Difference between revisions of "Basal-cell carcinoma"

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File:Nodular basal cell cancer with cleft.jpg|thumb|190px|'''Cleft''' formation is fairly specific, but may not be seen in smaller nests.
 
File:Nodular basal cell cancer with cleft.jpg|thumb|190px|'''Cleft''' formation is fairly specific, but may not be seen in smaller nests.
 
</gallery>
 
</gallery>
 +
[[File:Histopathology of a pigmented basal-cell carcinoma.jpg|thumb|220px|Basal-cell carcinomas may be pigmented as shown (but consider the possibility of '''[[melanoma]]''' in such cases).]]
 
In uncertain cases, [[immunohistochemistry]] using [[BerEP4]] can be used, having a high sensitivity and specificity in detecting only BCC cells.<ref name="SunjayaSunjaya2017"/>
 
In uncertain cases, [[immunohistochemistry]] using [[BerEP4]] can be used, having a high sensitivity and specificity in detecting only BCC cells.<ref name="SunjayaSunjaya2017"/>
  
 
===Differential diagnoses===
 
===Differential diagnoses===
Main histological differential diagnoses of basal cell carcinoma:<ref name="PaolinoDonati2017"/>
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Main histological differential diagnoses of basal cell carcinoma:
 +
;Hair follicles
 
<gallery mode=packed heights=200>
 
<gallery mode=packed heights=200>
 
File:Histopathology of hair follicle periphery.jpg|'''Hair follicles''': Peripheral sections may look like nests, but do not display atypia, and nuclei are smaller.
 
File:Histopathology of hair follicle periphery.jpg|'''Hair follicles''': Peripheral sections may look like nests, but do not display atypia, and nuclei are smaller.
File:Histology of a hair follicle at two levels.jpg|Also, '''hair follicles''' generally display more distinct features when looking at adjacent levels.
+
File:Histology of a hair follicle at two levels.jpg|Also, hair follicles generally display more distinct features when looking at adjacent levels.
File:BCC with squamous cell metaplasia with HE and BerEP4 staining.jpg|'''[[Squamous-cell carcinoma of the skin]]''': Generally distinguishable by for example relatively more cytoplasm, horn cyst formation and absence of palisading and cleft formations. Yet, a high prevalence means a relatively high incidence of borderline cases, such as basal-cell carcinoma with squamous cell metaplasia (H&E stain at left). BerEP4 staining helps in such cases, staining only basal-cell carcinoma cells (right image).
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File:Superficial hair follicle tissue.jpg|thumb|Hair follicle tissue may be superficial, resembling a superficial basal-cell carcinoma.
 +
</gallery>
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The edges of hair follicle cells may resemble palisades, but are less pronounced, and are generally more diffusely delineated compared to surroundings.
 +
 
 +
;Squamous-cell carcinoma
 +
'''[[Squamous-cell carcinoma of the skin]]''' is generally distinguishable by for example relatively more cytoplasm, horn cyst formation and absence of palisading and cleft formations.
 +
{{Overlap of squamous-cell and basal-cell carcinoma}}
 +
;Others<ref name="Paolino-Donati2017"/>
 +
<gallery mode=packed heights=200>
 
File:Micrographs of trichoblastoma.jpg|'''[[Trichoblastoma]]''': Absence of cleft, rudimentary hair germs, papillary mesenchymal bodies.
 
File:Micrographs of trichoblastoma.jpg|'''[[Trichoblastoma]]''': Absence of cleft, rudimentary hair germs, papillary mesenchymal bodies.
 
