List of Abbreviations
AH – apocrine hidrocystoma |
|---|
HPV – human papillomavirus |
ICC – intercartilaginous cyst GCST – glucocorticoid therapy |
BN – blue nevus |
SGH – sebaceous gland hyperplasia |
DC – dermoid cyst |
DRT – distance radiotherapy GI – gastrointestinal tract |
KA – keratoacanthoma CT – computed tomography |
M – melanosis |
MN – melanocytic nevus MRI – magnetic resonance imaging |
HDD – hereditary benign dyskeratosis |
HDID – hereditary benign intraepithelial dyskeratosis |
OCT – optical coherence tomography |
PA – pleomorphic adenoma |
PM – pilomatricoma (Malherbe epithelioma) |
PAM – primary acquired melanosis |
PSS – papillary syringoadenoma |
REH – reactive epidermal hyperplasia |
SK – seborrheic keratoma |
CSS – papillary syringocystadenoma FNAB – fine-needle aspiration biopsy |
TL – trichilemmoma |
US – ultrasound examination |
EA – eccrine acrospiroma |
EH – eccrine hidrocystoma |
EIC – epidermal inclusion cyst |
ESA – eccrine syringoadenoma |
Terms and Definitions
Histological examination – microscopic study of tissue samples and organ fragments obtained from the pathological focus.
Laser surgery using a CO2 laser – a photodesructive procedure where thermal, hydrodynamic, and photochemical effects of light cause tissue destruction.
Anterior segment optical coherence tomography (OCT) – a non-invasive, informative, and sensitive method that allows for in vivo "optical biomicrometry".
Tumor surface imprint – a methodological technique used to obtain material for cytological examination.
First stage of rehabilitation – rehabilitation during the period of specialized treatment of the primary disease (including surgical treatment / chemotherapy / radiation therapy) in specialized departments of medical organizations.
Shave biopsy of skin neoplasms – a method of obtaining tissue samples for pathohistological examination of exophytic and flat skin neoplasms in the plane of the skin using a razor blade or scalpel.
Radiowave surgery – a non-contact method of cutting and coagulating soft tissues using high-frequency radiowaves (3.8–4.0 MHz).
Ultrasound biomicroscopy (UBM) – a high-precision ultrasound examination method of the anterior segment of the eye. It can be used for conjunctival and corneal neoplasms to obtain detailed characteristics of tumor structure, information on the condition of the anterior chamber angle and ciliary body, their involvement in the tumor process, and to determine the depth of scleral and/or corneal infiltration by the tumor.
Ocular ultrasound (ultrasound scanning) – scanning using ultrasonic waves. Ultrasound is a non-invasive, contact, instrumental method used in the diagnosis of eyelid skin tumors, including the eyelid commissure and conjunctiva, and for evaluating the efficacy of their treatment.
Cytological examination – an investigation based on the microscopic study of cellular structural features and the cellular composition of organs, tissues, and body fluids.
Excisional biopsy – a tissue sampling method in which the neoplasm is removed totally (completely) with a small (1–3 mm) margin of surrounding healthy tissue.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Benign neoplasms of the eyelids and conjunctiva, like those of other locations, are characterized by low mitotic activity and, consequently, slow growth, absence of infiltration into adjacent tissues, absence of metastatic potential, and the associated risk of generalization. Except when located in the central nervous system, these neoplasms are not life-threatening. Benign tumors consist of fairly well-differentiated cells that resemble the cells of normal corresponding tissue and largely retain the functions inherent to that tissue. Benign tumors predominate in the oncopathology structure of the eyelids and conjunctiva. Morphologically, these tumors are of epithelial, melanocytic, glandular, or embryogenetic origin.
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The etiology of benign neoplasms of the eyelids and conjunctiva is multifactorial. Risk factors include viral infection, exposure to physical factors, and embryogenesis disorders. A significant physical risk factor for the development of epithelial tumors, such as actinic keratosis, is exposure of the skin to ultraviolet B radiation (wavelength 290–320 nm) and ultraviolet A radiation (wavelength 320–400 nm). The etiology of certain benign eyelid and conjunctival tumors remains undetermined [1].
The development of a number of benign eyelid and conjunctival tumors is caused by genetic alterations. An example is deep penetrating plexiform melanocytoma, which is associated with genetic features of the WNT signaling pathway [2].
An example of the polyetiological nature of certain benign neoplasms of the eyelids and conjunctiva is eyelid skin keratosis, the occurrence of which can be determined by multiple factors: age, the influence of solar ultraviolet light, and genetic abnormalities [3].
1.3 Epidemiology of the Disease or Condition
Eyelid and conjunctival tumors account for 5–10% of skin and mucosal tumors at other sites and 15% of facial tumors. Benign forms represent 80% of eyelid and conjunctival tumors [4, 5, 6, 7, 8, 9, 10, 11]. Among all eyelid and conjunctival pathologies, true tumors constitute 47%. According to some data, melanocytic-type tumors predominate, while epithelial tumors are somewhat less common. Melanocytic nevus of both the eyelid skin and the conjunctiva ranks first in frequency [6, 8, 9, 11]. At the same time, some epidemiological studies of neoplasms of the ocular adnexa indicate a predominance of epithelial etiology among eyelid neoplasms compared to melanocytic ones (25.23% and 4.37%, respectively) and approximately equal ratios among conjunctival tumors (4.0% and 3.69%, respectively) [12].
1.4 Features of Coding the Disease or Condition
D21.0 Benign neoplasm of connective and other soft tissue of head, face and neck
D22.1 Melanocytic nevus of eyelid, including canthus
D23.1 Other benign neoplasms of skin of eyelid, including canthus
D31.0 Benign neoplasm of conjunctiva
1.5 Classification of the disease or condition
1.5.1 The classification of benign eyelid neoplasms is determined by their histological structure.
In accordance with the 5th edition of the World Health Organization classification, benign eyelid neoplasms are divided according to their origin and tissue type into:
Tumor-like conditions, hamartomas, and choristomas.
Epithelial tumors of the eyelids.
Tumors of the eyelid appendages.
Melanocytic tumors of the eyelids.
The diversity of benign eyelid neoplasms is presented in Table 1 [13].
Table 1. Classification of benign eyelid neoplasms
1.5.2 Classification of benign conjunctival neoplasms
According to the 5th edition of the World Health Organization classification, Table 2 presents the classification of benign conjunctival neoplasms [13]. The sources of benign conjunctival neoplasms are: conjunctival epithelium, stroma, and accessory structures of the conjunctiva [14, 15].
Table 2. Classification of benign conjunctival neoplasms
1.6 Clinical presentation of the disease or condition
The wide variety of benign tumors of the eyelids and conjunctiva determines the diversity of their clinical presentation.
1.6.1 Clinical presentation of benign eyelid tumors
A significant portion of the benign oncological pathologies of the eyelids and conjunctiva listed in Tables 1 and 2 is rare and represented by isolated cases described in the literature. The macroscopic manifestations of many benign neoplasms are uniform and, in non-melanocytic variants, consist of the appearance or presence of a well-circumscribed, slow-growing, flesh-colored or pale pink, painless solid mass [16].
The most frequently encountered benign eyelid neoplasms include papilloma, seborrheic and inverted follicular keratosis, melanocytic nevi, glandular tumors, Malherbe epithelioma, and cystic lesions [6, 8, 9, 11].
