Suspected malignant skin excisions

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Author: Mikael Häggström [notes 1]
Suspected malignant skin excisions:


Generally 10% neutral buffered formalin.

See also: General notes on fixation

Common targets

If directly suspected from the referral, see:

  • Melanoma

Gross processing

Gross examination


  • 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

If the lesion was pigmented on gross examination, evaluate as a dark skin focality. If not:

Look for atypical cells, possibly by scrolling through the epidermis at intermediate magnification and then through the dermis at a lower magnification. If atypical cells are found, look for:

  • Similarity to squamous cells: See below:

Squamous cell-like skin proliferations: Differential diagnosis

Condition[2] Characteristics[2] Image
Invasive squamous-cell carcinoma of the skin Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread. Micrograph of invasive squamous cell carcinoma - 150x.jpg
Squamous-cell carcinoma in situ (Bowen’s disease) Atypical keratinocytes at every layer of epidermis. Micrograph of squamous cell carcinoma in situ - 100x.jpg
Actinic keratosis Atypical keratinocytes that do not span the full thickness of the epidermis (or, in Bowenoid variant, are less disordered with less nuclear atypia and crowding). Micrograph of actinic keratosis - low magnification.jpg
Keratoacanthoma Symmetrical and circumscribed proliferation of keratinocytes, with central horn plug, with epidermis that extends over the tumor. Highly differentiated SCC. Keratoacanthoma (2197016163).jpg
Adnexal carcinomas Squamous differentiation, but does not show connection with the epidermis and highlights adnexal features. Micrograph of microcystic adnexal carcinoma - superficial follicular keratin-filled cysts.jpg
Adenosquamous carcinoma Mixed glandular and squamous differentiation. Micrograph of cutaneous adenosquamous carcinoma - 40x.jpg
Verrucous squamous cell carcinoma[notes 3] Exophytic squamous proliferation with marked papillomatosis and low atypia and the presence of koilocyte-like changes. Found in head and neck locations, as well as in the genitalia and sole of the foot. Micrograph of penile verrucous carcinoma - 20x.jpg Micrograph of penile verrucous carcinoma - 200x.jpg
Inverted follicular keratosis[notes 4] Sharply circumscribed endophytic verrucous proliferation with prominent squamous features. Inverted follicular keratosis 1 (3059309003).jpg Inverted follicular keratosis 3 (3060145758).jpg
Seborrheic keratosis Acanthosis, absence of atypia, pseudo-horn cysts, in inflamed lesions, mitoses may be present. Histopathology of seborrheic keratosis.jpg
Bowenoid papulosis Atypical keratinocytes and mitoses. Histology similar to Bowen’s disease. Low-magnification micrograph of oral bowenoid papulosis.jpg High-magnification micrograph of oral bowenoid papulosis.jpg
Metastasis Personal medical history of the patient, nodular proliferation without connection to epidermis, immunohistochemical evaluation.
Squamous-cell carcinoma metastasis from lungs to the skin

Further workup of malignant findings

In case of skin cancer, determine whether the peripheral/radial and deep margins are clear, close or continuous.[3][notes 5] A close margin has various definitions for different malignancies, but for basal-cell carcinoma and cutaneous squamous cell carcinoma it is defined as being closer than 1 mm from the edge (but yet non-continuous with it),[3][4] but 2-3 mm for melanoma.[5]


Preferably see specific article on the condition at hand, if available.

  • Optionally, the presence of a keratinized squamous epithelium.
  • Any abnormalities, generally preceded by location in terms of epidermal, dermal or more specific layers thereof.
  • If malignant:
  • Degree of differentiation
  • Radicality, mainly into either of the following: edit
  • >___ mm (Definitions vary for the distance as per Further workup of malignant findings above): "Clear margins".[notes 6]
  • <___ mm but not continuous with edge: "Close margins at __ mm at (location)[notes 7]." Numbers are generally given at an exactness of 0.1 mm.[3]
  • Continuous with margin: "Not radically excised at (location)[notes 7]."
  • Perineural or vascular invasion if present.


  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.
    • Buschke–Löwenstein tumor is an alternative name for verrucous squamous cell carcinoma in the ano-genital region.
    • Carcinoma cuniculatum is a characteristic form of verrucous squamous cell carcinoma on the sole.
  3. Inverted follicular keratosis is generally thought to be a rare variant of seborrheic keratosis, but this position is not universally accepted.
    - Karadag, AyseSerap; Ozlu, Emin; Uzuncakmak, TugbaKevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant (2016). "Inverted follicular keratosis successfully treated with imiquimod ". Indian Dermatology Online Journal 7 (3): 177. doi:10.4103/2229-5178.182354. ISSN 2229-5178. 
  4. "Peripheral" or "radial" margins are preferred rather than "lateral", since a "lateral" margin may be interpreted as opposite to the "medial margin".
  5. A more comprehensive report may state "Clear margins at over __ mm" or the value thereof if it has been measured more exactly.
  6. 7.0 7.1 Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.


  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. 2.0 2.1 Initially copied from: Paolino, Giovanni; Donati, Michele; Didona, Dario; Mercuri, Santo; Cantisani, Carmen (2017). "Histology of Non-Melanoma Skin Cancers: An Update ". Biomedicines 5 (4): 71. doi:10.3390/biomedicines5040071. ISSN 2227-9059.  - "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ("
  3. 3.0 3.1 3.2 David Slater, Paul Barrett. Standards and datasets for reporting cancers - Dataset for histopathological reporting of primary cutaneous basal cell carcinoma. The Royal College of Pathologists. February 2019
  4. 1 mm as cutoff fore close margin: Brodie M Elliott, Benjamin R Douglass, Daniel McConnell, Blair Johnson, Christopher Harmston (2018-12-14). New Zealand Medical Journal.
  5. Page 406 in: Klaus J. Busam, Richard A Scolyer, Pedram Gerami (2018). Pathology of Melanocytic Tumors . Elsevier Health Sciences. ISBN 9780323508681.