File:Micrograph of adenoid cystic carcinoma.jpg|'''[[Adenoid cystic carcinoma]]''': Lack of basaloid cells disposed in peripheral palisades; adenoid-cystic lesion without connection to the epidermis; absence of artefactual clefts
 
File:Micrograph of adenoid cystic carcinoma.jpg|'''[[Adenoid cystic carcinoma]]''': Lack of basaloid cells disposed in peripheral palisades; adenoid-cystic lesion without connection to the epidermis; absence of artefactual clefts
 
File:Micrograph of microcystic adnexal carcinoma - superficial follicular keratin-filled cysts - infiltrative aggregates.jpg|'''[[Microcystic adnexal carcinoma]]''': Bland keratinocytes, keratin cysts, ductal differentiation. BerEp4- (in 60% of cases)<ref name="InskipMagee2015">{{cite journal|last1=Inskip|first1=Mike|last2=Magee|first2=Jill|title=Microcystic adnexal carcinoma of the cheek—a case report with dermatoscopy and dermatopathology|journal=Dermatology Practical & Conceptual|volume=5|issue=1|year=2015|issn=21609381|doi=10.5826/dpc.0501a07}}</ref>, CEA+, EMA+  
 
File:Micrograph of microcystic adnexal carcinoma - superficial follicular keratin-filled cysts - infiltrative aggregates.jpg|'''[[Microcystic adnexal carcinoma]]''': Bland keratinocytes, keratin cysts, ductal differentiation. BerEp4- (in 60% of cases)<ref name="InskipMagee2015">{{cite journal|last1=Inskip|first1=Mike|last2=Magee|first2=Jill|title=Microcystic adnexal carcinoma of the cheek—a case report with dermatoscopy and dermatopathology|journal=Dermatology Practical & Conceptual|volume=5|issue=1|year=2015|issn=21609381|doi=10.5826/dpc.0501a07}}</ref>, CEA+, EMA+  
File:Trichoepithelioma (1338537528).jpg|'''[[Trichoepithelioma]]''':<ref group="notes>Desmoplastic tricoepithelioma is particularly similar to basal-cell carcinoma.</ref> Rims of collagen bundles, calcification, follicular/sebaceous/infundibular differentiation and cut artefacts. Cytokeratin (CK)20+, p75+, Pleckstrin homology-like domain family A member 1 + (PHLDA1+), common acute lymphoblastic leukemiaantigen + (CD10+) in tumor stroma, CK 6-, Ki-67- and Androgen Rceptor- (AR-)  
+
File:Trichoepithelioma (1338537528).jpg|'''[[Trichoepithelioma]]''':<ref group="note>Desmoplastic tricoepithelioma is particularly similar to basal-cell carcinoma.</ref> Rims of collagen bundles, calcification, follicular/sebaceous/infundibular differentiation and cut artefacts. Cytokeratin (CK)20+, p75+, Pleckstrin homology-like domain family A member 1 + (PHLDA1+), common acute lymphoblastic leukemiaantigen + (CD10+) in tumor stroma, CK 6-, Ki-67- and Androgen Rceptor- (AR-)  
 
File:Micrographs of a typical merkel cell carcinoma.jpg|'''[[Merkel cell carcinoma]]''': Cells arranged in a diffuse, trabecular and/or nested pattern, involving also the subcutis. Mouse Anti-Cytokeratin (CAM) 5.2+, CK20+, S100-, human leukocyte common antigen- ( LCA-), thyroid transcription factor 1- (TTF1-)  
 
File:Micrographs of a typical merkel cell carcinoma.jpg|'''[[Merkel cell carcinoma]]''': Cells arranged in a diffuse, trabecular and/or nested pattern, involving also the subcutis. Mouse Anti-Cytokeratin (CAM) 5.2+, CK20+, S100-, human leukocyte common antigen- ( LCA-), thyroid transcription factor 1- (TTF1-)  
 
</gallery>
 
</gallery>
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;Low-level aggressive patterns
 
