"Malpractice"
There are four critical aspects of medical negligence or "malpractice", namely duty, breach, proximal cause and damage [9, 11, 12, 13, 14] . As histopathologists, we clearly have a duty to render an interpretation of patients' specimens we receive [9]. We are also vicariously liable for those working under our direction, such as assistants and residents [9, 12] Breach is defined as failure to treat within the standard of care. A mistake is not necessarily malpractice, if it is a mistake that a reasonable number (not necessarily the majority) of appropriately trained and careful histopathologists in that region of the country would make, given the state of medicine at the time the mistake was committed. Standard of care must be established by expert testimony [11, 13] . It is a fluid concept, especially with regard to melanoma. On a practical level, it is essentially established by the experts involved in a given case [9, 12, 14, 15, 16] . In cases that go to trial, both the defense and plaintiff legal teams have experts who dispute whether the care rendered in a given case is within standard. As a result, it can become difficult for non-medical individuals who serve on juries to come to a decision regarding standard of care, and mistakes and/or bad outcomes can become equated with malpractice. Proximal cause (breach causes injury in fairly direct manner) is usually not at issue in medical malpractice [9]. Damage can be a difficult concept for non-medical individuals to grasp. When confronted with an ill patient or bereaved family members, it is often difficult to understand that a mistake may have had no relevance regarding progression of disease [1, 3] .

While the above information can induce depression, anger, and anxiety, one must keep these details in perspective [17]. Calls from patients to legal firms regarding medical issues do not necessarily result in a lawsuit, as about only one in thirty calls results in a suit [11]. Most suits result in no indemnity payment [1, 17] . In one large survey of medical lawsuits, only 3% of suits actually went to the jury and were decided for the plaintiff [8]. These figures would seem to imply that many malpractice suits are unwarranted [17]. States in which tort reform has occurred have shown a reduction in the insurance premiums and jury awards; pain and suffering (non-economic damage) caps appear to render medical malpractice suits less desirable to plaintiff's attorneys [1, 2, 18] .

Four Principles
In my opinion, there are four principles regarding melanocytic lesions which often place the dermatopathologist in a difficult position. First principle: melanocytic nevi are, arguably, the commonest neoplasms in man. Most individuals have at least a few nevi, and some have a hundred or more [19, 20] . Parenthetically, melanocytic nevi have been shown to be clonal, are likely neoplastic, and cannot be differentiated from melanoma based on clonality studies [21]. Second principle: malignant melanoma is, gram for gram, arguably the most malignant neoplasm in man. A 4 mm melanoma, which may approximate the size and shape of a green pea, is usually lethal [22]. A malignancy of similar size of the breast, colon, prostate, thyroid, or a variety of other organs, if removed, would likely result in cure. Third principle: nevi and melanomas may be very difficult to tell apart [23, 24] . Clinically this is well established [25, 26] . As such, histopathology is relied upon for diagnosis. However, recent studies have suggested a disturbing fact: interobserver studies on melanocytic lesions suggest even experts frequently disagree. Farmer et al demonstrated that a panel of eight pathologists, all experts in melanocytic lesions, were unable to agree unanimously (benign vs. malignant vs. indeterminate) on approximately two thirds of 37 "classic" melanomas and mimics of melanoma [27]. A participant in this study, A. Bernard Ackerman, in an editorial regarding it, noted "how… disastrous would the results have been had the examples been… unconventional?" "Lawyers… should take note… mistakes are not necessarily malpractice, and even experts make many of them." [28]

Subsequently, it was suggested that many of the cases in this series were not "classic" [29, 30] . Nevertheless, the findings remain striking. A similar study by Corona and coworkers involving 140 melanocytic lesions and four histopathologists showed significant disagreement (nevus vs. melanoma) on 26% of cases [31]. The statistics are as bad or worse when it comes to difficult melanocytic lesions of childhood. Barnhill et al, in a study of 30 tumors by 10 pathologists, found that "17 spitzoid lesions yielded no clear consensus as to diagnosis; in only one case did six or more pathologists agree on a single category… some lesions that proved fatal were categorized by most observers as either Spitz nevi or atypical Spitz tumors" [32]. More recently, Wechsler et al also showed similar poor agreement between expert histopathologists in the analysis of difficult melanocytic lesions of childhood [33]. While some defense lawyers have take appropriate advantage of these studies, this has not resulted in diminished malpractice claims regarding melanoma.

If experts frequently disagree regarding the diagnosis of melanocytic neoplasms, what can be expected from non-expert histopathologists? A study from the United Kingdom demonstrated that a group of 195 randomly selected pathologists were much more likely than a panel of histopathologists with expertise in melanocytic neoplasms to diagnose melanocytic lesions as malignant. The randomly selected group also demonstrated poor inter-observer agreement as compared to expert melanocytic histopathologists [34].

