Publications by authors named "Vitaly Terushkin"

40 Publications

An unusual presentation of calciphylaxis.

Cutis 2020 Mar;105(3):E24-E27

Department of Dermatology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.

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March 2020

Margin Assessment for Punch and Shave Biopsies of Dysplastic Nevi.

J Drugs Dermatol 2018 Jul;17(7):810-812

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.
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July 2018

Intraoperative Immunostaining for Cytokeratin-7 During Mohs Micrographic Surgery Demonstrates Low Local Recurrence Rates in Extramammary Paget's Disease.

Dermatol Surg 2018 Mar;44(3):354-364

Ali Hendi MD PC, Chevy Chase, Maryland.

Background: Extramammary Paget's disease (EMPD) is a rare intraepithelial malignancy with high recurrence rates following standard surgical treatments, ranging from 22% to 60% in large retrospective reviews.

Objective: To evaluate the local recurrence rate of Mohs micrographic surgery (MMS) supplemented with intraoperative immunohistochemistry for cytokeratin-7 (MMS + CK-7) for primary and recurrent EMPD.

Materials And Methods: Retrospective, multi-center, cross-sectional study of patients treated using MMS + CK-7. Demographic, clinicopathologic, treatment, and follow-up data were obtained by chart review.

Results: The observed local recurrence rate for MMS + CK-7 is 3.3% (2/61 tumors) with a mean follow-up of 43.5 months (1-120 months). Local recurrence occurred in 2.3% (1/43) of primary tumors and 5.6% (1/18) of recurrent tumors. Kaplan-Meier 5-year tumor-free rates are 94.6% overall, 97.1% for primary tumors, and 80.0% for recurrent tumors. The Kaplan-Meier 5-year tumor-free rates for all EMPD tumors treated with MMS + CK-7 versus a historical cohort of MMS alone are 94.6% versus 72.0% (p = .012).

Conclusion: MMS + CK-7 is an effective treatment for EMPD, demonstrating improved outcomes compared with historical controls.
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http://dx.doi.org/10.1097/DSS.0000000000001355DOI Listing
March 2018

A prospective study evaluating the utility of a 2-mm biopsy margin for complete removal of histologically atypical (dysplastic) nevi.

J Am Acad Dermatol 2017 Dec 2;77(6):1096-1099. Epub 2017 Oct 2.

Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York. Electronic address:

Background: Complete removal of individual dysplastic nevi (DN) is often accomplished by a second surgical procedure after the initial biopsy. The choice to perform the second procedure is strongly influenced by histopathologic margin status of the initial biopsy specimen.

Objective: To evaluate the clinical and histopathologic outcomes of in toto biopsy of DN using a predetermined margin of normal skin.

Methods: We conducted a prospective study of a saucerization method using a defined 2-mm margin in patients undergoing biopsy of a pigmented skin lesion.

Results: We performed 151 biopsies in 138 patients. Overall, 137 of 151 lesions subjected to biopsy (90.7%) were melanocytic: 86 DN (57.0%), 40 nevi without atypia (26.5%), and 11 melanomas (7.3%). Of 78 DN, 68 (87.2%) were removed with clear histopathologic margins (8 DN were excluded because of inadequate processing). There was no clinical evidence of recurrence at any of the biopsy sites that were simply observed (i.e., not re-excised) over a median of 16.9 months.

Limitations: There were few biopsies performed on the face.

Conclusions: The complete histopathologic removal of nearly 9 of 10 DN using a peripheral margin of 2 mm of normal skin and a depth at the dermis and subcutaneous fat junction has the potential to decrease second procedures at DN biopsy sites, thereby decreasing patient morbidity and saving health care dollars.
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http://dx.doi.org/10.1016/j.jaad.2017.07.016DOI Listing
December 2017

Effect of General Anesthesia on Neurodevelopmental Abnormalities in Children Undergoing Treatment of Vascular Anomalies With Laser Surgery: A Retrospective Review.

Dermatol Surg 2017 Apr;43(4):534-540

*The Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, New York; †Laser & Skin Surgery Center of New York, New York, New York.

Background: Multiple exposures to general anesthesia may be neurotoxic to the developing brain. This relationship has not been evaluated in children undergoing laser surgery for vascular anomalies.

