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Melanoma Expert Panel Report

As The Doctors Company insures almost 10 percent of pathologists practicing throughout the United States, our claims should be representative of problems occurring in many pathology practices.

A computer search of claims reported from 1990 through 2001 revealed that 8.6 percent of pathology claims and 14.2 percent of dermatology claims involved the key words “skin cancer” or “melanoma.”

A total of 218 surgical pathology and fine needle aspiration claims reported to The Doctors Company from 1995 to 1997 were individually reviewed. Eleven percent of these claims (23 claims) involved the misdiagnosis of melanoma; 70 percent involved a false-negative diagnosis. Melanoma claims were second only to claims involving breast biopsy. An additional 144 surgical pathology and cytology claims reported from 1998 through 2001 were subsequently reviewed. Sixteen percent of these claims (23 claims) involved misdiagnosed melanoma.

A panel of expert dermatopathologists was convened in April 2002 at The Doctors Company’s home office in Napa, California. The purpose of the meeting was to devise strategies that pathologists and dermatologists can use in their practices to reduce the risk of diagnostic error and/or patient mismanagement when dealing with melanocytic lesions and to focus on the recurrent problem areas identified in the claims reviewed. Ten recurrent problems were discussed:

1. Nodular melanomas were misdiagnosed as melanocytic nevi without an obvious explanation.
   Some managed care contracts restrict referrals and may not allow dermatologists to send specimens to their usual pathologist or dermatopathologist or to read their own cases. Some plans mandate referral to large central laboratories or contractors offering deeply discounted prices. These labs may employ their own pathologists, or they may subcontract with pathology groups or individual dermatopathologists. Pathologists employed in these labs may be reading too many slides too quickly due to the productivity standards required by the discounted charges and by the emphasis on rapid turnaround time. Multiple block levels and immunohistochemical stains may sometimes be discouraged due to cost. There may be minimal or no clinical information submitted with these specimens, and often the pathologist doesn’t know the referring physician, can’t reach him or her, or doesn’t have time to do so. This may lead to different levels of practice in the same practice setting depending on whether a case is deeply discounted under contract or billed directly.
   
   Pathologists are encouraged to contact referring physicians personally in order to discuss the importance of providing clinical information such as age, sex, site, working diagnosis, whether it is a new or recurrent lesion, and lesional diameter if it is a shave or punch biopsy. In many offices, the critical contact is with the nurse or other member of the office staff who fills out the pathology requisition. Pathologists should stress the value of complete biopsies versus partial biopsies that incompletely sample a lesion and the importance of completely re-excising a partially biopsied lesion when recommended.
   
   Pathologists should also focus on those factors that are under their control; e.g., thorough sampling of a lesion, looking at multiple levels through the block, insisting on good histologic sections, and not doing frozen sections on melanocytic lesions. Adequate sampling is important since diagnostic features may be seen in only one or two sections taken from one of multiple levels. A recommended approach is to serially section the entire biopsy and examine multiple sections from each of three levels. The intervening unstained sections are saved and can be subsequently stained if needed or used for immunohistochemical studies.
   
   
2. Nodular melanomas had the low-power architecture of a melanocytic nevus but the cytologic features of melanoma (nevoid melanoma).
   This suggests that these lesions were examined only under low power and not assessed cytologically.
   
   Pathologists should routinely examine all melanocytic lesions under high power—even if they appear to be typical nevi under low power. Look for mitoses (frequent and deep), cytologic atypia, coalescence of nests (loss of nesting pattern), melanin in deep tumor cells, and lymphohistiocytic infiltrates. Relying on low-power symmetry can be misleading.
   
   
3. Superficial spreading melanomas were misinterpreted as nevi showing chronic inflammation (some were partial biopsies).
   These cases suggest that melanocytic lesions containing numerous lymphocytes should be more carefully examined (especially under high power) for other features suggestive of melanoma—and they should be completely excised. Among dermatopathologists, there is an adage that “lymphocytes are better than pathologists in recognizing melanomas.”
   
