Mutação no gene BRAF em carcinoma diferenciado de tireoide avançado: um relato de caso

Introdução: o carcinoma diferenciado da tireoide corresponde aproximadamente a 90% dos casos de neoplasias da tireoide, sendo que, desses, 80-85% dos casos são de carcinoma papilífero da tireoide. Apesar de a maioria desses carcinomas serem bem diferenciados e com baixa taxa de invasão local, recidiva ou metástases (regionais ou distantes), existe um subgrupo que apresenta uma heterogeneidade genética com variantes mais agressivas, podendo tornar o câncer de tireoide mais invasivo e letal. Objetivos: 1) Relatar o caso de um paciente adulto portador de carcinoma diferenciado da tireoide avançado, com metástase pulmonar, em terapia supressiva com levotiroxina, após tratamento combinado com cirurgia e radioiodoterapia; 2) Discutir sobre as características patológicas e moleculares como fatores relevantes no direcionamento de condutas terapêuticas. Caso clínico: trata-se de um paciente do sexo masculino, com 39 anos de idade, cuja a punção aspirativa com agulha fina (PAAF) foi compatível com carcinoma papilífero da tireoide que, na sequência, foi submetido a tireoidectomia total, com esvaziamento cervical. O exame anatomopatológico revelou carcinoma papilífero da tireoide clássico, com metástase em cinco linfonodos. A análise molecular realizada por sequenciamento de nova geração evidenciou a mutação no gene BRAF (V600E), o qual tem associação significativa com estágios mais avançados do tumor, metástases e radioiodorefratariedade. Conclusão: este relato possibilita discutir a necessidade da avaliação molecular como direcionamento na conduta terapêutica de cada paciente oncológico.

Deciphering Tumor Niches: Lessons From Solid and Hematological Malignancies

Knowledge about the hematopoietic niche has evolved considerably in recent years, in particular through in vitro analyzes, mouse models and the use of xenografts. Its complexity in the human bone marrow, in particular in a context of hematological malignancy, is more difficult to decipher by these strategies and could benefit from the knowledge acquired on the niches of solid tumors. Indeed, some common features can be suspected, since the bone marrow is a frequent site of solid tumor metastases. Recent research on solid tumors has provided very interesting information on the interactions between tumoral cells and their microenvironment, composed notably of mesenchymal, endothelial and immune cells. This review thus focuses on recent discoveries on tumor niches that could help in understanding hematopoietic niches, with special attention to 4 particular points: i) the heterogeneity of carcinoma/cancer-associated fibroblasts (CAFs) and mesenchymal stem/stromal cells (MSCs), ii) niche cytokines and chemokines, iii) the energy/oxidative metabolism and communication, especially mitochondrial transfer, and iv) the vascular niche through angiogenesis and endothelial plasticity. This review highlights actors and/or pathways of the microenvironment broadly involved in cancer processes. This opens avenues for innovative therapeutic opportunities targeting not only cancer stem cells but also their regulatory tumor niche(s), in order to improve current antitumor therapies.

Burned-out testicular tumor: Two case reports

Spontaneous regression of a testicular tumor or burned-out testicular tumor is a rare phenomenon in patients with testicular germ cell tumors. The condition is characterized by tumor metastases, suspicious findings of the testicular tumor on ultrasound imaging, and partial or total histological regression of the primary testicular tumor after orchiectomy without treatment. Clinically, patients present with a disseminated tumor with symptoms related to the metastatic site without a palpable testicular tumor. Patients may also present with elevated levels of tumor biomarkers, depending on the histology. The etiopathogenesis of this phenomenon remains unclear and may involve immunologic factors as well as necrosis due to tumor growth beyond the available blood supply. We report here two clinical cases of patients treated at our center, both presenting with symptoms caused by retroperitoneal lymph node dissemination but different histologiesas well as a different clinical course. Keywords: germ cell tumor; testicular cancer; spontaneous regression.

Topical instillation of cell-penetrating peptide-conjugated melphalan blocks metastases of retinoblastoma

Retinoblastoma is the most common primary intraocular malignancy in infancy with a metastases-related death risk. However, a safe and convenient treatment without enucleation is still an unmet clinical need. In this work, a cell-penetrating peptide, 89WP, was conjugated with melphalan (89WP-Mel), which achieved comparable tumor inhibition effects to intravitreally injected melphalan via topical instillation for the first time. Notably, the “outside-in” diffusion of instilled 89WP-Mel created a protective shield surrounding the eye, efficiently preventing tumor metastases. In contrast, the mice treated with intravitreally injected melphalan suffered more brain metastases related death, probably due to the “inside-out” diffusion of injected melphalan expelling the tumor outside the eye. The ocular absorption of 89WP-conjugated melphalan and other small molecules, both hydrophobic and hydrophilic, occurred via non-corneal pathway with high safety and a prolonged residence duration in retina up to 24 h. The present work paves a new avenue for simultaneous intraocular tumor inhibition and extraocular metastases prevention in a safe and convenient way via topical instillation.

