Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern.

Neoplasms with a myopericytomatous pattern represent a morphological spectrum of lesions encompassing myopericytoma of the skin and soft tissue, angioleiomyoma, myofibromatosis/infantile haemangiopericytoma and putative neoplasms reported as malignant myopericytoma. Lack of reproducible phenotypic and genetic features of malignant myopericytic neoplasms have prevented the establishment of myopericytic sarcoma as an acceptable diagnostic category. Following detection of a LMNA-NTRK1 gene fusion in an index case of paediatric haemangiopericytoma-like sarcoma by combined whole-genome and RNA sequencing, we identified three additional sarcomas harbouring NTRK1 gene fusions, termed 'spindle cell sarcoma, NOS with myo/haemangiopericytic growth pattern'. The patients were two children aged 11 months and 2 years and two adults aged 51 and 80 years. While the tumours of the adults were strikingly myopericytoma-like, but with clear-cut atypical features, the paediatric cases were more akin to infantile myofibromatosis/haemangiopericytoma. All cases contained numerous thick-walled dysplastic-like vessels with segmental or diffuse nodular myxohyaline myo-intimal proliferations of smooth muscle actin-positive cells, occasionally associated with thrombosis. Immunohistochemistry showed variable expression of smooth muscle actin and CD34, but other mesenchymal markers, including STAT6, were negative. This study showed a novel variant of myo/haemangiopericytic sarcoma with recurrent NTRK1 gene fusions. Given the recent introduction of a novel therapeutic approach targeting NTRK fusion-positive neoplasms, recognition of this rare but likely under-reported sarcoma variant is strongly encouraged.

Clinicopathological, immunohistochemical, molecular-genetic and risk profiles of gastrointestinal stromal tumors in a cohort of Sudanese patients.

Background: Determining the risk of malignant behaviour and mutational status of gastrointestinal stromal tumours (GISTs) guide the management decision and allow optimal individualized patient treatment. Objectives: To determine clinicopathological, immunohistochemical (IHC), risk and KIT mutational findings of GISTs in Sudanese patients. Methods: Histological slides were reviewed, IHC for DOG-1 and CD117 performed and hotspot KIT mutations examined. The risk group was assigned using combined risk criteria. Results: 21 of the 36 patients (58.3%) were males (mean age, 54.83 ±12.57; range, 26-71). Abdominal pain and mass were the most frequent symptoms. Mean tumor size (±SD) was 11.6(±5.82) cm. Either CD117, DOG1 or both were positive in all cases. Using risk criteria, 33.3% (n=12) were clinically malignant at presentation, 13.9% (n=5) high risk, 16.7% (n=6) intermediate, 27.8% (n=10) low risk and 2.8% (n=1) very low risk. Sixteen of 23 (70%) tested cases had KIT (14 exon 11 and two exon 9) mutations. Six tumors were wild type. Exon 11 deletions (p.I563-L576 del and p.V559-N566delinsD) significantly correlate with disease recurrence (p-value: 0.028). Conclusions: Sudanese patients with GIST tend to present late. Nearly half of them correspond to the malignant/high-risk category. The frequency of KIT mutations (79.31%) is in line with the literature.

Differential diagnosis of malignant epithelial tumours in the liver: an immunohistochemical study on liver biopsy material.

INTRODUCTION: A variety of primary and secondary malignant tumours may present in the liver. In clinical practice the most commonly encountered hepatic tumours are primary hepatocellular carcinoma, metastatic carcinoma and primary cholangiocarcinoma, each with its separate prognostic and management implications. When these tumours are poorly differentiated and the biopsy size is limited to a needle core, the distinction can be extremely difficult. MATERIAL AND METHODS: All liver tumours reported between 1994 and 2004 were examined. Slides from each case were tested separately with each of nine antibodies (HepPar1, CD10, MOC31, Villin, pCEA, mCEA, CK7, CK19, and CK20). RESULTS: Liver biopsy tissue from 53 patients was examined in this retrospective study. The 53 liver biopsies were classified thus: hepatocellular carcinoma (n = 23); metastatic adenocarcinoma (n = 15); cholangiocarcinoma (n = 5); metastatic small cell carcinoma (n = 7); liver cell dysplasia (n = 1); carcinoid (n = 1); and unclassified (n = 1). Sensitivity and specificity values for different antibodies in relation to their positive staining of specific tumours was as follows: HepPar1 for HCC-81.8% and 100%; MOC31 for MA-73.3% and 92.1%; MOC31 for MA and CC as a combined group-65% and 100%; pCEA (canalicular) for HCC-82.6% and 83.3%; mCEA for MA-93.3% and 75.6%; CK7 for CC-100% and 68%; CK19 for MA and CC as a combined group-90% and 86.3%. CONCLUSIONS: An antibody panel consisting of HepPar1, pCEA, CK19 and CK7 together with either MOC31 or mCEA is recommended for use in the differential diagnosis of HCC, MA and CC.

