Síndrome de Hedinger secundario a Tumor neuroendocrino bronquial. Presentación de un caso

El síndrome carcinoide es un síndrome paraneoplásico que se presenta en tumores neuroendocrinos. Aunque es una entidad infrecuente suele ser la primera manifestación de la enfermedad. La baja incidencia junto a la presentación inespecífica genera retrasos diagnósticos importantes. Se presenta el caso de una paciente con síntomas digestivos y tuforadas que posteriormente agrega insuficiencia cardíaca, logrando mediante un ecocardiograma típico y marcadores analíticos el diagnóstico de síndrome carcinoide. Posteriormente se evidencia que su origen en un tumor neuroendocrino bronquial. Conocer las características de este síndrome es fundamental para mantener una alta sospecha clínica en pacientes con síntomas sugestivos logrando un diagnóstico precoz y adecuado.

Carcinoid syndrome is a paraneoplastic syndrome that occurs in neuroendocrine tumors. Although It is an uncommon entity, it is usually the first manifestation of the disease. The low incidence besides the non-specific presentation generates important diagnostic delays. We present the case of a patient presenting digestive symptoms and flushing that subsequently adds heart failure, achieving though a typical echocardiogram and analytical markers the diagnosis of carcinoid syndrome. Later it is discovered its origin in a bronchial neuroendocrine tumor. Knowing the characteristics of this syndrome is essential to maintain a high clinical suspicion in patients with suggestive symptoms, in order to achieve an early and adequate diagnosis.

El síndrome carcinoide é um síndrome paraneoplásico que ocorre em tumores neuroendócrinos. Embora seja uma entidade rara, geralmente é a primeira manifestação da doença. A baixa incidência, juntamente com a apresentação inespecífica, resulta em atrasos importantes no diagnóstico. Apresentamos o caso de uma paciente com sintomas digestivos e ruborização cutânea, que posteriormente desenvolve insuficiência cardíaca. O diagnóstico de síndrome carcinoide foi estabelecido por meio de um ecocardiograma característico e marcadores analíticos. Posteriormente, foi evidenciada a origem em um tumor neuroendócrino brônquico. Conhecer as características deste síndrome é fundamental para manter uma alta suspeita clínica em pacientes com sintomas sugestivos, permitindo um diagnóstico precoce e adequado.

Primordial Odontogenic Tumor: A Review of the Literature and Report of Three New Patients.

The primordial odontogenic tumor (POT) is a rare mixed odontogenic tumor composed of mesenchymal cells, columnar odontogenic epithelium, and fibromyxoid stroma affecting the posterior mandible of children and adolescents. Herein, we report 3 patients with POT and the clinicopathological features of POT previously reported in the literature. A 12-year-old, 19-year-old, and 4-year-old patient presented an asymptomatic swelling in the posterior maxilla and posterior mandible. Imaging exams revealed radiolucent lesions associated with unerupted teeth. The lesions were surgically removed, and the histopathological examination revealed spindle-to-ovoid mesenchymal cells in a fibromyxoid stroma surfaced by columnar odontogenic epithelial cells with reverse nuclear polarization. Deposition of mineralized tissue was observed. The final diagnosis was POT, and patients did not exhibit signs of recurrence. POT should be included in the differential diagnoses of intraosseous lesions in the posterior mandible in pediatric patients.

Tumor-Suppressive Cross-Linking of Anti-T. cruzi Antibodies in Acute Lymphoblastic Leukemia.

Parasites have been associated with possible anticancer activity, including Trypanosoma cruzi, which has been linked to inhibiting the growth of solid tumors. To better understand this antitumor effect, we investigated the association of anti-T. cruzi antibodies with B cells of the acute lymphoblastic leukemia (ALL) SUPB15 cell line. The antibodies were generated in rabbits. IgGs were purified by affinity chromatography. Two procedures (flow cytometry (CF) and Western blot(WB)) were employed to recognize anti-T. cruzi antibodies on SUPB15 cells. We also used CF to determine whether the anti-T. cruzi antibodies could suppress SUPB15 cells. The anti-T. cruzi antibodies recognized 35.5% of the surface antigens of SUPB15. The complement-dependent cytotoxicity (CDC) results demonstrate the cross-suppression of anti-T. cruzi antibodies on up to 8.4% of SUPB15 cells. For the WB analysis, a band at 100 kDa with high intensity was sequenced using mass spectrometry, identifying the protein as nucleolin. This protein may play a role in the antitumor effect on T. cruzi. The anti-T. cruzi antibodies represent promising polyclonal antibodies that have the effect of tumor-suppressive cross-linking on cancer cells, which should be further investigated.

