A case of Langerhans cell sarcoma on the scalp: Whole‐exome sequencing reveals a role of ultraviolet in the pathogenesis

Langerhans cell sarcoma (LCS) is a high‐grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. The underlying genetic features are poorly understood, and only a few alterations, such as those of the MARK pathway‐related genes, CDKN2A and TP53 have been reported. Here we present a 70‐year‐old male with LCS on the scalp and pulmonary metastasis. The multinodular tumor, 3.0 cm in diameter, consisted of diffusely proliferated pleomorphic cells with numerous mitoses (53/10 HPFs). Immunohistochemically, the tumor cells were positive for CD1a, Langerin and PD‐L1, and the Ki‐67 labeling index was 50%. These pathological features were consistent with LCS, and were also observed in the metastatic tumor. Whole‐exome sequencing revealed that both the primary and metastatic tumors harbored a large number of mutations (>20 mutations/megabase), with deletion of CDKN2A and TP53 mutation, and highlighted that the mutational signature was predominantly characteristic of ultraviolet (UV) exposure (W = 0.828). Our results suggest, for the first time, that DNA damage by UV could accumulate in Langerhans cells and play a role in the pathogenesis of LCS. The high mutational burden and PD‐L1 expression in the tumor would provide a rationale for the use of immune checkpoint inhibitors for treatment of unresectable LCS

CLINICAL PREDICTORS FOR ATHEROMA PROGRESSION DESPITE OPTIMAL GLYCEMIC CONTROL IN EARLY-STAGE DIABETIC PATIENTS: SUB-ANALYSIS FROM DIANA STUDY

Data de realització de les fotografies del Mercat aproximada (1994

Prognosis factors in the treatment of bisphosphonate-related osteonecrosis of the jaw - Prognostic factors in the treatment of BRONJ -

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a relatively rare but serious side effect of bisphosphonate (BP)-based treatments. This retrospective study aimed to investigate the risk factors and predictive markers in cases where patients were refractory to a recommended conservative treatment offered in our hospital. Patients and Methods: This single-center study collated the medical records of all patients treated for BRONJ between 2004 and 2011. A complete medical history, including detailed questionnaires, was collected for all patients, focusing on identifying underlying risk factors, clinical features, location and bone marker levels of BRONJ. Results: The mean BRONJ remission rate was 57.6%, and the median duration of remission was seven months. Eighteen patients (34.6%) had persistent or progressive disease with a recommended conservative treatment for BRONJ. Notably, urinary cross-linked N-terminal telopeptide of type 1 collagen (NTX) levels in those resistant to conservative treatment tended to be lower than in patients that healed well. Conclusions: We confirm that a significant proportion of BRONJ sufferers are refractory to a recommended conservative treatment and find that anticancer drugs, periodontal disease, the level of bone exposure and the dosage of intravenous BPs (e.g. zoledronate) represent specific risk factors in BRONJ that may determine the success of a recommended conservative treatment. Additionally, the NTX levels might be able to be a prognostic factor for the conservative treatment of BRONJ; additional research is necessary

Antibody to Propionibacterium acnes (P.acnes) in guinea pigs with pulmonary granulomatosis

P.acnesを皮内前感作した後、P.acnes菌体壁成分をimcomplete Freund's adjuvantと共に気管内に投与して作製した実験的肺肉芽腫症モルモットにおける抗P.acnes抗体について検討した。気管支肺胞洗浄液中抗P.acnes抗体価は気管内投与後1週目ピークを示し2週目までは上昇が認められ、4週目では気管内投与前の値に復した。この経過は肺胞内リンパ球数の変動と軌を一にしており、抗体価とリンパ球数の間には正の強い相関が認められた。血清中の抗P.acnes抗体価は1週目に低下が認められ、2週以後に徐々に回復して4週以後は元に戻った。P.acnesの気管内投与により血清中の抗体は肺へと移行し、リンパ球浸潤による胞隔炎、更には類上皮細胞肉芽腫の形成にP.acnesの関与を示すものであった。In guinia pig models of P.ances induced pulmonary granulomatosis, anti-P.acnes antibody activity in bronchoalveolar lavage fluid peaked at 1 week after the endotracheally injection and decreased progressively, attaining control animal value by 4 weeks. The change of lymphocyte counts paralleled the change of anti-P.acnes antibody activity levels in bronchoalveolar fluids. Furthermore, the degree of granuloma formation in the lung paralleled the rise of anti-P.acnes antibody activity level. This data suggests that the anti-P.acnes antibody play a central role in the induction of lymphocyte alveolitis in experimental pulmonary granulomatosis