Jump to content

Amelanotic melanoma

From Wikipedia, the free encyclopedia
(Redirected from Amelanotic melanomas)
Amelanotic melanoma
Amelanotic melanoma on a dog's toe
SpecialtyOncology, dermatology Edit this on Wikidata

Amelanotic melanoma is a type of skin cancer in which the cells do not make any melanin.[1]: 696 [2] They can be pink, red, purple or of normal skin color, and are therefore difficult to diagnose correctly. They can occur anywhere on the body, just as a typical melanoma can.

Often, amelanotic melanomas are mistaken for benign lesions, including dermatitis, benign neoplastic processes, or a different malignancy such as basal-cell carcinoma or squamous-cell carcinoma.[3] A poor prognosis is associated with amelanotic lesions, partially due to the difficulty in achieving a diagnosis; however, metastatic amelanotic melanoma has a worse prognosis than other subtypes.[3]

Survival after diagnosis of amelanotic melanoma was found in a 2014 seven-year study of 3,000 patients to be poorer than for pigmented melanoma, which was attributed to the more advanced stage at diagnosis due probably to difficulty of diagnosis. The study also suggested that amelanotic melanomas might grow faster than pigmented melanomas.[4]

Signs and symptoms

[edit]

Three primary clinical forms of amelanotic melanoma have been proposed: skin-colored dermal plaque with no epidermal alterations, papulonodular form, and erythematous macule along with epidermal changes on skin exposed to the sun.[5]

58% of cases of amelanotic melanoma are of the papulonodular form,[6] which can mimic pyogenic granuloma or hemangioma and present as an ulcerated nodule or vascular lesion.[7] 'ABCD' criteria (Asymmetry, Border irregularity, Color variegation, Diameter>6 mm) are rarely seen in non-papulonodular forms of amelanotic melanomas,[8][9] which can present as erythematous macules or patches, scaly eczema-like, or skin-colored dermal plaques.[10]

Though not around truly amelanotic melanomas,[6] a faint flush or periphery of the pigment is frequently seen surrounding amelanotic lesions.[11][12] The appearance of amelanotic melanomas can vary; they can be skin-colored, pink, red, or erythematous, with red amelanotic melanomas making up almost 70% of all amelanotic melanomas without melanin.[13]

Causes

[edit]

Risk factors

[edit]

Patients with amelanotic melanoma are typically diagnosed later in life—after age 50, in comparison to those with pigmented melanoma.[4][14] However, amelanotic melanoma accounts for about 70% of childhood cases.[15]

The relationship between amelanotic melanoma and sex is debatable; varying research indicates that the condition is more common in men,[16] women,[17] or neither sex.[18] The potential preference for women may stem from the fact that they self-report suspicious skin conditions more frequently than men,[4] while the potential predominance of men may be related to the fact that men expose themselves to more chronic outdoor sun exposure than women.[14]

The majority of patients with amelanotic melanomas are white,[14][19] and those with oculocutaneous albinism[20][21] or type I skin and red hair are more likely to have them.[19][11]

According to a population-based study, the likelihood of developing amelanotic melanoma is also increased by freckles, a sun-sensitive phenotype, the absence of nevi on the back, and a history of the disease in the past.[19]

Mechanism

[edit]

Amelanotic melanoma's underlying mechanism is still unknown. Previous research categorized amelanotic melanoma as either poorly differentiated or dedifferentiated.[16] Tyrosinase and microphthalmia-associated transcription factor (MITF) expression, however, allow amelanotic melanoma cells to retain their melanocytic lineage and melanin-forming capacity, just like their pigmented counterparts.[14] Furthermore, a study discovered a small number of poorly differentiated tumor cells in samples of amelanotic melanoma. Hence, rather than being dedifferentiated or inadequately differentiated, amelanotic melanoma is far more likely to be classified as a subtype of melanoma that maintains the capacity to form melanin.[16]

Amelanotic or hypomelanotic melanoma's may be caused by insufficient activity or quantity of tyrosinase, as evidenced by the decreased expressions of certain melanin-forming enzymes (such as tyrosinase) in amelanotic melanoma samples.[9][22] Furthermore, it has been suggested that downregulation of tyrosinase and other melanocyte-specific genes, mediated by the absence of MITF expression, may be the cause of the amelanotic melanoma phenotype, particularly in those with chromosomal copy number gains in 8q24.[23][24]

