Invasive melanoma of the skin

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Author: Mikael Häggström [notes 1]
Melanoma of the skin generally presents as a dark skin focality.

Fixation

Generally 10% neutral buffered formalin.

See also: General notes on fixation

Gross processing

Gross examination

Note:

  • Color
  • Well-defined or diffuse border
  • Size
  • Any elevation

Tissue selection

Tissue selection from suspected malignant skin lesions, by lesion size:[1][notes 2]
<4 mm 4 - 8 mm 9 - 15 mm
Tissue selection from skin excision with less than 4 mm suspected malignant lesion.png Tissue selection from skin excision with 4-8 mm suspected malignant lesion.png Tissue selection from skin excision with 9-15 mm suspected malignant lesion.png

In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used. Further information: Gross processing of skin excisions

Microscopic evaluation

Differential diagnoses

Dermal nevus

Comparison of dermal nevus and suspected invasive melanoma   edit
Parameter Non-dysplastic dermal nevus Low-grade dysplastic dermal nevus High-grade dysplastic dermal nevus Suspected invasive melanoma
Mild dysplasia Moderate dysplasia Severe dysplasia
Macroscopic Lateral circumscription[3] Sharp Slightly diminished Moderate Poor
Excised melanoma in situ.jpg
Symmetry[3] Good Often broken Rare
Structural
(Low
mag.)
Micrograph Histopathology of non-dysplastic dermal nevus, low magnification.jpg Histopathology of invasive acral lentiginous melanoma.jpg
Delimitation[4] Rarely diffuse Sometimes diffuse Often diffuse
Confluent nests[4] Rarely Sometimes Often Often widespread
Pigment distribution[4] Regular Irregular
Concentric fibrosis Regressive[3] Yes[4] Occasional[3]
Lamellar fibrosis Rarely[4] Often[4] Often pronounced[4] Occasional[3]
Lymphocytic infiltrate[4] Mild, perivascular Mild or moderate, perivascular Varying Varying
Cellular
(high
mag.)
Micrographs Histopathology of dermal nevus, high magnification.jpg Histopathology of invasive melanoma, high magnification.jpg
Nuclear size[3] Small Medium Large Medium or large. Pleomorphic[5]
Nuclear pleomorphism[6] Slight superficial Slight Prominent
Chromatin pattern Uniform[3] Condensed[3] Partically expanded[3] Expanded, coarse in some cells[3] Expanded, hyperchromatic, coarse.[3] Usually granular.[6]
Nucleoli[3] Small Medium Large Usually[6] large
Mitoses[3] Few superficial Superficial and deep
Histological regression[6][notes 3] Usually Usually not
Percentage of atypical melanocytes[4] <10% About 10 - 50% about 50-90% Usually> 90%

In suspected but not certain nevus or melanoma, generally perform immunohistochemistry with SOX10, whereby melanocyte proliferation and nuclear pleomorphism is easier to see:[notes 4]


Further workup

In case a diagnosis of invasive melanoma of the skin can be made, the following are essentially always mandatory:

  • Margins
  • Depth
  • Any ulceration

The following aspects are mandatory in some regions:

Margins

Determine if the distance to any margin is greater or lesser than 3 mm.[7] If a margin is closer, measure it at an exactness of 0.1 mm.

If margins are difficult to determine, consider immunohistochemistry with SOX10 to better visualize melanoma nests.[notes 4]

Depth and ulceration

For invasive melanoma, measure the depth and whether there is ulceration or not, so as to be able to classify the T stage (following table by AJCC, 8th edition):[8]

  • TX: Primary tumor thickness cannot be assessed (such as diagnosis by curettage)
  • T0: No evidence of primary tumor (such as unknown primary or completely regressed melanoma)
T (tumor)
Stage T category[8] Thickness[8] Ulceration[8]
Stage 0 Melanoma in situ
Stage I T1a Less than 0.8 mm No
T1b Less than 0.8 mm No
>0.8 to 1.0 mm Yes
T2a >1.0 to 2.0 mm No
Stage II T2b >1.0 to 2.0 mm Yes
T3a >2.0 to 4.0 mm No
T3b >2.0 to 4.0 mm Yes
T4a >4.0 mm No
T4b >4.0 mm Yes

Clark's level

If needing to evaluate,[notes 5] Clark's levels are:[9]

  • Level 1: Melanoma confined to the epidermis (melanoma in situ)
  • Level 2: Invasion into the papillary dermis
  • Level 3: Invasion to the junction of the papillary and reticular dermis
  • Level 4: Invasion into the reticular dermis
  • Level 5: Invasion into subcutaneous tissue.

