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Conjunctival leiomyosarcoma is a very rare soft tissue malignancy. Herein, we describe a conjunctival leiomyosarcoma case in a patient with another rare disease, xeroderma pigmentosum. The 27-year-old single-eyed xeroderma pigmentosum patient complained of exophytic mass covering the ocular surface in her left eye. A vascular, hemorrhagic mass covering the entire ocular surface of the left eye was identified on the examination. Thus, total mass excision surgery was performed. The pathological diagnosis was compatible with conjunctival leiomyosarcoma. Additional chemotherapy, radiotherapy, or surgery were not accepted by the patient. No recurrence or metastasis was observed during the 5-year follow-up. Both primary conjunctival leiomyosarcoma and xeroderma pigmentosum are very rare diseases. Conjunctival masses in xeroderma pigmentosum patients should be approached carefully, and histopathological examination is warranted. For conjunctival leiomyosarcoma, early diagnosis, localized, unspread disease, and complete resection provide the best prognosis. RESUMO O leiomiossarcoma da conjuntiva é um tumor maligno de tecidos moles muito raro. Aqui é descrito um caso de leiomiossarcoma da conjuntiva em um paciente com xeroderma pigmentoso, que também é uma doença rara. Um paciente de 27 anos de idade com xeroderma pigmentoso de olho único queixou-se de uma massa exofítica cobrindo a superfície ocular do olho esquerdo. Ao exame, foi observada uma massa vascular hemorrágica cobrindo toda a superfície ocular do olho esquerdo. Foi realizada uma cirurgia de excisão total dessa massa. O diagnóstico patológico foi compatível com leiomiossarcoma da conjuntiva. O paciente recusou qualquer quimioterapia, radioterapia ou cirurgia adicional. Nenhuma recidiva ou metástase foi observada durante o acompanhamento de 5 anos. Tanto o leiomiossarcoma primário da conjuntiva quanto o xeroderma pigmentoso são doenças muito raras. Massas conjuntivais em pacientes com xeroderma pigmentoso devem ser abordadas com cuidado e deve-se realizar um exame histopatológico. Para o leiomiossarcoma conjuntival, o diagnóstico precoce, uma doença localizada e não disseminada e a ressecção completa proporcionam o melhor prognóstico.

Conjunctival melanoma (CM) is a rare and fatal ocular tumour with poor prognosis. There is an urgent need of effective therapeutic drugs against CM. Here, we reported the discovery of a novel potential therapeutic target for CM. Through phenotypic screening of our in-house library, fangchinoline was discovered to significantly inhibit the growth of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1. Further mechanistic experiments indicated that fangchinoline suppressed the homologous recombination (HR)-directed DNA repair by binding with far upstream element binding protein 2 (FUBP2) and downregulating the expression of HR factors BRCA1 and RAD51. In vitro and in vivo antitumour experiments revealed that fangchinoline increased the efficacy of cisplatin by blocking HR factors and reduced the drug dose and toxicity. In conclusion, our work provides a promising therapeutic strategy for the treatment of CM that is worthy of extensive preclinical investigation.

