Original Contributions Intralymphatic nevus cells in benign nevi ☆ Cem Leblebici, MD a, ⁎, Canan Kelten, MD a , Mehmet Salih Gurel, MD b , Ezgi Hacıhasasanoglu, MD a a Department of Pathology, Istanbul Education and Research Hospital, Istanbul, Turkey b Department of Dermatology, Istanbul Medeniyet University School of Medicine, Istanbul, Turkey abstract article info Keywords: Nevus cells Intralymphatic Melanocytic nevus Mechanical transport theory Nevus cell aggregates in lymph nodes The histogenesis of nevus cell aggregates in lymph nodes lesion is controversial, and various hypotheses have been used to explain their origin. One of them is the transport of cells from cutaneous nevi or lesions to lymph nodes, called mechanical transport theory. We investigated in our cases of benign nevi to obtain evidence to substantiate this theory. A total of 369 benign cutaneous nevi were prospectively evaluated in excisional biopsy samples. Immunohistochemical stainings for CD31 and podoplanin (D2-40) were performed in the cases with intralymphatic nevus cell aggregate (ILNA), suspected for ILNA, and/or intralymphatic nevus cell protrusion. A total of 13 ILNAs were found in 10 patients. Six ILNA were verified with their histology as well as immunohistochemically with D2-40 and CD31. Protrusions of nevus cells inside the lymphatics (intralymphatic nevus cell protrusion) were seen in all cases of ILNA and also in 27 nevi where an ILNA was not observed. In most nevi, the perilymphatic orientation of nevus cells and their affinity to the lymphatics were observed. We suggested that ILNAs can be dislodged with local minor trauma and be carried inside the lymphatic vessel to the draining lymph node. Besides, whether ILNA or not, nevus cells could also move toward lymphatic spaces with mechanical effects due to their affinity to lymphatics and their localizations that are very close to the endothelium. Our findings might support the mechanical transport theory. © 2016 Elsevier Inc. All rights reserved. 1. Introduction Since the first description in 1931 by Stewart and Copeland [1], there have been a number of cases of benign nevus cells within lymph nodes reported in the literature [2,3]. At first, this entity was considered to be infrequent, but subsequent studies have indicated that nevus cell aggre- gates in lymph nodes (NALNs) can no longer be considered a rare phe- nomenon [4]. Although an NALN rate of 0.12% to 0.54% was observed in full lymph node dissections in melanoma patients [5,6], this rate can in- crease up to 3.9% to 13% in sentinel lymph nodes [3,7]. Besides, NALNs were found to accompany skin adnexal carcinoma and squamous cell carcinoma of the tonsil and were reported even in individuals without any malignancy [4]. Nevertheless, the origin of these cells remains unclear and has been the subject of academic interest for a long time. Various hypotheses have been used to explain their origin. Lymphatic nevus cell aggregates (ILNAs) in benign nevi indicate that nevus cells are probably transferred from a cutaneous nevus to the draining lymph node via the lymphatics [4]. However, there are only 8 reported cutaneous nevus cases with intralymphatic nevus cells as far as we are aware. We evaluated our benign nevi cases to look for evidence supporting this possibility. 2. Materials and methods 2.1. Case selection Benign cutaneous compound and intradermal nevi were prospec- tively evaluated in excisional biopsy samples by 2 separate pathologists during the routine reporting procedure at our pathology laboratory be- tween February and September 2015. Junctional nevi were excluded as they do not contain a dermal component. Four to 16 sections on 1 or 2 hematoxylin and eosin (H&E)–stained slides were screened with the objective ×20 for each nevus. The histologic criteria specified below were created based on lymphovascular invasion descriptions previously used in the literature for the detection of malignant tumor emboli with- in lymphatics [8-10]. According to these criteria, immunohistochemical stainings for CD31 and podoplanin (D2-40) were performed in the fol- lowing conditions: (i) cases with ILNA, (ii) cases with intralymphatic nevus cell protrusion (ILNP), and (iii) if differentiation was not possible morphologically between retraction artifact and ILNA. Immunohisto- chemical analyses were performed on 5-μm-thick formalin-fixed, paraffin-embedded sections. We used clone JC70 (mouse monoclonal, 1:50 dilution; Cell Marque, Rocklin, CA) for CD31 and clone D2-40 (mouse monoclonal, 1:50 dilution; Cell Marque) for podoplanin. Annals of Diagnostic Pathology 25 (2016) 1–6 ☆ We have no relevant financial interest in the products or companies described in this article. No actual or potential conflicts of interest exist. ⁎ Corresponding author at: Samatya Cad. Istanbul Egitim Hastanesi, Patoloji Lab, Koca M Pasa, Fatih, Istanbul, Turkey. Tel.: +90 5370227920. E-mail addresses: cleblebici@gmail.com (C. Leblebici), ecanankelten@gmail.com (C. Kelten), msgurel@gmail.com (M.S. Gurel), ezgihaci@yahoo.com (E. Hacıhasasanoglu). http://dx.doi.org/10.1016/j.anndiagpath.2016.08.003 1092-9134/© 2016 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Annals of Diagnostic Pathology