1.6.1.1 Tumor-like conditions, hamartomas, and choristomas
Epidermal inclusion cyst of the eyelid (epidermoid cyst) is a subcutaneous, soft, mobile, yellowish mass. It can be congenital or result from trauma or surgery. Spontaneous rupture of an EIC leads to an inflammatory reaction. Infection of the cyst sometimes occurs, most commonly by pathogens such as Staphylococcus aureus and Streptococcus pyogenes. Malignant transformation of an EIC is extremely rare. Multiple EICs occur in Muir–Torre and Gardner syndromes, which are characterized by multiple tumors. Unlike dermoid cysts, the lining of an EIC lacks skin appendages. EIC rupture causes a severe granulomatous inflammatory reaction and pseudocarcinomatous hyperplasia [17].
Intratarsal cyst of the eyelid (ITC). ITC ranks third in frequency among diseases of the tarsal plate after chalazion and sebaceous gland tumors. The clinical presentation resembles that of a chalazion, but ITC has more distinct margins and lacks signs of inflammation. They are predominantly localized on the upper eyelid. The histological picture of ITC is characterized by a capsule of wavy stratified squamous epithelium, the absence of keratohyalin granules, inflammatory cells, and hair elements, surrounded by a shell of dense collagen fibers. Correct diagnosis of the cyst is important as it determines the treatment strategy [18].
Dermoid cyst of the eyelid belongs to choristomas. It is a congenital condition that is extremely rarely presented in isolation on the eyelid and is more frequently combined with orbital involvement. The wall of the DC contains skin appendages: eccrine sweat glands, hair follicles, sebaceous glands. DC rupture causes a pronounced inflammatory reaction [19].
Phacomatous choristoma (Zimmerman tumor). This is a tumor of the lens placode localized in the deep layers of the eyelid or anterior orbit. It appears as a smooth subcutaneous mass, typically on the lower eyelid. It is formed as a result of the displacement of the lens placode into the mesoderm of the eyelid, while the child's own lenses are normal [20, 21].
1.6.1.2 Epithelial tumors
Verruca vulgaris. Common warts on the eyelids are rare. They are associated with HPV infection. Common warts are usually round with a rough surface. The histological signs of common warts are acanthosis, hyperkeratosis, orthokeratosis, and the presence in the granular layer of virus-infected cells with keratohyalin granules and vacuoles surrounding dark shrunken nuclei, so-called koilocytes. Squamous cells are densely packed and form papillary epidermal projections [23].
Squamous papilloma. Squamous papilloma of the eyelid is one of the most common benign eyelid tumors. It represents a hyperplasia of the squamous epithelium and appears as a flesh-colored mass on a broad base or stalk. Squamous papilloma on a stalk is often characterized by surface hyperkeratosis. Clinically, a sessile papilloma resembles an amelanotic melanocytic nevus and basal cell carcinoma, which necessitates differential diagnosis [24].
Keratoses of the eyelids include: seborrheic keratosis (SK), inverted follicular keratosis (IFK), and actinic keratosis (AK).
The clinical picture of IFK is typically represented by a slightly raised, light brown lesion with signs of hyperkeratosis. IFK frequently presents as a "cutaneous horn." A number of authors consider IFK to be a variant of seborrheic keratosis.
Seborrheic keratosis (SK) appears as a well-demarcated plaque elevated above the surrounding skin, ranging in color from flesh-colored to dark brown. SK is more common in elderly patients. Multiple rapidly appearing and growing foci of SK may indicate Leser–Trélat sign—an adenocarcinoma of the gastrointestinal tract (GIT).
The significance of early diagnosis and treatment of actinic keratosis (AK) is due to its potential for malignant transformation. It transforms into squamous cell carcinoma in approximately 20% of cases [24, 11, 25, 26].
Molluscum contagiosum (MC) is a fairly common pseudotumor disease that must be considered in the differential diagnosis of eyelid neoplasms. MC has a viral etiology; the causative agent is a poxvirus transmitted through direct contact from an infected person. Clinically, it appears as a flesh-colored mass, single or multiple, and can affect the skin of the face and other body areas. There is a central crater on top of the lesion from which a caseous mass can be expressed upon pressure. If these masses enter the conjunctiva, follicular conjunctivitis develops. Individuals with compromised immune systems, AIDS patients, and those on hormone therapy are most frequently affected [22].
1.6.1.3 Benign neoplasms of the accessory structures of the eyelid
Benign neoplasms of the eyelid appendages include tumors of eccrine and apocrine sweat glands, sebaceous glands, and hair follicles.
Glandular eyelid tumors include ductal syringoma (eccrine hydrocystoma of the eyelid), sebaceous gland hyperplasia and adenoma, eccrine syringadenoma, pleomorphic adenoma, tubular adenoma, and syringocystadenoma papilliferum. The external clinical manifestations of glandular lesions are largely similar, and differentiation is determined by histological structure. Multiple sebaceous gland tumors may be associated with Muir–Torre syndrome, which includes eyelid sebaceous gland tumors (adenoma or adenocarcinoma), keratoacanthomas, and malignant gastrointestinal tumors, a factor that must be considered when determining patient management strategy [27, 28, 29, 30, 31].
A specific feature of pleomorphic adenoma is its tendency toward recurrence and malignant transformation [30].
Syringocystadenoma papilliferum of the eyelid. SCAP most commonly develops on the scalp. The source of formation on the eyelids is the glands of Moll. In 75% of cases, it develops in a nevus sebaceus of Jadassohn during puberty as a component of organoid nevus syndrome and is frequently combined with epibulbar choristomatous malformations. The solitary variant of SCAP is usually confined to the eyelids and is not associated with organoid nevus syndrome [29].
Pilomatricoma (Malherbe epithelioma) and trichilemmoma are formed from hair follicles.
Pilomatricoma (benign calcifying epithelioma of Malherbe) is predominantly diagnosed in young individuals. In 17% of cases, it is localized in the periorbital region, most commonly on the upper eyelid or eyebrow. During its formation, which is sometimes characterized by rapid growth, the pilomatricoma acquires a stony-hard consistency, resulting in the " teeter-totter" sign—when pressure is applied to one edge of the nodule, the opposite edge rises [32].
Trichilemmoma of the eyelids (TL) is a benign tumor that develops from the trichilemmoma, a glycogen-rich zone of clear cells surrounding the hair shaft. Multiple forms of TL may be a manifestation of Cowden syndrome, inherited in an autosomal dominant manner, in which eyelid TLs are combined with papillomatous changes of the oral mucosa, thyroid nodules, lipomas, intestinal polyps, fibrous mastopathy, and breast and/or thyroid cancer [33, 34].
1.6.1.4 Melanocytic tumors
Melanocytic nevus (MN) usually appears at the age of 5–15 years. MN can be pigmented or amelanotic. MNs are subdivided into junctional, compound, and intradermal, which represent stages in the development of the same condition. A variant of MN can be congenital giant nevus, which is characterized by marked protrusion, hypertrichosis, and a tendency toward malignancy. There is also a variant of epithelioid cell nevus resembling melanoma, the so-called Spitz nevus [24].
Melanoma in situ of the eyelid skin (lentigo maligna). A fairly common skin pathology occurring exclusively among Caucasians. The incidence is 1 case per 300 people [11]. According to some data, in the absence of treatment for 10–15 years, it transforms into melanoma with a probability of up to 30% [11]. It is a disease of older age and develops in areas of the skin exposed to sun exposure. It appears as a flat brown patch of varying color intensity with clear borders. It is characterized by slow growth. Upon malignancy, the surface becomes uneven, and protruding areas appear. Histologically, melanocytes are detected at the level of the basal layer of the epidermis with a mild degree of atypia, and nuclear polymorphism is noted: nuclei of various sizes and shapes are present. It is believed that lentigo maligna is a manifestation of PAM [36, 37].
1.6.2 Clinical characteristics of benign conjunctival neoplasms
Benign conjunctival neoplasms frequently encountered by ophthalmologists in clinical practice include melanocytic nevi and melanoses, papillomas, congenital conditions, and cysts [4, 37, 38].
