Daniel D. Bennett

Biopsy Use in Skin Cancer Diagnosis: Comparing Dermatology Physicians and Advanced Practice Professionals

Author Affiliations: Department of Dermatology, University Clinic of Navarra, Pamplona, Navarra, Spain (Redondo, Gímenez de Azcarate, Aguado); Research Support Service, University Clinic of Navarra, Pamplona, Navarra, Spain (Núñez-Córdoba); Department of Preventive Medicine and Public Health, Medical School, University of Navarra, Pamplona, Navarra, Spain (Núñez-Córdoba); Area of Cell Therapy, University Clinic of Navarra, Pamplona, Navarra, Spain (Andreu, García-Guzman, Prosper).

Possible Association of Cutaneous Rosai-Dorfman Disease and Chronic Crohn Disease A Case Series Report

IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (P<.001). CONCLUSIONS AND RELEVANCE Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease.

Insulinoma-associated 1: A novel nuclear marker in Merkel cell carcinoma (cutaneous neuroendocrine carcinoma)

Merkel cell carcinoma (MCC) is a rare, clinically aggressive, cutaneous neuroendocrine (NE) neoplasm. As a tumor with small, round, blue cells, the histologic differential diagnosis for MCC can include melanoma, metastatic small cell carcinoma (SCC), nodular hematopoietic tumors, basal cell carcinoma (BCC), atypical variants of squamous carcinoma and the uncommon occurrence of primary cutaneous Ewing sarcoma. In cases with atypical histology or without the classic immunophenotype, the diagnosis can be challenging. Ultimately, immunohistochemistry (IHC) is essential to the definitive diagnosis of MCC and in difficult cases, the diagnosis may hinge entirely on the immunophenotype of the tumor cells. Insulinoma‐associated 1 (INSM1) is a transcription factor expressed in tissues undergoing terminal NE differentiation. As a nuclear protein tied to both differentiation and the cell cycle, INSM1 may offer additional utility in comparison to traditional, cytoplasmic markers of NE differentiation.

A cystic growth on the lower eyelid: a presentation of two cases.

Case 1 was a 62-year-old man with a history of hypertension and hyperlipidemia that presented with a translucent 8 mm papule on the medial aspect of his left lower eyelid present for nine months (Fig. 1). Previous treatments included a course of doxycycline without improvement. Case 2 was a 57-year-old man with a history of hypertension that presented with an asymptomatic 4 mm papule on the right lower eyelid present for two years.

Improving the Histologic Characterization of Burn Depth

Visual assessment of burn wound appearance is the standard of care to determine the depth of thermal injury but often incorrectly predicts wound healing potential. Histologic evaluation of hematoxylin and eosin (H&E) stained burn tissue is prone to subjectivity and is challenging for the novice. Lactate dehydrogenase (LDH) staining may offer a simplified and consistent technique to identify burn tissue viability.

The wart on fire.

To the Editor , We read with great interest the July 2015 article by de Andrade et al. entitled, ‘Oral verruciform xanthoma: a clinicopathologic and immunohistochemical study of 20 cases’ and would like to propose a unique descriptor that vividly illustrates a histopathologic hallmark of these lesions. While not hooks for hanging hats, the catchy colorful sayings that are common in dermatopathology and dermatology add character to our descriptive practice and aid in the education of the newly initiated. Here, we suggest a picturesque phrase to describe a feature that we venture many have noticed but that attention has forgotten. We propose ‘wart on fire’ to describe the blazingly eosinophilic keratin characteristic of the verruciform xanthoma. Verruciform xanthoma is an uncommon papillary or ‘cauliflower-like’ solitary nodule or plaque typically occurring on oral mucosa or the scrotal, vulvar and perianal regions. Clinically, it may be difficult to differentiate from squamous papilloma, verruca vulgaris, condyloma acuminatum and verrucous leukoplakia. Histopathologically, they are chiefly described as having verrucous acanthosis with deep crypts and parakeratotic keratin displaying an orange–pink hue as well as numerous foamy lipid-laden macrophages (xanthoma cells) filling the papillary dermis.1 The rub here, however, is that these ‘numerous’ foamy macrophages may not always be so numerous and from low power may be indistinct.2 That being so, it is often the consistent low-power characteristic appearance of orangeophilic to blazingly eosinophilic keratin on a verrucous lesion giving this characteristic ‘wart on fire’ appearance that prompts us to look closer at the papillary dermis (Fig. 1). This descriptive phrase is catchy and calls attention to the key low-power histopathologic characteristics of the lesion being verruciform Fig. 1. Verruciform xanthoma (original magnification ×200, H&E). The low-power appearance of a verrucous lesion with blazingly eosinophilic keratin beckons our attention to the inconspicuous xanthoma cells within the papillary dermis. This biopsy material shows verrucous acanthosis of the epidermis, with a strikingly bright pink character of the superficial keratin. The papillary dermis is filled with expanded superficial vessels, aggregations of pale xanthoma cells and a superficial lymphocytic infiltrate.

Integrating virtual dermatopathology as part of formative and summative assessment of residents: a feasibility pilot study.

