Clinical and histopathological spectrum of delayed adverse cutaneous reactions following COVID-19 vaccination.

BACKGROUND: As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS: In this IRB-approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS: Twelve cases were included. Histopathological features from two injection-site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small-vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS: Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid.

Histopathologic reaction patterns to differentially cross-linked hyaluronic acid fillers: A retrospective case series.

BACKGROUND: Hyaluronic acid filler reactions have been increasingly observed in recent years. Our study investigates whether the increased number of filler reactions observed since 2014 is associated with a specific histopathologic inflammatory pattern and type of filler. METHODS: The institution's dermatopathology electronic database was retrospectively searched for histopathologic reactions to hyaluronic acid from January 2014 to December 2019. The age, sex, type of filler, procedure, location, and histopathologic patterns were recorded. RESULTS: From 2014 to 2019, there were 15 cases of granulomatous reactions to hyaluronic acid filler. In 10 of these cases, there was a characteristic inflammatory pattern characterized by tightly cuffed palisades of histiocytes with varying numbers of eosinophils. Of the 11 cases in which the type of filler was known, all used Vycross technology, a novel manufacturing process in the production of hyaluronic acid filler. CONCLUSION: A characteristic histopathologic pattern of discrete foci of tightly cuffed palisaded granulomas with eosinophils is associated with fillers manufactured using Vycross technology.

The "bumpy" adolescent nose: Acne associated angiofibroma-like nasal papules.

BACKGROUND/OBJECTIVE: Papular scars are a recently described clinical phenotype of acne scarring characterized by papules occurring on the nose and chin. We have observed a similar presentation of nasal papules among patients seen in our clinic for acne and sought to further characterize the clinical and histopathological characteristics of this entity. METHODS: In this single-site case series, a retrospective review of electronic medical records of patients with nasal papules in association with acne vulgaris between April 2018 and April 2019 was performed. Clinical and histopathologic findings were recorded. RESULTS: We identified 20 patients who presented with a similar clinical phenotype of predominantly skin-colored, dome-shaped papules concentrated on the nose and chin in association with a history of more classic facial acne vulgaris. Papular lesions were seen predominately in adolescent Hispanic males. Concomitant acne on other areas of the face was identified in 18 patients at presentation while two patients had a history of adolescent acne. Biopsies were performed for five patients. Histopathologic examination demonstrated features of fibrosis and dilated thin-walled blood vessels, typical of angiofibromas. CONCLUSION: We present a series of adolescent patients with large, flesh-colored to erythematous papules seen predominantly on the nose. These lesions are histologically indistinguishable from angiofibromas and may represent an under-recognized yet disfiguring sequela of acne that may disproportionately affect adolescents with skin of color.

Neutrophilic panniculitis arising from hematogenous spread of methicillin-resistant Staphylococcus aureus.

Infectious panniculitis from hematogenous spread is uncommon and usually occurs in immunocompromised patients. Dissemination of gram-positive organisms to the subcutaneous tissue is rare with only several reports of disseminated panniculitis caused by Streptococcal species. We report a case of an immunocompetent 2-year-old boy presenting with diffuse neutrophilic panniculitis arising from methicillin-resistant Staphylococcus aureus septicemia. This case represents a highly atypical manifestation of severe MRSA infection and serves as a reminder to consider MRSA as a cause of disseminated neutrophilic panniculitis, particularly in high-risk populations.

Learning Analytics to Enhance Dermatopathology Education Among Dermatology Residents

BACKGROUND: With the advent of digital microscopy, learning analytics can be leveraged to advance teaching of dermatopathology in dermatology residency. OBJECTIVE: To analyze the acquisition and decay of dermatopathology visual recognition skills and areas of diagnostic confusion amongst residents using learning metrics generated by a web-based learning tool. METHODS: This was a prospective, longitudinal study of dermatology residents who studied digital photomicrographs of 18 routine diagnostic entities using an online software platform. Residents at different years of training were given 60 minutes to complete assessments on three occasions (initial test with follow-ups at one and three months). RESULTS: 4,938 responses were analyzed. Accuracy and time to diagnosis improved within each assessment and between the first and second assessments. First year residents showed knowledge decay when tested at three months (67% vs 64%; P=0.002) while third year residents retained knowledge and continued to improve upon their accuracy after three months (83% to 91%, <0.001). Learning analytics highlighted diagnostically challenging cases for residents that contradicted experts' predictions (R=0.48). CONCLUSIONS: The use of learning analytics and interactive digital platforms enhances dermatopathology curriculum development by identifying challenging diagnostic entities, assessing mastery of subject material, and optimizing review schedules. J Drugs Dermatol. 2019;18(12):1231-1236.

Evaluation of MITF, SOX10, MART-1, and R21 Immunostaining for the Diagnosis of Residual Melanoma In Situ on Chronically Sun-Damaged Skin.

