Premortem Skin Biopsy Assessing Microthrombi, Interferon Type I Antiviral and Regulatory Proteins, and Complement Deposition Correlates with Coronavirus Disease 2019 Clinical Stage.

Apart from autopsy, tissue correlates of coronavirus disease 2019 (COVID-19) clinical stage are lacking. In the current study, cutaneous punch biopsy specimens of 15 individuals with severe/critical COVID-19 and six with mild/moderate COVID-19 were examined. Evidence for arterial and venous microthrombi, deposition of C5b-9 and MASP2 (representative of alternative and lectin complement pathways, respectively), and differential expression of interferon type I-driven antiviral protein MxA (myxovirus resistance A) versus SIN3A, a promoter of interferon type I-based proinflammatory signaling, were assessed. Control subjects included nine patients with sepsis-related acute respiratory distress syndrome (ARDS) and/or acute kidney injury (AKI) pre-COVID-19. Microthrombi were detected in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P < 0.001) and none of the nine patients with pre-COVID-19 ARDS/AKI (P < 0.001). Cells lining the microvasculature staining for spike protein of severe acute respiratory syndrome coronavirus 2, the etiologic agent of COVID-19, also expressed tissue factor. C5b-9 deposition occurred in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P < 0.001) and none of the nine patients with pre-COVID-19 ARDS/AKI (P < 0.001). MASP2 deposition was also restricted to severe/critical COVID-19 cases. MxA expression occurred in all six mild/moderate versus two (15%) of 13 severe/critical cases (P < 0.001) of COVID-19. In contrast, SIN3A was restricted to severe/critical COVID-19 cases co-localizing with severe acute respiratory syndrome coronavirus 2 spike protein. SIN3A was also elevated in plasma of patients with severe/critical COVID-19 versus control subjects (P ≤ 0.02). In conclusion, the study identified premortem tissue correlates of COVID-19 clinical stage using skin. If validated in a longitudinal cohort, this approach could identify individuals at risk for disease progression and enable targeted interventions.

Severe COVID-19: A multifaceted viral vasculopathy syndrome.

The objective of this study was to elucidate the pathophysiology that underlies severe COVID-19 by assessing the histopathology and the in situ detection of infectious SARS-CoV-2 and viral capsid proteins along with the cellular target(s) and host response from twelve autopsies. There were three key findings: 1) high copy infectious virus was limited mostly to the alveolar macrophages and endothelial cells of the septal capillaries; 2) viral spike protein without viral RNA localized to ACE2+ endothelial cells in microvessels that were most abundant in the subcutaneous fat and brain; 3) although both infectious virus and docked viral spike protein was associated with complement activation, only the endocytosed pseudovirions induced a marked up-regulation of the key COVID-19 associated proteins IL6, TNF alpha, IL1 beta, p38, IL8, and caspase 3. Importantly, this microvasculitis was associated with characteristic findings on hematoxylin and eosin examination that included endothelial degeneration and resultant basement membrane zone disruption and reduplication. It is concluded that serious COVID-19 infection has two distinct mechanisms: 1) a microangiopathy of pulmonary capillaries associated with a high infectious viral load where endothelial cell death releases pseudovirions into the circulation, and 2) the pseudovirions dock on ACE2+ endothelial cells most prevalent in the skin/subcutaneous fat and brain that activates the complement pathway/coagulation cascade resulting in a systemic procoagulant state as well as the expression of cytokines that produce the cytokine storm. The data predicts a favorable response to therapies based on either removal of circulating viral proteins and/or blunting of the endothelial-induced response.

Targetoid lesions in a patient with systemic lupus erythematosus.

Rowell Syndrome is a rare presentation of lupus erythematosus manifesting as an eruption of erythema multiforme-like papules and plaques with immunological findings of positive rheumatoid factor, speckled antinuclear antibodies, and/or anti-Ro/La antibodies. This case highlights the unusual and highly debated presentation of Rowell Syndrome in a 66-year-old woman with newly-appearing erythematous, targetoid plaques in the setting of previously diagnosed systemic lupus erythematosus. Skin biopsy revealed histological features of full-thickness epidermal necrosis with focal sub-epidermal separation and a superficial perivascular lymphocytic infiltrate interpreted to favor Rowell Syndrome given her clinical history and presentation. Although no standard treatment exists, a prednisone taper and topical corticosteroids proved effective initially, with complete resolution at six months on mycophenolate mofetil and belimumab.

