BRAF and KIT somatic mutations are present in amelanotic melanoma

Massi, Daniela; Pinzani, Pamela; Simi, Lisa; Salvianti, Francesca; Giorgi, Vincenzo De; Pizzichetta, Maria Antonietta; Mirri, Francesco; Steffan, Agostino; Orlando, Claudio; Santucci, Marco; Canzonieri, Vincenzo

doi:10.1097/cmr.0b013e32836477d4

Cited by 20 publications

(20 citation statements)

References 18 publications

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“…6-11 Amelanotic melanomas can be found among all histologic subtypes, including superficial spreading (SSM), nodular (NM), lentigo maligna (LMM), and acral lentiginous (ALM) melanoma. 6,12 …”

Section: Introductionmentioning

confidence: 99%

Comparison of Clinicopathologic Features and Survival of Histopathologically Amelanotic and Pigmented Melanomas

et al. 2014

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Importance Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathology review, or no adjustment for stage limit interpretation or generalization of results from prior studies. Objective To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study. Design Survival analysis with median follow-up of 7.6 years. Setting The Genes, Environment, and Melanoma study enrolled incident cases of melanoma diagnosed in 1998-2003 from international population-based cancer registries. Participants A total of 2,995 patients with 3,486 invasive primary melanomas centrally scored for histologic pigmentation. Main Outcomes and Measurements Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively. Results Eight percent of melanomas (275 of 3,467) were histopathologically amelanotic. Female sex, nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a co-existing nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally of a higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (P for trend <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than pigmented melanoma [hazard ratio (HR), 2.0; 95% confidence interval (CI), 1.4-3.0; P< .001], adjusted for age, sex anatomic site, and study design variables; but survival did not differ once AJCC tumor stage was also taken into account, (HR, 0.8; 95% CI, 0.5-1.2; P = .36). Conclusions and Relevance At the population level, survival after diagnosis of amelanotic melanoma is poorer than after pigmented melanoma because of its more advanced stage at diagnosis. It is probable that amelanotic melanomas present at more advanced tumor stages because they are difficult to diagnose. The association of amelanotic melanoma with presence of mitoses independently of Breslow thickness and other clinicopathologic characteristics suggests that amelanotic melanomas might also grow faster than pigmented melanomas. New strategies for early diagnosis and investigation of the biology of amelanotic melanoma are warranted.

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Section: Introductionmentioning

confidence: 99%

Comparison of Clinicopathologic Features and Survival of Histopathologically Amelanotic and Pigmented Melanomas

et al. 2014

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“…Microscopically, AAM is often classified as a nodular melanoma, with a high Breslow thickness and significant mitotic activity. It's biological behavior may be intrinsically more aggressive than that of conventional pigmented melanomas 10 . The histopathological features of AAM are variable and challenging to define, and can be difficult to differentiate from other tumors such as desmoplastic, neurotropic, histiocytic, and small-cell variants.…”

Section: Discussionmentioning

confidence: 99%

Amelanotic Acral Melanoma Associated withKITMutation and Vitiligo

et al. 2015

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Amelanotic acral melanoma is rare and difficult to diagnose, both clinically and pathologically. KIT mutations are frequently found in acral melanomas and are considered a risk factor for poor prognosis. The presence of vitiligo in melanoma has been reported, and KIT is thought to be partly responsible for the dysfunction and loss of melanocytes observed in vitiligo. We report a case of amelanotic subungual melanoma with multiple metastases that was associated with KIT mutation and vitiligo. An 85-year-old man presented with a 3-year history of a tender erythematous ulcerated tumor on the left third fingertip and developed hypopigmented patches on the face and trunk. Histopathological examination of the ulcerative tumor showed aggregates of tumor cells that were pleomorphic epithelioid cells. Immunohistochemical staining of the tumor cells was positive for S100, HMB45, and c-Kit. Histopathological findings from the hypopigmented patch on the face were consistent with vitiligo. Mutation analysis showed a KIT mutation in exon 17 (Y823D). The patient had metastasis to the brain, liver, bone, and both lungs. The patient refused chemotherapy, and died 3 months after the first visit.

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“…Classically, BRAF mutations have been associated with highly pigmented MMs. However, Massi et al demonstrated a high BRAF mutation rate in amelanotic melanoma, suggesting that this characteristic could be used as a valuable diagnostic tool [ 39 ].…”

Section: Amelanotic Melanomamentioning

confidence: 99%

Unusual Clinical Presentations of Malignant Melanoma: A Review of Clinical and Histologic Features with Special Emphasis on Dermatoscopic Findings

Cabrera

Reculé

2018

Am J Clin Dermatol

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This review presents the main challenges encountered when diagnosing unusual variants of malignant melanoma with the aim of raising awareness to allow application of the most appropriate treatment strategies. Although these melanomas are often rare, their misdiagnosis potentially jeopardizes patients’ health and survival, and has medicolegal implications. The clinical and histologic presentations of melanoma vary greatly, and assessment of uncommon melanomas can be difficult for practitioners because of their scarcity and resemblance to other dermatologic entities. The most problematic melanoma types are desmoplastic melanoma, polypoid melanoma, primary dermal melanoma, verrucous malignant melanoma, pigmented epithelioid melanocytoma, mucosal melanoma, follicular melanoma and melanoma with non-melanocytic differentiation. The two most difficult-to-diagnose subtypes of melanoma are the nevoid and the amelanotic melanomas. Some specific attributes of these variants can be more easily recognized with digital dermatoscopy, facilitating early detection and possibly avoiding invasive procedures. Key cases with the most notable clinical, dermatoscopic, and histopathologic features are presented, highlighting the practical issues of making an accurate diagnosis and choosing the best therapy.

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BRAF and KIT somatic mutations are present in amelanotic melanoma

Cited by 20 publications

References 18 publications

Comparison of Clinicopathologic Features and Survival of Histopathologically Amelanotic and Pigmented Melanomas

Comparison of Clinicopathologic Features and Survival of Histopathologically Amelanotic and Pigmented Melanomas

Amelanotic Acral Melanoma Associated withKITMutation and Vitiligo

Unusual Clinical Presentations of Malignant Melanoma: A Review of Clinical and Histologic Features with Special Emphasis on Dermatoscopic Findings

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