Objective: To evaluate the prevalence of neurodevelopmental abnormalities in children who received multiple laser procedures under general anesthesia before the age of 4 years for the treatment of vascular anomalies.

Methods And Materials: Retrospective chart review of patients with contact of parents for telephone interview.

Results: Thirty-three patients were eligible. Average age at the time of survey was 7.8 years. Twenty-three (84.8%) patients were female, with average age at the time of first treatment at 1.9 years. Average number of treatments received before the age of 4 years was 6.7. Anesthetics included inhalational nitrous oxide and isoflurane and intravenous propofol. Seven patients carried one or more of the following diagnoses: attention-deficit hyperactivity disorder (3.0%), anxiety (6.1%), behavioral disorder (3.0%), language disorder (3.0%), speech disorder (3.0%), and motor disorder (6.1%). These prevalence rates are similar to those found in the US population.

Conclusion: This is the first report on the prevalence of neurodevelopmental disorders in children undergoing multiple laser treatments under general anesthesia. Although the study sample is small, no increased risks when comparing with prevalence rates reported in the literature were noted.
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http://dx.doi.org/10.1097/DSS.0000000000001003DOI Listing
April 2017

Panfolliculoma with an endophytic architecture resembling a hair follicle: a report of three cases.

J Cutan Pathol 2016 Nov 9;43(11):1074-1076. Epub 2016 Sep 9.

The Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, NY, USA.

Panfolliculoma is a benign follicular tumor comprised of all components of the hair follicle. We report three cases of panfolliculoma with a solid, endophytic architecture, which at scanning magnification had the profile of a hair follicle. The epithelial components included uniform dark blue germinative cells, matrical cells, clear cells and cells containing trichohyaline granules. All the cases also had a central hyperkeratotic horn resembling a hair shaft. Two patients were female and one was male. Two lesions were located on the head and neck, and one was located on the leg. Clinical differential diagnoses included basal cell carcinoma, foreign body and cyst.
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http://dx.doi.org/10.1111/cup.12799DOI Listing
November 2016

Dermatomyositis, clinically presenting with cutaneous ulcers, with histopathologic evidence of perforating collagenosis.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

Dermatomyositis is a systemic, autoimmune diseasewith a variety of clinical features that often includemyositis and characteristic cutaneous findings. Asubset of patients with dermatomyositis developcutaneous ulcers, often in the setting of vasculitis orvasculopathy. We present a case of dermatomyositiswith cutaneous ulcers that show perforatingcollagenosis on histopathologic examination.Acquired reactive perforating collagenosistypically occurs in the setting of diabetes mellitus,chronic renal failure, and other pruritic conditions,and this case represents a rare association withdermatomyositis, which may ultimately be helpful inelucidating the pathophysiology of this perforatingdisorder.
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December 2016

Eosinophilic dermatosis of hematologic malignancy.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

We report a 68-year-old woman with chroniclymphocytic leukemia, who developed numerous,pruritic, edematous, and vesicobullous skin lesionsof the face and extremities over the course of severalmonths. The diagnosis of eosinophilic dermatosis ofhematologic malignancy (EDHM) was made basedon the clinical history and histopathologic features.Owing to the possible link between EDHM and amore aggressive underlying CLL, she was startedagain on chemotherapy. This case serves as areminder that, although the precise pathogenesis ofEDHM remains unclear, the paraneoplastic disorderis the result of immune dysregulation. Patientswho develop EDHM should undergo prompthematologic/oncologic evaluation.
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December 2016

Diffuse sebaceous-gland hyperplasia.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

Diffuse sebaceous-gland hyperplasia is a rarevariant of sebaceous-gland hyperplasia that isdistinct from the well-known circumscribed type.The term presenile sebaceous hyperplasia has beenutilized to describe this entity that is distinguishedby specific features, which include confluence oflesions that results in the formation of large plaqueson the face, the sparing of periorificial regions, andhighly functional glandular hyperplasia that resultsin excessive sebaceous secretion. We present a43-year-old woman with monomorphous, skincoloredand yellow, smooth 1- to-3-mm papules,some with central umbilication, that spare theperiorificial zones. Histopathologic examination wassuggestive of diffuse sebaceous-gland hyperplasia.Differential diagnosis of this condition is broad andincludes syndromes that are associated with multiplefacial papules and malignant conditions, such asMuire-Torre syndrome and Cowden syndrome. Itis important to be aware of this condition in orderto consider appropriate treatment options, such asisotretinoin and to avoid unnecessary diagnostictests.
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December 2016

