Publications by authors named "Christine J Ko"

94 Publications

Post-COVID-19 vaccination IgA Vasculitis in an Adult.

J Cutan Pathol 2021 Nov 14. Epub 2021 Nov 14.

Department of Dematology, Yale University School of Medicine.

Leukocytoclastic vasculitis has been reported in the setting of COVID-19 infection and post-COVID-19 vaccination. We report a case of post-COVID-19 vaccination IgA vasculitis with IgA immune deposits in the skin and renal involvement; SARS-CoV spike protein immunohistochemical staining was negative. IgA vasculitis with skin and renal involvement is a potential reaction to COVID-19 vaccination. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/cup.14168DOI Listing
November 2021

Relationship-Centered Care in the Physician-Patient Interaction: Improving Your Understanding of Metacognitive Interventions.

Cutis 2021 Jun;107(6):320-324

Drs. Ko, Fortin, and Hafler as well as Ms. Spak are from Yale University, New Haven, Connecticut. Drs. Ko, Fortin, and Hafler are from the School of Medicine. Dr. Kim is from Cooper Medical School of Rowan University, Camden, New Jersey.

The concept of relationship-centered care was first introduced approximately 20 years ago, but this important concept has not yet been widely disseminated in clinical practice. Relationship-centered care in the health profession focuses on all relevant relationships in health care, not only between health care professionals and patients but also among colleagues, staff members, students, community, and self. This review summarizes the key literature to date on relationship-centered care as it pertains to the physician-patient relationship. Becoming more aware of the physician (self) and patient is a form of metacognition, thinking about what is happening in the moment as physicians and patients come together. Considering the complexity of the physician-patient relationship, we can implement simple metacognitive techniques toward the daily habitual practice of relationship-centered care.
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http://dx.doi.org/10.12788/cutis.0266DOI Listing
June 2021

Leukocytoclastic Vasculitis and Microvascular Occlusion: Key Concepts for the Working Pathologist.

Surg Pathol Clin 2021 Jun 28;14(2):309-325. Epub 2021 Apr 28.

Department of Dermatology, Yale University, 333 Cedar Street, PO Box 208059, New Haven, CT 06520, USA; Department of Pathology, Yale University, 310 Cedar St, New Haven, CT 06511, USA.

Although clinicians often put vasculitis and microvascular occlusion in the same differential diagnosis, biopsy findings often are either vasculitis or occlusion. However, both vasculitis and occlusion are present in some cases of levamisole-associated vasculopathy and certain infections. Depth of dermal involvement and vessel size should be reported, because superficial and deep small vessel leukocytoclastic vasculitis and/or involvement of medium-sized vessels may be associated with systemic disease. Microvascular occlusion of vessels in the fat should prompt consideration of calciphylaxis. Clues to ultimate clinical diagnosis can be garnered from depth of involvement, size of vessels affected, and presence of both vasculitis and occlusion.
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http://dx.doi.org/10.1016/j.path.2021.01.006DOI Listing
June 2021

Cutaneous and hepatic vascular lesions due to a recurrent somatic mutation reveal a pathway for vascular malformation.

HGG Adv 2021 Apr 1;2(2). Epub 2021 Mar 1.

Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06510, USA.