Doege-Potter syndrome due to a solitary fibrous tumor of the pleura: a case report.

BACKGROUND: Doege-Potter syndrome is a rare paraneoplastic phenomenon associated with solitary fibrous tumors of the pleura (SFTPs). It is characterized by the presence of severe, sustained, and treatment-refractory hypoglycemia. Hypoglycaemia, which may be the sole symptom at disease onset, is mediated by the secretion of high-molecular-weight insulin-like growth factor (IGF-2). Most tumors exhibit benign behavior, with a 100% survival rate at 5 years. However, 10% of these tumors may display aggressive behavior with local or metastatic recurrence. We present a clinical case of a patient with a benign solitary fibrous tumor of the pleura who presented with symptomatic hypoglycemia and required pulmonary and pleural surgical resection to control the paraneoplastic phenomenon. CASE PRESENTATION: A Hispanic 46-year-old man presented with a 15-day history of transient alterations in consciousness worsened by fasting. The relevant medical history included obstructive sleep apnea treated with continuous positive air pressure (CPAP) and previous smoking. In-hospital studies revealed noninsulinemic hypoglycemia and a benign SFTP. Complete surgical resection was performed while the patient received dextrose fluids and corticosteroids perioperatively for hypoglycemia. Subsequently, the hypoglycemia resolved, and the patient was followed-up without disease recurrence. CONCLUSION: Doege-Potter syndrome is challenging to recognize. However, effective treatment can be achieved with a high survival rate. Raising awareness among healthcare professionals about the recognition of this paraneoplasic syndrome patients will improve diagnostic suspicion, biochemical confirmation, the development of diagnostic and therapeutic guidelines, and the creation of predictive indices for aggressive presentations requiring closer monitoring.

Nephroblastoma in Older Adult: Case Report and Review of Literature.

Introduction: Nephroblastoma, or Wilms' tumor, is a malignant renal neoplasm commonly found in children, is extremely rare in adults representing only 0.5% of all renal neoplasms. Adult Wilms tumor is rare, to our knowledge fewer than 300 cases have been reported in the English literature to date. However, in older adults after 60 years of age, only less than 45 cases have been reported. For this reason, treatment guidelines in adults still are lacking. Prognosis in nephroblastoma for adult patients is found to be worse than in children. Case Presentation: We report the case of a 65-year-old female with lumbar fossa mass, flank pain and hematuria, and pathologic diagnosis of Wilms tumor. We performed nephrectomy. No adjuvant treatment was given. Our patient remains asymptomatic and without evidence of recurrence 12 months after the surgery. Conclusion: Nephroblastoma in the elderly presents different clinical behavior and prognosis compared to nephroblastoma in children.

Synthesis and preclinical evaluation of [18F]AlF-NODA-MP-C6-CTHRSSVVC as a PET tracer for CD163-positive tumor-infiltrating macrophages.