To the Editor , We are writing in response to the innovative articles published by Mooney et al. and Brick et al. about employing virtual dermatopathology (DP) for clinical use and pathology education.1,2 Because the diagnostic equivalence between virtual and conventional microscopy has been supported by comparative studies, virtual DP has been implemented in the certifying examination for dermatology.3 The literature has focused on the implementation of this technology in postgraduate education but with mixed results. Brick et al. noted no preference for glass or virtual slides among their residents,1 in contrast to Koch et al. who found that residents preferred virtual DP to conventional slides as a regular study aid but not as a testing media.3 Given the rising utilization of virtual DP on certifying examinations and differing resident attitudes about this technology for formative (e.g. low stakes pop quiz, self-assessment) vs. summative (e.g. high stakes exam) purposes, we conducted a study to explore the feasibility and acceptability of implementing this technology for residents for both formative and summative purposes.1,3 This research project was conducted under the University of Wisconsin-Madison Minimal Risk Institutional Review Board (IRB) approval number M-2012-0466. Dermatology and pathology residents at the University of Wisconsin-Madison consented to participate. Our prior curriculum consisted of self-directed reading with review of corresponding glass slides followed by ‘sign out’ time with a dermatopathologist. A pretest anonymous survey was administered to assess current and ‘ideal’ DP study habits as well as perceptions of virtual DP (free-text and Likert scale ratings). Next, residents completed a 21-item multiple-choice, single correct answer, self-assessment quiz that tested recognition of inflammatory and neoplastic histopathology using whole-slide scanned images (Aperio Technologies, Inc, Vista, CA, USA) on a proprietary, server-based learning platform (University of Wisconsin, Madison, USA). Residents were permitted to take the test at any time over a 2-week period and at any location using the computer, operating system and internet browser of their choice. A posttest survey was administered that assessed difficulties experienced during the test as well as perceptions of virtual DP. Scores were linked to survey responses by a study coordinator and given as aggregated, deidentified data to the investigators. A statistician (VR) performed chi-square test for comparison analysis. Poststudy semistructured debriefing sessions with dermatology and pathology residents were conducted to discuss the study results and obtain further qualitative data. JE and RG performed qualitative analysis using open coding and constant comparative method of free-text survey items and the poststudy debriefing sessions.4 Twenty-seven residents submitted a pretest survey; 20 residents completed the self-assessment virtual DP quiz (mean completion time 85.7 min); 18 residents completed the quiz and both pretest and posttest surveys. Only nine residents who completed the pretest survey

Eosinophil-rich syphilis: a report of four cases

The differential diagnosis for eosinophil‐rich skin lesions often includes a drug reaction, allergic contact dermatitis and rarely, response to a helminth infection. However, many unrelated entities, such as infections, neoplasms and inflammatory dermatoses, can have a prominent eosinophilic infiltrate. Syphilis is classically associated with plasma cells, but other patterns of inflammation have been reported, including ulcerative, granulomatous and eosinophil‐rich. Classic teaching might indicate that the presence of eosinophils argues against a diagnosis of syphilis. We present four cases of secondary syphilis with increased eosinophils, ranging from 8 to >200 eosinophils per 10 high‐power fields (×400 magnification). Patient 1 had lesions on the penis and scrotum, with greater than 200 eosinophils per 10 high‐power fields. Patient 2 had lesions on the back, with 150 eosinophils per 10 high‐power fields. Patient 3 had lesions on the bilateral arms, with 8 eosinophils per 10 high‐power fields. Patient 4 had lesions involving the anus, with 17 eosinophils per 10 high‐power fields. These cases highlight that the presence of an eosinophil‐rich infiltrate on skin biopsy should not exclude syphilis from the differential diagnosis.

Multispectral Imaging Approach to the Diagnosis of a CD20+ Cutaneous T-cell Lymphoproliferative Disorder: A Case Report.

Abstract:Expression of the pan B-cell marker CD20 by T-cell lymphoproliferative disorders is exceedingly rare. We present a 52-year-old man with a unilesional cutaneous CD20+ T-cell lymphoproliferative disorder. Multispectral imaging analysis of CD3–CD20 double-stained lesional tissue sections allowed (1) the visualization of double-positive T lymphocytes in situ with sensitivity superior to that of conventional immunohistochemistry and (2) the quantitative assessment of marker coexpression. Here, 23% of CD3+ signals in the patients lesion were also CD20+, whereas 38% of CD20 + signals were also CD3+. In contrast, both parameters were below 1% in the tonsil control. Overall, the percentage of double-positive cells in lesional skin was 35%, although only 0.4% of such cells were detected in the tonsil. This is the first demonstration of aberrant CD20 expression by skin-infiltrating T cells using multispectral imaging.

An eruption of angiokeratomas in the setting of enoxaparin injections.

References 1 Chan LS, Ahmed AR, Anhalt GJ, et al. The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol 2002; 138: 370–379. 2 Chan LS. Ocular and oral mucous membrane pemphigoid (cicatricial pemphigoid). Clin Dermatol 2012; 30: 34–37. 3 Egan CA, Lazarova Z, Darling TN, et al. Anti-epiligrin cicatricial pemphigoid and relative risk for cancer. Lancet 2001; 357: 1850–1851. 4 Oyama N, Setterfield JF, Powell AM, et al. Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity. Br J Dermatol 2006; 154: 90–98. 5 Setterfield J, Theron J, Vaughan RW, et al. Mucous membrane pemphigoid: HLA-DQB1*0301 is associated with all clinical sites of involvement and may be linked to antibasement membrane IgG production. Br J Dermatol 2001; 145: 406–414. 6 Tsuruta D, Kanwar AJ, Vinay K, et al. Clinical and immunologic characterization in 26 Indian pemphigus patients. J Cutan Med Surg 2013; 17: 321–331. 7 Taylor J, McMillan R, Shephard M, et al. World Workshop on Oral Medicine VI: a systematic review of the treatment of mucous membrane pemphigoid. Oral Surg Oral Med Oral Pathol Oral Radiol 2015; 120: 161– 171e20.