The term "cavernous hemangioma" has been used to describe vascular anomalies with histology featuring dilated vascular spaces, vessel walls consisting mainly of fibrous stromal bands lined by a layer of flattened endothelial cells, and an irregular outer rim of interrupted smooth muscle cells. Hepatic hemangiomas (HHs) and cutaneous venous malformations (VMs) share this histologic pattern, and we examined lesions in both tissues to identify genetic drivers. Paired whole-exome sequencing (WES) of lesional tissue and normal liver in HH subjects revealed a recurrent c.121G>T (p.Gly41Cys) somatic mutation in four of five unrelated individuals, and targeted sequencing in paired tissue from 9 additional HH individuals identified the same mutation in 8. In cutaneous lesions, paired targeted sequencing in 5 VMs and normal epidermis found the same c.121G>T (p.Gly41Cys) somatic mutation in three. encodes gap junction protein alpha 4, also called connexin 37 (Cx37), and the p.Gly41Cys mutation falls within the first transmembrane domain at a residue highly conserved among vertebrates. We interrogated the impact of the Cx37 mutant via lentiviral transduction of primary human endothelial cells. We found that the mutant induced changes in cell morphology and activated serum/glucocorticoid-regulated kinase 1 (SGK1), a serine/threonine kinase known to regulate cell proliferation and apoptosis, via non-canonical activation. Treatment with spironolactone, an inhibitor of angiogenesis, suppressed mutant SGK1 activation and reversed changes in cell morphology. These findings identify a recurrent somatic c.121G>T mutation as a driver of hepatic and cutaneous VMs, revealing a new pathway for vascular anomalies, with spironolactone a potential pathogenesis-based therapy.
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http://dx.doi.org/10.1016/j.xhgg.2021.100028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078848PMC
April 2021

HPyV6- and HPyV7-negative parakeratosis and dyskeratosis in squamous cell carcinoma in situ.

J Cutan Pathol 2021 Jul 16;48(7):998-1000. Epub 2021 Apr 16.

Department of Dermatology, Yale University Medical School, New Haven, Connecticut, USA.

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http://dx.doi.org/10.1111/cup.14022DOI Listing
July 2021

Discordant anti-SARS-CoV-2 spike protein and RNA staining in cutaneous perniotic lesions suggests endothelial deposition of cleaved spike protein.

J Cutan Pathol 2021 Jan 1;48(1):47-52. Epub 2020 Oct 1.

Department of Dermatology, Yale Medical School, New Haven, Connecticut, USA.

Background: Prior studies have shown the presence of immunohistochemical staining for the SARS-CoV-2 spike protein (SP) in endothelial cells and eccrine epithelium of acral perniosis classified as "COVID toes." Yet, other studies have been unable to detect SARS-CoV-2 RNA in skin biopsies of "COVID toes" by reverse-transcriptase polymerase chain reaction testing.

Objective: In order to address these apparently conflicting findings, we compared detection of SARS-CoV-2 SP, through RNA in situ hybridization (ISH) vs immunohistochemistry (IHC), in skin biopsies of acral perniotic lesions presenting during the COVID-19 pandemic.

Results: Three of six cases showed positive immunohistochemical labeling of endothelial cells, with one of three cases with sufficient depth also having labeling of eccrine glands, using an anti-SP SARS-CoV-2 antibody. These three cases positive with IHC were negative for SP by RNA ISH.

Conclusion: While the gold standard for detection of SARS-CoV-2 in tissue sections has yet to be determined, the detection of SARS-CoV-2 SP alone without spike RNA suggests that cleaved SP may be present in cutaneous endothelial cells and eccrine epithelium, providing a potential pathogenetic mechanism of COVID-19 endotheliitis.
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http://dx.doi.org/10.1111/cup.13866DOI Listing
January 2021

Cutaneous Involvement in Plasma Cell Myeloma.

Am J Clin Pathol 2021 01;155(1):106-116

Department of Pathology, Yale School of Medicine, New Haven, CT.

Objectives: Plasma cell myeloma (PCM) involving skin is rare and occurs in 1% to 4% of patients with PCM. We evaluated the clinicopathologic features, cytogenetic findings and clinical follow-up in a series of PCM cases with cutaneous involvement.

Methods: Cases of PCM with cutaneous involvement were retrospectively reviewed with clinical data.

Results: Skin involvement in PCM occurred in older individuals (mean, 75 years) and was more frequent in men (7/10 patients). All cases showed bone marrow involvement preceding the cutaneous lesions. Histopathologically, the infiltrate was plasmacytic (n = 5) or primitive or plasmablastic (n = 4), and 1 case showed predominantly lymphoplasmacytic features with cyclin D1 immunoreactivity and CCND1 gene rearrangement. Concurrent amyloid deposition was seen in one biopsy, and another case demonstrated coexisting squamous cell carcinoma. The most common immunophenotype was CD138+, CD20-, and CD56+ with light chain restriction. Cytogenetic analysis (available for 7 cases) showed multiple hyperdiploid abnormalities. Follow-up was available for 8 cases (mean, 42 months; range, 11-156 months) and showed short-term disease-related death in 7 of 8 patients.