1.6.2.1 Tumor-like conditions and choristomas
Epithelial inclusion cyst of the conjunctiva. Forms spontaneously or as a result of trauma, including surgical trauma, or inflammation. Histologically, the cysts are lined with epithelium and contain clear fluid, sometimes cellular detritus [39].
Pseudoepitheliomatous hyperplasia (PEH) and keratoacanthoma (KA). Benign proliferation of conjunctival epithelial cells. It may develop against the background of chronic inflammation, especially at the site of a pinguecula, pterygium, or foreign body. A variant of hyperplasia—keratoacanthoma—is characterized by rapid growth and hyperkeratosis. In appearance and histology, KA is similar to squamous cell carcinoma. A relative difference is its rapid onset. KA is distinguished by its ability to spontaneously regress. KA looks like an area of leukoplakia or a gelatinous lesion. Histologically, massive acanthosis, keratinization, and parakeratosis are revealed [40].
Pterygium and pinguecula are degenerative actinic conditions that can simulate tumors. Pterygium occurs in approximately 10% of the population [41]. The predominant localization is the limbal area, often bilaterally within the palpebral fissure.
Tumor-like conditions that must be considered in the differential diagnosis of benign eyelid and conjunctiva neoplasms also include keratotic plaque and actinic keratosis.
Choristomatous anomalies of the conjunctiva. Depending on the presence of one or more cell types, choristomas are subdivided into simple and complex. The more common conjunctival choristomas are dermolipoma or lipodermoid and dermoid [42, 43].
When localized in the conjunctival fornix, it often manifests only in adolescence as a fluctuating pale yellow protrusion.
The rare epibulbar osseous choristoma has a dense bone consistency and is sometimes fixed to the sclera [44].
1.6.2.2 Epithelial benign neoplasms
Squamous papilloma of the conjunctiva (SPC). The development of SPC is associated with HPV infection. It occurs at any age. The lesion appears as a protruding nodule with a papillary structure and abundant vessels. Its occurrence in newborns is associated with HPV infection from the mother during childbirth [11, 45, 46].
Hereditary benign intraepithelial dyskeratosis (HBID) develops in the first decade of life as the appearance of dense plaques, often V-shaped, in the temporal or nasal areas of the perilimbal conjunctiva. HBID is inherited in an autosomal dominant manner and occurs in isolated populations with a high frequency of consanguineous marriages—African Americans, American Indians, and less frequently Caucasians in certain regions of the USA. Cases of malignant transformation are not known [44, 47].
The lacrimal caruncle has a complex structure and includes conjunctival and skin elements. 95% of tumors in this localization are benign. A specific tumor developing on the lacrimal caruncle is oncocytoma. Oncocytoma appears as a solid or cystic reddish lesion with a bluish tint. It grows slowly and is usually asymptomatic. Cases of malignant transformation have not been described [48, 49].
1.6.2.3 Melanocytic benign tumors
Benign epithelial melanoses of the conjunctiva include constitutional and primary acquired melanosis.
Constitutional or racial melanosis. A relatively common condition in dark-skinned individuals. Flat pigmentation is noted in the limbal area, often annularly arranged, less frequently in the fornices and on the palpebral conjunctiva. Malignant transformation occurs extremely rarely.
Primary acquired melanosis of the conjunctiva (PAM) tends to transform into melanoma. Unlike nevus, PAM appears in middle age. Diffuse brown pigmentation that changes over time is characteristic. PAM is more common in light-skinned individuals. Binocular involvement is extremely rare. In the presence of atypia in melanocytes, the risk of developing melanoma is 50%, while in the absence of atypia, there is no risk of malignant transformation [50].
Nevus. Circumscribed nevus is the most common melanocytic pathology of the conjunctiva. The presence of cysts is characteristic of a nevus. The degree of pigmentation varies. The lesion is slightly elevated above the surrounding conjunctiva and has clear borders. The risk of malignant transformation is less than 1%. Pigmentation may increase over time and can acquire a nested pattern. Histologically, it represents a nested accumulation of benign melanocytes in the stroma at the level of the basal layer. It can be junctional, compound, or deep intrastromal [44, 47].
Juvenile conjunctival nevus (JCN). JCN with signs of inflammation is a fairly common pathology. It develops in puberty or early adolescence. The lesion appears as a bright pink, slightly protruding nodule, most often localized in the limbal area. The lesion is characterized by the presence of cysts of various sizes, intrinsic and nourishing vessels. A history of systemic allergy, atopic dermatitis, asthma, or allergic conjunctivitis is frequent. Although JCN is a benign condition, the detection of activity signs is an indication for surgical treatment. Topical administration of antiallergic and anti-inflammatory drugs reduces inflammatory symptoms, which can mimic nevus regression [51, 56].
Blue nevus of the conjunctiva. A rare congenital conjunctival pathology. It can be located in any areas of the conjunctiva, most often in the stroma of the bulbar conjunctiva. Transformation into melanoma is extremely rare [52, 53].
WNT-activated deep penetrating plexiform melanocytoma (nevus). Deep penetrating plexiform melanocytoma of the conjunctiva is clinically and histologically similar to malignant melanoma. In its clinical presentation, it resembles pigmented nevus, blue nevus, and melanoma. Histologically, an inverted triangle-shaped nevus lesion is revealed, with its apex deeply penetrating the conjunctival stroma. The condition is characterized by a low degree of cellular atypia and low mitotic activity. This is a genetically determined condition associated with the WNT signaling pathway, which is involved in cell growth, mobility, and differentiation during embryonic development [53].
Mixed nevus accounts for 20–24% of conjunctival nevi. It is a combination of typical nevus cells and blue nevus cells [55].
1.6.2.4 Vascular neoplasms of the eyelid and conjunctiva
Vascular lesions found on the eyelids and conjunctiva are not true neoplasms, but rather malformations or hamartomas. Nevertheless, these pathologies may eventually progress or undergo involution, change in size, and thus exhibit properties characteristic of true benign neoplasms. Cavernous hemangiomas, lymphangiomas, and varices are rarely found in isolation on the eyelids and/or conjunctiva and predominantly represent orbital pathology. Capillary hemangiomas localized to the eyelids and/or conjunctiva are more common [35, 36, 37, 38, 59, 60, 61, 62].
Infantile capillary hemangiomas (ICHs) often manifest immediately at birth. Clinically, an ICH presents as a red vascular birthmark ("strawberry" hemangioma) and is characterized by stages of development: it progresses during the first few months of life and then gradually regresses over 1–3 years. By the age of 7, 75% of ICHs undergo involution and disappear. Histologically, an ICH consists of capillary-formed lobules separated by connective tissue septa. The regression process involves the replacement of capillaries with fibrous tissue [58].
On the conjunctiva, a capillary hemangioma appears as a bright red, sometimes bleeding ("bloody tears"), protruding lesion. Like eyelid ICHs, conjunctival hemangiomas may initially increase in size over several months and then spontaneously regress [34].
2. Diagnostics, medical indications and contraindications for diagnostic methods
Introduction: the clinical picture forms the basis of diagnosis. In many cases, a biomicroscopic examination is sufficient to make a correct diagnosis. In some instances, the clinical presentations of benign eyelid and conjunctival neoplasms are similar; therefore, additional diagnostic methods are employed, such as ultrasound, OCT, MRI, and CT. These additional methods allow the physician not only to clarify the diagnosis, but also to determine the extent of the tumor process and involvement of adjacent structures, as well as to plan the timing, scope, and tactics of treatment.
Criteria for establishing the diagnosis of benign neoplasms of the eyelids and conjunctiva:
anamnestic data, physical examination, biomicroscopy, optical coherence tomography, photographic documentation, and the results of cytological and histological examinations.
