Item Open AccessFumarate hydratase deficient renal cell carcinoma: a retrospective study performed at NHLS Universitas Academic laboratories, 2001 to 2017(University of the Free State, 2021-12) Du Preez, Michelle; Goedhals, JacquelineBackground: Fumarate hydratase deficient renal cell carcinoma (FH deficient RCC) has, in recent years, been described as part of a morphologic spectrum of renal tumours associated with hereditary leiomyomatosis and renal cell carcinoma (HLCRCC) syndrome and is currently recognized as a distinct entity in the 2013 International Society of Urological Pathology (ISUP) Vancouver classification of renal tumours and is included in the 2016 World Health Organization (WHO) classification. FH deficient RCC is an aggressive neoplasm which often presents at a high pathologic stage, with local and distant metastases at the time of diagnosis. FH deficient RCC has a wide variety of morphological patterns, however, the presence of pattern multiplicity, sarcomatoid/rhabdoid morphology and the presence of characteristic nuclear features, i.e. nuclei with prominent viral inclusion-like macronucleoli and perinuclear halos should prompt genetic testing of the tumour. Characteristic immunohistochemical staining patterns, i.e. loss of cytoplasmic expression of fumarate hydratase (FH) and aberrant nuclear expression of S-(2-succino)-cyteine (2SC) have a 100% positive predictive value for identifying FH deficient RCC, however, only FH is available for commercial use. Retention of cytoplasmic staining for FH does not exclude FH deficient RCC since the gene may still be functional in missense variants of the FH gene. To our knowledge, there is presently no published research regarding FH deficient RCC and its association with HLRCC syndrome in Africa. The impact of this disorder in South African patients, is therefore unknown. Aim: The aim of this study was to determine the number and profile of patients with FH deficient RCC seen by the Department of Anatomical Pathology, University of the Free State over a 17-year period, from 1 January 2001 to 31 December 2017. Methods: A retrospective, cross-sectional study was performed. All cases of primary renal cell carcinoma and RCC subtypes diagnosed between 1 January 2001 and 31 December 2017 were included. An immunohistochemical stain for FH was performed on all the cases. All the cases with the typical phenotype for FH deficient RCC were submitted for molecular analysis and genotyping. Results: 172 patients were included in the study. Ninety (52.33%) were male and 82 (47.67%) were female. The mean age at presentation was 54.2 years and most patients presented in the 5th to 6th decades of life. All cases showed retained cytoplasmic staining with FH. One (0.58%) case of FH deficient RCC with the characteristic phenotype and a missense mutation in Exon 7 of the FH gene was identified. The patient was a 53-year-old black female and no information regarding the presence of uterine leiomyomas or family history of RCC was available. Conclusion: All cases of RCC displaying the typical phenotype of FH deficient RCC (whether immunolabeling for FH is retained or lost) should be submitted for molecular testing in order to identify patients with HLRCC syndrome or confirm the diagnosis of sporadic FH deficient RCC to minimize morbidity and mortality in such patients and their families. Item Open AccessNUT midline carcinoma in the state sector of the Free State province, South Africa(University of the Free State, 2020-06) Roets, Antoinette Elisabeth; Goedhals, JacquelineBackground: NUT midline carcinoma (NMC) is a recently described, rare tumour that can easily be mistaken for a number of other tumours if a NUT immunohistochemical stain is not performed. The tumour is caused by a translocation involving the NUT gene and most cases involve BRD4 - NUT t(15;19) which results in loss of differentiation and uninhibited proliferation. The loss of differentiation is responsible for the monomorphic, primitive morphology of the tumour. The reporting Pathologist should have a high index of suspicion as the tumour shows positively for numerous immunohistochemical markers that vary from case to case. Positivity for CD34, which is unusual in carcinomas, together with positivity for cytokeratins, is a strong diagnostic clue that should prompt testing for the tumour. Previously thought to occur only in midline structures and young patients, recent research has proven the occurrence in a wider age distribution and outside the midline. This tumour is exceptionally aggressive, with only isolated survivors and early identification and aggressive treatment is needed. No research on NMC has been done in South Africa and there is only one case report from the rest of Africa. The incidence of this tumour in South Africa is therefore unknown. Aim: The aim of this study was to determine the number of cases of NMC seen over a twelve year period by the Department of Anatomical Pathology, University of the Free State and National Health Laboratory Service and to describe the demographic features of any patients identified. Methods: A retrospective study was performed. All undifferentiated malignant tumours and tumours with evidence of squamous differentiation from the head, neck and thorax seen between 1 January 2005 and 31 December 2016 were included. A NUT immunohistochemical stain was performed on all cases. The stain was regarded as positive if there was speckled nuclear staining in more than 50% of the tumour cells. Results: Four hundred and ninety eight cases were included in the study of which 424 (85.1%) were male and 74 (14.9%) were female. The mean age was 58.6 years. Only one positive case was identified. The patient was a 30-year-old female with a lung mass and lymph node metastases. Conclusion: This study confirms the rarity of this entity. Additional research is needed in other provinces of South Africa, including the private sector to provide a comprehensive patient profile of NMC in South Africa.