Amelanotic melanoma may also be caused by germline mutations in the MC1R, MITF, and P14arf genes in addition to increased copy number gains in 8q24.[19][23][25] Research findings vary regarding the contribution of somatic gene mutations to the development of amelanotic melanoma. There have been reports of a higher incidence of KIT aberrations in entirely amelanotic acral melanoma compared to pigmented acral melanomas,[26] as well as an elevated incidence of BRAF and KIT mutations in amelanotic melanomas.[10][27] Other research, however, discovered a strong correlation between BRAF mutations[28][10] and KIT alterations and melanoma hyperpigmentation.[29]

Diagnosis

[edit]

The most reliable method for identifying amelanotic melanoma is histology combined with immunohistochemistry.[9] Upon histopathologic examination, the presence of cords or nests of atypical melanocytes in the dermis typically results in the diagnosis of melanoma.[30] Nevertheless, amelanotic melanoma can present with a variety of histopathologic or cytological characteristics, so the accurate diagnosis depends on immunohistochemical staining.[16]

Markers like S100, MelanA, HMB-45, tyrosinase, MITF, and Ki-67 are often used. The most sensitive marker is S100 protein staining; other markers are relatively specific and include HMB-45, Melan-A, MITF, and tyrosinase.[31] Specifically, HMB-45 staining intensity is highly specific and correlates well with melanin content; some amelanotic melanomas, especially true amelanotic melanomas, can even be negative for HMB-45.[32][33] When separating benign melanocytic lesions from malignancies, Ki-67 is a useful tool.[31]

The Fontana–Masson stain for melanin deposits may reveal pigment within lesions that are not visible on routine hematoxylin-eosin-stained sections.[16] Additionally, melanosomes in hard-to-diagnose lesions can be found using electron microscopy.[30]

Treatment

[edit]

Surgical excision with a large safety margin is the main treatment for localized amelanotic melanoma. The suggested margin size for amelanotic melanoma is debatable since it varies according to the lesion's development, thickness, and invasion depth.[34] Guidelines from the Annals of Surgery, however, suggest that melanomas larger than 2 mm be removed with 2 cm margins.[35]

It is advised to have a sentinel lymph node biopsy for lesions that are thicker or have high-risk characteristics. According to one study, patients who underwent an immediate lymph node dissection at presentation had a higher five-year survival rate than patients who underwent a delayed lymph node dissection. This provided better chances of survival for people with node metastases.[36]

Adjuvant therapy may also be taken into consideration in advanced cases when patients exhibit high-risk characteristics like ulceration, a high rate of mitosis, or involvement of lymph nodes. Targeted therapies and systemic therapy using immune checkpoint inhibitors might be necessary.[34] Both ipilimumab and nivolumab have demonstrated encouraging outcomes when used to treat amelanotic melanoma.[37] But according to other research, postoperative radiation therapy only improved locoregional spread; no evidence has yet indicated that it improved overall survival.[38]

Outlook

[edit]

A poor prognosis is typically observed in patients with amelanotic melanomas.[39] While some research indicates that there is no statistically significant difference in survival between patients with pigmented melanoma and those with amelanotic melanoma,[13][18] other studies involving larger case series indicate that patients with amelanotic melanomas frequently exhibit significantly higher risks of death and recurrence, as well as lower survival rates in terms of melanoma-specific survival, melanoma-free survival, 5-year survival, and overall survival.[40][14]

Epidemiology

[edit]

Amelanotic melanomas are thought to account for 8% of all melanomas, making them extremely uncommon.[4]

See also

[edit]