2.1 Complaints and Anamnesis
It is recommended to take a medical history (collection of history and complaints in eye disorders) in all patients or parents of pediatric patients to obtain diagnostically significant information: time of onset, dynamics, and family history [3, 24].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: when taking the history, attention should be paid to the time of onset of the lesion, specifying its size and location, coloration, presence of triggering factors, and the nature of changes in the pathological focus.
2.2 Physical Examination
It is recommended that all patients with neoplasms of the eyelids and conjunctiva undergo an initial ophthalmological examination (initial ophthalmologist examination [evaluation and consultation]) to identify local pathological processes as an etiological factor, as well as concomitant systemic diseases. During the physical examination (palpation in eye disorders, visual examination of the eyes), attention should be paid to changes in the skin of the face, eyelids, edema, asymmetries, and lymphadenopathy [44, 64].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: in addition to examining the neoplasm and surrounding tissues (palpation in eye disorders), if a malignant or systemic nature of the pathological process is suspected, palpation of the regional lymph nodes of the head and neck should be performed.
2.3 Laboratory Diagnostics
Cytological and/or histological examination
It is recommended that all patients undergo a pathomorphological examination of biopsy (surgical) material (pathoanatomical examination of biopsy [surgical] material of the eyeball, its accessory apparatus, orbit, and exudate during surgery) to verify the diagnosis upon tumor removal and/or biopsy [64].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
It is recommended to perform a cytological examination—scraping from the conjunctival neoplasm (cytological examination of conjunctival scraping) or eyelid (cytological examination of eyelid scraping)—in patients with a somatically burdened status and/or when the expediency of surgical removal of the neoplasm is not obvious in order to verify the diagnosis; for melanocytic tumors with suspected malignancy, cytological examination of conjunctival imprints and/or eyelid imprints is performed [64, 77].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
It is recommended to perform a puncture biopsy (fine-needle aspiration biopsy) in patients with large neoplasms (at least 10 mm in minimal measurement) with subcutaneous or subconjunctival localization and unaltered epidermis or conjunctival epithelium, when imprints or scrapings do not yield sufficient diagnostic material for morphological verification of neoplasms suspected of being malignant [79].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
2.4 Instrumental Diagnostics
2.4.1 Visometry
It is recommended to perform visometry in all patients when the neoplasm is localized in the limbus and/or cornea due to the potential impact of the neoplasm on refraction or its spread to the optical zone of the cornea, as well as in pediatric patients at risk of developing deprivation amblyopia [44, 64, 84].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: the examination is performed in a lighted room using specialized charts.
2.4.2 Biomicroscopy
It is recommended to perform biomicroscopy (eye biomicroscopy) in all patients with neoplasms of the eyelids and conjunctiva to assess the condition of the skin and eyelid accessories, their shape and position, the state of the conjunctiva and cornea, and to determine the size, color, pigmentation, margins, and structure of the neoplasm, the presence of intrinsic blood vessels, and the condition of surrounding tissues [3, 4, 6, 57, 64, 85].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
2.4.3 Anterior segment optical coherence tomography (OCT)
It is recommended to perform anterior segment optical coherence tomography (OCT) (optical examination of the anterior segment of the eye using a computer analyzer) in patients with conjunctival neoplasms to clarify the diagnosis, extent of the process, and evaluate the condition of surrounding tissues [57].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: performed to determine dimensions, assess the internal structure of the neoplasm and the condition of surrounding tissues, and in the postoperative period—to evaluate the scar and the radicality of the treatment performed.
2.4.4 Ultrasound examination of the eyelids and anterior segment
It is recommended to perform ultrasound scanning of the eyeball, eyelids, and anterior segment of the eye (ultrasound scanning of the anterior segment of the eye, ultrasonic Dopplerography of orbital and eyeball vessels, ultrasound scanning of the orbit) in patients with neoplasms of the eyelids and conjunctiva to clarify the diagnosis based on their echographic characteristics, the extent of the process, and to assess the condition of surrounding tissues [57, 76, 78].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: if invasion of the conjunctival neoplasm into the sclera and/or cornea, anterior chamber angle structures, or uveal tract is suspected, ultrasound scanning of the anterior segment of the eye (ultrasound scanning of the anterior segment of the eye) is performed to determine the involvement of these structures in the tumor process and to plan the scope of surgical treatment. Anterior segment ultrasound is also used to analyze the outcomes of surgical interventions [57, 76, 78].
2.4.5 Computed tomography and/or magnetic resonance imaging
It is recommended to perform CT (computed tomography of the orbits) or orbital MRI (magnetic resonance imaging of the orbit), in the absence of contraindications, with intravenous bolus contrast enhancement (computed tomography of the orbits with intravenous bolus contrast enhancement and magnetic resonance imaging of the orbits with contrast, respectively) in patients suspected of having the process spread beyond a single anatomical region to determine the exact extent of the lesion [57, 82].
Level of Evidence 4Confidence Level C (Level of Evidence – 4).
Comments: CT is recommended for dermoid cysts and eyelid and conjunctival hemangiomas when orbital tissue involvement is suspected and to assess the condition of the bone walls.
Compared to CT, MRI allows for a more detailed examination of soft tissue status, but does not provide adequate information regarding bone structure, calcifications, or angioliths. It is the preferred imaging method in children as it does not involve ionizing radiation.
2.4.6 Photoregistration
It is recommended to perform photographic documentation (biomicrophotography of the eye and its accessory apparatus) of the pathological focus in all patients with eyelid and/or conjunctival tumors for dynamic monitoring [83, 86].
Confidence Level C (Level of Evidence – 4).
2.5 Other Procedures
None provided.
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
Introduction.
Surgical treatment.
The treatment of eyelid and conjunctival tumors falls within the purview of an ophthalmologist specializing in the treatment of oncological diseases of the eye and its accessory apparatus, and possessing appropriate training.
Main methods include radiowave surgery, carbon dioxide laser surgery, electrocoagulation, and combinations thereof, as well as traditional microsurgery for the removal of small cystic lesions.
Radiosurgery holds a priority position due to a number of parameters, such as precision and ablasticity. The impact of high-frequency radio waves (3.8–4.0 MHz) on tissues causes cellular fluid "vaporization," with a coagulative effect 2–3 times lower than that of laser and electrosurgery. A variety of electrode types are designed for removing lesions of various sizes and shapes.
Laser surgery
Focused coherent light produces a photodesstructive effect via thermal, photochemical, and hydrodynamic mechanisms. This ensures wound sterility, rapid healing (in 10–14 days), ablasticity, antiblasticity, and minimal trauma to surrounding healthy tissues.
Electrocoagulation causes thermal constriction of blood vessels and ensures hemostasis.
The choice of method depends on the localization, volume of the lesion, and extent of the process.
It should be noted that the choice of surgical method is determined by the surgeon and is based on the nature of the tumor process, its localization, volume of the lesion, and extent of the process.
Surgical treatment of eyelid and conjunctival tumors is a microsurgical intervention performed exclusively in an operating room setting using high-resolution operating microscopes and microsurgical instruments. Compliance with the above recommendations makes it possible to achieve the best cosmetic and functional outcome, reduce the frequency and severity of complications, and significantly lower the risk of recurrence.
3.1 Conservative Treatment
Conservative treatment as monotherapy is not performed.
3.2 Surgical Treatment
Recommended mandatory surgical treatment of eyelid and conjunctival tumors in the presence of progression signs in all patients to prevent malignant transformation and tumor spread [65, 66, 67].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: signs of tumor progression are considered to be: increase in the volume of the lesion, change in color, including the appearance of nested and/or perifocal pigmentation, and the presence of feeder vessels. The surgical management strategy for benign eyelid and conjunctival tumors depends on the type of tumor process, localization, volume of the lesion, its extent, and the patient's age.
