Unmasking Hidden Clues in Cutaneous Viral Infections - Histopathological Insights Into Keratinocytic Features of Herpes Simplex Virus - Varicella Zoster Virus - and Molluscum Contagiosum

Sep 30, 2026

Objective: explore keratinocytic changes in cutaneous viral infections caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and molluscum contagiosum (MC), emphasizing diagnostic clues in cases lacking typical findings. Methods: conduct a retrospective analysis of 14 HSV/VZV cases (Jan 2000–Oct 2023) and 22 MC cases (Jan 2013–Dec 2015). Results: adjacent keratinocytes show distinctive histopathological features in HSV/VZV cases, and MC shows a characteristic keratinocyte appearance around molluscum bodies. Conclusion: keratinocytic alterations can guide additional studies for accurate diagnosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

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Abstract

Objective

Methods

Results

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Introduction

Materials and Methods

Materials and methods

Study design and data collection

Review began 06/24/2025 Review ended 07/30/2025 Published 12/10/2025 © Copyright 2025 Platero Portillo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CCBY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited. DOI: 10.7759/cureus.98882 Open Access Original Article Unmasking Hidden Clues in Cutaneous Viral Infections: Histopathological Insights Into Keratinocytic Features of Herpes Simplex Virus, Varicella Zoster Virus, and Molluscum Contagiosum Tania Platero Portillo 1, Dilshad Dhaliwal 1, Sepideh Mehravaran 2 , Megan Ketcham 3, Julie Wu 4, Nisha Ramani 1 , Abdul Hafeez Diwan 1 1. Department of Pathology and Immunology, Baylor College of Medicine, Houston, USA 2. Department of Pathology, Moffitt Cancer Center, Tampa, USA 3. Department of Pathology, Houston Methodist Hospital, Houston, USA 4. Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, USA Corresponding author: Tania Platero Portillo, [taniaplatero@gmail.com](taniaplatero@gmail.com) Abstract Objective: This case study aimed to explore primarily the keratinocytic changes of cutaneous viral infections caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and molluscum contagiosum (MC) . The focus was on identifying features and diagnostic clues in cases without typical findings. Methods: A retrospective analysis encompassing 14 HSV/VZV cases (January 2000 to October 2023) and 22 MC cases (January 2013 to December 2015) was conducted. Results: In HSV/VZV cases, 71%(10 of 14) exhibited distinctive histopathological features in the adjacent keratinocytes, including nucleolar enlargement and atypical features. Immunohistochemical studies in 40% of the cases (4 of 10) revealed positive staining in cells with cytopathic changes and negative staining in adjacent atypical keratinocytes. Conversely, MC cases consistently demonstrate an enlarged, stuffed"pregnant seahorse appearance " of keratinocytes around molluscum bodies. Conclusion: This study highlights the diagnostic significance of keratinocytic changes in these viral infections, allowing pathologists to perform additional studies to make the correct diagnosis in cases where typical viral changes are not readily apparent. Categories: Pathology, Dermatology Keywords: cutaneous viral infections, hsv, molluscum contagiosum, viral infections of the skin, vzv Introduction Dermatological manifestations of viral infections, particularly those caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and molluscum contagiosum (MC), often present with characteristic clinical features that aid in their diagnosis [1, 2]. For HSV/VZV infections, it is well-documented that specific patient groups, such as those with compromised immune systems, may exhibit atypical presentations, posing challenges that require supplementary testing and histopathological examination for precise diagnosis [3, 4]. Skin biopsies of HSV/VZV infections reveal comparable histopathological findings, making it impossible to definitively distinguish between HSV and VZV infections based on morphology alone. Pathologic features include multinucleation, nuclei with a ground-glass or steel-gray appearance, eosinophilic intranuclear inclusions (Cowdry A bodies), marginated chromatin [1, 3, 5], and the presence of eosinophils [6] . Although typically straightforward, the confirmatory features of cutaneous HSV/VZV infection may not consistently appear in biopsy specimens. The causative agent of MC infection is the molluscum contagiosum virus (MCV), a double-stranded DNA virus belonging to the Poxviridae family, exclusive to humans as hosts. MCV infects the epidermis and undergoes replication in the cytoplasm of cells, with an incubation period ranging between two and six weeks [7, 8]. MC is a naturally resolv

FAQs

What was the study’s primary objective?

To explore primarily the keratinocytic changes seen in cutaneous viral infections caused by HSV, VZV, and molluscum contagiosum, especially when typical findings are absent.

How were HSV/VZV and MC cases selected?

The study used a retrospective review of 14 HSV/VZV cases from January 2000 to October 2023 and 22 MC cases from January 2013 to December 2015.

What histopathological clue was highlighted for HSV/VZV?

Distinctive features in adjacent keratinocytes, including nucleolar enlargement and atypical findings, plus immunohistochemical staining patterns associated with cytopathic changes.

What keratinocyte appearance characterized MC cases?

MC cases consistently showed enlarged keratinocytes with a “stuffed” “pregnant seahorse” appearance around molluscum bodies.

Sep 30, 2026

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