Original article
Primary dermal melanoma: A unique subtype of melanoma to be distinguished from cutaneous metastatic melanoma: A clinical, histologic, and gene expression–profiling study

https://doi.org/10.1016/j.jaad.2014.07.051Get rights and content

Background

Primary dermal melanoma (PDM) is a subtype of melanoma confined to the dermis that may be morphologically impossible to distinguish from cutaneous metastatic melanoma (CMM).

Objective

We sought to better characterize PDM by describing the clinical, histologic, and molecular features of 49 cases of PDM and determine whether a gene expression–profiling test could help distinguish PDM from CMM.

Methods

We describe 49 cases of PDM and determined whether any clinical or histopathologic features had a statistically significant relationship with outcome. Secondly, we performed a melanoma gene expression–profiling test on a subset of the PDM and CMM cases.

Results

Overall recurrence was infrequent and seen in 9 of 49 cases. Six patients had locoregional recurrences and 3 patients had distant metastasis. None of the clinical or histologic parameters showed a statistically significant relationship with recurrence. There was a statistically significant association of a class I signature by DecisionDx-Melanoma assay (Castle Biosciences Inc, Friendswood, TX) for PDM whereas CMM were more frequently class II (P value = .023).

Limitations

The mean follow-up time was 26 months.

Conclusions

Most conventional staging parameters used for prognosis in cutaneous melanoma have limited applicability to PDM. The melanoma prognostic assay may be a useful tool for distinguishing PDM from CMM.

Section snippets

Methods

After obtaining approval from the Northwestern University Cancer Center, Chicago, IL, and internal institutional review board, 49 cases of PDM and 15 cases of CMM were identified in our dermatopathology database at Northwestern University. All lesions were evaluated by 3 dermatopathologists (J. G., P. G., and M. S.). Clinical histories and descriptions of lesions were obtained from medical records. Fourteen cases were diagnosed within our institution and 35 cases were external consultation

Results

The clinical findings for the 49 PDM cases are summarized in Table I. The database review of 6000 patients resulted in 49 patients (0.82%) with a diagnosis of PDM. The 49 PDM included 25 (51%) male and 24 (49%) female patients, ranging in age from 8 to 83 years (mean 51.2 years). The most common anatomic site of involvement was the trunk (19/49; 39%), followed by the head and neck (16/49; 33%), extremities (11/49; 22%) and acral area (3/49; 6%).

The histopathologic and IHC findings are

Discussion

Numerous previous studies, mostly reported as single-center series and case reports, have identified patients with a solitary focus of melanoma confined to the dermis with no known separate primary melanoma and negative metastatic findings on workup, who largely remain disease free with a favorable prognosis.1, 2, 3, 4, 5, 6, 7, 8, 9 As the prognosis and treatment for a PDM differs greatly from that of a stage IIIC or stage IV M1a metastatic melanoma, the distinction is critical. At the

References (19)

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    The possibility of metastasis from cutaneous or occult extracutaneous sites must be excluded [1,3]. The available literature suggests a remarkably good long-term survival of a PDM in comparison with similarly staged conventional cutaneous melanomas; the 5-year survival rate of PDM is 73–100% [2,4–7] against a 5–19% 5-year survival for epidermal involved melanoma with similar Breslow thickness [4,7]. Therefore it is of great importance for the clinician to be familiar with the possibility a subcutaneous tumor can be a primary dermal melanoma, and it would be beneficial that this unique melanoma subtype with relatively excellent prognosis will be appointed in the current melanoma treatment guidelines and AJCC staging system.

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    Initial immunohistochemical studies performed on a larger series of 13 PDM suggested lower expression of p53, Ki-67, cyclin D-1, and D2-40 in PDM as compared with metastatic melanoma and nodular melanoma, but these markers do not allow definitive distinction in the routine diagnostic setting [1]. Sidiropoulos et al. [4] described that specific fluorescence in situ hybridization (FISH) abnormalities may be associated with particular morphologic patterns such as spitzoid and blue-nevus type PDM, and furthermore found a significant association of a favorable gene expression signature with PDM; however, two cases analyzed in that series metastasized. Fewer data exist regarding more comprehensive genomic analysis.

  • Primary dermal melanoma: clinical behaviour, prognosis and treatment

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    This developmental theory is unlikely to apply to this study's cohort where cases were specifically excluded on the basis of a prior history of self-inflicted or iatrogenic trauma or pathological evidence of epidermal regression. In addition, it is possible that presumed PDMs are in fact dermal metastases from occult or regressed primary melanomas elsewhere [8] especially in the setting of low grade tumours in immunocompetent individuals. This theory is unlikely, however, in light of the survival data in the present study which are far too favorable to align with metastatic disease.

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    Survival rates are based on the TNM classification (which assesses thickness of the primary tumor and presence of distant or lymph node metastatic disease) and vary significantly according to these aggravating factors.5 Thus, timely detection, assessment and management should be a high public health priority, and the dermatologist plays a crucial role in this process.6-8 In Brazil, epidemiological data on CM are limited at both the national and regional levels.9

  • Asymptomatic Facial Nodule

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Supported by the Irene D. Pritzker Foundation and partially supported by Castle Biosciences Inc.

Disclosure: Dr Gerami has served as a consultant to Castle Biosciences Inc, Myriad Genetics, and DermTech Inc, receiving honoraria. Dr Guitart has served as a consultant to Castle Biosciences Inc, receiving honoraria. The other authors declared no conflicts of interest.

Dr Sidiropoulos and Ms Obregon contributed equally to this article.

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