Conclusions: Cutaneous involvement in PCM demonstrates a diverse cytomorphologic spectrum with plasmacytic, plasmablastic, or lymphoplasmacytic features and may show concurrent amyloid deposition or neoplasms such as squamous cell carcinoma. Cutaneous involvement typically occurs late in the course of the disease and likely portends poor outcome.
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http://dx.doi.org/10.1093/ajcp/aqaa122DOI Listing
January 2021

Primary cutaneous adenoid cystic carcinoma: Characterizing US demographics, clinical course, and prognostic factors.

J Am Acad Dermatol 2021 Jul 14;85(1):245-247. Epub 2020 Aug 14.

Department of Dermatology, Yale School of Medicine, New Haven, Connecticut. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.08.040DOI Listing
July 2021

Perniosis during the COVID-19 pandemic: Negative anti-SARS-CoV-2 immunohistochemistry in six patients and comparison to perniosis before the emergence of SARS-CoV-2.

J Cutan Pathol 2020 Nov 9;47(11):997-1002. Epub 2020 Sep 9.

Department of Dermatology, Yale Department of Dermatology, Yale University, New Haven, Connecticut, USA.

Background: Acral inflammatory lesions that have some resemblance to idiopathic or autoimmune-associated perniosis (chilblains) have been described in multiple countries during the COVID-19 pandemic.

Methods: We examined histopathologic findings in six consecutive such cases from five patients received in mid-May to mid-June of 2020, evaluating immunohistochemical staining for the SARS-CoV-2 nucleocapsid protein. We compared these six cases to eight cases diagnosed as perniosis between January and June of 2019.

Results: Five of six lesions with perniosis-like histopathology during the COVID-19 pandemic had distinctive tight cuffing of lymphocytes; intravascular material was present in one case. SARS-CoV-2 immunohistochemical staining using an antibody directed at the nucleocapsid protein was negative in all six cases. Only one of eight specimens with microscopic findings of perniosis received prior to the COVID-19 pandemic had tightly cuffed perivascular lymphocytes, and none had obvious intravascular occlusion.

Conclusions: A tightly cuffed pattern of perivascular lymphocytes is a feature of perniosis during the COVID-19 pandemic. The absence of SARS-CoV-2 nucleocapsid protein in these cases suggests against the virus being directly present in these lesions.
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http://dx.doi.org/10.1111/cup.13830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436569PMC
November 2020

Cutaneous Involvement by Mantle Cell Lymphoma: Expanding the Spectrum of Histopathologic Findings in a Series of 9 Cases.

Am J Dermatopathol 2020 Nov;42(11):848-853

Departments of Dermatology, and.

Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm with cutaneous involvement in ∼1% of cases. We present a single institutional series of nine patients (12 specimens) with cutaneous involvement by systemic MCL and review the clinicopathologic features. Six males and 3 females (age range 55-87 years) were included. Sites of involvement were head and neck (n = 3), trunk (n = 5), and extremities (n = 4). Histopathologically, 3 showed classic cytomorphology, 2 were blastoid, 3 pleomorphic, and 1 showed features resembling marginal zone lymphoma. Two cases presented with cutaneous lesions as the first tissue manifestation of the disease. A second malignancy was identified in 3/9 cases (2 melanomas and 1 papillary thyroid carcinoma). In one patient, MCL was juxtaposed with metastatic melanoma within the same biopsy specimen. Fluorescence in situ hybridization studies, when available, demonstrated the characteristic t(11,14) translocation. Direct immunofluorescence was performed on one case and showed immunoglobulin M (IgM) expression on the tumor cells. Follow-up was available in 7 cases (mean 42 months, range 6-78 months) and revealed death from disease for 6 patients that occurred within 1 week to 11 months (mean 4 months) after cutaneous involvement. In our series, 6/9 cases demonstrated blastoid, pleomorphic, or marginal zone lymphoma-like morphologies that could potentially mimic other hematolymphoid neoplasms. MCL may show surface IgM expression on DIF or may occur in association with other solid tumors. Immunohistochemistry for cyclin D1 and/or SOX-11 may be helpful for diagnosis, and imaging studies may be necessary to detect systemic involvement when cutaneous involvement is the first manifestation of the disease.
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http://dx.doi.org/10.1097/DAD.0000000000001742DOI Listing
November 2020

