Medicine and Health Sciences Commons^™

Intrahepatic Cholangiocarcinoma Presenting As Li-Rads 5 "Hcc", Raja K. Dhanekula, Md, Donald Mitchell, Md, John Farber, Md, Ashwin R. Sama, Md, Jesse M. Civan, Md

Division of Gastroenterology and Hepatology Posters

Background

• Hepatocellular Carcinoma (HCC), if within Milan Criteria, is an indication for liver transplantation.

• In contrast, intrahepatic cholangiocarcinoma (IHCC) is a contra-indication to liver transplantation due to high rates of recurrence.

• LI-RADS 5 classification (synonymous with OPTN-5) carries a near 100% positive predictive value for HCC, allowing prioritization of patients for liver transplantation without histological confirmation.

• The “LI-RADS M” classification indicates the presence of malignancy not meeting diagnostic criteria for HCC. In theory, IHCC lesions should be identified as LI-RADS M and not LI-RADS 5.

A Novel Comparative Pattern Analysis Approach Identifies Chronic Alcohol Mediated Dysregulation Of Transcriptomic Dynamics During Liver Regeneration., Lakshmi Kuttippurathu, Egle Juskeviciute, Rachael P Dippold, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Liver regeneration is inhibited by chronic ethanol consumption and this impaired repair response may contribute to the risk for alcoholic liver disease. We developed and applied a novel data analysis approach to assess the effect of chronic ethanol intake in the mechanisms responsible for liver regeneration. We performed a time series transcriptomic profiling study of the regeneration response after 2/3(rd) partial hepatectomy (PHx) in ethanol-fed and isocaloric control rats.

RESULTS: We developed a novel data analysis approach focusing on comparative pattern counts (COMPACT) to exhaustively identify the dominant and subtle differential expression patterns. Approximately 6500 genes were differentially regulated …

Mouse Hepatitis Virus Infection Upregulates Genes Involved In Innate Immune Responses., Dhriti Chatterjee, Sankar Addya, Reas S Khan, Lawrence C. Kenyon, Alexander Choe, Randall J Cohrs, Kenneth S Shindler, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Neurotropic recombinant strain of Mouse Hepatitis Virus, RSA59, induces meningo-encephalitis, myelitis and demyelination following intracranial inoculation. RSA59 induced neuropathology is partially caused by activation of CNS resident microglia, as demonstrated by changes in cellular morphology and increased expression of a microglia/macrophage specific calcium ion binding factor, Iba1. Affymetrix Microarray analysis for mRNA expression data reveals expression of inflammatory mediators that are known to be released by activated microglia. Microglia-specific cell surface molecules, including CD11b, CD74, CD52 and CD68, are significantly upregulated in contrast to CD4, CD8 and CD19. Protein analysis of spinal cord extracts taken from mice 6 days post-inoculation, …

Adiponectin Inhibits Tumor Necrosis Factor-Α-Induced Vascular Inflammatory Response Via Caveolin-Mediated Ceramidase Recruitment And Activation., Yajing Wang, Xiaoliang Wang, Wayne Bond Lau, Yuexing Yuan, David Booth, Jing-Jing Li, Rosario Scalia, Kyle Preston, Erhe Gao, Walter Koch, Xin-Liang Ma

Department of Medicine Faculty Papers

RATIONALE: Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered.

OBJECTIVE: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling.

METHODS AND RESULTS: Adiponectin significantly reduced tumor necrosis factor (TNF)α-induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P87% of adiponectin-induced nCDase …

A Case Of Hemoglobinopathy-Thalassemia Syndrome, Michele C. Khurana, B.S., Gene Gulati, Ph.D

Department of Pathology Honors Program Student Research Symposium

Patient Presentation

• 43 year-old African American female presents with left lower extremity pain
• Physical exam: unremarkable
• Past medical history:

Anemic since childhood

Avascular necrosis of left hip

DVT

Chronic illnesses: asthma, depression

Surgical history: appendectomy, tubal ligation, splenectomy, cholecystectomy, L hip replacement

• Family history: mother has lupus

The Line Between Addiction And Medication: Alcohol, Anesthesia, And Analgesia, Priya Joshi, B.S., Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

Alcohol is a particularly dangerous addiction because its consumption is legal even in excess, despite its harmful effects. Because alcohol has a multitude of targets in the central nervous system that are modified during chronic exposure, medications with overlapping targets such as anesthetics and analgesics must be modified when given to alcoholics. Unfortunately, as relatively little is known about the mechanism of addiction, it is difficult to predict how medications will be affected by central adaptation to chronic alcohol exposure. This review summarizes the consequences of alcohol exposure with particular attention to the GABA_Areceptor, and discusses the reasons …

