Difference between revisions of "Malignant melanoma"

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Malignant melanoma (view source)

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| LMDDx      = [[dysplastic nevus]], [[Spitz nevus]], [[common nevus]] (nevoid melanoma), [[atypical fibroxanthoma]], (spindle cell) [[squamous cell carcinoma]], [[leiomyosarcoma]], [[serous carcinoma]], [[clear cell sarcoma]], others
| LMDDx      = [[dysplastic nevus]], [[Spitz nevus]], [[common nevus]] (nevoid melanoma), [[atypical fibroxanthoma]], (spindle cell) [[squamous cell carcinoma]], [[leiomyosarcoma]], [[serous carcinoma]], [[clear cell sarcoma]], others
| Stains    = melanin
| Stains    = melanin
| IHC        = S-100, Melan A, HMB-45, MITF, tyrosinase
| IHC        = S-100, Melan A, HMB-45, [[MITF]], tyrosinase
| EM        = melanosomes
| EM        = melanosomes
| Molecular  =
| Molecular  = +/-[[BRAF mutation]]
| IF        =
| IF        =
| Gross      =
| Gross      =
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*Regression - >75% of tumour.
*Regression - >75% of tumour.
*Microsatellitosis - nest of tumour cells > 0.05 mm size, separated from primary tumour >=0.3 mm and <= 2 cm.
*Microsatellitosis - nest of tumour cells > 0.05 mm size, separated from primary tumour >=0.3 mm and <= 2 cm.
*In transist metastasis.
*[[In transit metastasis]].
*[[Lymphovascular invasion]].
*[[Lymphovascular invasion]].
*[[Perineural invasion]].
*[[Perineural invasion]].
*Lack of tumour infiltrating lymphocytes (TILs).{{fact}}
*Lack of [[tumour infiltrating lymphocytes]] (TILs).{{fact}}


===Clinical===
===Clinical===
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==Microscopic==
==Microscopic==
===Metatstatic/non-skin===
===Metastatic/non-skin===
Features (non-skin):
Features (non-skin):
*Classic appearance of melanoma:  
*Classic appearance of melanoma:  
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**Epithelioid [[angiosarcoma]].
**Epithelioid [[angiosarcoma]].
*Lymphoma.
*Lymphoma.
*Other [[melanocytic lesions]].
*[[Nodal nevus]] - benign nevus in lymph node.
*Other (benign) [[melanocytic lesions]].


Images:
Images:
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**[[Blue nevus]].
**[[Blue nevus]].


Images:
=====Images=====
*[[WC]]:
======www======
**[http://commons.wikimedia.org/wiki/File:Lentigo_maligna_-_intermed_mag.jpg Melanoma in situ - intermed. mag. (WC)].
*[http://path.upmc.edu/cases/case429.html Malignant melanoma - several images (upmc.edu)].
**[http://commons.wikimedia.org/wiki/File:Lentigo_maligna_-_very_high_mag.jpg Melanoma in situ - very high mag. (WC)].
======MIS======
*www:
<gallery>
**[http://path.upmc.edu/cases/case429.html Malignant melanoma - several images (upmc.edu)].
Image: Malignant melanoma in situ -- very low mag.jpg | MIS - very low mag. (WC/Nephron)
Image: Malignant melanoma in situ -- low mag.jpg | MIS - low mag. (WC/Nephron)
Image: Malignant melanoma in situ -- intermed mag.jpg | MIS - intermed. mag. (WC/Nephron)
Image: Malignant melanoma in situ -- high mag.jpg | MIS - high mag. (WC/Nephron)
Image: Malignant melanoma in situ - alt -- very high mag.jpg | MIS - very high mag. (WC/Nephron)
</gallery>