BACKGROUND: Melanocytic immunostains can assist in margin evaluation of melanoma in situ (MIS) excisions; however, their accuracy and reliability relative to hematoxylin & eosin (H&E) is yet to be determined. OBJECTIVE: The objective of this study was to evaluate the sensitivity, specificity, and concordance of 4 melanocyte-specific immunostains for diagnosing MIS occurring on chronically sun-damaged skin. MATERIALS AND METHODS: Serial permanent sections from representative areas of negative margin and residual tumor were stained using H&E, MITF, MART-1, SOX10, and R21 and examined in a blinded fashion. The study set included 100 digital microscopy images from 10 cases of MIS excisions from the face. Two board-certified dermatopathologists, 4 fellowship-trained Mohs surgeons, 2 Mohs fellows, and 2 dermatology residents independently reviewed the 100 images. RESULTS: The average melanocyte density was 11 versus 28 melanocytes per 0.5 mm for chronically sun-damaged skin versus residual MIS on H&E, respectively. Statistically significantly higher melanocyte densities were observed using MITF, MART-1, and SOX10 on negative margins. The sensitivity and interobserver concordance was highest using MITF and SOX10. The intraobserver agreement on 4 duplicate images was 85%. CONCLUSION: In conclusion, the nuclear immunostains (MITF and SOX10) show the most promise for improving the diagnosis of MIS in chronically sun-damaged skin.

Margin Assessment for Punch and Shave Biopsies of Dysplastic Nevi.

INTRODUCTION: Biopsies of atypical melanocytic nevi are among the most commonly performed procedures by dermatologists. Margin assessment is often used to guide re-excision, but can be a point of confusion as negative margins reported in the planes of sections examined do not always reflect complete removal of a lesion. This study investigates the rates of false negative margins after both punch and shave biopsies. METHODS: We performed a retrospective analysis of 50 consecutive punch and shave biopsy specimens (1) diagnosed as DN, and (2) reported as having clear margins in the planes of section examined. Identified specimen blocks were then sectioned through to examine true margin involvement. RESULTS: Of the 50 specimens identified, 20% (n = 10) were found to have positive margins upon additional sectioning. We found no difference between the groups with respect to biopsy technique, type of nevus, degree of atypia, or gender. CONCLUSION: This study observed false negative peripheral margin status in a sizeable proportion of biopsy specimens, which did not vary significantly based on biopsy technique or pathologic characteristics. This finding reflects a limitation of standard tissue processing, in which a limited proportion of the true margin is evaluated, and may be of note to many dermatologists who base their decision to re-excise on the reporting of margin involvement. J Drugs Dermatol. 2018;17(7):810-812.

Necrobiosis lipoidica.

We present a case of necrobiosis lipoidica (NL) of the right abdomen in a 75-year-old man. A skin biopsy performed showed a layered infiltrate of mono and multinucleated histiocytes palisaded around degenerated collagen bundles. Laboratory workup was unremarkable. The patient was treated with topical corticosteroids with cessation of progression of his disease, although the eruption did not resolve. There are a number of treatments for NL reported in the literature, all with varying efficacy. Although NL lesions are usually asymptomatic, patients with NL must be monitored closely for signs of ulceration or malignant transformation, in which case more aggressive treatment options may be warranted.

Generalized essential telangiectasia.

The pathophysiology of generalized essential telangiectasia is not well understood. Generalized essential telangiectasia is an uncommon disorder in which widespread telangiectasias of unknown cause develop without associated systemic or antecedent dermatologic disease. We report a case of generalized essential telangiectasia in an otherwise healthy 49-year-old man.

Lymphomatoid papulosis.

Lymphomatoid papulosis is often regarded as a low-grade variant of cutaneous T cell lymphoma (CTCL). Given the excellent long-term prognosis, recent consensus guidelines indicate that patients can be monitored off therapy. We report a case of a 67-year-old man who presented with lymphomatoid papulosis, with necrotic papules that have been intermittently present for over forty years.

Immunostain use in the diagnosis of melanomas referred to a tertiary medical center: a 15-year retrospective review (2001-2015).

BACKGROUND: Little is known regarding the clinical practice of immunohistochemistry in the diagnosis of melanoma. We aimed to assess the incidence of immunostain usage by referring pathologists and dermatopathologists in melanoma cases sent for consultative review. As a secondary objective, associations between immunostain use and specific melanoma characteristics were also evaluated. METHODS: This is a retrospective review of consultation reports of referred melanomas at a tertiary academic center in New York, NY from 2001 to 2015. Univariate regression analysis was performed on melanomas with accompanying immunostains and on characteristics such as Breslow's depth, location, prognostic factors and morphologic subtypes. Associations between immunostain usage and these characteristics were analyzed using Fisher's exact test. RESULTS: Immunostain use significantly increased over the study period (p < 0.001) and was more likely to be associated with melanomas that were thicker [odds ratio (OR) = 2.5; 1.7-3.6]; located on the head and neck (OR = 1.6; 1.4-1.9) or acral sites (OR = 1.5; 1.1-2.0); had ulceration (OR = 2.1; 1.6-2.8), dermal mitoses (OR = 1.3; 1.1-1.5), or perineural invasion (OR = 3.6; 2.0-6.5); or were of desmoplastic (OR = 7.4; 4.5-12), amelanotic (OR = 7.1; 3.6-14), or nevoid subtypes (OR = 4.0; 1.7-8.9). CONCLUSIONS: Immunostain use in the diagnosis of melanoma has increased significantly in the past 15 years for reasons that remain unclear.

