Pseudomelanocytic Nests Research Articles

ORAL MELANOACANTHOMA ASSOCIATED WITH PSEUDOMELANOCYTIC NESTS: AN IMMUNOHISTOCHEMICAL STUDY

Oral melanoacanthoma is an uncommon pigmented lesion of the oral mucosa characterized by the presence of acanthosis and dendritic pigment-laden melanocytes located in the prickle cell layer of the epithelium. Pseudomelanocytic nests (PNs) represent cellular aggregates of keratinocytes, macrophages, and melanocytes, usually located in close relationship with lichenoid inflammation, which if not recognized can be misdiagnosed as melanoma. A 41-year-old white woman was referred presenting a pigmented gingival lesion located between the left maxillary central and lateral incisors with 1 year of evolution. After excisional biopsy, microscopy showed typical melanoacanthoma associated with PNs. PNs and dendritic melanocytes were evidenced by Fontana-Masson stain. Immunohistochemistry revealed positivity for AE1/AE3, CD68, and CD163 in PNs, while HMB-45 and Melan-A highlighted dendritic melanocytes. SOX-10 positivity was observed in few melanocytes in basal location. To our knowledge, this is the first report of oral melanoacanthoma associated with PNs. FAPESP (2016/11419-0 and 2017/02502-4).

Pseudomelanocytic nests leading to a misdiagnosis of lentigo maligna

Pseudomelanocytic nests leading to a misdiagnosis of lentigo maligna

Gingival melanoacanthoma associated with pseudomelanocytic nests: Expanding the clinicopathological spectrum of a recently described oral lesion.

Gingival melanoacanthoma associated with pseudomelanocytic nests: Expanding the clinicopathological spectrum of a recently described oral lesion.

Report of two cases of vacuolar interface dermatitis initially suspected as melanomain situand review of the literature

The diagnosis of melanocytic lesions can be challenging and immunohistochemical study is a valuable tool for dermatopathologists. We report two cases initially simulating melanoma in situ, reviewing the histopathological and immunohistochemical findings and the cases published in the literature with similar findings/results. We emphasize the importance of clinicopathological correlation in the evaluation of lesions with interface changes and in the pseudomelanocytic nests, which may simulate melanoma in situ. We also highlight the importance of using a immunohistochemistry panel in addition to Melan-A, in the study of these lesions.

Microphthalmia-Associated Transcription Factor-Positive Pseudonests in Cutaneous Lupus Erythematosus