Cutis verticis gyrata.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

Cutis verticis gyrata that involves only the face isa rare presentation of this even rarer cutaneousanomaly. We present a 61-year-old man, whodeveloped primary essential progressive cutis verticisgyrata of the face.
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December 2016

A case of perniosis.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

Perniosis is a localized, inflammatory reaction that ischaracterized by erythematous papules and nodulesthat often are located on the acral surfaces in youngwomen. The lesions of perniosis are thought to bedue to cold-induced vasoconstriction that leadsto hypoxemia and inflammation of the vessel wall.Histopathologic and laboratory studies are indicatedfor patients with suspected perniosis to distinguishbetween idiopathic perniosis and secondaryperniosis. Treatment includes adequate heating andclothing, proper food intake, nifedipine, ultravioletA1 phototherapy, topical glucocorticoids, andvasodilators.
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December 2016

Cowden syndrome presenting with trichilemmomas.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

Cowden syndrome (CS) is a genetic cancerpredisposition syndrome that is associated withgermline mutations in the phosphate and tensinhomologue deleted on chromosome ten (PTEN)tumor suppressor gene. It is characterizedby the formation of benign and malignanttumors. Characteristic benign tumors includetrichilemmommas, acral keratoses, mucocutaneousneuromas, and oral papillomas. The most commonmalignant condition include breast, thyroid, andendometrial cancers. We present a case of a30-year-old woman with CS, who initially presentedwith trichilemmomas that were misdiagnosed ascomedonal acne. Recognition of the presentingfeatures of CS is important to ensure proper referral,management, and treatment for these patients.
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December 2016

Acral keratoses and squamous-cell carcinomas likely associated with arsenic exposure.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

Chronic arsenic exposure is known to inducepunctate keratoses with an increased risk ofprimary squamous-cell carcinoma. Drinking wateris currently the major source of arsenic exposureworldwide and is considered one of the mostsubstantial environmental carcinogens. We describethe case of a 61-year-old Hungarian woman withscattered, acral, hyperkeratotic papules and a historyof five palmoplantar squamous-cell carcinomasas well as two other extremity non-melanomaskin cancers. Prior to immigration, she had livedin a county of Southern Hungary that is known tohave elevated concentrations of inorganic arsenicin the drinking water above the World HealthOrganization's current maximum threshold forsafety. To date, this report is the first to describethe phenomenon of palmoplantar squamouscellcarcinomas in a patient from this region andunderscores the importance of vigilant screening inthose individuals who have spent substantial time inhigh-risk regions internationally and domestically.
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December 2016

Gyrate erythema in the setting of tinea pedis.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

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.
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December 2016

Primary cutaneous smoldering adult T-cell leukemia/ lymphoma.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches.
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December 2016

Multiple pilomatricomas in the setting of myotonic dystrophy.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

The association between multiple pilomatricomasand the autosomal dominant neurodegenerativedisorder myotonic dystrophy has been described inthe literature. Although the mechanism is unknown,it is hypothesized that the dystrophia myotonicaprotein kinase mutation in myotonic dystrophyaffects intracellular calcium levels, which alterproliferation and terminal differentiation that leads tocells that are observed in pilomatricomas. We presenta patient with multiple, symptomatic pilomatricomasand myotonic dystrophy, with a strong family historyof both of these rare disorders.
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December 2016

Idiopathic scleredema.

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

Scleredema, which also is known as scleredemaadultorum of Buschke, is an uncommonsclerodermiform condition that is characterizedby progressive thickening and hardening of theskin due to excessive dermal mucin and collagendeposition. The clinical course is variable, andprogression of disease may lead to functionalimpairment with limitations in mobility. The etiologyand pathogenesis are unknown although severalwell-known associations include streptococcalinfection; diabetes mellitus, particularly withmetabolic syndrome; and monoclonal gammopathy.We present a case of scleredema in a 52-year-oldman with no identifiable associated condition,who experienced improvemement with UVBphototherapy.
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December 2016

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

Dermatol Online J 2016 Dec 15;22(12). Epub 2016 Dec 15.

Ronald O. Perelman Department of Dermatology, NYU School of Medicine, NYU Langone Medical Center.

