Malignant Melanocytic Matricoma: A Rare Skin Tumor That Can Clinically Mimic Melanoma

Malignant melanocytic matricoma (MMM) is an extremely rare skin malignant neoplasm composed of epithelial cells with matrical differentiation and dendritic melanocytes. We found only 11 cases reported in the literature to date according to the databases consulted (PubMed/Medline, Scopus, and Web of Science). Here, we report a case of MMM in an 86-year-old woman. A histological examination showed a dermal tumor with a deep infiltrative pattern, without an epidermal connection. On immunohistochemical staining, tumor cells were positive for cytokeratin AE1/AE3, p63, and beta-catenin (nuclear and cytoplasmic staining) and negative for HMB45, Melan-A, S-100 protein, and androgen receptor. Melanic antibodies highlighted scattered dendritic melanocytes in tumor sheets. The findings did not support the diagnosis of melanoma, poorly differentiated sebaceous carcinoma, and basal cell carcinoma, but supported the diagnosis of MMM.


Introduction
Malignant melanocytic matricoma (MMM) is considered the malignant counterpart of melanotic matricoma which is a rare benign skin adnexal neoplasm composed of epithelial cells exhibiting matrical differentiation admixed with pigmented dendritic melanocytes [1]. MMM is even rarer than benign melanotic matricoma [1]. Although features for differentiating benign and MMM are controversial, we found marked cytological atypia, infiltrative growth pattern, necrosis, ulceration, recurrence, and metastasis. However, a high mitotic count would not constitute a criterion of aggressive behavior [2]. This tumor predominates in the head and neck, is more often reported in the elderly, and presents as a solitary pigmented nodule occurring on sun-damaged skin, which leads to a clinical diagnosis of melanoma or pigmented basal cell carcinoma. The histological analysis shows a dermal proliferation of atypical matrix epithelial cells admixed with varying proportions of pigmented dendritic melanocytes [3]. Here, we report the 12th reported case of MMM in an 86-year-old woman with sun-damaged skin who presented with a pigmented nodular tumor that mistakenly suggested melanoma, pigmented basal cell carcinoma, or trichoblastoma.

Case Presentation
An 86-year-old woman with the risk factor of chronic sun exposure consulted for a pigmented nodular tumor surmounted by scales on the right cheek. It was progressively increasing in size for three years and bled on contact for a few months. On clinical examination, we found a nodular and blackish tumor of firm consistency with a pedunculated and infiltrated base measuring 4 cm ( Figure 1). Dermoscopy revealed a chaotic pattern with a blue-white veil and tree-trunk vascular pattern ( Figure 2). Suggested clinical diagnoses included melanoma, pigmented basal cell carcinoma, or trichoblastoma. Excision of the pedunculated nodule with its base was performed. The sample was fixed in 10% tamponed formalin, impregnated, and then included in a paraffin block. Subsequently, 4 μm sections were made and stained with standard hematoxylin-eosin-saffron (HES) staining. Optical microscopic examination showed an ulcerated skin lesion whose dermis contained a pigmented tumor arranged in lobules and sheets without connection with the epidermis (Figures 3, 4).

FIGURE 11: Melanin markers (Melan A and HMB45) highlight nonatypical dendritic melanocytes (×200).
All of these findings confirmed the diagnosis of MMM. A cervico-thoraco-abdominal CT scan was indicated to search for lymph node involvement or distant metastasis, which revealed no abnormalities. Carcinological re-excision of the tumoral site for margins was performed, and it is free of tumor residue. No treatment with chemotherapy or radiotherapy was indicated. Follow-up at six months showed no evidence of recurrence or metastasis.

Discussion
To our knowledge, to date, only 11 cases have been reported in the literature, according to our research using PubMed/Medline, Scopus, and Web of Science databases, with the search terms "malignant melanocytic matricoma" and "matrical carcinoma" [1,[3][4][5][6][7][8][9][10]. The epidemiological, clinical, histopathological, immunohistochemical, and behavioral features of the reported cases of MMM are detailed in Table 1.   The term MMM was first proposed in 2003 by Monteagudo et al. in their study which reported two cases of matrix carcinoma with prominent melanocytic hyperplasia and considered it to be the malignant counterpart of melanocytic matricoma [1]. The latter is a rare benign adnexal tumor first described in 1992 by Carlson et al. [2]. Since then, approximately 20 cases of melanotic matricoma have been reported [2].
On pathogenic findings, the bulb of hair follicles in the anagen phase is known to contain matrix and supramatrix cells, as well as pigmented dendritic melanocytes. Because melanocytes are most important at the beginning of the anagen phase, it is suggested that melanotic matricoma results from hair follicles at an early stage of the anagen phase as a biphasic proliferation of matrix epithelial cells admixed with increased numbers of pigmented dendritic melanocytes and rare foci of ghost cells [10,11]. Therefore, when these features are associated with histological malignancies, such as severe cytological atypia, atypical mitosis, infiltrating growth pattern, necrosis, ulceration, and recurrence [8], the diagnosis of MMM should be considered.
On histological examination, MMM must be differentiated from pigmented basal cell carcinoma, trichoblastoma, basal cell carcinoma with matrical differentiation, melanoma, and benign melanocytic matricoma. The severe cytological atypia of MMM argues against trichoblastoma and basal cell carcinoma. Strong diffuse nuclear and cytoplasmic expression of beta-catenin and melanic makers negativity differentiate MMM from melanoma and support matrical differentiation [11].
The treatment of MMM is not yet codified given the rarity of this entity and the absence of a large series investigation. However, the review of the 11 reported cases allowed us to deduce that surgical excision with a free margin is the most reliable option to avoid recurrences. Of the eight cases for which follow-up was available (see Table 1), two presented a recurrence at the resection site, and no lymph node or distant metastasis was revealed in these cases. This lets us reflect on the real aggressiveness of this tumor.

Conclusions
MMM is an extremely rare malignant skin tumor with matrix differentiation. Clinically, this lesion mimics malignant melanoma or pigmented basal cell carcinoma. Histopathologically, it is characterized by biphasic proliferation of atypical matrix epithelial cells admixed with increased numbers of pigmented dendritic melanocytes and rare foci of ghost cells. The immunohistochemical study makes it possible to confirm the matrix origin of the proliferation by the positivity of cytokeratin AE1/AE3 and strong diffuse beta-catenin and the negativity of the melanotic markers which underline the component of non-atypical dendritic melanocytes. However, the histological criteria of malignancy are largely dominated by cytological atypia, atypical mitosis, infiltrative growth pattern, necrosis, ulceration, and recurrence. Hence, pathologists must have this rare entity in mind when faced with a pigmented lesion of the sun-damaged skin in the elderly with a biphasic epithelial and melanocytic component to avoid misdiagnosis.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.