3.2.1 Surgical treatment methods
Recommended surgical treatment for patients with progressive solid eyelid lesions (with/without grafting) (radioexcision (Radioexcision of accessory visual organ neoplasms), laser destruction/excision (Laser destruction of neoplasms of the retina, eyelids, conjunctiva, choroid; Laser vaporization of accessory visual organ neoplasms; Laser excision of accessory visual organ neoplasms), removal (Removal of eyelid neoplasm, Free skin grafting with a dermatome perforated graft, Upper eyelid plastic surgery without tissue transplantation via transconjunctival approach, Eyelid plastic surgery (blepharoplasty) with and without tissue transplantation) with the aim of removing the lesion and subsequent morphological verification of the diagnosis [63, 66, 67].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: surgical methods of eyelid tumor removal (radiowave surgery, laser excision, and/or vaporization) without grafting are highly effective for removing small, well-circumscribed lesions that do not lead to impaired eyelid position and function. When a significant defect is formed, various plastic surgery techniques should be performed to create anatomical and functional integrity and improve reparative processes. The choice of plastic surgery procedures (free skin grafting (Free skin grafting with a dermatome perforated graft), advancement musculocutaneous flap grafting, pedicle flap grafting (upper eyelid plastic surgery without tissue transplantation via transconjunctival approach)) after surgery depends on the volume of removed tissue and aims to preserve the integrity of the organ and maximize the restoration of its function.
Recommended for patients with bulbar conjunctival lesions: radioexcision (Radioexcision of accessory visual organ neoplasms) with local tissue grafting (Conjunctival cavity plastic surgery) to achieve radical removal of the lesion with minimal trauma to surrounding tissues and to repair the conjunctival defect [63, 66, 67].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: this group includes patients with isolated lesions of the bulbar conjunctiva without extension to other tissue structures (cornea). Closure of the conjunctival defect is performed to prevent the development of granulation polyps and infection of the surgical wound.
Recommended for patients with conjunctival lesions extending to the cornea: combined surgical tumor removal to prevent tumor growth, which reduces the degree of refractive errors [65, 66]. In case of deep infiltrative tumor growth into the corneal layers, lamellar or penetrating keratoplasty using donor cornea (Keratoplasty (corneal transplantation), Lamellar keratoplasty, Penetrating keratoplasty) may be performed [85, 87].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: combined removal of the lesion in this group of patients involves excision of the tumor from the corneal side using a "round" microknife, followed by radiosurgical removal of the tumor from the conjunctival side and closure of the conjunctival defect in the limbal region using the adjacent conjunctiva via an advanced flap technique. In this case, the superficial corneal defect is left for secondary healing.
3.2.1.1 Surgical treatment of giant (systemic) melanocytic neoplasms of the eyelids and conjunctiva
Recommended staged combined surgical treatment (Radioexcision of accessory visual organ neoplasms, Laser destruction of neoplasms of the retina, eyelids, conjunctiva, choroid, Laser vaporization of accessory visual organ neoplasms, Myotomy, tenotomy of the extraocular muscle) for patients with systemic (giant) melanocytic nevi of the eyelids and conjunctiva to prevent malignant transformation and improve the cosmetic and functional state of the organ [80, 81].
le CLoE 4Level of Evidence C (level of reliability of evidence – 4).
Comment:
The necessity of treating systemic pigmented lesions is due to reducing the risk of melanoma development. Early initiation of treatment (in childhood) allows for better tolerance of the treatment stages.
The choice of surgical management strategy for systemic eyelid and conjunctival tumors is determined by the extent of the process. The staged nature of surgical treatment aims to reduce the risk of postoperative complications associated with severe scarring in tissues (ectropion, entropion, lagophthalmos, symblepharon, incomplete closure of the palpebral fissure, etc.), as well as to decrease the risk of wound infection and cosmetic and functional damage.
Recommended combined (using radiowave and laser surgery) surgical treatment for patients with systemic (giant) melanocytic nevi of eyelid and conjunctival tumors to prevent the development of postoperative complications (Radioexcision of accessory visual organ neoplasms, Laser destruction of neoplasms of the retina, eyelids, conjunctiva, choroid, Laser vaporization of accessory visual organ neoplasms, Myotomy, tenotomy of the extraocular muscle) [65, 69, 70].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: combining surgical treatment methods allows for the best cosmetic and functional treatment outcomes, taking into account various anatomical features.
3.2.1.2 Surgical treatment of cystic lesions of the eyelids and conjunctiva
Recommended for patients with cystic lesions: radioexcision and/or traditional excision (Radioexcision of accessory visual organ neoplasms, Laser destruction of neoplasms of the retina, eyelids, conjunctiva, choroid, Removal of eyelid xanthelasmas, Removal of corneal and conjunctival neoplasms) of cystic (except for blood cysts) eyelid and conjunctival lesions to prevent their growth and improve the cosmetic effect [69, 71, 72].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: radiosurgical technique for tumor removal is preferred because it does not cause a pronounced burn reaction in surrounding tissues, while allowing complete removal of the lesion capsule and providing good vascular coagulation, which prevents recurrences.
3.2.1.3 Surgical treatment of vascular neoplasms of the eyelids and conjunctiva
Recommended performance of radioexcision (Radioexcision of accessory visual organ neoplasms) and/or laser destruction (Laser destruction of neoplasms of the retina, eyelids, conjunctiva, choroid) of capillary hemangioma of the eyelids in children (10–15% in the first year of life) to prevent spontaneous bleeding and disease progression [73].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).
Comment: radiocoagulation is the preferred treatment method for small nodular capillary hemangiomas of the skin in children, as it allows not only excision of the lesion while minimizing trauma to surrounding tissues, but also coagulation of the feeder vessel.
It is recommended to perform immersion diathermy coagulation (Immersion diathermy coagulation for neoplasms of the eye adnexa) in older patients with mixed eyelid hemangiomas to achieve ablation of pathological vessels. Depending on the extent of the lesion, immersion diathermy coagulation (Immersion diathermy coagulation for neoplasms of the eye adnexa) can be performed in several stages. The timing and staging are determined strictly individually [63, 69, 67, 71].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: immersion electrocoagulation is preferred in the treatment of deeply localized vascular malformations of the eyelids.
It is recommended to perform combined surgical treatment (Radioexcision for neoplasms of the eye adnexa, Laser destruction of neoplasms of the retina, eyelids, conjunctiva, choroid, Removal of eyelid xanthelasmas, Removal of corneal and conjunctival neoplasms) in patients with large eyelid and conjunctival hemangiomas to normalize the organ's function, prevent lesion growth, and improve the cosmetic outcome [65, 71, 68].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: the choice of treatment tactics and the scope of surgical intervention depend on the examination results, operating room equipment, and the surgeon's preferences.
3.3 Treatment of infantile hemangiomas of the eyelid and conjunctiva
It is recommended to perform external beam radiation therapy (EBRT) for neoplasms of the eye and its adnexa with/without oral systemic corticosteroids in patients with racemose (infantile) and capillary hemangiomas of the eyelid and conjunctival tumors under the age of 2.5 years to achieve tumor resorption, restore organ function, and provide a cosmetic effect [67, 74, 75, 76].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: EBRT is most effective in early childhood. Systemic corticosteroid therapy is prescribed by a radiation oncologist individually, depending on the nature and extent of the lesion and the prevalence of the process. If a residual tumor persists, its surgical removal is possible.
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Specific rehabilitation is not indicated for patients who have undergone treatment for a benign neoplasm.