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.
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December 2016

Digit-Sparing Mohs Surgery for Melanoma.

Dermatol Surg 2016 Jan;42(1):83-93

*Zitelli and Brodland Skin Cancer Center, Pittsburgh, Pennsylvania; †Adolos Strategic, San Antonio, Texas.

Background: Digital melanoma is commonly treated with amputation or wide local excision. Mohs micrographic surgery (MMS) may offer an alternative treatment modality.

Objective: To describe outcomes of digital melanomas treated with MMS over a 35-year period.

Methods: A retrospective series of digital melanomas treated with MMS was studied. Tumor and treatment characteristics were described and follow-up was assessed.

Results: Sixty-two digital (1.2%) tumors were identified from 4995 melanomas, of which 57 (91.9%) were primary and 5 (8.1%) were recurrent on enrollment. Melanocytic antigen recognized by cytotoxic T lymphocytes from melanoma patients (MART)-1 and HMB-45 immunostains were used in 34 (54.8%) and 14 (22.6%) cases, respectively. Five (8.2%) tumors recurred locally during the course of the study, none of which occurred with MART-1 use. Three (60.0%) local recurrences were salvaged with additional MMS. Local recurrence-free survival rates for primary melanomas at 5 and 10 years were 91.8% and 82.6%, respectively. Overall, 55 (96.5%) patients with primary digital melanomas avoided amputation. Five and 10-year melanoma-specific survival rates for all patients were 95.0% and 81.2%, respectively.

Limitations: A formal comparison group was not studied.

Conclusion: In the management of digital melanoma, MMS conserves function by avoiding amputation and offers a low local recurrence rate. Outcomes are improved with the use of MART-1.
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http://dx.doi.org/10.1097/DSS.0000000000000587DOI Listing
January 2016

Primary localized cutaneous amyloidosis.

Dermatol Online J 2013 Dec 16;19(12):20711. Epub 2013 Dec 16.

New York University School of Medicine.

A 61-year-old man presented for evaluation of a bruise-like lesion of the right knee. He was found to have an ill-defined, light brown patch with focal areas of dark red and brown. The histopathologic diagnosis was consistent with amyloidosis. Further subtyping showed that the amyloid protein was AL (κ). A systemic evaluation failed to show internal involvement. Amyloidosis comprises a spectrum of diseases, which range from systemic to localized cutaneous types, and is characterized by the extracellular deposition of amyloidosis protein as beta-pleated sheets. The forms of amyloidosis are differentiated by the specific types of protein-derived amyloidosis fibers. Both nodular and primary systemic amyloidosis can present as nodules on the skin owing to deposition of AL type amyloid protein. Primary systemic amyloidosis, which carries a poorer prognosis than does nodular amyloidosis, also may give rise to ecchymoses and many other cutaneous and extracutaneous findings. Histopathologic features are similar in both cases and involve the deposition of amorphous, eosinophilic material in the dermis. Nodular amyloidosis may progress to primary systemic disease in up to 50% of cases. Because our patient had no systemic involvement and the lesions did not appear nodular in nature, the patient was given a diagnosis of primary localized AL cutaneous amyloidosis. Routine follow-up for this patient is necessary to detect any potential disease progression.
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December 2013

Diffuse large B-cell lymphoma.

Dermatol Online J 2012 Dec 15;18(12):25. Epub 2012 Dec 15.

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, USA.

We present a 56-year-old man with a two-year history of erythematous nodules and plaques on the forehead, frontal aspect of the scalp, and left side of the neck. Histopathologic findings are compatible with a diagnosis of diffuse large B-cell lymphoma (DLBCL). We present a brief review of primary cutaneous DLBCLs and address the putative association between DLBCLs and hepatitis C virus infection.
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December 2012

Erythema annulare centrifugum.

Dermatol Online J 2012 Dec 15;18(12):21. Epub 2012 Dec 15.

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, USA.

Erythema annulare centrifugum (EAC) is a gyrate erythema, which is typically characterized by annular, erythematous plaques with trailing scale. It is considered to be a reactive condition with a wide variety of inciting causes but unclear pathophysiology. The mean duration of the eruption is 11 months. We present a patient with a 50-year history of recurrent EAC with no known cause. Although it does follow a previously reported pattern of seasonal recurrence, this case represents the longest reported duration of EAC.
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December 2012

Verrucous lymphangioma circumscriptum.

