Melanoma natural history, complications and prognosis: Difference between revisions

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{{Melanoma}}
{{CMG}} {{AE}} {{SSK}}; {{YD}}


{{CMG}}
{{Melanoma}}
==Overview==
==Overview==
==Natural history==
If left untreated, [[melanoma]] progression occurs horizontally (radial growth plate) and vertically (vertical growth plate) and is then followed by [[Dermis|dermal]] invasion and distant [[metastasis]]. [[Melanoma]] is an aggressive [[tumor]] characterized by early [[metastasis]]. Common sites of [[metastasis]] include [[Bone|bones]], [[brain]], [[Kidney|kidneys]], [[Lung|lungs]], [[liver]] and [[skin]] ([[secondary]] distant site). [[Complication (medicine)|Complications]] of [[melanoma]] are usually related to the site of [[metastasis]]. The 5-year relative survival of [[Patient|patients]] with [[melanoma]] is approximately 93%. Features associated with worse [[prognosis]] are [[tumor]] thickness ([[Breslow's depth|Breslow thickness]]), depth related to [[skin]] structures (Clark level), type of [[melanoma]], presence of [[Ulcer|ulceration]], presence of [[Lymphatic system|lymphatic]]/[[Perineurium|perineural]] invasion, location of [[lesion]], presence of [[Satellite (biology)|satellite]] [[Lesion|lesions]], and the presence of regional or distant [[metastasis]].
 
==Natural History==
*If left untreated, [[Melanocyte|melanocytes]] first [[Cell growth|proliferate]] randomly with an aberrant growth within an existing [[nevus]].
*More advanced stages are characterized by a radial growth phase with [[Epidermis (skin)|intraepidermal]] growth and penetration into the papillary [[dermis]].
*Final stages demonstrate a vertical growth phase with [[Dermis|dermal]] invasion and widening of the papillary [[dermis]] before [[Cancer|cancerous]] [[Cell (biology)|cells]] finally [[Metastasis|metastasize]] to other parts of the [[skin]] and other [[Organ (anatomy)|organs]].


==Complications==
==Complications==
[[Complication (medicine)|Complications]] of [[melanoma]] are usually due to distant [[metastasis]]. Common sites of [[metastasis]] are shown below:
*[[Bone]]
*[[Brain]]
*[[Liver]]
*[[Kidney]]
*[[Skin]] (secondary distant site)
*Lungs<ref name="pmid25032021">{{cite journal |vauthors=Brant JM |title=Breathlessness with pulmonary metastases: a multimodal approach |journal=J Adv Pract Oncol |volume=4 |issue=6 |pages=415–22 |date=November 2013 |pmid=25032021 |pmc=4093448 |doi= |url=}}</ref>


==Prognosis==
==Prognosis==
Features that affect [[prognosis]] are [[tumor]] thickness in millimeters ([[Breslow's depth]]), depth related to skin structures (Clark level), type of melanoma, presence of ulceration, presence of lymphatic/perineural invasion, presence of tumor infiltrating [[lymphocyte]]s (if present, prognosis is better), location of lesion, presence of satellite lesions, and presence of regional or distant [[metastasis]].<ref>{{cite journal | author = Homsi J, Kashani-Sabet M, Messina J, Daud A | title = Cutaneous melanoma: prognostic factors. | journal = Cancer Control | volume = 12 | issue = 4 | pages = 223-9 | year = 2005 | id = PMID 16258493}}''[https://www.moffitt.usf.edu/pubs/ccj/v12n4/pdf/223.pdf Full text (PDF)]''</ref>
===Determinants of Prognosis===
*Features that affect [[prognosis]] include:<ref>{{cite journal | author = Homsi J, Kashani-Sabet M, Messina J, Daud A | title = Cutaneous melanoma: prognostic factors. | journal = Cancer Control | volume = 12 | issue = 4 | pages = 223-9 | year = 2005 | id = PMID 16258493}}''[https://www.moffitt.usf.edu/pubs/ccj/v12n4/pdf/223.pdf Full text (PDF)]''</ref>


