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Speaking for myselfTHE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 14, No.6, 2001

Barriers to good diagnosis and practice in developing countries

K. N. NARESH

WHAT IS 'GOOD' DIAGNOSIS?This article was initially prepared as a talk for a recent interna-tional meeting in the field of oncology. Most of what I have writtencannot be referenced; my views have been shaped through discus-sions with many knowledgeable and experienced practitioners ofoncology in association with whom I practice. The article dealsprimarily with the practice of surgical pathology and allied disci-plines, particularly in an oncology setting.

Before I discuss the 'barriers', I will dwell on what is 'good'diagnosis. If this question is posed to different people, the answerswould be many and varied.

To pathologists, this often means a diagnosis that will beaccepted by an overwhelming majority of experienced fellowpathologists. This portrays a 'good diagnosis' as one that can bevalidated by a majority (election). An alternative method could bematching the diagnosis with a 'gold standard', which couldrepresent an extreme minority, but this has inherent problems ofwhom or what evidence to consider as 'gold standard'.

Histological diagnoses are based on morphological appear-. ances of the lesion at one particular time-point (time of biopsy) inthe evolution of the disease. A pathologist should be able to,through the morphological appearance, conceptualize the entiredisease course till it has reached the particular time-point and alsobeyond, had the lesion been left undisturbed.

To clinicians, a good diagnosis could be one that: (i) fits theirclinical impression; (ii) has clearly laid down treatment policies instandard textbooks; (iii) could guide the tailoring of treatment; (iv)is acceptable to other pathologists or clinicians if a second opinionis sought; and (v) is helpful for formulation of new hypotheses andstrategies about the disease and its management.

For a medical researcher, good diagnosis can be: (i) the basisfor disease stratification that helps in understanding diseaseprocesses; (ii) an impediment to understanding if one forgets thatdiagnoses and classifications are made more for wider acceptanceand clinical utility than for definite biological relevance.

To some patients, a diagnosis might mean just a label withwhich their suffering is identified, and with this identificationthey move from a pathologist to a clinician and from oneclinician to another. To others, it could mean a label on whichprojections of their survival, quality of life and financial aspectsare made. Decisions on family and social commitments are alsoinfluenced.

Diagnosis could also be made to suit clinical situations. Out ofcontext, it might be difficult to slot them as 'good' or 'bad'. Inpatients presenting with advanced disseminated cancers, wherepalliation is the only option, ruling out a lymphoma or a germ celltumour may be all that would be required for treatment. If it is a

Department of Pathology, Tata Memorial Hospital, Parel, Mumbai 400012,Maharashtra, India; knnareshtehotmail.com

© The National Medical Journal of India 2001

metastatic adenocarcinoma, one may only have to suggest whetheror not it represents one of the more easily treatable cancers such asthose from the thyroid, prostate or breast. Such an approach maynot suffice in an institution with a large research component.

Another important aspect is the mode of functioning of the'health care systems' in developing countries. Cancer diagnosisand management is undertaken to a great extent by individualpractitioners and is not institution-based. Many of the barriersencountered are a fall-out of this.

So, in the 'game' of 'diagnosis', pathologists and cliniciansform the principal 'players', and the medical researcher has a roleof sometimes being an onlooker and sometimes a guiding force.Unfortunately, the patient who is actually at the centre of all thisis a highly concerned but often mute recipient.

'QUALITY' OF DIAGNOSISClinicians are the first people to encounter the patient, and thusplaya pivotal role. Broadly, clinicians can be slotted into threecategories:

1. Those relying heavily on clinical acumen. These clinicians givemuch importance to a meticulous clinical examination, docu-mentation and interpretation of findings. They may use patho-logical diagnosis for mere confirmation of their clinical diag-nosis and any deviation is looked at with suspicion. At times,they can overwhelm a less experienced pathologist to recon-sider the histological diagnosis in view of the clinical diagno-sis. Nevertheless, pathologists and patients benefit a great dealby reviewing cases upon such clinicians' requests.