Follicular psoriasis: a report of 5 cases and review of the literature, likely an under-recognized yet distinctive variant of psoriasis.

Psoriasis is a common autoimmune dermatosis representing an interplay between certain genetic predisposing factors along with clonally restricted Th1 T cells responding to epidermal keratinocyte derived antigen. A unique IL17/IL23 cytokine-rich milieu is pathogenetically significant and conducive to its salient histomorphologic features, such as epidermal hyperplasia and intraepidermal influx of neutrophils. The classic cutaneous manifestation is that of plaque psoriasis also referred to as psoriasis vulgaris with characteristic well-circumscribed erythematous plaques covered by silvery scales. Follicular psoriasis is an uncommon variant manifesting as a scaly folliculocentric hyperkeratotic eruption of the trunk and extremities, irrespective of the presence or absence of conventional lesions of psoriasis vulgaris. In this study we present 5 cases of follicular psoriasis, review the literature, and provide a proposal regarding relevant pathologic findings and potential pathogenetic mechanisms. The incidence of follicular psoriasis is unknown, emphasizing its rarity given the overall incidence of conventional psoriasis in the general population. Owing to the lack of awareness, this clinical presentation is often mistaken for other follicular dermatoses, including bacterial folliculitis, pityriasis rubra pilaris, keratosis pilaris, or follicular eczema.

Histopathology of sabra dermatitis: A case report.

Sabra dermatitis (SD) is a form of irritant contact dermatitis caused by penetration of small, hair-like glochids from Opuntia cactus into the skin. SD is a common problem among the farmers who are in close contact with prickly pears; however, the histopathologic criteria for this condition are not well defined. The purpose of this article is to present a well-documented case of SD and to acquaint pathologists with the entity.

Data warehouse strategies and the modern anatomic pathology laboratory: Quality management, patient safety, and pathology productivity issues and opportunities.

Application of lean process management strategies to process improvement in clinical and anatomic pathology laboratories afford opportunities to enhance workflow process to lower costs and simultaneously to improve patient safety. Bar-codes are now employed in most modern anatomic pathology laboratories to track specimens from the clinicians' office or the operating room all through the continuum of service to specimen disposal. In order to enhance patient safety and workload optimization strategies, novel computer hardware and software assets are being developed to enable monitoring, analysis, and improvement of specimen workflow and diagnostic accuracy. More recently, data warehouse technologies from the retail industry have been optimized to permit high-throughput analysis of granular data in the laboratory arena. These optimize mass-data analysis in real time in the information technology space. In this review we describe the application of an in-house designed data warehouse to the anatomic pathology assets of a large regional reference laboratory.

Drug induced pseudolymphoma.

Atypical lymphocytic infiltrates of the skin comprise a broad spectrum of entities ranging from benign infiltrates to those that are malignant. Many of these infiltrates are in fact reactive lymphomatoid ones related to drug therapy falling under the general category of drug associated pseudolymphoma. Within this nosologic umbrella are nodular and diffuse infiltrates resembling low grade T and B cell lymphoma consistent with lymphocytoma cutis, drug associated reversible T cell dyscrasias which draw a strong morphologic and phenotypic parallel with mycosis fungoides and the various pre-lymphomatous T cell dyscrasias, and angiocentric CD30 positive infiltrates mirroring lymphomatoid papulosis. The implicated drug classes are quite varied and include antidepressants, antihistamines, calcium channel blockers, statins, anticonvulsants, and various biologic drugs. The drugs from these various drug classes exert certain effects on lymphoid function including evoking overzealous responses to other antigenic stimuli. As the adverse effect on lymphocyte function may be cumulative over years and or reflect the interplay of other drugs, a temporal association may not exist between the onset of the rash/lesion and the initiation of the drug. In certain lymphomatoid reactions however such as DRESS syndrome the drug may function as both an antigen as well as an immune dysregulating agent. It is critical that the pathologist works carefully with the clinician in the evaluation of all atypical cutaneous lymphoid infiltrates where the distinction between pseudolymphoma versus lymphoma cannot be reliably made based on pathologic analysis alone.