Positron emission tomography (PET) can provide information about tumor-associated macrophage (TAM) infiltration, as long as a suitable tracer is available. This study aimed to evaluate the radiolabeled peptide [18F]AlF-NODA-MP-C6-CTHRSSVVC as a potential PET tracer for imaging of the CD163 receptor, which is expressed on M2-type tumor-associated macrophages. The conjugated peptide NODA-MP-C6-CTHRSSVVC was labeled with aluminum [18F]fluoride. Tracer binding and its biodistribution were evaluated in an in vitro binding assay and in healthy BALB/c mice, respectively. In addition, different treatments with cyclophosphamide in tumor-bearing mice were used to assess whether the tracer could detect differences in CD163 expression caused by differential TAM infiltration. After 7 days of treatment, animals were injected with [18F]AlF-NODA-MP-C6-CTHRSSVVC, and a 60-min dynamic PET scan was performed, followed by an ex vivo biodistribution study. [18F]AlF-NODA-MP-C6-CTHRSSVVC was prepared in 23 ± 6 % radiochemical yield and showed approximately 50 % of specific receptor-mediated binding in an in vitro binding assay on human CD163-expressing tissue homogenates. No CD163-mediated binding of [18F]AlF-NODA-MP-C6-CTHRSSVVC was detected by PET under normal physiological conditions in healthy BALB/c mice. On the other hand, CD163-positive xenograft tumors were clearly visualized with PET and a positive correlation was found between CD163 levels and the [18F]AlF-NODA-MP-C6-CTHRSSVVC tumor-to-muscle ratio (TMR) obtained from the PET images (Pearson r = 0.76, p = 0.002). No significant differences in the CD163 protein level and in the tracer uptake between treatment groups were found in the tumors. Taken together, [18F]AlF-NODA-MP-C6-CTHRSSVVC appears a promising candidate PET tracer for M2-type TAM, as it binds specifically to CD163 in vitro and its tumor uptake correlates well with CD163 expression in vivo.

A CT-based radiomics tumor quality and quantity model to predict early recurrence after radical surgery for colorectal liver metastases.

PURPOSE: This study aimed to develop a tumor radiomics quality and quantity model (RQQM) based on preoperative enhanced CT to predict early recurrence after radical surgery for colorectal liver metastases (CRLM). METHODS: A retrospective analysis was conducted on 282 cases from 3 centers. Clinical risk factors were examined using univariate and multivariate logistic regression (LR) to construct the clinical model. Radiomics features were extracted using the least absolute shrinkage and selection operator (LASSO) for dimensionality reduction. The LR learning algorithm was employed to construct the radiomics model, RQQM (radiomics-TBS), combined model (radiomics-clinical), clinical risk score (CRS) model and tumor burden score (TBS) model. Inter-model comparisons were made using area under the curve (AUC), decision curve analysis (DCA) and calibration curve. Log-rank tests assessed differences in disease-free survival (DFS) and overall survival (OS). RESULTS: Clinical features screening identified CRS, KRAS/NRAS/BRAF and liver lobe distribution as risk factors. Radiomics model, RQQM, combined model demonstrated higher AUC values compared to CRS and TBS model in training, internal and external validation cohorts (Delong-test P < 0.05). RQQM outperformed the radiomics model, but was slightly inferior to the combined model. Survival curves revealed statistically significant differences in 1-year DFS and 3-year OS for the RQQM (P < 0.001). CONCLUSIONS: RQQM integrates both "quality" (radiomics) and "quantity" (TBS). The radiomics model is superior to the TBS model and has a greater impact on patient prognosis. In the absence of clinical data, RQQM, relying solely on imaging data, shows an advantage in predicting early recurrence after radical surgery for CRLM.

Association of tumor-infiltrating lymphocytes with clinical outcomes in patients with triple-negative breast cancer receiving neoadjuvant chemotherapy: a systematic review and meta-analysis.

OBJECTIVE: Triple-negative breast cancer (TNBC) presents a clinical challenge as an aggressive tumor, correlated with unfavorable prognosis. Tumor-infiltrating lymphocytes (TILs) have garnered interest as a potential prognostic biomarker. However, the disparity in outcomes between varying TILs rates remains inadequately explored. METHODS: PubMed, Scopus, Web of Science, and Cochrane databases were searched for studies about the prognostic value of TILs in patients with TNBC receiving neoadjuvant chemotherapy. The hazard ratios (HRs) or odds ratios (ORs) were computed for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Twenty-nine studies were included, involving a population of six thousand one hundred sixty-one (80.41%) with TNBC. The cut-off TILs value ranged from 10 to 60%, with 50% being the most related value. Compared with the low-TIL expression group, the disease-free survival (DFS) (HR 0.71; 95% CI 0.61-0.82; p < 0.00001) and overall survival (OS) (HR 0.76; 95% CI 0.63-0.90; p = 0.002) rates showed significant improvement with higher TIL infiltrations. In the subgroup analyses of the lymphocyte subtypes CD4 + and CD8 + , there was statistical significance favoring higher TILs rates in both subtypes, each associated with improved DFS (HR 0.48; 95% CI 0.33-0.71; p = 0.0002) and OS (HR 0.53; 95% CI 0.36-0.78; p = 0.001), regardless of which cell subtype was predominantly infiltrated. The complete pathological response analysis showed better rates for the higher TIL group than the control for both the TIL (OR 1.29; 95% CI 1.13-1.48; p = 0.0003) and Ki-67 (OR 2.74; 95% CI 2.01-3.73; p < 0.00001) analyses. CONCLUSION: Higher expressions of TILs in patients with TNBC were associated with improved significantly DFS, OS, and pCR outcomes.