;Low-level aggressive patterns
 
<gallery mode=packed heights=200>
 
<gallery mode=packed heights=200>
File:Low-level aggressive basal-cell carcinoma.jpg|'''Nodular'''. Also known as "classic basal-cell carcinoma". It accounts for 50% of all BCC.<ref name="PaolinoDonati2017"/> It typically has relatively cohesive aggregates of basaloid cells with well-defined borders, showing palisading and one or more clefts.<ref name="PaolinoDonati2017">{{cite journal|last1=Paolino|first1=Giovanni|last2=Donati|first2=Michele|last3=Didona|first3=Dario|last4=Mercuri|first4=Santo|last5=Cantisani|first5=Carmen|title=Histology of Non-Melanoma Skin Cancers: An Update|journal=Biomedicines|volume=5|issue=4|year=2017|pages=71|issn=2227-9059|doi=10.3390/biomedicines5040071}}</ref> Central necrosis with eosinophilic, granular features may be also present, as well as mucin. The heavy aggregates of mucin determine a cystic structure. Calcification may be also present, especially in long-standing lesions.<ref name="PaolinoDonati2017"/> Mitotic activity is usually not so evident, but a high mitotic rate may be present in more aggressive lesions.<ref name="PaolinoDonati2017"/>  
+
File:Low-level aggressive basal-cell carcinoma.jpg|'''Nodular'''. Also known as "classic basal-cell carcinoma". It accounts for 50% of all BCC.<ref name="Paolino-Donati2017"/> It typically has relatively cohesive aggregates of basaloid cells with well-defined borders, showing palisading and one or more clefts.<ref name="Paolino-Donati2017">{{cite journal|last1=Paolino|first1=Giovanni|last2=Donati|first2=Michele|last3=Didona|first3=Dario|last4=Mercuri|first4=Santo|last5=Cantisani|first5=Carmen|title=Histology of Non-Melanoma Skin Cancers: An Update|journal=Biomedicines|volume=5|issue=4|year=2017|pages=71|issn=2227-9059|doi=10.3390/biomedicines5040071}}</ref> Central necrosis with eosinophilic, granular features may be also present, as well as mucin. The heavy aggregates of mucin determine a cystic structure. Calcification may be also present, especially in long-standing lesions.<ref name="Paolino-Donati2017"/> Mitotic activity is usually not so evident, but a high mitotic rate may be present in more aggressive lesions.<ref name="Paolino-Donati2017"/>  
 
File:Micrograph of superficial basal-cell carcinoma.jpg|'''Superficial'''
 
File:Micrograph of superficial basal-cell carcinoma.jpg|'''Superficial'''
 
File:Micrograph of basal-cell carcinoma with fibroepitheliomatous pattern.jpg|'''Fibroepitheliomatous''' pattern: anastomosing basaloid epithelial strands enclosing round islands of fibrous stroma<ref>{{cite journal|last1=Yonan|first1=Yousif|last2=Maly|first2=Connor|last3=DiCaudo|first3=David|last4=Mangold|first4=Aaron|last5=Pittelkow|first5=Mark|last6=Swanson|first6=David|title=Dermoscopic Description of Fibroepithelioma of Pinkus with Negative Network|journal=Dermatology Practical & Conceptual|year=2019|pages=246–247|issn=2160-9381|doi=10.5826/dpc.0903a23}} Creative Commons Attribution License</ref>
 
File:Micrograph of basal-cell carcinoma with fibroepitheliomatous pattern.jpg|'''Fibroepitheliomatous''' pattern: anastomosing basaloid epithelial strands enclosing round islands of fibrous stroma<ref>{{cite journal|last1=Yonan|first1=Yousif|last2=Maly|first2=Connor|last3=DiCaudo|first3=David|last4=Mangold|first4=Aaron|last5=Pittelkow|first5=Mark|last6=Swanson|first6=David|title=Dermoscopic Description of Fibroepithelioma of Pinkus with Negative Network|journal=Dermatology Practical & Conceptual|year=2019|pages=246–247|issn=2160-9381|doi=10.5826/dpc.0903a23}} Creative Commons Attribution License</ref>
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If uncertain, immunohistochemistry with BerEP4 helps in distinguishing the BCC cells.
 