Folliculocentric Herpes: A Clinicopathological Study of 28 Patients.

BACKGROUND: The cutaneous manifestations of herpes infection are primarily in the context of active infection and of the post-herpetic zosteriform eruption. The former manifests cytopathic alterations diagnostic of herpes. The latter includes lichen planus-like and granuloma annulare-like eruptions and lymphocytoma cutis. METHODS: We encountered skin biopsies from 28 patients whose acute or chronic herpetic or post-herpetic zosteriform lesions manifested folliculocentricity. The clinical appearance of the lesions was correlated with the histopathologic and immunohistochemical features of paraffin-embedded skin biopsies to determine the specific viral etiology. A history of underlying medical disease was noted if present. RESULTS: There were 16 men and 12 women with a folliculocentric eruption occurring after a known herpetic eruption or manifesting cytopathic changes and/or immunohistochemical findings compatible with herpes virus in lesional skin biopsies. Underlying immune dysregulatory states were present in most cases, namely, malignancy, anticonvulsant or antidepressant therapy, diabetes mellitus, psoriasis, Crohn disease, and other conditions. All biopsies demonstrated dense lymphohistiocytic infiltrates in or around hair follicles with variable necrosis, while active infections also showed cytopathic and/or immunohistochemical evidence of herpetic alterations, most commonly varicella zoster. Other features included interfollicular interface dermatitis, lymphocytic eccrine hidradenitis, neuritis, and folliculocentric vasculitis. CONCLUSIONS: Cutaneous herpetic eruptions can evoke a predominantly folliculocentric mononuclear cell reaction and vasculitis; there is an association with underlying endogenous and/or iatrogenic immune dysregulation. Most cases are secondary to reactivation of varicella zoster. The histomorphology suggests a role for cell-mediated immunity. Antigenic homology of an endogenous 72-kd heat shock protein in follicles with that of a herpetic heat shock protein, in concert with an intrafollicular proliferative response of γ-δ T lymphocytes, may explain the follicular localization and composition of the infiltrate.

A case of generalized red sweating.

We report a case of a 70-year-old man with a 5-year history of red pigmented sweating on the axillae, groin, forearms, trunk, and and peri-nuchal sites. No identifiable cause of the pigmented sweat was identified. Biopsy revealed lipofuscin pigment leading to the diagnosis of idiopathic chromhidrosis. This case represents an unusual presentation of chromhidrosis that was not limited to the apocrine sweat gland distribution and ultimately revealed no identifiable cause. After failing multiple treatment options, the patient elected for a trial of treatment with 20% aluminum chloride solution.

Onycholemmal carcinoma: a morphologic comparison of 6 reported cases.

BACKGROUND: We report 6 new cases of onycholemmal carcinoma, a rare, often misdiagnosed, subcategory of squamous cell carcinoma. All reported cases to date have been treated with amputation of the affected digit. OBJECTIVE: The purpose of this study was to present the clinical and pathological features of each new case and to discuss treatment options that spare digit functionality. METHODS: Hematoxylin-eosin stains were performed on tumor sections and examined using light microscopy. In situ hybridization using probes against human papillomavirus were examined in 1 case. RESULTS: The female to male ratio was 1:1 with involvement of fingers in 3, thumb in 1, and toe in 1. Among the symptoms were onycholysis, periungual erythema, and pain; symptom duration ranged from 6 months to 2 years. Histologically, all cases showed a well-differentiated atypical infiltrative squamous proliferative lesion exhibiting a lobulated and cystic pattern of growth in the dermis. Abrupt keratinization reminiscent of trichilemmal keratinization was noted. Mohs micrographic surgery and radiation therapy were used as primary treatment modalities, maintaining digit functionality and achieving remission. LIMITATIONS: Limitations of this study included the small number of cases, the infrequency with which this tumor has been reported in the literature, and the inability to obtain follow-up on an older archival case. CONCLUSIONS: Onycholemmal carcinoma is a distinct type of squamous cell carcinoma arising from the nail isthmus; its natural clinical course is indolent. In this regard less aggressive digit-sparing treatment modalities such as radiation or Mohs micrographic surgery should be considered.

Malignant peripheral nerve sheath tumor with glandular differentiation in a patient with neurofibromatosis type 1.

