Circulating low density neutrophils are associated with resistance to anti-PD1 immunotherapy in squamous head and neck cancer.

BACKGROUND: Identification of predictive biomarkers to Immune checkpoint inhibitors (ICIs) in head and neck cancer (HNSCC) is an unmet need. METHODS: This was a prospective observational study including 25 patients with HNSCC treated with immunotherapy or chemotherapy after a prior platinum-based regimen. Low density neutrophils (LDNs) and serum markers were analyzed. RESULTS: In the immunotherapy cohort, patients with high LDN levels had a shorter progression free survival (PFS) (1.8 months vs. 10.9 months; *p = 0.034). Also, progressors showed higher percentage of LDNs compared to non-progressors although significance was not reached (mean 20.68% vs. 4.095%, p = 0.0875). These findings were not replicated in patients treated with chemotherapy. High levels of interleukin-7 (IL7) were correlated with a significantly longer overall survival (OS) (13.47 months 3.51 vs. months, *p = 0.013). CONCLUSIONS: High baseline circulating LDNs and low IL7 could identify a subset of patients intrinsically refractory to ICIs as monotherapy in HNSCC.

Diaphanospondylodysostosis: Full Case Report with Novel Pathogenic BMPER Mutation.

Diaphanospondylodysostosis is an extremely rare, recessively inherited, perinatal lethal skeletal disorder associated with BMPER gene mutations. Clinically it is characterized by defects in costovertebral ossification, absent ribs, hypertelorism, short nose with depressed nasal bridge, low-set ears, and short neck. At the extraosseous level, the most frequent pathologic finding is nephroblastomatosis with multicystic kidneys. We present the case of a child of non-consanguineous parents who died at 2 months of age in our center. Autopsy showed a marked costovertebral ossification defect, perilobar nephrogenic rests and loss of white matter with periventricular leukomalacia. After genetic study, the diagnosis of diaphanospondylodysostosis was confirmed. A previously undescribed germinal mutation in the BMPER gene (c.576 + 2dupT) was found.

Histiocitosis de células de Langerhans nodular hepática / Nodular Langerhans cell histiocytosis of the liver

Planteamiento: La histiocitosis de células de Langerhans es una enfermedad caracterizada por la acumulación, uni o multifocal, de células de Langerhans que rara vez afecta al hígado. Los hallazgos histopatológicos más comunes son la infiltración y destrucción de pequeños conductos biliares, la colangitis destructiva de grandes conductos o masas de células de Langerhans en el parénquima hepático. Los pacientes con manifestaciones hepáticas suelen tener enfermedad diseminada. Material y método: Se presenta el caso de un paciente con histiocitosis de células de Langerhans nodular hepática asociada a un adenocarcinoma rectal. La lesión se detectó de manera incidental durante la resección del tumor rectal y se interpretó macroscópicamente como un nódulo metastásico. Resultados: El nódulo estaba constituido por células de Langerhans positivas para CD1a y proteína S100, con numerosos eosinófilos. El paciente se encuentra sin evidencia de enfermedad después de 14 meses de seguimiento. Conclusiones: La histiocitosis de células de Langerhans nodular hepática sin afectación extrahepática es poco frecuente. En nuestro caso se puede interpretar como un proceso reactivo frente al adenocarcinoma rectal. Lesiones semejantes se deberían tener en cuenta en el diagnóstico intraoperatorio de nódulos hepáticos en pacientes con tumores gastrointestinales

Background: Langerhans cell histiocytosis is a disease whose hallmark is the accumulation, uni or multifocal, of Langerhans cells. Liver is rarely affected. Small bile duct infiltration and destruction, destructive cholangitis of larger bile ducts or masses of Langerhans cells are common findings. Patients with liver manifestations usually have disseminated disease. Material and methods: A nodular Langerhans cells histiocytosis of the liver in a patient with concomitant rectal adenocarcinoma is presented. The lesion was incidentally found during the resection of a rectal tumour and it was macroscopically thought to be a metastatic nodule. Results: The nodule was made of Langerhans cells that reacted with CD1a and S100 protein, with numerous eosinophils. The patient is well and no evidence of disease exists after 14 months of follow-up. Conclusions: Nodular Langerhans cell histiocytosis of the liver without extrahepatic involvement is not usual. In this case the nodule is probably a reactive response to the rectal carcinoma. Similar lesions must be kept in mind in the intraoperative diagnosis of liver nodules in patients with gastrointestinal tumors

Histiocitosis de células de Langerhans nodular hepática / Nodular Langerhans cell histiocytosis of the liver

Planteamiento: La histiocitosis de células de Langerhans es una enfermedad caracterizadapor la acumulación, uni o multifocal, de células de Langerhans que rara vez afecta al hígado. Loshallazgos histopatológicos más comunes son la infiltración y destrucción de pequeños conductosbiliares, la colangitis destructiva de grandes conductos o masas de células de Langerhansen el parénquima hepático. Los pacientes con manifestaciones hepáticas suelen tener enfermedaddiseminada. Material y método: Se presenta el caso de un paciente con histiocitosis decélulas de Langerhans nodular hepática asociada a un adenocarcinoma rectal. La lesión sedetectó de manera incidental durante la resección del tumor rectal y se interpretó macroscópicamentecomo un nódulo metastásico. Resultados: El nódulo estaba constituido por células deLangerhans positivas para CD1a y proteína S100, con numerosos eosinófilos. El paciente seencuentra sin evidencia de enfermedad después de 14 meses de seguimiento. Conclusiones:La histiocitosis de células de Langerhans nodular hepática sin afectación extrahepática es pocofrecuente. En nuestro caso se puede interpretar como un proceso reactivo frente al adenocarcinomarectal. Lesiones semejantes se deberían tener en cuenta en el diagnóstico intraoperatoriode nódulos hepáticos en pacientes con tumores gastrointestinales

Background: Langerhans cell histiocytosis is a disease whose hallmark is the accumulation, unior multifocal, of Langerhans cells. Liver is rarely affected. Small bile duct infiltration and destruction,destructive cholangitis of larger bile ducts or masses of Langerhans cells are common findings.Patients with liver manifestations usually have disseminated disease. Material and methods: Anodular Langerhans cells histiocytosis of the liver in a patient with concomitant rectal adenocarcinomais presented. The lesion was incidentally found during the resection of a rectal tumour and it wasmacroscopically thought to be a metastatic nodule. Results: The nodule was made of Langerhanscells that reacted with CD1a and S100 protein, with numerous eosinophils. The patient is well andno evidence of disease exists after 14 months of follow-up. Conclusions: Nodular Langerhans cellhistiocytosis of the liver without extrahepatic involvement is not usual. In this case the nodule is probablya reactive response to the rectal carcinoma. Similar lesions must be kept in mind in the intraoperativediagnosis of liver nodules in patients with gastrointestinal tumors