The Use of Pan-Tropomyosin Receptor Kinase Immunohistochemistry as a Screening Tool for the Detection of Neurotrophic Tropomyosin-Related Kinase Fusions: Real-World Data from a National Multicentric Retrospective Study.

INTRODUCTION: The neurotrophic tropomyosin-related kinase (NTRK) genes encode the tropomyosin receptor kinases (TRKs). Patients with solid tumors harboring an oncogenic NTRK fusion are eligible for treatment with TRK inhibitors. NTRK fusion is often associated with TRK overexpression. Pan-TRK immunohistochemistry (IHC) is used to screen for NTRK fusions, but immunoreactivity patterns are poorly defined. METHODS: Data on pan-TRK immunoreactivity patterns in 2,669 solid tumors (comprising carcinomas, sarcomas, and melanocytic lesions) were retrospectively collected by nine laboratories and comprised tumor type, percentage of pan-TRK-positive tumor cells, staining intensity, cytoplasmic, membrane and/or nuclear staining pattern, and the presence or absence of NTRK fusion. RESULTS: Overall, 2,457 tumors (92%) were pan-TRK negative and 212 neoplasms (8%) were pan-TRK positive. Twenty-two pan-TRK-positive tumors (0.8%) harbored an NTRK fusion, representing 10% of all pan-TRK-positive tumors. Cytoplasmic immunoreactivity was most often observed, followed by membrane immunoreactivity. Nuclear pan-TRK positivity was least frequent, but was most often (33%) associated with NTRK fusion. CONCLUSION: Pan-TRK IHC can be used to screen for NTRK fusions, especially in commonly diagnosed solid tumors with low NTRK fusion prevalence. In case of pan-TRK immunoreactivity, regardless of its intensity and tumor cell percentage, subsequent molecular tests should be performed to formally confirm the presence or absence of NTRK fusions.

Sclerotic Lesions of the Jaw: A Pictorial Review.

Sclerotic lesions of the jaw are uncommon but may be clinically relevant. In this pictorial review, the most common sclerotic lesions are discussed. Three categories of lesions are distinguished; odontogenic sclerotic lesions, non-odontogenic sclerotic lesions, and mixed lytic-sclerotic lesions. In each group, non-neoplastic conditions are discussed first, followed by benign and malignant neoplasms. For each disease a brief overview is given, including histological features, epidemiology, symptoms, typical location, imaging features, and treatment. This review emphasizes which basic observations are essential to the evaluation of sclerotic jaw lesions and what elements have to be taken into account to create a proper differential diagnosis.

An unusual cause of severe, persistent diarrhoea.

We present two cases of patients with severe persistent diarrhoea, in whom duodenal biopsies revealed villous atrophy that could be attributed to the use of olmesartan. The differential diagnosis of villous atrophy without serological markers of celiac disease should include drugs as possible cause, with olmesartan as a recently discovered culprit. Gastroenterologist should be aware of this entity.

A tale of medical shopping or the hazards of repetitious cytological screening of the cervix.

A 65-year-old woman had on her own initiative three cervical smears taken at very short intervals. The second smear was taken only 1 day after the first one. It contained necrotic cellular material with atypia due to the scraping on the day before; it was at first mistakenly interpreted as showing malignant features. This led to the performance of various diagnostic procedures, and a considerably greater cost for the medical insurance system.