Article Text

Download PDFPDF
Combined deep penetrating nevi of the conjunctiva are relatively common lesions characterised by BRAFV600E mutation and activation of the beta catenin pathway: a clinicopathological analysis of 34 lesions
  1. Daja Šekoranja1,
  2. Katarina Vergot2,
  3. Gregor Hawlina2,
  4. Jože Pižem1
  1. 1 Institute of Pathology, University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia
  2. 2 Eye Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
  1. Correspondence to Dr Jože Pižem, Institute of Pathology, University of Ljubljana, Faculty of Medicine, Ljubljana 1000, Slovenia; joze.pizem{at}


Background Deep penetrating nevus (DPN) is not a widely recognised lesion on the conjunctiva and only a few cases consistent with combined DPN have been reported.

Methods A review of all excised and histopathologically diagnosed conjunctival melanocytic lesions between 2003 and 2018 was performed in order to identify melanocytic nevi morphologically consistent with DPN.

Results Thirty-four DPN were identified among 361 histopathologically examined conjunctival nevi (9.4%), including 33 (97%) combined with a common nevus and 1 (3%) pure DPN. The patients’ age ranged from 7 to 51 years (median, 22 years). Clinically, 21 of 29 (72%) lesions with available data were darkly pigmented, and an increase in size and/or pigmentation was noted in 13 of 18 (72%) lesions with known history. All 24 lesions in which an immunohistochemical analysis was possible were diffusely positive for BRAFV600E (in DPN and common nevus components) and showed a diffuse nuclear positivity for beta catenin and cyclin D1 in the DPN component. None of the 21 lesions with available follow-up data recurred during a follow-up period from 0.3 to 16.3 years (median, 7.5 years).

Conclusions DPN of the conjunctiva is a relatively common lesion and usually presents as a combined nevus. Genetically, DPN of the conjunctiva are characterised by a combination of BRAFV600E mutation and activation of the beta catenin pathway. Recognition of DPN of the conjunctiva is important in order not to overdiagnose it as a melanoma, and to explain its potential atypical clinical features. DPN of the conjunctiva seems to be a benign lesion.

  • conjunctiva
  • deep penetrating nevus
  • combined nevus
  • clonal nevus
  • BRAF
  • NRAS
  • beta catenin

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors JP, the corresponding author, contributed with the first idea of the study and its outline. All four authors (JP, DŠ, KV and GH) actively contributed to planning the study and writing the manuscript, with JP and DŠ mainly focused on histopathological part of the study and obtaining patient data, whereas KV and GH focused on the clinical aspect. KV and GH also provided clinical images, whereas JP provided histological images.

  • Funding The study was financially supported by the Slovenian Research Agency (research core funding number P3-0054).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Review Board of the Institute of Pathology, University of Ljubljana, Faculty of Medicine (ID 2/2019).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

Linked Articles

  • At a glance
    Keith Barton James Chodosh Jost B Jonas