====Regression of melanoma====
====Regression of melanoma====
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Note:  
Note:  
*Histology is '''not definitive''' for metastatic melanoma vs. primary melanoma; epidermal involvement may be seen in mets.
*Histology is '''not definitive''' for metastatic melanoma vs. primary melanoma; epidermal involvement may be seen in mets.
**IHC (like histology) is ''not definitive''.<ref name=pmid15272532>{{Cite journal  | last1 = Guerriere-Kovach | first1 = PM. | last2 = Hunt | first2 = EL. | last3 = Patterson | first3 = JW. | last4 = Glembocki | first4 = DJ. | last5 = English | first5 = JC. | last6 = Wick | first6 = MR. | title = Primary melanoma of the skin and cutaneous melanomatous metastases: comparative histologic features and immunophenotypes. | journal = Am J Clin Pathol | volume = 122 | issue = 1 | pages = 70-7 | month = Jul | year = 2004 | doi = 10.1309/FUQH-92B0-3902-5LHG | PMID = 15272532 }}</ref>
**History/clinical is important for differentiation.
**History/clinical is important for differentiation.


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====Breslow thickness====
====Breslow thickness====
*[[AKA]] ''maximum tumour thickness''.
*[[AKA]] ''maximum tumour thickness''.
*Depth measured from stratum granulosum to deepest intradermal tumour cell - predictive of survival.<ref name=Ref_PCPBoD8>{{Ref PCPBoD8|595}}</ref>
*Depth measured from [[stratum granulosum]] to deepest intradermal tumour cell - predictive of survival.<ref name=Ref_PCPBoD8>{{Ref PCPBoD8|595}}</ref>


=====Tumour stage=====
=====Tumour stage=====
Melanoma staging is based primarily on the Breslow thickness:<ref>{{Cite journal  | last1 = Nowecki | first1 = ZI. | last2 = Rutkowski | first2 = P. | last3 = Michej | first3 = W. | title = The survival benefit to patients with positive sentinel node melanoma after completion lymph node dissection may be limited to the subgroup with a primary lesion Breslow thickness greater than 1.0 and less than or equal to 4 mm (pT2-pT3). | journal = Ann Surg Oncol | volume = 15 | issue = 8 | pages = 2223-34 | month = Aug | year = 2008 | doi = 10.1245/s10434-008-9965-3 | PMID = 18506535 }}</ref><ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2013/SkinMelanoma_13protocol_3300.doc http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2013/SkinMelanoma_13protocol_3300.doc]. Accessed on: 2 January 2014.</ref>
Melanoma staging is based primarily on the Breslow thickness:<ref>{{Cite journal  | last1 = Nowecki | first1 = ZI. | last2 = Rutkowski | first2 = P. | last3 = Michej | first3 = W. | title = The survival benefit to patients with positive sentinel node melanoma after completion lymph node dissection may be limited to the subgroup with a primary lesion Breslow thickness greater than 1.0 and less than or equal to 4 mm (pT2-pT3). | journal = Ann Surg Oncol | volume = 15 | issue = 8 | pages = 2223-34 | month = Aug | year = 2008 | doi = 10.1245/s10434-008-9965-3 | PMID = 18506535 }}</ref><ref>URL: [https://documents.cap.org/protocols/Skin.Melanoma.Bx_4.3.0.1.REL_CAPCP.pdf https://documents.cap.org/protocols/Skin.Melanoma.Bx_4.3.0.1.REL_CAPCP.pdf]. Accessed on: 14 September 2021.</ref>
*pT1 <= 1.0 mm.
*pT1 ≤ 1.0 mm.
**pT1a: no ulceration, <1 mitoses/mm<sup>2</sup>.
**pT1a: ≤ 0.8 mm, no ulceration.
**pT1b: ulceration present ''or'' >=1 mitoses/mm<sup>2</sup>.
**pT1b: ulceration present ''or'' 0.8 mm  < thickness ≤ 1.0 mm (with or without ulceration).
*pT2 1.01 mm to 2.0 mm.
*pT2 1.01 mm to 2.0 mm.
**pT2a: no ulceration.
**pT2a: no ulceration.
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===Others===
===Others===
*SOX10 +ve -- useful for differentiate from excision scar.<ref name=pmid20653825>{{cite journal |author=Ramos-Herberth FI, Karamchandani J, Kim J, Dadras SS |title=SOX10 immunostaining distinguishes desmoplastic melanoma from excision scar |journal=J. Cutan. Pathol. |volume=37 |issue=9 |pages=944–52 |year=2010 |month=September |pmid=20653825 |doi=10.1111/j.1600-0560.2010.01568.x |url=}}</ref>
*[[SOX10]] +ve -- useful for differentiate from excision scar.<ref name=pmid20653825>{{cite journal |author=Ramos-Herberth FI, Karamchandani J, Kim J, Dadras SS |title=SOX10 immunostaining distinguishes desmoplastic melanoma from excision scar |journal=J. Cutan. Pathol. |volume=37 |issue=9 |pages=944–52 |year=2010 |month=September |pmid=20653825 |doi=10.1111/j.1600-0560.2010.01568.x |url=}}</ref>
**SOX-10 = pan-schwannian and melanocytic marker.
**SOX10 = pan-schwannian and melanocytic marker.
*[[CD99]] +ve.  