Amelanotic Cellular Blue Nevus of the Eyelid.

The authors describe an isolated, yellowish papular lesion of the upper eyelid in a 63-year-old man. Following excision, histopathologic analysis showed the features of a benign hypopigmented cellular blue nevus, the first and only case involving the eyelid skin.

Segmental stiff skin syndrome (SSS): A distinct clinical entity.

BACKGROUND: Stiff skin syndrome (SSS) is a noninflammatory, fibrosing condition of the skin, often affecting the limb girdles. OBJECTIVE: We present 4 new patients with SSS with largely unilateral, segmental distribution. To date, reported cases of SSS have been grouped based on generally accepted clinical and histopathologic findings. The purpose of this study was to analyze differences in clinical and histopathologic findings between previously reported SSS cases. METHODS: This is a retrospective review of 4 new cases and 48 previously published cases of SSS obtained from PubMed search. RESULTS: Of 52 total cases, 18 (35%) were segmentally distributed and 34 (65%) were widespread. The average age of onset was 4.1 years versus 1.6 years for segmental versus widespread SSS, respectively. Limitation in joint mobility affected 44% of patients with segmental SSS and 97% of patients with widespread SSS. Histopathologic findings were common between the 2 groups. LIMITATIONS: This was a retrospective study of previously published cases limited by the completeness and accuracy of the reviewed cases. CONCLUSIONS: We propose a distinct clinical entity, segmental SSS, characterized by a segmental distribution, later age of onset, and less severe functional limitation. Both segmental SSS and widespread SSS share common diagnostic histopathologic features.

Metastatic Cutaneous Squamous Cell Carcinoma: The Importance of T2 Stratification and Hematologic Malignancy in Prognostication.

BACKGROUND: While infrequent, nodal metastases in cutaneous squamous cell carcinoma (cSCC) can result in death from disease. Identification of those at risk for metastases is key to improved prognostication and treatment. OBJECTIVE: To review metastatic cSCC at the study institution. METHODS AND MATERIALS: Sixteen patients with metastatic cSCC were identified at the New York University Dermatologic Associates and Cancer Associates from 1998 to 2013. Patients were staged with American Joint Committee on Cancer (AJCC) and modified Brigham and Women's Hospital (BWH) criteria and compared to 32 control subjects. RESULTS: Seven of 16 patients were identified as Stage T2 by AJCC criteria and Stage T2b by BWH criteria; two patients were on Stage T1, three patients were on more advanced T stages, and four patients lacked primary tumor data. Five patients had hematologic malignancy, and one patient had a solid-organ transplant. CONCLUSION: The modified BWH criteria aims to better prognosticate the large group of T2 AJCC tumors, resulting in the majority of mortality. In the experience of the authors, the majority of patients with metastatic disease were on T2, stratifying to stage T2b by BWH criteria, or more advanced T stages. The findings of this study support BWH stratification of T2 tumors and also indicate that hematologic malignancy is a significant comorbidity associated with a poor outcome.

Skin-limited relapse of systemic anaplastic large-cell lymphoma.

Anaplastic large-cell lymphomas (ALCLs) are agroup of CD30-positive non-Hodgkin lymphomasthat are linked by common morphologic andimmunophenotypic features but have varyingclinical and genetic characteristics. The World HealthOrganization classification currently recognizes threesubtypes of ALCL: systemic anaplastic lymphomakinase-positive ALCL, systemic anaplastic lymphomakinase-negative (ALK-) ALCL, and primary cutaneousALCL. Here we present a 42-year-old man with ahistory of systemic ALK- ALCL, who was in remissionfor six months before relapsing with skin-limitedanaplastic large-cell lymphoma.

Gyrate erythema in the setting of tinea pedis.

Gyrate erythema, which also is known as erythemaannulare centrifugum (EAC), is a reactive dermatitisthat is thought to occur in response to an underlyingtrigger. The superficial form is characterized bythe typical, centrifugally-expanding, annular,erythematous patches or plaques with a distincttrailing scale. The deep form also is a centrifugallyexpanding,erythematous plaque but with induratedborders and absence of scale. These cutaneousfindings are thought to be reactive, most often inresponse to infections or drugs and, less likely, tounderlying malignant conditions.

White fibrous papulosis of the neck.

White fibrous papulosis of the neck is a rare diagnosisthat typically presents with white, 2-to-3-mmpapules on the posterior aspect of the neck. Wepresent an elderly woman with diffuse involvementon her abdomen and back.