With these studies in mind, it is interesting to speculate that melanocytic lesions may share some characteristics with their neural crest relative, adrenal pheochromocytoma. It is well known that histopathologic features cannot accurately predict behavior of most pheochromocytomas [35, 36] . Fortunately, histology is much more predictive in melanocytic lesions. I suspect that experts would disagree significantly (benign vs. malignant) on less than 1% of randomly selected melanocytic neoplasms. However, as melanocytic lesions are so common, even a small percentage of cases which are difficult results in a large number of problematic cases. Certainly there is much literature to suggest that there is disagreement regarding histopathologic diagnosis of many diseases from virtually all organ systems [37, 38, 39, 40, 41] . However, when it comes to the topic of malpractice in the setting of melanocytic neoplasms, a fourth principal may be added to the three above: melanoma results in more lost years of life per fatal case than any other common malignancy except leukemia [42].

Russian Roulette?
Given the dismal statistics noted above, working in a high volume dermatopathology practice can begin to feel, at times, like playing Russian roulette. It is not so much a matter of whether an untoward event will occur, but when. Our only "defense" is to load the gun as ably as possible, with appropriate history, adequate tissue and excellent histology.

History
The pathology requisition form has been referred to as "one of the most underutilized documents in medicine" [43]. When searching for a blank sheet of paper on which to write something in the laboratory, the requisition form would all too often suffice. When I asked one clinician why he failed to provide history, he responded that he "didn't want to bias me". Another said "why do you need history…it's just a lab test". Of course, we know that histopathologic examination is not simply a laboratory test but, rather, a consultation between physicians. We don't see the whole patient, but we certainly look hard at part of him or her. Regarding this consultation, it is likely that no individual has more impact on the professional life of a dermatologist than his or her dermatopathologist.

Those readers of this journal who are pathologists by training know especially well that there are two aspects of pathologic diagnosis: gross and microscopic examination. As histopathologists usually do not have an opportunity to see the patient, history plays an even greater role in dermatopathology, supplanting gross examination. Elements of adequate history regarding melanocytic lesions have been well documented and include patient age, biopsy site, ethnicity, a description of the lesion, and history of change, among other factors [43]. It is also well known that a variety of factors can, on occasion, cause benign lesions to demonstrate some histologic features which appear malignant. These include early evolving lesions, trauma, sunburn, PUVA therapy, prior biopsy, coexistent blistering disorder and nevi of unusual sites [44, 45, 46, 47, 48, 49] . Alerting the histopathologist to unusual foci, such as light areas (possible regression) or dark spots is also important. Most "black dots" within nevi have been shown to be benign foci of hyperpigmentation; however, a small percent represent melanoma [50]. In such instances, if we have been alerted to the presence of a dark spot, we can order deeper sections until we find it or until the specimen block has been exhausted. Additionally, knowing a clinician's level of concern can also useful to us, but only if we know our clinicians well.

Tissue is the Issue
Can you imagine the result of a fine needle aspiration of a Spitz nevus or of a nevoid melanoma? In both cases, there would be a high likelihood of misdiagnosis. And while no one would recommend doing such a procedure, small partial biopsies, which are not much better, are performed frequently. The partial biopsy assumption is that a clinician can consistently predict the portion of a suspicious pigmented lesion that will have the worst or "representative" histologic features. This assumption has been proven wrong on many occasions [51, 52] .

Those with little experience regarding the histopathology of melanoma may ask what a larger biopsy can provide other than a greater number of inscrutable cells. Most readers of this journal are aware that what it provides is the ability to assess pattern of growth. Pattern of growth can be thought of as a snap shot in time of the behavior of a lesion and convey much regarding its biologic potential [48]. Of course, some lesions cannot be sampled in their entirety. In such cases larger biopsies are preferable to smaller ones, and multiple biopsies are useful in some circumstances. Perhaps the most critical historical feature we can receive is the percentage of a lesion which has been biopsied. While we would all like to receive the entirety of every lesion we review, sometimes this will not occur. If we are aware that the biopsy is partial, we can put the histologic features in better context and qualify our diagnosis if necessary.

Histology
History and adequacy of tissue are features are not entirely in our control. However, the final chamber in the Russian roulette revolver, histology, is. Melanoma malpractice cases have demonstrated at least 7 types of histologic problems which can singly or together lead to misdiagnosis. 1. Pieces of tissue that are too far apart from one another within the specimen block (Figure 1). This has resulted in a number of malpractice cases, including the one involving A. Bernard Ackerman's "A Trial in Philadelphia" [53]. In our laboratory, whenever possible, we assign embedding to our most experienced histotechnologists and require that these technicians place sections in the block such that they are immediately contiguous and show the same orientation; when scanning along the dermal-epidermal junction of this type of section, one virtually "bumps into" the adjacent portion of tissue (Figure 2). Problem 2: Too many pieces in the specimen block (Figure 3). If there are more than 2 or 3 portions of tissue in a specimen block, not only is it difficult for the histotechnologist to orient all of these properly, but it is easy to miss seeing one under the microscope (Figure 3). Problem 3: incomplete sections. Sections of melanocytic lesions, especially challenging ones, which are not "full face" generally require recut sections. Problem 4: Tangential sectioning. Tangential sectioning often results in a lesion showing a more concerning or malignant histopathologic appearance (Figure 4). For this additional reason, it is important for experienced histotechnologists to perform embedding. Problem 5: Inadequate dehydration. Inadequate tissue dehydration during processing, when severe, can render tissue nearly uninterpretable. More commonly, one encounters this to a lesser degree. In these cases, melanocytes often show a distorted appearance with vacuoles around them which can lend a pseudomalignant appearance to a benign lesion (Figure 5). Inadequate dehydration can usually be remidied by ensuring that the dehydrating alcohols are of proper concentration. It is especially important that the final (100%) alcohol be uncontaminated by water and be changed daily [54]. Problem 6: Biopsies which are too small to bisect. One must bear in mind that the center of the biopsy, which the clinician presumably would like us to review, may not be present in initial sections from such biopsies. Problem 7: Curettings. While curettings may be adequate for basal cell carcinomas and some seborrheic keratoses, one must interpret a melanocytic lesion in their context cautiously, as curettings have contributed to allegations of malpractice [55].

