found to have metastases in the FS and consisted of 5 LNs of isolated tumor cells, 15 of micrometastasis, and 62 of macrometastasis. TIC identified metastases in 69 of these 82 SLNs (sensitivity: 84.1%, specificity: 100%, and accuracy: 97.4%). All macrometastases could be detected by TIC, whereas TIC identified approximately 50% of micrometastases and none of isolated tumor cells. The size detection limit of metastatic foci, defined as the smallest dimension of metastasis detected without false negatives, was 2 mm. The smallest metastatic focus identified was 0.8 mm. Conclusions: TIC of SLNs is of great use given its negative predictive value of 100% for identification of macrometastasis in our study. For intraoperative evaluation of SLNs, based on our data, a practical two-step approach is proposed: SLN evaluation should be initially performed by TIC and then proceed to FS histological analysis only when cytologically positive to determine the size of metastatic focus.

Head and neck cutaneous metastasis of testicular choriocarcinoma

Testicular choriocarcinoma (CC) is a malignant germ cell tumour which most frequently presents with disseminated metastasis, often involving the lungs, brain and liver. Metastatic are characterised by extensive vascularity, often causing patients to present emergently with potentially life-threatening haemorrhagic complications. We report a patient with disseminated testicular CC, presenting with haemorrhage from a dermal metastatic focus involving the lower lip and mentum, requiring surgical intervention. This unique case illustrates the potential utility of palliative surgery, for the management of symptomatic metastatic disease, such as those caused by testicular CC.

Vitreous Metastasis in a Case of Metastatic Breast Cancer

A 35-year-old female with a history of metastatic breast cancer (BC) presented with unilateral blurred vision and floaters over 6 weeks. Examination findings showed vitreous opacities and a vasculitis concerning for an infectious process. Diagnostic vitrectomy revealed no infectious cause, but rather metastatic cells in the vitreous, with no obvious retinal or choroidal metastatic focus. In this report we illustrate a case of vitreous metastasis in a patient with metastatic BC, highlighting the importance of recognizing this rare entity which can mimic an inflammatory or infectious process. Novel to this report is the use of modern wide-field retinal imaging, spectral-domain optical coherence tomography, and a surgical video to document the findings of this disease entity.