Hereditary Leiomyomatosis and Renal Cell Carcinoma: A Case Report and Review of the Literature.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic disorder, and individuals tend to develop multiple cutaneous leiomyomas, uterine leiomyomas, and renal cell cancer (RCC). In our study, we report the first case in Saudi Arabia, to our knowledge - a 28-year-old male with a history of right leg leiomyosarcoma post excision two years back who was referred to us with incidental finding of right kidney mass measuring 1.8x2x2.2 cm who underwent right laparoscopic radical nephrectomy, and histopathology reported it as HLRCC and RCC.

Clinicopathologic features and therapy outcome in childhood Hodgkin's lymphoma: a report from tertiary care center in Saudi Arabia.

BACKGROUND: Hodgkin lymphoma (HL) is lymphoid neoplasm usually affecting lymphatic system; it accounts 3.6% of cancers in Saudi Arabia. Modern treatment protocols had shown particular success rates in overall-survival (OS) and event-free-survival (EFS). In our study, we reviewed the medical records of 80 pediatric and young adolescent patients diagnosed HL from January 2006 to July 2020, treated at tertiary care hospital in Riyadh, Saudi Arabia. Demographic, clinical, and pathological data were explored. First line therapy was ABVD, COG, COPP, R-CHOP, or radiotherapy alone in 53/80 (66.4%), 24/80 (30%), 1/80 (1.2%), 1/80 (1.2%), or 1/80 (1.2%) patients; respectively. Response assessment was done by CT + / - PET scan after first 2 cycles then every 2 cycle and end of therapy. Another assessment was done if any clinical suspicion of recurrence. RESULTS: Median age 11 (range 3-16) years. Males to females 1.3:1. Seventy-two out of eighty (90%) patients showed first complete remission (CR1) and maintained remission for median 40 (range 7-136) months. Eight out of eighty (10%) patients showed refractory disease. Nineteen patients received salvage therapy (ICE or ESHAP/brentuximab vedotin or gemcitabine/brentuximab vedotin), 14/19 (73.7%) had 2nd complete remission (CR2) for median time 24 (ranged 9-78) months, while 5/19 (26.3%) did not show any response. Five-year OS and EFS were 95% and 75%. Two patients had 2ry malignant neoplasms, one had AML and died, the other had malignant fibrous histocytoma and still alive. None of our patients had fertility problem. Also, they did not experience chronic pulmonary or cardiotoxicity. Classic Hodgkin's lymphoma: nodular sclerosis subtype was more prominent (55%) than mixed cellularity subtype (22.5%), which is similar to several European and US studies, lymphocyte rich (11.25%) and lymphocyte depleted (0%), while nodular lymphocyte predominant Hodgkin's lymphoma (11.25%). CONCLUSIONS: Our study provided unique descriptive study of childhood HL, in Saudi Arabia, with valuable insight into the long-term outcome and late toxicity. Our results are comparable to other studies in the Middle East and European countries.

Risk Stratification of Thyroid Nodules with Bethesda III Category: The Experience of a Territorial Healthcare Hospital.

Background The Bethesda System for Reporting Thyroid Cytolopathology (TBSRTC) is the standardized category-based reporting system for thyroid nodule (TN) aspirations; however, atypia of undetermined significance/follicular lesion of undetermined significance (Bethesda category III, AUS/FLUS) is the most controversial category. The aim of this study was to identify the degree of malignancy risk and the related risk factors in the surgical pathology of the Bethesda Category III thyroid nodules.  Methods A total of 4074 patients (15-90 years, 81.5% of females) were subjected to retrospective analysis, and a total of 463 nodules were classified as Bethesda Class III and included in the analysis. Once all the thyroid cytopathological slides and ultrasound (US) reports were reviewed, they were classified according to the Bethesda System for Reporting Thyroid Cytology, the American College of Radiology (ACR) and the Thyroid Imaging Reporting and Data System (TI-RADS). Results Among the 463 Bethesda class III nodules, 167 nodules were surgically excised, showing an overall malignancy of 27.6% (n = 46/167). Patients having thyroid-stimulating hormone (TSH) levels of >4.5 mIU/L (35%), TN <2 cm (34.6%), solid or nearly solid (28.7%), highly hypoechoic (58.3%), longer than wide (50%), lobulated (45.5%), punctate echogenic (48.6%), ACR TI-RAD 5 (55.2%) and falling under the ATA category of high suspicion (50%), displayed a higher risk of malignancy (ROM). The chi-square test revealed a strong association between the echogenicity, echogenic foci, ACR TI-RAD and American Thyroid Association (ATA) category between the malignant and benign nodules. The papillary thyroid carcinoma (PTC) follicular variant (39%) and PTC classical (27%) were identified, in this study population, as the commonest forms of thyroid cancer. Conclusion The nodules with AUS/FLUS cytology malignancy rate are comparable with the earlier estimations of other countries. The ACR TI-RAD displayed more accurate diagnostic performances in predicting malignancy in the Bethesda III nodules. However, to confirm the accuracy of the molecular marker tests in specific cytological scenarios, more extensive studies are required in the future.

Biallelic Mutations in Tetratricopeptide Repeat Domain 26 (Intraflagellar Transport 56) Cause Severe Biliary Ciliopathy in Humans.

BACKGROUND AND AIMS: The clinical consequences of defective primary cilium (ciliopathies) are characterized by marked phenotypic and genetic heterogeneity. Although fibrocystic liver disease is an established ciliopathy phenotype, severe neonatal cholestasis is rarely recognized as such. APPROACH AND RESULTS: We describe seven individuals from seven families with syndromic ciliopathy clinical features, including severe neonatal cholestasis (lethal in one and necessitating liver transplant in two). Positional mapping revealed a single critical locus on chromosome 7. Whole-exome sequencing revealed three different homozygous variants in Tetratricopeptide Repeat Domain 26 (TTC26) that fully segregated with the phenotype. TTC26 (intraflagellar transport [IFT] 56/DYF13) is an atypical component of IFT-B complex, and deficiency of its highly conserved orthologs has been consistently shown to cause defective ciliary function in several model organisms. We show that cilia in TTC26-mutated patient cells display variable length and impaired function, as indicated by dysregulated sonic hedgehog signaling, abnormal staining for IFT-B components, and transcriptomic clustering with cells derived from individuals with closely related ciliopathies. We also demonstrate a strong expression of Ttc26 in the embryonic mouse liver in a pattern consistent with its proposed role in the normal development of the intrahepatic biliary system. CONCLUSIONS: In addition to establishing a TTC26-related ciliopathy phenotype in humans, our results highlight the importance of considering ciliopathies in the differential diagnosis of severe neonatal cholestasis even in the absence of more typical features.