   
4. There were claims that involved partial biopsies (shave or punch biopsies).
   Of the 144 surgical pathology and cytology claims reviewed that were reported from 1998 through 2001, 16 percent (23 claims) involved misdiagnosed melanoma. Thirty percent of these claims involved shave biopsies (seven claims), 26 percent involved punch biopsies (six claims), 26 percent involved melanomas that recurred locally (six claims) and were therefore incompletely excised (type of biopsy unknown), and only 17 percent (four claims) involved melanomas adequately excised. Overall, 56 percent of claims involved punch or shave biopsies misdiagnosed as benign nevi that were incompletely excised (many were superficial spreading melanomas), and 83 percent of all claims involved melanomas that were incompletely excised.
   
   Excisional biopsy is recommended for all melanocytic lesions because a partial biopsy may result in a partial diagnosis, which may be a misdiagnosis.
   
   Nevertheless, despite admonitions to excise melanocytic lesions completely, primary care clinicians and dermatologists continue to perform punch and shave biopsies—and this practice appears to be increasing under managed care. These partial biopsies may sample nondiagnostic areas of a melanoma or an associated benign nevus; they don’t include the deepest portion of the lesion or the diagnostically helpful radial growth phase; and, unlike excisional biopsy specimens, there is a residual lesion that may recur and/or metastasize.
   
   Punch and shave biopsies are often driven by cost considerations: Scalpels cost more than razor blades, sutures are expensive, and a return visit is often required if a lesion is completely removed and sutured. However, these savings are trivial compared with the cost of a malpractice claim. If referring physicians continue to send partial biopsies, it is important for the pathologist to know the lesional diameter on the patient since this allows an estimate of the extent to which the biopsy sampled the lesion. Pathologists should encourage their referring physicians to provide this information on all partial biopsies.
   
   It is important to comment on the presence of nevocytes at margins—even for benign lesions—and to ask for re-excision of problem lesions (lesions showing some but not all of the features required for a diagnosis of melanoma): A 0.5 cm margin for superficial lesions and a 1.0 cm margin for deep lesions are generally appropriate. A partial skin biopsy is analogous to a colonoscopic biopsy of a dysplastic adenomatous polyp; i.e., if the biopsy is not excisional, the entire lesion is always removed. Suggested comments to add to the pathology report to encourage re-excision of partial biopsies include:
   • When there is little concern: “One might consider re-excision,” or “If this biopsy is part of a larger clinically suspicious lesion, complete excision is advised.”
   • When there is major concern: “Re-excision of this lesion is mandatory”; “Re-excision of this lesion is warranted”; or “This is a partial biopsy of a larger lesion, which should prompt complete excision of the entire lesion.” Such comments will often precipitate a phone call from the referring physician or a request for consultation, which is apt to assure appropriate follow-up.
     
     
5. Sixteen percent of total claims involved melanomas misdiagnosed as Spitz nevi (several of these were shave biopsies).
   The diagnosis of Spitz nevus in an adult is a high-risk and difficult diagnosis for most pathologists. Several areas of particular risk involving the diagnosis of adult Spitz nevus include:
   • lesions composed predominantly of epithelioid melanocytes
   • large lesions (over 6mm in diameter)
   • lesions on sun-damaged skin
   • broadly transected lesions
   • lesions in which more than one population of melanocytes is present
   
   When considering this diagnosis in an adult, it is advisable and prudent to obtain consultation from an expert dermatopathologist. Spitz nevus is a high-risk, low-frequency diagnosis—analogous to soft tissue tumors or bone tumors. If a pathologist is not seeing Spitz nevi on a regular basis and the patient is over 20 years old, the case should be sent to an expert. If Spitz nevi are being seen on a regular basis and the patient is over 20 years old, unless all of the typical diagnostic criteria are present, send the case to an expert. All Spitz nevi should be completely excised—even if the patient is under 20 years old. Even experts may disagree on problematic or atypical Spitzoid lesions; when this occurs, some referral centers may perform sentinel lymph node biopsy, and in one published report, metastatic cells were found in the sentinel node in five of 10 cases.
   