References

[edit]
  1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
  2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
  3. ^ a b Cabrera, Raúl; Recule, Francisca (2018). "Unusual Clinical Presentations of Malignant Melanoma: A Review of Clinical and Histologic Features with Special Emphasis on Dermatoscopic Findings". American Journal of Clinical Dermatology. 19 (Suppl 1): 15–23. doi:10.1007/s40257-018-0373-6. ISSN 1175-0561. PMC 6244635. PMID 30374898.
  4. ^ a b c d Thomas, Nancy E.; Kricker, Anne; Waxweiler, Weston T.; et al. (2014). "Comparison of Clinicopathologic Features and Survival of Histopathologically Amelanotic and Pigmented Melanomas". JAMA Dermatology. 150 (12): 1306–1314. doi:10.1001/jamadermatol.2014.1348. ISSN 2168-6068. PMC 4262611. PMID 25162299.
  5. ^ Adler, Michael J.; White, Clifton R. (1997). "Amelanotic malignant melanoma". Seminars in Cutaneous Medicine and Surgery. 16 (2). Frontline Medical Communications, Inc.: 122–130. doi:10.1016/s1085-5629(97)80006-5. ISSN 1085-5629. PMID 9220551.
  6. ^ a b Gualandri, L; Betti, R; Crosti, C (February 9, 2009). "Clinical features of 36 cases of amelanotic melanomas and considerations about the relationship between histologic subtypes and diagnostic delay". Journal of the European Academy of Dermatology and Venereology. 23 (3). Wiley: 283–287. doi:10.1111/j.1468-3083.2008.03041.x. ISSN 0926-9959. PMID 19207640. S2CID 33209919.
  7. ^ Grant-Kels, Jane M.; Bason, Elizabeth T.; Grin, Caron M. (1999). "The misdiagnosis of malignant melanoma". Journal of the American Academy of Dermatology. 40 (4). Elsevier BV: 539–548. doi:10.1016/s0190-9622(99)70435-4. ISSN 0190-9622. PMID 10188671.
  8. ^ Jaimes, N.; Braun, R.P.; Thomas, L.; Marghoob, A.A. (May 18, 2011). "Clinical and dermoscopic characteristics of amelanotic melanomas that are not of the nodular subtype". Journal of the European Academy of Dermatology and Venereology. 26 (5). Wiley: 591–596. doi:10.1111/j.1468-3083.2011.04122.x. ISSN 0926-9959. PMID 21585561. S2CID 12200321.
  9. ^ a b c Detrixhe, Audrey; Libon, Florence; Mansuy, Marion; Nikkels-Tassoudji, Nazli; Rorive, Andrée; Arrese, Jorge E.; Quatresooz, Pascale; Reginster, Marie-Annick; Nikkels, Arjen F. (2016). "Melanoma masquerading as nonmelanocytic lesions". Melanoma Research. 26 (6). Ovid Technologies (Wolters Kluwer Health): 631–634. doi:10.1097/cmr.0000000000000294. ISSN 0960-8931. PMID 27537773. S2CID 46766290.
  10. ^ a b c Massi, Daniela; Pinzani, Pamela; Simi, Lisa; Salvianti, Francesca; De Giorgi, Vincenzo; Pizzichetta, Maria A.; Mirri, Francesco; Steffan, Agostino; Orlando, Claudio; Santucci, Marco; Canzonieri, Vincenzo (2013). "BRAF and KIT somatic mutations are present in amelanotic melanoma". Melanoma Research. 23 (5). Ovid Technologies (Wolters Kluwer Health): 414–419. doi:10.1097/cmr.0b013e32836477d4. ISSN 0960-8931. PMID 23938765. S2CID 43076961.
  11. ^ a b Chamberlain, Alexander J.; Fritschi, Lin; Kelly, John W. (2003). "Nodular melanoma: Patients' perceptions of presenting features and implications for earlier detection". Journal of the American Academy of Dermatology. 48 (5). Elsevier BV: 694–701. doi:10.1067/mjd.2003.216. ISSN 0190-9622. PMID 12734497.