Histopathologic type

If needing to evaluate,[notes 6] the main types of invasive melanoma are:[10]

Type Features Relative incidence[10][notes 8] Photograph Micrograph
Superficial spreading melanoma Melanoma cells with nest formation along the dermo-epidermal junction. 70% Superficial spreading melanoma in situ on dermoscopy.jpg Histopathology of superficial spreading melanoma.jpg
Nodular melanoma Grows relatively more in depth than in width. 15% - 20% Photography of nodular melanoma.jpg Histopathology of nodular melanoma.jpg
Lentigo maligna melanoma Atypical epidermal melanocytes as well as invasion into the dermis.[11] 5% - 10% Photograph of lentigo maligna melanoma.jpg Histopathology of lentigo maligna melanoma.jpg
Acral lentiginous melanoma Continuous proliferation of atypical melanocytes at the dermoepidermal junction.[12] 7% - 10% Photography of a large acral lentiginous melanoma.jpg Histopathology of invasive acral lentiginous melanoma.jpg

Other parameters

Optionally, the following parameters can be given:[13]

  • histological regression, with complete or partial disappearance from areas of the dermis (and occasionally from the epidermis), which have been replaced by fibrosis, accompanied by melanophages, new blood vessels, and a variable degree of inflammation.[14]
Further information: Evaluation of tumors

Report

Report when evaluated (as per mandatory vs. optional in Further workup above):

  • Melanoma area dimensions (width x width)[15]
  • Radicality,[15] mainly into either of the following: edit
  • >3 mm : "Clear margins".[notes 9]
  • <3 mm but not continuous with edge: "Close margins at __ mm at (location)[notes 10]." Numbers are generally given at an exactness of 0.1 mm.
  • Continuous with margin: "Not radically excised at (location)[notes 10]."
  • Depth or most distant invasion of melanoma cells.[15]
  • Ulceration or not
  • Stage as per AJCC
  • Clark's level
  • Histopathologic type
  • Presence of mitoses, reported only if found.[notes 7]
  • Significant signs of regression
  • Cytoplasmic pigmentation
  • Melanoma cell shapes

Example:

Sun-damaged skin with central diffusely delimited proliferation of melanocytic cells having polymorphic cell nuclei, distinct nucleoli and uneven light brown pigmentation. An area of pagetoid migration is seen. There is ulceration of a smaller area. The radial margin is over 3.0 mm and the deep margin is 2.0 mm.

  • Free margin: Yes
  • Margin in mm: 2.0 mm
  • Tumor depth: 1.2 mm
  • Ulceration: Yes
  • Stage: T2b
  • Clark's level: IV
  • Histopathologic type: Superficial spreading melanoma
  • Presence of mitoses: Yes
  • Significant signs of regression: No
See also: General notes on reporting

Notes

  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
  2. The excision example shows a superficial basal cell carcinoma.
  3. Histological regression is one or more areas within a tumor in which neoplastic cells have disappeared or decreased in number. In this case, this means complete or partial disappearance from areas of the dermis (and occasionally from the epidermis), which have been replaced by fibrosis, accompanied by melanophages, new blood vessels, and a variable degree of inflammation.
    - Ribero, Simone; Gualano, Maria Rosaria; Osella-Abate, Simona; Scaioli, Giacomo; Bert, Fabrizio; Sanlorenzo, Martina; Balagna, Elena; Fierro, Maria Teresa; et al. (2015). "Association of Histologic Regression in Primary Melanoma With Sentinel Lymph Node Status ". JAMA Dermatology 151 (12): 1301. doi:10.1001/jamadermatol.2015.2235. ISSN 2168-6068. 
  4. 4.0 4.1 SOX10 stains cell nuclei of melanocytes.
    - Miettinen, Markku; McCue, Peter A.; Sarlomo-Rikala, Maarit; Biernat, Wojciech; Czapiewski, Piotr; Kopczynski, Janusz; Thompson, Lester D.; Lasota, Jerzy; et al. (2015). "Sox10—A Marker for Not Only Schwannian and Melanocytic Neoplasms But Also Myoepithelial Cell Tumors of Soft Tissue ". The American Journal of Surgical Pathology 39 (6): 826–835. doi:10.1097/PAS.0000000000000398. ISSN 0147-5185. 
  5. 5.0 5.1 Clark's level is not included in United States AJCC guidelines, but is mandatory for melanomas in Sweden.
    -. Breslow Depth and Clark Level. Melanoma Research Alliance. Retrieved on 2020-02-13.
    - . Bilaga 6. Kvalitetsbilaga för patologi (KVAST-bilaga). Regionala Cancercentrum i Samverkan, guidelines by Swedish Society of Pathology. Retrieved on 2020-02-13.
  6. 6.0 6.1 An attempt to determine histopathologic type is mandatory for melanomas in Sweden.
    - . Bilaga 6. Kvalitetsbilaga för patologi (KVAST-bilaga). Regionala Cancercentrum i Samverkan, guidelines by Swedish Society of Pathology. Retrieved on 2020-02-13.
  7. 7.0 7.1 Presence of mitoses in the intradermal component is mandatory for melanomas in Sweden.
    - . Bilaga 6. Kvalitetsbilaga för patologi (KVAST-bilaga). Regionala Cancercentrum i Samverkan, guidelines by Swedish Society of Pathology. Retrieved on 2020-02-13.
  8. Incidence is in comparison to all melanomas.
  9. A more comprehensive report may state "Clear margins at over __ mm" or the value thereof if it has been measured more exactly.
  10. 10.0 10.1 Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.