Translational insights into the hormetic potential of carbon dioxide: from physiological mechanisms to innovative adjunct therapeutic potential for cancer.

Background: Carbon dioxide (CO2), traditionally viewed as a mere byproduct of cellular respiration, plays a multifaceted role in human physiology beyond simple elimination through respiration. CO2 may regulate the tumor microenvironment by significantly affecting the release of oxygen (O2) to tissues through the Bohr effect and by modulating blood pH and vasodilation. Previous studies suggest hypercapnia (elevated CO2 levels) might trigger optimized cellular mechanisms with potential therapeutic benefits. The role of CO2 in cellular stress conditions within tumor environments and its impact on O2 utilization offers a new investigative area in oncology. Objectives: This study aims to explore CO2's role in the tumor environment, particularly how its physiological properties and adaptive responses can influence therapeutic strategies. Methods: By applying a structured translational approach using the Work Breakdown Structure method, the study divided the analysis into six interconnected work packages to comprehensively analyze the interactions between carbon dioxide and the tumor microenvironment. Methods included systematic literature reviews, data analyses, data integration for identifying critical success factors and exploring extracellular environment modulation. The research used SMART criteria for assessing innovation and the applicability of results. Results: The research revealed that the human body's adaptability to hypercapnic conditions could potentially inform innovative strategies for manipulating the tumor microenvironment. This could enhance O2 utilization efficiency and manage adaptive responses to cellular stress. The study proposed that carbon dioxide's hormetic potential could induce beneficial responses in the tumor microenvironment, prompting clinical protocols for experimental validation. The research underscored the importance of pH regulation, emphasizing CO2 and carbonic acid's role in modulating metabolic and signaling pathways related to cancer. Conclusion: The study underscores CO2 as vital to our physiology and suggests potential therapeutic uses within the tumor microenvironment. pH modulation and cellular oxygenation optimization via CO2 manipulation could offer innovative strategies to enhance existing cancer therapies. These findings encourage further exploration of CO2's therapeutic potential. Future research should focus on experimental validation and exploration of clinical applications, emphasizing the need for interdisciplinary and collaborative approaches to tackle current challenges in cancer treatment.

Anaplastic thyroid cancer cell-secreted TGFß1 plays a key role in inducing macrophage polarization of human monocytes.

Anaplastic thyroid cancer (ATC) is a clinically aggressive form of undifferentiated thyroid cancer with limited treatment options. Tumor-associated macrophages (TAMs) constitute over 50% of ATC-infiltrating cells, and their presence is associated with a poor prognosis. We have previously shown that paracrine signals released by ATC cells induced pro-tumor M2-like polarization of human monocytes. However, which soluble factors derived from ATC cells drive monocyte activation, are largely unknown. In this study we investigated the participation of transforming growth factor ß1 (TGFß1) on the phenotype of macrophage activation induced by ATC cell-derived conditioned media (CM). THP-1 cells exposed to CM derived from ATC cells and recombinant human TGFß1 induced M2-like macrophage polarization, showing high CD163 and Dectin1 expression. Moreover, we showed that TGFß1 induced the messenger RNA (mRNA) and protein expression of the transcription factors SNAIL and SLUG. Accordingly, increased TGFß1 secretion from ATC cells was confirmed by enzyme-linked immunosorbent assay (ELISA). Addition of SB431542, a TGFß receptor inhibitor, significantly decreased the Dectin1, CD163, SNAIL and SLUG expression stimulated by ATC cell-derived CM. We validated the clinical significance of the expression of TGFß ligands, their receptors, as well as SNAIL and SLUG in human ATC by analyzing public microarray datasets. We found that the expression of the main TGFß ligands, TGFß1 and TGFß3, along with their receptors, TGFR1 and TGFR2, as well as SLUG, was significantly higher in human ATC tissue samples than in normal thyroid tissues. Our findings indicate that ATC cell-secreted TGFß1 may play a key role in M2-like macrophage polarization of human monocytes and in the up-regulation of SNAIL and SLUG transcription factors. Thus, ours results uncovered a novel mechanism involved in the activation of TAMs by soluble factors released by ATC cells, which suggest potential therapeutic targets for ATC.

