Atilano Lacson

Expression of C-kit in Ewing Family of Tumors: A Comparison of Different Immunohistochemical Protocols

Ewing sarcoma is a small round blue cell tumor with a high incidence of metastasis and poor survival. The tyrosine kinase receptor, c-kit, is a growth factor receptor that is expressed in a variety of tumors including Ewing sarcoma. Blockade of c-kit by imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp, East Hanover, NJ) has been successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal tumors. Detection of c-kit expression in Ewing sarcoma indicates a possible role of c-kit in tumor progression and a potential use of anti-c-kit therapy in Ewing sarcoma. Ki-67 is a proliferation marker found at all stages of the cell cycle. Expression of c-kit and Ki-67 was studied in 17 patients with Ewing sarcoma. Sections from paraffin-embedded tumor samples were immunostained, using standard immunohistochemical protocols, with c-kit and Ki-67 monoclonal antibodies, polyclonal c-kit antibody without antigen retrieval, and c-kit polyclonal antibody with antigen retrieval. Eleven out of 17 cases (65%) stained with c-kit monoclonal antibody; the staining was diffuse in 6/17 (35%) cases. C-kit expression did not correlate with Ki-67 proliferation rates. Using the polyclonal c-kit-antibody without antigen retrieval methods, c-kit expression was demonstrated in 1/11 (9%) cases. Incorporating antigen retrieval methods, c-kit expression increased to 53%. Concordance between monoclonal antibodies in detecting c-kit expression was observed in 12/17 cases (71%). We conclude that c-kit is variably expressed in Ewing sarcoma, using either monoclonal or polyclonal antibodies. Detection of c-kit expression in Ewing sarcoma improves with the use of antigen retrieval methods.

Seckel-like Syndrome in Three Siblings

ABSTRACT Seckel syndrome has been described as the prototype of the primordial bird-headed type of dwarfism. Since Seckel originally defined the disorder, less than 60 cases have been reported. In addition to the characteristic craniofacial dysmorphism and skeletal defects, abnormalities have been described in the cardiovascular, hematopoietic, endocrine, and central nervous systems. This pleiotropy has implied genetic heterogeneity and prompted reviews of previously reported cases of Seckel syndrome. As a result, the characteristic diagnostic features of Seckel syndrome have been highly debated. Although deletions in chromosome 2q have been described, to date, no genetic defect has been defined. We report three cases of Seckel-like syndrome in siblings from nonconsanguinous Caucasian parents. In addition to the typical Seckel phenotypic features, all three cases were characterized by severe hydrocephalus. We review the literature and propose that there is a spectrum of Seckel conditions that share some common key features, but also demonstrate a wide range of phenotypic features.

Atypical dendritic cell–related histiocytosis with goiter and primary hypothyroidism

Langerhans cell histiocytosis may be seen with goiter and histiocytic infiltration of the thyroid. We report a 2 1/2-year-old boy who had goiter and primary hypothyroidism develop, later had pulmonary disease, and died of neurologic involvement. Autopsy lesions suggested a transitional dendritic cell precursor of the epidermal Langerhans cell. Of the reported cases of Langerhans cell histiocytosis with goiter in children and adolescents, 82% were male when the relative incidence of Langerhans cell histiocytosis is two males to one female.

CLINICO PATHOLOGY CONFERENCE: INFANT WITH HIGH ARCHED PALATE, BELL-SHAPED CHEST, JOINT CONTRACTURES, AND INTRAUTERINE FRACTURES

A case is presented of a female newborn infant delivered with an Apgar Score of 1, who could not be resuscitated. There was a high arched palate, bell-shaped chest, contractures of writes inflexion, ankles and knees in extension, and intrauterine fractures. Clinical discussion led to a diagnosis of arthrogryposis secondary to fetal akinesia syndrome caused by nemaline myopathy. Pathology and pathologic discussion confirmed this diagnosis.

CLINICO-PATHOLOGIC CONFERENCE: NEWBORN WITH HYDROPS FETALIS CAUSED BY CMV INFECTION CASE REPORT

Jorge Lujan-Zilbermann u Assistant Professor of Pediatrics, University of South Florida College ofMedicine,Tampa, Florida, USA Atilano Lacson u Clinical Associate Professor of Pediatrics, University of South Florida College ofMedicine and Pediatric Pathologist, All Children’s Hospital, St. Petersburg, Florida, USA Enid Gilbert-Barness u Professor of Pathology and LaboratoryMedicine, Pediatrics, and Obstetrics and Gynecology, University of South Florida College ofMedicine,Tampa, Florida, USA Herbert H. Pomerance u Professor of Pediatrics, University of South Florida College of Medicine,Tampa, Florida, USA

Pulmonary vasculitis presenting as atypical asthma

CASE REPORT A 9-year-old female was referred to our clinics in January 1998 because of multisystem complaints. The patient had a 2-year history of cough, episodes of chest pain, and tightness upon increasing activity. The patient had minimal response to 2-agonists and was noted to improve upon treatment with oral glucocorticosteroids. She was diagnosed with atypical asthma and was treated with inhaled glucocorticosteroids and 2-agonists. Concomitant with chest symptoms, the patient experienced frequent arthralgias, fatigue, generalized lymphadenopathy, hypertension, transient ischemic attacks, Raynaud’s phenomenon, growth failure, abdominal pain, headaches, and frequent infections characterized as recurrent otitis media and sinusitis. Her medications included beclomethasone inhaler double strength 2 puffs bid, albuterol inhaler every 4 to 6 hours as needed, fluticasone nasal spray 1 spray qd, loratidine 5 mg qd, sucralfate 1 g tid, nifidipine 30 mg qd, baby aspirin 81 mg qd, ibuprofen every 6 to 8 hours as needed and growth hormone injection qd. The patient was admitted to the hospital for further evaluation and treatment. On physical examination, the patient weighed 25.6 kg (5th percentile) and was 126 cm in height ( 5th percentile). Pertinent findings included mobile and tender cervical, axillary, and inguinal lymphadenopathy; clear breath sounds; mild epigastric tenderness; and hepatosplenomegaly. Capillary nail beds were abnormal in that they exhibited telangiectasia and vascular dropout. The skin was dry with a fixed salmoncolored macular rash on the upper chest and neck. The rest of the physical examination was unremarkable.

