The ñ sign in this specimen is formed by the sum of the fragmentation and separation of the laminar parakeratotic stratum corneum (top) and hyperplasia with regular elongation of the rete ridges (bottom) (hematoxylin-eosin, original magnification ×200).
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Camporro ÁF, Roncero-Riesco M, Revelles-Peñas L, et al. The ñ Sign: A Visual Clue for the Histopathologic Diagnosis of Psoriasis. JAMA Dermatol. 2022;158(4):451–452. doi:10.1001/jamadermatol.2022.0015
The clinical and histopathologic diagnosis of inflammatory skin disorders can be challenging. Psoriasis, the paradigm for the psoriasiform reaction pattern, is heterogeneous and dynamic. Therefore, classical histologic results can vary markedly throughout the clinical evolution of psoriasis. Skin biopsies of mature psoriatic lesions often show regular (psoriasiform) epidermal hyperplasia, elongation of the rete ridges with a thin suprapapillary epidermis, dilated vessels in the upper dermis, and hyperkeratosis with parakeratotic mounds that commonly appear to be cracked and detached after sample processing.1
We have observed that the union of 2 well-established histologic criteria for psoriasis, (1) fragmentation and separation of the laminar parakeratotic stratum corneum and (2) epidermal hyperplasia with elongation of the rete ridges, which can resemble the lowercase ñ (pronounced “eɲe”) in the modern Latin alphabet (Figure). We refer to the sum of these 2 histologic criteria as the “ñ sign,” in which (1) the tilde represents a wavy laminar, parakeratotic, and separated stratum corneum and (2) the n denotes epidermal hyperplasia and regularly elongated rete ridges. Here, we describe the potential use of the ñ sign as a visual clue for the diagnosis of psoriasis in clinical practice.
This study was approved by the Hospital Universitario de Cabueñes Ethics Committee and by the Instituto de Investigación Biomédica de Salamanca. Written informed consent was obtained from patients at the time the biopsies and clinical photographs were taken. The study followed the Standards for Reporting Qualitative Research (SRQR) reporting guideline.
To assess the usefulness of the ñ sign in daily clinical practice, we randomly selected lesion biopsy specimens from patients in our hospital data bank (on November 1, 2021) with a previous histologic diagnosis of psoriasis (patient group) or a previous diagnosis of an inflammatory skin disorder other than psoriasis (control group). Biopsy specimens with diseases that are not usually considered frequently within the differential diagnosis of psoriasis were excluded. Two observers analyzed the biopsy specimens simultaneously in random order to determine the presence or absence of the ñ sign. Statistical analysis was performed with IBM SPSS Statistics software (version 21).
Biopsy specimens from 136 patients were analyzed. Of these patients, 67 had a previous histologic diagnosis of psoriasis and 69 had a previous diagnosis of an inflammatory skin disorder other than psoriasis (control group; 29 with eczema, 11 with pityriasis lichenoides, 12 with pityriasis rosea, and 17 with chronic lupus erythematous). The ñ sign was present in lesion biopsy specimens from 54 of 67 patients with psoriasis (80.6%) and from 1 of 69 patients in the control group (1.5%) (Table).
In dermatopathology, the diagnostic process is based on the recognition of histologic patterns and their correlation with clinical data. Visual recognition in dermatology and dermatopathology is often instantaneous, as the brain of experienced physicians can process large amounts of information rapidly and effortlessly. This cognitive phenomenon is part of so-called system 1 (automatic, effortless, unconscious, experience-based) thinking.2
When first-sight recognition is not possible, system 2 (slow, conscious, effortful, consequential) thinking is activated. In these cases, mnemonics are useful.3 There are visual clues (so-called pearls or tips) that can facilitate reaching a final diagnosis in dermatopathology.4,5 These mnemonic devices are often easily recognizable at first glance, even for individuals with less experience, and they can be extremely useful in daily clinical practice.
A limitation of this study is that it was a single-center study with a limited number of cases and controls. More extensive studies are required to determine the sensitivity and specificity of the ñ sign as well as its predictive values.
In this qualitative study, we propose the ñ sign as a visual clue for the histopathologic diagnosis of psoriasis based on the sum of 2 well-characterized histologic criteria. These findings are not specific to psoriasis and can be observed separately in other inflammatory skin conditions such as pityriasis lichenoides or subacute eczema.1,6 However, the sum of both criteria (ie, the ñ sign) is a distinctive histologic finding of psoriasis.
In conclusion, the ñ sign may be a useful mnemonic device for dermatology and pathology residents and even for experienced physicians in distinguishing between psoriasis and other inflammatory skin disorders.
Accepted for Publication: December 29, 2021.
Published Online: February 23, 2022. doi:10.1001/jamadermatol.2022.0015
Corresponding Author: Ángel Fernández Camporro, MD, Department of Dermatology, Hospital Universitario de Cabueñes, 395 Los Prados, 33394 Gijón, Spain (firstname.lastname@example.org).
Author Contributions: Dr Fernández Camporro had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: Fernández Camporro, Revilla Nebreda, Santos-Briz Terrón.
Drafting of the manuscript: Fernández Camporro, Revelles-Peñas, Estenaga.
Critical revision of the manuscript for important intellectual content: Roncero-Riesco, Revilla Nebreda, Díaz de la Pinta, Santos-Briz Terrón.
Statistical analysis: Fernández Camporro.
Administrative, technical, or material support: Revelles-Peñas, Santos-Briz Terrón.
Supervision: Roncero-Riesco, Revelles-Peñas, Revilla Nebreda, Díaz de la Pinta, Santos-Briz Terrón.
Other (grammatical and English language corrections): Estenaga.
Conflict of Interest Disclosures: None reported.