A rare case of lupoid leishmaniasis defying diagnosis for a decade.

J Cutan Pathol 2020 Nov 6;47(11):1054-1057. Epub 2020 Sep 6.

Department of Dermatology, Yale University, School of Medicine, New Haven, Connecticut, USA.

Cutaneous leishmaniasis (CL) is a common disease affecting millions in endemic areas worldwide. We present a case of lupoid leishmaniasis, a rare variant of CL, which clinically mimicked sarcoidosis and/or granulomatous rosacea for 10 years until ultimate diagnosis. An 82-year-old U.S. citizen with an extensive travel history presented with a 10-year history of facial plaques on the cheeks and was previously diagnosed and treated as sarcoidosis. Multiple biopsies (previously and at presentation) revealed tuberculoid granulomas with negative special stains for microorganisms and negative sterile tissue cultures for acid-fast bacilli, bacteria, and fungal organisms. A diagnosis of granulomatous rosacea was rendered and multiple medical therapies were attempted, none with sustained improvement. Repeat biopsy of a new lesion revealed intracellular organisms consistent with leishmaniasis, which was confirmed by polymerase chain reaction (PCR). Lupoid leishmaniasis is a rare presentation of CL including facial plaques that can mimic granulomatous diseases affecting the face including sarcoidosis and granulomatous rosacea. CL can sometimes be challenging to diagnose through standard histopathologic examination; immunohistochemistry for CD1a can be used to augment tissue-based examination and PCR should be sent early in cases with sufficient concern.
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http://dx.doi.org/10.1111/cup.13793DOI Listing
November 2020

A detailed analysis of the distribution, morphology, and histopathology of complex purpura in hospitalized patients: A case series of 68 patients.

J Am Acad Dermatol 2021 Apr 4;84(4):1188-1196. Epub 2020 May 4.

Yale School of Medicine Department of Dermatology, New Haven, Connecticut; Department of Pathology, New Haven, Connecticut. Electronic address:

Background: Purpura in inpatients commonly leads to dermatologic consultation. The differential diagnosis is broad and algorithms are intricate.

Objective: We evaluated inpatient consultations for complex purpura to document the most common diagnoses and to validate the true diagnostic utility of histopathology, clinical morphology, and distribution.

Methods: We reviewed a case series of 68 inpatients during a 4-year period with a dermatologic consultation for purpura and biopsy findings of vasculitis or microvascular occlusion.

Results: Key features of complex purpura are nonbranching (round) versus branching (retiform) morphology, dependent versus acral or generalized distribution, and leukocytoclastic vasculitis versus microvascular occlusion (with emphasis on depth of involvement). Dependent nonbranching purpura with only superficial vessels involved by leukocytoclastic vasculitis was most often due to IgA vasculitis or cutaneous single-organ small-vessel vasculitis. In contrast, deeper involvement by leukocytoclastic vasculitis was suggestive of systemic disease (eg, antineutrophil cytoplasmic antibody-associated vasculitis). Branching purpura was concerning, with greater than 90% sensitivity and specificity for microvascular occlusion and associated high mortality (≈50%). The majority of patients who died had acral branching lesions.

Limitations: Small sample size, inpatients at a tertiary care center, and retrospective nature are some limitations.

