Successful Response to Cyclophosphamide, Vincristine, and Dacarbazine Chemotherapy in a Patient with Metastatic Carotid Body Paraganglioma

Carotid body paraganglioma is a rare neuroendocrine tumor presenting with low-grade histological and clinical features. However, the tumor has the potential to produce distant metastasis, and due to its rarity, little information is available regarding chemotherapy for such metastatic lesions. Here, we report a case of carotid body paraganglioma with development of pulmonary and bone metastases 10 years after radical surgery for the primary lesion in the neck. The lesions showed a good response to cyclophosphamide, vincristine, and dacarbazine chemotherapy. A beneficial therapeutic outcome by chemotherapy is extremely rare in patients with metastatic carotid body paraganglioma.

Canonical Wnt Signaling Inhibition in Renal Cell Carcinoma Bone Metastasis: Immunohistochemical Study of DKK1 and LRP5 Expression

Introduction & Objectives: Canonical Wnt signaling (Wnt/β-catenin signaling) maintains the bone homeostasis by promoting the osteoblastic activities. The inhibitory factor, Dickkopf (DKK)1, enhances the bone resorption, especially in malignancies. The low density lipoprotein related protein (LRP) 5 is a component of membranous co-receptor of Wnt/β-catenin signaling and is also involved in serum low density lipoprotein cholestrol (LDL-C) level regulation. The clear cell renal cell carcinoma bone metastasis (ccRCC-BM) is characterized by osteolytic bone resorption. Whether and how Wnt/β-catenin signaling plays roles in regulating the invasion, metastasis and osteolytic process of ccRCC to bone remain unclear. This study investigated the expression of DKK1, LRP5 proteins in primary and metastatic lesions of RCC-BM. The therapeutic potential of Wnt/β-catenin signaling target medication was also evaluated.Materials & Methods: ccRCC-BM patients with paired samples of primary and metastatic lesions were selected. ccRCC patients without any metastasis (ccRCC-only) were set as control. Slides of paraffin-embedded tissue underwent immunohistochemical staining with monoclonalanti-DKK1 antibody and polyclonal anti-LRP5 antibody. Semi-quantitatively scoring according to staining intensity was performed. The staining results in the renal tissue adjacent to RCC, the primary RCC lesions (with BM or without BM), and the RCC-BM lesions were recorded. The expression difference was analyzed by univariate analysis of variance (ANOVA).Results: The expression of DKK1 was significantly different amid renal tissue adjacent to RCC, primary RCC and RCC-BM tissues (p< 0.001). The expression of DKK1 in primary RCC was significantly lower than that in renal tissue adjacent to RCC (p<0.001). No difference was found between ccRCC-BM group and ccRCC-only group. DKK1 expression in bone metastasis was significantly higher than that in primary tumor (p < 0.001). The expression of LRP5 in the primary tumor of ccRCC-BM group was significantly lower than that of adjacent renal tissue (p<0.01). Tendency of decreasing expression was found between primary lesion of ccRCC-BM group and primary lesion of ccRCC-only group (p=0.073). In bone metastasis, the expression of LRP5 protein was not significantly different from that in adjacent renal tissue and RCC primary lesion.Conclusions: A "rebound" of DKK1 expression was found in bone metastasis lesions. Along with the decreasing LRP5 expression in primary lesions of RCC-BM patients, this suggests that the canonical Wnt signaling (Wnt/β-catenin signaling) is inhibited during the bone metastasis process in ccRCC. The overexpression of DKK1 and the down-regulation of LRP5 receptor are involved.

Leptomeningeal metastasis from melanoma emulating chronic subdural hematoma: a case report

Background Melanoma is a disease in which the patient doesn’t know about the primary lesion, and it has a propensity to metastases to any organ in the human body. Amongst melanoma, leptomeningeal metastasis has the least incidence. Case presentation In this case, we report a 56-year-old lady presenting with headache, recurrent vomiting and slurring of speech which on imaging was suggestive of chronic subdural hematoma which had led to surgical preparation but upon further examination, and radioimaging was found to be leptomeningeal metastasis from melanoma for which systemic therapy was started. Conclusions The concern is vigilance that is much needed in any case presenting in emergency. When the diagnosis is chronic subdural hematoma, it is followed by surgical treatment which is not done for leptomeningeal metastasis.

Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report

Microsatellite instability-high (MSI-H) is widely believed to be a biomarker for immune checkpoint inhibitors (ICIs) such as pembrolizumab in solid tumors. However, due to the low prevalence of MSI-H in most cancers, it tends to be insufficient to identify whether patients should receive ICIs according to this biomarker alone. Here, we report a Chinese esophageal squamous cell carcinoma (ESCC) patient with unusual divergent MSI status between the primary lesion (MSS) and metastatic lesion (MSI-H) which developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained a complete response for over 24 months. Whole-exome sequencing and multiplex immunohistochemistry were used to examine his tissue specimens. Notably, there were multiple high-frequency mutations of DDR (DNA damage repair) genes shared in the primary lesion and metastatic lesion, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastatic tumor without obvious difference, suggesting that the conversion of microsatellite status had little effect on the infiltration of lymphocytes. Collectively, given the predictive role of DDR alterations for ICIs in other malignancies, the alterations of DDR genes might also be promising biomarkers in ESCC individuals receiving ICIs.

