What is the outcome of a second opinion in BSTT pathology?
As bone and soft tissue tumours (BSTTs) are collectively uncommon and individually comprise many rare entities, pathologists outside specialist sarcoma units will have limited opportunity to develop expertise in their diagnosis. This has been made even more challenging in the past decade, with an increasing trend to preoperative diagnosis by core needle biopsy (which provides limited material for ancillary studies and makes appreciation of tumour heterogeneity and diagnostic architectural features more difficult). Therefore, whenever a sarcoma is biopsied or even possibly resected outside a specialist multidisciplinary team (MDT) setting, timely review of the diagnosis (including histologic subtype and grade) is warranted.
Expert pathologist review
Clearly this sort of question does not lend itself to investigation through a randomised trial; but there is ample and consistent “low level” evidence that expert review results in a change to diagnosis in a significant proportion of cases (ranging from a minor disagreement over tumour grade, which may nonetheless influence treatment decisions, to a false positive - or false negative - diagnosis of malignancy. Expert review of cases may occur in a variety of settings, for example:
- 1. initial diagnosis of sarcoma results in referral to a specialist centre, and the sarcoma MDT’s pathologist undertakes routine review of original material from another centre
- 2. diagnostic material is sent for central review as part of a clinical trial
- 3. studies conducted through institutions or tumour registries specifically review “outside” diagnoses to investigate this question
- 4. the “non-expert” pathologist is aware of their limitations in this area and sends a difficult case for an “expert” second opinion
- 5. initial material (biopsy and/or resection) is reviewed when the patient’s clinical course seems out of keeping with the initial diagnosis
Clearly one would expect the level of discrepancy between the referring and receiving pathologists’ diagnoses to be greater in the last case, but even in examples 1-3 the level of disagreement can be disturbingly high. In some cases, discordant results may have little or no impact on the patient (such as particular sub-types of high grade sarcoma for which management will be the same), but in other cases the impact of a discordant diagnosis may be significant. For this reason, many studies in this area divide the rates of discordance along the lines of “minor” and “major” disagreement, as well as an overall “concordance rate”. Disturbingly, reported rates of overall discordance approach or even exceed 50% in some studies, with even “major” disagreement occurring in over 25% of cases, but more often between 10 and 20%. And in some cases there is even disagreement over whether a tumour is truly a sarcoma, or another malignancy (typically melanoma, carcinoma or germ cell tumour), or a benign mesenchymal lesion (often variants of fasciitis, or benign fatty, vascular or smooth muscle proliferations). Interestingly, in at least one study it was felt that in many of the misdiagnosed cases, the target diagnosis could have been made with hematoxylin and eosin (H&E) stained sections and a limited range of immunohistochemical stains, without recourse to highly specialised antibodies or molecular genetic techniques. This suggests that in many cases the missed diagnosis was due to lack of familiarity with rare entities on the part of the pathologist, emphasising the importance of experience and sub-specialty training over “high-tech” approaches.
Effect of altered diagnosis
Delayed or incorrect diagnosis can lead to inappropriate or unnecessary surgery, chemo- or radiotherapy, or withholding of potentially life-saving therapy. Even if a diagnosis of sarcoma is correct, failure to recognise a particular tumour sub-type may preclude the employment of specific targeted therapies, and errors in grading or risk stratification may lead to more or less vigorous therapy than would otherwise have been recommended (such as whether or not to administer adjuvant treatment). In the case of aggressive tumours, even relatively short delays in accurate diagnosis can impact on patient survival.
Access to expert review/second opinions
Timely expert review is, therefore, in the best interests of the patient, but many pathologists are faced with questions over how, and to whom, these cases should be referred. Sending cases to outside institutions incurs a cost for both the referring and the receiving laboratory, and these costs are poorly accounted for, if at all. Currently, expert review of diagnostic material is not funded in the Medicare Benefits Schedule, and whilst many experts choose not to charge a fee for these referrals, institutions are increasingly demanding a fee – a cost which the referring laboratories cannot meet and which is therefore often passed on to the patient. Yet failure to obtain a timely correct diagnosis can result in unnecessary and inappropriate treatment, which in drug costs alone may be far more expensive than the pathologist’s review.
Evidence summary and recommendations
|Expert review of bone and soft tissue tumours (BSTTs) diagnosed in non-specialist centres results in changes to the diagnosis and/or grading in a significant proportion of cases.||IV||, , , , , , |
|Whenever a primary diagnosis of bone or soft tissue sarcoma is made outside the context of a specialist sarcoma unit, wherever possible, referral to an expert pathologist (within a specialist sarcoma unit) for review of the diagnosis and grade should be undertaken before definitive management is instituted.||D|
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