2. Those depending on pathologists and radiologists to providethem a label with clearly laid down treatment policies-aradiologist to provide the anatomical extent and context oflesion and a pathologist, often a cytopathologist, to interpret afine needle aspiration (FNA) and provide a label. This, in myview, is a dangerous concoction and, unfortunately, not un-common.

3. Clinicians who as team members along with pathologists,radiologists and others work out a diagnosis and subsequentmanagement.

On many occasions, the principal clinician is not a surgeon,and the patient gets referred to a surgeon for a biopsy. Thesurgeon who functions as an intermediary may limit herlhis roleto the technical aspect of performing a biopsy. Further, (s)he maynot be in a position to render adequate clinical information to thepathologist, or discuss the case and the diagnosis in detail.Furthermore, requests for biopsy procedures sent to surgicaldepartments may be delegated to junior colleagues or residentswithin the surgical unit. Many biopsy procedures are technicallyless demanding and senior surgeons may not feel the need toperform them. The junior surgeon's inexperience may be reflected

SPEAKING FOR MYSELF

in improper selection of the site, improper timing and selecting animproper modality for the biopsy (FNA, needle core, open orexcision biopsy).

For good diagnosis, optimal tissue fixation and preservationare the most important. This involves slicing the tissue into 3-4mm pieces and fixing it in a good amount of the right fixative andfor an optimal time. Neutral buffered formalin of good qualitydispensed in proper containers is essential and should be easilyavailable to pathologists and surgeons. Improper fixation is themost common problem encountered in surgical pathology prac-tice.

It would be ideal to have the fresh biopsy material collected bypathology staff within minutes of the surgical procedure. Thepathology staff in turn should preserve the material for conven-tional histology, electron microscopy, flow cytometry, immuno-histochemistry, molecular pathology and other specialized tech-niques. This should be practised in major institutions. If thiscannot be achieved, especially where procedures are performed atperipheral clinics, surgeons and surgical residents need to beeducated about how to handle fresh biopsy material and ofmodalities of tissue preservation.

Medical researchers should realize that diagnoses can varybetween pathologists and there can be subtle differences in thediagnoses offered by the same pathologist on re-review of casesaccrued over a period of time. Hence, at the time of a study, onepathologist or a panel of pathologists should review the diagnosesof all cases to perform meaningful research. Yet another aspectthat is often forgotten is that it takes a long time for medicalresearchers to sort out the temporal relationship of their scientificfindings to overall disease evolution. This could result in investi-gating the wrong candidates as diagnostic or prognostic markersby pathologists and clinicians.

In major institutions, one point that has to be clearly made toall concerned is that a biopsy is performed primarily to provide anadequate diagnosis to the patient. All other goals are secondary. Inthe enthusiasm to perform research, this is often forgotten, espe-cially when the biopsy sample is relatively small. Researchinterests cannot and should not jeopardize the patient's interest.

Osler once said: 'As is your pathology, so is your practice.' Tothis one may add: 'As is your technical support and infrastructure,so is your pathology.' The primary requirement for a 'good'diagnosis is a good haematoxylin and eosin (H&E) section.Nothing can replace the information provided by this. This doesnot need very expensive equipment. What it needs is: (i) ajudicious investment on equipment that can perform well underthe prevailing circumstances; and (ii) dedicated technical person-nel. Often, pathologists invest a fortune on expensive automatedequipment, but cut comers while buying the right kind of micro-tomes, knives or disposable blades. Similarly, using suboptimalprocessing methods, and poor quality fixatives and reagents forparaffin embedding is rather common. This inevitably results in atechnically suboptimal histological preparation that is difficult tointerpret.

Automation in surgical pathology may not be the right answerfor a good diagnosis in developing countries. Lack of reliablesupport facilities for the upkeep of such equipment in a non-urbansetting makes it more of a liability. In contrast, grooming andfostering technical expertise is a very sound investment. Expertisein histological techniques is acquired over a long period of timeand needs proper planning.

