Abstract
Primary dermal melanoma (PDM) is a rare subtype of cutaneous melanoma, with involvement of the dermis/subcutaneous tissue or both, but no involvement of the epidermis. PDM could not be distinguished histologically from metastasis of primary cutaneous melanoma. PDM has a longer life expectancy compared to cutaneous metastatic melanoma. Therefore, it is important to recognize PDM and make a correct diagnosis. We present a case of primary dermal melanoma on the left leg of a 38-year-old woman.
1. Introduction
Primary dermal melanoma (PDM) is a rare subtype of cutaneous melanoma, with involvement of the dermis/subcutaneous tissue or both, but no involvement of the epidermis [1]. The rate of primary dermal melanomas, rarely reported in the literature, is 0.4–0.9% of all melanomas [2].
PDM could not be distinguished histologically from primary cutaneous melanoma metastases, therefore primary cutaneous melanoma elsewhere in the body must be excluded [3]. It is extremely important to distinguish between PDM and cutaneous melanoma metastases. While the melanoma specific 5-year survival rate in cases with cutaneous melanoma metastasis is 10–26% in the literature, the 5-year survival rate in cases with primary dermal melanoma is 73–100%, although it is highly variable in the published literature [4–6]. We report a case of 38-year-old woman with a primary dermal melanoma on the left lower limb.
2. Case report
A 38-year-old woman, who applied to another clinic with a complaint of a pinkish color nodular lesion on her distal leg, was admitted to our clinic after an excisional biopsy. As far as learned from the patient, this lesion was painless and she had no other additional clinical findings. The patient had no known disease and only a history of using birth control pills.
On physical examination, there was a 2.5-centimeter vertical incision scar on the posterior-distal area of the left leg and a 2.5-centimeter horizontal incision scar distal to it (Figure 1). There was no other associated nevus. In the whole body examination, the patient did not have any other cutaneous, mucosal or uveal lesions.
Figure 1.
Scar after excisional biopsy on the patient’s left leg.
Laboratory results, including complete blood count and metabolic panels, were within normal limits. Pathology preparations examined by Department of Pathology, Trakya University Faculty of Medicine. The pathology report resulted as dermal malign melanoma infiltration (Figure 2). Tumor size was measured as 2 mm and invasion depth as 1 mm. Lymph-vascular infiltration was not identified. Immunohistochemical staining reported that the biopsy was weakly positive for actin and negative for SOX-10. Gene mutation analysis showed that there was a pathological BRAF mutation variation. The tumor was diagnosed as T1b melanoma and a treatment plan was created accordingly.
Figure 2.
(A) Nodular tumoral infiltration located in the dermis. (B) The tumoral infiltrate consists of pleomorphic cells with large cytoplasm that form nests. It does not show intraepidermal involvement. It is limited to the dermis. (C) Nuclear positive staining with S100 immunohistochemistry. (D) Nuclear positive staining with Prame immunohistochemistry.
Re-excision of the primary lesion area was performed with a wide surgical margin of 1 cm. In the same session, left inguinal sentinel lymph node excision was also performed. The result of the left inguinal sentinel lymph node biopsy was reported as malignant melanoma metastasis. The pathology result of the re-excisional biopsy supported the diagnosis of primary dermal melanoma. On immunohistochemical staining, the biopsy was noted to be positive for HMB45 and Melan-A.
Following these results, the patient underwent left inguinal lymph nodes dissection. The pathology report showed that no malignant metastasis was observed in the removed lymph nodes, and there were signs of reactive hyperplasia.
The patient was the referred to the oncology department for further medical treatments with the result. The patient was called for regular follow-up for whole body examination.
3. Discussion
Primary dermal melanoma is not clinically similar to cutaneous melanoma. Unlike cutaneous melanoma, it is difficult to diagnose due to its appearance similar to subcutaneous cystic mass, vascular proliferation or non melanoma skin cancers [7]. Therefore, the differential diagnosis should include nodular melanoma, non-melanoma skin cancers, blue nevus, hemangioma, dermatofibroma, cysts, scars, and cutaneous sarcomas; however, definitive distinction must be made through histopathological and immunohistochemical evaluation. Primary dermal melanoma is mostly seen in patients younger than 60 years old age and male patients. Moreover, it is most commonly seen in the extremities but can also be seen in different parts of the body [5].
Histopatological criteria for diagnosis are dermally located melanocytic neoplasm with nodular or multinodular structure, cytological signs of malignancy such as atypia, multiple mitosis and areas of necrosis, absence of evidence of an intraepidermal (in situ) component, no ulceration, S100 positivity, lack of continuity with peripheral nerves, no previous melanocytic nevus and absence of regression [7]. Due to the scarcity of definitively diagnosed cases of primary dermal melanoma, there is lack of molecular profiles to distinguish them from cutaneous metastatic melanoma or primary nodular melanoma.
