What clinical information should the clinician give the pathologist to aid diagnosis of melanoma?
The accuracy of any histopathology report is at least partly dependent on the amount of tissue provided and the availability of relevant clinical details. Some of this clinical information may be received in generic pathology request forms, however, there is also specific additional information required by the pathologist for the accurate diagnosis and optimal reporting of primary cutaneous melanoma.
Most of the evidence about the clinical information that the clinician should provide to the pathologist to aid in the diagnosis of melanoma is derived from review articles and opinion pieces. There is a paucity of evidence correlating the clinical details provided and the accuracy of pathological diagnosis of melanoma (and melanocytic lesions) linked to clinical follow up data. No randomised trials exist and the recommendations below are all based on level IV evidence.
Primary melanoma specimens
A number of studies have demonstrated that the interobserver reproducibility of pathological diagnosis of melanocytic tumours is increased when clinical information is provided to the pathologist. Furthermore, it has also been shown that the histopathological diagnosis may change when appropriate clinical information is provided.
Clinical information that may assist pathologists when interpreting specimens of possible melanoma include: patient age, sex, ethnicity, tumour site, specimen laterality, specimen type, specimen orientation (if appropriate), history of the current lesion (duration, history or duration/tempo of change, clinical features suspicious for malignancy, size of lesion and ulceration), presence of any clinically or dermatoscopically suspicious areas focally within the lesion (including the presence of regression), interpretation of dermoscopy, confocal microscopy or other imaging findings, copies of (or access to) any relevant clinical photographs or prior pathology reports, relevant melanoma risk factors (including number of previous melanomas, presence of dysplastic nevi, total number of naevi, family history of melanoma or dysplastic naevus syndrome and personal history of nonmelanoma skin cancer), history of concurrent or recent pregnancy, details of previous primary melanoma (at this or any other site), evidence and sites of metastatic disease, serum LDH level (when distant metastatic disease is present), and whether this is a new primary melanoma or a recurrence of a previous melanoma, if known (Table 1).
Clinical factors relevant to diagnosis include patient age and sex, and the site of the lesion. The diagnostic significance of any atypical pathological feature varies with the age of the patient and the site of the lesion. For example, the presence of some mitotic activity within a Spitz naevus in a preadolescent child would be compatible with this diagnosis, however, the same frequency of mitoses in an elderly patient would usually signify melanoma.
Naevi occurring on certain sites (including the palms, sole, fingers and toes, flexural sites, genitalia, breast, and ear) often display irregular architecture (i.e., asymmetry, single-cell growth, focal pagetoid migration) that would be considered evidence favouring melanoma in melanocytic tumours occurring on other sites.
It is particularly important that clinicians record factors that may induce atypical pathological features in melanocytic naevi (e.g., previous biopsy, trauma, surface irritation, pregnancy, topical treatment, recent prolonged sunlight exposure, laser or radiation therapy) and that may lead to an overdiagnosis of melanoma.
Following lesional trauma, biopsy, irritation or topical treatment, melanocytic naevi may display many histopathological features that commonly occur in melanomas (including pagetoid epidermal invasion, cytological atypia, occasional dermal mitotic figures and HMB45 positivity). Such regenerating naevi have been termed ‘pseudomelanomas’ and are prone to overdiagnosis as melanomas. Changes typically occur within 6 months of a previous injury, and the pathological changes are usually confined to the area affected by the inciting agent. This may be a “portion” of a naevus in the case of trauma/irritation/biopsy, but it may also be the entire lesion in the case of topical treatment (or even trauma/irritation). Since the histological changes of naevi or melanoma recurring after trauma may be very similar, it is essential that the previous biopsy and, if available, any relevant clinical and dermoscopic photographs, be reviewed. Another important consequence of trauma is that it may result in ulceration. Therefore, in most cases of re-excision of melanoma it is difficult to determine if such ulceration is “spontaneous” and should therefore be considered as a negative prognostic factor, or if it is not “spontaneous” and should therefore be ignored (see also section below on evaluation of re-excision specimens).
Excision specimens should be oriented if the status of specific surgical margins is critical in determining the need for, or the extent of, further surgery. Specimen orientation may be indicated with marking sutures or other techniques. If a specimen is oriented, the orientation should be indicated on the specimen request form (and this may be facilitated by the use of a diagram or provision of a photographic image).
