RESUMO
We report a diagnostically challenging case of a SMARCA4-deficient undifferentiated tumour to emphasize its potential to mimic other malignant tumours on histology, especially in small biopsies and where rhabdoid morphology is lacking. A 48-year-old man, who was known for chronic obstructive pulmonary disease and polysubstance use, presented with dyspnoea and an anterior mediastinal mass that had grown rapidly over a seven-month period. The rapid growth and location in the anterior mediastinum raised clinical suspicion for lymphoma or a germ cell tumour. Microscopic examination of a transthoracic, ultrasound-guided, core needle biopsy revealed relatively uniform, malignant epithelioid cells with clear cytoplasm, but lacking any rhabdoid features. Tumour necrosis was prominent. The immunohistochemistry panel was negative for lymphoma markers, but positive for SALL4 (a marker typically associated with germ cell tumours), CD34, EMA, and HepPar1, while expression of SMARCA4 and claudin-4 was entirely lost. Only focal cytokeratin expression was demonstrated. SMARCB1 (INI1) expression was retained. The diagnosis of SMARCA4-DUT was made based on these findings. Unfortunately, the tumour was already at an advanced stage at diagnosis (stage IVA) and the patient had a poor performance status. He was treated with palliative radiotherapy with no significant improvement in performance status and passed away 3 months after diagnosis. The case highlights the importance of considering SMARCA4-DUT in the differential diagnosis of an undifferentiated, rapidly growing thoracic tumour and the potential for misdiagnosis on a small tissue sample, particularly as rhabdoid morphology may be absent.
RESUMO
Congenital long QT syndrome (cLQTS) is a genetic disorder predisposing to ventricular arrhythmia, syncope and sudden death. Over 700 different cLQTS-causing mutations in 13 genes are known. The genetic spectrum of LQTS in 44 South African cLQTS patients (23 known to carry the South African founder mutation p.A341V in KCNQ1) was established by screening for mutations in the coding regions of KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A, the most frequently implicated cLQTS-causing genes (five-gene screening). Fourteen disease-causing mutations were identified, eight (including the founder mutation) in KCNQ1, five in KCNH2 and one in KCNE1. Two mutations were novel. Two double heterozygotes were found among the 23 families (8.5%) carrying the founder mutation. In conclusion, cLQTS in South Africa reflects both a strong founder effect and a genetic spectrum similar to that seen in other populations. Consequently, five-gene screening should be offered as a standard screening option, as is the case internationally. This will disclose compound and double heterozygotes. Fivegene screening will most likely be even more informative in other South African sub-populations with a greater genetic diversity.
