Atypical Presentation of Transcranial Extension of Intracranial Meningiomas.

ABSTRACT: Meningiomas are the most common primary central nervous system tumors. These tumors predominantly arise from the neural crest-derived meningothelial cells of the arachnoid dural layer. Intracranial meningiomas are stratified with the World Health Organization classification of tumors. Cutaneous meningiomas present rarely and have their own criteria classification (Lopez classification) of 3 types. The first type is congenital. The second consists of ectopic soft-tissue meningiomas. The third involves tumors that extended into the dermis or subcutis that include the neuroaxis. We present a case of a 56-year-old woman with 4 facial tumors that clinically seemed to be cutaneous cysts or lipomas. She reported a history of surgical resection of an intracranial meningioma on the left forehead scalp line 15 years ago. A recent surgical resection of a glabellar tumor revealed a glistening white mass. Pathologic examination revealed a poorly circumscribed mass in the deep dermis and subcutaneous area with sheets of epithelioid and plasmacytoid tumor cells with nuclear pleomorphism. Mitotic figures and necrosis were also evident. Immunohistochemistry revealed positivity for epithelial membrane antigen, p63, and ERG. The tissue had negative staining for p40, CK7, SOX10, CD68, SMA, desmin, and CD34. The patient's medical history was remarkable in that these tumors had only been growing for several months. Brain magnetic resonance imaging demonstrated widespread tumors in bilateral frontal lobes, skull, orbits, and sinuses. Considering the transcranial extensions and 15-year recurrence time, she was diagnosed with a recurrent atypical brain meningioma type II and cutaneous meningioma Lopez type III.

Osteosarcomatous Divergence in Dedifferentiated Liposarcoma Presenting as a Colonic Mass.

Dedifferentiated liposarcomas most commonly arise in the retroperitoneum, accounting for 10% of liposarcomas. Heterologous differentiation occurs in 5-10% of dedifferentiated liposarcomas; however, divergent osteosarcomatous differentiation is rare. We report a rare case of initial presentation of dedifferentiated liposarcoma with osteosarcomatous component as a colonic mass in a 72-year-old man. The tumor is mainly composed of bony trabeculae with intervening highly atypical cells and adjacent high-grade mesenchymal nonlipogenic tumor, as well as areas of well-differentiated liposarcoma. Immunohistochemical studies showed diffuse positivity for SATB2 in the atypical cells and fluorescence in situ hybridization revealed high-level amplification of MDM2 gene, supporting the diagnosis of well-differentiated and dedifferentiated liposarcoma with heterologous osteosarcomatous differentiation.

Comparative functional characterization of novel non-syndromic GJB2 gene variant p.Gly45Arg and lethal syndromic variant p.Gly45Glu.

We characterized a novel GJB2 missense variant, c.133G>A, p.Gly45Arg, and compared it with the only other variant at the same amino acid position of the connexin 26 protein (Cx26) reported to date: c.134G>A, p.Gly45Glu. Whereas both variants are associated with hearing loss and are dominantly inherited, p.Gly45Glu has been implicated in the rare fatal keratitis-ichthyosis-deafness (KID) syndrome, which results in cutaneous infections and septicemia with premature demise in the first year of life. In contrast, p.Gly45Arg appears to be non-syndromic. Subcellular localization experiments in transiently co-transfected HeLa cells demonstrated that Cx26-WT (wild-type) and p.Gly45Arg form gap junctions, whereas Cx26-WT with p.Gly45Glu protein does not. The substitution of a nonpolar amino acid glycine in wildtype Cx26 at position 45 with a negatively charged glutamic acid (acidic) has previously been shown to interfere with Ca2+ regulation of hemichannel gating and to inhibit the formation of gap junctions, resulting in cell death. The novel variant p.Gly45Arg, however, changes this glycine to a positively charged arginine (basic), resulting in the formation of dysfunctional gap junctions that selectively affect the permeation of negatively charged inositol 1,4,5-trisphosphate (IP3) and contribute to hearing loss. Cx26 p.Gly45Arg transfected cells, unlike cells transfected with p.Gly45Glu, thrived at physiologic Ca2+ concentrations, suggesting that Ca2+ regulation of hemichannel gating is unaffected in Cx26 p.Gly45Arg transfected cells. Thus, the two oppositely charged amino acids that replace the highly conserved uncharged glycine in p.Gly45Glu and p.Gly45Arg, respectively, produce strikingly different effects on the structure and function of the Cx26 protein.