Epithelial conjunctival neoplasias – the importance of an early diagnosis and optimal treatment

oc000157 10.3205/oc000157 urn:nbn:de:0183-oc0001576 Case Report Epithelial conjunctival neoplasias – the importance of an early diagnosis and optimal treatment Tabuenca Del Barrio Tabuenca Del Barrio Laura L

Ophthalmology, Complejo Hospitalario de Navarra, Calle Irunlarrea, 31008 Pamplona, Navarra, SpainOphthalmology, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain

lauratabuillueca@gmail.com author Mozo Cuadrado Mozo Cuadrado Marcos M

Ophthalmology, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain

author Nova Camacho Nova Camacho Luiz Miguel LM

Pathology, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain

author Zubicoa Enériz Zubicoa Enériz Alicia A

Ophthalmology, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain

author Aranguren Laflin Aranguren Laflin Miren Dolores MD

Ophthalmology, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain

author Alcaine Soler Alcaine Soler Araceli A

Ophthalmology, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain

author German Medical Science GMS Publishing House

Düsseldorf

610 squamous cell carcinoma conjunctival malignancies CIN exenteration excisional biopsy radiotherapy 20200806 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). 2193-1496 10 GMS Ophthalmology Cases GMS Ophthalmol Cases 30 Objective: To emphasize the importance of an early diagnosis and an adequate treatment in conjunctival tumors.Methods: We present two clinical cases and compare the course of each case: one of conjunctival intraepithelial neoplasia (CIN) which took a positive course, and a fatal case of squamous cell carcinoma (SCC) with intraocular and orbital extension.Results: Epithelial conjunctival malignancies are one of the most prevalent ocular surface tumors. Among these, CIN are the most common. CIN have an excellent prognosis, given adequate treatment. However, when the diagnosis of CIN is late, the epithelial basement membrane will be affected, resulting in SCC. SCC may have poorer results due to its capacity to infiltrate near tissues and create distant metastasis.Conclusion: It is not common today to treat patients with orbital extension of SCC; however, it is crucial to note the importance of an early diagnosis of conjunctival malignancies. An early diagnosis is essential to prevent the transformation to other life-threatening types. IntroductionConjunctival tumors are one of the most common ocular surface malignancies , . Their most frequent cell origin is located on epithelial and melanocytic cells. Since in most cases it is very difficult to differentiate between premalignant and malignant lesions, a biopsy is necessary to determine their nature .Epithelial neoplasms can be divided intocarcinoma in situ/conjunctival intraepithelial neoplasia (CIN), which exclusively affect the epithelium;invasive squamous cell carcinomas (SCC), when the epithelial basement membrane is damaged and neoplastic cells are present in the corneal stroma .We report two clinical cases of conjunctival neoplasm. The first one exhibits a patient affected by CIN with an early diagnosis and effective treatment based on topical chemotherapy and surgical excision. In contrast, the second case shows a patient with SCC with an aggressive clinical course and intraocular and orbital extension.The fact that the cell origin was the same in both cases shows that an adequate diagnosis and optimal treatment are required to control the progression of these types of tumors. Intraocular and orbital extension is infrequent but commonly fatal. Case descriptionsCase 1A 70-year-old man presented with a conjunctival lesion in his left eye that had appeared four months earlier. Visual acuity (VA) was 20/200 in both eyes. Slit-lamp examinatio</PlainText></TextGroup>n showed a nasal limbal gelatinous mass wit<TextGroup><PlainText>h i</PlainText></TextGroup>nferior corneal infiltration and cataract (Figure 1 <ImgLink imgNo="1" imgType="figure"/>). Intraocular pressure and fundoscopy were unremarkable. An excisional biopsy was performed: A CIN with free margins was confirmed by the histopathological study (Figure 2 <ImgLink imgNo="2" imgType="figure"/>). Topical adjuvant treatment with interferon (IFN)-α2β drops/6 hours was initiated. One month later, the lesion decreased in size (Figure 3A <ImgLink imgNo="3" imgType="figure"/>), and topical treatment was reduced to 1 drop three times a day. A<TextGroup><PlainText>t the t</PlainText></TextGroup>hird month, no evidence of CIN was observed (<TextGroup><PlainText>Figure 3B </PlainText></TextGroup><ImgLink imgNo="3" imgType="figure"/>), and the patient has since remained free of disease.