Conclusion: Nonbranching dependent purpura corresponded to leukocytoclastic vasculitis, with the most common diagnoses being IgA vasculitis or skin-limited small-vessel vasculitis; patients with deep involvement often had systemic diseases. In this series, branching purpura was due to microvascular occlusion rather than medium-vessel vasculitis, and had associated high mortality.
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http://dx.doi.org/10.1016/j.jaad.2020.04.149DOI Listing
April 2021

Diltiazem-associated Photodistributed Hyperpigmentation.

Yale J Biol Med 2020 03 27;93(1):45-47. Epub 2020 Mar 27.

Department of Dermatology, Yale University School of Medicine, New Haven, CT.

Diltiazem is a calcium-channel blocker commonly used for the treatment of hypertension. Common adverse effects include dizziness, headache, and edema. Fewer than 20 cases of diltiazem-associated photodistributed hyperpigmentation have been reported in the literature. Here, we present the case of a 71-year-old woman with new-onset facial hyperpigmentation 6 months after initiating treatment with diltiazem.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087047PMC
March 2020

Intravascular Large B-Cell Lymphoma: Clinical and Histopathologic Findings.

Yale J Biol Med 2020 03 27;93(1):35-40. Epub 2020 Mar 27.

Department of Pathology, Yale University School of Medicine, New Haven, CT.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subset of extranodal non-Hodgkin lymphoma characterized by neoplastic lymphocytes within the lumina of small to medium-sized blood vessels. IVLBCLs are B-cell tumors that can present in essentially any organ system, including the skin. Cutaneous manifestations vary greatly and can mimic other skin disease which may delay diagnosis; in the absence of skin lesions, blind skin biopsies can be utilized for diagnosis. Early studies suggested that IVLBCL is a very aggressive lymphoma with high overall mortality rate and short survival times. However, earlier diagnosis and use of new treatment modalities have shown promise in recent studies. This case series illustrates the heterogeneity of clinical and pathologic presentations of this uncommon lymphoma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087051PMC
March 2020

Histopathologic findings characteristic of CARD14-associated papulosquamous eruption.

J Cutan Pathol 2020 May 26;47(5):425-430. Epub 2019 Dec 26.

Department of Dermatology, Yale University, New Haven, Connecticut.

Background: Pathogenic mutations in caspase recruitment domain-containing protein 14 (CARD14) lead to CARD14-associated papulosquamous eruption, which shares clinicopathologic findings with psoriasis and pityriasis rubra pilaris. We aimed to describe distinguishing histopathologic features of CARD14-associated papulosquamous eruption.

Methods: This retrospective study examined the histopathologic features of specimens from patients with confirmed CARD14-associated papulosquamous eruption and adult patients with plaque psoriasis and pityriasis rubra pilaris.

Results: Lesional skin biopsies from patients with CARD14-associated papulosquamous eruption consistently showed alternating checkerboard parakeratosis and orthokeratosis, acanthosis without acantholysis, and dilated vessels in the dermal papillae, with some cases also showing follicular plugging.

Conclusion: CARD14-associated papulosquamous eruption has a range of findings, with a predominance of features typically associated with pityriasis rubra pilaris.
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http://dx.doi.org/10.1111/cup.13633DOI Listing
May 2020

Human papillomavirus-related verrucous cysts and hypergranulotic dyscornification within a cyst are likely distinct entities.

J Cutan Pathol 2020 03 19;47(3):314-315. Epub 2019 Dec 19.

Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1111/cup.13625DOI Listing
March 2020

Squamous Cell Carcinoma of the Lip in a Patient With Graft-Versus-Host Disease.

Dermatol Surg 2019 07;45(7):1002-1005

Department of Dermatology, Yale University New Haven, Connecticut.

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http://dx.doi.org/10.1097/DSS.0000000000001706DOI Listing
July 2019

Hypergranulotic dyscornification: 30 cases of a striking epithelial reaction pattern.