If uncertain, immunohistochemistry with BerEP4 helps in distinguishing the BCC cells.
[[File:BCC with squamous cell metaplasia with HE and BerEP4 staining.jpg|thumb|400px|center|Comparison H&E stain (left) with BerEP4 immunohistochemistry staining (right) on a pathological section having BCC with squamous cell metaplasia. Only BCC cells are stained with BerEP4.<ref name="SunjayaSunjaya2017">{{cite journal|last1=Sunjaya|first1=Anthony Paulo|last2=Sunjaya|first2=Angela Felicia|last3=Tan|first3=Sukmawati Tansil|title=The Use of BEREP4 Immunohistochemistry Staining for Detection of Basal Cell Carcinoma|journal=Journal of Skin Cancer|volume=2017|year=2017|pages=1–10|issn=2090-2905|doi=10.1155/2017/2692604}}</ref>]]
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[[File:BCC with squamous cell metaplasia with HE and BerEP4 staining.jpg|thumb|500px|center|Comparison H&E stain (left) with BerEP4 immunohistochemistry staining (right) on a pathological section having BCC with squamous cell metaplasia. Only BCC cells are stained with BerEP4.<ref name="SunjayaSunjaya2017">{{cite journal|last1=Sunjaya|first1=Anthony Paulo|last2=Sunjaya|first2=Angela Felicia|last3=Tan|first3=Sukmawati Tansil|title=The Use of BEREP4 Immunohistochemistry Staining for Detection of Basal Cell Carcinoma|journal=Journal of Skin Cancer|volume=2017|year=2017|pages=1–10|issn=2090-2905|doi=10.1155/2017/2692604}}</ref>]]
  
 
{{Evaluation of tumors}}
 
{{Evaluation of tumors}}
  
 
==Reporting==
 
==Reporting==
*'''Aggressiveness''' pattern if possible
+
*'''Aggressiveness''' pattern, at least if highly aggressive.
 
{{Skin radicality report|margin=1|margin-comment=as per [[#Radicality|Radicality]] above|exactness-ref=<ref name=rcpath/>}}
 
{{Skin radicality report|margin=1|margin-comment=as per [[#Radicality|Radicality]] above|exactness-ref=<ref name=rcpath/>}}
  
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Example:
 
Example:
 
{|class="wikitable"
 
{|class="wikitable"
| [[File:Non-radical basal-cell cancer.jpg|200px|left]] (Skin excision with stratified squamous keratinized epithelium, where the dermis contains) moderately aggressive basal-cell carcinoma, not radically excised at the right margin.<ref group="notes">The direction was known from needle marking.</ref>
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| [[File:Non-radical basal-cell cancer.jpg|200px|left]] (Skin excision with stratified squamous keratinized epithelium, where the dermis contains) moderately aggressive basal-cell carcinoma, not radically excised at the right margin.<ref group=note>The direction was known from needle marking.</ref>
 
|}
 
|}
 
{{Reporting}}
 
{{Reporting}}
 
{{Bottom}}
 
{{Bottom}}

Latest revision as of 16:47, 19 June 2022

Author: Mikael Häggström [note 1]

Nodular basal-cell carcinoma.

Basal-cell carcinoma (BCC):

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][note 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

Broadly consists of determining the following:

  • Whether it is basal-cell carcinoma or a differential diagnosis.
  • Aggressiveness pattern
  • Radicality

Optionally, further subtyping of basal-cell carcinoma can be made.

Characteristics

Basal-cell carcinomas may be pigmented as shown (but consider the possibility of melanoma in such cases).

In uncertain cases, immunohistochemistry using BerEP4 can be used, having a high sensitivity and specificity in detecting only BCC cells.[3]

Differential diagnoses

Main histological differential diagnoses of basal cell carcinoma:

Hair follicles

The edges of hair follicle cells may resemble palisades, but are less pronounced, and are generally more diffusely delineated compared to surroundings.

Squamous-cell carcinoma

Squamous-cell carcinoma of the skin is generally distinguishable by for example relatively more cytoplasm, horn cyst formation and absence of palisading and cleft formations.

edit

Yet, a high prevalence means a relatively high incidence of borderline cases. In such cases, look particularly at the surface and attempt to classify as either of the following:

In unclear cases, the most useful immunohistochemistry marker appears to be MOC-31, which essentially always stains metatypical basal-cell carcinomas but not basaloid squamous-cell carcinomas.[5] UEA-1 appears to be the second most useful marker, staining almost all basaloid squamous-cell carcinomas but only a few metatypical basal-cell carcinomas.[5]

Others[6]

Aggressiveness

Aggressiveness can be classified as low-level aggressive, moderately aggressive and highly aggressive, based mainly the cohesion of cancer cells, but also upon other histopathologic subtypes:

Low-level aggressive patterns
Moderately aggressive pattern
Highly aggressive patterns

Radicality

Determine if there are basal-cell formations continuous with resection margins, or if they are closer or farther than 1 mm from the closest edge.[10] If closer, measure the distance.