Lumbar Chordoma: A Primary Bone Tumor, Andrew N. Fleischman, Bs, Brian O'Hara, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

• Primary malignant bone tumor of embryonic notochord remnants
• 1-4% of primary bone tumors, <0.1 per 100,000
• Location: Sacral (50%), Skull base (35%), Vertebral column (15%)
• Classic, chondroid (5-15%), and dedifferentiated (5%) variants
• Most commonly in late middle age (50s to 60s)
• Low-grade, slow growing tumor
• But locally aggressive, high rate of local recurrence (20% in 1^st year)
• Local recurrence is most important predictor of mortality
• Metastasis only occurs very late in disease
• Median survival of about 6 years, less than 12 months with mets
• 5 year survival of 70%, 10 year survival of 40%
• Primary therapy- aggressive surgical resection (if possible) …

Transfusion Related Acute Lung Injury, Nadia Abidi, Jay Herman, Md, Julie Karp, Md

Department of Pathology Honors Program Student Research Symposium

A 74 year old woman presented with hematemesis. Her medical history was significant for pulmonary embolism treated with warfarin anticoagulation, fibromyalgia treated with NSAIDs/steroids, and a prior bleeding event from a gastric ulcer. On admission she was stable with a hemoglobin of 8.7 g/dL and a therapeutic INR of 3.19. A type and screen determined a blood type of AB positive. In anticipation of endoscopy, the patient received one unit of red blood cells and four units of type AB plasma. Following transfusion, her INR was 1.83. The patient received an additional four units of type AB plasma to further …

Morphologic And Endoscopic Evaluation Of Collagenous Gastritis, Annie Ashok, Ashlie L. Burkart, Md, Cm

Department of Pathology Honors Program Student Research Symposium

Collagenous gastritis (CG) is a rare gastrointestinal condition of unknown etiology and pathogenesis characterized by the presence of a gastric subepithelial collagen band of variable thickness. While little is known about the disease, children and young adults often present with anemia, abdominal pain, and nodular gastric mucosa on endoscopy. In contrast, adults often present with chronic watery diarrhea and normal gastric mucosa on endoscopy. Disease associations (usually in adult cases) include celiac disease, collagenous colitis, collagenous sprue, and lymphocytic colitis. This study aims to further characterize the clinical, endoscopic and morphologic spectrum of CG.

Thoracic Dissecting Aneurysm And The Importance Of Genetics, Dan Kramer, Ba, Anthony Prestipino, M.D.

Department of Pathology Honors Program Student Research Symposium

Patient Presentation

• 28 year old white male with a past medical history significant for untreated hypertension
• Presents with 3 day history of chest discomfort, lower extremity weakness, bowel and bladder dysfunction, near-syncopal episodes
• Absent pulse in right femoral artery, weak pulse in left femoral artery
• Echosonography showed acute Type A dissecting aortic aneurysm
• Treatment

Immediately taken to surgery for repair of aorta with a graft and replacement of the aortic valve

• Outcome

Unstable after surgery

Biventricular heart failure

Persistent bleeding into mediastinum due to DIC

Required massive transfusion of RBCs, FFP, Cryoprecipitate, and Platelets

Became anuric and acidotic

Became fluid …

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (Dipnech) To Carcinoid: Exploring The Link, Jacob D. Mcfadden Msii, Jeffrey P. Baliff Md

Department of Pathology Honors Program Student Research Symposium

Neuroendocrine cells (NECs) play important roles in normal lung development, autonomic regulation of lung function, and response to hypoxia or injury. They are located between the respiratory epithelium and the basement membrane of bronchi and bronchioles (below), often as single cells or small clusters.

NEC proliferation is a common pathologic occurrence, well established as a reactive response to chronic lung injury. Much less commonly, NEC proliferation is observed in the absence of apparent inciting factors. This neoplastic phenomenon is termed “diffuse idiopathic pulmonary neuroendocrine cell hyperplasia” (DIPNECH).

