Evolution of a melanoma in situ to a sarcomatoid dedifferentiated melanoma

Abstract

Sarcomatoid dedifferentiated melanoma (SDDM) is a recently recognized subtype of melanoma that stains diffusely for CD10 and lacks the expression of the usual melanocytic markers including S100, SOX10, MITF, and Melan A. Advances in next‐generation DNA sequencing technology have facilitated the increased recognition of this rare, aggressive spindle cell melanoma. Herein, a case of relatively early lesion of SDDM arising in association with melanoma in situ is highlighted. A 72‐year‐old man with a history of previously treated melanoma in situ on the face five years prior presented with a new rapidly growing lesion within the scar of the treated site. A shave biopsy of the lesion revealed a centrally located 1.8‐mm deep, poorly differentiated spindle cell neoplasm in association with an adjacent recurrent melanoma in situ. The spindle cell component stained diffusely for CD10, but failed to stain for S100, SOX10, and Melan‐A while the melanoma in situ expressed all three melanocytic markers. Next‐generation DNA sequencing assay revealed mutations in NF1, CDKN2A, TP53, and TSC1. A diagnosis of stage 2B SDDM arising in association with melanoma in situ was established based on the clinical context and genomic assay results.

Dedifferentiated Melanoma: A Diagnostic Histological Pitfall—Review of the Literature with Case Presentation

“…Additionally, in our case, the dedifferentiation within the morphologically characterizable malignant melanoma created some diagnostic questions regarding the possibility that it was a collision lesion rather than a melanoma with a real portion of dedifferentiation. This issue has been extensively discussed in the literature [ 7 , 8 , 9 , 10 ], and a case has been reported very recently by Saldana et al [ 11 ] in which the amplification in FISH of the MDM2 gene was described for the first time in a lesion of a 73-year-old subject, which had led, in the first instance, to hypothesize a liposarcoma. A careful analysis involving also the determination of BRAFV600 allowed to reach the correct diagnosis of DM.…”

“…In the last 10 years, various authors have tried to shed light on what may be the potential biological pathways that melanocyte cells follow until they lose the common immunohistochemical markers [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Therefore, the concept of “phenotypic plasticity” of melanocyte cells has been developed, as it has been demonstrated that the microenvironment where melanocytes operate is able to bi-directionally influence the following phenotype: in particular, the study of melanocytes has been deepened, inducing the transcription factor (MITF) whose expression (also detectable in immunohistochemistry) was correlated with a different biological behavior of melanoma cells.…”

The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma

“…Rb1 immunoreactivity has been reported in 66% of these sarcoma subtypes [ 46 ]. Scientists have observed a significant overexpression of CDK4 and CDK6 in mouse model, linked with the progression and occurrence of both dedifferentiated (DDLPSs) and well-differentiated liposarcomas (WDLPSs) [ 47 , 48 ].…”

Sarcomatoid Dedifferentiated Melanoma: The Diagnostic Role of Next-Generation Sequencing

“…Sarcomatoid dedifferentiated melanoma (SDDM) represents a unique diagnostic challenge as this cutaneous spindle cell malignancy lacks expression of classic melanocytic markers including S100, SOX10, Melan-A/Mart-1, HMB45, and MITF. [1][2][3][4][5] The neoplasm also demonstrates diffuse staining for CD10, which may result in misinterpreting this subtype of melanoma as an atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), or a collision neoplasm. Consequently, SDDM is often diagnosed at an advanced stage with significant depth or once it has already metastasized.…”

“…Consequently, SDDM is often diagnosed at an advanced stage with significant depth or once it has already metastasized. 2,5 Recognition of an associated conventional melanoma is an essential clue in diagnosis of SDDM as immunohistochemical (IHC) evaluation is largely unrevealing beyond confirmation of the dedifferentiated spindled component. Preferentially expressed antigen in melanoma is a promising marker for conventional melanoma diagnosis, but its diagnostic potential in SDDM has yet to be explored with mixed results in other dedifferentiated melanomas.…”