Salivary biomarkers for the diagnosis of gastric cancer: a systematic review.

Background: Recent advancements reveal saliva as a crucial source of diagnostic biomarkers for various diseases, notably gastric cancer. This systematic review evaluates these biomarkers, emphasizing their clinical applicability and potential in early detection. Methods: An extensive electronic search was conducted across PubMed/MEDLINE, Scopus, and Web of Science to identify relevant studies. Salivary biomarkers were analyzed as independent variables, with gastric cancer as the dependent variable. The study adhered to a protocol registered with PROSPERO (CRD42021259519). Results: Our analysis identified a range of biomarkers, highlighting three proteins - cystatin-B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1) - as particularly accurate for gastric cancer diagnosis. Conclusions: Salivary biomarkers hold substantial promise for the early detection of gastric cancer. Future research should aim to refine study design and validation for enhancing the quality and applicability of these biomarkers.

Introducción: Avances recientes revelan la saliva como una fuente crucial de biomarcadores diagnósticos para diversas enfermedades, especialmente el cáncer gástrico. Esta revisión sistemática evalúa estos biomarcadores, con énfasis en su aplicabilidad clínica y potencial para la detección temprana. Métodos: Se realizó una extensa búsqueda electrónica en PubMed/MEDLINE, Scopus y Web of Science para identificar estudios relevantes. Los biomarcadores salivales fueron analizados como variables independientes, con el cáncer gástrico como variable dependiente. El estudio siguió un protocolo registrado en PROSPERO (CRD42021259519). Resultados: Nuestro análisis identificó una gama de biomarcadores entre los que destacan tres proteínas: cistatina-B (CSTB), triosa fosfato isomerasa (TPI1) y proteína 1 eliminada en tumores cerebrales malignos (DMBT1), como particularmente precisas para el diagnóstico del cáncer gástrico. Conclusiones: : Los biomarcadores salivales tienen un gran potencial para la detección temprana del cáncer gástrico. La investigación futura debería apuntar a refinar el diseño del estudio y la validación para mejorar la calidad y aplicabilidad de estos biomarcadores.

Assessing the diagnostic utility of serum tumor markers for lung cancer detection in patients with interstitial pneumonia.

BACKGROUND: The prevalence of lung cancer among individuals afflicted with interstitial pneumonia (IP) stands at approximately 20%. The early detection of lung cancer via chest computed tomography (CT) surveillance proves challenging in IP patients. Our investigation sought to identify a potential biomarker capable of providing early indications of the presence of lung tumors in such patients. MATERIALS AND METHODS: We examined the attributes of serum tumor markers, imaging characteristics, and histological findings in individuals diagnosed with IP, both with and without concurrent lung cancer. RESULTS: 106 patients diagnosed with IP were included in the study, comprising 36 individuals with concurrent lung cancer and 70 patients solely diagnosed with IP. Serum concentrations of CEA and CA12-5 were notably elevated in IP patients with lung cancer, compared to those with IP alone. Logistic regression analyses revealed that, in comparison to IP patients within the first quartile of CEA levels, the relative risk of developing lung cancer associated with IP escalated by 4.0-fold, 3.1-fold, 11.0-fold, and 13.3-fold in the second, third, fourth, and fifth quartiles, respectively. Upon controlling for gender and age, statistical significance in risk was observed solely for the fourth and fifth quartiles. Receiver operating characteristic (ROC) curve analysis conducted in patients diagnosed with ILD-CA identified a CEA cutoff point of 6.9 ng/mL, demonstrating sensitivities of 61.1% and specificities of 78.5%. The area under the curve was calculated as 0.7(95% CI: 0.63-0.81). CONCLUSION: The serum levels of CEA were notably elevated in IP patients with concurrent lung cancer in contrast to those who were just suffering from IP. The heightened serum CEA levels correlate with an escalated risk of cancer occurrence among IP patients, suggesting that serum CEA levels could potentially serve as an indicative marker for the presence of cancer in IP patients.