Immunohistochemical studies in patients with primary dermal melanoma have shown that the expression of p53, Ki67, cyclin D1 and cyclin D2-40 is at lower levels than other types of melanoma, but these markers cannot provide definitive discrimination in routine diagnosis [3]. Therefore, the main diagnostic tool is to show that there is no other primary malignant melanoma during physical examination [8].
There is no consensus on the diagnosis, staging and management of primary dermal melanoma. In a retrospective study of 26 patients, Zamir et al. found that patients with primary dermal melanoma benefited from wide local excision, sentinel lymph node biopsy, and lymph node dissection when necessary [9].
The prognosis of patients with PDM is quite good compared of metastatic malignant melanoma and primary cutaneous melanomas. Harris et al. [10] found that the 5-year survival was 87.1% in 62 patients with a mean follow-up period of 6.3 years. Furthermore, when compared with a similar cohort, the overall survival and melanoma-specific survival of patients with primary dermal melanoma were higher than those with stage 1–2 and stage M1a melanoma. Swetter et al. [7] found that the 5-year survival rate was 100% in a cohort of 7 patients with primary dermal melanoma. A review of the published literature reveals that the reported overall survival rates for patients with primary dermal melanoma vary between 66 and 100% over follow-up periods ranging from 4 to 8 years (Table 1).
Table 1.
Site, mean age, treatment, sentinel lymph node biopsy (SLNB), and survival of patients with primary dermal melanoma.
| Study | No. of patients | Site | Mean age (range) | Treatment | SLNB | Survival rate |
|---|---|---|---|---|---|---|
| Swetter et al. [7] | 7 | Head (4), upper extremity (2), lower extremity (1) | 67.4 (22–85) | Wide local excision (7), high dose interferon alfa (2) | 6 Negative, 1 lost | %100 (5 Years) |
| Cassarino et al. [11] | 13 | Head (6), upper extremity (3), lower extremity (3), back (1) | 70 (21–85) | Wide local excision with 2 cm margin(9) | 10 Negative, 1 lost | %92 (44 Months) |
| Lee et al. [5] | 101a 71b |
Head and neck (13), trunk (27), upper and lower extremity(31) | <60 (50) ≥60 (21) |
Wide local excision, Elective lymhadenectomy (17) | 17 Negative, 3 positive | %66 (5 Years) %73 (5 years) |
| Zamir et al. [9] | 26 | Head (7), back (6), upper extremity (6), other (7) | 69 (3.5–85) | Wide local excision (26), lymph node dissection (5), local radiotherapy (1), high dose interferon (1), chemobiotherapy (1) | 15 Negative, 5 positive | %77 (62 Months) |
| Bowen et al. [12] | 11 | Head and neck (3), upper extremity (4), lower extremity (1), back (3) | 55.7 (28–90) | Wide local excision with 1–2 cm margin (11), Interferone alfa (1) | – | %83 (8 Years) |
| Anbari et al. [13] | 3 | Trunk (2), lower extremity (1) | 49.5 (29–74) | Local excision | – | %100 (4 Years) |
| Harris at al. [10] | 62 | Trunk (24), head and neck (15), upper extremity (13), lower extremity (10) | 64.1 | Local excision | 32 Negative | %87.1 (5 Years) |
| Benlier et al. | 1 | Lower extremity | 38 | Wide local excision with 1 cm margin Inguinal lymph node dissection |
Positive | %100 (1 Year) |
aTotal number of patients with solitary dermal melanoma.
bThe number of solitary dermal melanoma patients remaining after excluding those with regional and distant metastases.
The diagnostic reliability of patients diagnosed with primary dermal melanoma does not depend solely on the absence of a primary lesion in another part of the body at the time of diagnosis. At the same time, no evidence of an occult primary lesion should be observed during the clinical follow-up course. For these reasons, the clinical follow-up processes of these patients after diagnosis and treatment are extremely important. Our patient was diagnosed 1 year ago and no occult primary lesion was found in her follow-up. On physical examination, no lesion suggestive of a potential primary focus was identified elsewhere on the patient’s body, thereby allowing for the exclusion of a cutaneous metastatic melanoma. In addition, PET-CT imaging revealed no FDG uptake consistent with a primary lesion or distant metastasis in other regions of the body. The absence of any occult primary lesion during clinical follow-up further supports our diagnosis of primary dermal melanoma.
4. Conclusion
In conclusion, it is important for dermatologists, pathologists and even surgeons to recognize primary dermal melanoma, which is difficult to distinguish from cutaneous metastatic melanoma but has a better prognosis. Thus, in the future, research and studies on primary dermal melanoma will enable a consensus to be reached in diagnosing and treating the disease.
Acknowledgment
This paper was not funded.
Ethical declaration
Written informed consent was obtained from the patient for publication of this case report and accompanying images.
Author contributions
Erol Benlier: Conceptualization, surgical procedure, manuscript supervision and critical review.
Fatih Akyar: Data collection, literature review, manuscript writing and figure preparation, surgical procedure.
Kübra Afşaroğlu Zöhra: Data collection, literature review, surgical procedure.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Writing assistance
No writing assistance was utilized in the production of this manuscript.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
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