Vitamin D level and its determinants among Sudanese Women: Does it matter in a sunshine African Country?

BACKGROUND: Vitamin D deficiency is a worldwide concern. The aim of the current study was to determine the vitamin D level and its contributing factors in Sudanese women. METHODS: In this cross-sectional study, 251 Sudanese women attending Family Health Centers in Khartoum, Sudan were interviewed. Following the exclusion of confounding factors, samples from 190 women were analzsed. Serum 25 hydroxyvitamin D "25(OH) D" was quantified using competitive electrochemiluminescence immunoassay. RESULTS: Participants' age ranged from 18 to 85 years with a mean age (±SD) of 40.2 (±14.06) years. The mean (±SD) vitamin D level was 13.4 (±6.72) ng/ml, ranged 3.00-36.5 ng/ml and the median was 12.7 ng/mL. In total, 157 out of 190 (82.6%) had vitamin D serum levels below 20 ng/ml (deficient); of whom, 52 (27.4%) were in the age group 21-30 years (P value = 0.228). The correlation between vitamin D level and residence outside Khartoum, sun-exposed face and hands, and face and limbs in comparison with being completely covered were found to be statistically significant (p values 0.008, 0.023, and 0.036). CONCLUSION: This study displayed a high percentage (82.6%.) of vitamin D deficiency among women in Sudan, and this in part may indicate that sunshine alone cannot guarantee vitamin D sufficiency in the tropics. Family physicians in tropical countries should screen those with clinical presentations related to vitamin D deficiency.

Serum vitamin D level, sun-exposed area, dietary factors, and physical activity as predictors of invasive breast cancer risk among Sudanese women: A case-control study.

BACKGROUND: The role of vitamin D in the development, progression, and prognosis of breast cancer, though widely studied worldwide, has been inconclusive. This study intended to assess the role of some factors (including serum vitamin D level, sun-exposed area, dietary factors, and physical activity) as predictors of the development of invasive breast cancer (IBC) among Sudanese women. METHODS: A case-control study was conducted on 200 Sudanese women (100 with newly diagnosed IBC and 100 matched healthy females). Serum 25-hydroxyvitamin D was measured through a competitive electrochemiluminescence immunoassay. Matching analysis was adopted by R version 3.4.1 making use of the "MatchIt" package for calculating propensity scores to build a confounder-adjusted, multiple generalized, linear logistic regression model. RESULTS: Participants' age ranged from 28 to 85 years with a mean [±standard deviation (SD)] of 48.10 (±12.11) years. The mean (±SD) serum vitamin D level was 12.97 (±8.60) and 13.79 (±6.79) ng/mL in breast cancer and noncancer Sudanese women, respectively [P = 0.013; odds ratio (OR) 0.862; 95% confidence interval (CI) 0.766-0.969; ß = 0.149)]. Sun-exposed area (P = 0.038; OR 0.013; 95% CI 0.000-0.782; ß = 4.339) is significantly and negatively associated with breast cancer development. While moderate physical activity (P = 0.0008; OR 2625.430; 95% CI 26.647-258673.001; ß = 7.873) is significantly and positively associated with IBC risk. Occasional consumption of milk, dairy products, eggs, and fish reduces the risk of developing IBC by 78.1%, 75.0%, 78.4%, and 76.4%, respectively. CONCLUSION: The higher the plasma vitamin D level by one unit, the lower the risk of breast cancer by 13.84%. Sedentary lifestyle, reduced sun-exposed skin area, and low serum vitamin D levels can be considered as predictors of IBC. Encouraging moderate physical activity and consumption of certain foods may, in part, decrease the precipitating risks of breast cancer. More studies and research are needed to confirm these findings.