Purpose: Conjunctival melanoma is a rare and aggressive tumor with a propensity for regional and distant metastases. This study aimed to analyze BRAF/NRAS markers in conjunctival melanoma and their relationship with tumor recurrences and patient prognosis. Methods: This retrospective, observational, single-center study included consecutive patients with an anatomopathological diagnosis of conjunctival melanoma, registered between January 1992 and December 2019. BRAF/NRAS mutations were analyzed using cobas®4800 kit (Roche®) in samples obtained by excisional or map biopsy. Additionally, the presence of other associated precancerous or tumor lesions was assessed. Results: A total of 12 patients with positive histological samples for conjunctival melanoma were included (7 women, 5 men), with a mean age at diagnosis of 60 years and a mean evolution time of 6.38 ± 3.4 years. BRAF V600E mutation was observed in three biopsies (25%), similar to NRAS Q61X (25%). Recurrences occurred in all patients with positive BRAF or NRAS mutation, and five of these patients developed systemic dissemination (83.33%). Moreover, four of six patients with mutated BRAF or NRAS (66.66%) had histopathological findings of tumor or precancerous lesions. Conclusions: BRAF and NRAS mutations may be risk factors for recurrence and shorter survival in conjunctival melanoma, which would make these patients candidates for targeted therapies and comprehensive and individualized follow-up. All these data warrant standardized prospective studies. RESUMO Objetivo: O melanoma da conjuntiva é um tumor raro e agressivo, com propensão à disseminação metastática regional e distante. Este estudo tem como objetivo analisar os marcadores BRAF e NRAS no melanoma da conjuntiva e sua relação com recidivas tumorais e com o prognóstico do paciente. Métodos: Este foi um estudo retrospectivo, observacional e unicêntrico de pacientes consecutivos com diagnóstico anatomopatológico de melanoma da conjuntiva feito entre janeiro de 1992 e dezembro de 2019. As mutações BRAF e NRAS foram analisadas com o kit cobas® 4800 (Roche®) em amostras obtidas através de biópsia excisional ou por mapa. Além disso, foi avaliada a presença de lesões pré-cancerosas ou tumorais associadas. Resultados: Foram incluídos 12 pacientes com amostras histológicas positivas para melanoma da conjuntiva (7 mulheres e 5 homens), com idade média ao diagnóstico de 60 anos e tempo médio de evolução de 6,38 ± 3,4 anos. A mutação BRAF V600E foi encontrada em 3 biópsias (25%), bem como a NRAS Q61X (25%). Ocorreram recidivas em todos os pacientes positivos para mutações de BRAF ou NRAS e 5 desses pacientes desenvolveram disseminação sistêmica (83,33%). Além disso, 4 dos 6 pacientes com BRAF ou NRAS mutante (66,66%) apresentaram achados histopatológicos de lesões tumorais ou pré-cancerosas. Conclusões: As mutações BRAF e NRAS podem ser fatores de risco para recorrência e menor sobrevida no melanoma da conjuntiva, o que tornaria esses pacientes candidatos a terapias direcionadas e a um acompanhamento mais abrangente e individualizado. Todos esses dados justificam mais estudos prospectivos padronizados.

SUMMARY Objective: The aim of this study was to evaluate the expression of endoglin and its correlation with histopathological and clinical findings in conjunctival nevi. Methods: The study included archival formalin-fixed, paraffin-embedded tissue sections of 44 patients with conjunctival nevi. Immunohistochemical staining for CD105 had been performed with monoclonal mouse antihuman CD105 antibodies. The intratumoral microvessel density for quantification of tumoral vascularization had been determined by this marker. Results: The expression of CD105 was positive in 30 (68.2%) cases. There was a statistically significant difference in the level of CD105 expression regarding the histological type of nevus (p=0.03) and intralesional cysts status (p=0.02). Spearman's rho (ρ −0.316) revealed a significant negative correlation between the expression of endoglin and the histological type of nevus (p=0.03) and between the expression of endoglin and the presence of intralesional cysts (ρ −0.380, p=0.01). Conclusion: This study suggests that endoglin could be a useful diagnostic and prognostic marker in differentiating between benign and malignant melanocytic ocular lesions.

Purpose To report the unexpected finding of ocular surface neoplasia (OSSN) on conjunctival tissue removed during pterygium surgery and subjected to histopathology analysis. Methods This is an observational, descriptive retrospective study in which all the samples removed during surgery between 1997 and 2020 with a clinical diagnosis of pterygium were sent for histopathology analysis in which an unexpected OSSN was found. Results There were 461 cases with a preoperative diagnosis of pterygium, with a mean age of 30.14 ± 10.6 years. In this group, there was an unexpected finding of OSSN in 69 cases (14.96%) of the surgical samples, with a mean age of 46 ± 8.2 years (31.86 ± 12.13). Conclusions The unexpected coincidence of pterygium and OSSN is frequent, although varies depending on the geographical location. We recommend performing a histopathology analysis on every pterygium removed.