DIPNECH is recognized as a precursor lesion for carcinoid tumors. While the progression …

Correlations Between Gene Amplification And Protein Expression Of Topoisomerase 2a (Top2a) In Squamous Cell Carcinoma Of The Lung, Anita Modi, Msii, Charalambos C. Solomides, Md

Department of Pathology Honors Program Student Research Symposium

Background: While DNA topoisomerase 2A (TOP2A) plays an essential role in maintaining the structural integrity of the double helix during replication and recombination, excessive expression of this enzyme may promote malignant cell transformations. In fact, increased levels of TOP2A have been observed in various cancer cell lines including squamous cell carcinoma of the lung. This study sought to identify correlations between genotypic and phenotypic evidence of TOP2A obtained via in situ hybridization (ISH) and immunohistochemistry (IHC) techniques.

Methods Tissue microarrays created from 29 samples of Stage I Squamous Cell Carcinoma of the lung were stained with VENTANA BenchMark ULTRA platform …

Temporal Lobe Ganglioglioma In An Epilepsy Patient With Worsening Seizures: Case Study And Future Directions, Adam M. Olszewski, Mark Curtis, Md Phd.

Department of Pathology Honors Program Student Research Symposium

Gangliogliomas are rare brain tumors that have both neuronal and glial components. They hold a better prognosis than other infiltrative glial tumors, but differentiating between them can be challenging. While molecular markers are being studied, it is currently a histologic diagnosis.

In this case, the patient presented with epilepsy and worsening seizures secondary to a medial temporal lobe mass. Radiology report was inconclusive. Surgical resection was achieved and based on histologic examination the lesion was diagnosed as ganglioglioma, WHO grade I.

In this patient, pathological diagnosis of ganglioglioma offers a favorable prognosis and low risk of recurrence. In the future, …

An Unexpected Immunohistochemical Profile In An Ovarian Lesion, Kate Fritton, Joanna Chan, Md

Department of Pathology Honors Program Student Research Symposium

A 27 year old female presented with pelvic pain and a palpable pelvic mass. Upon histological examination, the cystic mass contained a multi-cellular lining with nuclear grooves. Negative inhibin staining ruled out a follicular cyst and granulosa cell tumor while pan-cytokeratin positivity suggested an epithelial lesion. The lesion stained positive for thrombomodulin, ultimately suggesting a diagnosis of a Brenner cell tumor, although CD56 positivity in the tumor questions the known immunohistochemical profile of Brenner cell tumors. This unusual result opens the door to future research into the role CD56 in the diagnosis of ovarian neoplasms.

Myeloid Sarcoma: Extramedullary Relapse After Allogeneic Bone Marrow Transplant For Chronic Myelogenous Leukemia, Maria Gubbiotti, Alina Dulau Florea, Md, Renu Bajaj, Phd

Department of Pathology Honors Program Student Research Symposium

Myeloid sarcoma (MS) is an extramedullary tumor of myeloid precursor cells, which can precede or occur concomitantly with acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms. Although MS can involve any organ, it is more common in the central nervous system (CNS) and gonads, sites known as “pharmacologic sanctuaries” where leukemic cells can survive despite systemic chemotherapy. Less often, this tumor can be the manner of relapse after allogeneic bone marrow transplantation.

The diagnosis is based on morphology and immunophenotype by either flow cytometry or immunohistochemistry of paraffin-embedded tissue, and confirmed by FISH or molecular studies. Myeloid sarcomas usually express …

Adenoid Cystic Carcinoma In Unusual Locations – Differential Diagnosis Difficulties, Heather A. Mcmahon, B.S., Madalina Tuluc, Md

Department of Pathology Honors Program Student Research Symposium

Adenoid Cystic Carcinoma (ACC) is an uncommon malignant salivary gland tumor, representing 1% of all malignant tumors of the oral and maxillofacial region and 22% of all salivary gland malignancies. Although in the majority of cases ACC manifests in the major salivary glands, in rare instances it can be found in locations such as the esophagus, larynx, trachea, lacrimal gland, breast, prostate, lungs, or auditory canal. These unusual locations of ACC often pose a diagnostic challenge to the clinician and are associated with poorer outcomes for patients as compared to those ACC of a more typical presentation. In this study …

Ocular Manifestations Of Rosai-Dorfman Disease, Phoebe L. Mellen, B.S., Ralph C. Eagle Jr., M.D.