Certain types of melanoma have worse prognoses but this is explained by their [[Breslow's depth|thickness]]. Interestingly, less invasive melanomas even with lymph node metastases carry a better prognosis than deep melanomas without regional metastasis at time of staging.  Local recurrences tend to behave similarly to a primary unless they are at the site of a [[wide local excision]] (as opposed to a staged excision or punch/shave excision) since these recurrences tend to indicate lymphatic invasion.
:*[[Tumor]] thickness in millimeters ([[Breslow's depth]])
:*Depth related to [[skin]] structures (Clark level)
:*Type of [[melanoma]]
:*Presence of [[Ulcer|ulceration]]
:*Presence of [[Lymphatic system|lymphatic]]/[[Perineurium|perineural]] invasion
:*Presence of [[tumor]] infiltrating [[lymphocyte]]s (if present, [[prognosis]] is better)
:*Location of [[lesion]]
:*Presence of [[Satellite (biology)|satellite]] [[Lesion|lesions]]
:*Presence of regional or distant [[metastasis]]


When melanomas have spread to the [[lymph node]]s, one of the most important factors is the number of nodes with malignancy.  Extent of malignancy within a node is also important; micrometastases in which malignancy is only microscopic have a more favorable prognosis than macrometastases.  In some cases micrometastases may only be detected by special staining, and if malignancy is only detectable by a rarely-employed test known as [[polymerase chain reaction]] (PCR), the prognosis is better. Macrometastases in which malignancy is clinically apparent (in some cases cancer completely replaces a node) have a far worse prognosis, and if nodes are matted or if there is extracapsular extension, the prognosis is still worse.
===TNM Staging===
*The [[TNM]] staging classification summarizes most of the above mentioned findings. Using the [[TNM|TNM classification]], [[prognosis]] can be determined based on the stage of the [[disease]] as follows:
:*'''Stage 0''': [[Melanoma]] [[in situ]], 100% Survival
:*'''Stage I''': Invasive [[Melanoma]], 85-95% Survival
:*'''Stage II''': High Risk [[Melanoma]], 40-85% Survival
:*'''Stage III''': Regional [[Metastasis]], 25-60% Survival
:*'''Stage IV''': Distant [[Metastasis]], 9-15% Survival


When there is distant metastasis, the cancer is generally considered incurable. The five year survival rate is less than 10%.<ref name=AJCC>{{cite journal | author = Balch C, Buzaid A, Soong S, Atkins M, Cascinelli N, Coit D, Fleming I, Gershenwald J, Houghton A, Kirkwood J, McMasters K, Mihm M, Morton D, Reintgen D, Ross M, Sober A, Thompson J, Thompson J | title = Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. | journal = J Clin Oncol | volume = 19 | issue = 16 | pages = 3635-48 | year = 2001 | id = PMID 11504745}}''[http://www.jco.org/cgi/content/full/19/16/3635 Full text]''</ref> The median survival is 6 to 12 months. Treatment is [[Palliative care|palliative]], focusing on life-extension and quality of life.  In some cases, patients may live many months or even years with metastatic melanoma (depending on the aggressiveness of the treatment).  Metastases to skin and lungs have a better prognosis. Metastases to brain, bone and liver are associated with a worse prognosis.  
'''''Please check the [[Melanoma staging|staging]] page for more details about the staging scheme and the [[TNM|TNM classification]].'''''


There is not enough definitive evidence to adequately stage, and thus give a prognosis for ocular melanoma and melanoma of soft parts, or mucosal melanoma (e.g. rectal melanoma), although these tend to metastasize more easily.  Even though regression may increase survival, when a melanoma has regressed, it is impossible to know its original size and thus the original tumor is often worse than a [[Pathology|pathology report]] might indicate.
===Breslow's Depth===
{{see also|Breslow's depth}}
*The [[Breslow's depth]] is independent of other features of the [[tumor]] and has been demonstrated to be associated with 5-year survival:
[[Image:Melanoma 2.jpg|thumb|center|220px|Black, irregularly shaped, uniformly brown pigmented nevus on a 19-year-old man's right cheek. The Breslow index measured 2.88 mm, and a thorough medical evaluation revealed no evidence of metastases. The scar was reexcised with a 2-cm margin, and the skin was repaired with a graft.]]
{| {{table}} cellpadding="4" cellspacing="0" style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;"
! style="background: #4479BA;" | {{fontcolor|#FFF|'''Breslow's Depth'''}}
! style="background: #4479BA;" | {{fontcolor|#FFF|'''5-year survival'''}}
|-
| < 0.76 mm||95% to 100%
|-
| 0.76-1.5 mm||80% to 96%
|-
| 1.5-4 mm||60% to 75%
|-
| > 4 mm||37% to 50%
|}
 