Reported error rates in surgical pathology range from 0.25%to 43%. The error rates differ between anatomical regions and

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specimen types and they also vary when categorized according tothe clinical significance of the error. I In a study by the College ofAmerican Pathologists on 1 667547 cases (not limited to oncol-ogy), the rate of amended reports was 1.9 per 1000 cases.'Similarly, a questionnaire-based study from the UK reported 244errors from 119 pathologists and 42% of these errors affectedpatient management. In the latter study, an unduly large propor-tion of errors were on samples from the lymphoreticular system.'

Mistakes in diagnosis by pathologists are universal and aremore often due to errors in interpretation. With experience, theproportion of errors is likely to reduce. However, a more experi-enced pathologist is also likely to be referred more problematiccases. Thus, errors of interpretation can never be completelyovercome. To find a pathologist who has never made a diagnosticerror is to find a liar or an absolute novice.

A pathologist's mistakes are more likely to come to lightbecause tissue sections and paraffin blocks can be preservedindefinitely and not only can the slides be reviewed by the originalpathologist, but also by other pathologists. Newer techniques,previously not available, can also be performed on the archivedmaterial. This is something unique to pathology practice.

THE BARRIERSPathologist-related barriers for a good diagnosis can be catego-rized as those related to (i) training, (ii) approach, (iii) organiza-tional policies, and (iv) infrastructure.

Inadequate training of pathologists during postgraduation is aproblem in developing countries, as the standards of practice ofsurgical pathology differ widely. A constant scrutiny to identifythose at unacceptably low standards is not available and, if found,is not enforced. A formal continuing medical education systemawarding scores to candidates and a body to revive licensing basedon performance is not available.

There are some problems that are innate to the field and areuniversal. Surgical pathologists in most places, even in majorinstitutions, do not restrict themselves to specific specialties. Asa fall out, there are many areas in pathology where most patholo-gists do not see a particular entity in adequate numbers to carryproper morphological impressions. This lacuna makes them missthe diagnosis and the mistake is not even realized. Thus, thequestion of referring to a specialist pathologist does not arise.Furthermore, we are today faced with an explosion of informationand rapid technological advances. It is extremely difficult to keepabreast with a rapidly changing and an ever-expanding scenario inmany different fields.

Non-availability of clinical information is a severe handicap.Pathologists should interpret histological information in lieu ofthe clinical presentation before conveying the final diagnosis. Thiscould reduce mistakes to a great extent, but one should not base thehistological diagnosis on the clinical information alone. It ispossible that clinical information could bias the histologicalinterpretation. Hence, my personal approach, which is a littledifferent from the standard protocol, has been to make an initialimpression based purely on morphology and then reassess themorphological interpretation in the clinical context before render-ing the diagnosis.

Policies that could improve the standards of diagnosis are: (i)subspecialty practice; (ii) internal auditing; and (iii) externalauditing. Specialization within surgical pathology has been ahighly debated issue and opinions do not converge. In the initialyears ofa surgical pathologist's career, acquiring morphologicalskills in multiple areas of pathology is definitely beneficial.

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However, in the later years of one's career, the institution andcommunity at large would probably benefit by pathologists'specializing in specific fields. If subspecialization is not possible,internal auditing of all diagnoses by an expert in the correspondingsubject on a continuing basis should be encouraged. Intra-departmental consultation on problematic cases is also helpful. Aproportion of cases should also be submitted for inter-institutionalauditing by an external expert or a panel of experts. Audits can alsoprovide information about errors, their nature and the types ofspecimens more commonly affected.'> In a study from California,a second pathologist through routine review (before release of thereport) detected an error rate of 0.26% of potential clinical signifi-cance."

