Evaluation of epidermal growth factor receptor mutations based on mutation specific immunohistochemistry in non-small cell lung cancer: A preliminary study.

Background & objectives: Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC). Methods: Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed. Results: Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon20 variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases. Interpretation & conclusions: In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.

1p/14q co-deletion: A determinant of recurrence in histologically benign meningiomas.

Background: Meningiomas are the most common benign central nervous system tumors. However, a sizeable fraction recurs, irrespective of histological grade. No molecular marker is available for prediction of recurrence in these tumors. Materials and Methods: We analyzed recurrent meningiomas with paired parent and recurrent tumors by fluorescence in situ hybridization for 1p36 and 14q32 deletion, AKT and SMO mutations by sequencing, and immunohistochemistry for GAB1, progesterone receptor (PR), p53, and MIB-1. Results: 18 recurrent meningiomas (11 grade I, 3 grade II, 4 grade III) with their parent tumors (14 grade I, 2 grade II and 2 grade III) were identified. Overall, 61% of parent and 78% of recurrent meningiomas showed 1p/14q co-deletion. Notably, grade I parent tumors showed 1p/14q co-deletion in 64% cases while 82% of grade I recurrent tumors were co-deleted. AKT mutation was seen in two cases, in both parent and recurrent tumors. SMO mutations were absent. GAB1 was immunopositive in 80% parent and 56.3% recurrent tumors. MIB-1 labeling index (LI), PR and p53 expression did not appear to have any significant contribution in possible prediction of recurrence. Conclusion: Identification of 1p/14q co-deletion in a significant proportion of histologically benign (grade I) meningiomas that recurred suggests its utility as a marker for prediction of recurrence. It appears to be a better predictive marker than MIB1-LI, PR and p53 expression. Recognition of AKT mutation in a subset of meningiomas may help identify patients that may benefit from PI3K/AKT pathway inhibitors, particularly among those at risk for development of recurrence, as determined by presence of 1p/14q co-deletion.

Rare manifestations of sarcoidosis in modern era of new diagnostic tools.

Background & objectives: Growing body of literature on sarcoidosis in India has led to an increased awareness of the disease. With the advent of better imaging tools hitherto under-recognized manifestations of sarcoidosis are likely to be better recognized. We sought to study the rare clinical and radiological manifestations (<5%) in patients with sarcoidosis. Methods: Retrospective review of records of 164 patients with histopathologically proven sarcoidosis seen over six years in a tertiary care centre in north India, was done. Results: Fifty four rare manifestations were observed in 164 patients. Acute presentation in the form of Lofgren syndrome was seen in eight (4.9%) and Heerfordt's syndrome in two (1.2%) patients. Musculoskeletal manifestations included chronic sarcoid arthritis in three (1.8%), deforming arthritis and bone erosion in one (0.6%) each. Rare initial presentation with dilated cardiomyopathy in one (0.6%), complete heart block in two (1.2%), bilateral sequential facial nerve palsy in two (1.2%), and pyrexia of unknown origin was seen in one (0.6%) patient. Other rare manifestations included chronic respiratory failure in one (0.6%), dysphagia in one (0.6%), sicca syndrome in five (3%), massive splenomegaly in one (0.6%), portal hypertension in two (1.2%), hypersplenism, gastric sarcoidosis, ninth and tenth cranial nerve palsies, moderate pericardial effusion and nephrocalcinosis in one (0.6%) each, and pulmonary artery hypertension in two (1.2%) patients. Rare radiological manifestations included moderate pleural effusion in two (1.2%), pleural thickening in five (3%), calcification of intrathoracic lymph nodes in four (2.4%), alveolar (nodular) sarcoidosis in three (1.8%), and myocardial uptake of 18F-fluorodeoxyglucose (F-18 FDG) in two (1.2%) patients. Fourteen patients had airways obstruction and behaved typically like seasonal bronchial asthma with excellent response to corticosteroids. Interpretation & conclusions: Increased awareness of rare manifestations will facilitate better management of these patients. With increasing use of modern diagnostic tools, manifestations hitherto considered rare, are likely to be recognized more frequently in the future.

Mixed schwannoma with meningioma of the trigeminal nerve.

Mixed tumors composed of schwannoma and meningiomas are extremely rare and are usually associated with neurofibromatosis-2 (NF-2). So far, all the cases reported have involved the cerebello-pontine angle. Only two cases did not have a clear association with NF-2. We report a mixed tumor comprising of meningioma admixed with schwannoma in a 33-year-old male with bilateral trigeminal nerve schwannomas. The patient did not fit the existing diagnostic criteria of NF-2. The relevant literature, along with diagnostic criteria for NF-2 is discussed.

Congenital myopathies: a clinicopathological study of 25 cases.

OBJECTIVE: Congenital myopathies are rare. Through this article, the authors want to present a clinicopathological analysis of 25 new cases. MATERIALS AND METHODS: The clinical data of patients who were diagnosed with congenital myopathy between 2001 and 2006 was retrieved. Muscle biopsies were processed for H&E staining, enzyme histochemistry, and immunohistochemistry. Biopsies were also processed for ultrastructural analysis. RESULTS: During a period of 6 years, 1.12% of the muscle biopsies were diagnosed as congenital myopathies. The most common congenital myopathy was central core disease followed by nemaline rod myopathy and multi-mini core disease. Clinically, they have variable features. The final diagnosis was made with the help of enzyme histochemistry and ultrastructural features. CONCLUSION: This study emphasizes the importance of enzyme histochemistry and electron microscopic examination in the diagnosis of congenital myopathies especially in the absence of genetic studies.