Significance of Staining Intensity in Ki-67 Proliferation Index in Meningiomas, and a Critical Review of the Literature on Proliferation Index Assessment.

OBJECTIVE: Meningioma is the most common primary adult intracranial neoplasm, and proliferation indices (PI) rise with increasing grade from WHO CNS grade 1 to 3. Ki-67 immunohistochemistry (IHC) poses a variety of technical and interpretative challenges. Here, we specifically investigated the staining intensity and its effect on interpretation and final diagnosis. METHODS: 124 high and low-grade meningiomas of various grades were blindly evaluated using different counting strategies (CS) based on the staining intensity of the nuclei as darkest (CS1), darkest+intermediate (CS2), and any staining (CS3) in hot-spots (HS) and in the context of overall proliferative activity (OPA). RESULT: CSs in HS, OPA, and their average results were significantly different between low-grade and high-grade groups. PI obtained using CS3 yielded results that matched best with values expected for the corresponding WHO grade. CS had a profound impact on whether a LG meningioma would be diagnosed as one with a "high proliferation index." CONCLUSION: A large body of work exists on the counting methods, clinically significant cut-off values, and inter- and intra-observer variability for Ki-67 PI interpretation. We show that Ki-67 IHC staining intensity, which to our knowledge has not been previously systematically investigated, can have a significant effect on PI interpretation in settings that influence diagnostic and clinical management decisions.

Basal cell carcinoma appearing to emanate from the punctum.

Purpose: To present the clinical and histological characteristics of a basal cell carcinoma, which appears to emanate from the lacrimal punctum. Observations: An 81-year-old caucasian female presented with an irritating lesion arising from the left upper punctum for approximately four months. Examination demonstrated a pedunculated pinkish lesion emerging from the left upper punctum. The patient elected to pursue the removal of the lesion. An excisional biopsy was performed by placing a curette within the upper eyelid punctum, and the lesion was scooped out. Pathology showed invasive nodular basal cell carcinoma. Following the diagnosis, a wedge resection of the left upper punctal region was performed, which showed no residual carcinoma. Conclusion and importance: This case describes a unique instance of a basal cell carcinoma clinically appearing to arise solely from the upper eyelid punctum. A level of suspicion should be maintained when excising benign-appearing eyelid lesions, and a histopathological analysis is warranted.

Miyoshi Muscular Dystrophy Due to Novel Splice Site Variants in DYSF Gene.

Dysferlinopathies are a group of phenotypically heterogeneous disorders caused by pathogenic variants in the DYSF (DYStrophy-associated Fer-1-like) gene encoding dysferlin. The phenotypic spectrum includes Miyoshi muscular dystrophy (MMD), limb-girdle muscular dystrophy type R2, distal myopathy with anterior tibial onset, and isolated hyperCKemia. MMD is characterized by muscle weakness and atrophy predominantly affecting the calf muscles with symptoms onset between 14 and 40 years of age. There is no clear phenotype - genotype correlation for dysferlinopathy. We describe a 15-year-old girl who presented with a phenotype consistent with MMD. However, she was initially treated for presumed polymyositis without improvement. Subsequent genetic testing revealed two novel variants in DYSF: c.3225dup (p.Gly1076Trpfs*38) in exon 30 and c.3349-2A > G (Splice acceptor) in intron 30. No dysferlin was detected in a muscle biopsy using immunostains and western blots, a result consistent with dysferlinopathy that supports the pathogenicity of the DYSF variants.

What Every Neuropathologist Needs to Know: The Muscle Biopsy.

Competence in muscle biopsy evaluation is a core component of neuropathology practice. The practicing neuropathologist should be able to prepare frozen sections of muscle biopsies with minimal artifacts and identify key histopathologic features of neuromuscular disease in hematoxylin and eosin-stained sections as well as implement and interpret a basic panel of additional histochemical, enzyme histochemical, and immunohistochemical stains. Important to everyday practice is a working knowledge of normal muscle histology at different ages, muscle motor units, pitfalls of myotendinous junctions, nonpathologic variations encountered at traditional and nontraditional muscle sites, the pathophysiology of myonecrosis and regeneration, and approaches to distinguish muscular dystrophies from inflammatory myopathies and other necrotizing myopathies. Here, we provide a brief overview of what every neuropathologist needs to know concerning the muscle biopsy.

Neuropathology Education Using Social Media.

Social media use continues to grow among pathologists. Discussions of current topics, posts of educational information, and images of pathological entities are commonly found and distributed on popular sites such as Facebook and Twitter. However, little is known about the presence of neuropathology content in social media and the audience for such content. We designed and distributed a survey to assess the demographics of users viewing neuropathology content and their opinions about neuropathology in social media. User posts on the Facebook group, Surgical Neuropathology, were also analyzed. The results show that there is a demand for neuropathology content of high quality, curated by experts, and that this demand is present among both specialists and nonspecialists. These findings suggest that social media may be useful for rapid dissemination of information in the field of neuropathology. This format also offers a unique opportunity to extend the reach of information to nonneuropathologists who may not receive neuropathology journals or have access to specialty-level neuropathology training, to build networks between professionals, and potentially to influence public opinion of neuropathology on an international scale.