J Cutan Pathol 2019 Oct 5;46(10):742-747. Epub 2019 Jul 5.

Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.

Background: Hypergranulotic dyscornification (HD) is a rarely reported histological reaction pattern that may be observed in solitary benign keratoses.

Objective And Methods: We retrospectively reviewed all cases described as displaying "hypergranulotic dyscornification" at our institution between January 1st 1990 to September 1st 2018. We excluded cases that on retrospective review displayed changes of epidermolytic hyperkeratosis. We conducted electron microscopy (EM) of two lesions.

Results: Thirty cases were identified in our search. Eleven patients were men and 19 were women. Their mean age was 56.9 ± 21.2 years. In contrast to previous reports, we found that HD does not spare the head and neck area. Frequent clinical impressions were inflamed seborrheic keratosis, Bowen disease or inflamed verruca. The most distinctive histopathologic finding was the presence of a prominent granular layer with clumped perinuclear keratohyaline granules. Some cases had mounds of rounded, anucleate glassy eosinophilic corneocytes in the stratum corneum. We observed one case of incidental HD occurring in an epidermoid cyst. EM of HD showed dense perinuclear bands which appeared to match areas of positive staining by keratin immunohistochemistry, without evidence of pale cytoplasmic areas devoid of keratin filaments, characteristic of epidermolytic hyperkeratosis.

Conclusion: HD is a reproducible finding in some benign keratoses, probably because of abnormal keratinization. Awareness of this unique reaction pattern will help prevent misdiagnosis.
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http://dx.doi.org/10.1111/cup.13522DOI Listing
October 2019

Review of genodermatoses with characteristic histopathology and potential diagnostic delay.

J Cutan Pathol 2019 Oct 27;46(10):756-765. Epub 2019 Jun 27.

Department of Dermatology, Yale University Medical School, New Haven, Connecticut.

Advances in human genetics have enabled discovery of new genes for inherited skin diseases and cutaneous malformations as well as refined categorization of genodermatoses. Careful phenotyping has been central to genetic discoveries, and it provides critical clues for clinical diagnoses, particularly when the skin disorder is not congenital. This article will review several lesser-known genodermatoses that often present after infancy with recognizable histopathologic features.
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http://dx.doi.org/10.1111/cup.13520DOI Listing
October 2019

Second-Hit, Postzygotic PMVK and MVD Mutations in Linear Porokeratosis.

JAMA Dermatol 2019 05;155(5):548-555

Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.

Importance: Linear porokeratosis features linear and whorled configurations of keratotic papules and plaques, with coronoid lamellae present on histologic examination. Because linear porokeratosis manifests in the lines of Blaschko representing the dorsoventral migration patterns of keratinocyte precursors, it has been suggested that postzygotic somatic mutation underlies the disease. However, no genetic evidence has supported this hypothesis to date.

Objective: To identify genetic mutations associated with linear porokeratosis.

Design, Setting, And Participants: Paired whole-exome sequencing of affected skin and blood/saliva samples from 3 participants from 3 academic medical centers with clinical and histologic diagnoses of linear porokeratosis.

Interventions Or Exposures: Whole-exome sequencing of paired blood/saliva and affected tissue samples isolated from linear porokeratosis lesions.

Main Outcomes And Measures: Germline and somatic genomic characteristics of participants with linear porokeratosis.

Results: Of the 3 participants, 2 were male. Participant ages ranged from 5 to 20 years old. We found a combination of a novel germline mutation and a novel somatic mutation within affected tissue in all cases. One participant had a germline heterozygous PMVK c.329G>A mutation and a somatic copy-neutral loss of heterozygosity confined to the lesional skin, while a second had a germline heterozygous PMVK c.79G>T mutation and an additional PMVK c.379C>T mutation in the lesional skin. In a third participant, there was a germline splice-site mutation in MVD (c.70 + 5G>A) and a somatic deletion in MVD causing frameshift and premature codon termination within the lesional skin (c.811_815del, p.F271Afs*33 frameshift).

