Hemic and Lymphatic Diseases Commons^™

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Clinical Outcomes Of Splenectomy In Children: Report Of The Splenectomy In Congenital Hemolytic Anemia Registry., Henry E. Rice, Brian R. Englum, Jennifer Rothman, Sarah Leonard, Audra Reiter, Courtney Thornburg, Mary Brindle, Nicola Wright, Matthew M. Heeney, Charles Smithers, Rebeccah L. Brown, Theodosia Kalfa, Jacob C. Langer, Michaela Cada, Keith T. Oldham, J Paul Scott, Shawn D. St Peter, Mukta Sharma, Andrew M. Davidoff, Kerri Nottage, Kathryn Bernabe, David B. Wilson, Sanjeev Dutta, Bertil Glader, Shelley E. Crary, Melvin S. Dassinger, Levette Dunbar, Saleem Islam, Manjusha Kumar, Fred Rescorla, Steve Bruch, Andrew Campbell, Mary Austin, Robert Sidonio, Martin L Blakely, Splenectomy In Congenital Hemolytic Anemia (Sicha) Consortium

Manuscripts, Articles, Book Chapters and Other Papers

The outcomes of children with congenital hemolytic anemia (CHA) undergoing total splenectomy (TS) or partial splenectomy (PS) remain unclear. In this study, we collected data from 100 children with CHA who underwent TS or PS from 2005 to 2013 at 16 sites in the Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium using a patient registry. We analyzed demographics and baseline clinical status, operative details, and outcomes at 4, 24, and 52 weeks after surgery. Results were summarized as hematologic outcomes, short-term adverse events (AEs) (≤30 days after surgery), and long-term AEs (31-365 days after surgery). For children with hereditary spherocytosis, …

Hereditary Spherocytosis, Dolores Loeser

Nursing Student Class Projects (Formerly MSN)

Hereditary Spherocytosis (HS) is a hemolytic anemia where red blood cell membranes are spherical unlike common red blood cells, which are flat and round. In individuals with HS the spleen does not recognize these amorphous cells and destroys—rather filters—them them, making the individual anemic (MedlinePlus, 2013). HS is an autosomal dominant, or recessive autosomal inherited blood disease (Huq, Pietroni, Rahman & Alam, 2010) HS happens in 1 in 2,000 of the Caucasian population in or from Northern Europe (MedlinePlus, 2013). The proteins involved in HS are ankyrin-1, ά-spectrin, β-spectrin, band 3, and protein 4.2. Hyperbilirubinemia is a common symptoms in …

Hemophilia A: Pathophysiology And Treatment Strategies, Daniel Dinneen

Nursing Student Class Projects (Formerly MSN)

Hemophilia is a sex-linked recessive coagulation disorder that varies in severity. The implications and complications of hemophilia can be life threatening; pathology is usually diagnosed during childhood and adequate management is essential in maintaining health. Advanced practice nurses treat a variety of hemophilia patients in varying roles throughout the lifespan as hemostasis is a constant physiologic process. Thorough knowledge of the pathophysiology, signs/symptoms, and treatment modalities related to hemophilia is necessary to provide the highest level of comprehensive medical care to such patients. Hemophilia care is continued throughout the lifespan, and newer research indicates that current treatment modalities can initiate …

Lymphedema: Pathophysiology, Diagnosis & Management, Bernadine Cruz

Nursing Student Class Projects (Formerly MSN)

Lymphedema is a disfiguring condition whose hallmark is progressive, increasing swelling which occurs as a result of the accumulation of protein rich fluid in interstitial spaces. Those individuals who are affected suffer from either primary lymphedema or secondary lymphedema; the pathophysiology of both conditions is similar. Lymphedema can be a chronic, acute, or transient alteration, which can eventually lead to keratinization of the skin. An increase in the incidence of lymphedema has also been observed with increase in levels of obesity.