*Melanoma cocktail (HMB-45, MART-1).<ref name=pmid18360125>{{cite journal |author=Jani P, Chetty R, Ghazarian DM |title=An unusual composite pilomatrix carcinoma with intralesional melanocytes: differential diagnosis, immunohistochemical evaluation, and review of the literature |journal=Am J Dermatopathol |volume=30 |issue=2 |pages=174–7 |year=2008 |month=April |pmid=18360125 |doi=10.1097/DAD.0b013e318165b8fe |url=}}</ref>
*Melanoma cocktail (HMB-45, MART-1).<ref name=pmid18360125>{{cite journal |author=Jani P, Chetty R, Ghazarian DM |title=An unusual composite pilomatrix carcinoma with intralesional melanocytes: differential diagnosis, immunohistochemical evaluation, and review of the literature |journal=Am J Dermatopathol |volume=30 |issue=2 |pages=174–7 |year=2008 |month=April |pmid=18360125 |doi=10.1097/DAD.0b013e318165b8fe |url=}}</ref>
*Microphthalmia (MITF) - easy to interpret as it is a nuclear stain.<ref>{{OMIM|156845}}</ref><ref name=pmid16899407>{{Cite journal  | last1 = Levy | first1 = C. | last2 = Khaled | first2 = M. | last3 = Fisher | first3 = DE. | title = MITF: master regulator of melanocyte development and melanoma oncogene. | journal = Trends Mol Med | volume = 12 | issue = 9 | pages = 406-14 | month = Sep | year = 2006 | doi = 10.1016/j.molmed.2006.07.008 | PMID = 16899407 }}</ref>
*[[Microphthalmia transcription factor]] (MITF) - easy to interpret as it is a nuclear stain.<ref>{{OMIM|156845}}</ref><ref name=pmid16899407>{{Cite journal  | last1 = Levy | first1 = C. | last2 = Khaled | first2 = M. | last3 = Fisher | first3 = DE. | title = MITF: master regulator of melanocyte development and melanoma oncogene. | journal = Trends Mol Med | volume = 12 | issue = 9 | pages = 406-14 | month = Sep | year = 2006 | doi = 10.1016/j.molmed.2006.07.008 | PMID = 16899407 }}</ref>
*Tyrosinase.<ref name=pmid17227112>{{Cite journal  | last1 = Roma | first1 = AA. | last2 = Magi-Galluzzi | first2 = C. | last3 = Zhou | first3 = M. | title = Differential expression of melanocytic markers in myoid, lipomatous, and vascular components of renal angiomyolipomas. | journal = Arch Pathol Lab Med | volume = 131 | issue = 1 | pages = 122-5 | month = Jan | year = 2007 | doi = 10.1043/1543-2165(2007)131[122:DEOMMI]2.0.CO;2 | PMID = 17227112 }}</ref>
*Tyrosinase.<ref name=pmid17227112>{{Cite journal  | last1 = Roma | first1 = AA. | last2 = Magi-Galluzzi | first2 = C. | last3 = Zhou | first3 = M. | title = Differential expression of melanocytic markers in myoid, lipomatous, and vascular components of renal angiomyolipomas. | journal = Arch Pathol Lab Med | volume = 131 | issue = 1 | pages = 122-5 | month = Jan | year = 2007 | doi = 10.1043/1543-2165(2007)131[122:DEOMMI]2.0.CO;2 | PMID = 17227112 }}</ref>
*WT1 usually +ve<ref name=pmid17927581>{{cite journal |author=Wilsher M, Cheerala B |title=WT1 as a complementary marker of malignant melanoma: an immunohistochemical study of whole sections |journal=Histopathology |volume=51 |issue=5 |pages=605–10 |year=2007 |month=November |pmid=17927581 |doi=10.1111/j.1365-2559.2007.02843.x |url=}}</ref> - not commonly used.
*WT1 usually +ve<ref name=pmid17927581>{{cite journal |author=Wilsher M, Cheerala B |title=WT1 as a complementary marker of malignant melanoma: an immunohistochemical study of whole sections |journal=Histopathology |volume=51 |issue=5 |pages=605–10 |year=2007 |month=November |pmid=17927581 |doi=10.1111/j.1365-2559.2007.02843.x |url=}}</ref> - not commonly used.
==Molecular==
* Commonly have [[BRAF mutation]]s.<ref name=pmid12460918>{{Cite journal  | last1 = Brose | first1 = MS. | last2 = Volpe | first2 = P. | last3 = Feldman | first3 = M. | last4 = Kumar | first4 = M. | last5 = Rishi | first5 = I. | last6 = Gerrero | first6 = R. | last7 = Einhorn | first7 = E. | last8 = Herlyn | first8 = M. | last9 = Minna | first9 = J. | title = BRAF and RAS mutations in human lung cancer and melanoma. | journal = Cancer Res | volume = 62 | issue = 23 | pages = 6997-7000 | month = Dec | year = 2002 | doi =  | PMID = 12460918 }}
</ref>
* Desmoplastic melanoma has the highest number of mutations (62 per megabase).<ref>{{Cite journal  | last1 = Shain | first1 = AH. | last2 = Garrido | first2 = M. | last3 = Botton | first3 = T. | last4 = Talevich | first4 = E. | last5 = Yeh | first5 = I. | last6 = Sanborn | first6 = JZ. | last7 = Chung | first7 = J. | last8 = Wang | first8 = NJ. | last9 = Kakavand | first9 = H. | title = Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway. | journal = Nat Genet | volume = 47 | issue = 10 | pages = 1194-9 | month = Oct | year = 2015 | doi = 10.1038/ng.3382 | PMID = 26343386 }}</ref>
**The high number of (C>T) transitions suggest UV radiation as main cause.
**Approx. 15% of the cases have NFKBIE amplifications.