Immunohistochemical expression of endothelial nitric oxide synthase and C-kit in the placenta of complete hydatidiform mole.

Complete hydatidiform mole is an abnormal conceptus characterized by hydropic villi accompanied by proliferating trophoblasts. Its pathogenesis is largely unknown. Endothelial nitric oxide synthase is induced by vascular endothelial growth factor and has been implicated in the pathogenesis of preeclampsia and other physiologic conditions in the placenta. C-kit is the tyrosine kinase receptor and is involved in tumor formation elsewhere in the body. Using standard immunohistochemical protocols, we studied the expression of C-kit and endothelial nitric oxide synthase in the placenta of 10 patients with complete hydatidiform mole. Cytoplasmic and nuclear staining with endothelial nitric oxide synthase was identified in the cytotrophoblast and intermediate trophoblast layers in all cases, with high staining in 7/10 and 6/8 cases, respectively. Minimal staining is identified in the syncytiotrophoblast layer. Hofbauer stromal cells were identified in 9 cases and showed low staining intensity in 7/9 cases. Cytoplasmic C-kit staining was diffuse and of low intensity. The cytotrophoblast, the syncytiotrophoblast, intermediate trophoblast, and the stromal cells had low C-kit staining intensity in 8/10, 8/10, 7/9, and 5/9 cases. These results indicate that C-kit and endothelial nitric oxide are expressed in the placentas of complete hydatidiform mole and may play a role in the pathogenesis of trophoblastic proliferation in this condition.

CLINICO-PATHOLOGIC CONFERENCE: STATUS EPILEPTICUS IN A 5-YEAR-OLD GIRL

The patient was a 5-year old Caucasian female admitted in status epilepticus. At 5 months prior to the most recent admission, the patient presented to hospital with seizures. There was no history o...

CLINICO-PATHOLOGIC CONFERENCE: CONGENITAL HYPOMYELINATING NEUROPATHY IN TWO INFANTS OF A TRIPLET BIRTH

Maria Gieron-Korthals u Professor of Pediatrics, University of South Florida College of Medicine,Tampa, Florida, USA Atilano Lacson u Clinical Associate Professor of Pediatrics and Pathology, University of South Florida College ofMedicine,Tampa, Florida and Pathologist, All Children’s Hospital, St. Petersburg, Florida, USA Herbert H. Pomerance u Professor of Pediatrics, University of South Florida, College of Medicine,Tampa, Florida, USA

15‐Month‐old infant with failure to thrive, hepatomegaly, increased liver enzymes, hypoproteinemia, and seizures

Department of Pediatric Pathology, All Children’s Hospital, St. Petersburg, FloridaCASE PRESENTATIONHerbert H. Pomerance, M.D., andRobert F. Patterson, M.D.The patient was a white female who at age 15 monthswasadmittedtothehospitalbecauseoffailuretothrive,recent onset of focal motor seizures, and occasionalvomiting. She had been born to a G1P0 mother after anapparently normal pregnancy. She was breast fed for 3months, when breast feeding was stopped, apparentlybecause of the patient’s ‘‘crankiness and irritability.’’Shewaspoorlyreceptiveofformulafeedingsthereafter,and exhibited poor weight gain. Her diet consistedprimarily of potato chips and pickles. Prior to this ad-mission, she had had occasional ear and throat infec-tions. A number of outpatient tests were carried out,including examination for ovaandparasites, whichwasreported as negative. An immunoglobulin screen wasobtained and showed normal results. A blood count andurinalysis were normal. Antimicrosomal antibodieswere not found. The sweat chloride result was 10. Itwasnotedthattheseizureshadstarted1weekfollowingimmunization with MMR.Physical examination. The body habitus of thechild was described as petite to frail, and the hair wassparse. Weight and height were below the 5th centile.The liver was palpable one finger-breadth below theright costal margin. The spleen tip was palpable. Therewere no other positive findings.The laboratory findings on admission are shown inTable I. Later findings are included in Tables I–V.Includedinthisworkupwasaurineorganicacidprofile,which revealed increased hydroxyphenyllactate andno other abnormalities. Amino acid blood and urinescreens were negative. Direct bilirubin was 0.6 mg%.Calcium levels were consistently low to boderline, withvarious measurements from 6.7–7.3 mg%. A lympho-cyteprofileshowednormalnumbers,withtheexceptionof a value of 224 for CD8 cells. A later antigen andmitogen profile revealed decreased but measurablelevels.About 3 weeks after admission, increased seizureactivity and increasing respiratory difficulties werenoted. Bronchial lavage showed some growth of Can-dida. A tracheal aspirate on day 10 revealed Strepto-coccus pneumoniae in large numbers, and this wastreated. Her course continued downhill and she diedapproximately 1 month after admission.CLINICAL DISCUSSIONLewis A. Barness, M.D.TheimportantfeaturesofthiscasearesummarizedinTable VI. An infant may voluntarily select a dieteliminating a food to which he or she is intolerant. Suchself-selection has been recognized against food aller-gies, milk, gluten, galactose, lactose, fruit, and variousproteins.