Ponatinib-Induced Adverse Effects: Thrombocytopenia, Pancreatitis And Hepatoxicity-- A Case Report, Saba Hasan, Crystal Fedorkiv, Naba Rahman, Jennifer Andres

Research Day

Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disease that generates from malignant transformation of pluripotent hematopoietic stem cells. First line treatment for CML is the tyrosine kinase inhibitor (TKI), imatinib. For patients resistant or intolerant to imatinib, other TKIs, dasatinib, nilotinib, and ponatinib, are approved treatments. Patients who are resistant or intolerant to other agents are started on ponatinib as a last line option. Common adverse events of ponatinib are hypertension, dry skin, rash, abdominal pain, constipation, and nausea. More serious adverse effects include cardiovascular effects, fluid retention, pancreatitis, severe myelosuppression, and hepatotoxicity. Treatment for these adverse effects can …

Concurrent Non-Ketotic Hyperglycinemia And Propionic Acidemia In An Eight Year Old Boy, Paul Kruszka, Brian Kirmse, Dina Zand, Kristina Cusmano-Ozog, Elaine Spector, John Hove, Kimberly A. Chapman

Pathology Faculty Publications

This is the first reported case of a patient with both non-ketotic hyperglycinemia and propionic acidemia. At 2 years of age, the patient was diagnosed with non-ketotic hyperglycinemia by elevated glycine levels and mutations in the GLDC gene (paternal allele: c.1576_1577insC delT and c.1580delGinsCAA; p.S527Tfs*13, and maternal allele: c.1819G>A; p.G607S). At 8 years of age after having been placed on ketogenic diet, he became lethargic and had severe metabolic acidosis with ketonuria. Urine organic acid analysis and plasma acylcarnitine profile were consistent with propionic acidemia. He was found to have an apparently homozygous mutation in the PCCB gene: c.49C …

Scanned Ion Beam Therapy For Thoracic Tumors, John Gordon Eley

Dissertations and Theses (Open Access)

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some …

High Hiv Incidence Among Persons Who Inject Drugs In Pakistan: Greater Risk With Needle Sharing And Injecting Frequently Among The Homeless., Rab Nawaz Samo, Arshad Altaf, Ajmal Agha, Omrana Pasha, Shafquat Rozi, Ashraf Memon, Saleem Azam, Meridith Blevins, Sten Vermund, Sharaf Ali Shah

Community Health Sciences

BACKGROUND:

The incidence of HIV among persons who inject drugs (PWIDU) has fallen in many nations, likely due to successes of clean needle/syringe exchange and substance abuse treatment and service programs. However in Pakistan, prevalence rates for PWID have risen dramatically. In several cities, prevalence exceeded 20% by 2009 compared to a 2003 baseline of just 0.5%. However, no cohort study of PWID has ever been conducted.

METHODS:

We enrolled a cohort of 636 HIV seronegative PWID registered with three drop-in centers that focus on risk reduction and basic social services in Karachi. Recruitment began in 2009 (March to June) …

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

Dissertations and Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …

Biological Mechanisms And Clinical Implications Of Bcr-Abl-Induced Mitochondrial Oxidative Stress And Cell Survival In Chronic Myeloid Leukemia, Hui Zhang

Dissertations and Theses (Open Access)

Chronic myeloid leukemia (CML), a myeloproliferative disorder, represents approximately 15-20% of all adult leukemia. The development of CML is clearly linked to the constitutively active protein-tyrosine kinase BCR-ABL, which is encoded by BCR-ABL fusion gene as the result of chromosome 9/22 translocation (Philadelphia chromosome). Previous studies have demonstrated that oxidative stress-associated genetic, metabolic and biological alterations contribute to CML cell survival and drug refractory. Mitochondria and NAD(P)H oxidase (NOX) are the major sources of BCR-ABL-induced cellular reactive oxygen species (ROS) production. However, it is still unknown how CML cells maintain the altered redox status, while escaping from the persistent oxidative …

Identifying The Relationship Between Benzene Exposure And The Development Of Acute Myeloid Leukemia, Jacqueline G. Tally

Senior Honors Projects

My interest in epigenetic carcinogenesis-related research stems from both academic and personal experiences. I have come to recognize the significance of environmental chemical exposures in the development of cancer through my studies in nursing, and nutrition and food science. I am particularly interested in the epigenetics of acute myeloid leukemia (AML) because I am an AML survivor.