===Micro-metastasis vs. Macro-metastasis===
*Extent of [[Cancer|malignancy]] within a [[Lymph node|node]] is also important; micro-[[Metastasis|metastases]] in which [[Cancer|malignancy]] is only [[microscopic]] have a more favorable [[prognosis]] than macro-[[Metastasis|metastases]].
*In some cases, micro-[[Metastasis|metastases]] may only be detected by special [[staining]], and if [[Cancer|malignancy]] is only detectable [[polymerase chain reaction|polymerase chain reaction (PCR)]], the [[prognosis]] is better.
*Macro-[[Metastasis|metastases]] in which [[Cancer|malignancy]] is clinically apparent (in some cases [[cancer]] completely replaces a node) have a far worse [[prognosis]], and if [[Lymph nodew|nodes]] are matted or if there is [[Lymph node capsule|extra-capsular]] extension, the [[prognosis]] is still worse.


===5-Year Survival===
===5-Year Survival===
* Between 2004 and 2010, the 5-year relative survival of patients with melanoma was 92.9%.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
* Between 2004 and 2010, the 5-year relative survival of [[Patient|patients]] with [[melanoma]] was 92.9%.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>


* When stratified by age, the 5-year relative survival of patients with melanoma was 92.7% and 88.2% for patients <65 and ≥ 65 years of age respectively.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
* When stratified by age, the 5-year relative survival of [[Patient|patients]] with [[melanoma]] was 92.7% and 88.2% for [[Patient|patients]] <65 and ≥ 65 years of age respectively.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>


* The survival of patients with melanoma varies with the stage of the disease. Shown below is a table depicting the 5-year relative survival by the stage of melanoma:<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
*When there is distant [[metastasis]], the cancer is generally considered [[Cure|incurable]]. The five year survival rate is less than 10%.<ref name="AJCC">{{cite journal | author = Balch C, Buzaid A, Soong S, Atkins M, Cascinelli N, Coit D, Fleming I, Gershenwald J, Houghton A, Kirkwood J, McMasters K, Mihm M, Morton D, Reintgen D, Ross M, Sober A, Thompson J, Thompson J | title = Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. | journal = J Clin Oncol | volume = 19 | issue = 16 | pages = 3635-48 | year = 2001 | id = PMID 11504745}}''[http://www.jco.org/cgi/content/full/19/16/3635 Full text]''</ref>  


{| style="cellpadding=0; cellspacing= 0; width: 600px;"
* The survival of [[Patient|patients]] with [[melanoma]] varies with the [[Cancer staging|stage]] of the [[disease]].  Shown below is a table depicting the 5-year relative survival by the [[Cancer staging|stage]] of [[melanoma]]:<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
|-
 
|style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align=center |'''Stage'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align=center | '''5-year relative survival (%), (2004-2010)'''
{| {{table}} cellpadding="4" cellspacing="0" style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;"
! style="background: #4479BA;" | {{fontcolor|#FFF|'''Stage'''}}
! style="background: #4479BA;" | {{fontcolor|#FFF|'''5-year relative survival (%), 2004-2010'''}}
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |'''All stages'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |91.3%
| '''All stages'''|| 91.3%
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |'''Localized'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left  |98.1%
| '''Localized'''|| 98.1%
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |'''Regional'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |62.6%
| '''Regional'''|| 62.6%
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left  |'''Distant'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left  |16.1%
| '''Distant'''|| 16.1%
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left  |'''Unstaged'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |78.4%
| '''Unstaged'''|| 78.4%
|}
|}