The aim of this study was to alert the ophthalmic community to an atypical manifestation of ocular surface squamous neoplasia, which may delay diagnosis and treatment and result in a guarded visual prognosis and significant sequelae. A 61-year-old immunocompetent man presented with an initial diagnosis of necrotizing scleritis in the right eye for 3 months. He was treated with systemic prednisone but experienced persistent pain and low visual acuity. Conjunctival biopsy of the affected region confirmed the diagnosis of invasive ocular surface squamous neoplasia, which progressed with intraocular and orbital invasion; thus, exenteration was performed. Masquerade syndrome should be suspected in patients with nodulo-ulcerative lesions of the conjunctiva and sclera. This clinical can be more aggressive, with a greater likelihood of intraocular and orbital involvement. The earlier the diagnosis and treatment, the better the patient prognosis. RESUMO O objetivo é alertar a comunidade oftalmológica sobre uma manifestação atípica de neoplasia escamosa da superfície ocular (OSSN) que pode levar a um atraso no diagnóstico e tratamento, evoluindo com prognóstico reservado e significativas sequelas. Homem, imunocompetente, 61 anos com diagnóstico inicial de esclerite necrosante em olho direito há 3 meses, em tratamento com prednisona sistêmica porém com persistência da dor e baixa acuidade visual. Realizado biópsia conjuntival em região acometida e diagnosticado como neoplasia escamosa da superfície ocular invasiva. Evolui com invasão intraocular e orbital sendo submetido a exenteração. Assim sendo, deve-se suspeitar de síndrome mascarada frente a um paciente com lesões nódulo-ulcerativas da conjuntiva e esclera. Essa forma clínica pode ser mais agressiva, com maior chance de comprometimento intraocular e orbital. Quanto mais precoces o diagnóstico e o tratamento, melhor o prognóstico para o paciente.

This study characterizes the transcriptome and the cellular tumor microenvironment (TME) of conjunctival melanoma (CM) and identifies prognostically relevant biomarkers. 12 formalin-fixed and paraffin-embedded CM were analyzed by MACE RNA sequencing, including six cases each with good or poor clinical outcome, the latter being defined by local recurrence and/or systemic metastases. Eight healthy conjunctival specimens served as controls. The TME of CM, as determined by bioinformatic cell type enrichment analysis, was characterized by the enrichment of melanocytes, pericytes and especially various immune cell types, such as plasmacytoid dendritic cells, natural killer T cells, B cells and mast cells. Differentially expressed genes between CM and control were mainly involved in inhibition of apoptosis, proteolysis and response to growth factors. POU3F3, BIRC5 and 7 were among the top expressed genes associated with inhibition of apoptosis. 20 genes, among them CENPK, INHA, USP33, CASP3, SNORA73B, AAR2, SNRNP48 and GPN1, were identified as prognostically relevant factors reaching high classification accuracy (area under the curve: 1.0). The present study provides new insights into the TME and the transcriptional profile of CM and additionally identifies new prognostic biomarkers. These results add new diagnostic tools and may lead to new options of targeted therapy for CM.

Purpose: Conjunctival melanoma is a rare and aggressive tumor with a propensity for regional and distant metastases. This study aimed to analyze BRAF/NRAS markers in conjunctival melanoma and their relationship with tumor recurrences and patient prognosis. Methods: This retrospective, observational, single-center study included consecutive patients with an anatomopathological diagnosis of conjunctival melanoma, registered between January 1992 and December 2019. BRAF/NRAS mutations were analyzed using cobas®4800 kit (Roche®) in samples obtained by excisional or map biopsy. Additionally, the presence of other associated precancerous or tumor lesions was assessed. Results: A total of 12 patients with positive histological samples for conjunctival melanoma were included (7 women, 5 men), with a mean age at diagnosis of 60 years and a mean evolution time of 6.38 ± 3.4 years. BRAF V600E mutation was observed in three biopsies (25%), similar to NRAS Q61X (25%). Recurrences occurred in all patients with positive BRAF or NRAS mutation, and five of these patients developed systemic dissemination (83.33%). Moreover, four of six patients with mutated BRAF or NRAS (66.66%) had histopathological findings of tumor or precancerous lesions. Conclusions: BRAF and NRAS mutations may be risk factors for recurrence and shorter survival in conjunctival melanoma, which would make these patients candidates for targeted therapies and comprehensive and individualized follow-up. All these data warrant standardized prospective studies.