To the Editor: Nicholson and Gerami1 recently reported 2 cases where microphthalmia-associated transcription factor (MITF) aided in distinguishing Mart-1-positive pseudomelanocytic nests from true melanocytic nests in the setting of lichenoid dermatitis. We have been interested in the pseudomelanocytic nest phenomenon since it was first reported by Maize et al2 in 2003. The difficulty of differentiating true Mart-1/Melan-A-positive melanocytic nests from pseudonests is a practical dilemma, as both may occur in the setting of lichenoid tissue reactions, and there is a potential for misdiagnosis if pathologists rely on a single immunostain.1-5 We have found that even combinations of stains like Mart-1 plus MITF have the potential to result in misdiagnosis and wish to alert the pathologists to this potential pitfall. Most of the reports of pseudomelanocytic nests have been described in pigmented actinic keratosis, cutaneous lupus erythematosus (CLE), or lichenoid inflammatory lesions from the head and neck suggesting some relationship to chronically sun-damaged skin.2,4-5 We previously determined that the Mart-1-positive pseudonest phenomenon is uncommon in cases of lichen planus, suggesting that it may be uncommon in sun-protected skin.6 Our current study sought to establish the frequency of pseudonests in the setting of CLE on sun-damaged skin. A search was preformed for cases of CLE from the files of Brooke Army Medical Center and Wilford Hall Medical Center from 1999 to 2009. Each of the cases was initially reviewed by one pathologist to make sure that the biopsies demonstrated marked solar elastosis within the dermis. Cases without significant solar elastosis were excluded from the study. Fresh sections from 53 cases of CLE on sun-damaged skin were stained with hematoxylin and eosin (H&E), Mart-1, and MITF. Three dermatopathologists reviewed the (H&E) slides to determine whether a vacuolar interface or lichenoid interface reaction pattern was present and if collections of cells were present at the dermal-epidermal junction suspicious for pseudonests. Both the Mart-1 and MITF stains were then reviewed in each case. Of the 53 cases of CLE, 30 showed lichenoid interface dermatitis, whereas the other 23 showed a vacuolar interface dermatitis. A total of 6 cases demonstrated areas suspicious with pseudonests on H&E stain (Table 1). Each of these cases demonstrated a lichenoid interface dermatitis. One case (case 30) was remarkable for nested cells that were strongly positive for both Mart-1 and MITF but negative for S100 (Fig. 1A-D). The MITF stain demonstrated at least 2 nonlabeling nuclei (Fig. 1C, inset), which could have alerted the pathologist to the possibility of an aberrant staining pattern. S100 is highly sensitive for melanocytes, and S100-negative melanocytic lesions are rare.7-9 The patient has been followed since 2004 for cutaneous lupus and has developed additional morphologically similar lesions that responded to topical fluocinonide and oral plaquenil but has not demonstrated any evidence of a melanocytic lesion at the biopsy site. In the clinical context of CLE, there is little chance that the solitary aggregate represented an incidental melanocytic nest. Failure to stain with S100 and clinical follow-up support our contention.FIGURE 1: A, Case of CLE with a small nest of cells at the dermal-epidermal junction (H&E: ×20; inset ×60). B, Avid cytoplasmic staining for Mart-1 (×20; inset ×60). C, MITF positive, note that 2 nuclei in the aggregate lack staining (×20; inset ×60). D, Negative staining with S100 (×20; inset ×60).TABLE 1: Cases With Pseudonests Present in H&E or Immunostained SectionsThe pathogenesis of the pseudonest phenomenon remains speculative.2,5 A combination of melanocytes, degenerated keratinocytes, and macrophages has been proposed. Ultimately, studies of the ultrastructural characteristics of pseudonests may help to determine their composition. Our results suggest that MITF may stain pseudonests in a manner similar to Mart-1/Melan-A and cannot be relied upon to distinguish pseudonests from true melanocytic nests. A recent poster at a national dermatopathology conference also described the presence of MITF-positive pseudonests in a case of lichen planus pigmentosus, suggesting our experience is not unique.10 We caution pathologists about overreliance on MITF. We believe that clinical correlation is essential, and when Mart-1/Melan-A-positive and MITF-positive aggregates are noted in the setting of lichenoid dermatitis, S100 staining should be performed. CPT Margaret Abuzeid, MD* LTC Scott R. Dalton, DO† Tammie Ferringer, MD†‡ Richard Bernert, MD§ Dirk M. Elston, MD†‡ Department of *Pathology, Brooke Army Medical Center and Wilford Hall Medical Center, San Antonio, TX Department of †Dermatology; and ‡Pathology, Geisinger Medical Center, Danville, PA §Arizona Dermatopathology, Scottsdale, AZ

Nests with numerous SOX10 and MiTF-positive cells in lichenoid inflammation: pseudomelanocytic nests or authentic melanocytic proliferation?

Pseudomelanocytic nests in the setting of lichenoid inflammation can mimic atypical melanocytic proliferations. Both melanocytic and cytokeratin immunohistochemical stains may be utilized to differentiate these entities. Unlike true melanocytic nests, pseudomelanocytic nests contain Melanoma Antigen Recognized by T-cells 1 (MART-1)/ Melan-A-positive cells and cells positive for pan-cytokeratins, CD3 and/or CD68. Recently, rare (1-2 cells/nest) microphthalmia- associated transcription factor (MiTF)-positive cells were also reported in pseudomelanocytic nests. We present a 48-year-old man with a 2 × 3 cm violaceous to hyperpigmented, non-blanching, polygonal patch on the neck. Histopathology showed focal epidermal atrophy, irregularly distributed junctional nests and a lichenoid infiltrate with colloid bodies. Immunoperoxidase studies revealed occasional pan-cytokeratin and MART-1/Melan-A-positive staining in nests as well as focal S-100 protein-positive cells. Importantly, the majority of nests showed numerous cells positive for MiTF and SOX10 (>2 cells/nest and some the majority of cells). This combined staining pattern confounds the above-described immunohistochemical distinction between pseudo and true melanocytic nests. Clinically felt to represent unilateral lichen planus pigmentosus/erythema dyschromicum perstans and not malignant melanoma in situ, this lesion highlights the importance of clinicopathologic correlation and suggests either a new melanocytic entity or a novel pattern of benign melanocytic reorganization in a subset of lichenoid dermatitides.

