Localisation Buccale Secondaire D’un Carcinome Renal

Renal cell carcinomas are tumors known for their metastatic potential. The lungs, the lymph nodes, the lungs, the spleen, the adrenal gland and the cervix remain the metastatic sites of predisposition. The symptoms of metastatic lesion may be due to the initial manifestation of renal malignancy. We report in this work a buccal localization of metastases from renal cell carcinoma to clear cells in a patient aged 65 years or less in our department of otolaryngology and cervical-facial surgery.

Possibility of SARS-CoV-2 Infection in the Metastatic Microenvironment of Cancer

According to a report from the World Health Organization (WHO), the mortality and disease severity induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are significantly higher in cancer patients than those of individuals with no known condition. Common and cancer-specific risk factors might be involved in the mortality and severity rates observed in the coronavirus disease 2019 (COVID-19). Similarly, various factors might contribute to the aggravation of COVID-19 in patients with cancer. However, the factors involved in the aggravation of COVID-19 in cancer patients have not been fully investigated so far. The formation of metastases in other organs is common in cancer patients. Therefore, the present study investigated the association between lung metastatic lesion formation and SARS-CoV-2 infectivity. In the pulmonary micrometastatic niche of patients with ovarian cancer, alveolar epithelial stem-like cells were found adjacent to ovarian cancer. Moreover, angiotensin-converting enzyme 2, a host-side receptor for SARS-CoV-2, was expressed in these alveolar epithelial stem-like cells. Furthermore, the spike glycoprotein receptor-binding domain (RBD) of SARS-CoV-2 was bound to alveolar epithelial stem-like cells. Altogether, these data suggested that patients with cancer and pulmonary micrometastases are more susceptible to SARS-CoV-2. The prevention of de novo niche formation in metastatic diseases might constitute a new strategy for the clinical treatment of COVID-19 for patients with cancer.

Usual acinar adenocarcinoma and osteoblastic lesion in the distal middle third of the femur, an unusual finding: a case report / Adenocarcinoma acinar usual e lesão osteoblástica no terço médio distal do fêmur, um achado incomum: relato de caso

A patient with prostate cancer may initially be asymptomatic, compromising early diagnosis and treatment. A 42-year-old male patient on a routine examination had a PSA of 4.18 ng / ml. Prostate biopsy revealed usual Gleason 7 stage T2a acinar adenocarcinoma. Magnetic resonance imaging revealed a nodule in the prostate. Bone scintigraphy showed osteoblastic lesion of the left femur, considered a possibility of a secondary lesion to adenocarcinoma, but his biopsy showed tissue without significant histological changes, ruling out malignancy. The patient was submitted to a radical prostatectomy and bilateral lymphadenectomy, evolving without complications. Follow-up tests showed reactive Protein C negative, alkaline phosphatase, lactate dehydrogenase and total testosterone without changes, total PSA 0.011; Free PSA less than 0.01. The total PSA 0.3 indicated a possible recurrence after 3 years. Magnetic resonance imaging showed no suspicious lesions, PET / CT was performed, which showed molecular hyperexpression of specific membrane antigen for the prostate, confirming local recurrence. Therefore, he was submitted to 36 radiotherapy sessions in the prostate bed from July to August. In October, the total PSA was performed, which decreased sharply. The early stage of prostate cancer may show only benign prostate growth, while the advanced stage may reveal bone pain. Bone tissue often develops a metastatic lesion, resulting in a worse prognosis. In this patient, a link between prostate carcinoma and bone lesion was ruled out by biopsy, which demonstrated the absence of spread of the disease.

Blindness paving the path to the diagnosis of metastatic prostate carcinoma: A unique case presentation

Background: Intracranial metastases from prostate adenocarcinoma are very unusual and typically occur late in the course of the disease, and initial presentation with symptomatic brain involvement, especially vision loss is very rare (with this being only the sixth such reported case to the best of our knowledge). The present case elucidates how a diagnosis was reached in such a scenario and the management provided. Case presentation: A 66-year-old gentleman presented with loss of vision and headache with no other ocular or neurological complaint. Computed tomography (CT) of his head revealed a destructive lesion involving the clivus and a space-occupying lesion (SOL) in occipito-parietal region. Detailed inquiry regarding the possible primary source of suspected the metastatic lesion revealed an increased frequency of urination, nocturia, and significant weight loss. His serum prostate-specific antigen (PSA) levels were raised. He was treated by surgical hormonal therapy and his visual symptoms improved. Conclusion: Awareness of such a presentation can lead to an accurate diagnosis. Initiation of appropriate therapy can successfully alleviate the neurologic deficits.

