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The COVID-19 pandemic brought not only a huge healthcare challenge to the world but also introduced many questions of how the human immune system reacts to counter viral invasion, including vaccination. Unlike most vaccinations that are not usually linked to any specific skin eruptions, COVID-19 vaccination has been linked to a variety of skin lesions. In this paper, we present two patients who developed granulomatous skin lesions post-COVID-19 vaccination, one patient has generalised granuloma annulare (GA) and the other patient develops localised GA. Both patients have good responses to treatment regimens containing systemic corticosteroids. We review the literature pertaining to COVID-19-linked skin diseases, particularly granulomatous diseases and discuss the possible pathomechanism of granulomatous eruptions in relation to COVID-19 vaccination.

BACKGROUND: The elastic scattering spectroscopy (ESS) device (DermaSensor Inc., Miami, FL) is a noninvasive, painless, adjunctive tool for skin cancer detection. OBJECTIVES: To investigate the performance of the ESS device in the detection of melanoma. METHODS: A prospective, investigator-blinded, multicenter study was conducted at 8 United States (US) and 2 Australian sites. All eligible skin lesions were clinically concerning for melanoma, examined with the ESS device, subsequently biopsied according to dermatologists standard of care, and evaluated with histopathology. A total of 311 participants with 440 lesions were enrolled, including 44 melanomas (63.6% in situ and 36.4% invasive) and 44 severely dysplastic nevi. RESULTS: The observed sensitivity of the ESS device for melanoma detection was 95.5% (95% CI, 84.5% to 98.8%, 42 of 44 melanomas), and the observed specificity was 32.5% (95% CI, 27.2% to 38.3%). The positive and negative predictive values were 16.0% and 98.1%, respectively. LIMITATIONS: The device was tested in a high-risk population with lesions selected for biopsy based on clinical and dermoscopic assessments of board-certified dermatologists. Most enrolled lesions were pigmented. CONCLUSION: The ESS devices high sensitivity and NPV for the detection of melanoma suggest the device may be a useful adjunctive, point-of-care tool for melanoma detection.

BackgroundS100A8 is a melanoma biomarker expressed in the melanoma-associated epidermal keratinocytes, but its diagnostic utility has not been compared with other biomarkers, including PRAME.ObjectivesTo compare the utility of S100A8 and PRAME immunohistochemistry (IHC) in the differential diagnosis of melanoma and naevi in a case-control study.MethodsA previously described cohort of 209 melanomas (case samples) and naevi (control samples) dual-immunostained for S100A8 and PRAME were included. For S100A8, previously reported scores indicating the proportion of tumour-associated epidermis stained (0 = indeterminate; 1 = 0-4%; 2 = 5-25%; 3 = 26-50%; 4 = 51-75%; 5 = > 75%) were utilized. PRAME IHC was reviewed by at least two reviewers and a consensus score assigned, with score indicating the proportion of tumour stained (0 = indeterminate; 1 = 0%; 2 = 1-50%; 3 = > 50%). A positive test was defined as > 50% staining.ResultsThe area under the receiver operating characteristic curves for S100A8 (0.833) and PRAME (0.874) were not significantly different from each other (P = 0.22). The diagnostic sensitivity and specificity were 42.4% [95% confidence interval (CI) 32.6-52.8%] and 98.2% (95% CI 93.6-99.8%) for S100A8, and 79.8% (95% CI 70.5-87.2%) and 87.3% (95% CI 79.6-92.9%) for PRAME, respectively. A combined test requiring both S100A8 and PRAME IHC positivity had a sensitivity of 39.4% (95% CI 29.7-49.7%) and specificity of 99.1% (95% CI 95.0-100.0%).ConclusionsS100A8 and PRAME have utility in the diagnostic workup of melanoma, with S100A8 being more specific and PRAME being more sensitive when using this threshold. Our findings suggest that these two immunohistochemical markers may favourably complement one another to improve the detection of melanoma.

PURPOSE: To report the clinical and histopathologic features of necrobiosis lipoidica and associated retinal vasculitis and describe successful treatment of both skin and eye manifestations with adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. OBSERVATIONS: A 35-year-old patient with bipolar disorder and ocular hypertension was referred for evaluation of bilateral retinal vasculitis. Fluorescein angiography revealed bilateral occlusive retinal vasculitis. Physical exam was notable for multiple annular and round erythematous hyperpigmented and atrophic patches and plaques on both lower extremities. Skin biopsy revealed a diagnosis of necrobiosis lipoidica, a rare granulomatous skin disease. Both the patients retinal vasculitis and skin patches responded favorably to treatment with adalimumab, a TNF-alpha inhibitor. CONCLUSIONS AND IMPORTANCE: This case highlights the importance of obtaining a complete history and physical exam in patients who present with ocular inflammation, as extraocular manifestations of disease may be present. It also demonstrates the effectiveness of a multidisciplinary approach to evaluation and management of these patients, as both skin and eye involvement were successfully treated with adalimumab, a TNF-alpha inhibitor.

BackgroundThe Floating Sign is a histopathologic clue to the diagnosis of autoimmune sclerosing skin disorders such as morphea and interstitial granulomatous dermatitis (IGD). On the other hand, the "free-floating" sign has been associated with neoplasms, for example, dermatofibroma and interstitial mycosis fungoides. Herein, we report the Free Sign in sclerosing skin disorders.MethodsIn a case-control study, we applied detailed histopathologic definitions of Floating Sign and Free Sign to assess their presence in morphea, IGD, and other sclerosing disorders.ResultsFree Sign was present in most cases of morphea (46/55, 84%) and IGD (7/13, 54%) but not necrobiosis lipoidica (NL) (6/14, 42.8%) or sclerodermoid graft versus host disease (SGVHD) (2/7, 28.5%). The sensitivity and specificity of Free Sign for morphea versus other disorders was 84% and 56%, respectively. Floating Sign was not identified in most cases: NL (3/14, 21.4%), SGVHD (1/7, 14.2%), morphea (5/55, 9%), IGD (1/13, 7.7%). The diagnostic sensitivity of Floating Sign in morphea was 9%.ConclusionsThe Free Sign was present in most cases of morphea in our series and may represent a clue to the presence of evolving sclerosis. Free Sign may be seen in other sclerosing disorders. Technical artifact is a potential cause of a false-positive Free Sign.

The histopathology of sebaceous carcinoma (SBC) can mimic other skin neoplasms, including basal cell carcinoma (BCC).Therefore, diagnostic biomarkers are needed for a subset of cases. Normal sebaceous glands express PRAME (PRAME nuclearreceptor transcriptional regulator), a melanoma-associated biomarker.Donell et al. showed that PRAME has strong immunoreactivity with basaloid sebocytes in SBC. Ng et al. reported patchy cytoplasmic staining in the germinative sebocytes only.Sebaceous glands (H&E stain and PRAME stain)Objective: to evaluate the utility of PRAME immunohistochemistry as a diagnostic biomarker for SBC and its usefulness in the distinction of SBC from BCC.

Localized myxedema is a rare complication ofautoimmune thyroid diseases including the Hashimoto thyroiditis and Graves’ disease.Localized myxedema results from the accumulation of glycosaminoglycans in the dermis and subcutaneous layer of the skin.Fibroblast-produced hyaluronic acid is the mainglycosaminoglycan in localized myxedema. Localized myxedema presents bilaterally with a “boggy” thickening of the skin. Lesions classically have “waxy” swelling and induration.Myxedematous lesions of the skin most often appear on the anterior aspects of the legs and dorsum of the feet. They are often asymptomatic. Targeted treatment to cutaneous lesions is usually reserved for symptomatic cases.

African tick bite fever, resulting from Rickettsia africae inoculation, is endemic in sub-Saharan Africa. We present a United States traveler with African tick bite fever 5 days after she returned from a mission trip to Zimbabwe. The patient exhibited symptomatic hypotension in addition to more typical findings, including fever, fatigue, and a necrotic eschar. The diagnosis was supported by histopathological findings and the patient's symptoms rapidly resolved with oral doxycycline therapy. We believe this case represents the first African tick bite fever diagnosis associated with symptomatic hypotension. This case additionally serves as a reminder of the importance of evaluating patient travel history.

Pemphigus vulgaris (PV) is a rare immunobullous disease. Although it classically presents as generalized flaccid blisters affecting the skin and mucosae, atypical cases of PV can be diagnostically challenging. Herein, we report an underrecognized non-blistering manifestation of pemphigus vulgaris, which we call mounded and refractory keratoses (MARK). MARK presents as exuberant scaling plaques on the scalp, often in the skin of color. When MARK features are present, pemphigus vulgaris is prone to misdiagnosis, clinically and histopathologically, leading to delays in appropriate treatment. Specifically, biopsies from these patients may resemble acantholytic dyskeratosis, resulting in initial misdiagnosis. Thus, recognizing this presentation may aid physicians in diagnosing and monitoring the recurrence of pemphigus vulgaris.

Myxedema is a rare, cutaneous complication of autoimmune thyroid diseases that most often affects the anterior shins. Herein, we report a patient with a history of Graves disease and Hashimoto thyroiditis who presented with boggy, alopecic patches associated with scalp pruritus. Punch biopsies from these lesions showed increased interstitial mucin in the reticular dermis, consistent with localized myxedema. This report showcases a rare presentation of localized myxedema of the scalp, highlighting the diverse cutaneous manifestations of autoimmune thyroid diseases.

BackgroundAppropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests.MethodsRAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2.ResultsFor 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain."LimitationsThe study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded.ConclusionsAUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

Early diagnosis of melanoma is crucial to improved patient survival. Some melanomas can be difficult to diagnose from histopathology alone, and inter-observer disagreement among dermatopathologists in 15-35% of cases1 can delay diagnosis. PRAME (PReferentially expressed Antigen in MElanoma) is a tumorassociated antigen found to be overexpressed in human melanomas, making it a helpful tool in differentiating between benign vs. malignant melanocytic lesions. PRAME immunohistochemistry (IHC) has been used increasingly in dermatopathology practice, but there is currently no single biomarker or IHC stain that is diagnostic when used alone. S100A8 is a calcium-binding protein found to be highly expressed in certain inflammatory conditions and human cancers2,3. It was recently found by Kiuru et al. to be expressed by the keratinocyte microenvironment of melanomas but not that of melanocytic nevi4 , suggesting its role as a melanoma biomarker. The diagnostic utility of S100A8 IHC when compared to other commonly used melanoma biomarkers, including PRAME, has not yet been assessed. The objective of this study was to compare S100A8 immunohistochemistry with PRAME immunohistochemistry in benign and malignant melanocytic tumors to determine the diagnostic utility of S100A8.

Trichodysplasia spinulosa (TS) is a rare skin condition that occurs mainly in immunosuppressed patients. Although initially postulated to be an adverse effect of immunosuppressants, TS-associated polyomavirus (TSPyV) has since been isolated from TS lesions and is now considered to be the causative agent. Trichodysplasia spinulosa presents with folliculocentric papules with protruding keratin spines, most commonly on the central face. Trichodysplasia spinulosa can be diagnosed clinically, but the diagnosis can be confirmed with histopathological examination. Histological findings include the presence of hyperproliferating inner root sheath cells containing large eosinophilic trichohyaline granules. Polymerase chain reaction (PCR) can also be used to detect and quantify TSPyV viral load. Owing to the paucity of reports in the literature, TS is frequently misdiagnosed and there is no high-quality evidence to guide management. Herein, we present a renal transplant recipient with TS that did not respond to topical imiquimod but improved upon treatment with valganciclovir and reduction of the mycophenolate mofetil dose. Our case highlights the inverse relationship between immune status and disease progression in this condition.

Orf virus causes a self-limited infection in humans that resolves without scarring within 6-12 weeks. However, lesions in the immunocompromised can be progressive and disfiguring. The lesions frequently recur after treatment. To our knowledge, there are eleven published cases of these infections. We propose the name orf progressiva to call attention to this progressive, treatment-resistant entity. We present a 43-year-old male ranch owner with a history of renal transplantation who contracted an orf infection from his lamb. The infection recurred despite attempts at debridement, but achieved near complete resolution after treatment with imiquimod and valacyclovir. The histologic findings of orf progressiva are identical to the early stages of classic orf infection and are characterized by epithelial hyperplasia, intracytoplasmic eosinophilic inclusions, and an edematous, vascular dermis. There is no standard treatment for orf progressiva. Surgical excision has frequently resulted in rapid reoccurrence. Topical therapies such as imiquimod and cidofovir cream in combination with excision have been successful in some cases. Acyclovir or valacyclovir with imiquimod has been reported to be effective. Two patients achieved cure with imiquimod alone. We summarize these cases to prompt recognition of orf progressiva as a distinct clinical entity that requires treatment.

Ochronosis is a cutaneous disorder caused by the accumulation of phenols, either endogenously as homogentisic acid in patients with alkaptonuria (autosomal recessive disorder with deficiency of the enzyme homogentisic acid oxidase), or exogenously in patients using phenol products such as topical creams containing hydroquinone or the intramuscular application of antimalarial drugs. Exogenous ochronosis (EO) typically affects the face and was reported in patients with dark skin such as Black South Africans or Hispanics who use skin-lightening products containing hydroquinone for extended periods. Recently more cases have been reported worldwide even in patients with lighter skin tones, to include Eastern Indians, Asians, and Europeans. However, just 39 cases of EO have been reported in the US literature from 1983 to 2020. Here we present two cases; a 69 and a 45-year-old female who were seen for melasma, given hydroquinone 4% cream daily and tretinoin 0.05%. Both patients noticed brown spots on their cheeks, which progressively enlarged and darkened in color. The diagnosis of ochronosis was confirmed by characteristic histopathological features on the punch biopsy. Unfortunately, neither patient responded to multiple treatments (to include, tazarotene 0.1% gel and pimecrolimus ointment, topical corticosteroids, and avoidance of hydroquinone containing products). We also present a case of classic (endogenous) ochronosis in a patient with alkaptonuria to picture the histological similarities of these two entities. EO is an important clinical consideration because early diagnosis and treatment may offer the best outcome for this notoriously refractory clinical diagnosis.

Ochronosis is a cutaneous disorder caused by the accumulation of phenols, either endogenously as homogentisic acid in patients with alkaptonuria (autosomal recessive disorder with deficiency of the enzyme homogentisic acid oxidase), or exogenously in patients using phenol products such as topical creams containing hydroquinone or the intramuscular application of antimalarial drugs. Exogenous ochronosis (EO) typically affects the face and was reported in patients with dark skin such as Black South Africans or Hispanics who use skin-lightening products containing hydroquinone for extended periods. Recently more cases have been reported worldwide even in patients with lighter skin tones, to include Eastern Indians, Asians, and Europeans. However, just 39 cases of EO have been reported in the US literature from 1983 to 2020. Here we present two cases; a 69 and a 45-year-old female who were seen for melasma, given hydroquinone 4% cream daily and tretinoin 0.05%. Both patients noticed brown spots on their cheeks, which progressively enlarged and darkened in color. The diagnosis of ochronosis was confirmed by characteristic histopathological features on the punch biopsy. Unfortunately, neither patient responded to multiple treatments (to include, tazarotene 0.1% gel and pimecrolimus ointment, topical corticosteroids, and avoidance of hydroquinone containing products). We also present a case of classic (endogenous) ochronosis in a patient with alkaptonuria to picture the histological similarities of these two entities. EO is an important clinical consideration because early diagnosis and treatment may offer the best outcome for this notoriously refractory clinical diagnosis.

• Early diagnosis of melanoma is imperative for improved survival• The diagnosis of melanoma is based on histopathologic evaluation but lacks interobserver agreement in up to 10-25% of cases1 , showing the diagnostic difficulty in a subset of melanocytic neoplasms• Improved molecular diagnostic markers are needed, which may impact diagnosis and treatment recommendations2• p16, the protein product of CDKN2A, is a gene frequently mutated in melanomagenesis3,4• p16 immunohistochemistry (IHC) is becoming a commonly used marker for evaluating challenging melanocytic neoplasms• Prospective studies on the impact of p16 IHC on the diagnosis, diagnostic confidence, and treatment recommendations by dermatopathologists of melanocytic neoplasms are lacking

We report a patient with new-onset ulcerated granuloma annulare with concomitant involvement of B-cell leukemia. A granuloma annulare-like eruption with concomitant B cell chronic lymphocytic leukemia involvement in the skin is extremely rare, as only three cases have been previously reported in the literature to our knowledge. Given the rarity of ulceration in conventional granuloma annulare, it is possible this finding may serve as a diagnostic clue for underlying malignancy.

BACKGROUND: Dietary interventions are implicated in the development of atopic dermatitis, psoriasis, and acne. OBJECTIVE: To investigate the effect of diet and the bile acid (BA) receptors, such as TGR5 (Takeda G protein receptor 5) and S1PR2 (sphingosine-1-phosphate receptor 2) in the development of dermatitis. METHODS: C57BL/6 mice were fed a control diet (CD) or Western diet (WD) since weaning until they were 10 months old followed by analyzing histology, gene expression, and BA profiling. RESULTS: Mice developed dermatitis as they aged and the incidence was higher in females than males. Additionally, WD intake substantially increased the incidence of dermatitis. Cutaneous antimicrobial peptide genesS100A8, S100A9, and Defb4 were reduced in WD-fed mice, but increased when mice developed skin lesions. In addition, Tgr5 and TGR5-regulated Dio2 and Nos3 were reduced in WD intake but induced in dermatitic lesions. Trpa1 and Trpv1, which mediate itch, were also increased in dermatitic lesions. The expression of S1pr2 and genes encoding sphingosine kinases, S1P phosphatases, binding protein, and transporter were all reduced by WD intake but elevated in dermatitic lesions. Furthermore, dermatitis development increased total cutaneous BA with an altered profile, which may change TGR5 and S1PR2 activity. Moreover, supplementation with BA sequestrant cholestyramine reduced epidermal thickening as well as cutaneous inflammatory cytokines. CONCLUSION: In summary, activation of TGR5 and S1PR2, which regulate itch, keratinocyte proliferation, metabolism, and inflammation, may contribute to WD-exacerbated dermatitis with Th2 and Th17 features. In addition, elevated total BA play a significant role in inducing dermatitis and cutaneous inflammation.

BackgroundDietary interventions are implicated in the development of atopic dermatitis, psoriasis, and acne.ObjectiveTo investigate the effect of diet and the bile acid (BA) receptors, such as TGR5 (Takeda G protein receptor 5) and S1PR2 (sphingosine-1-phosphate receptor 2) in the development of dermatitis.MethodsC57BL/6 mice were fed a control diet (CD) or Western diet (WD) since weaning until they were 10 months old followed by analyzing histology, gene expression, and BA profiling.ResultsMice developed dermatitis as they aged and the incidence was higher in females than males. Additionally, WD intake substantially increased the incidence of dermatitis. Cutaneous antimicrobial peptide genesS100A8, S100A9, and Defb4 were reduced in WD-fed mice, but increased when mice developed skin lesions. In addition, Tgr5 and TGR5-regulated Dio2 and Nos3 were reduced in WD intake but induced in dermatitic lesions. Trpa1 and Trpv1, which mediate itch, were also increased in dermatitic lesions. The expression of S1pr2 and genes encoding sphingosine kinases, S1P phosphatases, binding protein, and transporter were all reduced by WD intake but elevated in dermatitic lesions. Furthermore, dermatitis development increased total cutaneous BA with an altered profile, which may change TGR5 and S1PR2 activity. Moreover, supplementation with BA sequestrant cholestyramine reduced epidermal thickening as well as cutaneous inflammatory cytokines.ConclusionIn summary, activation of TGR5 and S1PR2, which regulate itch, keratinocyte proliferation, metabolism, and inflammation, may contribute to WD-exacerbated dermatitis with Th2 and Th17 features. In addition, elevated total BA play a significant role in inducing dermatitis and cutaneous inflammation.

BackgroundDietary interventions are implicated in the development of atopic dermatitis, psoriasis, and acne.ObjectiveTo investigate the effect of diet and the bile acid (BA) receptors, such as TGR5 (Takeda G protein receptor 5) and S1PR2 (sphingosine-1-phosphate receptor 2) in the development of dermatitis.MethodsC57BL/6 mice were fed a control diet (CD) or Western diet (WD) since weaning until they were 10 months old followed by analyzing histology, gene expression, and BA profiling.ResultsMice developed dermatitis as they aged and the incidence was higher in females than males. Additionally, WD intake substantially increased the incidence of dermatitis. Cutaneous antimicrobial peptide genesS100A8, S100A9, and Defb4 were reduced in WD-fed mice, but increased when mice developed skin lesions. In addition, Tgr5 and TGR5-regulated Dio2 and Nos3 were reduced in WD intake but induced in dermatitic lesions. Trpa1 and Trpv1, which mediate itch, were also increased in dermatitic lesions. The expression of S1pr2 and genes encoding sphingosine kinases, S1P phosphatases, binding protein, and transporter were all reduced by WD intake but elevated in dermatitic lesions. Furthermore, dermatitis development increased total cutaneous BA with an altered profile, which may change TGR5 and S1PR2 activity. Moreover, supplementation with BA sequestrant cholestyramine reduced epidermal thickening as well as cutaneous inflammatory cytokines.ConclusionIn summary, activation of TGR5 and S1PR2, which regulate itch, keratinocyte proliferation, metabolism, and inflammation, may contribute to WD-exacerbated dermatitis with Th2 and Th17 features. In addition, elevated total BA play a significant role in inducing dermatitis and cutaneous inflammation.

Porokeratosis ptychotropica is a rare and commonly misdiagnosed subtype of porokeratosis involving the body folds. We present a 53-year-old man with systemic mastocytosis who presented with a pruritic, verrucous plaque in the gluteal fold that showed multiple cornoid lamellae on histopathologic evaluation, diagnostic of porokeratosis ptychotropica. Various treatments have been reported, including topical corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors, imiquimod, phototherapy, cryotherapy, or ablative laser therapy, but recurrences are common.

Condyloma lata, a cutaneous manifestation of secondary syphilis, usually appear as verrucous papules and plaques in the anogenital area. Involvement of the umbilicus is very uncommon. Thus, awareness of this presentation, along with appropriate history, physical exam, and laboratory testing may aid clinicians in prompt and accurate diagnosis. We describe a patient with an unusual presentation of condyloma lata on the umbilicus.

BackgroundA subset of melanomas carrying a B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E mutation, which is the most common targetable mutation in melanoma, arise in association with a melanocytic nevus that is also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of nevi positive for BRAF V600E have not been systematically documented.ObjectiveTo identify histomorphologic features correlating with BRAF V600E status in nevi.MethodsWe retrospectively identified melanocytic nevi from our laboratory reporting system. We performed a histomorphologic analysis and analysis of BRAF V600E expression by immunohistochemistry.ResultsThirteen nevi (14.8%) were negative and 76 (86.4%) were positive for BRAF V600E. The nevi positive for BRAF V600E were predominantly dermal (predominantly dermal growth in 55.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P = .01]) and showed a congenital growth pattern (congenital growth pattern in 51.3% of nevi positive for BRAF V600E and 15.4% of nevi negative for BRAF V600E [P = .02]). Compared with nevi negative for BRAF V600E, those that were positive for BRAF V600E often exhibited predominantly nested intraepidermal melanocytes, larger junctional nests, abrupt lateral circumscription, and larger cell size. Architectural disorder and inflammatory infiltrates were seen more often in nevi negative for BRAF V600E. BRAF sequencing of a subset of nevi confirmed the immunohistochemical results.LimitationsLimitations include the study's retrospective design and the small sample size of nevi negative for BRAF V600E.ConclusionsBRAF V600E is associated with distinct histomorphologic features in nevi. These features may contribute to improving the accuracy of classification and diagnosis of melanocytic neoplasms.

Traditional histology relies on processing and physically sectioning either frozen or formalin-fixed paraffin-embedded (FFPE) tissue into thin slices (typically 4-6 μm) prior to staining and viewing on a standard wide-field microscope. Microscopy using ultraviolet (UV) surface excitation (MUSE) represents a novel alternative microscopy method that works with UV excitation using oblique cis-illumination, which can generate high-quality images from the cut surface of fresh or fixed tissue after brief staining, with no requirement for fixation, embedding and histological sectioning of tissue specimens. We examined its potential utility in dermatopathology. Concordance between MUSE images and hematoxylin and eosin (H&E) slides was assessed by the scoring of MUSE images on their suitability for identifying 10 selected epidermal and dermal structures obtained from minimally fixed tissue, including stratum corneum, stratum granulosum, stratum spinosum, stratum basale, nerve, vasculature, collagen and elastin, sweat glands, adipose tissue and inflammatory cells, as well as 4 cases of basal cell carcinoma and 1 case of pseudoxanthoma elasticum deparaffinized out of histology blocks. Our results indicate that MUSE can identify nearly all normal skin structures seen on routine H&E as well as some histopathologic features, and appears promising as a fast, reliable and cost-effective diagnostic approach in dermatopathology.

BackgroundPyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood.ObjectiveUse data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology.MethodsTen PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR.ResultsAll PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype.LimitationsSmall sample size was the main limitation.ConclusionWe put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.

Fixed drug eruption (FDE) is an adverse drug reaction characterized by the development of well-circumscribed, round, dusky erythematous macules and plaques on cutaneous or mucosal surfaces. The reaction occurs on the same mucosal or cutaneous site with subsequent exposures to the offending drug. Although FDE usually manifests as a single lesion, in rare instances, more than one lesion may arise and this is referred to as a generalized eruption. Herein, we present a 31year-old man with history of cystic fibrosis who developed a generalized fixed drug eruption to piperacillin/tazobactam (Zosyn, Pfizer). We discuss our patient’s course and review causes and outcomes of generalized fixed drug eruptions in the literature.

As the list of anti-tumor immunotherapy agents and the list of cancers treated by these novel agents grow, a subset of patients are experiencing immune-related adverse events as a result of prolonged stimulation of the immune system. Many different immune related adverse events including colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis, and cutaneous reactions can result from blocking these inhibitory pathways. The full spectrum of cutaneous immune related adverse events secondary to checkpoint inhibitor therapy is still being defined. The reported varied presentations include lichenoid reactions and bullous pemphigoid, amongst others. We present a severe cutaneous reaction, a case of debilitating erosive lichenoid dermatitis. This case emphasizes both the wide range of possible cutaneous reactions and the potential severity of these reactions.

The original article was published on July19, 2017 and corrected on May 15, 2018. The revised version of the article includes a funding source for Dr. Maija Kiuru’s participation in this case report, awarded by the National Cancer Institute, National Institutes of Health grant K12CA138464. This change appears in the revised online PDF copy of this article.

Lichen planus follicularis tumidus (LPFT) is a rare subtype of lichen planus (LP) that has been most commonly described in middle-aged women. LPFT clinically manifests as recurrent cystic follicular nodules that preferentially involve the retroauricular area; concurrent classic LP lesions on the extremities and mucosal surfaces may also be present. Histologically, LPFT demonstrates epithelial-lined follicular cysts filled with orthokeratotic keratin surrounded by a dense lichenoid infiltrate. We present a case of a 67-year-old man with clinical and histopathologic findings consistent with LPFT and discuss differential diagnostic considerations for entities resembling LPFT. Lastly, treatment options for LPFT are reviewed.

BackgroundAcantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited.ObjectiveWe sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases.MethodsDefinitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records.ResultsOf 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented.LimitationsThis was a single-institution retrospective study from the United States.ConclusionsThe presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines.

ObjectiveWe describe the case of a patient with metastatic breast cancer who presented with eyelid margin thickening and madarosis more suggestive of sebaceous cell carcinoma than metastatic disease. Histopathology confirmed metastatic breast adenocarcinoma.Case reportA 59-year-old woman with a known history of metastatic breast carcinoma actively enrolled in a clinical trial presented with a thickened right upper eyelid margin with madarosis and without ulceration. Although the possibility of metastasis was considered, a biopsy was performed to ensure the patient did not have a primary eyelid malignancy such as sebaceous cell carcinoma given her immunocompromised state. Histopathology revealed metastatic breast adenocarcinoma.ConclusionsTo the authors' best knowledge, metastatic breast carcinoma presenting as eyelid margin thickening without ulceration has not previously been reported. Eyelid metastasis is rare, and this patient's clinical presentation was found to be unusual as well. It is important to establish metastatic disease even in a small focus such as the eyelid, as it may alter disease management.

A 60-year-old man with chronic lymphocytic leukemiadeveloped a deeply violaceous annular patchwith a halo of erythema on the right thigh duringhospitalization for neutropenic fever. Associatedsymptoms included chronic cough and fatigue.Bilateral lung opacities with hilar lymphadenopathywere noted on chest computed tomographyscan. Punch biopsy and tissue culture confirmeda diagnosis of secondary disseminated cutaneousmucormycosis. Although rare, physicians shouldinclude mucormycosis in the differential diagnosisof purpuric patches in immunosuppressed patients.Prompt skin biopsy and tissue culture may optimizethe success of treatment.

We present a rare case of acute febrile neutrophilicdermatosis, also known as Sweet syndrome,associated with recurrence of metastatic cervicalcancer. This report highlights similar reports andserves as an important reminder of the relationshipbetween Sweet syndrome and cervical cancer.Increasing awareness of Sweet syndrome assistsclinicians in recognizing characteristic findings andencourages evaluation of patients for new-onsetor recurrent neoplastic disease. Additionally, wediscuss the typical presentation of the syndrome, theproper workup and treatment, and a common pitfallencountered in the diagnosis of Sweet syndrome.

Acquired zinc deficiency can develop as a consequence of poor nutritional intake or from dependence on total parenteral nutrition. Acquired zinc deficiency dermatitis classically manifests with erosions and scaly plaques in a periorificial and acral distribution. We present a case of a woman on parenteral nutrition who presented with bullous acrodermatitis mimicking pemphigus foliaceus histopathologically. This case highlights clinical and histopathologic variants of zinc deficiency that may lead to a delay in diagnosis.

Sporotrichosis is a subcutaneous mycotic infection caused by Sporothrix schenckii, a group of common saprophytes of soil, plants, and organic debris. Disseminated forms may be seen in the setting of immunosuppression and are typically treated initially with intravenous lipidized amphotericin B. We report an unusual case of a 65-year-old woman who developed disseminated cutaneous sporotrichosis with extensive facial involvement in the absence of a known primary inoculation. Her cutaneous lesions completely resolved after treatment with intravenous posaconazole without amphotericin B.

The histopathologic characteristics of reactions caused by the many novel anticancer agents are under-recognized. We report a case of a 67-year-old female with locally advanced metastatic breast cancer, who initially presented with an extensive reticulated erythematous patch on the trunk caused by intravascular metastases confirmed by a skin biopsy. Owing to disease progression, she was started on ixabepilone, a mitotic inhibitor. While receiving ixabepilone, another skin biopsy was obtained and initially interpreted as extramammary Paget's disease. However, the biopsy showed metaphase arrest of numerous keratinocytes in the basilar and suprabasilar epidermis. Atypical epithelial cells were only present in the intravascular spaces similar to the initial biopsy. Given the temporal association between the initiation of ixabepilone therapy and the epidermal mitotic arrest, a diagnosis of chemotherapy reaction to ixabepilone was rendered. Ixabepilone is an analog of epothilone, a microtubule stabilizer causing mitotic arrest of the cell cycle approved for the treatment of metastatic and locally advanced treatment-resistant breast cancer. The demonstration of epidermal mitotic arrest caused by ixabepilone is without precedent. The case emphasizes the importance of considering a chemotherapy reaction in the histologic differential diagnosis of epidermal mitotic arrest in a cancer patient receiving chemotherapy.

[This corrects the article DOI: 10.1155/2014/840845.].

[This corrects the article DOI: 10.1155/2014/840845.].

Cyclosporine-induced sebaceous hyperplasia (SH) is a well-documented entity, occurring in up to 30% of renal transplant patients treated with cyclosporine and has also been reported to occur following heart or hematopoetic stem cell transplantation (HCST). Cyclosporine has a stimulatory effect on undifferentiated sebocytes, resulting in the clinical and histologic findings in these patients. Sebaceous hyperplasia most commonly presents as asymptomatic papules over the face, chest, or groin. Herein we describe a case of a 27-year-old man who developed facial sebaceous hyperplasia five months after completing cyclosporine therapy for cutaneous graft versus host disease (GVHD) following HSCT.

Eccrine spiroadenocarcinoma is an extremely rare malignant eccrine gland tumor which may masquerade as other more common malignancies such as poorly differentiated squamous carcinoma or metastatic breast cancer. We report a case of an ulcerated axillary skin lesion with bulky adenopathy in a 77 year-old female with a prior history of ipsilateral triple negative breast carcinoma. The clear transition of benign spiradenoma to malignant carcinoma was essential to establishing a definitive diagnosis and treatment plan.

Eccrine spiroadenocarcinoma is an extremely rare malignant eccrine gland tumor which may masquerade as other more common malignancies such as poorly differentiated squamous carcinoma or metastatic breast cancer. We report a case of an ulcerated axillary skin lesion with bulky adenopathy in a 77 year-old female with a prior history of ipsilateral triple negative breast carcinoma. The clear transition of benign spiradenoma to malignant carcinoma was essential to establishing a definitive diagnosis and treatment plan.

Coccidioidomycosis (AKA “Valley fever”) is a primary pulmonary infection via airborne spores released from coccidioides immitis in the soil. Reactive cutaneous eruptions resulting from the pulmonary infection are difficult to diagnose because skin biopsies do not contain the organism. We present an adolescent male with primary pulmonary C.immitis infection manifesting with biopsy proven subcorneal pustular dermatosis. Serological studies revealed increasingly positive titers for coccidioidomycosis and symptoms resolved promptly following initiation of systemic antifungal therapy. Our unique case presentation illustrates subcorneal pustular dermatosis as a reactive eruption owing to primary pulmonary coccidioidomycosis. An association between the two conditions warrants further investigation.

Importance: Granuloma annulare is typically a benign, self-limited disease. Atypical presentations have been reported in association with systemic disease, including malignancy. Such patients may require additional diagnostic studies to assess for underlying malignancy. We report a patient with extensive sporotrichoid granuloma annulare-like dermatitis in association with systemic B-cell lymphoma.Observations: An 83-year-old man with a three-year history of progressive sporotrichoid annular plaques and nodules on the arm developed ipsilateral retroauricular palpable lymphadenopathy, the latter consistent with B-cell lymphoma. Multiple skin biopsies of the plaques and nodules revealed granuloma annulare-like dermatitis. Lesions were unresponsive to intralesional and intramuscular corticosteroids, antibiotics, and antifungal agents, but rapidly improved following initiation of rituximab to treat his underlying lymphoma.Conclusions and Relevance: Atypical presentations of granuloma annulare including granuloma annulare-like dermatitis warrant evaluation for systemic malignancy in a subset of patients.

Importance. Cutaneous and systemic plasmacytosis are rare conditions of unknown etiology with characteristic red-brown skin lesions and a mature polyclonal plasma cell infiltrate within the dermis. Perineural plasma cell infiltrates may be a histologic clue to the diagnosis of cutaneous plasmacytosis. Observations. Our patient had a five-year history of persistent reddish-brown plaques on the neck and trunk without systemic symptoms. Histologic examination showed dermal perivascular and perineural plasma cells with excess lambda light chain expression. Due to decreased quality of life caused by his skin lesions, he was placed on a chemotherapeutic regimen with bortezomib. Conclusions and Relevance. The patient was diagnosed with cutaneous plasmacytosis based on classic histopathology results with a recently characterized pattern of perineural involvement. Bortezomib therapy was initiated to manage his skin eruption, which has not been previously described as a treatment for this chronic condition.

Importance. Cutaneous and systemic plasmacytosis are rare conditions of unknown etiology with characteristic red-brown skin lesions and a mature polyclonal plasma cell infiltrate within the dermis. Perineural plasma cell infiltrates may be a histologic clue to the diagnosis of cutaneous plasmacytosis. Observations. Our patient had a five-year history of persistent reddish-brown plaques on the neck and trunk without systemic symptoms. Histologic examination showed dermal perivascular and perineural plasma cells with excess lambda light chain expression. Due to decreased quality of life caused by his skin lesions, he was placed on a chemotherapeutic regimen with bortezomib. Conclusions and Relevance. The patient was diagnosed with cutaneous plasmacytosis based on classic histopathology results with a recently characterized pattern of perineural involvement. Bortezomib therapy was initiated to manage his skin eruption, which has not been previously described as a treatment for this chronic condition.

Although the dermatologic community rarely uses “Weber-Christian Disease” as a diagnosis, it still appears in the internal medicine literature.  Herein we present a patient with recurrent cutaneous and subcutaneous nodules who was initially treated with aggressive immunosupression for a presumptive diagnosis of Weber-Christian Disease.  After more than a decade the patient was diagnosed with cutaneous Mycobacterium chelonea.  This case is an excellent example of the difficulty in diagnosing mycobacterial infections and underscores the importance of having a high suspicion for infectious etiologies for unresponsive cutaneous eruptions in patients on immunosuppressive medications.

Necrolytic acral erythema (NAE) is a rare cutaneous sign of hepatitis C virus infection and has recently been linked to zinc deficiency. It presents as well-demarcated erythematous plaques in a sandal-like distribution on the dorsal feet with psoriasiform epidermal hyperplasia on histology. Our patient reported a 9-month history of progressive bilateral lower extremity erythema, swelling, erosions, and nail dystrophy that failed to improve despite multiple courses of antibiotics for presumed lower extremity cellulitis. Serum studies revealed zinc deficiency. This case supports the association of NAE with both HCV infection and zinc deficiency and highlights the pitfalls in the diagnosis of chronic unrecognized NAE. Suspected cases of NAE should prompt evaluation for underlying HCV and zinc deficiency to avoid treatment delay and associated complications.

The dimorphic fungus Sporothrix schenckii commonly causes localized cutaneous disease with lymphocutaneous distribution. However, disseminated sporotrichosis occurs predominantly in immunocompromised patients.  We report a case of disseminated cutaneous sporotrichosis in a patient with newly diagnosed HIV with a CD4 count of 208.  The patient presented with multiple cutaneous and subcutaneous nodules as well as fever and malaise. Tissue culture and skin biopsy confirmed the diagnosis of sporotrichosis. He was started on itraconazole 200mg twice a day with rapid resolution of fever along with cessation of the development of new lesions.

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine neoplasm of possible viral origin and is known for its aggressive behavior. The incidence of MCC has increased in the last 15 years. Merkel cell carcinoma has the potential to metastasize, but rarely involves the central nervous system. Herein, we report three consecutive surgical cases of MCC presenting at a single institution within 1 year. We used intracavitary BCNU wafers (Gliadel(®)) in two cases. Pathological features, including CK20 positivity, consistent with MCC, were present in all cases. We found 33 published cases of MCC with CNS involvement. We suggest that the incidence of neurometastatic MCC may be increasing, parallel to the increasing incidence of primary MCC. We propose a role for intracavitary BCNU wafers in the treatment of intra-axial neurometastatic MCC.