Efficient Identification of Patients With NTRK Fusions Using a Supervised Tumor-Agnostic Approach.

CONTEXT.­: The neurotrophic tropomyosin receptor kinase (NTRK) family gene rearrangements have been recently incorporated as predictive biomarkers in a "tumor-agnostic" manner. However, the identification of these patients is extremely challenging because the overall frequency of NTRK fusions is below 1%. Academic groups and professional organizations have released recommendations on the algorithms to detect NTRK fusions. The European Society for Medical Oncology proposal encourages the use of next-generation sequencing (NGS) if available, or alternatively immunohistochemistry (IHC) could be used for screening with NGS confirmation of all positive IHC results. Other academic groups have included histologic and genomic information in the testing algorithm. OBJECTIVE.­: To apply some of these triaging strategies for a more efficient identification of NTRK fusions within a single institution, so pathologists can gain practical insight on how to start looking for NTRK fusions. DESIGN.­: A multiparametric strategy combining histologic (secretory carcinomas of the breast and salivary gland; papillary thyroid carcinomas; infantile fibrosarcoma) and genomic (driver-negative non-small cell lung carcinomas, microsatellite instability-high colorectal adenocarcinomas, and wild-type gastrointestinal stromal tumors) triaging was put forward. RESULTS.­: Samples from 323 tumors were stained with the VENTANA pan-TRK EPR17341 Assay as a screening method. All positive IHC cases were simultaneously studied by 2 NGS tests, Oncomine Comprehensive Assay v3 and FoundationOne CDx. With this approach, the detection rate of NTRK fusions was 20 times higher (5.57%) by only screening 323 patients than the largest cohort in the literature (0.30%) comprising several hundred thousand patients. CONCLUSIONS.­: Based on our findings, we propose a multiparametric strategy (ie, "supervised tumor-agnostic approach") when pathologists start searching for NTRK fusions.

Lobular Endocervical Glandular Hyperplasia, a mimicker and potential pitfall for HPV-independent well differentiated Gastric-type Endocervical Adenocarcinoma: Case report and literature review focusing on histology, immunophenotype, and molecular findings.

Lobular glandular endocervical hyperplasia is an uncommon benign entity within the spectrum of gastric-type endocervical lesions. We report a case of a 48-year-old woman who presented with a palpable mass and watery vaginal discharge. Ultrasound revealed an 8 cm × 4 cm × 3 cm multicystic mass affecting the cervix, and hysterectomy was performed. The well-delimited multicystic, mucinous mass distorted the entire cervix. Microscopically, endocervical glandular proliferation with a lobular architecture was observed. The glands were lined with a single layer of tall, mucin-rich, columnar cells with basal and bland nuclei. The lesion was positive for MUC6 marker and hormonal receptors were negative, while P53 expression was normal. Three years later, the patient remained disease free. Here, we discuss the differential diagnosis between lobular glandular endocervical hyperplasia and similar conditions, particularly gastric-type endocervical adenocarcinoma, and review the literature focusing on the molecular pathways underlying gastric-type endocervical lesions. This case highlights the importance of accurate diagnosis to ensure favorable outcomes.

When should a nephrologist suspect a mitochondrial disease?

Mitochondrial diseases, taking into account those that affect the processes of the respiratory chain (RC) and mitochondrial oxidative phosphorylation system (OXPHOS), make up a relatively frequent group within rare diseases that usually have multisystem involvement, a very variable phenotypic expression and a complex genetic base. Renal involvement is uncommon, with the tubule being the most affected, specifically its proximal portion, developing into full Toni-Debré-Fanconi syndrome in the most serious cases. However, in some cases the glomerulus is involved, fundamentally in focal segmental glomerulosclerosis form (FSGS), expressed by proteinuria and renal failure. It is important that the Nephrologist keeps in mind the possibility of a mitochondrial disease in patients with this type of renal involvement that present clinical data with these characteristics, especially diabetes mellitus and deafness. In cases with FSGS, a correct diagnosis will avoid the inappropriate use of immunosuppressive medication. Specific treatments do not exist for the majority of mitochondrial diseases, but it is likely that the intense research that currently exists for these diseases will eventually produce effective treatment possibilities.

DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure.

Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis.

Síndrome DRESS secundario a ibuprofeno como causa de fallo hepático hiperagudo / DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure

El fallo hepático agudo presenta alta mortalidad, siendo su primera etiología en España la viral. Presentamos un caso de fallo fulminante secundario a una reacción idiosincrásica a ibuprofeno, englobado en el síndrome de DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Dicho síndrome constituye un diagnóstico clave en el diagnóstico diferencial del fracaso hepático agudo, ya que su curso infausto obliga en muchas ocasiones a la realización de trasplante hepático como única terapéutica útil. Este caso es un buen ejemplo de la necesidad de la rapidez y la eficiencia en la coordinación a nivel intrahospitalario y entre centros sanitarios como factor clave en la mejoría del pronóstico (AU)

Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis (AU)