• Adenochondroma of the Thyroid in a 3-Year-Old Female: A Case Report

      Teplitzky, T.B.; Okonkwo, N.; Papadimitriou, J.C.; Pereira, K.D. (SAGE Publications Ltd, 2019)
      Follicular adenomas are the most common benign thyroid neoplasm but are unusual in children. However, other rare degenerative lesions and those of developmental origin can also present as thyroid masses. This article reports the first described pediatric thyroid adenochondroma. A 3-year-old female presented with a hard mass in the right lobe of her thyroid with nondiagnostic imaging and cytology findings. She underwent a right thyroid lobectomy uneventfully. Final histopathology examination confirmed an adenochondroma. To the best of our knowledge, an adenochondroma of the thyroid gland in a child has not been previously reported in literature. Though a rare and benign entity, thyroid adenochondromas present clinically with many features concerning for malignancy. Therefore, these lesions should be considered in the differential diagnosis of pediatric thyroid masses. Copyright: The Author(s) 2019.
    • Epidemiology and Pathophysiology of Glomerular C4d Staining in Native Kidney Biopsies

      Drachenberg, C.B.; Papadimitriou, J.C.; Chandra, P.; Haririan, A.; Mendley, S.; Weir, M.R; Rubin, M.F. (Elsevier Inc, 2019)
      Introduction: Routine C4d staining in renal transplantation has stimulated its use in kidney biopsies with glomerulonephritis (GN). Methodical description on staining patterns in the native kidney is not available. Methods: We retrospectively evaluated C4d staining in formalin-fixed paraffin-embedded sections from 519 native kidney biopsies (bx) with and without glomerular disease. Results: Strong C4d staining was consistently present in immune-complex GN, including lupus nephritis (LN) (n = 68), membranous GN (n = 24), membranoproliferative glomerulonephritis (MPGN) pattern (n = 22), fibrillary GN (n = 3), and proliferative GN with monoclonal IgG (n = 3). C4d stained all cases of postinfectious GN (n = 7) amyloidosis (n = 20) and C1q GN (n = 3). In contrast, IgA nephropathy (IgAN) (n = 34), was negative in 62% of bx, with the rest staining variably. The E1 Oxford classification score correlated with capillary wall C4d staining (P = 0.05). C4d marked the glomerular and arteriolar lesions in thrombotic microangiopathy (TMA; n = 16), the glomerular sclerotic segments in focal segmental glomerulosclerosis (FSGS; n = 77), and marked areas of necrosis in crescentic GN (n = 21). In diabetic glomerulopathy (n = 70), C4d marked advanced insudative lesions but was negative otherwise. C4d weakly stained the mesangium, or was negative in normal biopsies (n = 13), minimal change disease (MCD; n = 21), thin basement membrane disease (n = 20), Alport (n = 3), IgM nephropathy (n = 2), C3 glomerulopathy (n = 5), acute interstitial nephritis (n = 12), acute tubular necrosis (n = 22), ischemic glomerulopathy/nephrosclerosis (n = 23), and other miscellaneous processes (n = 14). Staining in tubular basement membranes and peritubular capillaries was most common in lupus. Conclusion: Based on reliable staining in lupus and membranous GN, C4d staining is potentially useful as a screening and diagnostic tool, if only paraffin-embedded tissue is available. Knowledge of C4d staining patterns in normal and pathological tissues enhances its diagnostic value.
    • Soluble Sema4D in Plasma of Head and Neck Squamous Cell Carcinoma Patients Is Associated With Underlying Non-Inflamed Tumor Profile

      Younis, R.H.; Ghita, I.; Elnaggar, M.; Chaisuparat, R.; Theofilou, V.I.; Dyalram, D.; Ord, R.A.; Davila, E.; Tallon, L.J.; Papadimitriou, J.C.; et al. (Frontiers Media S.A., 2021-03-11)
      Semaphorin 4D (Sema4D) is a glycoprotein that is expressed by several tumors and immune cells. It can function as a membrane bound protein or as a cleaved soluble protein (sSema4D). We sought to investigate the translational potential of plasma sSema4D as an immune marker in plasma of patients with head and neck squamous cell carcinoma (HNSCC). Paired peripheral blood and tumor tissue samples of 104 patients with HNSCC were collected at the same time point to allow for real time analysis. Scoring of the histological inflammatory subtype (HIS) was carried out using Sema4D immunohistochemistry on the tumor tissue. sSema4D was detected in plasma using direct ELISA assay. Defining elevated sSema4D as values above the 95th percentile in healthy controls, our data showed that sSema4D levels in plasma were elevated in 25.0% (95% CI, 16.7-34.9%) of the patients with HNSCC and showed significant association with HIS immune excluded (HIS-IE) (p = 0.007), Sema4D+ve tumor cells (TCs) (p = 0.018) and PD-L1+ve immune cells (ICs) (p = 0.038). A multi-variable logistic regression analysis showed that HIS was significantly (P = 0.004) associated with elevated sSema4D, an association not explained by available patient-level factors. Using the IO-360 nanoString platform, differential gene expression (DGE) analysis of 10 HNSCC tumor tissues showed that patients with high sSema4D in plasma (HsS4D) clustered as IFN-? negative tumor immune signature and were mostly HIS-IE. The IC type in the HsS4D paired tumor tissue was predominantly myeloid, while the lymphoid compartment was higher in the low sSema4D (LsS4D). The Wnt signaling pathway was upregulated in the HsS4D group. Further analysis using the IO-360, 770 gene set, showed significant non-inflamed profile of the HsS4D tumors compared to the LsS4D. In conclusion, our data reveals an association between sSema4D and the histological inflammatory subtype. Copyright Copyright Copyright 2021 Younis, Ghita, Elnaggar, Chaisuparat, Theofilou, Dyalram, Ord, Davila, Tallon, Papadimitriou, Webb, Bentzen and Lubek.
    • Tubular Epithelial and Peritubular Capillary Endothelial Injury in COVID-19 AKI

      Papadimitriou, J.C.; Drachenberg, C.B.; Kleiner, D.; Choudhri, N.; Haririan, A.; Cebotaru, V. (Elsevier Inc., 2020-11-05)