Recurrent subependymoma of fourth ventricle with unusual atypical histological features: A case report

Subependymoma is a rare subtype of benign ependymal neoplasm with distinct histological features. Anaplastic transformation has not yet been reported in this tumor to date. We present here a very unusual case of a 62‐year‐old woman with recurrent subependymoma of the fourth ventricle with multiple atypical histological features. Histologically, the resected recurrent tumor showed characteristic small cell clusters and nests of ependymal cells with an interspersed gliofibrillary matrix as seen in a classic subependymoma. In addition, there were very unusual histological features, including multiple areas of necrosis, microvascular proliferation, thrombosed blood vessels, and scattered mitotic figures. No coexisting ependymoma component of higher World Health Organization (WHO) grade was present. Immunohistochemically, MIB‐1 labeling index was high, with up to 15% in the highest areas. Review of this patient's initial tumor, which was resected 6 years prior to recurrence, demonstrated features of a typical classic subependymoma without atypical features or a secondary tumor component. Subependymomas are known to be low‐grade tumors and are usually cured if completely excised. The tumor presented here is unique in that several atypical pathological features were found in an otherwise typical subependymoma. Our case may represent anaplastic transformation of subependymoma, although no such examples have been reported to date.     

ShcC proteins: Brain aging and beyond

To date, most studies of Shc family of signaling adaptor proteins have been focused on the near-ubiquitously expressed ShcA, indicating its relevance to age-related diseases and longevity. Although the role of the neuronal ShcC protein is much less investigated, accumulated evidence suggests its importance for neuroprotection against such aging-associated conditions as brain ischemia and oxidative stress. Here, we summarize more than decade of studies on the ShcC expression and function in normal brain, age-related brain pathologies and immune disorders with a focus on the interactions of ShcC with signaling proteins/pathways, and the possible implications of these interactions for changes associated with aging.     

Two‐faced haemophagocytic lymphohistiocytosis: comparative review of two cases of adult haemophagocytic lymphohistiocytosis

Haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease of children and adults. Cytokine dysfunction, uncontrolled accumulation of activated T‐cells and histiocytes, and the inability to terminate the immune response lead to the clinical manifestations of extreme inflammation and end‐organ damage. HLH is notoriously underreported because of its ability to mimic many other common diseases. Here, we outline two cases of HLH, one primary and the other secondary, to highlight some of the differences and to discuss therapeutic principles and emerging concepts.     

IgG4 Overexpression Is Rare in Meningiomas with a Prominent Inflammatory Component: A Review of 16 Cases

Meningiomas with prominent inflammation are traditionally classified as “lymphoplasmacyte‐rich meningioma” (LPM). Both inflammatory and neoplastic meningeal proliferations have recently been linked to IgG4 disease, although a potential association with LPM has not been previously explored. Sixteen meningiomas with inflammatory cells outnumbering tumor cells were further characterized by CD3, CD20, CD68 and/or CD163, CD138, kappa, lambda, IgG and IgG4 immunostains. There were 11 female and 4 male patients, ranging from 22 to 78 (median 59) years of age. Tumors consisted of 10 World Health Organization (WHO) grade I, 5 grade II and 1 grade III LPMs. Immunohistochemically, the most numerous cell type was the macrophage in all cases followed by CD3‐positive T cells and fewer CD20‐positive B cells. Plasma cells ranged from moderate‐marked (N = 5) to rare (N = 7), or absent (N = 4). Maximal numbers of IgG4 plasma cells per high power field (HPF) ranged from 0 to 32, with only two cases having counts exceeding 10/HPF. The IgG4/IgG ratio was increased focally in only two cases (30% and 31%). Additionally, plasma cells represented only a minor component in most examples, whereas macrophages predominated, suggesting that “inflammation‐rich meningioma” may be a more accurate term. The inflammatory stimulus for most cases remains to be elucidated.     

High Incidence of Activating TERT Promoter Mutations in Meningiomas Undergoing Malignant Progression

Meningiomas are common central nervous system tumors. The World Health Organization (WHO) defines three grades, predictive of the risk of recurrence. These tumors can relapse frequently and sometimes undergo malignant transformation. Maintenance of telomere length is a key process in malignant progression, and mutations in TERT promoter have recently been identified in various types of cancer. We sequenced the TERT promoter in 85 meningiomas from 73 patients. We found a high incidence of TERT promoter mutations in patients with meningiomas undergoing malignant histological progression (28%, n = 5/18 patients). In this subset of patients with histological progression, TERT promoter mutations were found in both the lowest and the highest grade tumors, and in both NF2‐mutated and nonmutated samples. In contrast, one mutation was identified in 35 meningiomas without recurrence or progression, belonging to various histological grades. This sample was an aggressive meningioma in a patient who died shortly after surgery. Interestingly, tumors showing relapse without histological progression were not mutated for TERT promoter (n = 20). Finally, TERT promoter mutations were associated with a marked increase in TERT expression. Thus, TERT promoter mutations are pivotal genetic alterations involved in malignant progression of meningiomas and could be used as a biomarker to identify meningiomas at risk of malignant transformation.     