Conclusions And Relevance: Our findings suggest that linear porokeratosis is associated with the presence of second-hit postzygotic mutations in the genes that encode enzymes within the mevalonate biosynthesis pathway, and provide further evidence that the mevalonate pathway may be a potential target for therapeutic intervention in porokeratosis.
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http://dx.doi.org/10.1001/jamadermatol.2019.0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506890PMC
May 2019

An Algorithm for Evaluating Challenging Lip Cases: Neoplastic Versus Inflammatory.

Dermatol Surg 2020 05;46(5):700-702

Department of Dermatology Yale School of Medicine New Haven, Connecticut.

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http://dx.doi.org/10.1097/DSS.0000000000001849DOI Listing
May 2020

Visual perception, cognition, and error in dermatologic diagnosis: Diagnosis and error.

J Am Acad Dermatol 2019 Dec 21;81(6):1237-1245. Epub 2019 Feb 21.

Department of Dermatology, Yale University Medical School, New Haven, Connecticut; Department of Pathology, Yale University Medical School, New Haven, Connecticut.

Diagnostic error in dermatology is a large practice gap that has received little attention. Diagnosis in dermatology relies heavily on a heuristic approach that is responsible for our perception of clinical findings. To improve our diagnostic accuracy, a better understanding of the strengths and limitations of heuristics (cognitive shortcuts) used in dermatology is essential. Numerous methods have been proposed to improve diagnostic accuracy, including brain training, reducing cognitive load, and getting feedback and second opinions. Becoming comfortable with the uncertainty intrinsic to medicine is essential. Ultimately, the practice of metacognition, or thinking about how we think, can offer corrective insights to improve accuracy in diagnosis.
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http://dx.doi.org/10.1016/j.jaad.2018.12.072DOI Listing
December 2019

Visual perception, cognition, and error in dermatologic diagnosis: Key cognitive principles.

J Am Acad Dermatol 2019 Dec 21;81(6):1227-1234. Epub 2019 Feb 21.

Department of Dermatology, SUNY Health Science Center at Brooklyn, Brooklyn, New York; Kings County Hospital Center, Brooklyn, New York; South Nassau Dermatology PC, Oceanside and Long Beach, New York.

Dermatologic diagnosis relies on vision primarily and auditory and verbal input secondarily. Accurate dermatologic diagnosis is predicated on seeing and perceiving a skin finding, categorizing and naming the finding correctly, and comparing the visual data and data obtained from the totality of the clinical encounter (ie, from other sensory modalities) with one's working mental database of dermatologic diagnoses. The baseline assumption-which is false-is that a dermatologist is an expert at each of the aforementioned steps and transitions sequentially between them seamlessly in an error-free fashion. Each of these steps has inherent challenges, and the transitions between steps can also be problematic. In part 1 of this 2-part report, we describe the pitfalls associated with visual recognition. In part 2, we discuss cognitive heuristics as they relate to the dermatologic diagnostic process and prevention of diagnostic error.
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http://dx.doi.org/10.1016/j.jaad.2018.10.082DOI Listing
December 2019

Coccygeal Polypoid Eccrine Nevus.

Arch Pathol Lab Med 2019 07 28;143(7):890-892. Epub 2018 Dec 28.

From the Department of Pathology (Dr Charifa) and the Department of Dermatology (Dr Ko), Yale School of Medicine, New Haven, Connecticut.

Skin tags are fairly common lesions usually seen in adults on the neck and in body folds. The sacrococcygeal region is an unusual location for skin tags in children and may represent a congenital malformation of the spine or an isolated skin lesion. In this review, we summarize the clinical presentation, histopathologic changes, and differential diagnosis of coccygeal polypoid eccrine nevus as a rare cause of sacrococcygeal papules in children.
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http://dx.doi.org/10.5858/arpa.2018-0055-RSDOI Listing
July 2019

Cutaneous immunohistochemical staining pattern of p53β isoforms.

J Clin Pathol 2018 Dec 10;71(12):1120-1122. Epub 2018 Oct 10.

