NEH may, to a degree, be a marker of airway immaturity rather than the direct cause of NEHI. This possibility is supported by the fact that the number of bombesin-positive NECs decreased with age in this cohort, independent of disease type. The average percentage of bombesin-positive NECs per airway appears to be the best histological criterion for assessing the extent of NECs in the context of NEHI.
Introduction:Detection of the ALK rearrangement in a solid tumor gives these patients the option of crizotinib as an oral form of anticancer treatment. The current test of choice is fluorescence in situ hybridization (FISH), but various cheaper and more convenient immunohistochemical (IHC) assays have been proposed as alternatives.Methods:Fifteen FISH-positive cases from patients, seven with data on crizotinib therapy and clinical response, were evaluated for the presence of ALK protein using three different commercially available antibodies: D5F3, using the proprietary automated system (Ventana), ALK1 (Dako), and 5A4 (Abcam). A further 14 FISH-negative and three uncertain (<15% rearrangement detected) cases were also retrieved. Of the total 32 specimens, 17 were excisions and 15 were computed tomography-guided biopsies or cytological specimens. All three antibodies were applied to all cases. Antibodies were semiquantitatively scored on intensity, and the proportion of malignant cells stained was documented. Cutoffs were set by receiver operating curve analysis for positivity to optimize correct classification.Results:All three IHC assays were 100% specific but sensitivity did vary: D5F3 86%, ALK 79%, 5A4 71%. Intensity was the most discriminating measure overall, with a combination of proportion and intensity not improving the test. No FISH-negative IHC-positive cases were seen. Two FISH-positive cases were negative with all three IHC assays. One of these had been treated with crizotinib and had failed to show clinical response. The other harbored a second driving mutation in the EGFR gene.Conclusions:IHC with all three antibodies is especially highly specific (100%) although variably sensitive (71%-86%), specifically in cases with scanty material. D5F3 assay was most sensitive in these latter cases. Occasional cases are IHC-positive but FISH-negative, suggesting either inaccuracy of one assay or occasional tumors with ALK rearrangement that do not express high levels of ALK protein.
Whilst meningiomas are common neoplasms of the central nervous system; ectopic meningiomas are very rare. When they do occur, they are typically in the head and neck. Due to their rarity, they propose a diagnostic challenge with interesting pathological findings. To date, only seven ectopic meningiomas arising in the mediastinum have been reported in the literature. We aim to shift the focus on the diagnostic journey of this rare entity which involved various imaging and histopathological techniques. Our patient was successfully treated with no complications after four years through input from specialists and the multidisciplinary team.
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