Fine needle aspiration cytology (FNAC) has gained tremen-dous popularity because ofthe ease ofthe procedure and its shortturnaround time. Its role is immense when it is followed by asurgical modality of treatment, because evaluation of the surgicalspecimen compliments and also serves as an audit for the earlierFNA evaluation. However, the role ofFNA in the management ofcancers that are primarily treated by non-surgical modalitiesshould be critically assessed. Extreme examples are those inwhich treatment for lymphomas or for paediatric malignant smallround cell tumours is instituted based only on FNA diagnosis. Toprovide a 'good' primary diagnosis, an adequate surgical speci-men is essential.

Non-availability of some of the ancillary techniques could bea barrier to 'good' diagnosis. Immunohistochemistry and molecu-lar pathology have come as a big boon to conventional surgicalpathology and have revolutionized our concepts. The criteria fordiagnosis in recent times, especially in some areas of pathology,have been based on the knowledge obtained from these tech-niques. However, questions of when to use, how much to use andwho is to bear the cost of these ancillary techniques need to beaddressed cautiously.

In centres where these techniques are available, there is alwaysa tendency to fall back on them even when they are not absolutelyessential. Of course, concepts and confidence in interpretingresults are built on cases that could be diagnosed purely onmorphological assessment. In such situations, should patients bemade to pay for the procedure is an ethical dilemma. In the eventof a disagreement between morphological assessment and theresults of these techniques, what is the gold standard? Can theresults of these newly identified techniques overrule a diligentlymade morphological diagnosis? What measures should the medi-cal fraternity take to curb abuse of these techniques for financialgains? Using ancillary techniques as a crutch by practitioners whoare inadequately trained in conventional morphology should bethoroughly discouraged. In the event of non-availability of thesetechniques, how pathologists should give a reasonably 'good'diagnosis is an issue in itself.

The issue of quality control attains enormous significance inthese fields. Maintaining high standards is extremely difficult inlaboratories that do not process a large number of samples on aregular basis. Improperly performed ancillary techniques can domore damage than good in the pursuit of a precise diagnosis. Oneof the options would be to have a few referral laboratories thatundertake these techniques. Thereby, costs can be reduced to agreat extent and expertise can be developed and availed. Govern-

THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 14, No.6, 2001

mental funding and funds from other agencies should playa majorrole in such pursuits. Though it is not possible to train allpathologists in molecular medicine, the awareness of the utility ofancillary procedures is crucial and pathologists should have theknow-how of preserving tissues for them. Unbiased tissue preser-vation is essential as diagnostic problems and dilemmas come upwithout prior notice.

The one advantage with pathology practice is that materialsuch as slides and blocks and even DNA and cDNA can betransported to far off places with ease. So, can telepathology be analternative to a conventional second opinion rendered on physi-cally transported material? We don't have an answer yet.

WHAT ARE THE SOLUTIONS?Disease-specific registriesThese are useful for relatively less common diseases wherediagnostic difficulties are common and where facilities beyondconventional morphology are often required. Having many spe-cialized centres is impractical in developing countries both foreconomic and quality control reasons.

Specialty combined clinicsTo establish clinics composed of a group of experts in a particularfield, irrespective of their primary training. For example, a groupcomposed of medical oncologists, surgical oncologists, radiationoncologists and pathologists interested in lymphoid neoplasia,could make joint decisions on individual patients.

In the prevailing scenario in developing countries, 'joint clin-ics' are impractical outside institutions. Apart from developingdisease-specific registries, other avenues such as pursuing exter-nal audits, external quality control and revival of pathologylicences based on performance are the possible solutions.

Medical professionals in developing countries, especially thosein institutions, take pride in the abundance of clinical material thatthey are exposed to. This abundance of material in developingcountries can be both an asset and a liability. If special attentionis not paid and proper planning is not drafted, quality and quantitycould get mutually exclusive. While the abundance can expose aperson to material of a lifetime in possibly a couple of years, it canalso make him/her (i) learn and perfect a completely wrongapproach, (ii) obtain a very 'spinal' -callous-approach to diag-nosis and management, let alone allowing himlher to ask ques-tions and deduce answers. Thus, policy-makers have a major rolein making the clinical material a true 'asset' to generations ofmedical personnel who train in developing countries.

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