==Sign out==
==Sign out==
===Melanoma in situ===
===Melanoma in situ===
<pre>
Skin Lesion, Left Upper Back, Re-excision:
- Melanoma in situ, completely excised.
-- Surgical clearance 8 millimetres.
- Dermal scar.
- Solar elastosis.
Comment:
The case was partially reviewed with Dr. X; he agrees melanoma in situ is present.
</pre>
====Block letters====
<pre>
<pre>
SKIN LESION, MID-MIDDLE BACK, PUNCH BIOPSY:
SKIN LESION, MID-MIDDLE BACK, PUNCH BIOPSY:
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The lesion is very close to the margin (<0.1 mm clearance).
The lesion is very close to the margin (<0.1 mm clearance).
=====Alternate=====
The sections show skin with pigmented atypical melanocytes confined to the epidermis. The melanocytes scatter upwards, and have focal confluent growth and nucleoli.  Mitotic activity is not apparent. Solar elastosis is present in the background. The lesion extends to the edge of the tissue; it is incompletely excised.


===Invasive melanoma===
===Invasive melanoma===
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==References==
==References==
{{reflist|2}}
{{reflist|2}}
==External links==
*[https://www.youtube.com/watch?v=_4jgUcxMezM Dear 16-year-old me - DCMFCanada (youtube.com)].


[[Category:Dermatopathology]]
[[Category:Dermatopathology]]
[[Category:Diagnosis]]
[[Category:Diagnosis]]
Michael
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