Dermatopathology

Neuroendocrine Differentiation of Skin Tumors: A Comprehensive Review Abstract: Neuroendocrine differentiation is characterized by endocrine and neuronal features with prominent dense secretory granules and neuropeptides. Neuroendocrine differentiation of skin tumors is of unknown clinical significance. Nonetheless, the acknowledgment of this line of differentiation is important to prevent diagnostic pitfalls and subsequent inappropriate management. This review aims at summarizing the skin neoplasms that can express neuroendocrine markers.

Histological Evaluation of the Relationships Between Distal Interphalangeal Psoriatic Arthritis and Nail Psoriasis: Correlations With Anatomical Studies of the Normal Nail Unit and the Main Radiological Data Concerning Distal Interphalangeal Psoriatic Arthritis Abstract: To determine whether distal interphalangeal joint psoriatic arthritis (DIP PsA) and nail psoriasis are anatomically linked, we studied 2 fingers taken from a cadaver presenting a typical cutaneous and nail psoriasis in the setting of a dactylitis limited to the fourth toe. This comprehensive study of the inflammatory pattern of DIP PsA is discussed in the context of the controversial theory of the nail as a musculoskeletal appendage. Both the extensor and flexor entheses were focally and quite markedly infiltrated by lymphocytes and showed variable fibrosis and neovascularization. In addition, some clusters of giant cells were seen. Synovial perivascular inflammation was focally relatively dense. Discrete periostitis and bone inflammation of the intertrabecular spaces were seen, maximally at the insertion of the extensor and flexor tendons. The retained superficial fibrocartilaginous and tendinous cuff separated the inflamed extensor enthesis from the surrounding connective tissues. The thick proximal periosteum constituted a barrier between the inflamed bone and the matrical hypoderm. The lateral sections showed inflammation at 3 levels as follows: the enthesis of the interosseous ligament and collateral ligament, periosteum, and nail epithelium. In the 3 specimens, the inflammatory foci involving entheses and nails were prominent and never contiguous. This suggests that DIP PsA is not merely an extensor enthesitis and that the nail unit remains a microanatomical structure independent from the extensor enthesis, even with severe DIP PsA.

Desmoplastic Melanomas Mimicking Neurofibromas Abstract: Desmoplastic melanoma can be difficult to diagnose and on average have a significantly higher T stage at the time of diagnosis compared with conventional melanomas. Histologically, these tumors typically consist of spindle cells in a fibrous matrix. The spindle cells may display fibroblast and/or Schwann cell–like features. In this study, we describe the features of 12 cases of desmoplastic melanoma closely simulating neurofibroma. Although the spindle cells in these tumors may be indistinguishable from those of neurofibroma, features such as prominent fibroplasia (12/12), poor lateral circumscription (8/9), diffuse infiltration of subcutaneous tissue (7/9), and lymphoid aggregates (10/12) may be helpful clues to the diagnosis. No immunohistochemical markers were reliable in distinguishing neurofibroma-like desmoplastic melanomas from neurofibroma. Clinical follow-up was available in 8 cases, of which 4 were initially misdiagnosed as benign neoplasms and given no further re-excision. All 4 of these cases recurred; 2 of which showed transformation to a more aggressive phenotype.

Melanocytic Neoplasms With MAP2K1 in Frame Deletions and Spitz Morphology Abstract: With the advent of better molecular characterization of Spitz melanocytic neoplasms, there has been increasing effort to better understand and describe the relationships between specific driver fusion and/or mutations with the clinical and histomorphological characteristics of the lesions. Structural rearrangements in mitogen activated protein kinase genes have recently been noted to be important in Spitz neoplasms. Only very few reports, however, have described in detail melanocytic tumors with in frame deletions in MAP2K1. Cases in the literature with this aberration have been described as having a diagnosis of Spitz, deep penetrating nevi, or pigmented epithelioid melanocytoma. In this study, we describe a cohort of 6 cases with MAP2K1 activating in frame deletions. The morphologic spectrum of the cases was broad. Common features of these cases include Spitzoid cytomorphology (5/6) cases, prominent melanin pigmentation (4/6) cases, and deep penetrating nevi–like plexiform architecture (3/6) cases. The diagnoses at the time of clinical care of these cases included nevus of Reed (1/6), desmoplastic Spitz tumor (1/6), BAPoma (1/6), deep penetrating melanocytic nevus (2/6), and melanoma (1/6). Clinical follow-up was available in 3 of the 6 cases. None of the patients had a tumor recurrence. This builds on the growing literature to help expand the spectrum of changes associated with Spitzoid melanocytic neoplasms.