As the p53 tumor suppressor is rarely mutated in conjunctival melanoma (CM), we investigated its activation as a potential therapeutic strategy. Preventing p53/Mdm2 interaction by Nutlin-3, the prototypical Mdm2 antagonist, or via direct siRNA Mdm2 depletion, increased p53 and inhibited viability in CM cell lines. The sensitivity to Nutlin-3 p53 reactivation with concomitant Mdm2 stabilization was higher than that achieved by siRNA, indicative of effects on alternative Mdm2 targets, identified as the cancer-protective IGF-1R. Nutlin-3 treatment increased the association between IGF-1R and β-arrestin1, the adaptor protein that brings Mdm2 to the IGF-1R, initiating receptor degradation in a ligand-dependent manner. Controlled expression of β-arrestin1 augmented inhibitory Nutlin-3 effects on CM survival through enhanced IGF-1R degradation. Yet, the effect of IGF-1R downregulation on cell proliferation is balanced by β-arrestin1-induced p53 inhibition. As mitomycin (MMC) is a well-established adjuvant treatment for CM, and it triggers p53 activation through genotoxic stress, we evaluated how these alternative p53-targeting strategies alter the cancer-relevant bioactivities of CM. In 2D and 3D in vitro models, Nutlin-3 or MMC alone, or in combination, reduces the overall cell tumor growth ~30%, with double treatment inhibition rate only marginally higher than single-drug regimens. However, histopathological evaluation of the 3D models revealed that Nutlin-3 was the most effective, causing necrotic areas inside spheroids and complete loss of nuclear staining for the proliferative marker Ki67. These findings were further validated in vivo; zebrafish xenografts demonstrate that Nutlin-3 alone has higher efficacy in restraining CM tumor cell growth and preventing metastasis. Combined, these results reveal that β-arrestin1 directs Mdm2 toward different substrates, thus balancing IGF-1R pro-tumorigenic and p53-tumor suppressive signals. This study defines a potent dual-hit strategy: simultaneous control of a tumor-promoter (IGF-1R) and tumor-suppressor (p53), which ultimately mitigates recurrent and metastatic potential, thus opening up targeted therapy to CM.

Purpose To evaluate the role of sentinel lymph node (SLN) biopsy in patients with conjuctival melanoma (CjM). Study design Retrospective observational cohort study and literature review. Subjects Slovenian patients with CjM are included in the study. Methods Prospectively collected data of CjM patients treated from June 2005 to December 2016 were retrospectively analyzed. Main outcome measures The numbers of SLN biopsy procedures, positive and false positive SLN, and local and regional relapses have been described together with overall survival. Results From June 2005 until December 2016, 24 patients with CjM were treated. The median follow-up time was 65.3 months. The mean Breslow thickness was 1.5 mm (sd = 1.8 mm), and ulceration was present in 29% of cases. Altogether, 14/24 (58%) SLN biopsy procedures were performed. SLN was positive in 2/14 (14%) cases. The estimated 5-year overall survival (OS) of the group was 72.5%, with a median survival of 151 months (95% CI 77–224). From January 2013 to January 2020, five (5/140, 3%) authors reported results comparable to our study. Conclusion Our results confirm that CjM is a rare disease with approximately 14% of positive SLN. At the moment, there are no firm conclusions regarding who would benefit most from SLN biopsy or whether or not CLND should be offered. Data from literature emphasize the need for consistent and uniform staging and future multicentric studies.