: The authors report an unusual case of malignant peripheral nerve sheath tumor with malignant differentiation arising as a subcutaneous nodule in the thigh of a 53-year-old woman with a history significant for neurofibromatosis type 1. Peripheral nerve sheath tumors containing a glandular component, commonly referred to as glandular peripheral nerve sheath tumors, are rare neoplasms found largely in patients with neurofibromatosis type 1. These tumors are frequently malignant; recognition of metastatic potential is made based on the atypical spindle-cell component. Rarely, as in our case, the glandular component is also histologically malignant. Only 5 such tumors have been described in the literature to date. Glandular differentiation, particularly with malignant features, can be a potentially misleading feature when found as a component of malignant peripheral nerve sheath tumors and raise a wide spectrum of differential diagnoses, including metastatic Sertoli-Leydig tumors. The patient is free of disease for 22 months after wide tumor reexcision, which contrasts with previously reported devastatingly poor prognosis of these tumors.

Sinonasal non-keratinizing squamous cell carcinoma with nasal skin extension as the initial presentation.

Sinonasal non-keratinizing squamous cell carcinoma (SCC), previously designated as transitional cell carcinoma or cylindrical cell carcinoma, is an uncommon malignant neoplasm with distinct histopathological features, considered to be a low-grade malignancy that usually occurs in elderly patients. Extensive local invasion is uncommon. Here we report a case of 90-year-old woman whose original presentation was as erythematous nasal skin nodules, biopsy of which showed a dermal tumor with features of sinonasal non-keratinizing SCC. No epidermal dysplasia was present. A subsequent computed tomography scan confirmed the presence of an endophytic tumor on the nasal sidewall. The initial presentation of sinonasal non-keratinizing SCC as a skin lesion is previously unreported to our knowledge. Diagnosis in this context requires accurate evaluation of the histopathology as well as a comprehensive knowledge of pathology specific to this anatomic location.

Acantholytic squamous cell carcinoma: is it really a more-aggressive tumor?

BACKGROUND: Acantholytic squamous cell carcinoma (ASCC) is frequently considered to be a more-aggressive variant with worse prognosis than other squamous cell carcinoma (SCC) subtypes. OBJECTIVES: To analyze the biologic behavior of ASCC. METHODS: We conducted a literature search of articles in English plus a manual search of cited references and common dermatology textbooks. RESULTS: We found no comprehensive study on the biologic behavior of ASCC. Published data are scant, anecdotal, and contradictory. Of the articles investigated, the recurrence and metastasis rates ranged from 6% to 10% and 2% to 43%, respectively. CONCLUSION: Analysis of the published evidence does not support the assumption that ASCC is a more-aggressive tumor with higher potential for recurrence or metastasis. As with other SCC types, prognosis is more dependent on the characteristics of the host and the location, size, depth, differentiation, and previous treatment of tumors. The treatment and follow-up of patients with ASCC should be similar to those for other types of SCC. The authors have indicated no significant interest with commercial supporters.

The histologic and molecular correlates of COVID-19 vaccine-induced changes in the skin.

A total of 22 patients who had developed an adverse cutaneous reaction to the Moderna or Pfizer vaccine underwent biopsies. Each patient was assessed light microscopically, and, in select biopsies, spike glycoprotein and cytokine assessment were also conducted. The patients developed self-limited cutaneous reactions often described clinically as urticarial or eczematous within 1 day to 4 weeks after receiving the first or second dose of the Pfizer or Moderna vaccine. Classic clinical and morphologic depictions of type IV cutaneous hypersensitivity with features of eczematous dermatitis, interface dermatitis, granulomatous inflammation, and/or lymphocytic vasculitic component were observed. Clinical and/or histologic features of perniosis, pityriasis rosea, pityriasis rubra pilaris, and guttate psoriasis were seen in select cases. In 2 cases the dominant picture was urticarial vasculitis, possibly reflective of an Arthus type III immune complex action. The biopsy specimens of normal skin post vaccine and of skin affected by the post-vaccine eruption showed rare deep microvessels positive for spike glycoprotein with no complement deposition contrasting with greater vascular deposition of spike protein and complement in skin biopsies from patients experiencing severe coronavirus disease 2019 (COVID-19). It is concluded that self-limited hypersensitivity reactions to the vaccine occur possibly owing to a substance found in the vaccine vehicle (eg, polyethylene glycol). An immune response that is directed against human-manufactured spike has to be considered because some of the reactions clinically and or histologically closely resemble mild COVID-19. Finally, vaccine-associated immune enhancement largely attributable to the adjuvant properties of the vaccine may unmask certain inflammatory milieus operational in psoriasis, atopic dermatitis, and subclinical hypersensitivity.