If uncertain, immunohistochemistry with BerEP4 helps in distinguishing the BCC cells.

Comparison H&E stain (left) with BerEP4 immunohistochemistry staining (right) on a pathological section having BCC with squamous cell metaplasia. Only BCC cells are stained with BerEP4.[3]
Further information: Evaluation of tumors

Reporting

  • Aggressiveness pattern, at least if highly aggressive.
  • Radicality, mainly into either of the following: edit
  • >1 mm (as per Radicality above): "Clear margins" (or: "Clear margins at over __ mm")((or the exact distance thereof)).))
  • <1 mm but not continuous with edge: "Close margins at __ mm at (location). [[Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.]]." Numbers are generally given at an exactness of 0.1 mm.[10]
  • Continuous with margin: "Not radically excised at (location)."

Optionally, subtype of basal-cell carcinoma

Example:

Non-radical basal-cell cancer.jpg
(Skin excision with stratified squamous keratinized epithelium, where the dermis contains) moderately aggressive basal-cell carcinoma, not radically excised at the right margin.[note 4]

  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. Desmoplastic tricoepithelioma is particularly similar to basal-cell carcinoma.
  4. The direction was known from needle marking.

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. Robert S Bader. Which histologic findings are characteristic of basal cell carcinoma (BCC)?. Medscape. Updated: Feb 21, 2019
  3. 3.0 3.1 Sunjaya, Anthony Paulo; Sunjaya, Angela Felicia; Tan, Sukmawati Tansil (2017). "The Use of BEREP4 Immunohistochemistry Staining for Detection of Basal Cell Carcinoma ". Journal of Skin Cancer 2017: 1–10. doi:10.1155/2017/2692604. ISSN 2090-2905. 
  4. El-Mofty, SK. (2014). "Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas ". Medicina Oral Patología Oral y Cirugia Bucal: e377–e385. doi:10.4317/medoral.20184. ISSN 16986946. 
    License: CC BY 2.5
  5. 5.0 5.1 Webb, David V.; Mentrikoski, Mark J.; Verduin, Lindsey; Brill, Louis B.; Wick, Mark R. (2015). "Basal cell carcinoma vs basaloid squamous cell carcinoma of the skin: an immunohistochemical reappraisal ". Annals of Diagnostic Pathology 19 (2): 70–75. doi:10.1016/j.anndiagpath.2015.01.004. ISSN 10929134. 
  6. 6.0 6.1 6.2 6.3 6.4 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. 
  7. Inskip, Mike; Magee, Jill (2015). "Microcystic adnexal carcinoma of the cheek—a case report with dermatoscopy and dermatopathology ". Dermatology Practical & Conceptual 5 (1). doi:10.5826/dpc.0501a07. ISSN 21609381. 
  8. Yonan, Yousif; Maly, Connor; DiCaudo, David; Mangold, Aaron; Pittelkow, Mark; Swanson, David (2019). "Dermoscopic Description of Fibroepithelioma of Pinkus with Negative Network ". Dermatology Practical & Conceptual: 246–247. doi:10.5826/dpc.0903a23. ISSN 2160-9381.  Creative Commons Attribution License
  9. East, Ellen; Fullen, Douglas R.; Arps, David; Patel, Rajiv M.; Palanisamy, Nallasivam; Carskadon, Shannon; Harms, Paul W. (2016). "Morpheaform Basal Cell Carcinomas With Areas of Predominantly Single-Cell Pattern of Infiltration ". The American Journal of Dermatopathology 38 (10): 744–750. doi:10.1097/DAD.0000000000000541. ISSN 0193-1091. 
  10. 10.0 10.1 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

Image sources