Predictive value of morphological features and proliferative markers (mitotic index, Ki-67, PHH3) in bronchopulmonary neuroendocrine tumors

The aim of this study was to evaluate relations of mitotic index (MI), necrosis, IHC proliferative markers Ki-67 and PHH3, and their predictive value for lung neuroendocrine tumors (NETs) aggressiveness. Materials and methods. The study used surgical and biopsy material from 64 patients with lung NETs before chemotherapy prescribing. Morphological study and IHC was performed. MI, necrosis, Ki-67 and PHH3 expression and metastatic disease and survival were estimated using nonparametric statistics. Results. Statistically significant association of necrosis severity and survival rates was found (P = 0.021). This was true for comparing patients with no necrosis in tumor tissue and extensive foci of necrosis (P = 0.023). MI appeared to be associated with metastases in lymph nodes (P = 0.003) and with distant metastatic lesions (P = 0.029). Significant, direct association of Ki-67 and MI (P < 0.001), MI and PHH3 expression (P < 0.001) was found. However, there was no significant link between Ki-67 and PHH3 rates (P = 0.240). Ki-67 didn’t show any significant association with necrosis and metastases. Also, Ki-67 rates didn’t affect the patient survival. Data on PHH3 expression and their estimation appeared to be rather contradictory. PHH3 expression rates were lower than expected and did not exceed neither Ki-67 rates, nor MI. Conclusions. MI and necrosis are reliable markers for the assessment of lung NETs aggressiveness. MI is statistically associated with metastatic lesion, while extensive necrosis – with survival rates. Ki-67 expression was significantly associated with MI. No significant association of Ki-67 and PHH3 expression, tumor’s morphological features, disease progression and prognosis was found. Contrary to our expectations, PHH3 showed no diagnostic and prognostic value in lung NETs.

Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis

Bone marrow is a preferred metastatic site for multiple solid tumours and is associated with poor prognosis and significant morbidity. Accumulating evidence indicates that cancer cells colonise specialised niches within the bone marrow to support their long-term propagation, but the precise location and mechanisms that mediate niche interactions are unknown. Using breast cancer as a model of solid tumour metastasis to the bone marrow, we applied large-scale quantitative three-dimensional imaging to characterise temporal changes in the bone marrow microenvironment during disease progression. We show that mouse mammary tumour cells preferentially home to a pre-existing metaphyseal domain enriched for type H vessels. Metastatic lesion outgrowth rapidly remodelled the local vasculature through extensive sprouting to establish a tumour-supportive microenvironment. The evolution of this tumour microenvironment reflects direct remodelling of the vascular endothelium through tumour-derived granulocyte-colony stimulating factor (G-CSF) in a hematopoietic cell-independent manner. Therapeutic targeting of the metastatic niche by blocking G-CSF receptor inhibited pathological blood vessel remodelling and reduced bone metastasis burden. These findings elucidate a mechanism of ‘host’ microenvironment hijacking by mammary tumour cells to subvert the local microvasculature to form a specialised, pro-tumorigenic niche.

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.

Metastatic cluster 2-related pheochromocytoma/paraganglioma: a single-center experience and systematic review

Objective: Risk of metastatic disease in the cluster 2-related pheochromocytoma/paraganglioma (PPGL) is low. In MEN2 patients, identification of origin of metastases from pheochromocytoma (PCC) or medullary thyroid carcinoma (MTC) is challenging as both are of neuroendocrine origin. We aim to describe our experience and perform a systematic review to assess prevalence, demographics, biochemistry, diagnostic evaluation, management and predictors of cluster 2-related metastatic PPGL. Design: Retrospective study with systematic review of literature. Methods: Data of 3 cases from our cohort and 43 cases from world literature were analyzed. For calculation of prevalence, all reported patients (n=3063) of cluster 2 were included. Results: The risk of metastasis in cluster 2-related PPGL was 2.6% (2% in RET, 5% in NF1, 4.8% in TMEM127 and 16.7% in MAX variation). In metastatic PCC in MEN2, median age was 39 years, bilateral tumors were present in 71% and median tumor size was 9.7 cm (range 4-19) with 43.5% mortality. All patients had primary tumor size ≥4cm. Origin of primary was diagnosed by histopathology of metastatic lesion in 11(57.9%), 131I-MIBG scan in 6(31.6%), and selective venous sampling and computed tomography in one (5.3%) each. In subgroup of NF1, median age was 46 years (range 14-59) with median tumor size 6cm and 57% mortality. Conclusion: The risk of metastatic disease in cluster 2-related PPGL is 2.6%, being especially high in tumors with size ≥4cm and is associated with high mortality. One-third patients of NF1 with metastatic PPGL had presented in 2nd decade of life. Long-term studies are needed to formulate management recommendations.