Neoplasm?
Finally, even with excellent history, adequate tissue and the best of histology, the literature suggests that histopathology is not sufficient to render a specific diagnosis on a small subset of melanocytic lesions. If experts disagree frequently [27, 31-33] this conclusion is inevitable. The difficulty we face stems from the fact that virtually every difficult melanocytic lesion exhibits conflicting histologic criteria. A given case may demonstrate, for instance, circumscription, maturation, and an absence of mitotic activity; on the other hand there may be a predominance of single cells within the epidermis, solar elastosis, and a degree of asymmetry. Regrettably there is no literature which can tell us how to accurately diagnose most melanocytic neoplasms which demonstrate conflicting criteria [23]. Ultimately, balancing at least a dozen different criteria comes down to refined instinct and judgement. William Osler's words appear still true today and as applicable to histopathology as bedside medicine: "the practice of medicine is an art not a trade: a calling not a business; a calling in which your heart will be exercised equally with your head" [56, 57] .

The Epidemic
It is well known that we are experiencing a dramatic rise in the incidence of melanoma, which some have referred to as epidemic. The causes for this are not fully clear, but certainly sun exposure plays a role [58, 59] . There are also those who have proposed that histopathology plays an additional role [60-62]. Swerlick and Chen have suggested that histopathology may be causative and have argued if the melanoma epidemic were real, we would encounter a greater number of thick melanomas and a higher death rate from melanoma [61, 62] . They note that in the 1930's, most patients had lesions greater than 3 mm in depth, and most died from their disease. With biologic behavior as gold standard, histopathology approximated this gold standard. Swerlick and Chen have argued that we may be applying the same criteria to a different set of (thin) lesions. Additionally, histopathologists naturally feel strong moral and ethical pressure not to miss a melanoma. Strong medicolegal pressure might also contribute to more lesions being diagnosed as melanoma. By contrast, the best decision for a given patient, especially a young patient with a relatively thin lesion, may be to call a borderline lesion something other than melanoma and to ensure that the lesion is adequately re-excised. This form of decision can put us at greater risk, but may be better medicine.

The problems associated with screening for early malignancy are not limited to melanoma and have received greater notoriety with regard to other malignancies, such as carcinomas of the prostate and breast [63-67]. Cancer screening has become an ever more prominent topic, as highlighted by a recent New York Times article in which Evan Farmer was interviewed regarding his study on the accuracy of diagnosis in melanoma [27, 65] . A recent editorial by Philip LeBoit regarding melanocytic lesions seems to apply: "The capacity to err should not be a 'dirty little secret' but openly acknowledged" [29, 30] .

Conclusions
Histopathology has proven less than fully reliable regarding diagnosis of melanocytic neoplasms. Until better tests are developed, however, histopathology remains the putative gold standard. As such, mistakes and lawsuits will continue to occur. Most of us, at some point in our careers, will be made aware that we have failed to diagnose a condition of significance. Well-diagnosed difficult cases come and go. Mistakes, though they may be few in number, are preserved forever in wax and glass.

Most of us will likely also have the opportunity to formally re-review cases in which mistakes have been made by other histopathologists. In such cases, it is important to remember that often we are seeing these cases "through the retrospectoscope". While this artificial situation can hardly be fixed, it is important to bear in mind that the circumstances of our review, often with known outcome, are usually different from those of the original pathologist.

There are things we can do to minimize mistakes. In addition to those already mentioned, these include obtaining expert opinions, saying what we mean on pathology reports (including qualifying them or describing conflicting characteristics), looking up old material when necessary, deferring difficult frozen sections, getting recuts (we are responsible for the whole block), indicating inadequacy (crush, cautery, small specimen} and being hesitant to issue preliminary diagnoses [9, 68] . It is important to remember that "consistent with" equals "is" in a court of law [9]. It is also important for us to know ourselves, not only our general tendencies, but how we are feeling on a given day. Sometimes an additional day is as valuable as more tissue when ordering additional sections. Jonathan Epstein, expert histopathologist of the prostate, has written an informative article regarding pathologists and the legal process [9]. It serves as an important resource for any histopathologist who faces a lawsuit. Epstein notes that if a significant mistake is discovered, it is prudent to addend reports clearly with a qualifying statement, contact the patient's clinician, contact one's insurer, and, of course, document everything [9].

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