Main page

References

  1. There are many variants for the processing of skin excisions. These examples use aspects from the following sources: ". Ochsner J 5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . 
    - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen.
    - It also shows an example of circular coverage, with equal coverage distance in all four directions.
    - The entire specimen may be submitted if the risk of malignancy is high.
  2. . Melanoma in situ (stage 0). Cancer Research UK. Last reviewed: 27 Jun 2019
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 Arumi-Uria, Montserrat; McNutt, N Scott; Finnerty, Bridget (2003). "Grading of Atypia in Nevi: Correlation with Melanoma Risk ". Modern Pathology 16 (8): 764–771. doi:10.1097/01.MP.0000082394.91761.E5. ISSN 0893-3952. 
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Katarzyna Lundmark, Britta Krynitz, Ismini Vassilaki, Lena Mölne, Annika Ternesten Bratel. Histopatologisk bedömning och gradering av dysplastiskt nevus samt gränsdragning mot melanom in situ/melanom (Histopathological assessment and grading of dysplastic nevus and distinction from melanoma in situ/melanoma). KVAST (Swedish Society of Pathology). Retrieved on 2019-09-18.
  5. Christopher S. Hale. Skin melanocytic tumor - Melanoma - Invasive melanoma. Topic Completed: 1 May 2013. Revised: 17 September 2019
  6. 6.0 6.1 6.2 6.3 Husain, Ehab A; Mein, Charles; Pozo, Lucia; Blanes, Alfredo; Diaz-Cano, Salvador J (2011). "Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi ". Modern Pathology 24 (4): 471–486. doi:10.1038/modpathol.2010.143. ISSN 0893-3952. 
  7. Definition of "thin margin": Wolf, Y.; Balicer, R.D.; Amir, A.; Feinmesser, M.; Hauben, D.J. (2001). "The vertical dimension in the surgical treatment of cutaneous malignant melanoma – how deep is deep? ". European Journal of Plastic Surgery 24 (2): 74–77. doi:10.1007/s002380100225. ISSN 0930-343X. 
  8. 8.0 8.1 8.2 8.3 Gershenwald, Jeffrey E.; Scolyer, Richard A.; Hess, Kenneth R.; Sondak, Vernon K.; Long, Georgina V.; Ross, Merrick I.; Lazar, Alexander J.; Faries, Mark B.; et al. (2017). "Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual ". CA: A Cancer Journal for Clinicians 67 (6): 472–492. doi:10.3322/caac.21409. ISSN 00079235. , citing
    Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York: Springer International Publishing; 2017:563‐585).
  9. . NCI Dictionary of Cancer Terms. National Cancer Institute. Retrieved on 2020-02-13.
  10. 10.0 10.1 [https://books.google.se/books?id=wGclDwAAQBAJ&pg=PA805 Page 805 in: Ferri, Fred (2019). Ferri's clinical advisor 2019 : 5 books in 1 . Philadelphia, PA: Elsevier. ISBN 978-0-323-52957-0. OCLC 1040695302. 
  11. Michael Xiong; Ahmad Charifa; Chih Shan J. Chen.. Cancer, Lentigo Maligna Melanoma. StatPearls, National Center for Biotechnology Information. Last Update: May 18, 2019.
  12. Piliang, Melissa Peck (2009). "Acral Lentiginous Melanoma ". Surgical Pathology Clinics 2 (3): 535–541. doi:10.1016/j.path.2009.08.005. ISSN 18759181. 
  13. Rees, Jonathan; Viros, Amaya; Fridlyand, Jane; Bauer, Juergen; Lasithiotakis, Konstantin; Garbe, Claus; Pinkel, Daniel; Bastian, Boris C (2008). "Improving Melanoma Classification by Integrating Genetic and Morphologic Features ". PLoS Medicine 5 (6): e120. doi:10.1371/journal.pmed.0050120. ISSN 1549-1676. 
  14. Ribero, Simone; Gualano, Maria Rosaria; Osella-Abate, Simona; Scaioli, Giacomo; Bert, Fabrizio; Sanlorenzo, Martina; Balagna, Elena; Fierro, Maria Teresa; et al. (2015). "Association of Histologic Regression in Primary Melanoma With Sentinel Lymph Node Status ". JAMA Dermatology 151 (12): 1301. doi:10.1001/jamadermatol.2015.2235. ISSN 2168-6068. 
  15. 15.0 15.1 15.2 . An Example of a Melanoma Pathology Report. Melanoma Foundation. Retrieved on 2019-09-24.