The skin as a critical window in unveiling the pathophysiologic principles of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is a single-stranded RNA virus whose sequence is known. COVID-19 is associated with a heterogeneous clinical phenotype ranging from asymptomatic to fatal disease. It appears that access to nasopharyngeal respiratory epithelia expressing angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV-2, is followed by viral replication in the pulmonary alveolar septal capillary bed. We have demonstrated in earlier studies that incomplete viral particles, termed pseudovirions, dock to deep subcutaneous and other vascular beds, potentially contributing to the prothrombotic state and systemic complement activation that characterizes severe and critical COVID-19. A variety of skin eruptions have been described in the setting of SARS-CoV-2 infection and more recently, after COVID-19 vaccination. The vaccines deliver a laboratory-synthesized mRNA that encodes a protein that is identical to the spike glycoprotein of SARS-CoV-2, allowing the production of immunogenic spike glycoprotein that will then elicit T cell and B cell adaptive immune responses. In this contribution, we review an array of cutaneous manifestations of COVID-19 that provide an opportunity to study critical pathophysiologic mechanisms that underlie all clinical facets of COVID-19, ranging from asymptomatic/mild to severe and critical COVID-19. We classify cutaneous COVID-19 according to underlying pathophysiologic principles. In this regard we propose three main pathways: (1) complement mediated thrombotic vascular injury syndromes deploying the alternative and mannan binding lectin pathways and resulting in the elaboration of cytokines like interleukin 6 from endothelium in the setting of severe and critical COVID-19 and (2) the robust T cell and type I interferon-driven inflammatory and (3) humoral-driven immune complex mediated vasculitic cutaneous reactions observed with mild and moderate COVID-19. Presented are novel data on cutaneous vaccine reactions that manifest a clinical and morphologic parallel with similar eruptions observed in patients with mild and moderate COVID-19 and in some cases represent systemic eczematoid hypersensitivity reactions to a putative vaccine-based antigen versus unmasking subclinical hypersensitivity due to immune enhancing effects of the vaccine. Finally, we demonstrate for the first time the localization of human synthesized spike glycoprotein after the COVID-19 vaccine to the cutaneous and subcutaneous vasculature confirming the ability of SARS-CoV-2 spike glycoprotein to bind endothelium in the absence of intact virus.

The dermal-based borderline melanocytic tumor: a categorical approach.

BACKGROUND: The borderline melanocytic tumor (BMT) is a morphologically and biologically indeterminate melanocytic proliferation manifesting worrisome architectural features and cytologic atypia exceeding that encountered in melanocytic nevi yet insufficient to warrant designation as melanoma. The criteria that define the BMT are not well defined nor is the concept widely recognized. OBJECTIVE: The purpose of this study is to provide a practical framework for the approach to the dermal BMT. METHODS: Thirty-two patients with BMTs extending into the reticular dermis and at a depth of 0.75 mm or more underwent local excision and sentinel lymph node biopsy between 2000 and 2006. Four categories of BMT were recognized: (1) nevoid BMT (BNM); (2) the atypical Spitz tumor (AST); (3) pigmented epithelioid melanocytoma (PEM); and (4) BMT arising in a deep penetrating nevus (B-DPN). RESULTS: Four patients were in the BNM category (male/female ratio [M:F] = 1:3; mean age = 27 years, range = 15-36), 14 in the AST category (M:F = 7:7; mean age = 20.9, range = 3-58), 7 in the PEM category (M:F = 4:3; mean age = 23.5, range = 3-39), and 7 in the B-DPN category (M:F = 5:2; mean age = 22.3, range = 14-36). The percentages of patients with positive sentinel nodes in each category were 25% (1/4), 35% (5/14), 14% (1/7), and 57% (4/7), respectively. The average time of follow-up was approximately 4.2 years. One patient, a 36-year-old man, died of disease, while the others are alive and well. In the one death attributable to widespread metastatic disease, the lesion was initially interpreted as a deep penetrating nevus; however, retrospective review revealed features compatible with a B-DPN; the review was prompted by a recurrence that was morphologically compatible with a Clark level V malignant melanoma, reflecting clinical and morphologic progression. LIMITATIONS: The mean follow-up was less than 5 years. Molecular studies to further explore the biologic commonality with melanoma were not performed. CONCLUSION: The dermal variant of BMT is a tumor of younger adults and children that can be associated with lymph node disease and a potential for morphologic and biologic progression when inadequately treated.

