Publications Spotlighted

Johns Hopkins Pathology Takes Center Stage:

Johns Hopkins Pathology has been the number one NIH funded pathology department for 11 of the past 12 years.

Our research interests span a broad area— we highlighted a few research discoveries.

• Unique T Cells Grab Attention in AKI

Abdel-Rahim A. Hamad, M.V.Sc., Ph.D.
Hamad Lab website

Unique T Cells Grab Attention in AKI

Sadasivam M, Noel S, Lee SA, Gong J, Allaf ME, Pierorazio P, Rabb H, Hamad ARA. Activation and Proliferation of PD-1+ Kidney Double-Negative T Cells Is Dependent on Nonclassical MHC Proteins and IL-2. J Am Soc Nephrol 2019 Feb;30(2):277-92.

The kidney is the most transplanted human organ and a major autoimmune target. T cells play central roles in mediating both conditions. They do so by recognizing antigens derived from donated organs or autoantigens tethered to clefts in major histocompatibility (MHC) molecules. In this study, Dr. Sadasivam from Hamad's lab and his colleagues in Dr. H. Rabb demonstrated that a unique non-conventional T cell population that resides in mouse kidney is not restricted by MHC molecules. These lymphocytes are referred to as double negative (DN) T cells because they lack expression of CD4 and CD8 coreceptors. These DN T cells, led by a subset that expressed the checkpoint inhibitor PD-1, are highly responsive to changes in their milieu (e.g. ischemia or blood transfusion) and have potent immunoregulatory functions. A phenotypically similar population is identified in biopsies samples from human kidneys. Given the deciding role for MHC molecules in determining the outcome of organ transplant and autoimmune processes, better understanding of kidney DN T cells could have important implications for developing immunomodulatory strategies that promote kidney transplant and ameliorate kidney autoimmune diseases.

• New Clues Found to Distinguish ALES from Other Salivary Gland Carcinomas

Lisa Michelle Rooper, M.D.
Faculty Profile

New Clues Found to Distinguish ALES from Other Salivary Gland Carcinomas

Rooper LM, Jo VY, Antonescu CR, Nose V, Westra WH, Seethala RR, Bishop JA. Adamantinoma-like Ewing Sarcoma of the Salivary Glands: A Newly Recognized Mimicker of Basaloid Salivary Carcinomas. Am J Surg Pathol. 2019 Feb;43(2):187-94.

Adamantinoma-like Ewing Sarcoma (ALES) is a rare subtype of Ewing Sarcoma that demonstrates diffuse cytokeratin positivity and overt squamous differentiation and most commonly arises in head and neck sites. Although classification of these lesions remains controversial, differentiating these tumors from the carcinomas they mimic is important to allow consideration of Ewing Sarcoma-specific therapy. This paper provides the first immunohistochemical and molecular characterization of a large series of 10 ALES involving major salivary glands and discusses how to differentiate them from basaloid salivary carcinomas.

• Crucial Role for Cytopathology in HPV-Related Small Cell Carcinoma of Oropharynx

Syed Z. Ali, M.B.B.S., M.D.
Faculty Profile

Crucial Role for Cytopathology in HPV-Related Small Cell Carcinoma of Oropharynx

Allison DB, Rooper LM, Mustafa S, Maleki Z, Wakely PE Jr, Ali SZ. Cytopathologic characteristics of HPV-related small cell carcinoma of the oropharynx. Cancer Cytopathol 2019 Feb;127(1):35-43. PMID: 30468701

Human papillomavirus-related small cell carcinoma of the oropharynx is a rare and newly described entity with an aggressive clinical course. Herein, the authors present the first study of human papillomavirus-related small cell carcinoma of the oropharynx in cytology preparations. Both squamous and small cell components were present in half of the cases; however, all samples from distant metastases showed exclusively small cell differentiation, supporting the hypothesis that it is this component that drives the aggressive clinical course. Importantly, the recognition of small cell morphology can be reliably distinguished on FNA material without the need for immunohistochemical studies. This finding is crucial because recognizing a component of small cell differentiation (and not the HPV status) in an oropharyngeal squamous cell carcinoma determines the prognosis. Unfortunately, all patients in this study died of disease within 12 to 48 months from the time of their first diagnosis.

• Accessory to Crime: Pro-tumorigenic Activity of Paracrine IL-6 Signaling in Prostate Cancer

Karen Sandell Sfanos, Ph.D.
Sfanos Lab website

Accessory to Crime: Pro-tumorigenic Activity of Paracrine IL-6 Signaling in Prostate Cancer

Yu SH, Maynard JP, Vaghasia AM, De Marzo AM, Drake CG, Sfanos KS. A role for paracrine interleukin-6 signaling in the tumor microenvironment in prostate tumor growth. Prostate 2019 Feb;79(2):215-22.

Interleukin-6 (IL-6) is a mediator of inflammation that can facilitate prostate cancer progression. Shu-Han Yu, Karen Sfanos and colleagues previously demonstrated that IL-6 is present in the prostate tumor microenvironment and is restricted almost exclusively to the stromal compartment. In this new study, the investigators show a significant reduction in tumor growth of allografted mouse prostate cancer cells in mice lacking IL-6. Tumor growth was further shown to likely be dependent on IL-6 expression in cells in the tumor microenvironment, not from tumor cells and elevated systemic IL-6 levels may be involved in tumor growth regulation in prostate cancer. Dr. Shu-Han Yu is a former graduate of the Pathobiology graduate program and is now an Assistant Professor at the National Defense Medical Center, Graduate Institute of Life Science, in Taiwan.