Study of Tattoo Colorants in Skin by Conventional and Polarized Light Microscopy Abstract: Tattoos are a common practice in the 21st century. Although most modern pigments are organic and made of vegetable or plastic compounds, they still sometimes elicit an adverse reaction in the skin. Identifying the tattoo pigment in such biopsies is not always an easy task. To study how tattoo inks appear in the skin, we injected 14 different colors of commercial tattoo ink into normal skin obtained from a mastectomy specimen. One unstained section was obtained from each case, as well as one section stained with hematoxylin-eosin from each case. All sections were observed under the microscope. Stained and unstained sections were also examined under polarized light. We did not observe any modification of the ink color with the staining process with hematoxylin-eosin. However, some pigments appeared differently in stained and unstained sections than in the vial. Pink was the most difficult color to identify from the eosinophilic tissue. None of the colors showed any birefringent particles. However, in some unstained slides under polarized light, the color of the pigment appeared more similar to the one in the vial than in the stained slide.

Concordance Analysis of the 23-Gene Expression Signature (myPath Melanoma) With Fluorescence In Situ Hybridization Assay and Single Nucleotide Polymorphism Array in the Analysis of Challenging Melanocytic Lesions: Results From an Academic Medical Center Background: Fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) arrays are well-established molecular tests for the analysis of challenging melanocytic lesions. A 23-gene expression signature (GES), marketed as myPath Melanoma, is a recently introduced molecular test that categorizes melanocytic lesions as "benign," "malignant," and "indeterminate." There are few studies on the concordance between FISH, SNP, and GES in the analysis of melanocytic lesions. Methods: A single-institution retrospective analysis of 61 contiguous cases of challenging melanocytic lesions with molecular analysis by 2 or more techniques. The primary objective was to determine the intertest agreement, which was calculated as percent agreement. A secondary objective was to determine the combined-test performance, that is, the frequency of obtaining a successful test (a test with an abnormal or normal, benign or malignant result) when 2 or more molecular tests were performed. Results: Of the 61 cases, 58 cases were submitted for analysis using the GES assay, 44 cases were submitted for FISH analysis, and 21 cases were submitted for SNP array analysis. Percent agreement between GES and FISH array was 50.9% (18/34), which improved to 69.7% (18/23) when indeterminate/equivocal results were excluded. Similarly, percent agreement between GES and SNP array was 57.1% (8/14); this improved to 77.8% (7/9) when indeterminate/equivocal results were excluded. In 44% of cases submitted for GES and FISH and in 39% of cases submitted for GES and SNP, one test was successful and the other was not. Conclusion: For challenging melanocytic lesions, the choice of a molecular test is consequential as the GES assay correlated with FISH and SNP arrays approximately only half of the time. This improved when cases with indeterminate/equivocal results were excluded from the calculations. The combined-test analysis supports the utility of conducting more than one molecular test, as this increased the odds of obtaining a successful test.

Combination of Congenital and Deep Penetrating Nevus by Acquisition of β-Catenin Activation Abstract: Deep penetrating nevus (DPN) is an intradermal, sometimes compound benign melanocytic lesion, which involves the reticular dermis, occasionally reaching the subcutis, which can raise concern for melanoma both clinically and histologically. Recently, it has been genetically defined by the combination of MAPK activating and β-catenin activating mutations. We sought to investigate genetic alterations in 2 cases of combined nevi of congenital melanocytic and DPN. Case 1 was a 16-year-old woman with a pigmented lesion on the trunk since birth, which was completely excised. Histopathological examination revealed a combined congenital nevus with a DPN. Comparative genomic hybridization showed no major genetic alterations, except for gain of 6q11.1 and point mutation of B-RAF V600E. Case 2 was a 62-year-old woman with a congenital pigmented lesion on the back. The lesion was diagnosed as a combined nevus of congenital and DPN. Comparative genomic hybridization showed no genetic alterations, and the NRAS Q61K was detected in both components. DPN is in most cases part of a combined nevus. Our cases showed strong and uniform nuclear expression of β-catenin and cyclin D1 in the DPN component suggesting the evolution of the congenital nevus to the DPN clone by acquiring β-catenin activating mutation.