Paediatric anaplastic large cell lymphoma with leukaemic presentation in children: a report of nine French cases

This study aimed to describe the clinical features and outcome of anaplastic large cell lymphoma (ALCL) with leukaemic presentation in children. Among 267 patients included in the French paediatric ALCL database between 1989 and 2012, nine (3%) were described as having cytologically detectable circulating tumour cells. Clinical features combined fever (8/9), nodal and extra‐nodal disease (9/9), including hepato‐splenic (9/9) and lung involvement (7/9). The level of hyperleucocytosis ranged from 30 to 120 × 10⁹/l, with 12–90% of tumour cells. Diagnosis relied on a lymph node biopsy, with a positive ALK+ antibody immunostain in all nine cases, a T‐cell immunophenotype in 7/9 cases and CD3 positivity in 5/9 cases. A small cell component was present in 6/9 cases. Only four patients achieved a complete remission with first‐line therapy and 3/4 relapsed. Four patients are alive with a median follow‐up of 31 months, two of them after allogeneic haematopoietic stem cell transplantation (HSCT), and five patients died, two of them of disease. In conclusion, ALCL with leukaemic presentation is very unusual and should be considered as high‐risk lymphoma requiring new therapeutic strategies. The respective role of new agents and allogeneic HSCT in first complete remission still has to be assessed.     

Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis‐associated anaplastic large cell lymphoma in children

Haemophagocytic lymphohistiocytosis (HLH) has been rarely described in children treated for an anaplastic large‐cell lymphoma (ALCL). We evaluated the incidence, the clinical and histological characteristics and the prognosis of HLH associated‐ALCL. The medical, biological, cytological and histological data of patients treated for ALK‐positive ALCL in the paediatric department of a single institution between 1975 and 2008 were analysed and assessed for HLH according to diagnosis criteria of the Histiocyte Society. Data concerning a series of 50 consecutive children with ALCL were reviewed. HLH‐associated ALCL was observed in 12% of the patients. Lung involvement was significantly more frequent in HLH‐associated ALCL patients than in the group without HLH (P = 0·004), as well as central nervous system (CNS) and bone marrow involvement (P = 0·001 and P = 0·007 respectively). The histological subtype in children with HLH‐associated ALCL did not differ from that of the group without HLH. There was no significant difference between the two groups in 5‐year EFS and OS (P = 0·91 and P > 0·99 respectively). In conclusion, HLH is not rare in paediatric ALCL. Despite a high incidence of visceral, CNS and bone marrow involvement, HLH does not seem to exert a significant impact on outcome in children treated for ALCL.     

Porous polyethylene implant reconstruction of the orbit after resection of spheno-orbital meningiomas: A novel technique

Background

Spheno-orbital meningiomas (SOM) are complex tumors involving the middle cranial fossa and orbit. Following resection of these tumors, reconstruction of the orbit can be challenging. Inadequate reconstruction may lead to cosmetic deformities and functional complications.

Objective

The development of a technique for orbital reconstruction which is technically straightforward, cost-effective, with an excellent functional and cosmetic outcome.

Technique

Twelve patients with SOM each underwent a modified orbital-zygomatic craniotomy with osteotomies based on individual tumor location. After tumor resection, the lateral orbit and orbital roof, where necessary, were reconstructed using a 1 mm porous polyethylene sheet, customized to reconstruct the bony anatomy of the lateral and superior orbit and secured with 1.5 × 4 mm titanium screws into the orbital roof and rim.

Results

All patients demonstrated stabilization or improvement of vision and satisfactory cosmetic outcomes. One complication (surgical site infection) was noted. Follow-up imaging was obtained at regular intervals. The resection cavity was easily visualized without interference from the implant in each case. One patient developed tumor recurrence requiring re-operation 20 months after the initial procedure.

Conclusions

Use of a 1 mm porous polyethylene sheet for reconstruction of the lateral orbit offers an excellent functional and cosmetic outcome, does not interfere with postoperative imaging, is technically straightforward, and is cost-effective.