   
6. Fourteen percent of total claims involved unrecognized desmoplastic melanoma.
   More than half of these were shave biopsies (often misdiagnosed microscopically as dermatofibroma).
   
   Most desmoplastic melanomas are associated with lentigo maligna or atypical lentiginous proliferations. At times, a pigmented actinic keratosis can be difficult to differentiate from lentigo maligna. In the presence of an actinic keratosis, it is always prudent to assess whether lentigo maligna may coexist. In sun-damaged skin there is often an increased number of single basally located enlarged melanocytes that may be mildly atypical. In the absence of substantial cytologic atypia, formation of junctional nests and extension down the hair follicles, this is insufficient to justify a diagnosis of lentigo maligna. If the microscopic appearances are less than clear-cut, suggest in the report that the clinician review the clinical aspects of the case to exclude lentigo maligna and undertake additional sampling if indicated.
   
   The diagnosis of lentigo maligna is indicated when, in atrophic skin with solar elastosis, there is an increased frequency of atypical melanocytes, singly and in nests in the basal layer of the interfollicular epidermis with extension of the melanocytic proliferation into the skin appendages. While the melanocytes are largely present in the basal layer, some may be crowded into the suprabasal epidermis; full thickness migration of single cells and nests is not seen. The papillary dermis is usually widened by fibrosis and lymphohistiocytic infiltrates, often with some pigment incontinence. Atypical melanocytes often extend beyond the clinically visible lesion, and surgical margins often transect skin that contains atypical melanocytes. Pathologists need to evaluate margins carefully, which often requires use of immunohistochemical stains for MART-1 and Melan-A.
   
   While invasive melanomas arising from lentigo maligna most often take the form of a vertical growth phase nodule, a proportion of them are desmoplastic melanomas. These comprise spindle-shaped cells that resemble myofibroblasts and are associated with abundant fibrous stroma that may resemble a scar. Their appearance is often deceptively subtle, and the only protection against missing them is to look routinely for desmoplastic melanoma in all biopsies of lentigo maligna. A useful rule is: Actinic damaged skin + scar or desmoplasia = rule out desmoplastic melanoma This often requires immunohistochemical stains for S100 protein; HMB45 has a low sensitivity for desmoplastic melanoma and is not useful.
   
   Desmoplastic melanoma is often present in and around cutaneous nerves (neurotropism) and can extend for considerable distances peripherally via this route. Surgical margin evaluation requires margin-parallel “en-face” blocks, inked to determine the true margin, using S100 stains to highlight nerves present at the margin and any neurotropic cells associated with them.
   
   Pathologists should be alert for the presence of scars in the dermis of all melanocytic lesions. A scar often indicates that there was a previous attempt at biopsy or therapy. Since the clinician frequently does not provide this important information, it is essential that pathologists become familiar with the histologic features of a scar. These include:
   
   
   • loss of normal rete ridges
   • loss of adnexal structures
   • horizontally orientated fibroblasts and collagen bundles
   • vertically or diagonally orientated, thin straight vessels
   
   Benign melanocytic nevi may recur following partial biopsy and may produce a pseudomelanoma in situ pattern. Typically, one sees small individual melanocytes scattered in a haphazard fashion throughout the suprabasal epidermis overlying a dermal scar; junctional nests of melanocytes may also be present. This simulates Pagetoid melanocytosis, and, if the pathologist is unaware of the prior biopsy history, it may be misdiagnosed as in situ melanoma. An important diagnostic clue is that the melanocytes do not extend within the epidermis beyond the margins of the dermal scar.
   
   If a scar is present in a melanocytic lesion, contact the referring physician’s office to see if they have a record of a previous biopsy. It is often necessary to have them ask the patient. Many times they will simply check their records and answer no if the biopsy was not performed in their office. Reviewing any previous biopsies is essential in providing comprehensive evaluation of a recurrent melanocytic lesion. This may prevent both under- and overdiagnosis.
   
