Valspodar

Hemophagocytic lymphohistiocytosis (HLH) is a common and highly fatal hyperinflammatory syndrome characterized by the aberrant activation of macrophages. To date, there is a lack of targeted therapies for HLH. It is validated that macrophages in HLH efficiently phagocytose anti‐CD41‐platelets (anti‐CD41‐PLTs) from immune thrombocytopenia (ITP) patients in previous research. Hence, the pathological mechanisms of ITP are mimicked and anti‐CD41‐PLTs are utilized to load the macrophage‐toxic drug VP16 to construct macrophage‐targetable engineered platelets anti‐CD41‐PLT‐VP16, which is a novel targeted therapy against HLH. Both in vitro and in vivo studies demonstrate that anti‐CD41‐PLT‐VP16 has excellent targeting and pro‐macrophage apoptotic effects. In HLH model mice, anti‐CD41‐PLT‐VP16 prevents hemophagocytosis and inhibits the cytokine storm. Mechanistic studies reveal that anti‐CD41‐PLT‐VP16 increases the cytotoxicity of VP16, facilitating precise intervention in macrophages. Furthermore, it operates as a strategic “besieger” in diminishing hyperinflammation syndrome, which can indirectly prevent the abnormal activation of T cells and NK cells and reduce the Ab‐dependent cell‐mediated cytotoxicity effect. The first platelet‐based clinical trial is ongoing. The results show that after treatment with anti‐CD41‐PLT‐VP16, HLH patients have a threefold increase in the overall response rate compared to patients receiving conventional chemotherapy. In conclusion, anti‐CD41‐PLT‐VP16 provides a general insight into hyperinflammation syndrome and offers a novel clinical therapeutic strategy for HLH.

The location in the neck of small cell neuroendocrine carcinoma (SCNEC) is rare and aggressive with a poor prognosis. We herein describe an extremely uncommon example of cervical SCNEC probably arising in the parotid gland, diagnosed at an advanced metastatic stage.

A 76 year old man, non-smoking, non-alcoholic presented a left cervical and rapidly progressive mass. It was suspicious of malignancy and located in the parotid space and II, III, IV and V lymph node groups. In two weeks, the patient had presented a rapid increase in size, with extensive skin permeation. CT scan revealed a large mass infiltrating the left parotid and submandibular glands compressing the jugulo-carotid vascular axis and liver metastases. Diagnosis was made on the morphological pathological examination supplemented by the immunohistochemistry examination, indeed, cells were immunoreactive for chromogranin A as well as synaptophysin. Chemotherapy based on cisplatin and Etoposide VP 16 was started but the evolution was unfavorable: death occurred after 2 cycles.

Neuroendocrine neoplasm arises from neural crest cells. Its location in the head and neck is extremely rare with a tendency for aggressive local invasion and a strong propensity for both regional and distant metastasis. Treatment may include surgical resection, radiotherapy, chemotherapy, or combination of these modalities. The prognosis is poor.

The clinician must discuss the diagnosis of cervical SCNEC when faced with a man in the seventh decade who presents an agressive rapidly expanding cervical mass. The diagnosis confirmation is pathological combining morphological and immunohistochemical evaluations.