Pitfalls in diagnostic hematopathology �C Part II

The overlapping features of malignant lymphomas create a diagnostic “grey zone” , and lead to the invention of “grey zone lymphomas”. There are several major grey zone lymphomas: 1) Lymphomas with overlapping features of Hodgkin lymphoma and large B-cell lymphoma; 2) Lymphomas with overlapping features of Burkitt lymphoma and diffuse large B-cell lymphoma; 3) Lymphomas with overlapping features of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte rich large B-cell lymphoma; 4) Lymphomas with overlapping features of Hodgkin lymphoma, anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma (PTCL); 5) T-cell classical Hodgkin lymphoma and ALCL-HL. The second review of this series will be dedicated to discussion of the “grey zone” features of the lymphomas and how to narrow down the “grey zone” between those lymphomas.     

Bilateral synchronous primary orbital lymphoma

Extranodal marginal zone B-cell non-Hodgkin’s lymphoma affecting bilateral orbital regions was diagnosed in an 80-year-old man. He was given chemotherapy and external beam irradiation therapy. Two months after treatment, repeat orbital magnetic resonance imaging showed dramatically improved lesions. In this case report, orbital non-Hodgkin’s lymphoma and treatment options are discussed.     

Somatic hypermutation and VH gene usage in hairy cell leukaemia

To examine the usage and mutational status of VH genes in hairy cell leukaemia (HCL), we analysed 24 immunoglobulin heavy chain (IgH) sequences expressed in 23 patients. None had premature stop codons. VH3-23 was the most common gene and a VH6 gene was observed for the first time in HCL. Although the mean mutation frequency was 6.1%, slightly higher than in previous HCL series, four patients had 99.6-100% homology to germline sequences, three of whom had high tumour burdens and poor outcomes. Despite the high mutation frequency, only two of 24 rearrangements had clear statistical evidence of antigen-dependent somatic mutation. Our results increase the database of reported functional HCL rearrangements to 94 in 92 patients. Overall, both gene usage and mutation frequency are very similar to mucosa-associated lymphoid tissue-type marginal zone lymphoma. The data are consistent with HCL originating from post-germinal centre marginal zone B cells, although the heterogeneity observed suggests that HCL may originate differently in some patients, and this could have implications for prognosis and treatment.     

Phenotypic and functional heterogeneity of GFAP-expressing cells in vitro: differential expression of LeX/CD15 by GFAP-expressing multipotent neural stem cells and non-neurogenic astrocytes

Recent findings show that the predominant multipotent neural stem cells (NSCs) isolated from postnatal and adult mouse brain express glial fibrillary acid protein (GFAP), a protein commonly associated with astrocytes, and that primary astrocyte cultures can contain GFAP-expressing cells that act as multipotent NSCs when transferred to neurogenic conditions. The relationship of GFAP-expressing NSCs to GFAP-expressing astrocytes is unclear, but has important implications. We compared the phenotype and neurogenic potential of GFAP-expressing cells derived from different CNS regions and maintained in vitro under different conditions. Multiple labeling immunohistochemistry revealed that both primary astrocyte cultures and adherent neurogenic cultures derived from postnatal or adult periventricular tissue contained subpopulations of GFAP-expressing cells that co-expressed nestin and LeX/CD15, two molecules associated with NSCs. In contrast, GFAP-expressing cells in similar cultures prepared from adult cerebral cortex did not express detectable levels of LeX/CD15, and exhibited no neurogenic potential. Fluorescence-activated cell sorting (FACS) of both primary astrocyte cultures and adherent neurogenic cultures for LeX/CD15 showed that GFAP-expressing cells competent to act as multipotent NSCs were concentrated in the LeX-positive fraction. Using neurosphere assays and a transgenic ablation strategy, we confirmed that the predominant NSCs in primary astrocyte and adherent neurogenic cultures were GFAP-expressing cells. These findings demonstrate that GFAP-expressing cells derived from postnatal and adult forebrain are heterogeneous in both molecular phenotype and neurogenic potential in vitro, and that this heterogeneity exists before exposure to neurogenic conditions. The findings provide evidence that GFAP-expressing NSCs are phenotypically and functionally distinct from non-neurogenic astrocytes.     