S100-Negative Junctional Melanocytic Proliferations

To the Editor: It has been shown that the skin within and adjacent to actinic keratoses may demonstrate a disproportionate increase in melanoma antigen recognized by T-cells 1 melanoma Antigen Recognized by T-cells 1 (MART-1)-positive cells in the absence of other evidence of a melanocytic proliferation, creating a potential for overdiagnosis of melanoma in situ.1 Additionally, “pseudomelanocytic nests” have been described as MART-1 positive, S100-negative nonmelanocytic cellular aggregates at the dermoepidermal junction of sun-damaged skin, often in the setting of interface dermatitis. The aberrant MART-1 staining of such nests may likewise lead to a false impression of melanoma.2,3 Despite these difficulties, we continue to find MART-1 to be valuable in the diagnosis of melanocytic neoplasms, and caution that aberrant immunostaining may occur with any antibody. To illustrate this point, we present 2 cases of junctional proliferations on sun-damaged skin which were MART-1 positive, but S100 negative. Both were clinically and histologically suspicious for melanoma, and proved to be positive for microphthalmia-associated transcription factor microphthalmia-associated Transcription Factor (MITF) and vimentin. CASE 1 A 75-year-old man presented with a several month history of an enlarging, irregularly pigmented brown patch on the left cheek. The clinical diagnosis was lentigo maligna, and a shave biopsy was performed. Hematoxylin and eosin-stained sections demonstrated small, irregularly spaced junctional nests overlying solar elastosis (Fig. 1). MART-1 highlighted these nests, and an increased number of single-unit junctional melanocytes, with areas of follicular extension. S100 did not stain the junctional nests, but appropriately stained internal and external positive controls. Both the single-unit and nested components observed with MART-1 were also positive with MITF, human melanoma black-45 (HMB-45), and vimentin. The nests did not stain with pancytokeratin. Based on clinicopathologic correlation, a diagnosis of lentigo maligna was made.FIGURE 1: Hematoxylin and eosin-stained sections show scattered small junctional nests on sun-damaged skin (A). Increased single-unit and nested junctional melanocytes are largely negative with S100 (B), but positive with MART-1 (C) and MITF (D).CASE 2 A biopsy was taken from a dark brown macule on the upper back of a 72-year-old man. The preoperative differential diagnosis included melanoma. Histologic sections showed vacuolation and increased pigmentation at the dermoepidermal junction (Fig. 2). Immunohistochemistry demonstrated a nearly confluent proliferation of MART-1-positive junctional cells, with occasional small MART-1-positive nests. S100 showed good staining of internal and external positive controls, but little staining of the population highlighted by MART-1. HMB-45 was similarly weak in this population, despite strong staining of positive control tissue on the same slide. MITF and vimentin strongly stained the junctional proliferation, and a diagnosis of melanoma in situ was made.FIGURE 2: Hematoxylin and eosin-stained sections show vacuolation and small nests at the dermoepidermal junction (A). A regionally confluent junctional proliferation is negative with S100 (B), but positive with MART-1 (C) and MITF (D).DISCUSSION It has been demonstrated that in sun-damaged skin, MART-1/Melan-A may stain a greater number of nested and single-unit junctional cells than S100, and that this increase in MART-1 staining does not necessarily imply a junctional melanocytic neoplasm,1,3 making it necessary to exercise caution with these stains to avoid overdiagnosis of melanoma. The cases presented above demonstrate that a converse difficulty may also occur. In both cases, a MART-1-positive junctional proliferation showed little positivity with S100, prompting us to pursue additional immunohistochemical evaluation. The junctional proliferation stained with HMB-45 in case 1, and vimentin and MITF were positive in both cases. Although the latter stains are not specific for melanocytes, the combined immunohistochemical findings together with the hematoxylin-eosin morphology and the available clinical information were supportive of a diagnosis of a melanocytic lesion in both cases. Although S100 is considered a relatively sensitive stain for melanocytes, cases of S100-negative invasive melanoma have been documented, as has variability in staining of melanocytes with different clones of S100.4 The negative S100 staining observed in our cases may have resulted from a lack of expression of S100 protein, or a failure of expressed S100 to stain with the clone utilized in our laboratory (Ventana monoclonal 4C4.9). These cases illustrate the potential for diagnostic confusion based on negative staining with S100 in junctional melanocytic proliferations on sun-damaged skin. Even as caution is necessary to avoid overinterpretation of MART-1 positivity, it also seems unwise to rely solely upon S100 to distinguish MART-1-positive melanocytes from pseudomelanocytic proliferations. Morgan L Wilson, MD Eric W Hossler, MD Tammie C Ferringer, MD Dirk M Elston, MD Geisinger Medical Center, Departments of Dermatology and Pathology, Danville, PA