</Pgraph><SubHeadline>Case 2</SubHeadline><Pgraph>A 90-year-old man was referred to us with a mass in hi<TextGroup><PlainText>s r</PlainText></TextGroup>ight eye that had first been noticed three months earlier and had been growing progressively since then. VA was 20/200 in the right eye and hand movement in the left eye. Slit-lamp examination revealed a gelatinous temporal conjunctival mass (7 mm long, 10 mm wide) with dilated superficial vessels (Figure 4A <ImgLink imgNo="4" imgType="figure"/>). Fundus e<TextGroup><PlainText>xamination showe</PlainText></TextGroup>d age-related macular degeneration (AMD) in both eyes. Ocular movements were affected in th<TextGroup><PlainText>e form of abduction limitation in the right eye (Figure 4B </PlainText></TextGroup><ImgLink imgNo="4" imgType="figure"/>). An incisional biopsy was performed and a moderately differentiated SCC was confirmed (Figure 5 <ImgLink imgNo="5" imgType="figure"/>). Magnetic resonance imaging (MRI) showed malignant infiltration of the lateral rectus muscle (Figure 6A <ImgLink imgNo="6" imgType="figure"/>). Anterior segment optical coherence tomography (AS-OCT) displayed a hyperreflective lesion which involved the conjunctival tissue and spread over the corneal surface (Figure 6B). Due to the advanced stage of the tumor, an exenteration or radiotherapy treatment was offered, but the patient rejected both. After five months, the tumor had progressed and involved ocular globe tissues and soft periorbital structures (<TextGroup><PlainText>Figure 7 </PlainText></TextGroup><ImgLink imgNo="7" imgType="figure"/>). The patient died due to metastatic disease nine months after the initial diagnosis.</Pgraph></TextBlock> <TextBlock linked="yes" name="Discussion"> <MainHeadline>Discussion</MainHeadline><Pgraph>The incidence of epithelial conjunctival tumors is increasing due to higher ultraviolet light exposure, increased human papillomavirus infection rate <TextLink reference="1"></TextLink>, <TextLink reference="4"></TextLink>, and the rise in life expectancy. Other risk factors include a weakened immune system and tobacco exposure <TextLink reference="5"></TextLink>.</Pgraph><Pgraph>Epithelial conjunctival tumors are classified into one of two categories, depending on the degree to which the epithelial basement membrane is affected: CIN only affect the epithelium, while SCC spread to the basement membrane <TextLink reference="1"></TextLink>, <TextLink reference="3"></TextLink>. The classification for conjunctival squamous neoplasia has been reviewed by the American Joint Committee on Cancer (AJCC) and is based on the depth of invasion as well as the size and extent of the affected adjacent structures <TextLink reference="3"></TextLink>.</Pgraph><Pgraph>CIN most commonly occurs in individuals in their 6<Superscript>th</Superscript> or 7<Superscript>th</Superscript> decade of life, and is divided into three dysplasia types: mild, moderate, and severe. It usually affects the interpalpebral fissure area in the form of a gelatinous, sessile, or papillomatous mass with irregular margins, which can spread over the corneal epithelium <TextLink reference="1"></TextLink>. It is considered as a premalignant lesion and has a low risk of metastasizing. However, without rapid diagnosis and the establishment of appropriate treatment, there is a risk that atypical cells will invade the epithelial basement membrane and that the tumor will become a more malignant lesion with a worse prognosis.</Pgraph><Pgraph>Treatment is based on surgical excision with clear margins in combination with cryotherapy of the excised conjunctival edge. Cases with corneal involvement might also be managed with an alcohol epitheliectomy, which is in fact recommended <TextLink reference="4"></TextLink>. Due to the irregular and unclear margins of the tumor, its correct excisional surgery can in some cases be a challenge for the surgeon. Recurrence rates range from 5 to 53% <TextLink reference="1"></TextLink>, <TextLink reference="4"></TextLink>, <TextLink reference="6"></TextLink>. Adjuvant treatments with topical mitomycin C (MMC), 5-fluorouracil, or IFN-α2β are commonly used in order to avoid surgical procedures <TextLink reference="4"></TextLink>. Excellent outcomes have been reported with topical IFN-α2β as primary treatment for conjunctival and/or corneal disease. It also plays a role as adjuvant therapy in cases with positive margins or recurrence after surgical excision <TextLink reference="3"></TextLink>. As there is no established treatment protocol in terms of the duration over which IFN-α2β is administered, treatment must be individualized <TextLink reference="2"></TextLink>.</Pgraph><Pgraph>One third of patients develop irritative symptoms as side effects of surgery and chemotherapy, which often resolve quickly. One third of patients show radiation-induced complications that persist in the long term and consist of dry eye syndrome, lid alopecia, rubeosis, and secondary glaucoma <TextLink reference="4"></TextLink>.