Any clinically or dermoscopically identified suspicious areas should be examined histopathologically, because they may represent melanoma. As an example, a long-standing lesion with a recent change in colour or texture may suggest a melanoma developing within a pre-existing naevus. Such areas should be identified, documented and marked for sectioning (e.g., with a suture or by superficially scoring the epidermis and superficial dermis around the area of concern, using a suitably-sized punch or other technique) to allow identification at the time of processing the specimen and assessing the slides.
Clinical findings and/or the results of diagnostic imaging (e.g., dermoscopy or confocal microscopy) and/or a diagram should be included with the clinical request form if this information is likely to be useful to direct the pathologist to areas of particular clinical concern in the specimen, or to improve clinicopathological correlation. Photographic images can also be helpful when assessing clinically or dermoscopically heterogeneous lesions to direct the pathologist to areas of particular clinical concern.
If there is a discrepancy between the clinical features and the pathological interpretation, the clinician and pathologist should discuss the case and seek to determine the cause of the discrepancy. If a reason for the discrepancy cannot be determined, it may be appropriate for the pathologist to consider whether additional sections of the specimen should be examined to ensure that the reason for the discrepancy is not related to non-representative sampling. If the specimen is a partial biopsy and a clinicopathological discrepancy exists, consideration should be given to whether an excision biopsy should be performed. When there is difficulty in resolving the reason(s) for any discrepancy, it may be appropriate to consider referring the case to a pathologist with special expertise in the interpretation of melanocytic tumours.
Table 1. Clinical information that may aid pathologists in the diagnosis of melanoma of the skin
|Clinical Factor||Information required||Comments|
|Specimen type||Type of specimen:
|If ‘other’ is selected, record the other specimen type.|
|For re-excision specimens||Previous laboratory
Previous laboratory accession number Findings in previous biopsy
|A copy of, or access to, the pathology report for the previous biopsy or excision is often the most practical method to provide the required information. Alternatively important findings of the previous biopsy may be provided on the pathology request form.|
|Clinical diagnosis or differential diagnosis||Text|
|History of current lesion||Text||Duration, history or duration/tempo of change, size of lesion and ulceration|
|The history and timing of lesional trauma, biopsy, irritation or treatment with topical agent, laser or radiation therapy||Details||Many histopathological features that commonly occur in melanomas may occur in naevi that have undergone trauma, previous biopsy, irritation or topical treatment. These naevi may be overdiagnosed as melanoma unless the clinical context is known to the pathologist.|
|A past history of melanoma?||Details||Site, thickness, timing, treatment, previous metastasis|
|Evidence of current or previous metastatic disease?||Yes/no||If yes, when and where and consider recording the serum LDH for patients with stage IV disease|
|Other relevant history||Text||Family history of melanoma or dysplastic naevus syndrome, current or recent pregnancy|
|Details of specimen orientation||A diagram or clinical photograph may assist|
|Any clinically or dermatoscopically suspicious areas?||Yes/no||A diagram or clinical photograph may assist|
|Clinical or other relevant diagnostic imaging results|
|New primary melanoma or recurrence||
Melanoma wide excision specimens
When a diagnosis of melanoma is established, it usually requires a re-excision to ensure that the entire lesion is removed, primarily with the intention of reducing the risk of local recurrence. It is important that it is communicated to the pathologist whether or not the melanoma was reported to be completely excised originally, and whether it had unusual features, such as a desmoplastic component or neurotropism because in many laboratories this will alter how the specimen is sampled for microscopic examination. Knowledge of the presence of a Spitziod, naevoid or heavily pigmented component in the prior biopsy may aid pathological interpretation of re-excision specimens, particularly if incompletely excised in the prior biopsy. Provision at, or access to a copy of the previous pathology report can facilitate optimal communication. If the melanoma includes a desmoplastic component or shows neurotropism, the entire scar area should be sampled and placed in tissue blocks for microscopic examination. The evaluation of surgical margins and identification of residual desmoplastic melanoma in re-excision specimens can be very difficult and the use of immunohistochemical stains such as S100 and SOX10 may be very helpful in distinguishing melanoma cells from scar tissue.
