Cardiac Melanoma Metastasis with ERBB2 Gene Amplification: A Potential for Future Targeted Therapy.

Cardiac tumors are rare, and their treatment differs interindividually regarding the histopathological proprieties and the stage of disease. Authors present a case of symptomatic cardiac melanoma metastasis that expressed an ERBB2 (HER2) gene amplification in a course of the disease that has not yet been reported. The frail patient with a history of pulmonary and renal carcinoma, was admitted to the hospital due to a symptomatic left atrial tumor mass. The patient underwent a tumor-resecting cardiac surgery. At first mistaken for myxoma on echocardiography, the histopathological examination of the tumor revealed a melanoma of acral or mucosal origin. The melanoma metastasis was negative for common genetic mutations in BRAF, NRAS or KIT genes, and for the presence of NTRK genes fusions, but carried ERBB2 (HER2) gene amplification. The absence of standard gene mutations rendered it unresponsive to treatment with BRAF and MEK inhibitors. This molecular finding is rare in melanomas and represented a therapeutic target for off-label systemic treatment with drugs, primarily aimed at ERBB2 positive breast, gastric, and gastroesophageal junction cancers. A rare finding like this justifies molecular genetic analysis of unusual tumor specimen and guarantees optimal treatment for uncommon types of cardiac metastatic tumors.

Reparative Perineural Hyperplasia in the Gastric Wall: A Histologic Mimic of Perineural Invasion.

Reparative perineural hyperplasia is an incidental and probably underreported reactive histologic finding thus far only reported in the setting of healing wounds or adjacent to a dermatofibroma in cutaneous specimens. It is characterized by a focal concentric proliferation of cytologically bland spindled perineurial cells and is hence considered a benign histologic mimic of neoplastic perineural invasion. Thus, it may present a diagnostic pitfall and we therefore consider it as a valuable entity to be aware of. To the best of our knowledge, this brief case report is the first to convey that reparative perineural hyperplasia may also occur in the gastrointestinal tract. It may therefore be a ubiquitous reactive histological phenomenon relating to previous surgical or traumatic wounds in various sites, that is, outside the thus far established setting of skin reexcision specimens.

Renal Tissue miRNA Expression Profiles in ANCA-Associated Vasculitis-A Comparative Analysis.

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises autoimmune disease entities that cause target organ damage due to relapsing-remitting small vessel necrotizing vasculitis, and which affects various vascular beds. The pathogenesis of AAV is incompletely understood, which translates to considerable disease- and treatment-related morbidity and mortality. Recent advances have implicated microRNAs (miRNAs) in AAV; however, their accurate characterization in renal tissue is lacking. The goal of this study was to identify the intrarenal miRNA expression profile in AAV relative to healthy, non-inflammatory and inflammatory controls to identify candidate-specific miRNAs. Formalin-fixed, paraffin-embedded renal biopsy tissue samples from 85 patients were obtained. Comprehensive miRNA expression profiles were performed using panels with 752 miRNAs and revealed 17 miRNA that differentiated AAV from both controls. Identified miRNAs were annotated to characterize their involvement in pathways and to define their targets. A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results. Interestingly, several members of the miR-30 family were detected. However, a validation study of these differentially expressed miRNAs in an independent, larger sample cohort is needed to establish their potential diagnostic utility.

A case of MV2K subtype of sporadic Creutzfeldt-Jakob disease with florid-like plaques: Similarities and differences to variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease (vCJD) is traditionally regarded as having a distinct clinical course, imaging study findings and neuropathological features, which in combination should allow a clear distinction from the six currently well-defined subtypes of sporadic Creutzfeldt-Jakob disease (sCJD). This is of major importance, especially from the standpoint of epidemiology. As we would like to demonstrate through this case report, the MV2K subtype of sCJD, being rare and heterogeneous in both clinical and neuropathological presentations, might challenge this concept by virtue of partial overlapping, both clinically and neuropathologically, with the characteristic phenotype of vCJD. Chiefly, we observed prolonged isolated psychiatric prodrome, new onset limb pain and late cognitive decline clinically, while florid-like plaques were present on routine histology, albeit in scarce and regionally restricted distribution when compared to vCJD. However, the issue is further complicated by the fact that a case of vCJD in a heterozygous (i.e. methionine - M and valine - V) allelic state with regard to the polymorphic codon 129 of the prion protein gene (PRNP) has recently been described in the UK, which deviated from the otherwise well-defined and constant clinicopathological phenotype that vCJD had thus far demonstrated. Taking both the facts into account, we would like to emphasize the use of complementary diagnostic methods to the established and otherwise reliable histological type-based model, particularly when confronted with a rare or atypical phenotype such as ours.