An Immunohistochemical Analysis of Pseudomelanocytic Nests Mimicking Melanoma In Situ: Report of 2 Cases

Several case reports have discussed the difficulty in differentiating junctional pseudomelanocytic nests as a result of lichenoid inflammation from a true melanocytic neoplasm. Even immunohistochemistry can be misleading in these cases with both Melan-A and Mart-1 frequently resulting in false positivity as a result of nonspecific labeling of nonmelanocytic cells containing melanosomes. We present a series of 2 similar cases which were initially misdiagnosed as melanoma in situ likely as a result of Mart-1 positivity of the pseudomelanocytic nests. However, in our review, a significant lichenoid reaction was apparent at the dermal-epidermal junction. Staining with microphthalmia-associated transcription factor (MITF) showed a normal density of melanocytes along the dermal-epidermal junction and failed to uniformly label the Mart-1-positive pseudomelanocytic nests. In both patients, medications frequently resulting in fixed drug eruptions were identified, and a final diagnosis of fixed drug eruption was rendered in both cases. In light of these findings we suggest MITF is a more useful marker for evaluating lentiginous proliferations along the dermal-epidermal junction particularly when dealing with the differential diagnosis of lichenoid reaction with pseudomelanocytic nests versus melanoma in situ.

Melan-A-Positive “Pseudomelanocytic Nests”: A Pitfall in the Histopathologic and Immunohistochemical Diagnosis of Pigmented Lesions on Sun-Damaged Skin

We encountered recently 3 cases with a histopathologic diagnosis of melanoma in situ on sun-damaged skin (male = 2, female = 1; median age: 59 years; range: 52-60 years). The diagnosis was based mainly on the finding of actinic elastosis in the dermis and increased number of melanocytes in the epidermis and was confirmed by strong positivity for Melan-A in single cells and in small nests ("pseudomelanocytic nests"), located at the dermoepidermal junction. Indeed, examination of slides stained with hematoxylin and eosin revealed the presence of marked hyperpigmentation and small nests of partially pigmented cells at the dermoepidermal junction, positive for Melan-A. The histologic and especially the immunohistochemical features were indistinguishable from those of melanoma in situ on chronic sun-damaged skin. In addition, a variably dense lichenoid inflammation was present. Clinicopathologic correlation, however, showed, in all patients, the presence of a lichenoid dermatitis (phototoxic reaction, 1 case; lichen planus pigmentosus, 1 case; and pigmented lichenoid keratosis, 1 case). Our cases clearly show the histopathologic pitfalls represented by lichenoid reactions on chronic sun-damaged skin. Immunohistochemical investigations, especially if performed with Melan-A alone, may lead to confusing and potentially disastrous results. The unexpected staining pattern of Melan-A in cases like ours raises concern about the utility of this antibody in the setting of a lichenoid tissue reaction on chronic sun-damaged skin. It should be underlined that pigmented lesions represent a paradigmatic example of how immunohistochemical results should be interpreted carefully and always in conjunction with histologic and clinical features.