Difference between revisions of "Malignant melanoma"

Jump to navigation Jump to search

Malignant melanoma (view source)

Revision as of 15:32, 5 November 2021

11,415 bytes added ,  15:32, 5 November 2021
→‎Others
(→‎Skin: more)
 
(52 intermediate revisions by 5 users not shown)
Line 1: Line 1:
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Melanoma40x.JPG
| Width      =
| Caption    = Malignant melanoma. [[H&E stain]].
| Micro      = melanocytic differentiation (e.g. pigment), abnormal architecture, lack of maturation, +/-nuclear atypia - esp. nucleoli, +/-upward scatter of melanocytes, +/-asymmetry of pigmentation
| Subtypes  =
| 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
| IHC        = S-100, Melan A, HMB-45, [[MITF]], tyrosinase
| EM        = melanosomes
| Molecular  = +/-[[BRAF mutation]]
| IF        =
| Gross      =
| Grossing  =
| Site      = [[skin]] (usu. sun exposed areas), oral mucosa, others
| Assdx      =
| Syndromes  = familial melanoma
| Clinicalhx =
| Signs      = ABCDE <nowiki>=</nowiki> asymmetrical, border irregular, colour (black), diameter (>6 mm), evolving (growing)
| Symptoms  =
| Prevalence = common
| Bloodwork  =
| Rads      =
| Endoscopy  =
| Prognosis  = good to very poor (dependent on stage)
| Other      =
| ClinDDx    = pigmented skin lesions, esp. [[melanocytic lesions]]
| Tx        = wide excision if possible
}}
{{ Infobox external links
| Name          = Melanoma in situ
| EHVSC          = 10171
| pathprotocols  =
| wikipedia      =
| pathoutlines  =
}}
'''Malignant melanoma''', also '''melanoma''', is an aggressive type of skin cancer that can be diagnostically challenging for pathologists.   
'''Malignant melanoma''', also '''melanoma''', is an aggressive type of skin cancer that can be diagnostically challenging for pathologists.   


Line 13: Line 50:
*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===
Line 37: Line 74:


==Microscopic==
==Microscopic==
===Metatstatic/non-skin===
===Metastatic/non-skin===
Features (non-skin):
Features (non-skin):
*Classic appearance of melanoma:  
*Classic appearance of melanoma:  
Line 60: Line 97:
*Sarcoma - as may have spindle cells.
*Sarcoma - as may have spindle cells.
**[[Clear cell sarcoma]] ([[AKA]] melanoma of the soft parts).
**[[Clear cell sarcoma]] ([[AKA]] melanoma of the soft parts).
**Metaplastic carcinoma.
**[[Metaplastic carcinoma]].
**[[Spindle cell squamous carcinoma]].
**Epithelioid [[angiosarcoma]].
**Epithelioid [[angiosarcoma]].
*Lymphoma.
*Lymphoma.
*Other [[melanocytic lesions]].
*[[Nodal nevus]] - benign nevus in lymph node.
*Other (benign) [[melanocytic lesions]].


Images:
Images:
Line 109: Line 148:
**[[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====
Line 145: Line 189:
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.
====Breslow 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>
====Clark level====
*[[AKA]] ''anatomic level''.
*Not as reproducible as ''Breslow thickness'' - not used.
Anatomic level - definition:
*I = epidermis only ([[AKA]] melanoma in situ).
*II = extends into [[papillary dermis]] but does '''not''' fill or expand.
*III = fills and expands papillary dermis.
*IV = extends into reticular dermis.
*V = extends into subdermis.


====Margin assessment====
====Margin assessment====
Line 190: Line 220:
*'''I'''ncreased basal melanocytes.
*'''I'''ncreased basal melanocytes.
*'''N'''ests of melanocytes.
*'''N'''ests of melanocytes.
=====Assessment/reporting of margins=====
*There is no general agreement on how to report margins in melanoma.
It is suggested that one should:
#Try to tease apart melanoma cells from benign melanocytes.
#*Use the ''MARGIN'' mnemonic above.
#**Melanocytes with nuclear atypia = melanoma cells.
#Report the clearance of the nearest melanoma cell to the margin.
#*Positive margin = melanoma cell is touching ink.
#*Very close is reported as "clearance < 0.1 mm".
#Use [[immunostain]]s to assist the assessment of difficult cases:
#*MiTF is considered the preferred marker.
#*MART-1 (Melan A) is considered to overestimate melanocytes; it should ''not'' be used.<ref name=pmid21797920>{{Cite journal  | last1 = Kim | first1 = J. | last2 = Taube | first2 = JM. | last3 = McCalmont | first3 = TH. | last4 = Glusac | first4 = EJ. | title = Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ. | journal = J Cutan Pathol | volume = 38 | issue = 10 | pages = 775-9 | month = Oct | year = 2011 | doi = 10.1111/j.1600-0560.2011.01763.x | PMID = 21797920 }}</ref>
#*S-100 also marks follicular dendritic cells; it is ''not'' a preferred marker.
====Breslow 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>
=====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: [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.
**pT1a: ≤ 0.8 mm, no ulceration.
**pT1b: ulceration present ''or'' 0.8 mm  < thickness ≤ 1.0 mm (with or without ulceration).
*pT2 1.01 mm to 2.0 mm.
**pT2a: no ulceration.
**pT2b: ulceration present.
*pT3 2.01 mm to 4.0 mm.
**pT3a: no ulceration.
**pT3b: ulceration present.
*pT4 >4.0 mm.
**pT4a: no ulceration.
**pT4b: ulceration present.
=====Clark level=====
*[[AKA]] ''anatomic level''.
*''Not'' as reproducible as ''Breslow thickness''. It is not used for this reason.
Anatomic level - definition:
*I = epidermis only ([[AKA]] melanoma in situ).
*II = extends into [[papillary dermis]] but does '''not''' fill or expand.
*III = fills and expands papillary dermis.
*IV = extends into reticular dermis.
*V = extends into subdermis.