5. Prevention and Dispensary Observation
It is recommended to monitor patients after treatment for a benign neoplasm of the eyelids and conjunctiva without signs of recurrence and with a satisfactory cosmetic and functional-anatomical result at medical organizations at their territorial place of registration. The frequency of examinations is determined by the general schedule of dispensary follow-up by an ophthalmologist (Dispensary visit (examination, consultation) of an ophthalmologist) at least twice a year during the first 2 years of dispensary follow-up, and thereafter once a year [88, 89].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: dispensary follow-up for adult patients is established in accordance with Order of the Russian Ministry of Health No. 168n dated March 15, 2022 (as amended on February 28, 2024) "On Approval of the Procedure for Dispensary Follow-up of Adults".
It is recommended as part of dispensary follow-up, when indicated, to perform photoregistration (Biomicrophotography of the eye and its adnexa) of the pathological focus of the anterior and posterior segments of the eye, ultrasound examination of the eyeball, ultrasonic scanning of the anterior segment of the eye, ultrasonic dopplerography of orbital and eyeball vessels, ultrasonic scanning of the orbit, fluorescence angiography of the eye, optical examination of the anterior segment of the eye using a computer analyzer, computed tomography of the orbit, magnetic resonance imaging of the orbit, and pathomorphological examination of biopsy (surgical) material of the eyeball, its adnexa, orbit, and exudate for the early detection of tumor recurrence and timely referral for a primary oncologist consultation (examination, evaluation) [90–92].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
Comment: if recurrence or continued growth of the lesion is detected, the patient may be referred to a level III–IV medical organization.
Rehabilitation
Specific rehabilitation is not indicated for patients who have undergone treatment for a benign neoplasm.
6. Organization of Medical Care
Primary specialized health care is provided by an ophthalmologist and, if necessary, an oncologist in a polyclinic, ophthalmology office of a consultative and diagnostic center, consultative and polyclinic department of an ophthalmological hospital or clinic.
When an eyelid and/or conjunctival tumor is suspected or detected in a patient, general practitioners, district general practitioners, general practice physicians (family physicians), medical specialists, and mid-level medical personnel shall refer the patient in the established manner for a consultation with an ophthalmologist, who subsequently decides on the patient management tactics; keeps the patient under observation or routinely refers them to a specialized ophthalmological institution providing health care to ocular oncology patients. If a malignant neoplasm is suspected, the ophthalmologist refers the patient for a consultation with an oncologist.
An ophthalmologist at a specialized ophthalmological institution with training in ocular oncology, together with an oncologist, when a malignant neoplasm is suspected, arranges for the collection of cytological and/or biopsy (surgical) material, as well as the performance of other diagnostic tests necessary to establish a diagnosis.
Treatment of small, locally situated benign neoplasms of the eyelids and conjunctiva that do not involve adjacent structures, such as the orbital region or periorbital tissues, and do not require reconstructive and plastic procedures, is performed in level II medical institutions as part of specialized medical care not classified as high-tech medical care. Specialized medical care for adult patients in this context may be provided in either a day hospital or a 24-hour inpatient setting. Surgical treatment of children with benign neoplasms of the eyelids and/or conjunctiva is performed exclusively in a 24-hour inpatient setting.
Patients with a benign neoplasm of the eyelids and/or conjunctiva affecting more than 1/3 of the eyelid length with involvement of the eyelid tarsus or the fibrous capsule of the eye, sclera and/or cornea, such as a dermoid cyst or limbal dermolipoma involving the cornea, requiring extensive reconstructive plastics, i.e., high-tech medical care, must be referred to a level III medical organization. Patients with vascular benign neoplasms of the eyelids and/or conjunctiva, such as infantile hemangiomas, who are scheduled to undergo radiation therapy for regression or stabilization of the neoplasm, for cosmetic purposes, or to make the tumor operable, must also be referred to a level III medical organization with appropriate staffing and technical conditions.
The provision of medical care to patients with benign tumors of the eyelids and/0r conjunctiva is carried out on a scheduled basis.
Indications for emergency or urgent hospitalization in a medical organization are:
- cases where the neoplasm is complicated by bleeding or an acute inflammatory reaction resulting from trauma or infection, such as bleeding from a hemangioma or vascular malformation or inflammation of a dermoid cyst.
Indications for hospitalization in a medical organization in a planned form are:
- the need for specialized antineoplastic treatment (surgical intervention, radiation therapy, reconstructive plastics).
Indications for patient discharge from a medical organization:
- completion of a course of treatment or one of the stages of specialized, including high-tech, medical care in a 24-hour or day hospital setting in the absence of treatment complications requiring drug correction and/or medical interventions in an inpatient setting.
Medical care, with the exception of medical care provided as part of clinical approbation, in accordance with Federal Law No. 323-FZ dated November 21, 2011 (as amended on November 17, 2025)
"On the Fundamentals of Health Protection in the Russian Federation", is organized and provided:
1) In accordance with the regulation on the organization of medical care by types of medical care, which is approved by the authorized federal executive body;
2) In accordance with the procedure for the provision of care in the "oncology" profile, which is mandatory for execution throughout the Russian Federation by all medical organizations;
3) Based on these clinical guidelines;
4) Taking into account the standards of medical care approved by the authorized federal executive body.
7. Additional Information
Not applicable.
Criteria for Evaluating the Quality of Medical Care
№ | Quality criteria | Performance assessment (yes/no) |
|---|---|---|
1 | Complaints and anamnesis were collected (Collection of anamnesis and complaints in eye pathology) | yes/no |
2 | A physical examination was performed (Initial examination by an ophthalmologist with visual examination of the eyes and palpation in eye pathology) | yes/no |
3 | Slit-lamp biomicroscopy of the eye was performed | yes/no |
4 | Anterior segment optical coherence tomography of the eye was performed (optical examination of the anterior segment using a computerized analyzer) | yes/no |
5 | Ultrasonography of the eyeball, ultrasound scanning of the anterior segment, color Doppler ultrasound of orbital and eyeball vessels, and ultrasound scanning of the orbit were performed | yes/no |
6 | For benign neoplasms of the eyelid and/or conjunctiva with suspected involvement of orbital tissues, computed tomography (computed tomography of the orbit, computed tomography of the orbit with intravenous bolus contrast enhancement and/or magnetic resonance imaging (magnetic resonance imaging of the orbit, magnetic resonance imaging of the orbits with contrast enhancement) was performed | yes/no |
7 | Cytological examination was performed (cytological examination of a conjunctival scraping or cytological examination of conjunctival impressions, or cytological examination of an eyelid scraping, or cytological examination of an impression from an eyelid neoplasm, or cytological examination of a fine-needle aspiration biopsy smear, or pathological anatomical examination of biopsy (surgical) material of the eyeball, its accessory apparatus, orbit, and exudate during surgery) | yes/no |
8 | Biomicrophotography of the eye and its accessory apparatus was performed | yes/no |
9 | Surgical removal of eyelid neoplasms and/or removal of corneal and conjunctival neoplasms was performed | yes/no |
10 | Radioexcision for neoplasms of the ocular accessory apparatus was performed | yes/no |
11 | Free skin grafting with a dermatome-perforated graft, transposition musculocutaneous flap plasty, pedicle flap plasty (eyelid plasty [blepharoplasty] with and without tissue transplantation) were performed | yes/no |
12 | Laserexcision and/or laser vaporization for neoplasms of the ocular accessory apparatus were performed | yes/no |
13 | Immersion diathermy coagulation for neoplasms of the ocular accessory apparatus was performed | yes/no |
14 | External beam radiation therapy for neoplasms of the eye and its accessory apparatus was performed in patients under 2.5 years of age with racemose (infantile) and capillary hemangiomas of the eyelid and conjunctiva tumors | yes/no |
15 | Follow-up examination (evaluation, consultation) by an ophthalmologist after treatment of a patient with a benign neoplasm of the eyelid and/or conjunctiva was performed | yes/no |
References
Show references
Hafner, C. Benign Epithelial Tumors. In: Plewig, G., French, L., Ruzicka, T., Kaufmann, R., Hertl, M. (eds) Braun-Falco´s Dermatology. Springer, Berlin. 2022; p.1767-1777.
