Medicine and Health Sciences Commons^™

Comparison Of Two Quantitative Image Analysis Systems For Breast Cancer Immunohistochemistry, Reid H. Phillips, Bs, Sue Direnzo, Bs, Charalambos C. Solomides, Md

Department of Pathology Honors Program Student Research Symposium

Automated image analysis systems for breast cancer immunohistochemistry promise efficiency and reliability in the quantification of therapy targets such as the estrogen receptor (ER) or human epidermal growth factor receptor (Her2). Thomas Jefferson University Hospital owns two such systems, the Aperio ScanScope AT (Leica Biosystems) and Ventana iScan Coreo (Roche). A comparison study was performed to determine if choice of system affects target quantification and subsequent clinical tumor classification. Tumor expressions of ER, progesterone receptor (PR), proliferation marker Ki67, and Her2 were quantified with both systems for tissue samples from twenty breast cancer patients. Positive tumor classification was based on …

Evaluating The Utility Of Thyroglobulin Wash Testing In The Management Of Well-Differentiated Thyroid Carcinoma, Katelyn M. Seither, Rossitza Draganova-Tacheva, Md

Department of Pathology Honors Program Student Research Symposium

Introduction

• Thyroid cancer is the most common endocrine neoplasm worldwide, representing 1.7% of new cancer diagnoses and 0.5% of cancer deaths each year (Baldini et al.)
• The majority of thyroid cancers are primary (originating within the gland itself), are well-differentiated, and are derived from follicular epithelial cells
• Papillary thyroid cancer is the most common subtype

70-80% of all thyroid cancers

Peak incidence in women of child-bearing age

Generally indolent behavior, excellent prognosis with total thyroidectomy

30-90% of patients exhibit recurrent or persistent metastasis to the cervical lymph nodes (Torres et al.) and 20% of cases present with occult cancer that …

The Intersection Between Hpv And Hiv Infections: Is There An Increased Susceptibility To Hiv Acquisition In Hpv-Infected Women?, Montida Fleming, Ba, Fred Gorstein, Md

Department of Pathology Honors Program Student Research Symposium

It has been well documented that HIV infection is associated with HPV infection and the progression to cervical carcinoma. Since the spread of HIV/AIDS epidemic, HPV-related cervical carcinoma had such a high prevalence in HIV-infected individuals that it became established as an AIDS-defining illness. Cervical cancer is the most common AIDS-related malignancy, and the sixth most common presenting AIDS-defining illness in women.¹ Additionally, HIV infection leads to a 5-fold increase in multiple new HPV infections within 6 weeks of seroconversion.² Not only does HIV impact acquisition of HPV at molecular and cellular levels, HIV and HPV viruses interact …

20 Year-Old Male With Destructive Lesion Of Orbital Roof, Paris A. Barkan, Bs, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Patient History

Mr. G.R. is a 20-year-old man with no significant past medical history. He presented in July of 2013 with two months of worsening pain over the right orbit. Periorbital edema was also present. Initial treatment with eye drops, antibiotics (erythromycin followed by cephalexin), and steroids (prednisone) failed to control his symptoms.

In October of 2013, CT and MRI scans revealed a permeative destructive lesion centered in the right orbital roof with extension into the superior orbit and the floor of the anterior cranial fossa. There was no abnormal enhancement in the visualized brain parenchyma.

The radiologic appearance of …

Mechanisms That Modify Immune Response In Neonatal Alloimmune Thrombocytopenia, Robert Cooper, Jay H. Herman

Department of Pathology Honors Program Student Research Symposium

What is NAIT?

Neonatal alloimmune thrombocytopenia (NAIT) is a form of fetal and neonatal thrombocytopenia caused by maternal-fetal platelet antigen incompatibility that results in placental transfer of maternal IgG alloantibodies against the platelet antigen. Currently, there are 28 human platelet antigen systems (HPA) that are polymorphisms of various membrane glycoprotein (GP) integrins. The first HPA and most immunogenic was discovered in the 1960’s and is now termed HPA-1, a diallelic system with HPA-1a and HPA-1b on the GPβ3 subunit of the fibrinogen receptor (Murphy). Approximate HPA-1 phenotype frequencies are: homozygous 1a,1a (~70%); heterozygous 1a,1b (~28%); homozygous 1b,1b (~2%).