Purpose: The aim of this study was to determine if the initial tumor size correlates with the time to regression after topical interferon alfa-2b (1 million IU/mL) therapy in the treatment of ocular surface squamous neoplasia. Methods: A retrospective study was performed in 15 patients clinically diagnosed as having ocular surface squamous neoplasia and treated with topical interferon alfa-2b (1 million IU/mL, four times a day). All the cases of ocular surface squamous neoplasia included in the study had corneo-limbal involvement. The initial extension of the ocular surface squamous neoplasia was measured in square millimeters using the program ImageJ (LOCI, University of Wisconsin, Madison, USA) on images taken from the eyes of each patient immediately before the beginning of the treatment. The time until tumor resolution was measured for each case. Results: Complete tumor resolution was achieved in all the cases, with a mean initial tumor extension of 26.71 mm² (standard deviation ± 17.21 mm²) and a mean time until resolution of 77 days (standard deviation ± 32 days). An increased tumor volume after 15 days of treatment was obser ved in 2 patients, which completely resolved. No significant correlation was found between the time to resolution and the initial tumor extension measured in square millimeters (Spear man test, p=0.347). Conclusions: Our study suggests that the duration of topical interferon alfa-2b treatment required does not depend on the initial tumor size of the ocular surface squamous neoplasia usually found in clinical practice. Objetivo: O objetivo deste estudo é determinar se o tamanho inicial do tumor se correlaciona com o tempo de regressão após terapia tópica com interferon alfa- 2b (1 milhão de UI/ml) no tratamento da neoplasia escamosa da superfície ocular. Métodos: Foi realizado um estudo retrospectivo em 15 doentes clinicamente diagnosticados com neoplasia escamosa da superfície ocular e tratados com interferon tópico alfa- 2b (1 milhão de UI/ml, quatro vezes ao dia). Todos os casos de neoplasia escamosa da superfície ocular incluídos no estudo apresentaram envolvimento da córnea e do limbo. A extensão inicial da neoplasia escamosa da superfície ocular foi medida em milímetros quadrados usando o programa ImageJ (LOCI, University of Wisconsin, Madison, EUA) em imagens feitas dos olhos de cada paciente imediatamente antes do início do tratamento. O tempo até a resolução do tumor foi observado em cada caso. Resulta dos: A resolução tumoral completa foi alcançada em todos os casos, com média da extensão inicial de 26,71 mm² (desvio padrão ± 17,21 mm²) e tempo médio até a resolução de 77 dias (desvio padrão ± 32 dias). Um aumento do volume tumoral após 15 dias de tratamento foi observado em 2 pacientes com resolução completa do tumor. Não houve correlação significativa entre o tempo até a resolução e a extensão inicial do tumor medida em milímetros quadrados (teste de Spearman, p=0,347). Conclusões: Nosso estudo sugere que a duração do tratamento necessário com interferon alfa- 2b tópico não depende do tamanho inicial do tumor de neoplasia escamosa da superfície ocular geralmente encontrada na prática clínica. Descritores: Neoplasia da túnica conjuntiva; Doença da córnea/tratamento farmacológico; Carcinoma de célula escamosa; In terferon alfa-2/ uso terapêutico