Department of Pathology Honors Program Student Research Symposium

History of Rosai-Dorfman Disease

In 1969, Dr. Juan Rosai and Dr. Ronald F. Dorfman reported four cases of an entity that previously had puzzled pathologists and clinicians. The four cases had failed to fit under any diagnosis, but shared a few common characteristics. Each patient presented with painless, massive lymphadenopathy, most commonly of the cervical lymph nodes¹. Other locations included the inguinal, intra-parotid, and axillary lymph nodes. The patients all presented with fever and leukocytosis¹. The differential diagnosis included malignant lymphoma, malignant histiocytosis, reticuloendotheliosis, and chronic inflammation. However, the histopathological characteristics of the cases did not …

Diagnostic Yield Of Endobronchial Ultrasound-Guided Fine Needle Aspiration (Ebus-Fna) In Lung Cancer Staging, Subtyping And Diagnosis Of Unexplained Mediastinal Lymphadenopathy, Rino Sato, Rossitza Draganova-Tacheva, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

• Lung cancer (LC) is the most commonly diagnosed cancer worldwide and the most frequent cause of cancer death in both men and women in the US (more deaths than the next three most common cancers combined)¹
• Clinical staging of LC is an integral part of patient care because it directs therapy and has prognostic value

Patients are routinely investigated with a conventional workup (medical history, PE, lab tests, bronchoscopy), CT and integrated whole-body PET-CT, followed by mediastinal tissue staging for enlarged or PET-positive intrathoracic nodes²

• Mediastinal tissue staging has been classically performed by mediastinoscopy, but they can …

Melanocytoma Of The Cerebellopontine Angle, Pranay Soni, M.D, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Ms. M.G. is a 46-year-old woman with a history of hypertension and prior bilateral laser eye surgery. In 2009, she presented with vertigo, tinnitus, and decreased hearing in the left ear. An MRI scan revealed an enhancing mass in the posterior fossa that was thought to be an acoustic neuroma. In May of 2009, she underwent gamma-knife radiotherapy for the 2.7 cm mass.

In September of 2012, M.G. noted progressive change in her voice quality as well as a swallowing disturbance and left facial spasms. A subsequent MRI showed significant enlargement of the tumor to a maximal size of 3.7 …

Aplastic Anemia Post Liver Transplant Due To Graft-Versus-Host Disease, Ping Gong, Md, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Poster presented at: American society for clinical pathology (ASCP) conference 2012, Boston MA, USA.

Introduction:

The patient was a 64-year-old male presented with a 2 day history of increasing fevers and altered mental status. He underwent orthotopic liver transplant for cryptogenic cirrhosis, probably secondary to non-alcoholic steatohepatitis, 45 days before. The head and neck imaging showed pancytopenia with WBC 0.6 x 109 /L., hemoglobin 6.8 g/dl and platelet 29 x 109 /L.

An Autopsy Case Of Alveolar Capillary Dysplasia, Yu Shi, John Farber

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Poster presented at College of American Pathologist 2012 in San Diego California.

Patient:

Chief Complaint: A full term, newborn girl developed respiratory distress shortly after birth.

Proline-Rich Tyrosine Kinase 2 (Pyk2) Regulates Igf-I-Induced Cell Motility And Invasion Of Urothelial Carcinoma Cells, Marco Genua, Shi-Qiong Xu, Simone Buraschi, Stephen C. Peiper, Leonard G. Gomella, Antonio Belfiore, Renato V. Iozzo, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The insulin-like growth factor receptor I (IGF-IR) plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. We have recently demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues and promotes motility and invasion of urothelial carcinoma cells. These effects require IGF-I-induced Akt- and MAPK-dependent activation of paxillin. The latter co-localizes with focal adhesion kinases (FAK) at dynamic focal adhesions and is critical for promoting motility of urothelial cancer cells. FAK and its homolog Proline-rich tyrosine kinase 2 (Pyk2) modulate paxillin activation; however, their role in regulating IGF-IR-dependent signaling and motility in …

P16/Rb Correlations In Oropharyngeal Squamous Cell Carcinoma (Oscc), Madalina Tuluc, Voichita Bar-Ad, David Cognetti

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The objective of this study is to explore the patterns of Rb expression in p16 positive and negative OSCC, in relation to patient's smoking history.

Expression Of Stem Cell Marker Aldh1 In Cervical Intraepithelial Neoplasia, Ping Gong, Juan Palazzo, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Cervical dysplasia show positive staining for ALDH1 compared to normal cervical mucosa.

ALDH1 positive cells distribution parallels the dysplastic cells in cervical dysplasia.

CSC, as detected by ALDH1 expression, may play a role in the progression of cervical intraepithelial neoplasia and carcinogenesis.