* Shown below is an image depicting the 5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between 1998 and 2010 of melanoma by stage at diagnosis according to [[SEER]]. These graphs are adapted from [[SEER]]: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
* Shown below is an image depicting the 5-year conditional relative survival (probability of surviving in the next 5-years given the [[Cohort study|cohort]] has already survived 0, 1, 3 years) between 1998 and 2010 of [[melanoma]] by [[Cancer staging|stage]] at [[diagnosis]] according to [[SEER]]. These graphs are adapted from [[SEER]]: The Surveillance, [[Epidemiology]], and End Results Program of the National [[Cancer]] Institute.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>


[[Image:5 year survival in melanoma in USA.png|5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between 1998 and 2010 of melanoma by stage at diagnosis according to SEER]]
[[Image:5 year survival in melanoma in USA.png|5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between 1998 and 2010 of melanoma by stage at diagnosis according to SEER]]

Latest revision as of 16:52, 4 January 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Serge Korjian M.D.; Yazan Daaboul, M.D.

Overview

If left untreated, melanoma progression occurs horizontally (radial growth plate) and vertically (vertical growth plate) and is then followed by dermal invasion and distant metastasis. Melanoma is an aggressive tumor characterized by early metastasis. Common sites of metastasis include bones, brain, kidneys, lungs, liver and skin (secondary distant site). Complications of melanoma are usually related to the site of metastasis. The 5-year relative survival of patients with melanoma is approximately 93%. Features associated with worse prognosis are tumor thickness (Breslow thickness), depth related to skin structures (Clark level), type of melanoma, presence of ulceration, presence of lymphatic/perineural invasion, location of lesion, presence of satellite lesions, and the presence of regional or distant metastasis.

Natural History

Complications

Complications of melanoma are usually due to distant metastasis. Common sites of metastasis are shown below:

Prognosis

Determinants of Prognosis

TNM Staging

Please check the staging page for more details about the staging scheme and the TNM classification.

Breslow's Depth

  • The Breslow's depth is independent of other features of the tumor and has been demonstrated to be associated with 5-year survival:
Breslow's Depth 5-year survival
< 0.76 mm 95% to 100%
0.76-1.5 mm 80% to 96%
1.5-4 mm 60% to 75%
> 4 mm 37% to 50%

Micro-metastasis vs. Macro-metastasis

5-Year Survival

  • When stratified by age, the 5-year relative survival of patients with melanoma was 92.7% and 88.2% for patients <65 and ≥ 65 years of age respectively.[3]
  • When there is distant metastasis, the cancer is generally considered incurable. The five year survival rate is less than 10%.[4]
Stage 5-year relative survival (%), 2004-2010
All stages 91.3%
Localized 98.1%
Regional 62.6%
Distant 16.1%
Unstaged 78.4%
  • Shown below is an image depicting the 5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between 1998 and 2010 of melanoma by stage at diagnosis according to SEER. These graphs are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.[3]

5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between 1998 and 2010 of melanoma by stage at diagnosis according to SEER

References

  1. ↑ Brant JM (November 2013). "Breathlessness with pulmonary metastases: a multimodal approach". J Adv Pract Oncol. 4 (6): 415–22. PMC 4093448. PMID 25032021.
  2. ↑ Homsi J, Kashani-Sabet M, Messina J, Daud A (2005). "Cutaneous melanoma: prognostic factors". Cancer Control. 12 (4): 223–9. PMID 16258493.Full text (PDF)
  3. ↑ 3.0 3.1 3.2 3.3 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.
  4. ↑ Balch C, Buzaid A, Soong S, Atkins M, Cascinelli N, Coit D, Fleming I, Gershenwald J, Houghton A, Kirkwood J, McMasters K, Mihm M, Morton D, Reintgen D, Ross M, Sober A, Thompson J, Thompson J (2001). "Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma". J Clin Oncol. 19 (16): 3635–48. PMID 11504745.Full text

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