Dermatol Online J 2012 Dec 15;18(12). Epub 2012 Dec 15.

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, USA.

A 19-year-old woman with a seven-year history of pruritic, grouped, verrucous papules and plaques on the left arm presented for consultation. The lesion slightly flattened in appearance with topical glucocorticoid treatment. The histopathological features were consistent with lymphangioma circumscriptum. This entity is the most common subtype of lymphangioma and presents with grouped, clear vesicles that may appear pink to purple. However, a rare verrucous type can present a diagnostic challenge. Whereas the definitive treatment option is surgical excision, other treatments, which include sclerotherapy, radiotherapy, and laser therapy, have been reported to cause resolution or improvement. In the future, propranolol may hold promise as a medical therapy for lymphangioma.
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December 2012

Eruptive vellus hair cysts.

Dermatol Online J 2012 Dec 15;18(12). Epub 2012 Dec 15.

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, USA.

Eruptive vellus hair cyst (EVHC), described initially in 1977, is a benign dermatologic condition that is characterized by the sudden appearance of monomorphic, follicular, asymptomatic, small papules in children and young adults. The diagnosis is based on the histopathologic findings of stratified-squamous epithelium with a granular layer that surrounds a cystic space filled with laminated keratin and a variable number of vellus hair cysts. EVHC can be associated with steatocystoma multiplex. A current hypothesis suggests that EVHC originates from a cystic change at the insertion of the pilosebaceous duct. EVHC is primarily treated for cosmesis with retinoids, surgery, and lasers.
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December 2012

Ablative fractional resurfacing for involuted hemangioma residuum.

Arch Dermatol 2012 Nov;148(11):1294-8

BACKGROUND Given the natural tendency for 15% to 40% of infantile hemangiomas to spontaneously involute over time, much debate surrounds the issue of treatment. Until recently, effective therapies to improve the appearance of residual textural skin changes in these patients were lacking. We suggest the use of ablative fractional resurfacing for the treatment of textural skin changes resulting from involuted hemangiomas. OBSERVATIONS All patients treated with an ablative fractional carbon dioxide laser experienced considerable flattening of the fibrofatty residual tissue, with at least 50% to 75% improvement in color, texture, and overall appearance. CONCLUSION While additional future studies are needed, we believe that ablative fractional resurfacing should be considered for the treatment of textural skin changes associated with involuted infantile hemangiomas.
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http://dx.doi.org/10.1001/archdermatol.2012.2346DOI Listing
November 2012

TGF-β1 induces endothelial cell apoptosis by shifting VEGF activation of p38(MAPK) from the prosurvival p38β to proapoptotic p38α.

Mol Cancer Res 2012 May 20;10(5):605-14. Epub 2012 Apr 20.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

TGF-β1 and VEGF, both angiogenesis inducers, have opposing effects on vascular endothelial cells. TGF-β1 induces apoptosis; VEGF induces survival. We have previously shown that TGF-β1 induces endothelial cell expression of VEGF, which mediates TGF-β1 induction of apoptosis through activation of p38 mitogen-activated protein kinase (MAPK). Because VEGF activates p38(MAPK) but protects the cells from apoptosis, this finding suggested that TGF-β1 converts p38(MAPK) signaling from prosurvival to proapoptotic. Four isoforms of p38(MAPK) -α, β, γ, and δ-have been identified. Therefore, we hypothesized that different p38(MAPK) isoforms control endothelial cell apoptosis or survival, and that TGF-β1 directs VEGF activation of p38(MAPK) from a prosurvival to a proapoptotic isoform. Here, we report that cultured endothelial cells express p38α, β, and γ. VEGF activates p38β, whereas TGF-β1 activates p38α. TGF-β1 treatment rapidly induces p38α activation and apoptosis. Subsequently, p38α activation is downregulated, p38β is activated, and the surviving cells become refractory to TGF-β1 induction of apoptosis and proliferate. Gene silencing of p38α blocks TGF-β1 induction of apoptosis, whereas downregulation of p38β or p38γ expression results in massive apoptosis. Thus, in endothelial cells p38α mediates apoptotic signaling, whereas p38β and p38γ transduce survival signaling. TGF-β1 activation of p38α is mediated by VEGF, which in the absence of TGF-β1 activates p38β. Therefore, these results show that TGF-β1 induces endothelial cell apoptosis by shifting VEGF signaling from the prosurvival p38β to the proapoptotic p38α.
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http://dx.doi.org/10.1158/1541-7786.MCR-11-0507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356490PMC
May 2012

Agreement on the clinical diagnosis and management of cutaneous squamous neoplasms.

