Introduction: Inflammatory juvenile conjunctival nevus (IJCN) is a rare condition affecting both children and adolescents. It has misleading clinical and histopathological features; therefore, careful assessment is necessary. We present a case of IJCN with a rare pathological type and misleading histopathological features. Case Presentation: A 13-year-old girl with IJCN in the right eye was treated with antiallergic and steroid eye drops but showed no response and was referred to our hospital for excisional biopsy. Slit-lamp examination revealed a nonpigmented juxtalimbal tumor in the right eye. Histopathologically, nevus cells with mild nuclear atypia proliferated within the conjunctival epithelium. Confluent growth of junctional nests, conjunctival cysts, and prominent inflammatory infiltration were also observed. Considering the young age of the patient and immunohistochemical characteristics (HMB-45, SOX10, p16 and Ki-67), the patient was finally diagnosed with IJCN. IJCN has three pathological subtypes – compound, subepithelial, and junctional – depending on the location of the nevus cells. This case was diagnosed as a rare junctional type, as most of the examined sections only showed lesions within the epithelium; no lesions were clearly identified extending beneath the epithelium. Conclusion: The pathological diagnosis of IJCN is difficult because some features of IJCN suggest malignancy. Detailed microscopic examination, immunohistochemical staining, and the patient’s young age helped render a final diagnosis.

Inflammatory juvenile conjunctival nevus (IJCN) accounts for 75% of conjunctival nevi in young individuals [1]. In addition to being an infrequent specimen, the conjunctival nevus has misleading clinical and histopathological features, such as rapid growth and inflammatory infiltration through the lesion [1‒5]. All of these features suggest a diagnosis of malignancy, and an accurate diagnosis is difficult, even for experts; however, there are only a few reports on this topic. There are three histological types of conjunctival nevi: compound, junctional, and subepithelial; most cases are compound [2]. Here, we report a rare case of junctional IJCN that was difficult to differentiate from malignancy.

A 13-year-old female patient presented with a bulbar juxtalimbal conjunctival nonpigmented inflammatory tumor (Fig. 1a). The patient was treated with 0.01% betamethasone valerate, 0.1% tacrolimus hydrate, azithromycin hydrate, and 0.05% epinastine hydrochloride by a local ophthalmology clinic; however, she showed no response to the treatment for half a year. The patient was a steroid responder and could not use stronger steroids. She requested surgery and was sent to the University of Tokyo for an excisional biopsy. Her ocular history was notable only for heterochromia iris – which gradually improved – with no history of trauma, malignancy, or occupational exposure. She had no internal or family medical history. The patient also had allergic rhinitis.

Fig. 1.

IJCN. a Clinical photograph demonstrating a nonpigmented conjunctival lesion adjacent to the limbus. b Tumor invasion into the globe is not observed on anterior segment optical coherence tomography.

Fig. 1.

IJCN. a Clinical photograph demonstrating a nonpigmented conjunctival lesion adjacent to the limbus. b Tumor invasion into the globe is not observed on anterior segment optical coherence tomography.

Close modal

Visual acuity was 6/6 and 6/6 in the right and left eyes, respectively. The intraocular pressure was 10.6 mm Hg in the right and 14.6 mm Hg in the left eye. Slit-lamp microscopy revealed a temporal juxtalimbal conjunctival nonpigmented inflammatory tumor in the right eye. The right eye showed temporal hyperemia and palpebral conjunctival congestion. No abnormalities, including neoplastic diseases, were observed in the anterior chamber or fundus. The other eye also showed palpebral conjunctival congestion but no abnormal ophthalmic findings. No tumor invasion into the globe was observed on anterior segment optical coherence tomography (Fig. 1b). Therefore, we excised the tumor with a marginal area of 1 mm under topical anesthesia. To avoid making the surgery too invasive during the first surgery, additional resection and sclera freezing was planned in case of malignancy. Preoperative laboratory tests revealed no abnormalities.

The specimens were formalin-fixed and paraffin-embedded for routine examination. The lesion size was 6 × 5 × 2 mm and had well-demarcated borders. A dense proliferation of nevus cells with mild nuclear atypia was present within conjunctival epithelium; however, stromal infiltration was only slightly apparent. Cysts were observed in the epithelium. Dense lymphoid infiltration with lymphoid follicles was also observed (Fig. 2a). Higher-magnification examination showed a congregation of small foci consisting of nevus cells with moderately irregular nuclei (Fig. 2b). Immunohistochemically, nevus cells were positive for HMB-45 and SOX10 (Fig. 2c), and negative for AE1/AE3 and BRAF V600E. Expression of p16 and BAP1 was retained. The Ki-67 labeling index was 2–3%. Considering these pathological findings and the patient’s age, the final pathological diagnosis was junctional-type IJCN. No recurrence or postoperative complications were observed during the postoperative follow-up period of 3 months. The final visual acuity in the right eye was 6/6.

Fig. 2.

Pathological images of IJCN. a Excisional biopsy histology (H&E, ×100) demonstrating a prominent and dense infiltrate of nevus cells and cyst formation (yellow arrow) within the conjunctival epithelium with lymphocyte infiltration forming a lymphoid follicle (red arrow). b Excisional biopsy histology (H&E, ×200) demonstrating a congregation of small foci consisting of nevus cells with moderately irregular nuclei. c Nevus cells stain positive with SOX10 (SOX10, ×100).