Department of Dermatology, School of Medicine, University of Dundee, Dundee, UK.

p53 is considered the guardian of the genome and as such has numerous functions. The gene is the most commonly mutated gene in cancer, and yet the exact biological significance of such mutations remains unclear. There are at least 12 different isoforms of p53, and the complexity of the p53 pathway may be in part related to these isoforms. Prior research has often not teased out what isoforms of p53 are being studied, and there is evidence in the literature that p53 isoforms are expressed differently. In this paper, we document the staining pattern of p53β isoforms in the skin and correlate it with mutational status in a subgroup of squamous proliferations of the skin. p53β isoforms are present in the cytoplasm of the differentiated layer of the epidermis and hair follicles (granular layer, infundibular and isthmus-catagen). p53β isoforms are diffusely expressed within the cytoplasm of well-differentiated squamous tumours with tetramerisation (C-terminal) domain mutations in Our results lend support to p53β isoforms being a marker of differentiation in keratinocytes.
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http://dx.doi.org/10.1136/jclinpath-2018-205098DOI Listing
December 2018

A case of subungual tumors of incontinentia pigmenti: A rare manifestation and association with bipolar disease.

JAAD Case Rep 2018 Aug 17;4(7):737-741. Epub 2018 Aug 17.

Department of Dermatology, Yale School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1016/j.jdcr.2018.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113656PMC
August 2018

Predicting non-melanoma skin cancer via a multi-parameterized artificial neural network.

Sci Rep 2018 01 26;8(1):1701. Epub 2018 Jan 26.

Department of Therapeutic Radiology, School of Medicine, Yale University, New Haven, USA.

Ultraviolet radiation (UVR) exposure and family history are major associated risk factors for the development of non-melanoma skin cancer (NMSC). The objective of this study was to develop and validate a multi-parameterized artificial neural network based on available personal health information for early detection of NMSC with high sensitivity and specificity, even in the absence of known UVR exposure and family history. The 1997-2015 NHIS adult survey data used to train and validate our neural network (NN) comprised of 2,056 NMSC and 460,574 non-cancer cases. We extracted 13 parameters for our NN: gender, age, BMI, diabetic status, smoking status, emphysema, asthma, race, Hispanic ethnicity, hypertension, heart diseases, vigorous exercise habits, and history of stroke. This study yielded an area under the ROC curve of 0.81 and 0.81 for training and validation, respectively. Our results (training sensitivity 88.5% and specificity 62.2%, validation sensitivity 86.2% and specificity 62.7%) were comparable to a previous study of basal and squamous cell carcinoma prediction that also included UVR exposure and family history information. These results indicate that our NN is robust enough to make predictions, suggesting that we have identified novel associations and potential predictive parameters of NMSC.
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http://dx.doi.org/10.1038/s41598-018-19907-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786038PMC
January 2018

Hypertrophic Lichen Planus and Well-Differentiated Squamous Cell Carcinoma: A Diagnostic Conundrum.

Dermatol Surg 2018 11;44(11):1466-1470

Department of Dermatology, Yale School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1097/DSS.0000000000001465DOI Listing
November 2018

Dermatomyositis: Histopathologic findings of parakeratosis and dermal edema revisited.

J Cutan Pathol 2018 Apr 15;45(4):282-285. Epub 2018 Feb 15.

Department of Dermatology, Yale University Medical School, New Haven, Connecticut.

The cutaneous manifestations of dermatomyositis range from classical in the case of heliotrope rash and Gottron papules to less common papulosquamous and edematous/vesiculobullous lesions; histopathologic descriptions are dominated by interface dermatitis. We present a case of dermatomyositis with a combination of common and rare skin findings, both clinically and histologically. Increased awareness of papulosquamous and edematous lesions of dermatomyositis can help direct patient care. Although uncommon, confluent parakeratosis and dermal edema can be manifestations of dermatomyositis.
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http://dx.doi.org/10.1111/cup.13104DOI Listing
April 2018
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