  12. ^ Koch, Susan E.; Lange, Julie R. (2000). "Amelanotic melanoma: The great masquerader". Journal of the American Academy of Dermatology. 42 (5). Elsevier BV: 731–734. doi:10.1067/mjd.2000.103981. ISSN 0190-9622. PMID 10775846.
  13. ^ a b McClain, Susannah E.; Mayo, Kira B.; Shada, Amber L.; Smolkin, Mark E.; Patterson, James W.; Slingluff, Craig L. (March 21, 2012). "Amelanotic melanomas presenting as red skin lesions: a diagnostic challenge with potentially lethal consequences". International Journal of Dermatology. 51 (4). Wiley: 420–426. doi:10.1111/j.1365-4632.2011.05066.x. ISSN 0011-9059. PMC 4465919. PMID 22435430.
  14. ^ a b c d e Moreau, Jacqueline F.; Weissfeld, Joel L.; Ferris, Laura K. (2013). "Characteristics and survival of patients with invasive amelanotic melanoma in the USA". Melanoma Research. 23 (5). Ovid Technologies (Wolters Kluwer Health): 408–413. doi:10.1097/cmr.0b013e32836410fe. ISSN 0960-8931. PMID 23883947. S2CID 31173425.
  15. ^ Cordoro, Kelly M.; Gupta, Deepti; Frieden, Ilona J.; McCalmont, Timothy; Kashani-Sabet, Mohammed (2013). "Pediatric melanoma: Results of a large cohort study and proposal for modified ABCD detection criteria for children". Journal of the American Academy of Dermatology. 68 (6). Elsevier BV: 913–925. doi:10.1016/j.jaad.2012.12.953. ISSN 0190-9622. PMID 23395590.
  16. ^ a b c d e Cheung, Wang L.; Patel, Rishi R.; Leonard, Aimee; Firoz, Bahar; Meehan, Shane A. (November 3, 2011). "Amelanotic melanoma: a detailed morphologic analysis with clinicopathologic correlation of 75 cases". Journal of Cutaneous Pathology. 39 (1). Wiley: 33–39. doi:10.1111/j.1600-0560.2011.01808.x. ISSN 0303-6987. PMID 22050235. S2CID 21149897.
  17. ^ Nakhleh, Raouf E.; Wick, Mark R.; Rocamora, Antonio; Swanson, Paul E.; Dehner, Louis P. (June 1, 1990). "Morphologic Diversity in Malignant Melanomas". American Journal of Clinical Pathology. 93 (6). Oxford University Press (OUP): 731–740. doi:10.1093/ajcp/93.6.731. ISSN 1943-7722. PMID 2346132.
  18. ^ a b Giuliano, A E; Cochran, A J; Morton, D L (December 1982). "Melanoma from unknown primary site and amelanotic melanoma". Seminars in Oncology. 9 (4): 442–447. PMID 7170630.
  19. ^ a b c d Vernali, Steven; Waxweiler, Weston T.; Dillon, Patrick M.; Kanetsky, Peter A.; Orlow, Irene; Luo, Li; Busam, Klaus J.; Kricker, Anne; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Sacchetto, Lidia; Dwyer, Terence; Cust, Anne E.; Ollila, David W.; Begg, Colin B.; Berwick, Marianne; Thomas, Nancy E. (October 1, 2017). "Association of Incident Amelanotic Melanoma With Phenotypic Characteristics, MC1R Status, and Prior Amelanotic Melanoma". JAMA Dermatology. 153 (10). American Medical Association (AMA): 1026–1031. doi:10.1001/jamadermatol.2017.2444. ISSN 2168-6068. PMC 5650093. PMID 28746718.
  20. ^ Ribero, S.; Carrera, C.; Tell-Marti, G.; Pastorino, C.; Badenas, C.; Garcia, A.; Malvehy, J.; Puig, S. (November 22, 2017). "Amelanotic melanoma in oculocutaneous albinism: a genetic, dermoscopic and reflectance confocal microscopy study". British Journal of Dermatology. 177 (6). Oxford University Press (OUP): e333–e335. doi:10.1111/bjd.15687. ISSN 0007-0963. PMC 5704977. PMID 28555837.
  21. ^ De Luca, D.A.; Bollea Garlatti, L.A.; Galimberti, G.N.; Galimberti, R.L. (August 20, 2015). "Amelanotic melanoma in albinism: the power of dermatoscopy". Journal of the European Academy of Dermatology and Venereology. 30 (8). Wiley: 1422–1423. doi:10.1111/jdv.13264. ISSN 0926-9959. PMID 26290313. S2CID 29789114.
