Metastatic Malignant Melanoma With Complete Loss of Differentiation Markers (Undifferentiated/Dedifferentiated Melanoma)

Abstract

Metastatic malignant melanoma is notorious for its phenotypic diversity and loss of differentiation markers. We herein summarized our experience with 14 metastatic melanomas showing complete loss of immunohistochemical melanocytic markers (with or without heterologous differentiation). Patients included 11 men and 3 women aged 24 to 78 years (median, 67 y). Thirteen patients had histologically confirmed primary skin melanoma, and 1 had metastatic melanoma of unknown primary. Undifferentiated metastasis was diagnosed synchronous to primary tumor (n=1), following skin melanoma by 3 months to 9 years (n=11) and preceding it by 1 year (n=1). Sites of undifferentiated metastases were axillary (3), inguinal (1), or submandibular (1) lymph nodes, digestive tract (2), bone/soft tissue (2), lung/pleura (2), and disseminated (n=3). Histology of metastases mimicked undifferentiated pleomorphic or spindle cell sarcoma with variable myxoid and giant cell areas (n=10) and cytokeratin-positive undifferentiated small cell sarcoma (n=1). Three cases showed heterologous dedifferentiation: pleomorphic rhabdomyosarcoma (n=1), teratocarcinosarcoma-like with prominent rhabdomyoblasts (n=1), and adenocarcinoma-like with metaplastic bone (n=1). All cases were negative for S100, melanoma cocktail, HMB45, Melan A, and SOX10. Other markers showed following results: smooth muscle actin (1/14), p16 (1/14), TP53 (2/12), pancytokeratin (4/14), desmin (5/14), h-caldesmon (0/9), and MDM2/CDK4 (0/5). SMARCB1 was intact in 8/8 cases. Genotyping showed BRAF(V600E) mutation (5/14), NRAS mutation (5/14), and BRAF/NRAS wild-type (4/14). In conclusion, undifferentiated/dedifferentiated metastatic melanoma is likely underrecognized and frequently mistaken for undifferentiated sarcoma or other neoplasms. Diagnosis of undifferentiated sarcoma at sites where melanoma metastasis are frequent (eg, inguinal and axillary region) should be made with great caution and warrants exploration of the remote history. Genotyping is a helpful surrogate marker in classifying such difficult cases. In the light of available targeted therapies, recognition of undifferentiated/dedifferentiated metastatic melanoma is mandatory for appropriate treatment.

Bioinformatics analysis to identify the critical genes, microRNAs and long noncoding RNAs in melanoma

“…[1] Malignant melanoma has a strong tendency to spread to other parts of the body and causes serious illness and death. [2] In 2016, there was an estimation of 76,380 new diagnoses of cutaneous melanoma and 10,130 deaths related to melanoma in the United States. [3] Despite significant breakthroughs and advances in early diagnosis and prevention as well as targeted therapies, the prognosis of melanoma remains unoptimistic.…”

The undifferentiated carcinoma that became a melanoma: Re-biopsy of a cancer of an unknown primary site: a case report

“…Expression of various non-melanoma markers, including intermediate filaments and loss of classical melanoma markers is not unusual [8, 9] and awareness of the possibility of unusual immunophenotypes is crucial for the right diagnosis. BRAF mutations are most commonly associated with malignant melanomas, colorectal adenocarcinomas, and papillary thyroid carcinoma and could therefore be helpful in identifying the origin of the tumor [10, 11].…”

Pancreatic adenosquamous carcinoma and intraductal papillary mucinous neoplasm in aCDKN2Agermline mutation carrier

“…The differential diagnosis when squamous component is found in a pancreatic neoplasia also includes ductal squamous metaplasia, mucoepidermoid carcinoma (which is characterized by the presence of squamoid intermediate cells and the absence of individual cell keratinization and keratin pearls) and pancreatoblastoma, which is rarely found in adults. In addition, in a patient with a previous history of malignant melanoma the possibility of de-differentiated melanoma with adenocarcinoma-like component should be also excluded[ 27 ].…”