Is radiomics a useful addition to magnetic resonance imaging in the preoperative classification of PitNETs?

BACKGROUND: The WHO 2021 introduced the term pituitary neuroendocrine tumours (PitNETs) for pituitary adenomas and incorporated transcription factors for subtyping, prompting the need for fresh diagnostic methods. Current biomarkers struggle to distinguish between high- and low-risk non-functioning PitNETs. We explored if radiomics can enhance preoperative decision-making. METHODS: Pre-treatment magnetic resonance (MR) images of patients who underwent surgery between 2015 and 2019 with available WHO 2021 classification were used. The tumours were manually segmented on the T1w, T1-contrast enhanced, and T2w images using 3D Slicer. One hundred Pyradiomic features were extracted from each MR sequence. Models were built to classify (1) somatotroph and gonadotroph PitNETs and (2) high- and low-risk subtypes of non-functioning PitNETs. Feature were selected independently from the MR sequences and multi-sequence (combining data from more than one MR sequence) using Boruta and Pearson correlation. Support vector machine (SVM), logistic regression (LR), random forest (RF), and multi-layer perceptron (MLP) were the classifiers used. Data imbalance was addressed using the Synthetic Minority Oversampling TEchnique (SMOTE). Performance of the models were evaluated using area under the receiver operating curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 222 PitNET patients (train, n = 149; test, n = 73) were enrolled in this retrospective study. Multi-sequence-based LR model discriminated best between somatotroph and gonadotroph PitNETs, with a test AUC of 0.84, accuracy of 0.74, specificity of 0.81, and sensitivity of 0.70. Multi-sequence-based MLP model perfomed best for the high- and low-risk non-functioning PitNETs, achieving a test AUC of 0.76, accuracy of 0.67, specificity of 0.72, and sensitivity of 0.66. CONCLUSIONS: Utilizing pre-treatment MRI and radiomics holds promise for distinguishing high-risk from low-risk non-functioning PitNETs based on the latest WHO classification. This could assist neurosurgeons in making critical decisions regarding surgery or alternative management strategies for PitNETs after further clinical validation.

Supratentorial primary paraganglioma with good long-term outcome following radical excision.

BACKGROUND: Paragangliomas are tumours of extra-adrenal paraganglia. They may metastasize to the brain but primary paragangliomas are exceedingly rare in the supratentorial region and long-term outcomes after surgery is largely unknown. This description of an excellent outcome 13 years following surgery in a 40-year-old gentleman with a primary paraganglioma near the falx provides an important perspective on the value of gross total resection in these tumours. We also review the options for adjuvant therapy in tumours that cannot be excised completely. CASE DESCRIPTION: We describe a supratentorial paraganglioma in the parasagittal region in a 40-year-old gentleman who presented with clinical and radiological features suggestive of a right parafalcine meningioma. Histopathological examination following gross total excision of the tumour revealed histological and immunochemical features of a paraganglioma. A detailed search for a systemic primary was negative and the patient remains disease-free 13 years after the surgery. CONCLUSIONS: Differentiating between tumours arising primarily and those that are metastatic deposits in the central nervous system requires long-term follow-up and monitoring for the appearance of occult primary tumours. Gross total resection is likely to provide good long-term outcomes.

Trigeminal hybrid nerve sheath tumor - a case report and literature review.

BACKGROUND: Hybrid nerve sheath tumors (HNST) contain elements of more than one established sub-type of nerve sheath tumor and have been recently recognized in the 2016 WHO classification of central nervous system tumors. While common in the peripheral nerves and extracranial branches of cranial nerves, only one case has been previously documented of an intracranial HNST arising from a cranial nerve. CASE DESCRIPTION: We describe a large, multi-compartmental intracranial hybrid nerve sheath tumor arising from the trigeminal nerve in a 22-year-old lady who presented with clinical and radiological features suggestive of a right cerebellopontine angle mass. Histopathological examination following retrosigmoid excision of the tumor revealed histological and immunohistochemical features of a schwannoma and a perineurioma. CONCLUSIONS: HNSTs are likely to be underreported in the intracranial region. The clinical course of these tumors and the reason for their occurrence in this location are not known.

Neuroimaging of pediatric infratentorial tumors and the value of diffusion-weighted imaging (DWI) in determining tumor grade.

BACKGROUND: Diffusion-weighted imaging (DWI) provides information about the cellular density of tumors. This feature is useful in grading and identifying different tumor types. PURPOSE: To assess the value of diffusion restriction and apparent diffusion coefficient (ADC) values in differentiating pediatric infratentorial tumors. MATERIAL AND METHODS: This was a retrospective review of the magnetic resonance imaging (MRI) of 82 children (age range 1-16 years) with infratentorial tumors. Histopathological grading after surgical excision/biopsy was categorized as low grade (WHO grades I and II) (n = 31; 29 pilocytic astrocytomas, 2 ependymomas) and high grade (WHO grade III and IV) (n = 51; 40 medulloblastomas, 8 anaplastic ependymomas, 1 anaplastic astrocytoma, 2 atypical rhabdoid teratoid tumors [ATRT]). MRI features and ADC values were compared among tumor types and grades using a two-tailed t test, Mann-Whitney U test for continuous data and Chi-square test for categorical variables. RESULTS: Diffusion restriction and low ADC value was a feature of high-grade tumors (P<0.001). The mean ADC values of the low-grade and high-grade tumors were 1.567 × 10-3mm2/s and 0.661 × 10-3mm2/s, respectively. Using 0.9 × 10-3mm2/s as the cut-off value, the sensitivity, specificity, positive and negative predictive values for differentiating the grades was 87%, 100%, 100%, and 81.8%, respectively. Significant differences were found between the mean ADC values of the individual tumor types (P<0.05), except between medulloblastoma and ATRT. CONCLUSION: ADC values and visual assessment of diffusion restriction are useful in tumor grading. The individual tumor types can be identified by an algorithmic approach, using DWI in conjunction with other described MRI features.

Long-term outcomes following maximal safe resection in a contemporary series of childhood craniopharyngiomas.

BACKGROUND: The optimal management of pediatric craniopharyngiomas remains controversial. This study aimed to characterize long-term outcomes in a contemporary cohort of children undergoing surgery for craniopharyngiomas. METHODS: This was a retrospective review of 37 consecutive children who underwent surgery for craniopharyngioma with a median follow-up duration of 79 months (range 5-127 months). Patients were stratified by extent of resection (EOR) and need for adjuvant radiation therapy (RT). Imaging studies were reviewed to grade extent of hypothalamic involvement. Data on functional outcomes, pituitary function, and obesity were analyzed. RESULTS: Gross total resection was achieved in 16 patients (43.2%), near total resection in six patients (16.2%), and subtotal resection (STR) in 15 patients (40.5%). The recurrence-free survival rate was 81.1% and 70.3% at 5- and 10-year follow-up, respectively. Survival analysis showed superior disease control in patients undergoing STR + RT (p = 0.008). Functional outcomes were independent of EOR, postoperative RT or recurrence. Diabetes insipidus was present in 75% and 44.4% of patients required >2 hormone replacements at last follow-up. Obesity was present in 36.1% patients after treatment, and was associated with preoperative obesity (p = 0.019), preoperative hypothalamic involvement (p = 0.047) and STR + RT (p = 0.011). CONCLUSIONS: Gross or near total resection may be achieved safely in almost 60% of cases; however, radical surgery does not eliminate the risk of recurrence. Over long-term follow-up, STR + RT offers the best disease control rates. Patients with preoperative hypothalamic involvement, obesity, and those with tumors not amenable to radical resection are at risk for developing obesity on long-term follow-up.

A clinicoradiological analysis of silent corticotroph adenomas after the introduction of pituitary-specific transcription factors.

BACKGROUND: Silent corticotroph adenomas (SCAs) are a rare subtype of non-functional pituitary adenoma. While it has been suggested that they are more aggressive and recur more frequently following excision, there is limited literature on the optimum treatment strategy for these tumors, especially regarding the role of radiation therapy in incompletely resected tumors. METHOD: We assimilated data from 62 SCAs and 238 other non-functional adenomas (ONAs), defined according to the WHO 2017 criteria that incorporates transcription factor analysis. We compared their clinicoradiological characteristics, such as hormonal levels, tumor configuration, size, and invasiveness. For 52 SCAs and 205 ONAs with serial follow-up imaging, we studied outcomes for progression after subtotal resection with or without radiation therapy or recurrence after gross total resection. Kaplan Meier analysis for recurrence or progression was used to determine the need for a differential treatment strategy for SCAs compared with other non-functional adenomas specifically concerning the role of radiotherapy. RESULTS: Patients with SCAs present at a younger age than ONAs (43.9 years vs. 48.2 years, p = 0.014), with larger (14.9 cc vs. 9.7 cc, p = 0.006) and more invasive adenomas (61.2% vs. 45.8%, p = 0.021). Overall, SCAs are more likely to recur or progress (48.7 vs. 15.7%, p < 0.001) following excision than ONAs, with significantly poorer event-free survival (Log rank test p < 0.001). Early adjuvant radiotherapy provides favorable outcomes among SCAs with postoperative residual tumor, on par with ONAs. Multivariate analysis identified male gender (HR: 2.217; p = 0.017), MIB index ≥ 3% (HR: 2.116; p = 0.012), and SCA tumor pathology (HR: 3.787; p < 0.001) as factors predicting recurrence. CONCLUSIONS: Based on the results of this retrospective, single-center review of 300 non-functional adenomas, we conclude that silent corticotroph adenomas are an aggressive subtype of non-functional pituitary adenomas that are larger, more likely to be invasive, and tend to recur more frequently after a subtotal excision compared with other non-functional adenomas. A gross total resection must be attempted whenever possible and earlier adjuvant radiation is recommended when re-surgery for residual tumor is difficult.

Growth hormone storm following infarction of a residual growth hormone secreting pituitary macroadenoma.

BACKGROUND: Thyrotroph pituitary adenomas have been reported to be a rare cause of 'thyroid storms', causing myriad metabolic and autonomic disturbances. In this case, we describe the second reported case in literature of a 'GH storm' in an infarcted somatotroph adenoma.Case description: We describe a residual invasive somatotroph macroadenoma that underwent infarction, producing a dramatic elevation in serum GH levels. While infarction of adenomas may in some cases lead to remission, the patient went on to require re-surgery and re-radiation due to growth of the residual viable tumour.Conclusions- 'GH storms' are rare but interesting events that may occur in somatotroph adenomas. Infarction or apoplexy must be considered when managing residual adenomas.

An experimental study to test the efficacy of Mesenchymal Stem Cells in reducing corneal scarring in an ex-vivo organ culture model.

In this study, we evaluated the effect of placenta-derived Mesenchymal Stem Cells (MSCs) versus placebo in improving corneal transparency following experimental injury in an ex-vivo organ culture model of post-mortem human corneas. We also compared the influence of MSCs on the basic histopathology of the cornea and the immunohistochemistry markers of fibrotic corneal scarring. Mesenchymal Stem Cells extracted from the placenta were isolated and expanded in-vitro. Five pairs of post-mortem human corneas harvested for the corneal transplant of equal grade were included in the study. Corneas of the same pair were randomly assigned to either the case arm or the control arm. All corneas underwent a standardized superficial keratectomy, 4 mm in diameter. The case and control arm corneas received an intrastromal injection of MSCs and placebo respectively. The corneal button was maintained in an organ culture system for 28 days under the standard protocol. Laser light was passed through the corneas mounted on a self-styled modified artificial anterior chamber. Image analysis was used to quantify corneal transparency. Haematoxylin & Eosin staining and Immunohistochemistry was done for Alpha SMA (Smooth Muscle Actin). Laser scatter measurements were measured using Image Analysis (Image J Software). The difference in the mean of Full-Width Half Maximum (FWHM), Max intensity and Red pixel intensity between the cases and the controls was 101.5, 16.3 and 11.4 respectively which was found to be statistically significant (P < 0.05). Histopathology showed a disorganized Bowman's layer in the controls as compared to the cases. Alpha Smooth Muscle Actin at the injury site stained 3 + in all controls as compared to 1 + in the cases, showing a statistically significant difference (p = 0.005). Based on our findings, we consider that placenta-derived Mesenchymal Stem Cells can alter evolving corneal scarring into a more favourable outcome with better corneal transparency and lesser fibrotic corneal scarring.

Imaging Spectrum of Cavernous Sinus Lesions with Histopathologic Correlation.

Cavernous sinuses are paired interconnected venous plexuses situated in the floor of the middle cranial fossa on either side of the sella turcica and sphenoid sinus. They are lined by dura mater and consist of multiple venous channels within. The cavernous sinuses are intimately related to the internal carotid artery and its associated sympathetic plexus, the oculomotor nerve, the trochlear nerve, the abducens nerve, and the ophthalmic nerve. Cavernous sinuses are connected to the orbit, the pterygopalatine fossa, the infratemporal fossa, the nasopharynx, and the posterior cranial fossa by various foramina, fissures, and canals in the skull base. A multitude of structures in close relation to the cavernous sinus give rise to a myriad of possible pathologic conditions that can be broadly classified into (a) neoplastic, (b) vascular, (c) infective or inflammatory, or (d) miscellaneous lesions. These pathologic conditions can have overlapping clinical manifestations. Hence, imaging plays a crucial role in identifying the disease, assessing its extent, providing a pertinent differential diagnosis to guide further management, and suggesting a site or route for biopsy. MRI is the modality of choice to depict the cavernous sinuses, with CT and digital subtraction angiography playing supplementary roles in certain situations. In this article, the cavernous sinus lesions encountered in our institution during a 10-year period are reviewed. The purpose of the article is to (a) describe the anatomy of the cavernous sinus; (b) demonstrate the multimodality imaging spectrum of a wide variety of pathologic conditions involving the cavernous sinus, correlating with the histopathologic findings; (c) highlight important imaging clues for differential diagnosis; and (d) help the reader overcome potential pitfalls in interpretation. Online supplemental material is available for this article. ©RSNA, 2019.

ISNO consensus guidelines for practical adaptation of the WHO 2016 classification of adult diffuse gliomas.

INTRODUCTION: Recent advances in the molecular biology of adult diffuse gliomas have brought about a paradigm shift in their diagnostic criteria, as witnessed in the World Health Organization (WHO) 2016 guidelines for central nervous system tumors. It is now mandatory to perform several molecular tests to reach a definitive integrated diagnosis in most of the cases. This comes with additional cost and higher turnaround time, which is not always affordable in developing countries like India. In addition, the non-uniform distribution of advanced research and diagnostic testing centers adds to the difficulty. METHODS: The Indian Society of Neuro-oncology (ISNO) multidisciplinary expert panel consisting of neuropathologists, neurosurgeons, and radiation/medical oncologists convened to prepare the national consensus guidelines for approach to diagnosis of adult diffuse gliomas. RESULTS: Algorithms for arriving at an integrated diagnosis of adult diffuse gliomas predominantly using immunohistochemistry and with minimum possible additional molecular testing were agreed upon, thus addressing the problems of cost, accessibility, and turnaround time. Mandatory and optional tests were proposed for each case scenario. CONCLUSION: This document represents the consensus of the various neuro-oncology disciplines involved in diagnosis and management of patients with adult diffuse gliomas. The article reflects a practical adaptation of the WHO recommendations to suit a resource constrained setup.

Molecular profile of tumors with oligodendroglial morphology: Clinical relevance.

BACKGROUND: The plethora of biomarkers available for the diagnosis and prognostication of gliomas has refined the classification of gliomas. The new World Health Organization (WHO) 2016 classification integrates the phenotypic and genotyping features for a more robust diagnosis. MATERIALS AND METHODS: Fifty gliomas with oligodendroglial morphology according to the WHO 2007 classification were analyzed for isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations by polymerase chain reaction, 1p/19q status by fluorescent in situ hybridization (FISH), and IDH1 and X-linked alpha-thalassemia retardation (ATRX) expression by immunohistochemistry. Tumors were reclassified into oligodendrogliomas, astrocytomas, and glioblastomas (GBMs) according to the new "integrated" diagnostic approach. RESULTS: 30% of previously diagnosed oligodendrogliomas and almost 90% of oligoastrocytomas were reclassified as astrocytomas. Twenty gliomas showed 1p/19q co-deletion, while 18 gliomas showed polysomy of chromosome 1/19. Polysomy of chromosome 1/19 was significantly associated with astrocytic tumors (P ≤ 0.001). Loss of ATRX expression was seen in 20 of 23 WHO grade II/III astrocytomas and 3 of 7 GBMs. All WHO grade II and III gliomas in our cohort showed IDH1/2 mutations. Moreover, 4 of 7 GBMs showed the wild-type IDH1/2 mutation, and 2 of 3 GBMs which showed IDH1/2 mutations were secondary GBMs. There was no significant difference in progression-free and overall survival between WHO grade II and III gliomas, possibly because all these tumors showed IDH1/2 mutations. In multivariate analysis, only the WHO grade (grade IV versus II and III combined) was significantly associated with increased risk of recurrence and death (P = 0.016 and 0.02). CONCLUSION: The new integrated diagnosis provides a more meaningful classification, removing the considerable subjectivity that existed previously.

Implications of the World Health Organization definition of atypia on surgically treated functional and non-functional pituitary adenomas.

BACKGROUND: The World Health Organization (WHO) defines atypical pituitary adenomas as tumours with a MIB-1 labelling index ≥3%, p53 positivity and increased mitotic activity. Although a few reports have described the clinical and radiological correlates of atypia in pituitary adenomas, its impact on postoperative outcomes is not clearly defined. METHOD: We reviewed preoperative and postoperative records of patients undergoing surgery for pituitary adenomas. Postoperative outcomes for functional adenomas (FPAs) were assessed according to contemporary definitions of remission and recurrence. For non-functional pituitary adenomas (NFPAs), extent of resection and disease progression were defined on the basis of postoperative magnetic resonance imaging. RESULTS: Of 394 patients included for analysis, 29 cases (7.4%) fulfilled criteria for atypia. Patients with atypical tumours were significantly younger than those with typical adenomas. Remission was possible in 47.4% of FPAs, and was unrelated to the presence of atypia. In NFPAs, local invasiveness was negatively associated with extent of resection (OR, 0.255; 95% CI, 0.086-0.753; p < 0.001). In 93 NFPAs followed postoperatively with serial imaging over a mean duration of 37.5 months, disease progression/recurrence was significantly associated with the presence of atypia (OR, 5.058; 95% CI, 1.273-20.098; p = 0.021) on multivariate analysis. CONCLUSIONS: Patients with atypical non-functional pituitary adenomas are at risk for postoperative recurrence and disease progression, suggesting a need for adjuvant therapy. However, only a small fraction of pituitary tumours demonstrate atypia, as defined by the WHO, limiting its clinical utility.

Pure endoscopic transsphenoidal surgery for functional pituitary adenomas: outcomes with Cushing's disease.

BACKGROUND: This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing's disease (CD). METHOD: We studied 64 consecutive patients who underwent 69 endoscopic transsphenoidal procedures. Radiological evaluation comprised detailed examination of preoperative magnetic resonance images (MRI), including positron emission tomography (PET) for select cases. Inferior petrosal sinus sampling (IPSS) was not performed for any patient. Remission was defined by the presence of hypocortisolemia with requirement for steroid replacement therapy or eucortisolemia with suppression to <1.8 µg/dl after 1 mg dexamethasone on evaluation at least 3 months after surgery. RESULTS: Preoperative MRI was abnormal in 87.5 % of cases and included 11 macroadenomas (17.2 %). PET was used to localize the adenoma in four cases. For microadenomas, operative procedures executed were as follows: selective adenomectomy (n = 15), enlarged adenomectomy (n = 21) and subtotal/hemihypophysectomy (n = 17). Overall, pathological confirmation of an adenoma was possible in 58 patients (90.6 %). Forty-nine patients (76.6 %) developed hypocortisolemia (<5 µg/dl) in the early postoperative period. Mean follow-up was 20 months (range 6-18 months). Remission was confirmed in 79.7 % of the 59 cases followed up for >3 months and was superior for microadenomas (86.4 %) versus macroadenomas (55.6 %) and equivocal MRI adenomas (66.7 %). Postoperative CSF rhinorrhea occurred in five patients, and new endocrine deficits were noted in 17.1 % patients. A nadir postoperative cortisol <2 µg/dl in the 1st week after surgery was highly predictive of remission (p = 0.001). CONCLUSION: ETS allows for enhanced intrasellar identification of adenomatous tissue, providing remission rates that are comparable to traditional microsurgery for CD. The best predictor of remission remains induction of profound hypocortisolemia in the early postoperative period.

Fluorescence in situ hybridization for chromosome 14q deletion in subsets of meningioma segregated by MIB-1 labelling index.

AIM: To correlate histopathological grading of meningiomas segregated into subgroups based on the MIB-1 labelling index (MIB-1 LI) with chromosomal loss of 14q using fluorescence in situ hybridization (FISH). SETTINGS AND DESIGN: Retrospective study conducted in a tertiary hospital. METHODS AND MATERIAL: Forty-six cases from January to December 2011 were segregated into 5 categories based on the MIB-1 LI. Slides were reviewed to ascertain the grade. Immunohistochemical staining for MIB-1 was performed using a Ventana Benchmark XT autostainer. Commercially available FISH paraffin pretreatment kit and SpectrumOrange fluorophore labelled probe were used. The Statistical Package for the Social Sciences version 16.0 for Windows was used for statistical analysis. RESULTS: There were 21 World Health Organisation (WHO) grade I, 24 grade II, and 1 grade III meningiomas. There was a statistically significant difference between the mean duration of symptoms, maximum dimension, and the MIB-1 LI of grade I and grade II meningiomas. 33.3% grade I cases showed 14q deletion, compared to 84% of grade II and III meningiomas. Histologically, hypercellularity, small cell formation, prominent nucleoli, and sheet-like growth were significantly associated with 14q deletion. All brain invasive meningiomas had 14q deletion. As MIB-1% increased, the prevalence of deletions was significantly higher. The mean MIB-1 of the 7 grade I meningiomas that had 14q deletions was 8.86 ± 1.95% when compared to 4.14 ± 1.35% for those without 14q deletions. CONCLUSIONS: A strong association existed between histologic grade, MIB-1 LI, and the presence of chromosome 14q deletion. Association of high MIB-1 LI with 14q deletions, even in meningiomas with a Grade I histology, defines a distinct subset of benign meningiomas.

An unusual case of inflammatory necrotizing myopathy and neuropathy with pipestem capillaries.