AML is a rare and highly malignant cancer. It is estimated 13,780 new cases of AML will be identified in theUnited Statesthis year with a 74% mortality rate (calculated 10,200 deaths/13,780 new cases). AML develops from alterations in the survival and proliferation of …

Acute Myeloid Leukaemia In Children: Experience At A Tertiary Care Facility Of Pakistan, Zehra Fadoo, Naureen Mushtaq, Saima Alvi, Muhammad Ali

Department of Paediatrics and Child Health

Objective: To document the demographics and outcome of children with Acute Myeloid Leukemia (AML) treated at a tertiary care facility of Pakistan.

Methods: A retrospective study was conducted at Aga Khan University on children (less than 15 years) diagnosed to have AML between January 2000 to May 2007.Total 40 cases were diagnosed out of which 37 charts were available for review.

Results: The average age of presentation was 8.5±4.5 years and 75% were males. The most common presenting feature was fever in 83% followed by bleeding in 41% and pallor in 39%. Initial WBC of > 100,000 was seen in 19% …

Sickle Cell Anemia, Derek Hayse

A with Honors Projects

What Sickle Cell Anemia is, its symptoms, how it is acquired, how it can be prevented, and how to deal with having it.

The Role Of Protein Kinase C Epsilon In Hydrogen Peroxide And Nitric Oxide Release During Oxidative Stress Caused By Extracorporeal Shockwave Lithotripsy, Edward S. Iames

PCOM Biomedical Studies Student Scholarship

Clinical extracorporeal shock wave lithotripsy (ESWL) treatment to ablate kidney stones can cause acute damage to the renal microvasculature. Accumulation of continued treatment with shockwave therapy can lead to chronic damage to the kidney, and lead to clinical hypertension. Shockwaves have been shown to stimulate endothelial cells to release superoxide (SO), which is converted to hydrogen peroxide (H₂O₂), and reacts with nitric oxide (NO) to produce peroxynitrite anion (OONO^-), creating a powerful oxidant that increases oxidative stress while simultaneously reducing NO bioavailability. Increased oxidative stress during events such as ESWL, also uncouples NO production …

Use Of Phage Display To Isolate Specifi C Human Monoclonal Antibody Fragments Against A Potential Target For Multiple Myeloma, Pei Xiong Liew, Feng Ge, Charles A. Gullo, Gerrard Kh Teoh, William Yk Hwang

Biochemistry and Microbiology

Introduction: Multiple myeloma (MM), a malignancy of plasma cells, accounts for 10% of all haematological malignancies and is currently incurable. Although it can be treated, the disease tends to relapse after several years and becomes increasingly resistant to conventional therapy. Investigations into using humoral therapy for MM are now underway with a view that novel therapeutic agents may provide a more targeted therapy for MM.

Materials and Methods: Here, phage display, a faster and more efficient method compared to classical hybridoma fusion technology, was used as a proof-of-concept to isolate several single-chain Fragment variables (scFv) against Ku86.

Results …

C-Reactive Protein Polymorphism And Serum Levels As An Independent Risk Factor In Sickle Cell Disease, Elizabeth A. Chismark

Theses and Dissertations (ETD)

This study explored the relationship of a dinucleotide repeat polymorphism in the intron of the CRP gene and serum CRP levels as independent risk factors for end-organ dysfunction (mild vs. severe) in adults with sickle cell disease. The pathogenesis of secondary complications of sickle cell disease is complex and poorly understood. Predicting the severity of these complications could assist in therapeutic decision-making.