Sebaceous tumors of the conjunctiva and caruncle are rare conditions, accounting for 1% of caruncle lesions and even lower among conjunctival lesions. Almost 50% of cases are associated with Muir-Torre syndrome, a rare autosomal-dominant condition characterized by at least one sebaceous skin tumor and one visceral malignancy. We report 3 cases of sebaceous adenoma with different presentations that were submitted to excisional biopsy and immunohistochemical study. Diagnosis of these tumors should increase the level of suspicion and lead to clinical investigation to rule out neoplasms, particularly because in up to 41% of cases, these can be the first sign of the disease. RESUMO Tumores sebáceos da conjuntiva e carúncula são condições raras, sendo mais encontrados nas pálpebras. O ade noma sebáceo é responsável por 1% das lesões carunculares e ainda menos frequente nas lesões da conjuntiva. Esse diagnóstico é de suma importância pois quase 50% desses pacientes podem ser diagnosticados com a Síndrome de Muir-Torre, uma condição autossômica dominante rara que é caracterizada pela presença de ao menos um tumor de pele sebáceo e uma neoplasia visceral (gastrointestinal, câncer geniturinário e de mama). O estudo tem como objetivo relatar 3 casos de adenoma sebáceo com diferentes apresentações, que foram submetidos a biópsia excisional e estudo imuno-histoquímico. O diagnóstico desses tumores deve levantar suspeitas e aconselhar a investigação clínica para descartar outras neoplasias, principalmente porque em até 41% dos casos esse pode ser o primeiro sinal da Síndrome de Muir-Torre.

Surgical management of large tumors involving the conjunctival fornix can be challenging, as exposure and clear margins may be difficult to achieve. In this case series, we report our initial experience with the open book technique in 4 patients. Through a canthotomy and cantholysis, this surgical approach provides a wide surgical field and facilitates fornix reconstruction post large tumor excision. In our series, one patient had a lateral canthus dehiscence. RESUMO O manejo cirúrgico de grandes tumores envolvendo o fórnice conjuntival pode ser desafiador, onde a exposição e as margens livres podem ser difíceis de serem alcançadas. Nesta série de casos, relatamos nossa experiência inicial com 4 pacientes usando a técnica de livro aberto. Através da cantotomia e da cantólise, esta abordagem cirúrgica fornece um amplo campo cirúrgico e também facilita a reconstrução do fórnice após a excisão de um tumor grande. Em nossa série, um paciente apresentou deiscência no canto lateral.

Objective: To describe ocular surface findings in impression cytology obtained from healthy rabbit conjunctiva treated with interferon alpha-2b eyedrop, and compare them to findings after use of mitomycin C 0.02%. Methods: An experimental study using a rabbit model was performed between September 2013 and October 2014 at the Faculdade de Medicina de Marília, Universidade Federal de São Paulo, Clínica de Olhos Moacir Cunha. Thirty New Zealand white rabbits were divided into 6 groups and received interferon alpha-2b or mitomycin C 0.02%. Impression cytology (IC) was performed prior to topical applications and at15, 30 and 60 days of use. The following variables were analyzed in impression cytology: goblet cells, cellularity, cell-to-cell adhesion, nucleus/cytoplasm ratio, nuclear chromatin, inflammatory cells keratinization, and cytomegaly. Results: The major findings in impression cytology after us of interferon alpha-2b included loss of goblet cells (50.8%), reduced cell-to-cell adhesion (26.2%), abnormal nucleus/cytoplasm ratio (20%) and reduced cellularity (15.4%). After use of mitomycin C 0.02%, the most common changes included loss of goblet cells (46.2%), abnormal nucleus/cytoplasm ratio (25.6%), less cell-to-cell adhesion (23.1%), and reduced cellularity (20.5%). There were no significant differences in any variable when comparing impression cytology after interferon alpha-2b and after mitomycin C 0.02%. Goblet cell loss was more pronounced at days 30 and 60, as compared to impression cytology at day 15 for both drugs. Conclusion: The loss of goblet cells, reduced cell-to-cell adhesion and cellularity, along with abnormal nucleus/cytoplasm ratio were the most common findings in impression cytology after use of interferon alpha-2b. These findings are similar to those described for use of mitomycin C 0.02%. .. RESUMO Objetivo: Descrever os achados em citologia de impressão de conjuntiva sadia de coelho submetida ao uso de colírio de interferon alfa-2b e compará-los ao que foi encontrado após uso da mitomicina C 0,02%. Métodos: Estudo experimental realizado em modelo animal no período entre setembro de 2013 e outubro de 2014 nas dependências da Faculdade de Medicina de Marília, da Universidade Federal de São Paulo e da Clínica de Olhos Moacir Cunha. Trinta coelhos albinos da raça Nova Zelândia foram divididos em seis grupos e receberam interferon alfa-2b ou mitomicina C. A citologia de impressão foi realizada antes do início dos colírios e após 15, 30, 60 dias de seu uso. As seguintes variáveis foram analisadas na citologia de impressão: células caliciformes, celularidade, adesão intercelular, razão núcleo/citoplasma, cromatina, células inflamatórias, queratinização e citomegalia. Resultados: Os principais achados na citologia de impressão após o uso do interferon alfa-2b foram a redução de células caliciformes (50,8%), a diminuição da adesão intercelular (26,2%), a alteração da razão N/C (20%) e a redução da celularidade (15,4%). Após o uso da mitomicina C 0,02%, foram mais frequentes a redução das células caliciformes (46,2%), a alteração da razão N/C (25,6%), a adesão intercelular (23,1%) e a redução da celularidade (20,5%). Não houve diferença estatisticamente significante para nenhuma das variáveis estudas quando se compararam as citologias de impressão após interferon alfa-2b com as citologias de impressão após mitomicina C 0,02%. Independentemente da substância utilizada, as citologias colhidas 30 e 60 dias após início das drogas apresentaram maior redução de células caliciformes quando comparadas com as citologias de impressão colhidas após 15 dias. Conclusão: A redução das células caliciformes, a diminuição da adesão intercelular, a alteração da razão N/C e a diminuição da celularidade foram as alterações mais frequentes na citologia de impressão colhida após o uso de interferon alfa-2b. Os achados em citologias de impressão após o uso de interferon alfa-2b são semelhantes àqueles encontrados após o uso da mitomicina C 0,02%.