P53 Expression In Oropharyngeal Squamous Cell Carcinoma In Increased In Hpv Positive Smokers, Madalina Tuluc, Voichita Bar-Ad, Zi-Xuan Wang, Joseph Curry

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background and Objectives

High risk HPV is associated with oropharyngeal SCC (OSCC) and is responsible for the increasing incidence of this cancer type among younger patients.

Patients with HPV positive oropharyngeal SCC have a better prognosis when compared with HPV negative, tobacco induced SCC.

HPV E6 inactivates p53 leading to low expression of p53; tobacco induced oropharyngeal SCC is characterized by p53 overexpression, resistance to treatment and poor prognosis. However, in many cases of HPV OSCC, there is a history of current or remote smoking, making this disease a multifactorial process. We expect that smoking will influence the level of …

Aberrant Expression Of Cd56 On Granulocytes And Monocytes In Myeloproliferative Neoplasm And Myelodysplastic Syndrome, Ping Gong, Md, Fernanco Metrebian, Md, Alina Dulau-Florea, Md, Zi-Xuan Wang, Phd, Renu Bajaj, Phd, Stephen C Peiper, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Aberrant CD56 expression on granulocytes is seen in all aubtypes MPN and high grade MDS. CD56 expression in MPN correlated with bone marrow morphology, BCR/ABL transcript, and bone marrow engraftment study following treatment. Identification of abnormal CD56+ granulocytes and monocytes is helpful in both the initial diagnosis and long-term follow up of patients with MPN and MDS.

Loss Of Retinoblastoma (Rb) Tumor Suppressor Expression In Breast Cancer Correlates With Better Response To Neoadjuvant Chemotherapy, Jeanne Mcfalls, Md, Jessica Kline, Ba, Gordon Schwartz, Md, Mba, Facs, Angieszka Witkiewicz, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Loss of RB tumor suppressor staining in pre-treatment breast cancer biopsies can be used prior to initiation of neoadjuvant chemotherapy to predict good tumor response. This association between RB loss and good neoadjuvant response holds regardless of ER status and across various chemotherapy regimens. Assessment of RB status in the pre-treatment biopsy could be useful clinical tool to define patients who are most likely to benefit from neoadjuvant chemotherapy.

A Conserved Tissue-Specific Homeodomain-Less Isoform Of Meis1 Is Downregulated In Colorectal Cancer., Richard C Crist, Jacquelyn J Roth, Scott A Waldman, Arthur M Buchberg

Department of Microbiology and Immunology Faculty Papers

Colorectal cancer is one of the most common cancers in developed nations and is the result of both environmental and genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encode homeodomain transcription factors. The MEIS1 homeobox gene is known to be involved in several hematological malignancies and solid tumors and recent evidence suggests that expression of the MEIS1 transcript is altered in colorectal cancer. Despite this potential connection, little is known about the role of the gene in the intestines. We probed murine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing …

The Variable Presentations Of Anaplastic Spindle Cell Squamous Carcinoma Associated With Tall Cell Variant Of Papillary Thyroid Carcinoma., Pallavi P Gopal, Kathleen T Montone, Zubair Baloch, Madalina Tuluc, Virginia Livolsi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: In 1976, Hawk and Hazard described the tall cell variant (TCV) of papillary thyroid carcinoma (PTC). While the lesions they described had cytologic features of papillary carcinoma, they showed more aggressive behavior with a greater propensity for extrathyroid extension and lymphovascular invasion than classic PTC. In 1991, Bronner and LiVolsi described a series of patients with TCV that progressed to spindle cell squamous carcinoma (SCSC), a unique form of anaplastic thyroid carcinoma. This study describes the variable clinical and pathologic presentations in 31 patients with anaplastic SCSC arising in association with TCV.

METHODS: The surgical pathology archives as well …

A Compact Guide To The Diagnosis And Management Of Neurofibromatosis Type 1, Timothy Beer, David Strayer, Md, Phd

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Brief Introduction

Neurofibromatosis type 1 (NF-1) is a multisystem neurocutaneous disorder resulting from mutations in the NF-1 gene on chromosome 17 (q11.2). Mutations in NF-1 result in deficient activity of the tumor suppresor protein neurofibromin, allowing for uncontrolled constitutive activity of the proliferative Raspathway in several neural cell types, including neurons, oligodendrocytes, astrocytes and Schawnn cells. Half of NF-1 cases are inherited in autosomal dominant fashion, while half develop sporadically. The syndrome has 100% penetrance but highly variable expressivity. The prevalence of this syndrome is 1/3,000, making it common enough to warrant YOU, the physician, taking a moment to learn …