telepathology refers to the remote practice of pathology via transmitting digital images . since the introduction of telepathology almost 46 years ago wsi ( virtual microscopy ) refers to the digitization of glass slides by scanners to generate high - resolution digital slides . operationally , it is often easier to move an image than it is to move a pathologist or patient ( or the glass slides of a patient 's specimen ) . for the purpose of telepathology , digital files can either be accessed on a remotely shared server or transmitted and/or uploaded to a server hosted by a consulting group or vendor offering storage ( cloud ) services . telepathology has been reported to improve patient care by offering technology that facilitates access to pathology experts . over the years an early example of international teleconsultation is ipath , a telepathology platform developed by the university of basel in 2001 . international telepathology networks have since been created by several academic institutions including the university of pittsburgh medical center ( upmc ) . in addition , several commercial solutions have become available that offer clients the tools to partake in telepathology and purchase cloud services ( e.g. corista , xifin , proscia ) . most telepathology publications to date have dealt more with the technology aspects than the clinical experience of this practice . the aim of this study was to share 3 years worth of experience involving international teleconsultation between upmc and kingmed diagnostics in china . since 2012 , upmc and kingmed diagnostics in china established a upmc - kingmed international telepathology consultation center in guangzhou kingmed . the upmc is a tertiary academic medical center located in pittsburgh , pennsylvania in the usa . the anatomical pathology department within the academic medical centers ( upmc presbyterian , upmc shadyside , upmc magee , children 's hospital of pittsburgh ) is structured using a center of excellence model , where anatomical pathology cases are handled and signed out only by subspecialty pathologists ( e.g. neuropathology , dermatopathology , cytopathology , etc . ) . kingmed diagnostics is a large network with 27 central pathology laboratories serving 13,600 hospitals and clinics in china . guangzhou kingmed diagnostics ( guangzhou , china ) is the first pathology laboratory to be fully certified in both anatomic and clinical pathology by the college of american pathologists in china . guangzhou kingmed diagnostics was also certified by the international organization for standardization ( iso 15189 ) . the diagnosis rendered by expert pathologists from upmc is regarded as a second opinion and not used for primary diagnosis . since upmc pathologists were not licensed to practice medicine in china , kingmed were legally responsible for final diagnoses on consultation cases . the pathologists from guangzhou kingmed telepathology consultation center sign out a final report in chinese for each case . patients receive both an english report from the upmc pathologist and chinese report from kingmed pathologists . the pathologists at the guangzhou kingmed telepathology consultation center only gave a final diagnosis after slides had been reviewed by upmc pathologists . the technology employed to support telepathology between upmc and kingmed in china has been previously described . in brief , a customized web - based digital pathology consultation portal was developed [ figure 1 ] . glass slides were scanned in china using a nanozoomer scanner ( nanozoomer 2.0-ht , hamamatsu ) . all slides were scanned at 20 , except for hematopathology cases that were scanned at 40. the hematopathologists at upmc requested higher resolution images upfront to facilitate their interpretation of cases . for the first 2 years , wsi submitted for consultation resided on the client 's server ( hammamatsu ndp.serve ) in china . pathology consultants from pittsburgh in the usa used the upmc web portal to securely access these images on the client 's server . workflow ( e.g. , case triage , transcription ) and reporting were incorporated into this web - based application . in the 3 year , digital slides were transferred without compression to a server in pittsburgh , usa using commercial file transfer software ( aspera ) . customized university of pittsburgh medical center kingmed teleconsultation web portal in china , each kingmed branch located within different cities nationwide received telepathology consultation cases from local pathologists , clinicians , and/or at the request of patients to be sent to the kingmed consultation center in guangzhou . tissue sections for routine h & e staining and immunohistochemistry ( ihc ) were cut at 3 m . although attempts were made to enhance slide and stain quality as much as possible for telepathology purposes , there were still differences in slide quality depending on which kingmed site generated the slides . for difficult surgical pathology cases requiring consultation , initial glass slides ( h & e and when included immunohistochemical stained slides ) were screened at guangzhou kingmed center before being referred to upmc expert pathologists . glass slides and tissue blocks were not permitted to be physically mailed to upmc in the usa due to chinese regulations . in other words , this also limited glass slides being sent later to pittsburgh for quality assurance , re - review of a proportion of cases after diagnoses were rendered . upmc and kingmed pathologists had the ability to communicate bidirectionally [ figure 2 ] , which allowed pathologists to request additional information ( e.g. , clinical findings , gross pathology details , flow cytometry data , etc . ) and if necessary even radiology images . if required , upmc pathologists were allowed to order additional stains including immunostains to further work up cases . these additional slides were prepared at the guangzhou kingmed center , then digitized and added to the existing consult case . at the outset , both partners established an agreeable stain quality and menu of immunohistochemical stains available in china . at the start of this collaboration , upmc pathologists reviewed 10 cases with glass slides compared to scanned images to confirm quality . participating pathologists at upmc dedicated information technology ( it ) staff at both partnering institutions maintained the telepathology infrastructure , monitored turnaround time ( tat ) , and were involved in troubleshooting technical issues . screenshot from the telepathology portal illustrating the value of bidirectional communication a retrospective study using descriptive statistics was performed evaluating the consultation experience and diagnostic results between upmc and kingmed over a 36 month period ( january 2012 - december 2014 ) . tat was counted as the time when upmc received scanned images to the time when upmc pathologists signed out the case with a final diagnostic interpretation . when performed , tat included the time needed for additional procedures such as performing ihc stains or molecular analysis . based on the final diagnosis rendered by upmc expert pathologists , the cases were divided into three groups : those with definitive ( certain ) diagnoses , suggestive ( favored ) diagnoses , and atypical ( indeterminate ) diagnoses . since 2012 , upmc and kingmed diagnostics in china established a upmc - kingmed international telepathology consultation center in guangzhou kingmed . the upmc is a tertiary academic medical center located in pittsburgh , pennsylvania in the usa . the anatomical pathology department within the academic medical centers ( upmc presbyterian , upmc shadyside , upmc magee , children 's hospital of pittsburgh ) is structured using a center of excellence model , where anatomical pathology cases are handled and signed out only by subspecialty pathologists ( e.g. neuropathology , dermatopathology , cytopathology , etc . ) . kingmed diagnostics is a large network with 27 central pathology laboratories serving 13,600 hospitals and clinics in china . guangzhou kingmed diagnostics ( guangzhou , china ) is the first pathology laboratory to be fully certified in both anatomic and clinical pathology by the college of american pathologists in china . guangzhou kingmed diagnostics was also certified by the international organization for standardization ( iso 15189 ) . the diagnosis rendered by expert pathologists from upmc is regarded as a second opinion and not used for primary diagnosis . since upmc pathologists were not licensed to practice medicine in china , kingmed were legally responsible for final diagnoses on consultation cases . the pathologists from guangzhou kingmed telepathology consultation center sign out a final report in chinese for each case . patients receive both an english report from the upmc pathologist and chinese report from kingmed pathologists . the pathologists at the guangzhou kingmed telepathology consultation center only gave a final diagnosis after slides had been reviewed by upmc pathologists . the technology employed to support telepathology between upmc and kingmed in china has been previously described . in brief , a customized web - based digital pathology consultation portal was developed [ figure 1 ] . glass slides were scanned in china using a nanozoomer scanner ( nanozoomer 2.0-ht , hamamatsu ) . all slides were scanned at 20 , except for hematopathology cases that were scanned at 40. the hematopathologists at upmc requested higher resolution images upfront to facilitate their interpretation of cases . for the first 2 years , wsi submitted for consultation resided on the client 's server ( hammamatsu ndp.serve ) in china . pathology consultants from pittsburgh in the usa used the upmc web portal to securely access these images on the client 's server . workflow ( e.g. , case triage , transcription ) and reporting were incorporated into this web - based application . in the 3 year , digital slides were transferred without compression to a server in pittsburgh , usa using commercial file transfer software ( aspera ) . in china , each kingmed branch located within different cities nationwide received telepathology consultation cases from local pathologists , clinicians , and/or at the request of patients to be sent to the kingmed consultation center in guangzhou . tissue sections for routine h & e staining and immunohistochemistry ( ihc ) were cut at 3 m . although attempts were made to enhance slide and stain quality as much as possible for telepathology purposes , there were still differences in slide quality depending on which kingmed site generated the slides . for difficult surgical pathology cases requiring consultation , initial glass slides ( h & e and when included immunohistochemical stained slides ) were screened at guangzhou kingmed center before being referred to upmc expert pathologists . glass slides and tissue blocks were not permitted to be physically mailed to upmc in the usa due to chinese regulations . in other words , this also limited glass slides being sent later to pittsburgh for quality assurance , re - review of a proportion of cases after diagnoses were rendered . upmc and kingmed pathologists had the ability to communicate bidirectionally [ figure 2 ] , which allowed pathologists to request additional information ( e.g. , clinical findings , gross pathology details , flow cytometry data , etc . ) and if necessary even radiology images . if required , upmc pathologists were allowed to order additional stains including immunostains to further work up cases . these additional slides were prepared at the guangzhou kingmed center , then digitized and added to the existing consult case . at the outset , both partners established an agreeable stain quality and menu of immunohistochemical stains available in china . at the start of this collaboration , upmc pathologists reviewed 10 cases with glass slides compared to scanned images to confirm quality . dedicated information technology ( it ) staff at both partnering institutions maintained the telepathology infrastructure , monitored turnaround time ( tat ) , and were involved in troubleshooting technical issues . screenshot from the telepathology portal illustrating the value of bidirectional communication a retrospective study using descriptive statistics was performed evaluating the consultation experience and diagnostic results between upmc and kingmed over a 36 month period ( january 2012 - december 2014 ) . tat was counted as the time when upmc received scanned images to the time when upmc pathologists signed out the case with a final diagnostic interpretation . when performed , tat included the time needed for additional procedures such as performing ihc stains or molecular analysis . based on the final diagnosis rendered by upmc expert pathologists , the cases were divided into three groups : those with definitive ( certain ) diagnoses , suggestive ( favored ) diagnoses , and atypical ( indeterminate ) diagnoses . during the 3 year study period , there were 1561 cases sent for consultation to upmc including 144 cases in 2012 , 614 in 2013 , and 803 in 2014 . the distribution of cases among different body systems and the corresponding tat for rendering a final consultation diagnosis is listed in table 1 . hematopathology received the most cases ( 23.7% ) , followed by bone / soft tissue pathology ( 21.0% ) and gynecologic / breast ( 20.2% ) subspecialties . the average tat was 6.8 days in 2012 , 5.3 days in 2013 , and 5.0 days in 2014 . subsequent immunostains were ordered for most of the cases . for certain cases , especially in hematopathology , more than one round of immunostains was needed which increased the tat . overall , the average tat gradually improved as did user satisfaction with the system based on subjective evaluation . teleconsultation case distribution and turnaround time in most ( 82.4% ) cases , a definite diagnosis was provided [ table 2 ] . the main reasons for not providing a definite diagnosis included lack of clinical information , missing gross description , insufficient tissue sections submitted , and/or no material available to perform additional immunostains . cases sent for consultation in general were either difficult to diagnose or were rare entities [ figures 35 ] . since kingmed is an independent reference laboratory , information on follow - up surgical resection specimens was not made available to upmc . final diagnoses rendered by upmc expert pathologists diagnostic entities rendered by upmc expert pathologists examples of challenging soft tissue pathology consultation cases . ( top left ) recurrent acral myxoinflammatory fibroblastic sarcoma . the clinical image shown in this case ( bottom right ) pleomorphic hyalinizing angiectatic tumorwere examples of rare gynecologic and breast pathology consultation cases . ( left panel ) 17-year - old female with an ovarian embryonal carcinoma ( top left h & e ; bottom left positive cd30 immunostain ) . ( right panel ) 45-year - old female with a breast metaplastic carcinoma showing chondroid differentiation ( top right h & e ; bottom right cytokeratin 5/6 immunostain ) examples of challenging lymphoma consultation cases . ( top panel ) anaplastic lymphoma kinase - negative anaplastic large cell lymphoma ( top left h & e ; top right cd30 immunostain ) . ( bottom panel ) classical hodgkin lymphoma ( bottom left h & e ; bottom right cd30 immunostain ) the original diagnoses for cases submitted for consultation were recorded and analyzed . most cases were referred by pathologists , followed by requests from primary clinicians in china for cases to be sent to the usa for a second opinion [ table 4 ] . of 1561 consulted cases , 706 cases ( 45.2% ) were sent for consultation without an initial primary diagnosis or diagnostic impression . for the remaining 855 cases ( 54.7% ) where a primary diagnosis or initial impression was made by the primary pathologists in china , for cases were a primary diagnosis was submitted , upmc expert pathologists agreed with that primary diagnosis or impression in 25.6% of cases , and completely disagreed or considerably modified the primary diagnosis ( i.e. , the treatment plan was altered , and/or prognosis differed ) in 50.8% of cases [ table 5 ] , which included 278 cases of malignancies / cancers . the organ distribution for cases with primary diagnoses that had disagreements are listed in table 6 . of note , hematopathology , and bone / soft tissue cases received a lower percentage of cases with a primary diagnosis ( 45.7% and 43.7% ) , indicating the difficulty general pathologists have with pathological evaluation of these organs . the disagreement rates for hematopathology and bone / soft tissue cases were 53.3% and 55.9% , respectively . for the 59.5% of gynecology / breast cases that had primary diagnoses , the disagreement rate was 41.5% , which is