Dermatol Surg 2010 Oct;36(10):1514-20

Memorial Sloan-Kettering Cancer Center, New York, New York 10022, USA.

Background: Diagnostic accuracy and preferred therapeutic strategies for actinic keratoses (AKs) and squamous cell carcinoma (SCC) have significant public health implications.

Objective: To evaluate clinical-pathologic agreement on the diagnosis of AKs and early SCCs and to characterize the effect of diagnosis on therapeutic decisions.

Methods & Materials: Nine dermatologists and two dermatopathologists reviewed an image-based dataset of AKs and early SCCs. Clinical-pathologic agreement, inter- and intraobserver reliability for clinical diagnosis, and frequencies of therapies according to pathologic diagnosis were assessed.

Results: Clinical-pathologic (κ=0.10) agreement was poor, whereas interobserver (κ=0.24) and intraobserver (κ=0.28) agreements were fair. Participants were more likely to treat AKs with cryotherapy (64.2%) and to manage SCCs with surgery (72.8%). Therapeutic choice rarely changed after participants were shown histological photomicrographs. Participating clinicians treated most lesions histologically diagnosed as SCC in situ arising within AK using surgery, whereas pathologists selected cryotherapy or curettage and electrodesiccation for these lesions.

Conclusion: We found poor clinical-pathologic agreement and reproducibility for clinically distinguishing between AK and early SCC even between skin cancer specialists from a single academic group practice. Nomenclature used in the pathologic diagnosis of AK and SCC affects clinicians' therapeutic decisions. The authors have indicated no significant interest with commercial supporters.
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http://dx.doi.org/10.1111/j.1524-4725.2010.01675.xDOI Listing
October 2010

Pathways to involution of nevi: insights from dermoscopic follow-up.

Arch Dermatol 2010 Apr;146(4):459-60

Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

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http://dx.doi.org/10.1001/archdermatol.2010.20DOI Listing
April 2010

Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes.

J Am Acad Dermatol 2010 Jun 3;62(6):929.e1-9. Epub 2010 Apr 3.

Memorial Sloan-Kettering Cancer Center, New York, New York 10022, USA.

Background: The relationship between oral vitamin D supplementation and cutaneous photosynthesis is not well understood.

Objective: We sought to provide estimates of the equivalency of vitamin D production from natural sun exposure versus oral supplementation.

Methods: Using the FastRT simulation tool, we determined sun exposure times needed to achieve serum vitamin D(3) concentrations equivalent to 400 or 1000 IU vitamin D for individuals of various Fitzpatrick skin types living in Miami, FL, and Boston, MA, during the months of January, April, July, and October.

Results: Peak ultraviolet B irradiation for vitamin D synthesis occurs around 12 pm Eastern Standard Time (EST). In Boston, MA, from April to October at 12 pm EST an individual with type III skin, with 25.5% of the body surface area exposed, would need to spend 3 to 8 minutes in the sun to synthesize 400 IU of vitamin D. It is difficult to synthesize vitamin D during the winter in Boston, MA. For all study months in Miami, FL, an individual with type III skin would need to spend 3 to 6 minutes at 12 pm EST to synthesize 400 IU. Vitamin D synthesis occurs faster in individuals with lighter Fitzpatrick skin types. The duration to attain 1000 IU of vitamin D is longer in all scenarios.

Limitations: Results of the computer model are only approximations. In addition, calculations were made based on the assumption that (1/4) of 1 minimal erythema dose directed at (1/4) body surface area is equal to 1000 IU of oral vitamin D.

Conclusions: Although it may be tempting to recommend intentional sun exposure based on our findings, it is difficult, if not impossible to titrate one's exposure. There are well-known detrimental side effects of ultraviolet irradiation. Therefore, oral supplementation remains the safest way for increasing vitamin D status.
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http://dx.doi.org/10.1016/j.jaad.2009.07.028DOI Listing
June 2010