The Difficulties of Differential Diagnosis of the Bronchial Obstruction Syndrome

Bronchial obstructive syndrome is a violation of bronchial patency of functional or organic origin, which is manifested by shortness of breath, suffocation attacks, cough, tachycardia. The most common cause of bronchial obstructive syndrome is chronic obstructive pulmonary disease and bronchial asthma. In some cases, the cause of bronchial obstruction is tumors or tumor metastases to the lungs. The article describes a clinical case of bronchial obstructive syndrome, showing that all patients with bronchial asthma, in the absence of an effect from the prescribed adequate basic therapy, with no control over the disease, should be well examined for an alternative diagnosis. In our case, a thorough examination of the patient allowed the allergist to diagnose central lung cancer with metastases to the lymph nodes of the mediastinum. A feature of the case is the primary resistance to tyrosine kinase inhibitors, revealed during a genetic study, which determined the scheme of further polychemotherapy. This clinical case proves the need for differential diagnosis, with a comprehensive approach and the use of various examination methods.

Features of the lymphocytic microenvironment in metastatic uveal melanoma

Introduction. Uveal melanoma is a malignant neoplasm of the vascular tract of the eye. Prevention of metastasis of this tumor is one of the main tasks in order to increase the rates of relapse-free survival of patients. Despite the pronounced immunosuppressive activity of uveal melanoma cells, its lymphocytic microenvironment exerts its antitumor effect.Aim of the study. Compare the lymphocytic microenvironment of primary uveal melanomas and distant metastases (to the liver).Мaterials and methods. The tissue material of choroid melanoma after enucleation and the material of tumor metastases for the period 2013-2018 were studied. An immunohistochemical study was performed using CD8, CD4, and CD56 markers for the qualitative and quantitative assessment of lymphocytes in the tumor stroma.Results. Differences were found in the lymphocytic infiltration of the uveal melanoma stroma and its distant metastases. A statistically significantly greater representation of CD4, CD8-lymphocytes and CD56 cells in tumor metastases than in primary melanoma tissue samples, with CD4-lymphocytes predominant. A direct high-strength correlation was registered between the number of CD4-lymphocytes and CD8-lymphocytes.Discussion. Malignant cells actively modify their cellular and stromal-vascular environment, ensuring their active growth and reproduction. The question of the immune reactivity of the surrounding cells in relation to uveal melanoma remains debatable. According to our data, which is consistent with a number of other studies, uveal melanoma cells do not completely evade the body's immune response. Thus, the determination of possible points of antitumor exposure can be based on a detailed study of the microenvironment of uveal melanoma. Conclusions. The pronounced lymphocytic infiltrate found in uveal melanoma metastases in comparison with the primary tumor indicates an active immune response of the body to the tumor. These results of our study confirm the importance of further studying the immune-mediated antitumor effect on uveal melanoma and the need to investigate possible approaches to immunotherapy.

Phototherapy meets immunotherapy: a win–win strategy to fight against cancer

Phototherapy usually includes photodynamic therapy (PDT) and photothermal therapy (PTT) to induce cell death. PDT utilizes the sensitization of the photosensitizers to generate reactive oxygen species by the intersystem crossing while PTT undergoes nonradiative decay to generate heat. Cancer immunotherapy has evolved as a new therapeutic modality to eradicate tumor cells by activating antigen-presenting cells, and thus, inducing innate or adaptive immune responses. Phototherapy is able to stimulate the immune system, usually by inducing immunogenic cell death (ICD). Photoimmunotherapy (PIT) is an oncological treatment that combines the phototherapy of the tumor with immunotherapy treatment. Combining phototherapy with immunotherapy enhances the immunostimulating response and has synergistic effects for metastatic cancer treatment. PIT is able to enhance the antitumor immune response by ICD and prevent tumor metastases and recurrence. In this review article, we would like to summarize the recent advances in the development of phototherapy (such as PDT, PTT, and synergistic PDT/PTT) triggered immunotherapy for cancer treatment. In addition, immunotherapy triggered by phototherapy and other therapeutic modalities will be discussed. PIT may be a win-win strategy to fight against cancer.