BackgroundNationwide studies of ocular adnexal lymphoma (OAL) are very rare in the literature, and knowledge on incidence, subtype distribution and long-term survival data is limited. This is the largest national study of OAL to date. This study sought to find information on incidence, changes in incidence, clinical findings, distribution of subtypes, survival and prognostic factors.MethodsPatients diagnosed with OAL from January 1, 1980 to December 31, 2017 were identified in Danish registers, and clinical as well as survival data were collected. The data were analysed with Kaplan-Meier plots and log-rank test.Results387 patients were included in the study. The major lymphoma subtypes were extranodal marginal-zone B cell lymphoma (EMZL) (55%), diffuse large B cell lymphoma (DLBCL) (13%), mantle cell lymphoma (MCL) (11%) and follicular lymphoma (FL) (10%). OAL is a disease of the elderly (median age 69 years). The incidence of lymphoma of the ocular adnexal region has increased significantly throughout the time period of the study (Pearson correlation coefficient, r=0.65; PConclusionOAL is increasing in incidence in the Danish population for unknown reasons. However, the prognosis for most OAL is favourable, as highlighted in this national long-term study.

A 42-year-old male presented with a 4-week history of a mass in the right inferior palpebral conjunctiva close to the punctum. An excisional biopsy of the lesion and histopathological examination revealed that the mass was composed of Schwann cells with thin conical nuclei, fine chromatin, and unnoticeable nucleoli. Immunohistochemically, the spindle cells were diffusely and strongly positive for S100 protein. Neurofilament immunostaining was also positive, which highlighted axons. In light of these findings, the tumor was diagnosed as solitary circumscribed neuroma. A comprehensive evaluation for multiple endocrine neoplasia type 2b was performed. However, no multiple endocrine neoplasia type 2b stigmata and no family history were detected. The diagnosis was therefore finalized as solitary circumscribed neuroma, which is considered as a rare condition. The differential diagnosis is based on the histopathological examination and immunohistochemical evaluation. As the tumor can be related with multiple endocrine neoplasia type 2b, it is essential to systematically investigate for multiple endocrine neoplasia type 2b in such cases.