Cutaneous CD4+ CD56+ hematologic malignancies.

BACKGROUND: Hematologic malignancies expressing CD4 and CD56 are most commonly associated with the recently described CD4(+) CD56(+) hematodermic neoplasm. METHODS: Thirteen cases of CD4(+) CD56(+) hematologic malignancies were prospectively encountered in the routine and referral practices of the authors. RESULTS: Patients 1 and 2 were elderly men exhibiting an acute onset of skin, bone-marrow, and peripheral blood involvement, both dying of their disease within less than 12 months. CD3(+) phenotype and a clonal T-cell receptor beta rearrangement indicated categorization as a CD4(+) natural killer T-cell lymphoma. Patient 3 developed a CD56(+) anaplastic large cell lymphoma and is without disease after excision and radiation. Indolent CD4(+) CD56(+) poikilodermatous mycosis fungoides defined case 4. There were 7 patients with CD123(+) CD4(+) CD56(+) hematodermic neoplasm, 4 dying within 18 months of presentation with peripheral blood/marrow involvement in 6 of the 7 cases. Two patients with granulocytic sarcoma dying within 100 days of presentation defined the last two cases. LIMITATIONS: There were relatively small numbers in each of the categories and the follow-up was limited in those cases where death was not reported. CONCLUSION: Cutaneous malignancies composed of CD4(+) CD56(+) hematopoietic cells define a varied group and oftentimes have an aggressive clinical course although not in every case.

The phenotypic profile of dermatomyositis and lupus erythematosus: a comparative analysis.

BACKGROUND: The mechanisms which regulate cutaneous inflammation in the setting of collagen vascular disease have been a topic of recent interest; emphasis has been placed on type I interferon-associated recruitment of CXCR3+ lymphocytes in dermatomyositis (DM). METHODS: On a total of 42 biopsies from patients with DM, systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE) comprehensive phenotypic studies were performed to explore the practical value of phenotypic analysis in the subclassification of lesions of collagen vascular disease. RESULTS: The infiltrate in DM was of mild intensity compared to lupus erythematosus (LE). The dominant mononuclear cell in DM exhibited a CD4/CXCR3-positive phenotype while biopsies of SLE typically showed a dearth of CXCR3-positive cells. CD8 and CD20 lymphocytes were greatest in SLE and DLE, respectively. CD123 plasmacytoid dendritic cells, seen in most cases, were most frequent in cases of SCLE; CD83 expression was minimal. Endothelial MXA expression was a characteristic feature of DM. CD123 and MXA expression within inflammatory cells and keratinocytes was most conspicuous in areas of interface injury. Cutaneous lymphocyte antigen (CLA) expression was diminished in the dermal infiltrate in most cases of DM and LE. T regulatory cells never exceeded 15% of the infiltrate and were the least in the setting of DM and LE. CONCLUSIONS: An interferon-alpha-inducible cytokine milieu is common in SLE, DLE, SCLE and DM. In addition, there are phenotypic differences as alluded to above that may be of some practical value in separating these distinctive subsets. Features not previously emphasized such as MXA endothelial cell staining in DM and the lack of staining for CD83 and CLA in lesions of collagen vascular disease may be of diagnostic value.

De novo intraepidermal epithelioid melanocytic dysplasia: an emerging entity.

De novo intraepidermal epithelioid melanocytic dysplasia represents a distinctive form of intraepidermal melanocytic dysplasia. Although these lesions are atypical, they are not diagnostic of melanoma. They are considered a part of the atypical mole phenotype and may define a point in the natural course of melanomagenesis.