Retinoblastoma: the Zimmerman family story.

The2013annualmeetingof theAmericanAssociationofOphthalmic Oncologists and Pathologists was dedicated to celebrating the life and work of my father, Lorenz E. Zimmerman, MD. Although many may know of his contributions to the field of ophthalmic pathology and oncology, the story of his personal challenges in the field is not widely known. After earning his bachelor of science degree in 1943 and hisdoctorofmedicinedegree in 1945, both fromGeorgeWashington University in Washington, DC, my father completed a pathologyresidencyatWalterReedGeneralHospital.TheArmy then sent him to Korea to run a mobile Army hospital laboratory. That facility supported Chinese and Korean prisonersofwar, and themajorityof specimensobtained there werebacteriologic, thusprovidinganexcellentopportunity for the development of an interest in the pathology of infectious diseases. When he returned from Korea in 1951, he was stationed at Walter Reed General Hospital’s Armed Forces Institute of Pathology (AFIP); his intention was to become an expert in thepathologyofmycoticdiseases.Fortunately,however, the Army had other plans for him, and the result was a 50-year renaissance in the field of ophthalmic pathology. Theevolutionofophthalmicpathology in theUnitedStates began at the ArmyMedical Museum, which later became the AFIP.Early in the20thcentury,most enucleatedeyeswerediscarded because therewas no one trained in ocular pathology. Dr George Callendar, the director of the AFIP in the 1920s, developed aprocess for examining all the enucleated eyes of patients from military institutions, and by World War II, all of these specimenswere sent to theAFIP forhistopathology.This process resulted in theAmericanRegistry of Pathology,where ophthalmic pathology became the first registry. In the early 1950s, few general pathologists were interested in ocular pathology; in 1953,my fatherwas assigned to theDepartment of Ophthalmic Pathology at theAFIP.His response: “I thought it was a stroke of real good fortune for me personally, not because I had anypreconceivednotions or interest in pathology of the eye, but I just knew that itwas a goldmine...in the figurative sense...in terms of having a wealth of material available andhaving this tremendous inflowof cases,notonly from military institutions, but from the civilian sector.”1 Becauseof WorldWar II and the resulting lack ofmanpower, a backlog of 5000 eye pathology cases had accumulated, and this abundance of clinical andhistopathologicmaterialwas the perfect background for the development of my father’s interest in ocular oncology. My father’s willingness and enthusiasm to pursue passionately a field in pathology, aboutwhich he had no prior interest, set the stage for a series of more than 50 years of professionalandpersonalchallenges inandcontributions toocular pathology andoncology, particularly in the fieldof retinoblastoma. In his first 15 years at the AFIP, he publishedmore than 50ocular oncology articles, someofwhichwere landmark initial descriptions.2 This work became intimately intertwined withmyfather’spersonal lifewhen, in1967,myparents’youngest child, Larry, received a diagnosis of bilateral retinoblastomaat4monthsof age.Thisbegana seriesof ironies andcontributions, includingseveral “firsts” in retinoblastomascience, nomenclature, and treatment by 3 generations of theZimmerman family. At the time of Larry’s birth, my father was involved in a reviewofall the casesof retinoblastomaat theAFIP.Therewas no Zimmerman family history of retinoblastoma, but Lorenz E. Zimmerman Jr (Larry) developed bilateral retinoblastoma. Could this havebeenamere coincidence?Larryhada large tumor involving the macula of the right eye and 3 small perimacular tumors in his left eye. Routine treatment at the time was to enucleate the eye with the more advanced tumor and radiate the other. My parents were not satisfied with this and wanted to find a way to salvage vision and the right eye. Larry’s initial treatment, by Drs Algernon Reese and RobertEllsworth inNewYork,wasan intracarotid injectionof chemotherapy.When thiswas ineffective, hewas treatedwithbilateral external beam radiotherapy. Both were experimental treatments at the time. Although bilateral external beam radiotherapy later saved thevisionof countlesspatientsover the years, owing to amore than 30% chance of secondary tumors in the field of radiation,3 better treatments have replaced it. Larry responded positively to the treatment of his retinoblastoma, andhis visionwas salvaged inbotheyes (visual acuitywas counting fingersODand 20/40OS); hewent on to a careerasabanker inManhattan.Hemarried,andafterundergoing genetic counseling and after the identification of hisRB gene, he andhiswife, Anne, decided tohave a child. Perrywas born healthy,butby7weeksof age, shehaddevelopedbilateral retinoblastoma.DrDavidAbramsonsuccessfully treated these tumorswith laser therapy; she had no recurrence of intraocular retinoblastoma. Larry andAnnebecame aware of a newassisted reproductivetechnology, thatofpreimplantationgeneticdiagnosis (PGD), and they sought consultation at the Institute for Reproductive Medicine at NewYorkHospital. The team there developed the mutationanalysisprocedure for the retinoblastomagene (RB1) Related articles pages 605, 614, 622, 630 and 651 Opinion