Mucinous Syringometaplasia: Surrounding Acanthosis With Hyperkeratosis Tends to Conceal the Change Abstract: A 57-year-old man had a 2-year history of a painful nodule on the right sole. Physical examination revealed an 8 × 8 mm hyperkeratotic plaque with a central fissure. Excisional biopsy disclosed epithelial invagination surrounded by the acanthotic epidermis with parakeratotic hyperkeratosis and focal hypergranulosis. The invaginated epithelium lacked a cornified layer and was composed of a mixture of small basaloid squamous cells and goblet cells showing tubular structures. The patient was diagnosed with mucinous syringometaplasia. Our literature review established that surrounding acanthosis with hyperkeratosis typically tends to conceal mucinous syringometaplastic changes. Because mucinous syringometaplasia often presents as an asymptomatic papule/nodule with no distinct ulcer, fissure, or depressed area, cases may be overlooked.

Metastatic Melanoma Negative for 5 Melanocytic Markers, Complete Regressed Primary Cutaneous Melanoma, and Melanoma-Associated Leukoderma in the Same Patient Abstract: Melanomas with complete histological regression have been seen very infrequently. On the other hand, the diagnosis of metastatic melanoma is based on the histopathology and positivity of markers such as S100, Melan-A, and HMB-45 whose sensitivity is 99%, 82%, and 76%, respectively. It is very rare that metastatic melanomas and even more primary melanoma are negative for all of these markers. In these rare cases, there is usually a known primary. We present the case of a 82-year-old woman with a erythematous mass in the left groin and a 1-cm black–bluish irregular nodule on the skin of the ipsilateral foot. This lesion was clinical and dermoscopically compatible with primary melanoma. In the histological evaluation of the skin, a dermis full of melanophages and hemosiderophages were found in a background of fibrosis, scarce lymphocytic infiltrate, and neovascularization. Any cells expressing melanocytic markers were observed. It was diagnosed as tumoral melanosis. Lymph nodes showed a proliferation of atypical epithelioid cells with eosinophilic cytoplasm. Mitosis was conspicuous. Tumoral cells were vimentin and CD99 positive, and S100, CD34, HMB-45, Melan-A, SOX 10, tyrosinase, C-KIT, CD45, and CKAE1/AE3 negative, and BRAF-V600 mutated was detected. During follow-up, atypical vitiligo-like lesions were discovered, suggesting the diagnosis of metastatic melanoma totally regressed in our patient.

RAF1 Gene Fusions as a Possible Driver Mechanism in Rare BAP1-Inactivated Melanocytic Tumors: A Report of 2 Cases Abstract: BRCA1-associated protein (BAP1)-inactivated melanocytic tumor (BIMT) is a group of epithelioid melanocytic neoplasms characterized by the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21. They occur sporadically or in the setting of an autosomal-dominant cancer susceptibility syndrome that predisposes to the development of different internal malignancies. Most of these cutaneous lesions are associated with a BRAF-mutated melanocytic nevus and therefore are included in the group of combined nevi in the last WHO classification of skin tumors. Apart from a BRAF mutation, an NRAS mutation has been reported in rare cases, whereas in some lesions no driver mutation has been detected. Here, we report 2 cases of BIMTs with a BAP1 mutation and a RAF1 fusion. Both lesions proved to be BRAF and NRAS wild type and were associated with a conventional melanocytic nevus with dysplastic junctional features. We suggest that RAF1 fusions can represent an underlying driver genetic event in these cases. Our study extends the morphological and molecular spectrum in BIMTs.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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