Sentinel lymph node biopsy specimens
A sentinel lymph node is defined as any regional lymph node receiving direct drainage from a primary tumour site and is usually the first site of regional metastasis. The presence of sentinel lymph node metastasis is an adverse prognostic factor in melanoma. Sentinel lymph nodes from melanoma patients are usually examined pathologically with multiple sections and multiple immunostains from each block of tissue. To facilitate such a detailed pathological examination, it is important that sentinel lymph nodes are clearly identified both on the pathology request form and on the label of the specimen container.
Evidence summary and practice points
|There is consensus that clinical factors are relevant to the pathological diagnosis of melanoma (and other melanocytic tumours) and indeed may alter the pathological diagnosis||IV||, , , , , , , , , , , , , |
It is advisable that as much relevant clinical information (Table 1) as possible be provided to pathologists to aid in the diagnosis of melanoma.
- Ferrara G, Argenyi Z, Argenziano G, Cerio R, Cerroni L, Di Blasi A, et al. The influence of clinical information in the histopathologic diagnosis of melanocytic skin neoplasms. PLoS One 2009;4(4):e5375 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19404399.
- Ferrara G, Annessi G, Argenyi Z, Argenziano G, Beltraminelli H, Cerio R, et al. Prior knowledge of the clinical picture does not introduce bias in the histopathologic diagnosis of melanocytic skin lesions. J Cutan Pathol 2015 Aug 13 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26269032.
- Khalifeh I, Taraif S, Reed JA, Lazar AF, Diwan AH, Prieto VG. A subgroup of melanocytic nevi on the distal lower extremity (ankle) shares features of acral nevi, dysplastic nevi, and melanoma in situ: a potential misdiagnosis of melanoma in situ. Am J Surg Pathol 2007 Jul;31(7):1130-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17592281.
- Crotty KA, Scolyer RA, Li L, Palmer AA, Wang L, McCarthy SW. Spitz naevus versus Spitzoid melanoma: when and how can they be distinguished? Pathology 2002 Feb;34(1):6-12 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11902448.
- Dahlstrom JE, Scolyer RA, Thompson JF, Jain S. Spitz naevus: diagnostic problems and their management implications. Pathology 2004 Oct;36(5):452-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15370115.
- Barnhill RL, Cerroni L, Cook M, Elder DE, Kerl H, LeBoit PE, et al. State of the art, nomenclature, and points of consensus and controversy concerning benign melanocytic lesions: outcome of an international workshop. Adv Anat Pathol 2010 Mar;17(2):73-90 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20179431.
- McCarthy SW, Scolyer RA. Pitfalls and important issues in the pathologic diagnosis of melanocytic tumors. Ochsner J 2010;10(2):66-74 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21603360.
- Ahn CS, Guerra A, Sangüeza OP. Melanocytic Nevi of Special Sites. Am J Dermatopathol 2016 Dec;38(12):867-881 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27870726.
- McCarthy SW, Scolyer RA. Melanocytic lesions of the face: diagnostic pitfalls. Ann Acad Med Singapore 2004 Jul;33(4 Suppl):3-14 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15389301.
- Vilain RE, McCarthy SW, Scolyer RA. The regenerating naevus. Pathology 2016 Feb;48(2):108-12 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27020383.
- Adeniran AJ, Prieto VG, Chon S, Duvic M, Diwan AH. Atypical histologic and immunohistochemical findings in melanocytic nevi after liquid nitrogen cryotherapy. J Am Acad Dermatol 2009 Aug;61(2):341-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19362750.
- Kornberg R, Ackerman AB. Pseudomelanoma: recurrent melanocytic nevus following partial surgical removal. Arch Dermatol 1975 Dec;111(12):1588-90 Available from: http://www.ncbi.nlm.nih.gov/pubmed/1200664.
- Gershenwald JE, Scolyer RA, Hess KR et al. Melanoma of the Skin In: Amin, M.B., Edge, S., Greene, F., Byrd, D.R., Brookland, R.K., Washington, M.K., Gershenwald, J.E., Compton, C.C., Hess, K.R., Sullivan, D.C., Jessup, J.M., Brierley, J.D., Gaspar, L.E., Schilsky, R.L., Balch, C.M., Winchester, D.P., Asare, E.A., Madera, M., Gress, D.M., Meyer, L.R.. AJCC Cancer Staging Manual. 8th ed. Switzerland: Springer; 2017. p. 563-85.