lower than that seen with hematopathology and bone / soft tissue cases . surprisingly , 84.6% of head / endocrine cases submitted with a primary diagnosis showed that 72.7% of these cases had disagreement [ table 6 ] . referral nature of cases submitted for telepathology consultation agreement of diagnoses between upmc expert pathologists and the primary pathologists in china teleconsultation case distribution with significantly modified diagnoses report of a government supported telepathology consultation and quality control program for cancer diagnosis in china indicated that telepathology could play an important role in improving pathology diagnoses in china . to date , there have been no large studies showing the success of telepathology involving china and other countries . the results of this study indicate , for the first time , that international telepathology consultation can improve patient care in china by facilitating access to pathology expertise . the ongoing success and marketing effort of the telepathology collaboration between upmc and kingmed resulted in an increased number of cases being submitted for consultation each year . teleconsultation , in turn , improved the quality of care for patients since the second opinions modified the primary diagnosis ( i.e. , the treatment plan was likely to be altered , and/or prognosis differed ) in 50.8% of cases . of note , the shift in requests for consultation from pathologists at first to treating clinicians and then even to patients themselves later indicates the value placed on obtaining an expert pathology opinion . similar results were reported in a national telepathology consultation and quality control program in china . that study showed that 24.2% of cases had expert 's opinion significantly different from submitting pathologists . for the purposes of this study , significant difference means a change from malignant to benign or from benign to malignant . the rate increases to 28.8% if cases without a preliminary diagnosis were excluded . based on our experience , the highest disagreement rates were seen with head and neck / endocrine cases , hematopathology , bone / soft tissue and then gynecology / breast cases , which may indicate the difficulty general pathologists have with making pathology diagnoses in these cases . our study was not intended to compare diagnostic capabilities between pathologists in china and the usa , but rather to demonstrate that telepathology is a convenient mechanism to assist those seeking consultation . moreover , there are three general levels of hospitals in china : level 3 are the large hospitals located in big cities , level 2 are mid - sized hospitals located in small - middle cities , and level 1 which are hospitals present in the countryside , suburbs or small cities . hence , the primary diagnostic accuracy for this study does not fully represent the diagnostic skill of all chinese pathologists . in addition , immunohistochemical studies requested to subsequently work - up cases submitted for teleconsultation can be helpful in the final diagnosis . the pathology consultation service through the centers of excellence can offer comprehensive consultations in anatomic pathology , cytology , electron microscopy , ihc , flow cytometry , image analysis , cytogenetics , and molecular diagnostics to all levels of hospitals in the united states and other countries . indirect benefits of this telepathology partnership include education , skill enhancement for pathologists from both parties , and academic collaboration . a prior systematic review of general international telemedicine collaborations revealed several factors that were essential to success . they included low operating costs , use of simple technologies , bi - directional communication , incentive - based programs , locally responsive services , strong team leadership , appropriate training , and user acceptance . the success of our international digital consultation service was dependent on strong commitment and support from leadership , it expertise , and dedicated pathologists who understood the language and culture on both sides . in addition , we customized our web portal to satisfy the needs of both the referring site and consulting pathologists . this included a simple user interface and a built - in mechanism to support bi - directional discussions . pathologists also received extensive training and consultants were offered a financial incentive to participate . for any cross - border telemedicine venture , there are likely to be barriers . some of these obstacles include legal / regulatory issues , sustainability factors ( e.g. , high cost , inconsistent use , poor scalability ) , cultural factors ( e.g. , different language , trust issues ) , and contextual factors ( e.g. it infrastructure , network limitations , time zones ) . indeed , some of the challenges we encountered included internet speed restrictions and overcoming firewalls , differences in culture and health care systems , lack of clinical information and gross pathology descriptions with some cases , insufficient tissue sections submitted for evaluation , and difficulties related to direct communication with chinese clinicians . in summary , a retrospective review of teleconsultation experience between upmc in the usa and kingmed diagnostics in china shows a successful , sustainable and growing international partnership . leveraging technology to facilitate access to remote pathology experts has resulted in great improvement of patient care in china . therefore , international telepathology practice for second opinions should be encouraged .