Fig. 2.

Pathological images of IJCN. a Excisional biopsy histology (H&E, ×100) demonstrating a prominent and dense infiltrate of nevus cells and cyst formation (yellow arrow) within the conjunctival epithelium with lymphocyte infiltration forming a lymphoid follicle (red arrow). b Excisional biopsy histology (H&E, ×200) demonstrating a congregation of small foci consisting of nevus cells with moderately irregular nuclei. c Nevus cells stain positive with SOX10 (SOX10, ×100).

Close modal

IJCN cases are usually juxtalimbal, and approximately half of them involve pigmentation; moreover, 75% of patients have a history of allergic diseases. IJCN exhibits a period of rapid growth for several weeks or months and, in some cases, with increased pigmentation. Periods of rapid growth of inflamed nevi represent inflammatory infiltration and cystic enlargement, rather than malignant proliferation. IJCN cases usually exhibit periods of inflammatory reaction and are surrounded by vascular congestion [1]. This case was juxtalimbal and nonpigmented and showed no apparent rapid growth of the IJCN. The patient had a history of an allergic disease, which is consistent with the reported characteristics of the disease.

IJCN has three pathological types depending on the location of the nevus cells: compound, subepithelial, and junctional [2]. The compound type contains melanocytes, both in the epithelium and within the substantia propria. The subepithelial type contains nevus cells only within the substantia propria and is thus analogous to intradermal nevi in the skin. Junctional nevi, which are generally observed only in children, are characterized by discrete nests of benign nevus cells within the epithelium. It has been reported that among the three types of IJCN cases, the compound type is the most common, accounting for 73.3% of cases aged >30 years and 88.2% of cases aged <30 years. Conversely, the junctional type is the rarest of these three types and is not observed in people aged >30 years, and is reported to occur in 5.9% of patients aged <30 years [2].

Many nevomelanocytes usually become smaller as they descend into the substantia propria [6], which is called maturation. However, in conjunctival nevi in children, the subepithelial cells are observed to be larger than those in the junction, which is called a reverse maturation and should not necessarily be interpreted as evidence of malignancy [6, 7]. Additionally, a confluent junctional component and prominent inflammatory infiltrates are often present in the nevi of children. In this case, although a confluent junctional component and prominent inflammatory infiltrates were present, the lesion was localized within the epithelium; thus, maturation or reverse maturation could not be assessed.

Regarding immunohistochemical staining, HMB-45 is a monoclonal antibody that reacts against an antigen present in melanocytic tumors, whereas SOX10 is a nuclear transcription factor in the differentiation of neural crest progenitor cells to melanocytes; both are positive in conjunctival nevus and malignant melanoma. AE1/AE3 is an antibody cocktail that is generally positive in the cytoplasm of carcinomas and is useful in excluding epithelial tumors. BRAF V600E, an activating missense mutation in codon 600 of exon 15 (V600E) of the BRAF gene, is often observed in conjunctival malignant melanoma; however, it can also be positive in conjunctival nevus. BAP1 loss is often observed in uveal melanoma, and p16 expression is often attenuated in malignant melanoma. Ki-67 is a protein found in the nucleus of cells that are actively growing and dividing; thus, the Ki-67 labeling index tends to be higher in malignant tumors. This case was diagnosed as a rare junctional subtype of IJCN, as most of the examined sections only showed lesions within the epithelium; none clearly showed lesions extending beneath the epithelium. The formation of cysts in the epithelium; low mitotic activity in the substantia propria; mild nuclear atypia; immunostaining showing the following results: low Ki-67, normal p16 and BAP1; and negative results for BRAF V600E were also suggestive of IJCN, rather than conjunctival malignant melanoma.

Regarding the study limitations, since this case report lacks detailed information on long-term follow-up, future research should include extended follow-up data to provide insights into the prognosis, potential recurrence, and sustained effectiveness of the surgery. Further, genetic information of IJCN could contribute to a more detailed understanding of the condition in future research.

In conclusion, IJCN has clinical and histopathological features that may even lead experts in ophthalmic pathology to misdiagnose lesions as malignant. In the rare junctional disease subtype, the lesion is localized within the epithelium; thus, maturation cannot be assessed, and it may be difficult to differentiate it from malignancy. Therefore, careful morphological and immunohistochemical assessments are necessary prior to the final diagnosis. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000538593).

This study was conducted in accordance with the World Medical Association Declaration of Helsinki. This retrospective review of patient data did not require ethical approval in accordance with local and national guidelines. Written informed consent was obtained from the parent/legal guardian of the patient for publication of the details of their medical case and any accompanying images.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Chihiro Iwata reviewed medical literature and wrote the manuscript. Yuichi Asahina assessed histopathological samples and contributed equally to the study. Mariko Tanaka performed the histopathological examination. Takashi Miyai performed an excisional biopsy and examined the patient. Takashi Ono, Mikiko Kimakura, Yukako Taketani, Tetsuya Toyono, and Makoto Aihara reviewed and edited the manuscript. All authors have approved the final version of the manuscript for publication.

Additional Information

Chihiro Iwata and Yuichi Asahina contributed equally to this work.

All data supporting the findings of this study have been included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.

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