====Subtypes====
====Subtypes====
Line 289: Line 364:
==[[IHC]]==
==[[IHC]]==
===Standard panel===
===Standard panel===
#S100 +ve.
#S-100 +ve.
#*Negative staining pretty much excludes the diagnosis.
#*Negative staining pretty much excludes the diagnosis.
#HMB-45 +ve -- esp. deep.
#HMB-45 +ve -- especially deep, often patchy.
#Melan A (MART-1) +ve.
#Melan A (MART-1) +ve.


Notes:
Notes:
*The standard panel above (S100, HMB-45, MART-1) is also positive in other lesions, e.g. ''[[cellular blue nevus]]''.
*The standard panel above (S100, HMB-45, MART-1) is also positive in other lesions, e.g. ''[[cellular blue nevus]]''.
*Melan A tends to overestimate the number of melanocytes.<ref name=pmid21797920>{{Cite journal  | last1 = Kim | first1 = J. | last2 = Taube | first2 = JM. | last3 = McCalmont | first3 = TH. | last4 = Glusac | first4 = EJ. | title = Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ. | journal = J Cutan Pathol | volume = 38 | issue = 10 | pages = 775-9 | month = Oct | year = 2011 | doi = 10.1111/j.1600-0560.2011.01763.x | PMID = 21797920 }}</ref>
**Counting the cell bodies may give an accurate result.{{fact}}
*S-100 marks melanocytes and follicular dendritic cells.


===Threshold panel===
===Threshold panel===
When one it sure it is melanocyte... but unsure it is melanoma:
When one it sure it is melanocytic... but unsure whether it is melanoma:
*HMB-45 +ve deep melanocytes.
*HMB-45 +ve deep melanocytes.
**In benign lesions deep (mature) melanocytes are negative.
**In benign lesions deep (mature) melanocytes are negative.
Line 310: Line 388:
*MART-1.
*MART-1.
*HMB-45.
*HMB-45.
Notes:
*Positive in approximately 20% of cases - based on one series.<ref name=pmid24455276>{{cite journal |author=Teixeira V, Vieira R, Coutinho I, ''et al.'' |title=Prediction of sentinel node status and clinical outcome in a melanoma centre |journal=J Skin Cancer |volume=2013 |issue= |pages=904701 |year=2013 |pmid=24455276 |pmc=3886376 |doi=10.1155/2013/904701 |url=}}</ref>
**Strongly dependent on T-stage (T1 ~5%, T2 ~11%, T3 ~28%, T4 ~47%).


===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>
*[[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>
*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:
Line 325: Line 432:
It has lamellar fibrosis and multiple foci of complex rete ridge bridging and pagetoid  
It has lamellar fibrosis and multiple foci of complex rete ridge bridging and pagetoid  
spread of melanocytes. Mitotic activity is seen focally.
spread of melanocytes. Mitotic activity is seen focally.
</pre>
<pre>
SKIN LESION, MID BACK, EXCISION:
- LENTIGO MALIGNA (SOLAR ELASTOSIS AND MELANOMA IN SITU), MARGIN CLEARANCE < 0.1 MM.
COMMENT:
This lesion should be re-excised.
</pre>
<pre>
SKIN LESION, MID BACK, EXCISION:
- MELANOMA IN SITU AND SOLAR ELASTOSIS (LENTIGO MALIGNA), MARGIN CLEARANCE 2 MM.
COMMENT:
The presence of melanoma in situ is confirmed with immunostaining (HMB-45, MITF).
This lesion should be re-excised.
</pre>
====At least MIS====
<pre>
LEFT THUMB NAIL, AVULSION AND NAIL MATRIX BIOPSY:
- AT LEAST MALIGNANT MELANOMA IN SITU.
COMMENT:
The quantity of diagnostic material is suboptimal.
The limited number of lesional cells stain as follows:
POSITIVE: S-100, HMB-45, MITF, Melan A.
An internal review confirms the impression of at least melanoma in situ.
</pre>
====Micro====
The sections show hair-bearing skin with atypical melanocytes confined to the epidermis.
The melanocytes scatter upwards (focally), have confluent growth and nucleoli, and involve
the adnexal structures. Occasional large multi-nucleated melanocytes, with their nuclei
arranged around the cell periphery, are present. Mitotic activity is not apparent. Extensive solar elastosis is present.
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===
<pre>
SKIN LESION, LEFT LOWER BACK, SHAVE BIOPSY:
- INVASIVE MALIGNANT MELANOMA.
-- AT LEAST pT3a.
-- 6 MITOSES/MM*MM.
-- DEEP AND LATERAL MARGINS POSITIVE, WIDE RE-EXCISION SHOULD BE DONE.
-- PLEASE SEE TUMOUR SUMMARY.
-- PLEASE SEE COMMENT.
COMMENT:
The morphologic impression is confirmed by immunostains; the tumour is POSITIVE for
S-100, HMB-45, and MART-1.
</pre>
</pre>


Line 335: Line 500:
==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
48,584

edits

Retrieved from "https://librepathology.org/wiki/Special:MobileDiff/20779...51617"

Navigation menu