Aggressive natural killer cell leukemia or extranodal NK/T cell lymphoma? a case with nasal involvement

Abstract Background Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare and highly aggressive NK cell neoplasm with a short clinical course and poor prognosis and is often misdiagnosed and confused with NK/T cell lymphoma (NKTL), which has a very different prognosis. Here, we present a case with nasal and bone marrow involvement, provide a literature review and make a differential diagnosis. Case presentation A 41-year-old male presented nasal congestion pharyngalgia, palatal perforation, high fever and multiorgan dysfunction. Our diagnosis primarily relied on clinical features, the morphology and immunophenotype of the neoplastic cells and imaging studies. Characteristic large granular lymphocytes with azurophilic granules were visible in the bone marrow smears. In addition, the neoplastic cells expressed a typical immunophenotype, and the T cell receptor γ (TCR-γ) gene rearrangement analysis and presence of Epstein-Barr virus (EBV) were negative. The patient’s symptoms and signs were temporarily relieved after chemotherapy treatment, but after a short time, he underwent a rapid clinical decline and died 8 weeks later after admission due to multiorgan function failure. Conclusion Our case demonstrates that to avoid a misdiagnosis, bone marrow analyses and other examinations should be performed early when a patient initially presents nasal lesions and other systemic symptoms. To the best of our knowledge, this may be the first reported case of ANKL with sternal tenderness

Cerebrospinal Fluid Pulsation Stress Promotes the Angiogenesis of Tissue-Engineered Laminae

Background. Angiogenesis is a prerequisite step to achieve the success of bone regeneration by tissue engineering technology. Previous studies have shown the role of cerebrospinal fluid pulsation (CSFP) stress in the reconstruction of tissue-engineered laminae. In this study, we investigated the role of CSFP stress in the angiogenesis of tissue-engineered laminae. Methods. For the in vitro study, a CSFP bioreactor was used to investigate the impact of CSFP stress on the osteogenic mesenchymal stem cells (MSCs). For the in vivo study, forty-eight New Zealand rabbits were randomly divided into the CSFP group and the Non-CSFP group. Tissue-engineered laminae (TEL) was made by hydroxyapatite-collagen I scaffold and osteogenic MSCs and then implanted into the lamina defect in the two groups. The angiogenic and osteogenic abilities of newborn laminae were examined with histological staining, qRT-PCR, and radiological analysis. Results. The in vitro study showed that CSFP stress could promote the vascular endothelial growth factor A (VEGF-A) expression levels of osteogenic MSCs. In the animal study, the expression levels of angiogenic markers in the CSFP group were higher than those in the Non-CSFP group; moreover, in the CSFP group, their expression levels on the dura mater surface, which are closer to the CSFP stress stimulation, were also higher than those on the paraspinal muscle surface. The expression levels of osteogenic markers in the CSFP group were also higher than those in the Non-CSFP group. Conclusion. CSFP stress could promote the angiogenic ability of osteogenic MSCs and thus promote the angiogenesis of tissue-engineered laminae. The pretreatment of osteogenic MSC with a CSFP bioreactor may have important implications for vertebral lamina reconstruction with a tissue engineering technique

Micrographs of nHA-CS.

<p>The nHA-CS scaffold exhibited a three-dimensional porous structure in which the nHA particles were evenly distributed throughout the pore surface (figure magnification 500×).</p

Histological examination of HE staining.

<p><b>(A)</b> Representative HE images of implants from the two groups harvested at different time points (figure magnification 100×). <b>(B)</b> The analysis of the proportions of newly formed bone area indicated that the nHA-CS+cells group gained greater amounts of <i>de novo</i> bone compared with the nHA-CS group (*<i>P</i> < 0.05). <b>(C)</b> The analysis of the proportions of the scaffold area revealed that the nHA-CS+cells group exhibited significant scaffold degradation than the nHA-CS group (*<i>P</i> < 0.05).</p

BMSCs and identification of osteogenic differentiation at passage 3.

<p><b>(A)</b> BMSCs cultured in basic medium exhibited typical elongated fibroblast-like morphology. <b>(B)</b> ALP expression was identified by calcium-cobalt staining of black particle deposition in cells after one week of osteogenic induction. <b>(C)</b> Calcified nodules that formed in the extracellular matrix were detected by Alizarin red staining after three weeks of osteogenic induction. The red arrow indicates a calcified nodule (figure magnification 100×).</p

Fluorescent image of DAPI-labeled cells on pore surfaces of scaffolds.

<p>BMSCs adhered in the vicinity of the pores and its edges of a nHA-CS scaffold. Red arrows indicate labeled cells (figure magnification 100×).</p

Histological examination of Masson's trichrome staining.

<p><b>(A)</b> Representative Masson's trichrome staining images showing the expression of collagen in the two groups at different time points (figure magnification 100×). <b>(B)</b> The analysis of the proportions of the collagen area indicate that significantly more collagen was present in the nHA-CS+cells group than the nHA-CS group (*<i>P</i> < 0.05), indicating that the nHA-CS+cells group formed more <i>de novo</i> bone than the nHA-CS+cells group.</p