Necrotizing myopathy with pipestem capillaries is a form of chronic inflammatory myopathy, with histopathology showing necrotizing myopathy, minimal cellular infiltration, and microangiopathy. A 30-year-old female presented with progressive limb weakness of 6 months, with skin pigmentation and Raynaud's phenomenon. Serum creatine phosphokinase was 3990 u/L. Muscle biopsy showed necrotic fibers, focal sparse perivascular inflammation/perifascicular atrophy, endomysial/epimysial vessel wall thickening with luminal narrowing. The features were of inflammatory necrotizing myopathy and neuropathy with pipestem capillaries/microangiopathy. She was pulsed with intravenous immunoglobulin, methylprednisolone, and cyclophosphamide and showed a good improvement. In the absence of widespread inflammatory response and classical histopathology findings, it is important to diagnose this condition as it shows a good response to aggressive and prolonged immunotherapy.

Clinicopathological correlates of primary central nervous system lymphoma: experience from a tertiary care center in South India.

BACKGROUND: Primary central nervous system lymphomas (PCNSL) constitute a rare group of extranodal non-Hodgkin's lymphomas (NHLs). AIM: To study the clinical and immunophenotypic profile of patients with a PCNSL who presented between the years 2000 and 2013 in a tertiary care center in South India. MATERIALS AND METHODS: This was a retrospective study. Demographic and clinical data were obtained from the clinical case records. INCLUSION CRITERIA: Cases of PCNSL involving brain. EXCLUSION CRITERIA: Cases of PCNSL involving the spinal cord, meninges and orbit as well as intravascular large B-cell lymphoma, lymphomas with evidence of systemic disease or secondary lymphomas. Archived slides and tissue blocks were retrieved. All cases had hematoxylin and eosin stained sections and immunohistochemistry for CD20, CD3, and MIB-1. Additional immunohistochemistry was performed for CD10, BCL6, and MUM1 on paraffin blocks with sufficient tissue. RESULTS: There were a total of 73 cases with the mean age of presentation being 45.9 years (range 8-71 years) and with a male predominance (male: female (M:F) = 2.3:1). Headache was the commonest presenting complaint. The mean duration of symptoms was 10.6 weeks. All patients were immunocompetent. Most tumors were supratentorial in location. Out of 73 cases, 70 presented with a diffuse large B-cell lymphoma (DLBCL), two with a Burkitt's lymphoma, and one with a lymphomatoid granulomatosis. Only 51 of the DLBCL cases had sufficient tissue for additional studies. Non-germinal center was the most common phenotype seen in 65.7% (33/51) of cases. Germinal center B-cell (GCB) phenotype was seen in 18/51 cases (34.3%). CONCLUSION: DLBCL constituted the majority of PCNSLs and although non-germinal center was the predominant phenotype, more than a third of the cases were of the GCB phenotype. As the germinal center phenotype is known to have a better prognosis, further studies to explore its relevance in the Asian population are indicated.

An analysis of granulation patterns, MIB-1 proliferation indices and p53 expression in 101 patients with acromegaly.

BACKGROUND: Despite the wide spectrum of adenoma behavior in patients with acromegaly, the ability of most pathological markers to predict clinical and radiological behavior remains controversial. The authors sought to comprehensively examine clinical and radiological correlates of growth hormone (GH)-secreting pituitary adenomas with regard to several commonly used immunocytochemical techniques in patients undergoing transsphenoidal surgery for acromegaly. METHOD: We performed a retrospective review of histopathological findings in 101 surgically resected GH adenomas. Tumors were assessed radiologically for different patterns of extension. Each tumor specimen was subject to immunocytochemical analysis, including assessments of granulation patterns, MIB-1 labeling indices, prolactin cosecretion, p53 expression and mitotic activity. Endocrinological outcome was assessed in 93 patients, with remission defined by the 2010 consensus criteria. RESULTS: Most tumors were macroadenomas and almost half were invasive. When compared to densely granulated tumors, sparsely granulated adenomas were associated with a younger age at presentation, higher preoperative IGF-1 levels, elevated MIB-1 index and pure GH immunostaining, but did not differ significantly in terms of extrasellar invasion or outcome. Increased mitotic activity and p53 expression were also associated with higher proliferation indices and a younger age at presentation. Mixed GH/prolactin tumors demonstrated significantly higher remission rates, independent of variations in extrasellar growth. MIB-1 indices did not correlate with the preoperative GH/IGF-1 levels, adenoma size or Knosp grade. CONCLUSION: The pathobiology of acromegaly is complex, and the clinicoradiological significance of subtyping on the basis of the markers employed in this study is debatable. Further investigation of newer molecular markers is warranted.

