This study shows levels of interobserver and intra-observer variation similar to those found in other grading systems in histopathology, with no significant decrease in variability found by abridging the system. The WHO/IASLC system is therefore recommended for future use in both clinical and research fields.
Purpose
To evaluate the cellular nature of and diagnostic terminology used in connection with acquired retinal “vasoproliferative tumors.”
Design
Retrospective clinicopathologic study.
Methods
Clinical records and microscopic slides of 4 enucleated globes were reviewed. Special stains and immunohistochemical probes for CD31, CD34, p53, glial fibrillary acidic protein (GFAP), CD163, and Ki67 (cell replication) were employed; ultrastructural and fluorescence in situ hybridization (FISH) analyses were performed.
Results
Tumors were located inferotemporally in middle-aged patients. They were uniformly composed of compacted elongated, GFAP-positive spindle cells (due to intermediate filaments identified ultrastructurally) with a Ki67 index of less than 1%. Rosenthal fibers and eosinophilic granular bodies were observed. Hyalinized periodic acid–Schiff-positive vessels were widely separated. CD31 and CD34 revealed a sparse microvasculature. Tumor-associated exudate spread predominantly subretinally. The retinal pigment epithelium had undergone extensive placoid fibrous metaplasia with focal ossification. P53 upregulation, BRAF-KIAA gene rearrangement, and IDH1 R132H mutation typically associated with low-grade astrocytic neoplasms were absent.
Conclusions
Retinal “vasoproliferative” tumors have been mischaracterized, because they actually display a paucity of microvessels. Proliferating fibrous astrocytes with a very low proliferation index predominate, without immunohistochemical or genetic evidence favoring a neoplasm. Subretinal exudate appeared capable of provoking widespread fibrous metaplasia of the pigment epithelium that was mainly responsible for secondary retinal damage. The term “reactive retinal astrocytic tumor” is proposed as more appropriate for this entity. In carefully selected progressive lesions, consideration should be given to earlier surgical intervention before extensive subretinal exudate accumulates and pigment epithelial proliferation with fibrous metaplasia ensues.
Paraffin sections from 29 lung carcinomas (28 primary and 1 metastatic) and 9 pleural malignant mesotheliomas were immunostained with antisera to human hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, met. For HGF/SF, immunoreactivity was demonstrated in all 9 mesotheliomas, 9 of 12 adenocarcinomas, and 7 of 10 squamous cell carcinomas. None of seven cases of small cell anaplastic carcinoma was positive. The adenocarcinomas frequently showed enhanced luminal staining, suggesting possible secretion of HGF/SF, and this pattern of staining was also seen occasionally in bronchial epithelium adjacent to the tumour. Stromal fibroblasts also showed immunoreactivity for HGF/SF in 6/8 cases of mesothelioma but in only 3/12 adenocarcinomas, 1/10 squamous cell carcinomas, and 1/4 small cell anaplastic carcinomas. All tumours stained for met, usually strongly. The staining was mainly cytoplasmic in nature, but some plasma membrane staining was usually evident. Adenocarcinomas showed strong luminal membrane staining, as did adjacent, histologically normal bronchial epithelium. This study demonstrates the presence of HGF/SF and met in most of the tumour types described, particularly mesotheliomas, and suggests that the HGF/SF/met signalling system may play a role in the development of these tumours, either by autocrine or by paracrine mechanisms.
The 2 major types of lacrimal system concretions differ in their primary location and histopathologic composition. Further characterization may lead to an understanding of the mechanisms for their formation. Mucopeptide concretion is more appropriate than terms such as "dacryolith" and "mucolith," and bacterial concretion is a more appropriate term than "canaliculith," because of the absence of significant calcium or stone-like density in these masses.
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