Adrianna Eder, Tatyana Milman, Hardeep-Singh Mudhar, Sara E. Lally, Carol L. Shields, Khanh Bui, Jill R. Wells, Hans E. Grossniklaus. Unusual conjunctival melanocytic proliferations. Report of five cases and review of the literature. Survey of OphthalmologyVolume 69, Issue 2, March–April 2024, Pages 230-240 doi: 10.1016/j.survophthal.2023.10.012
Eren S, Fritz K, Salavastru CM, Tiplica GS. The most common benign cutaneous neoplasms of the epidermis and appendages and their treatment. Hautarzt. 2022 Feb; 73 (2):94-103.
Obata H. et al. Incidence of benign and malignant lesions of eyelid and conjunctival tumors Vol.109, Nippon Ganka Gakkai zasshi. 2005. p 573-9.
Borodin Yu.I., Valsky V.V. Preliminary results of treatment of malignant tumors of the ocular accessory apparatus with a reduced dose of proton radiation. Russian Ophthalmological Journal. 2009; 2 (3): 4–7.
Brovkina A.F. Ophthalmic Oncology. Moscow: Meditsina, 2002. 424 p.
Gabdrakhmanova A.F., Gallyamov M.K., Zhumaniyazov A.Zh., Babushkin A.E. Cases of Malherbe epithelioma and eyelid skin lymphocytoma. Vestnik Oftalmologii. 2003; 119 (1): 42–43.
Likhvantseva V.G., Anurova O.A. Eyelid Tumors: Clinical Presentation, Diagnostics, Treatment. Moscow: Goetar-Media, 2007. 447 p.
Chervonnaya L.V. Pigmented Skin Tumors. Moscow: GEOTAR-Media, 2016. 224 p.
Saakyan S.V., Ivanova O.A., Gusev G.A., Myakoshina E.B. Radiosurgical reconstructive and restorative treatment of conjunctival nevi. Modern Technologies and Capabilities of Reconstructive, Restorative, and Aesthetic Surgery: Collection of Articles of the II International Conference. Moscow, October 19–20, 2010. Moscow, 2010. 19–21.
Shields J.A., Shields C.L. Eyelid, Conjunctival, and Orbital Tumors. An Atlas and Textbook: in 2 vols. Vol. Moscow: Panfilov Publishing House, 2017. 448 p.
Golovanova M.A., Saakyan S.V., Denisenko A.N. Epidemiology of ophthalmic oncological diseases in the adult population of the Nizhny Novgorod Region. Head and Neck Tumors. 2019;9(4):43–48. doi: 10.17650/2222-1468-2019-9-4-43-48
Tatyana Milman, Hans E. Grossniklaus, Gabrielle Goldman-Levy, Tero T. Kivelä, Sarah E. Coupland, Valerie A. White, Hardeep Singh Mudhar, Charles G. Eberhart, Robert M. Verdijk, Steffen Heegaard, Anthony J. Gill, Martine J. Jager, Abelardo A. Rodríguez-Reyes, Bita Esmaeli, Jennelle C. Hodge, Ian A. Cree on behalf of the WHO Classification of Tumours Editorial Board The 5th Edition of the World Health Organization Classification of Tumours the Eye and Orbit Ocular Oncology and Pathology. April 18, 2023 doi: 10.1159/000530730
Marshall EC. Epidemiology of tumors affecting visual system. Optom Clin. 1993; 3(3): 1-16.
Sonal S., Chaugule, Santosh G. Hanovar, Paul T. Finger. Surgical Ophthalmic Oncology. Springe, 2019; p. 69-82.
Mi Jung Chi Se Hyun Baek. Clinical Analysis of Benign Eyelid and Conjunctival Tumors. Ophthalmologica 2006; 220:43–51.
Kirkham N. Tumors and cysts of epidermis. In: Elder D., Elenitsas R., Jaworsky C., et al. eds. Lever’s Hystopatholy of the skin. Philadelfia, PA: Lippincott-Raven; 1997; 695-696.
Frederick A Jakobiec 1, Manisha Mehta, Mami Iwamoto, Mark P Hatton, Manoj Thakker, Aaron Fay Intratarsal keratinous cysts of the Meibomian gland: distinctive clinicopathologic and immunohistochemical features in 6 cases. Am J Ophthalmol. 2010 Jan;149(1):82-94. doi: 10.1016/j.ajo.2009.07.033
Shields JS, Kaden IH, Eagle RC Jr, et al. Orbital dermoid cysts. Clinicopathologic correlations, classification, and management. The 1997 Josephine E Schueler Lecture. Ophthal Plast Reconstr Surg. 1997; 13; 265-27.
Zimmerman L.E., Phakomatous choristoma of the eyelid. A tumor of lenticular anlage. Am J Ophthalmol 1971; 71: 169-177.
Stefan Dithmar 1, Ingo Schmack, Hans E Völcker, Hans E Grossniklaus. Phakomatous choristoma of the eyelid. Graefes Arch Clin Exp Ophthalmol. 2004 Jan; 242(1):40-3.
Perez-Blazquez E, Villafruela I, Madero S. Eyelid molluscum contagiosum in patients with humanimmunodeficiency virus infection. Orbit, 1999; 18: 75-81 doi: 10.1076/orbi.18.2.75.2712
Ahmad M. Al Aboud; Pramod K. Nigam Wart StatPearls Publishing; 2024 Jan-
Deprez M., Uffer S. Clinicopathological features of eyelid skin tumors. A retrospective study of 5504 cases and review of literature. Am.J. of Dermatopathol. 2009; 31(3), 256-62.
Luiz Angelo Rossato, Rachel Camargo Carneiro, Erick Marcet Santiago de Macedo, Patricia Picciarelli de Lima, Mariana Ragassi Urbano, Suzana Matayoshi Relationship between actinic keratosis and malignant skin lesions on the eyelid. Arq Bras Oftalmol. 2023; 86(1):1-6.
López-Tizón E, Mencia-Gutiérrez E, Garrido-Ruíz M, Gutiérrez-Diaz E, López-Rios F. Clinicopathological study of 21 cases of eyelid actinic keratosis. Int Ophthalmol. 2009; 29(5):379-84.
Cordero AA, Montes LF. Eccrine hidrocystoma. J Cutan Pathol.; 1976; 3: 292-293.
Rishi K., Font R.L. Sebaceous gland tumors of the eyelids and conjunctiva in Muir-Torre syndrome: clinicopathological study of five cases and literature review. Ophthal Plast Reconstr Surg 2004; 10; 31- 36.
Ozdal P.C., Callejo S.A., Codore F., et al. Benign ocular adnexal tumors of apocrine, eccrine or hair follicle origin. Can J Ophthalmol. 2003; 38; 357-363.
Hilton JMN, Blackwell JB. Metastasizing Chondroid syringoma. J Pathol, 1973; 109:167-169.
Maya Eiger-Moscovich, Paul J.L. Zhang, Sara E. Lally, Carol L. Shields, Ralph C. Eagle Jr., Tatyana Milman. Tubular apocrine adenoma of the eyelid – A case report and literature review. Saudi Journal of Ophthalmology (2019) 33, 304–307.
Levy J, Ilsar M, Deckel Y., et al. Eyelid pilomatrixoma: a description of 16 cases and review of the literature. Surv Ophthalmol 2008; 53(5); 526-35.
Hidayat AA, Font RL. Trichilemmoma of eyelid and eyebrow. A clinicopathlogical study of 31 cases. Arch Ophthalmol. 1980; 98; 844-884.