Classic Kaposi Sarcoma in an Immunocompetent Male From Haiti: An Unusual Epidemiological Presentation.

Kaposi sarcoma (KS) is an angioproliferative disorder caused by human herpesvirus-8 (HHV-8) infection. KS manifests as vascular and mucosal nodules and is classified into four subtypes based on epidemiology, clinical presentation, histopathology, and HHV-8/human immunodeficiency virus serology. Here, we present a unique case of classic KS in an 84-year-old immunocompetent Haitian male patient, highlighting the rarity of this variant in this population. Additionally, our article delves into the broader context by reviewing a few documented cases of classic KS in the Caribbean region.

Diagnostic, therapeutic, and prognostic characteristics of patients with acromegaly according to tumor size at diagnosis.

PURPOSE: To evaluate clinical, laboratory, radiological, therapeutic, and prognostic characteristics of patients with acromegaly according to the size of the growth hormone (GH)-secreting pituitary adenoma at diagnosis. METHODS: Observational, retrospective, single-center study of patients with acromegaly followed at a tertiary center. Data were collected regarding clinical presentation, characteristics of the adenoma in the magnetic resonance imaging, GH and IGF-1 levels, and disease control after surgery or adjuvant treatment (normal IGF-1 levels). Patients were divided according to the adenoma size at diagnosis in: group I < 10 mm; II 10-19 mm; III 20-29 mm; IV 30-39 mm; and V ≥ 40 mm. Comparisons were made between the groups, and correlations of tumor size with disease parameters, ROC curves, and logistic regression analyses were performed to investigate tumor size and confounding factors that could impact the outcomes. RESULTS: 117 patients were studied [59 women, age at diagnosis 43 ± 13 years; group I = 11 patients (9%); group II 54 (46%); group III 34 (29%); group IV 10 (9%); group V 8 (7%)]. Hypopituitarism, cavernous sinus invasion, GH levels, and use of somatostatin receptor ligands had their prevalence increased according to the adenoma size. Age showed a negative correlation with tumor size. A tumor diameter around 20 mm was the best predictor for the presence of hypopituitarism, invasiveness, need of adjuvant therapies, and poorer disease control. CONCLUSION: Adenomas < 20 mm showed lower morbidity and better therapeutic response in acromegaly, while those ≥ 20 mm had similar clinical, therapeutic, and prognostic behavior.

Clinical effect of hepatic artery interventional embolization and chemotherapy and its influence on P16 protein expression in patients with liver cancer.

OBJECTIVE: To investigate clinical effects of hepatic artery interventional embolization chemotherapy (TACE) for primary hepatocellular carcinoma (PHC). METHODS: 73 patients with PHC in our hospital from January 2017 to January 2018 were selected and divided into 37 cases in study group and 36 cases in control group by random number table method. The control group received only ultrasound-guided microwave ablation treatment, and the study group received TACE treatment again before surgery based on control group. The expression levels of cancer antigen 125 (CA125), alpha-fetoprotein (AFP), multiple tumor suppressors 1 (P16) proteins, and cancer antigen 19-9 (CA19-9) were compared between the two groups at different time periods after treatment, and the remission rate (ORR), control rate (DCR), complication rate at 3 months after treatment and survival rate at 3 years after treatment were compared. RESULTS: After 1 year of treatment, ORR, DCR, and P16 protein levels in the study group were higher than those in the control group (P < 0.05), and differences were statistically significant; CA125, CA19-9, and AFP levels in study group were lower than those in the control group (P < 0.05), and differences were statistically significant. The regression equation showed that long-term survival rate of both groups showed decreasing trend over time, while long-term survival rate of study group was always higher than that of the control group. CONCLUSION: Comprehensive intervention for hepatic artery interventional chemoembolization in patients with primary hepatocellular carcinoma is more effective, which can effectively reduce incidence of complications and adverse effects in patients and help shorten treatment time of hepatic artery interventional chemoembolization in patients.