Typically an …

Lead Toxicity: What Is It And How Is It Happening?, Kimberly A. Parada, Ba, Jay S. Schneider, Phd

Department of Pathology Honors Program Student Research Symposium

EPIDEMIOLOGY

Lead poisoning accounts for 0.6% of the global burden of disease.

In Pennsylvania in 2010, 148,751 children under 72 months of age were tested for blood lead levels. Of those children, 19,176 had blood lead levels greater than 5 μg/dl.

• A lower socioeconomic status increases the chances for lead exposure.
• Lead toxicity is an under-appreciated problem that is entirely preventable.

Hiv Associated Neurocognitive Disorders In An Antiretroviral Therapy Era, Molly Halloran, David S. Strayer, Md, Phd

Department of Pathology Honors Program Student Research Symposium

HIV emerged as a major threat to world health over 30 years ago, and while its effects on the immune system are widely known, HIV also has broad and devastating effects on the nervous system. Despite our potent antiretroviral therapies (ART), these HIV-associated neurocognitive disorders (HAND) continue to afflict HIV infected individuals. With over 33 million people infected worldwide and evidence that neurological damage can accrue in virologically well controlled individuals, HAND is a pressing challenge. Nevertheless, many questions remain unanswered about this spectrum of disorders.

Her-2 Heterogeneity In Breast Cancer: A Case Study, Kinnari Patel, Theodore Parsons

Department of Pathology Honors Program Student Research Symposium

CASE

The patient is a 75 year-old female with a history of stage 1 invasive ductal carcinoma of the left breast measuring 1.2 cm. Core biopsy of the mass demonstrated Nottingham grade 3 invasive ductal carcinoma; ER negative, PR negative, HER-2 negative (1+). The patient underwent mastectomy in April 2013. Mastectomy confirmed Nottingham grade 3 invasive ductal carcinoma pT1c/pN0/pMX with peritumoral lymphovascular invasion and invasive tumor less than 1 mm from the superoanterior margin. Due to comorbidities the patient was not considered a candidate for adjuvant chemotherapy.

In January 2014 the patient presented with a mastectomy site recurrence. Needle core …

Plasmapheresis And Hiv-Associated Thrombotic Microangiopathy: An Institutional Review, Megan Fisher, Ms2, Nancy Edger Hall, Rn, Mba, Jennifer Webb, Md, Julie Karp, Md

Department of Pathology Honors Program Student Research Symposium

Thrombotic thrombocytopenic purpura (TTP) is a systemic disorder that classically results from a deficiency in the von Willebrand factor-cleaving enzyme, ADAMTS13. The human immunodeficiency virus (HIV) is a secondary cause of TTP. It has been recognized that some patients with HIV-associated TTP do not have a deficiency in ADAMTS13 activity. The role of plasmapheresis (PLEX) in these patients is unclear. This study reviewed 8 cases of HIV-associated TTP at Thomas Jefferson University Hospital. All patients responded to treatment; however, we were unable to make any conclusions regarding the use of PLEX in patients with normal ADAMTS13 activity. HAART initiation is …

Molecular Profiling Of Patients With Non Small Cell Lung Cancer At Jefferson University Hospital, Erin Bange, Renu Bajaj, Ms, Phd, Cg (Ascp), Cm, Facmg

Department of Pathology Honors Program Student Research Symposium

Companion diagnostics is the use of specific tests whose results are linked to a particular drug. It allows clinicians the ability to better target the mechanism of pathology in the patient and follow it up with a therapy specifically designed to treat the disease process at hand. This approach to medicine has particularly been championed in the field of oncology with the development of such drugs as Zelboraf for the treatment of metastatic melanoma with the BRAFV600 mutation or Xalkori for late stage lung cancer expressing an abnormal ALK protein. In the case of non-small cell lung cancer (NSCLC) Jefferson …

Personalized Immune Therapy For Cancer A Potential Game-Changing Treatment, Emily Evron, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

T-CELL RECEPTOR, NORMALLY

T-cell receptors reside on the surface of T-cells, and recognize a specific antigen presented by an MHC molecule

Next, the T-cells become either CD4 or CD8 cells

Co-stimulation is a key step in activating the T-cell; B7 proteins on the surface of antigen-presenting cells interact with CD28/CTLA-4 receptors on the T-cell.

