Papillary glioneuronal tumor: a new entity awaiting inclusion in WHO classification

Papillary glioneuronal tumor (PGNT) is a recently described lesion of the brain, which is still not included as a separate entity in WHO classification. To date 32 cases of PGNT have been reported in the world literature. We report the 33(rd )case, a 41-year-old male who presented with pain in the nape of the neck. MRI showed a large, predominantly solid mass involving the cerebral parenchyma of the left temporal and parieto-occipital lobes with extension across the midline. Histologically, it was a mixture of glial and neuronal components. Architecturally, the tumor was notable for its pseudopapillary pattern with hyalinized vessels. PGNT is considered as a low grade neoplasm and surgical excision has been curative in most of the cases. More cases of PGNT need to be reported as they may add further knowledge about its biologic behavior and allow its recognition and classification

Expression of nm23 in the spectrum of pre-invasive, invasive and metastatic breast lesions

BACKGROUND: Nm23 protein is a metastasis suppressor protein, expressed in all tissues. Reduced Nm23 expression is related to a high incidence of lymph node and distant metastasis and poor prognosis in patients with cancers. The present study was done to analyze the expression of Nm23 using immunohistochemistry in non-neoplastic and neoplastic breast lesions. METHODS: Sections from 93 samples were studied and classified into non-proliferative breast lesion (13), fibrodenoma (7), proliferative breast lesion (13), carcinoma in situ (20), invasive carcinoma (23) and metastatic deposits in lymph nodes (17). RESULTS: Nm23 expression in these groups showed a progressive down regulation with increasing neoplastic transformation. On comparing the various groups, nm23 expression was significantly different between the various subgroups with greatest expression in non-proliferative lesions and least in metastatic deposits (p < 0.050). CONCLUSION: It is concluded that the modulation of nm23 in a spectrum of breast lesions can be indicative of metastatic phenotype and help to predict the aggressiveness of disease

Phosphorylation of β-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours.

Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the β-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, β-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of β-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs

Case Report - Maxillary Mass as the Presenting Manifestation of Papillary Thyroid Carcinoma

A case of follicular variant of papillary thyroid carcinoma presenting with a right maxillary mass is described. This is perhaps the first instance of maxillary metastasis from papillary thyroid carcinoma

Thymoma: Clinical experience from a tertiary care institute from North India

Background: Thymomas are the most common tumors of the mediastinum. They have varied presentation ranging from asymptomatic incidental mediastinal masses to locally extensive tumor with compressive symptoms and distant metastases. The authors present our institute′s experience in combined modality management of thymomas. Materials and Methods: We retrospectively reviewed 36 patients of thymoma treated in our institute from January 2004 to December 2010. Clinical characteristics and treatment modality in form of surgery, radiotherapy (RT) and chemotherapy (CCT) were noted. Statistical analysis was done with regard to progression free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. Results: A total of 17 patients had associated Myasthenia gravis and 3 patients had associated Cushing syndrome. Masaoka Stage 4a was the most common stage (13 patients) followed by stage 3 (10 patients), stage 2 (9 patients) and stage 1 (4 patients). Twenty seven patients underwent primary surgery, out of which 20 received adjuvant RT and five received both RT and CCT. Of nine non-surgical cases, four received only palliative RT whereas 5 received systemic CCT followed by local mediastinal RT. Overall, 23 patients had complete response while 13 had partial response. 1 patient had local recurrence. Three year PFS was 60% and 3 year OS was 83%. Conclusions: Most common presentation in our series was locally advanced tumors. Most of these patients require adjuvant mediastinal radiation, which helps in significant loco-regional control. Systemic CCT benefits in inoperable, advanced and high-risk tumors. Risk-adapted and multimodality approach is the need of the hour to achieve good control rates while minimizing treatment related toxicity

ODP368 Hyper-phosphorylation of β-catenin at Serine552: predictive marker of invasion and recurrence of Non-Functioning Pituitary Tumours (NFPTs)

BACKGROUND: NFPTs are the most common operated pituitary tumours and can present with visual field defects, hormone deficiencies and headache. Surgery is treatment of choice but recurrence rate is high ranging from 10-50%, depending on the extent of tumour removal. No confirmed predictive biomarkers for NFPT recurrence have been identified, apart from Ki-67. We applied high-throughput mass spectrometry-based phosphoproteomic approach to explore the phosphorylation pattern of proteins in NFPTs in order to identify predictive markers of invasion and recurrence. METHODS: Based on radiological, histopathological, and surgical features, NFPTs were sub-grouped into three groups: non-invasive (n=5), invasive (n=10) and recurrent (n=5) subtypes. Invasiveness was determined by radiology (Knosp classification 3&4), histopathological invasion (bone, dura and mucosa) and intraoperative findings. Tumour recurrence was based on radiological data for a mean±SD follow-up of112±39 months. Fresh-frozen pituitary tumour tissues were used for protein extraction and phosphopeptides were enriched using TiO 2 and labelled with tandem mass tags and subjected tomass spectrometry (Orbitrap)for quantification. Candidate hyper-phosphorylated proteins were validated by immunohistochemistry in 200 additional tumour samples by immunoblotting (n=36). RESULTS: In total, we identified 3185 phosphopeptides and observed significant difference in phosphorylation levels of invasive and recurrent groups. Compared to non-invasive cases, in invasive group we found, 452 hyper and 93 hypo phosphorylated proteins, while in the recurrent group there were 790 hyper and 307 hypo phosphorylated proteins. Phospho-serine showed the highest level of difference (90.3%) among the groups, followed by threonine (8.9%) and tyrosine (0.8%). One of the top differentially phosphorylated proteins was Ser552 of β-catenin showing significant hyper-phosphorylation in recurrent (p<0. 001) and invasive (p<0. 001) NFPTs. We also observed hyper-phosphorylation in tumours with suprasellar (p<0. 05) and cavernous sinus extension (p<0. 01). There was no correlation with tumour diameter and volume. Receiver operating characteristics curve analysis was performed to find the optimal cut-off value of β-catenin pSer552 immunohistochemical H-score in patients who had recurrence (n=44) or non-recurrence (n=156)and observed an area under curve of 0.717 (95% CI: 0.61-0.80),indicating a good prognostic ability for theβ-catenin pSer552H-score. A cut-off value of 160 for theβ-catenin pSer552H-score gives a sensitivity of 69% and a specificity of 73% for tumour recurrence. Kaplan-Meier survival curve analysis shows strong statistical correlation in the recurrence free survival (p<0. 0001) and the nuclear positive staining of β-catenin pSer552 with a hazard ratio of 3.1 (95% CI 1.5-6.3). CONCLUSIONS: our study has identified hyper-phosphorylation of β-catenin at the Ser552 in recurrent and invasive NFPT subgroups. The H-score of β-catenin p552 correlates with tumour recurrence free survival in a large cohort of NFPT patients, which supports that β-catenin pSer552 could be used as predictive biomarker for NFPT recurrence. Presentation: No date and time liste