  22. ^ Beyeler, Mirjam; Dummer, Reinhard (2005). "Cutaneous melanoma: uncommon presentations". Clinics in Dermatology. 23 (6). Elsevier BV: 587–592. doi:10.1016/j.clindermatol.2005.01.010. ISSN 0738-081X. PMID 16325067.
  23. ^ a b Pouryazdanparast, Pedram; Brenner, Alex; Haghighat, Zahra; Guitart, Joan; Rademaker, Alfred; Gerami, Pedram (2012). "The role of 8q24 copy number gains and c-MYC expression in amelanotic cutaneous melanoma". Modern Pathology. 25 (9). Elsevier BV: 1221–1226. doi:10.1038/modpathol.2012.75. ISSN 0893-3952. PMID 22555175.
  24. ^ Pouryazdanparast, Pedram; Cowen, D. Patrick; Beilfuss, Beth Ann; Haghighat, Zahra; Guitart, Joan; Rademaker, Alfred; Gerami, Pedram (2012). "Distinctive Clinical and Histologic Features in Cutaneous Melanoma With Copy Number Gains in 8q24". American Journal of Surgical Pathology. 36 (2). Ovid Technologies (Wolters Kluwer Health): 253–264. doi:10.1097/pas.0b013e31823425cc. ISSN 0147-5185. PMID 22020039. S2CID 20951938.
  25. ^ Ghiorzo, Paola; Pastorino, Lorenza; Pizzichetta, Maria A.; Bono, Riccardo; Queirolo, Paola; Talamini, Renato; Annessi, Giorgio; Bruno, William; Nasti, Sabina; Gargiulo, Sara; Battistuzzi, Linda; Sini, Maria C.; Palmieri, Giuseppe; Scarrà, Giovanna Bianchi (2009). "CDKN2A and MC1R analysis in amelanotic and pigmented melanoma". Melanoma Research. 19 (3). Ovid Technologies (Wolters Kluwer Health): 142–145. doi:10.1097/cmr.0b013e32832a1e18. ISSN 0960-8931. PMID 19339902. S2CID 19473046.
  26. ^ Jin, Sun A.; Chun, Seung Min; Choi, Yoo Duk; Kweon, Sun-Seog; Jung, Sung Taek; Shim, Hyun Jeong; Yun, Sook Jung (2013). "BRAF Mutations and KIT Aberrations and Their Clinicopathological Correlation in 202 Korean Melanomas". Journal of Investigative Dermatology. 133 (2). Elsevier BV: 579–582. doi:10.1038/jid.2012.338. ISSN 0022-202X. PMID 23014346.
  27. ^ Choi, Yoo Duk; Chun, Seung Min; Jin, Sun A.; Lee, Jee-Bum; Yun, Sook Jung (2013). "Amelanotic acral melanomas: Clinicopathological, BRAF mutation, and KIT aberration analyses". Journal of the American Academy of Dermatology. 69 (5). Elsevier BV: 700–707. doi:10.1016/j.jaad.2013.06.035. ISSN 0190-9622. PMID 23972510.
  28. ^ Viros, Amaya; Fridlyand, Jane; Bauer, Juergen; Lasithiotakis, Konstantin; Garbe, Claus; Pinkel, Daniel; Bastian, Boris C (June 3, 2008). "Improving Melanoma Classification by Integrating Genetic and Morphologic Features". PLOS Medicine. 5 (6). Public Library of Science (PLoS): e120. doi:10.1371/journal.pmed.0050120. ISSN 1549-1676. PMC 2408611. PMID 18532874.
  29. ^ Wu, Julie M; Alvarez, Hector; García, Patricia; Rojas, Pamela L; Wong, Grace; Maitra, Anirban; Antonescu, Cristina; Montgomery, Elizabeth A (2009). "Melanoma Hyperpigmentation Is Strongly Associated With KIT Alterations". The American Journal of Dermatopathology. 31 (7). Ovid Technologies (Wolters Kluwer Health): 619–625. doi:10.1097/dad.0b013e3181a23f3b. ISSN 0193-1091. PMID 19652585. S2CID 41277317.
  30. ^ a b GIBSON, LAWRENCE E.; GOELLNER, JOHN R. (1988). "Amelanotic Melanoma: Cases Studied by Fontana Stain, S-100 Immunostain, and Ultrastructural Examination". Mayo Clinic Proceedings. 63 (8). Elsevier BV: 777–782. doi:10.1016/s0025-6196(12)62357-x. ISSN 0025-6196. PMID 2456432.