The study measured serum CRP levels and the number of CA intron repeats located on the CRP gene in 29 adults (31.74 ± 11.54 years) with sickle cell disease The hemoglobin genotypes were distributed as Hgb SS 48.6% …

Skeletal Abnormalities In Mice Lacking Extracellular Matrix Proteins, Thrombospondin-1, Thrombospondin-3, Thrombospondin-5, And Type Ix Collagen, Karen L Posey, Kurt Hankenson, Alka C Veerisetty, Paul Bornstein, Jack Lawler, Jacqueline T Hecht

Faculty, Staff and Student Publications

Thrombospondin-5 (TSP5) is a large extracellular matrix glycoprotein found in musculoskeletal tissues. TSP5 mutations cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia; both show a characteristic growth plate phenotype with retention of TSP5, type IX collagen (Col9), and matrillin-3 in the rough endoplasmic reticulum. Whereas most studies focus on defining the disease process, few functional studies have been performed. TSP5 knockout mice have no obvious skeletal abnormalities, suggesting that TSP5 is not essential in the growth plate and/or that other TSPs may compensate. In contrast, Col9 knockout mice have diminished matrillin-3 levels in the extracellular matrix and early-onset osteoarthritis. …

Knowledge And Beliefs Of Adolescents Regarding Sexually Transmitted Infections And Hiv/Aids In A Rural District In Pakistan, Hafsa Raheel, Franklin White, Muhammad Masood Kadir, Zafar Fatmi

Community Health Sciences

Objective:

To assess the knowledge and beliefs of adolescents (15-19 years girls and boys) regarding sexually transmitted infections (STIs) and HIV/AIDS.

Methods:

A community based cross-sectional survey was conducted in October 2002 in a rural district (Mirpurkhas) of Sindh province, Pakistan.

Results:

A total of 428 adolescent girls and boys were interviewed. Only 44% correctly named at least one STI, while 55% knew at least two modes of transmission for HIV/AIDS. Adolescents with education greater than or equal to secondary level, those who were able to read the newspaper, possessed electricity in their homes and were allowed to meet their …

P27kip1 And P130 Cooperate To Regulate Hematopoietic Cell Proliferation In Vivo, Inês Soeiro, Azim Mohamedali, Hanna M. Romanska, Nicholas C. Lea, Emma S. Child, Janet Glassford, Stephen J. Orr, Claudia Roberts, Kikkeri N. Naresh, El-Nasir Lalani, David J. Mann, Roger J. Watson, N. Shaun B. Thomas, Eric W. -F. Lam

Department of Pathology and Laboratory Medicine

To investigate the potential functional cooperation between p27^Kip1 and p130 in vivo, we generated mice deficient for both p27^Kip1 and p130. In p27^Kip1−/−;p130^−/− mice, the cellularity of the spleens but not the thymi is significantly increased compared with that of their p27^Kip1−/− counterparts, affecting the lymphoid, erythroid, and myeloid compartments. In vivo cell proliferation is significantly augmented in the B and T cells, monocytes, macrophages, and erythroid progenitors in the spleens of p27^Kip1−/−; p130^−/− animals. Immunoprecipitation and immunodepletion studies indicate that p130 can compensate for the absence …

Small B Cell Non-Hodgkins Lymphoma In Pakistan, Kanwal Aftab, Yasmin Bhurgri, Shahid Pervez

Department of Pathology and Laboratory Medicine

Objective: To study the pattern of small B cell lymphomas in Pakistan.

Methods: This descriptive study was carried out at the Aga Khan University Hospital pathology department including 1721 cases of Non-Hodgkins Lymphoma (NHL) diagnosed during a period of five years (1998-2002) and classified according to REAL/WHO classification. The antibodies used included Leukocyte Common Antigen (LCA), Pan B (CD20, CD79a), Pan T (UCHL-1), Bcl 2, Mib 1(Ki 67) and Cyclin D1 (Dako, Denmark).

Results: Out of the 1721 NHL cases, only 140 (8.1%) could be categorized as small B-cell NHL. The study group comprised small lymphocytic lymphoma/chronic lymphocytic leukemia (58 …

Flow Cytometric And Demographic Analysis Of T Cell Acute Lymphoblastic Leukemia In Pakistani Population., M R. Khawaja, S S. Allana, N N. Akbaral, S N. Adil, M. Khurshid, Shahid Pervez

Department of Pathology and Laboratory Medicine

Background: This study was carried out to analyze the proportion of T cell acute lymphoblastic leukemia (TALL) among all acute lymphoblastic leukemia (ALL) in Pakistani population and its correlation with the demographic features. Accuracy of cell surface markers used in flow cytometric analysis of the leukemic cells was also determined.

Methods: Data of 209 consecutive cases of acute lymphoblastic leukemia (ALL) presenting between July 1995 and July 2003 was analyzed. Flow cytometry was performed on all ALL cases using the standard protocols. TALL markers included CD3, CD5 and CD7.

Results: Proportion of TALL among known ALL Pakistani patients was 17.22%. …

Effects Of Sickle Cell Disease On Growth Of The Craniofacial Complexes, Timothy Charles Bandeen

Theses and Dissertations (ETD)

Sickle cell disease (SCD) is a genetic disorder affecting over 100,000 African Americans. While once lethal, medical treatment now allows those with SCD to lead comparatively normal lives, and these children are more frequently seeking orthodontic treatment. We report here on a cephalometric study of a contemporary cohort of 62 children with SCD (27 SC and 35 SS genotypes). This was a cross-sectional study of children from the MidSouth between 3 and 16 years of age, and results were co mpared to standards in Richardson’s Atlas of growth of American Black children in Nashville, TN. Raw values were converted to …

Expression Of Hepatocyte Growth Factor And Its Receptor C-Met, Correlates With Severity Of Pathological Injury In Experimental Alcoholic Liver Disease., El-Nasir Lalani, Richard Poulsom, Gordon Stamp, Franz Fogt, Peter Thomas, Amin A. Nanji

Department of Pathology and Laboratory Medicine

Expression of hepatocyte growth factor (HGF) and its receptor, c-met is up-regulated in various forms of liver injury. This study evaluated the relationship between HGF and c-met expression and pathological changes in experimental alcoholic liver disease. Rats (5 per group) were fed ethanol and a diet containing saturated fat corn oil or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in controls. In a second set of experiments, Kupffer cells, endothelial cells and hepatocytes were isolated from rats in each group. Pathological evaluation and analysis of HGF and c-met expression were performed in liver and the different cell types. …

Spectrum Of Hodgkin's Disease In Children And Adults: Impact Of Combined Morphologic And Phenotypic Approach For Exclusion Of Look-Alikes, Tanya Siddiqui, Shahid Pervez

Department of Pathology and Laboratory Medicine

Objective:

To determine the prevalence of Hodgkin’s disease (HD) and its various subtypes in children and adults and assess the use of immunohistochemical (IHC) studies in confirming HD cases and excluding its close mimicries/look-alikes.

Material and Methods:

All 265 Hodgkin’s disease cases diagnosed at The Aga Khan University Hospital, Karachi over the last 6 years (July 1991 - July 1997) were included. Of these 219 were diagnosed on routine H&E examination while in the remaining 46 cases, diagnosis was made after a thorough IHC workup. (This group initially included 161 cases labelled as lymphoproliferative disorder with HD as one of …

The Roles Of Transferrin Receptor In T Cell Activation, Allison Lorayne Bayer

MUSC Theses and Dissertations

Transferrin receptor (TfR) appears on activated T cells following interaction of the antigen-major histocompatibility complex (MHC) with the T cell receptor (TCR) and the resulting expression of IL-2 receptor (IL-2R). Previous work in the laboratory has demonstrated allograft prolongation following administration of anti-TfR monoclonal antibody (mAb). Studies in the area of cancer immunotherapy have shown that TfR blockade and modulation deprives the tumor of iron, which is essential for continued growth and proliferation, while TfR modulation results in poor T cell proliferation, respectively. This dissertation focuses on the hypothesis that modulation of T cell TfR expression is associated with altered …

Classification And Immunophenotyping Of Acute Leukemias: A Prospective Study., Shahid Pervez, M. Khurshid

Department of Pathology and Laboratory Medicine

Over a period of 3-1/2 years, 86 cases of acute leukemia were analyzed by immunohistochemical (IHC) means on ficoll separated cytospin preparations of peripheral blood and/or bone marrow samples. Antibodies included in the panel were specific against Tdt, HLA-DR, CD19/CD2O/CD22, CALLA (CD1O), CD2, CD11C as well as against Ig heavy chains. Of 86 cases analyzed, 48 cases were of ALL, (25 of common pre-B ALL, 15 of pre-B/NULL and 8 of T ALL phenotype), twenty-four (24) out of 86 cases were of non­lymphoblastic (AML/AMML) type. In six cases, there was suggestion of a mixed lineage, while in 8 cases there …

Immunophenotypic Analysis Of Non-Hodgkin's Lymphoma, Suhail Muzaffar, Shahid Pervez, Farrukh Aijaz, Syed Abdul Aziz, Sheema H. Hasan

Department of Pathology and Laboratory Medicine

One hundred and three cases of Non-Hodgkin’s lymphoma were evaluated immunohistochemically using a panel of monoclonal antibodies which includes leucocyte common antigen (LCA), CD45R (Pan-B marker), L-26 (CD 20-Pan-B marker) and UCHL-1 (Pan-T marker). Of the total 63 cases (61.17%) showed a B-cell phenotype while 40(38.83%) were of T-cell origin. Most B-cell neoplasms belonged to intermediate (79.36%) or high grade (15.87%) according to the international Working Formulation (WF). Most T- cell lymphomas were of either intermediate (52.5%) or high grade (32.5%) neoplasms. Some T-cell neoplasms presented as specific clinicopathological entities like lymphomatoid granulomatosis (2 cases), mycosis fungoides (1 case) and …

Localized Tuberculosis And Myelofibrosis With Myeloid Metaplasia : An Extremely Unusual Presentation, Suhail Muzaffar

Department of Pathology and Laboratory Medicine

Myelofibrosis with myeloid metaplasia (MMM) is usually considered primary agnogenic, however, it may be secondary to various diseases, The association of tuberculosis with MMIM is exceedingly rare, however, the pathogenetic relationship between the two is difficult to define. We present a case report showing simultaneous presentation of localized active tuberculosis and MMM The literature on the subject is also reviewed with special emphasis on pathogenic relation­ship between the two.

Efficient Immortalization Of Luminal Epithelial Cells From Human Mammary Gland By Introduction Of Simian Virus 40 Large Tumor Antigen With A Recombinant Retrovirus, Bartek J, Bartkova J, Kyprianou N, El-Nasir Lalani, Staskova Z, Shearer M, Chang S, Taylor Papadimitriou J

Department of Pathology and Laboratory Medicine

When defined in terms of markers for normal cell lineages, most invasive breast cancer cells correspond to the phenotype of the common luminal epithelial cell found in the terminal ductal lobular units. Luminal epithelial cells cultured from milk, which have limited proliferative potential, have now been immortalized by introducing the gene encoding simian virus 40 large tumor (T) antigen. Infection with a recombinant retrovirus proved to be 50-100 times more efficient than calcium phosphate transfection, and of the 17 cell lines isolated, only 5 passed through a crisis period as characterized by cessation of growth. When characterized by immunohistochemical staining …