Radiation-induced opticochiasmatic glioblastoma multiforme following conventional radiotherapy for Cushing's disease.

We report the rare occurrence of an opticochiasmatic glioblastoma multiforme 6 years following conventional radiotherapy for Cushing's disease. This article highlights the risks of collateral damage to the optic apparatus when irradiating the sellar region.

Fluorescence in situ hybridization for 1p, 19q status in a cohort of glial neoplasms.

OBJECTIVE: The objective of the following study is to determine 1p, 19q status in a cohort of glial neoplasms. materials and methods: Fluorescence in situ hybridization for determination of 1p, 19q deletions in 100 glial neoplasms diagnosed between January 2007 and March 2011, was performed using Vysis dual color probes localizing to 1p36/1q25; 19q13/19p13. RESULTS: Out of the 100 tumors, 78 tumors were either pure oligodendroglial (OD) neoplasms or had an OD component. 1p and 19q codeletions were seen in 72.7% of oligodendrogliomas (World Health Organization [WHO] Grade II), 90.9% of anaplastic oligodendrogliomas (WHO Grade III), 22.2% of mixed oligoastrocytomas (WHO Grade II) and 42.9% of the anaplastic oligoastrocytomas (WHO Grade III). Of the 29 tumors that were diagnosed as glioblastoma multiforme (GBM), 11 had an OD component of which four showed codeletions of 1p and 19q (36.4%) and two tumors showed epidermal growth factor receptor (EGFR) amplification (20%) without 1p19q codeletions. Amongst the remaining 18 GBMs without an OD component, three cases showed EGFR amplification (16.7%), one case showed isolated deletion of 1p and none showed 1p19q codeletions. Polysomies involving 1p and/or 19q with or without deletions were seen in 76.9% of mixed oligoastrocytic tumors, 7.7% of pure OD tumors and one glioblastoma. CONCLUSIONS: 1p19q codeletion is an early molecular change in the genesis of OD tumors, which is retained at the time of progression. Mixed tumors more frequently show polysomies of 1p and 19q. The presence of codeletion in a third of the GBMs with an OD component with its absence in GBMs without an OD component, justifies categorization of these tumors as a separate entity.

The current role of transcranial surgery in the management of pituitary adenomas.

The aim of this study was to determine the factors influencing the use of a transcranial (TC) approach in pituitary adenomas and suggest a decision-making tree for the surgical strategy. The data for 23 (4.6%) patients who underwent TC surgery from amongst 494 pituitary adenomas were retrospectively analyzed. Eight factors on magnetic resonance imaging (MRI) that could predict a difficult transsphenoidal (TS) surgery were noted. Adverse findings at TS surgery leading to a 2nd stage TC surgery were documented. Eighteen of the 23 cases were giant adenomas. Thirteen patients underwent TC surgery alone or as an initial approach when combined with TS while 10 underwent 2nd stage TC surgery following a TS approach. Most cases in the first group had 3 or more radiological factors in combination with a small sella. The 2nd group had higher sellar tumor volumes and fewer unfavourable radiological factors that led to the initial use of the TS approach. A hard, fibrous consistency or a significant residue obscured from the surgeon's view, and difficulty in hemostasis were additional factors prompting the use of a TC approach. Tumor excision ≥90% could be achieved in 13 cases (56.5%). Post-operative RT was administered in 12 patients. There were 2 deaths (8.7%) and the major morbidity rate was 43 %. Despite advances in endoscopic surgery the TC approach may be required in 5% of cases. A study of the preoperative MRI for factors that predict difficulty with the TS approach might encourage the surgeon to consider a TC surgery either as an initial approach or combined with a TS surgery.