  31. ^ a b Ohsie, Steven J.; Sarantopoulos, G. Peter; Cochran, Alistair J.; Binder, Scott W. (April 8, 2008). "Immunohistochemical characteristics of melanoma". Journal of Cutaneous Pathology. 35 (5). Wiley: 433–444. doi:10.1111/j.1600-0560.2007.00891.x. ISSN 0303-6987. PMID 18399807.
  32. ^ Trefzer, U.; Rietz, Nadine; Chen, Yingwen; Audring, Heike; Herberth, Gunda; Siegel, Petra; Reinke, Susanne; Königer, Peter; Wu, Shuguang; Ma, Jing; Liu, Yanjun; Wang, H.; Sterry, Wolfram; Guo, Yajun (December 25, 2000). "SM5-1: a new monoclonal antibody which is highly sensitive and specific for melanocytic lesions". Archives of Dermatological Research. 292 (12). Springer Science and Business Media LLC: 583–589. doi:10.1007/s004030000186. ISSN 0340-3696. PMID 11214818. S2CID 26373939.
  33. ^ Kim, You Chan; Lee, Min Geol; Choe, Sung Whan; Lee, Mn Cheol; Chung, Han Gil; Cho, Sang-Ho (2003). "Acral lentiginous melanoma: an immunohistochemical study of 20 cases". International Journal of Dermatology. 42 (2). Wiley: 123–129. doi:10.1046/j.1365-4362.2003.01583.x. ISSN 0011-9059. PMID 12709000. S2CID 9775861.
  34. ^ a b Karmilkar, Kunal; Norem, Richard F (July 10, 2023). "Amelanotic Malignant Melanoma: A Case Report". Cureus. 15 (7). Springer Science and Business Media LLC: e41665. doi:10.7759/cureus.41665. ISSN 2168-8184. PMC 10412465. PMID 37575793.
  35. ^ McKinnon, J Gregory; Starritt, Emma C.; Scolyer, Richard A.; McCarthy, William H.; Thompson, John F. (2005). "Histopathologic Excision Margin Affects Local Recurrence Rate". Annals of Surgery. 241 (2). Ovid Technologies (Wolters Kluwer Health): 326–333. doi:10.1097/01.sla.0000152014.89434.96. ISSN 0003-4932. PMC 1356919. PMID 15650644.
  36. ^ Cascinelli, N; Morabito, A; Santinami, M; MacKie, RM; Belli, F (1998). "Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial". The Lancet. 351 (9105). Elsevier BV: 793–796. doi:10.1016/s0140-6736(97)08260-3. ISSN 0140-6736. PMID 9519951. S2CID 40174535.
  37. ^ Furune, Satoshi; Kondo, Chiaki; Takano, Yuko; Shimokata, Tomoya; Sugishita, Mihoko; Mitsuma, Ayako; Maeda, Osamu; Ando, Yuichi (October 12, 2021). "Vitiligo and tumor response in a patient with amelanotic melanoma undergoing nivolumab treatment". International Cancer Conference Journal. 11 (1). Springer Science and Business Media LLC: 46–48. doi:10.1007/s13691-021-00515-w. ISSN 2192-3183. PMC 8787012. PMID 35116218.
  38. ^ Tahiri, Ilias; El Houari, Othman; Hajjij, Amal; Zalagh, Mohammed; Benariba, Fouad (February 21, 2022). "Amelanotic Malignant Mucosal Melanoma of the Nasal Cavity: Case Report and Literature Review". Cureus. 14 (2). Cureus, Inc.: e22442. doi:10.7759/cureus.22442. ISSN 2168-8184. PMC 8941970. PMID 35371814.
  39. ^ Gong, Hui-Zi; Zheng, He-Yi; Li, Jun (2019). "Amelanotic melanoma". Melanoma Research. 29 (3). Ovid Technologies (Wolters Kluwer Health): 221–230. doi:10.1097/cmr.0000000000000571. ISSN 0960-8931. PMID 30672881. S2CID 58946740.
  40. ^ Søndergaard, Knud; Schou, Geert (1985). "Survival with primary cutaneous malignant melanoma, evaluated from 2012 cases". Virchows Archiv A. 406 (2). Springer Science and Business Media LLC: 179–195. doi:10.1007/bf00737084. ISSN 0174-7398. PMID 3923697. S2CID 33946021.

Further reading

[edit]
[edit]

Public Domain This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute.