Assessing T-cell receptor clonality by next-generation sequencing in atypical cutaneous lymphoid infiltrates and cutaneous T-cell lymphoma: A scoping review.

The diagnosis of cutaneous T-cell lymphoma (CTCL) remains challenging. Demonstration of a clonal T-cell population using T-cell receptor (TCR) gene rearrangement studies by next-generation sequencing (NGS) has been explored in several studies. This review summarizes the current literature on NGS-based sequencing methods for the assessment of TCR clonality in the evaluation of atypical cutaneous lymphoid infiltrates and CTCL on behalf of the American Society of Dermatopathology Appropriate Use Criteria Committee (lymphoproliferative subgroup). PubMed was searched for relevant articles, including CTCL and NGS, for clonality from 1967 to 2022. Thirteen studies were included in the analysis. The skin was the most commonly assayed compartment with TCR NGS. Sensitivity for TCR NGS in the skin ranged between 69% and 100%, compared to 44%-72% for polymerase chain reaction (PCR)-capillary electrophoresis. Specificity for TCR NGS in the skin ranged from 86% to 100%, compared to 77%-88% for PCR capillary electrophoresis. TCR NGS was also reported to have potential prognostic value in CTCL and can also be used to detect relapse and/or minimal residual disease after treatment.

Comparison of S100A8 and PRAME as biomarkers for distinguishing melanoma from melanocytic naevus: a case-control analysis.

BACKGROUND: S100A8 is a melanoma biomarker expressed in the melanoma-associated epidermal keratinocytes, but its diagnostic utility has not been compared with other biomarkers, including PRAME. OBJECTIVES: To compare the utility of S100A8 and PRAME immunohistochemistry (IHC) in the differential diagnosis of melanoma and naevi in a case-control study. METHODS: A 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. RESULTS: The 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%). CONCLUSIONS: S100A8 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.

Eosinophils in psoriasis: A systematic review and meta-analysis introducing a study quality assessment tool for diagnostic pathology studies.

BACKGROUND: The histopathologic features of psoriasis are well-documented, but recent studies have highlighted atypical features, such as eosinophils, in clinically confirmed cases. METHODS: A systematic review exploring eosinophils in psoriasis was performed. A novel quality assessment tool (SQAT-Path) we designed for cross-sectional pathology studies was employed. RESULTS: Five studies (N = 218) were identified. The pooled prevalence of dermal eosinophils in psoriasis was 46% (95% confidence interval, 0.27-0.66). The prevalences of 1 to 5 lesional eosinophils (24%) compared to >5 eosinophils (26%) were similar. There was no association between eosinophils and prior treatment. There was also no association between eosinophils and spongiosis. In SQAT-Path, studies scored between 9 and 18 (out of a maximum of 27: "fair" to "good"), consistent with the ratings using other assessment tools. CONCLUSION: Eosinophils were found in approximately half of systematically studied and published cases of psoriasis. When present, their quantity is variable, with the likelihood of having greater than 5 eosinophils in a biopsy section comparable to having between 1 and 5. Greater than 5 eosinophils, as an isolated finding, would not be typical of psoriasis, but should not preclude its diagnosis without considering the overall histologic context.

Multicenter prospective blinded melanoma detection study with a handheld elastic scattering spectroscopy device.

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 device's high sensitivity and NPV for the detection of melanoma suggest the device may be a useful adjunctive, point-of-care tool for melanoma detection.

Localized calcium oxalate crystals in primary cutaneous aspergillosis.

Select Aspergillus species can produce oxalate as a fermentation byproduct, which may react with calcium ions to produce insoluble calcium oxalate crystals in tissues. These crystals are frequently associated with pulmonary Aspergillus infections, yet are rarely described in primary cutaneous aspergillosis. Herein, we report the presence of calcium oxalate crystals detected on cutaneous specimens from primary cutaneous Aspergillus niger and Aspergillus fumigatus infections in an immunocompromised, premature infant. No metabolic sources of oxalosis were found.

The Free Sign in morphea and other sclerosing disorders: A clue to the presence of early sclerosis?

BACKGROUND: The 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. METHODS: In 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. RESULTS: Free 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%. CONCLUSIONS: The 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.

Localized alopecic myxedema of the scalp.

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.

Successful treatment of necrobiosis lipoidica and associated retinal vasculitis with tumor necrosis factor (TNF)-alpha inhibitor.

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 patient's 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.

The role of eosinophils in the differential diagnosis of inflammatory skin diseases.

Eosinophils are known to be present in inflammatory skin diseases, but their diagnostic utility is not well established. Upon review of the published status of lesional eosinophils, several categories were identified. 1) Lesional eosinophils highly characteristic such that, in their absence, the pathologist may question the diagnosis. These include arthropod bite reactions and scabies, urticarial dermatitis, and other eosinophilic dermatoses. 2) Lesional eosinophils rare or absent, such that, in their presence, the pathologist may question the diagnosis. These include pityriasis lichenoides, graft versus host disease, and connective tissue disorders. 3) Lesional eosinophils variable and, while in some cases expected, are not required for diagnosis. These include drug reactions, atopic dermatitis and allergic contact dermatitis. 4) Lesional eosinophils variable and not expected but may be seen to a limited extent. These include lichen planus and psoriasis.

When a travel bug gets you down: severe, hypotensive African tick bite fever and response to therapy.

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.

IgA Vasculitis in the Setting of Biologic Therapy for Psoriasis and Recurrent Cutaneous Methicillin-Resistant Staphylococcus aureus Colonization.

IgA vasculitis is a form of cutaneous small-vessel leukocytoclastic vasculitis (LCV) that has various triggers, including anti-tumor necrosis factor (TNF) α therapy. As the use of more targeted biologic therapies such as the IL-17 inhibitor secukinumab increases, so do reports of associated adverse events. Herein, we describe an uncommon case of IgA vasculitis in a man undergoing biologic therapy with adalimumab and secukinumab for psoriasis with recurrent cutaneous methicillin-resistant Staphylococcus aureus (MRSA) colonization. A review of the current literature also is provided.

Pilot study of fluorescence imitating brightfield imaging for rapid, slide-free dermatopathology.

BACKGROUND: Fluorescence imitating brightfield imaging (FIBI) is a novel alternative microscopy method that can image freshly excised, non-sectioned tissue. We examine its potential utility in dermatopathology by examining readily available specimens embedded in paraffin blocks. METHODS: Nine skin samples embedded in paraffin blocks were superficially deparaffinized using xylene and ethanol and stained with H&E. FIBI captured tissue surface histopathology images using simple microscope optics and a color camera. We then applied deep-learning-based models to improve resemblance to standard H&E coloration and contrast. FIBI images were compared with corresponding standard H&E slides and concordance was assessed by two dermatopathologists who numerically scored epidermal and dermal structure appearance and overall diagnostic utility. RESULTS: Dermatopathologist scores indicate that FIBI images are at least equivalent to standard H&E slides for visualizing structures such as epidermal layers, sweat glands, and nerves. CONCLUSION: Images acquired with FIBI are comparable to traditional H&E-stained slides, suggesting that this rapid, inexpensive, and non-destructive microscopy technique is a conceivable alternative to standard histopathology processes especially for time-sensitive procedures and in settings with limited histopathology resources.