Impact of indolent inflammation on neonatal hypoxic-ischemic brain injury in mice

This report describes a new experimental model to evaluate the effect of a recurrent systemic inflammatory challenge, after cerebral hypoxia-ischemia in immature mice, on the progression of brain injury. Treatment with a low dose of lipopolysaccharide (E. coli O55:B5, 0.2mg/kg for 3 days, then 0.1mg/kg for 2 days) daily for 5 days after unilateral cerebral hypoxia-ischemia (right carotid ligation followed by 35min in 10% O2) in 10-day-old mice resulted in increased right forebrain tissue damage (35.6% reduction in right hemisphere volume compared to 20.6% reduction in saline-injected controls), in bilateral reductions in corpus callosum area (by 12%) and myelin basic protein immunostaining (by 19%), and in suppression of injury-related right subventricular zone cellular proliferation. The post-hypoxic-ischemic lipopolysaccharide regimen that amplified brain injury was not associated with increased mortality, nor with changes in body temperature, weight gain or blood glucose concentrations. The results of the present study demonstrate that systemic inflammation influences the evolution of tissue injury after neonatal cerebral hypoxia-ischemia and may also impair potential recovery mechanisms.     

Effects of prenatal gamma irradiation on the development of the corpus callosum of Swiss mice

The temporal sequence of events related to the effects of prenatal gamma irradiation on the development of the corpus callosum and cerebral cortex was studied in Swiss mice. Pregnant females on gestational day 16 were exposed to a 60Co source receiving total doses of 2 or 3 Gy. The offspring were analyzed at both prenatal and postnatal days. One day after irradiation, a great number of pyknotic figures was seen along the whole extension of the cerebral wall, especially in the proliferative zones. At perinatal ages, the thickness of the proliferative zones was reduced and the glial sling was never identified. From 5 days after birth onwards, we observed a severe shrinkage of layers II + III and IV. The majority of the irradiated mice were totally acallosal (particularly when the 3 Gy dose was used), but some animals presented callosal remnants. These remnants were identified above the ventral hippocampal commissure, except for two animals in which a larger callosal remnant extended from the columns of the fornix to the dorsal hippocampal commissure. The presence of callosal remnants in animals irradiated with 3 Gy was dependent on the age at which the animals were analyzed since remnants were observed in some animals analyzed at perinatal ages, but never in older animals. Callosal defects can be explained at least by three factors: (1) Death of a great part of callosal neurons located at layer III. (2) Postnatal axonal elimination. (3) Absence of the glial sling. The callosal agenesis in the absence of the glial sling indicates that this structure may play a crucial role in guiding callosal axons. However, the presence of callosal remnants indicates that surviving callosal axons can use structures other than the sling to cross the midplane. Our data indicate that axons of the middle portion of the callosum can cross the midplane using the ventral hippocampal commissure as a guide. Additionally, the dorsal hippocampal commissure may play a role in directing axons of the posterior part of the corpus callosum.     

美学区即刻种植即刻修复的临床研究

目的 探讨美学区即刻种植即刻修复的临床应用及疗效.方法 14例患者美学区新鲜拔牙创即刻植入22颗种植体并即刻临时修复,3～6个月后制作终义齿,临床观察12～22个月.结果 两颗失败后拔出,20颗无松动3～6个月后行永久修复,X线追踪观察永久修复后6～12个月种植体颈部边缘骨吸收均小于1.5 mm,获得临床成功.结论 严格掌握适应证,保证种植体良好的初期稳定性,行无功能的临时修复,美学区行即刻种植即刻修复能够获得良好的临床效果.     

Parapapillary atrophy in patients with intracranial tumours

Purpose: To examine size and frequency of parapapillary atrophy (beta zone) in patients with intrasellar or perisellar tumours and a glaucoma‐like appearance of the intrapapillary optic disc region. Methods: Thirty‐four Chinese subjects with intrasellar or perisellar tumours and a glaucoma‐like appearance of the intrapapillary optic disc region and 129 age‐matched subjects randomly selected from the population‐based Beijing Eye Study were enrolled. Beta zone was measured on fundus photographs. Size and location of the tumours were assessed on neuroradiological images. Results: Beta zone was significantly more common (79 ± 7% versus 46 ± 4%; p = 0.001), and it was significantly larger in the tumour group than in the control group (circumferential extent: 135 ± 99 versus 57 ± 72; p < 0.001; relative area: 1856 ± 1923 versus 759 ± 1390; p = 0.002). The width of the intracerebral tumours was significantly associated with the circumferential extent of beta zone (r = 0.36, p = 0.039) and with the area of beta zone (r = 0.37, p = 0.032). Tumour width, height and depth were significantly (p = 0.001; p = 0.012; and p < 0.001, respectively) larger in the group of patients with beta zone than in the subgroup of patients without beta zone of parapapillary atrophy. Conclusions: Patients with large intrasellar or perisellar tumours and a glaucoma‐like appearance of the intrapapillary region as compared with a population‐based control group had a significantly larger and more frequently occurring beta zone of parapapillary atrophy. It suggests that large parasellar or suprasellar tumours can be associated with typical glaucomatous abnormalities in the parapapillary and intrapapillary region of the optic nerve head. It may give hints for the pathogenesis of glaucomatous optic neuropathy.