- Grogan J, Cooper CL, Dodds TJ, Guitera P, Menzies SW, Scolyer RA. Punch "scoring": a technique that facilitates melanoma diagnosis of clinically suspicious pigmented lesions. Histopathology 2017 Aug 10 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28796900.
- Niebling MG, Haydu LE, Karim RZ, Thompson JF, Scolyer RA. Pathology review significantly affects diagnosis and treatment of melanoma patients: an analysis of 5011 patients treated at a melanoma treatment center. Ann Surg Oncol 2014 Jul;21(7):2245-51 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24748128.
- Varey AHR, Goumas C, Hong AM, Mann GJ, Fogarty GB, Stretch JR, et al. Neurotropic melanoma: an analysis of the clinicopathological features, management strategies and survival outcomes for 671 patients treated at a tertiary referral center. Mod Pathol 2017 Jul 21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28731051.
- McCarthy SW, Scolyer RA, Palmer AA. Desmoplastic melanoma: a diagnostic trap for the unwary. Pathology 2004 Oct;36(5):445-51 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15370114.
- Scolyer RA, Murali R, Satzger I, Thompson JF. The detection and significance of melanoma micrometastases in sentinel nodes. Surg Oncol 2008 Sep;17(3):165-74 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18639451.
- Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 2006 Sep 28;355(13):1307-17 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17005948.
- Scolyer RA, Murali R, McCarthy SW, Thompson JF. Pathologic examination of sentinel lymph nodes from melanoma patients. Semin Diagn Pathol 2008 May;25(2):100-11 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18697713.
- Scolyer RA, Prieto VG. Melanoma pathology: important issues for clinicians involved in the multidisciplinary care of melanoma patients. Surg Oncol Clin N Am 2011 Jan;20(1):19-37 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21111957.
- Scolyer RA, Thompson J, Stretch J. Collaboration between clinicians and pathologists: A necessity for the optimal management of melanoma patients. Cancer Forum 2005;29:76-81.
- Scolyer RA, Judge MJ, Evans A, Frishberg DP, Prieto VG, Thompson JF, et al. Data set for pathology reporting of cutaneous invasive melanoma: recommendations from the international collaboration on cancer reporting (ICCR). Am J Surg Pathol 2013 Dec;37(12):1797-814 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24061524.
- Waller JM, Zedek DC. How informative are dermatopathology requisition forms completed by dermatologists? A review of the clinical information provided for 100 consecutive melanocytic lesions. J Am Acad Dermatol 2010 Feb;62(2):257-61 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19962786.
- Nutt L, Zemlin AE, Erasmus RT. Incomplete laboratory request forms: the extent and impact on critical results at a tertiary hospital in South Africa. Ann Clin Biochem 2008 Sep;45(Pt 5):463-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18753417.
- Simionescu O, Blum A, Grigore M, Costache M, Avram A, Testori A. Learning from mistakes: errors in approaches to melanoma and the urgent need for updated national guidelines. Int J Dermatol 2016 Sep;55(9):970-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26712381.
- Tuong W, Cheng LS, Armstrong AW. Melanoma: epidemiology, diagnosis, treatment, and outcomes. Dermatol Clin 2012 Jan;30(1):113-24, ix Available from: http://www.ncbi.nlm.nih.gov/pubmed/22117873.
- Marghoob AA, Changchien L, DeFazio J, Dessio WC, Malvehy J, Zalaudek I, et al. The most common challenges in melanoma diagnosis and how to avoid them. Australas J Dermatol 2009 Feb;50(1):1-13; quiz 14-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19178485.
- Rademaker M, Thorburn M. Pathology referrals for skin lesions--are we giving the pathologist sufficient clinical information? N Z Med J 2010 Nov 5;123(1325):53-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21317961.
- Haydu LE, Holt PE, Karim RZ, Madronio CM, Thompson JF, Armstrong BK, et al. Quality of histopathological reporting on melanoma and influence of use of a synoptic template. Histopathology 2010 May;56(6):768-74 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20546342.
- Longo C, Piana S, Lallas A, Moscarella E, Lombardi M, Raucci M, et al. Routine Clinical-Pathologic Correlation of Pigmented Skin Tumors Can Influence Patient Management. PLoS One 2015;10(9):e0136031 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26325678.
- Nikoo A, Naraghi MM:. How informative are dermatopathology requisition forms completed by residents of dermatology? Iranian Journal of Dermatology 2012;15:15-17.