Surgical Management of Difficult Nail Glomus Tumors.

Background: Nail glomus tumor is a well-known tumor, with well-defined clinical characteristics and surgical treatment; however, some of these lesions occur in different locations and sizes with difficult surgical resolution. Summary: Clinical and imaging tests help in the diagnosis and tumor localization. Key Message: Adequate surgical knowledge for these cases ensures lower rates of recurrence and nail dystrophy.

Loss of ATRX Protein Expression in an Aggressive Null Cell Pituitary Tumor.

Somatic alpha thalassemia/mental retardation syndrome X-linked (ATRX) pathogenic variants have been shown to predict a malignant phenotype in neuroendocrine tumors. They were recently identified in aggressive pituitary tumors and carcinomas, mainly of corticotrophic origin. To our knowledge, these tumors are rare in a general cohort of pituitary tumors, with no cases described in null cell tumors. These variants can lead to loss of protein expression as revealed by immunohistochemistry. We describe a case of an aggressive null cell pituitary tumor with loss of ATRX expression. The patient underwent two transsphenoidal surgeries and radiotherapy and exhibited tumor growth despite conventional therapy. Analysis of the tumor samples revealed loss of ATRX expression in both surgical specimens, suggesting that ATRX may be a useful biomarker for the early identification of aggressive pituitary tumors.

Single-cell RNA sequencing and cell-cell communication analysis reveal tumor microenvironment associated with chemotherapy responsiveness in ovarian cancer.

BACKGROUND: To investigate the impact of the tumor microenvironment (TME) on the responsiveness to chemotherapy in ovarian cancer (OV). METHODS: We integrated single cell RNA-seq datasets of OV containing chemo-response information, and characterize their clusters based on different TME sections. We focus on analyzing cell-cell communication to elaborate on the mechanisms by which different components of the TME directly influence the chemo-response of tumor cells. RESULTS: scRNA-seq datasets were annotated according to specific markers for different cell types. Differential analysis of malignant epithelial cells revealed that chemoresistance was associated with the TME. Notably, distinct TME components exhibited varying effects on chemoresistance. Enriched SPP1+ tumor-associated macrophages in chemo-resistant patients could promote chemoresistance through SPP1 binding to CD44 on tumor cells. Additionally, the overexpression of THBS2 in stromal cells could promote chemoresistance through binding with CD47 on tumor cells. In contrast, GZMA in the lymphocytes could downregulate the expression of PARD3 through direct interaction with PARD3, thereby attenuating chemoresistance in tumor cells. CONCLUSION: Our study indicates that the non-tumor cell components of the TME (e.g. SPP1+ TAMs, stromal cells and lymphocytes) can directly impact the chemo-response of OV and targeting the TME was potentially crucial in chemotherapy of OV.

Diagnostic features of metastatic endometrioid carcinoma in a captive black-tufted marmoset (Callithrix penicillata).

A captive marmoset developed metastatic endometrioid carcinoma (EnC), a rare uterine tumor in non-human primates (NHPs). The neoplasm showed marked microscopical malignant and tubulopapillary aspects, immunopositivity for pan-cytokeratin, CK7, estrogen receptor, and a high mitotic index (Ki-67). These features may contribute to the diagnosis and therapeutics of EnC in NHPs.

Recurrence of fusocellular subtype GIST with SDHB mutation: A case of SDHB-loss and therapeutic challenges.

Gastrointestinal stromal tumors (GISTs) are sarcomas affecting the stomach and small intestine, with a rare subtype characterized by succinate dehydrogenase B (SDHB)-loss posing significant diagnostic and therapeutic challenges. A 62-year-old man with weight loss and abdominal pain was diagnosed with a gastric GIST showing SDHB-loss. Initial treatment with Imatinib reduced the tumor size, but surgery revealed no residual tumor. Despite adjuvant Imatinib, recurrence occurred, necessitating further surgical intervention. While GISTs typically benefit from surgery and tyrosine kinase inhibitors (TKIs), those with SDHB-loss are resistant to TKIs, requiring a different management approach. This case emphasizes the importance of surgical intervention for SDHB-deficient GISTs and the need for ongoing research into effective treatments for this subtype.