Unusual presentation of lung carcinoma as nasal tip metastasis: A review of literature

Lung carcinoma is the most common type of carcinoma seen in males and 4 most common in females. Skin metastasis from lung carcinoma is frequent with an incidence of 1%-12%, with most common site being the anterior chest wall. Skin metastasis from lung carcinoma to the tip of nose is very rare with only 12 cases being reported in literature(Table 1). It can be confused with other benign and malignant conditions, such as infection, lymphoma, hemangioma, rhinophyma, sarcoidosis, tuberculosis and carcinomas, making its diagnosis difficult. Less than 20 cases of cutaneous nasal tip metastasis are reported in literature out of which 12 are from malignancies of lung. Sometimes it can appear earlier than the primary lesion and thus delays the diagnosis of primary lesion. = In this case report, we report a case of nasal tip cutaneous metastasis from squamous cell carcinoma of lung.

A rare case of pancreatic metastasis of lung adenocarcinoma

ABSTRACT Metastases to the pancreas are rare in general and scares in cases of lungs primary lesion. They are discovered incidentally in most cases. Data on their incidence, diagnosis, prognosis and management remain insufficient. The discovery is usually made at an advanced stage of lung cancer with the presence of metastases to other organs. We reported the case of a patient undergoing oncology follow-up for lung adenocarcinoma with discovery of adrenal gland metastases and a solitary pancreatic metastatic mass. His management remains palliative chemotherapy. Surgical treatment is not yet codified in these cases and remains at the discretion of the multidisciplinary oncology teams.

Glucose Metabolism Reprogramming of Primary Tumor and the Liver Is Associated With Disease-Free Survival in Patients With Early NSCLC

PurposeTumor promote disease progression by reprogramming their metabolism and that of distal organs, so it is of great clinical significance to study the changes in glucose metabolism at different tumor stages and their effect on glucose metabolism in other organs.MethodsA retrospective single-centre study was conducted on 253 NSCLC (non-small cell lung cancer) patients with negative lymph nodes and no distant metastasis. According to the AJCC criteria, the patients were divided into different groups based on tumor size: stage IA, less than 3 cm (group 1, n = 121); stage IB, greater than 3-4 cm (group 2, n = 64); stage IIA, greater than 4-5 cm (group 3, n = 36); and stage IIB, greater than 5-7 cm (group 4, n = 32). All of the patients underwent baseline 18F-FDG PET/CT scans, and the primary lesion SUVmax (maximum standardized uptake value), liver SUVmean (mean standardized uptake value), spleen SUVmean, TLR (Tumor-to-liver SUV ratio) and TSR (Tumor-to-spleen SUV ratio) were included in the study, combined with clinical examination indicators to evaluate DFS (disease free survival).ResultsIn NSCLC patients, with the increase in the maximum diameter of the tumor, the SUVmax of the primary lesion gradually increased, and the SUVmean of the liver gradually decreased. The primary lesion SUVmax, liver SUVmean, TLR and TSR were related to disease recurrence or death. The best predictive parameters were different when the tumor size differed. SUVmax had the highest efficiency when the tumor size was less than 4 cm (AUC:0.707 (95% CI, 0.430-0.984) tumor size &lt; 3 cm), (AUC:0.726 (95% CI, 0.539-0.912) tumor size 3-4 cm), liver SUVmean had the highest efficiency when the tumor size was 4-5 cm (AUC:0.712 (95% CI, 0.535-0.889)), and TLR had the highest efficiency when the tumor size was 5-7 cm [AUC:0.925 (95%CI, 0.820-1.000)].ConclusionsIn patients with early NSCLC, glucose metabolism reprogramming occurs in the primary lesion and liver. With the increase in tumor size, different metabolic parameters should be selected to evaluate the prognosis of patients.

Prospects for the Etiotropic Treatment of Dysferlinopathy

Dysferlinopathies belong to a phenotypically heterogeneous group of neuromuscular diseases caused by mutations in the DYSF gene, which disrupt the expression of dysferlin protein in human skeletal muscle cells. These pathologies are of an autosomal recessive inheritance pattern, their prevalence is 1: 200000. Dysferlinopathies include diseases such as Miyoshi myopathy with primary lesion of the distal fragments of the lower extremities and limb-gridle muscular dystrophy type 2B with primary lesion of the proximal fragments of both the lower and upper limbs, also distal myopathy with anterior tibial onset (DMAT). Nowdays, there are various pathogenetic and symptomatic treatments for hereditary muscular dystrophies but there are very few registered drugs for the etiological treatment of these diseases. This review discusses the main modern methods of gene therapy that can be used to treat dysferlinopathies, such as stop-codon passing, exon skipping, overexpression of other genes, gene transfer, splicosome-mediated trans-splicing, and also describes the latest experimental studies using these methods. In conclusion, exon-skipping and trans-splicing have been identified as the most optimal approaches in the treatment of muscular dystrophies, in particular dysferlinopathies.