   
7. Several claims involved melanoma presenting as lymph node metastasis and misdiagnosed as large cell lymphoma.
   Since an undifferentiated tumor composed of large malignant cells with prominent nucleoli may be a large cell lymphoma or an undifferentiated carcinoma or a melanoma, a panel of immunohistochemical stains (CD45, CK AE1/AE3, S100) is required to make a definitive diagnosis. If ordering immunohistochemical stains requires preauthorization by an insurer and this is denied, document the informed refusal in the report.
   
   
8. A few claims resulted from melanomas misdiagnosed as dysplastic nevi involving margins.
   One of these was a punch biopsy and, in another, re-excision was requested but not performed.
   
   Claims involving dysplastic or atypical nevi appear to result in part from miscommunication between pathologists and dermatologists. A pathologist may use the term “atypical” or “dysplastic” in a generic sense—meaning that cytologically disturbing cells are present in a lesion lacking diagnostic criteria for melanoma. Complete excision is often requested, but the dermatologist may be reluctant to do so since to him or her, these terms have a more specific meaning and connote a clinical syndrome or benign clinical entity.
   
   For lesions falling in the diagnostic gray area between melanocytic nevus and melanoma—lesions for which the biologic potential is unpredictable—pathologists should use the term “atypical melanocytic neoplasm” and request complete excision. Pathologists should avoid the terms “atypical nevus” or “dysplastic nevus” for these lesions, since these terms connote a clinical syndrome or a benign clinical entity, and dermatologists may not perform the indicated re-excision. This reluctance to re-excise a lesion may be unconsciously reinforced by the economic disincentives of capitation.
   
   Nevi that show the architectural and cytologic features characteristic of dysplastic or atypical nevus should be completely excised. Dysplastic or atypical nevi can blend with and be difficult to differentiate from in situ melanoma and are referred to by some experts as “melanocytic lesions of unknown medicolegal or severe litigious potential.”
   
   
9. Two claims involved spindle cell melanomas called spindle cell squamous carcinoma (one on shave biopsy).
   Immunohistochemical stains were not performed in either of these cases. Whenever an amelanotic spindle cell skin lesion is seen, a panel of immunohistochemical stains (S100, MART-1, Melan-A, and CK AE1/AE3) is required to differentiate squamous carcinoma from desmoplastic or spindle cell melanoma and atypical fibroxanthoma. HMB45 has a low sensitivity for desmoplastic and spindle cell melanomas and is not useful in this differential diagnosis.
   
   
10. Two claims involved patients who presented with metastatic melanoma without a known primary.
    Each patient gave a history of having skin lesions (including “moles”) removed in a physician’s office. Since there were no pathology reports, the lesions were presumably discarded and not sent to a pathologist.

The Doctors Company encourages pathologists to issue written reports to document verbal consultations—particularly with dermatologists, since the melanocytic lesions they want an opinion on are apt to be from lesions they have clinical concern about. When pathologists are asked to look at a slide and give an opinion, they are giving a consultation for which they can be held liable. Without a written report, the only record is the clinician’s recollection of the conversation or a handwritten note made in the office record or chart, which is often incomplete or inaccurate.

Melanoma Risk Management Expert Panel Members

Alistair J. Cochran, MD
Professor of Pathology and Surgery
Department of Pathology and Laboratory Medicine
University of California at Los Angeles School of Medicine

Scott Binder, MD
Chief, Dermatopathology
Department of Pathology and Laboratory Medicine
University of California at Los Angeles School of Medicine

Philip LeBoit, MD
Professor of Pathology and Dermatology
Director, Dermatopathology Services
University of California at San Francisco

Clifton White, MD
Professor of Dermatology and Pathology
Director, Dermatopathology
Oregon Health Sciences University

Expert Panel Chair David B. Troxel, MD
Professor Emeritus
School of Public Health
Board Member and Medical Director, The Doctors Company

The Doctors Company Panel Participants

Richard E. Anderson, MD, FACP
Medical Oncologist
Chairman and Chief Executive Officer, The Doctors Company

David M. Charles, MD
Plastic Surgeon
Board Member, The Doctors Company

Mark Gorney, MD, FACS
Plastic Surgeon
Board Member and former Medical Director, The Doctors Company

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