Peripheral T-Cell Lymphoma Arising From Age-Related Ebv-Associated Lymphoproliferative Disorder (Ar-Ebvlpd), Alaina Chodoff, Msii, Guldeep Uppal, Md, Jerald Z. Gong, Md

Department of Pathology Honors Program Student Research Symposium

In the setting of underlying immune suppression, Epstein Barr Virus (EBV) is a well-recognized oncogenic agent that induces the malignant proliferation of B-cells. EBV-lymphoproliferative disorders (LPDs) have recently been linked to immunosenescence. We present a unique case of Age-Related EBV-Lymphoproliferative Disorder (AR-EBVLPD) in a 70 year old female that deviates from the characteristic progression of this disease. Over the course of 18 months, the patient’s clinical condition worsened without a definitive diagnosis to explain the severe, atypical widespread chronic inflammation spanning her gastrointestinal tract, from esophagus to small bowel. The diagnosis of AR-EBVLPD, polymorphic extranodal subtype, was delayed until the …

Giant Cell Tumor Of Soft Tissue: A Case Study, Rachel Schneider, Brian J. O'Hara

Department of Pathology Honors Program Student Research Symposium

BACKGROUND

Giant cell tumors of soft tissue are relatively uncommon tumors. They are considered to be the soft tissue counterpart to giant cell tumors of bone. Both tumors consist of multi-nucleated giant cells evenly distributed throughout a background of epithelioid mononuclear cells, and are usually benign, but can be locally invasive. Giant cell tumors of soft tissue typically occur in patients over age 40, and show no gender or racial predilection. They present as firm, well demarcated masses, which are not connected to the underlying muscle, tendon, or bone. Giant cell tumors of soft tissue are generally small, and tend …

Small Cell Carcinoma Of The Breast, Victor Carlson, Paolo Cotzia, Md, Juan P. Palazzo, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

Small cell carcinoma of the breast (SCCB) is a rare, highly aggressive neoplasm first reported in 1983. With striking histologic similarity to small cell carcinoma of the lung, it is comprised of small cells with relatively large, hyperchromatic nuclei and scanty cytoplasm. While capable of hormone secretion, this is a rare occurrence in this variant of small cell carcinoma. Patients typically present with a suspicious breast mass confirmed on imaging, with variable lymph node invasion.

Haploidentical Hematopoietic Stem Cell Transplantation: Rationale, Development, And Jefferson’S Method, Susan Mcilvaine, Dolores Grosso, Rn, Crnp, Dnp, Beth Colombe

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

There are many indications for hematopoietic stem cell transplantation. In addition to hematologic malignancies, transplants are performed in certain non-hematologic malignancies, for marrow disorders such as Sickle Cell Anemia, and for various inherited disorders such as SCID. Traditionally, transplants have been performed between donors and recipients that are a complete HLA match (typically matched siblings). That is, patients have identical HLA alleles on both copies of chromosome 6. HLA alleles code for major histocompatibility complex molecules, which are the proteins that cause transplant rejection when a mismatch between donor and recipient is present. Thus, matched transplants have been historically …

Small Cell Carcinoma Of The Bladder: A Rare Entity, Andrew H. Matthews, Ruth Birbe, Md

Department of Pathology Honors Program Student Research Symposium

BACKGROUND

Primary small cell carcinoma of the urinary bladder is a rare tumor, accounting for less than 1% of the annual 70,000 cases of urinary bladder cancer.¹ Accordingly, little data is available beyond case series to guide diagnosis or treatment. Overall prognosis remains poor with five year survival often markedly below 50%. Current staging and treatment remains largely based on extrapolation from small cell carcinoma of the lung. We review two recent cases of bladder small cell carcinoma with a focus on comparing and contrasting with lung small carcinoma.

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 …