</Pgraph><Pgraph>The finding of epidermal growth factor receptor (EGFR) overexpression was an important aspect when considering targeted therapies in cases of inoperable advanced orbit and periocular SCC. EGFR inhibitors such as erlotinib have shown the effect of a significant decrease of SCC tumor size. Targeted therapy might be appropriate for non-surgical candidates, comprising patients with advanced metastatic orbital disease involving regional lymph nodes, advanced age, and/or patients with multiple comorbidities. This therapy is associated with fewer side effects and is better tolerated by patients <TextLink reference="7"></TextLink>.</Pgraph><Pgraph>Patients who reject treatment have a high mortality risk: it has been shown that these patients die after 13 months due to cancer progression <TextLink reference="2"></TextLink>. The patient presented in case 2 chose to reject any treatment, resulting in cancer progression and death after 9 months.</Pgraph><Pgraph>All patients must be checked every 3–6 months because most recurrences occur during the first year of follow-up, and 30% of recurrences occur more than one year after surgical treatment.</Pgraph><Pgraph>Miller et al. recommended that advanced stage SCC should be closely monitored as recurrences can occur even more than 5 years after treatment <TextLink reference="2"></TextLink>.</Pgraph></TextBlock> <TextBlock linked="yes" name="Conclusion"> <MainHeadline>Conclusion</MainHeadline><Pgraph>Early diagnosis is essential in epithelial conjunctival tumors. Histopathological examination allows a classification of the lesions as premalignant or malignant, which is crucial for the development of a therapeutic strategy.</Pgraph><Pgraph>An excisional biopsy with cryotherapy and free margins is sufficient in most cases of CIN. Topical chemotherapy can be used additionally. In cases of SCC, surgical excision may be sufficient, but may also be combined with adjuvant topical therapy, which may enhance treatment in cases of insufficient surgical removal. 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DOI: 10.1097/IOP.0b013e3182831bf3</RefTotal> <RefLink>https://doi.org/10.1097/IOP.0b013e3182831bf3</RefLink> </Reference> </References> <Media> <Tables> <NoOfTables>0</NoOfTables> </Tables> <Figures> <Figure format="png" height="448" width="543"> <MediaNo>1</MediaNo> <MediaID>1</MediaID> <Caption><Pgraph><Mark1>Figure 1: Slit-lamp examination; nasal limbal gelatinous mass with inferior corneal infiltration</Mark1></Pgraph></Caption> </Figure> <Figure format="png" height="328" width="923"> <MediaNo>2</MediaNo> <MediaID>2</MediaID> <Caption><Pgraph><Mark1>Figure 2: CIN was confirmed by histopathological study with free margins; normal conjunctival epithelium at the top of the biopsy and dysplastic cells at the bottom in image 10x; dysplastic epithelium with high mitosis index in image 20x</Mark1></Pgraph></Caption> </Figure> <Figure format="png" height="424" width="922"> <MediaNo>3</MediaNo> <MediaID>3</MediaID> <Caption><Pgraph><Mark1>Figure 3: A) One month later, the lesion had decreased. B) At the third month, CIN had disappeared.</Mark1></Pgraph></Caption> </Figure> <Figure format="png" height="534" width="456"> <MediaNo>4</MediaNo> <MediaID>4</MediaID> <Caption><Pgraph><Mark1>Figure 4: A) Slit-lamp examination: a gelatinous temporal conjunctival mass (7x10 mm) with dilated superficial vessels without corneal involvement is exposed. B) Abduction limitation in right eye.</Mark1></Pgraph></Caption> </Figure> <Figure format="png" height="407" width="921"> <MediaNo>5</MediaNo> <MediaID>5</MediaID> <Caption><Pgraph><Mark1>Figure 5: Anatomopathological study: moderately differentiated squamous cell carcinoma was confirmed; tumour cells present in corion</Mark1></Pgraph></Caption> </Figure> <Figure format="png" height="582" width="802"> <MediaNo>6</MediaNo> <MediaID>6</MediaID> <Caption><Pgraph><Mark1>Figure 6: A) Magnetic Resonance Imaging showed lateral rectus muscle involvement. B) Anterior Segment – Optical Coherence Tomography (AS-OCT): a hyperreflective lesion involving conjunctival tissue and spread over corneal surface</Mark1></Pgraph></Caption> </Figure> <Figure format="png" height="420" width="455"> <MediaNo>7</MediaNo> <MediaID>7</MediaID> <Caption><Pgraph><Mark1>Figure 7: Tumor progression involving ocular globe tissues and soft periorbital structures</Mark1></Pgraph></Caption> </Figure> <NoOfPictures>7</NoOfPictures> </Figures> <InlineFigures> <NoOfPictures>0</NoOfPictures> </InlineFigures> <Attachments> <NoOfAttachments>0</NoOfAttachments> </Attachments> </Media> </OrigData> </GmsArticle>