Brownstein MH, Mehregan AH, Bikowski JB. Trichilemmoma in Cowden’s disease. JAMA. 1977, 238: 26.
Grossniklause HE, McLean IW. Cutaneous melanoma of the eyelids. Clinicopathologic features. Ophthalmology. 1991; 98: 1867-1873 doi: 10.1016/s0161-6420(91)32037-2.
Grossniklaus HE. Correspondence re: A. B. Ackerman, R. Sood, and M. Koenig, Primary acquired melanosis of the conjunctiva is melanoma in situ. Mod Pathol 4:253, 1991. Mod Pathol. 1992 Jul;5(4):473. PMID: 1495953.
Grossniklaus HE, Green WR, Luckenbach M, Chan CC. Conjunctival lesions in adults. A clinical and his-topathologic review. Cornea. 1987;6:78–116.
Shields CL, Alset AE, Boal NS, et al. Conjunctival tumors in 5002 cases. Comparative analysis of benign versus malignant counterparts. The 2016 James D. Allen lecture. Am J Ophthalmol. 2017; 173:106– 33.
Lu J, Chu F, Chen K. Conjunctival Inclusion Cyst. Hong Kong Journal of Emergency Medicine. 2013;20(3):184-185.
Gokhan Ozge, Uysuf Uysal, Osman Melih Ceylan, Onder Onguru, Fatih Mehmet Mutlu. Keratoacanthoma of the conjunctiva in a young patient. Case report. Arq Bras Oftalmol. 2016;79(3):195-6.
Borodin Yu.I., Valsky V.V., Verigo E.N. Long-term results of combined treatment for recurrent pterygium. Ophthalmology. 2007; 3: 29–33.
Martinez, L. Marty. (1998). Conjunctival Dermoid Cyst Seen on Examination as a Chronically Red Eye. Archives of Ophthalmology, 116(8), 1109–1111.
Flaka, S., Mire, H.-S., Fitore, S., Fjolla, S. and Avdyl, S. (2020) Surgical Treatment of Lipodermoids: Case Report. Open Journal of Ophthalmology, 10, 1-9.
Shields C.L., Shields J.A. Tumors of conjunctiva and cornea. Surv. Ophthalmol 2004, 49, Issue 12, p. 3-24.
Sjö NC, von Buchwald C, Cassonnet P, Norrild B, Prause JU, Vinding T, et al. Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: Types and frequencies in a large series. Br J Ophthalmol. 2007;91:1014–5.
Kaliki S, Arapali S, Shields CL. Conjunctival papilloma. Features and outcome based on age at initial examination. JAMA. Ophthalmol. 2013; 131: 585-593.
Shields CL, Demirci H, Karatza E, et al. Clinical survey of 1643 melanocytic and nonmelanocytic tumors of the conjunctiva. Ophthalmology 2004; 111:1747-1754.
Kaeser PE, Uffer S, Zografos L, et al. Tumors of the caruncle: a clinicopathologic study. Am J Ophthalmol. 2006; 142: 448-45.
Say EA, Shields CL, Bianciotto C, et al. Oncocytic lesions (oncocytoma) of the ocular adnexa; raport of 15 cases and review of literature. Ophthal Plast Reconstr Surg. 2012; 28(1): 14-21.
Shields JA, Shields CL. Eagle RC Jr, et al. Primary acquired melanosis of the conjunctiva. Experience with 11 eyes. Zimmerman Lecture. Ophthalmology. 2008; 115(3): 511-519).
Zamir E, Mechoulam H, Micera A, Levi-Schaffer F, Pe’er J. Inflamed juvenile conjunctival naevus: clinicopathological characterisation. Br J Ophthalmol. 2002;86(1):28–30. doi: 10.1136/bjo.86.1.2
Zimmerman LE. Melanocytes, melanocytic nevy and melanocytomas. Invest Ophthalmol. 1965 Feb; 4:11-41 PMID: 14271285.
Ibrahim Sayed-Ahmed, Juan Carlos Murillo, Pedro Monsalve, Jan Paul Ulloa, Maria P Fernandez, James Wong, George Elgart, Anat Galor1, Sander R. Dubovy, and Carol L. Karp Blue nevi of the ocular surface: Clinical characteristics, pathological features and clinical course Ophthalmology. 2018 August; 125(8): 1189–1198. doi:10.1016/j.ophtha.2018.02.006
Adrianna Eder, Tatyana Milman, Hardeep-Singh Mudhar, Sara E. Lally, Carol L. Shields, Khanh Bui, Jill R. Wells, Hans E. Grossniklaus. Unusual conjunctival melanocytic proliferations. Report of five cases and review of the literature. Survey of OphthalmologyVolume 69, Issue 2, March–April 2024, Pages 230-240 doi: 10.1016/j.survophthal.2023.10.012
J. Brooks Crawford, Edward L. Howes Jr, Devron H. Char. Combined Nevi of the Conjunctiva Arch Ophthalmol. 1999;117(9):1121-1127. doi: 10.1001/archopht.117.9.1121
Kumiko Kat, Maki Takeuch, Yuka Yonekaw, Yuzen Kashim, Koji Hirano, Mineo Kondo. Management of Inflamed Conjunctival Nevus with Topical Antiallergic Medications: Case Series Clinical Ophthalmology 2021:15.
Kiseleva T.N., Saakyan S.V., Makukhina V.V., Lugovkina K.V., Milash S.V., Musova N.F., Zharov A.A. Capabilities of optical coherence tomography angiography in assessing conjunctival angioarchitecture in health and disease. Vestnik Oftalmologii. 2022; 138(6):32–42.
Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. N Engl J Med. 1999; 341: 173-181.
Khushdeep Abhaypal, Manpreet Singh, Manu Saini, Kirti Gupta and Pankaj Gupta. Isolated cavernous venous malformation of the eyelid. Digit J Ophthalmol. 2024; 30(1): 11–14.
Wright JF, Sullivan TJ, Garner A, et al. Orbital venous anomalies. Ophthalmology 1997; 104: 905-913.
Horgan N, Shields CL, Minzter R, et al. Ultrasound biomicroscopy of eyelid hemangioma in a child. J Pediatr Ophthalmol Strabismus. 2008: 45(1): 55-56.
Rootman J, Hay E, Graeb D, et al. Orbital-adnexal Lymphangiomas. A spectrum of hemodynamically isolated vascular hamartomas. Ophthalmology. 1986; 93: 1558-1570.
Radiosurgical treatment of small benign eyelid tumors / S.V. Saakyan, M.P. Kharlampidi, E.B. Myakoshina [et al.] // Siberian Scientific Medical Journal. – 2019. – Vol. 39, No. 4. – P. 127–136.
Shields JA, Mashayekhi A, Kligman B, et al. Vascular tumors of the conjunctiva in 140 cases. The 2010 Melvin Rubin Lecture. Ophthalmology. 2011; 118: 1747-1753.
Brown R, Fard S, Feng P, Kerr PE. Evaluation and management of benign tumors of the eye and eyelid. Clin Dermatol. 2024 Jul-Aug; 42(4):343-350.
Drozdowski R, Grant-Kels JM, Falcone M, Stewart CL. Adnexal neoplasms of the eye. Clin Dermatol. 2024 Jul-Aug;42(4):321-342.
Varde MA, Heindl LM, Kakkassery V. Diagnose und Therapie der benignen Lidtumoren [Diagnosis and treatment of benign eyelid tumors]. Ophthalmologie. 2023 Mar;120(3):240-251. German.
Stokkermans TJ, Prendes M. Benign Eyelid Lesions. 2023 May 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan.
Grishina N.I. Radiosurgical treatment of eyelid tumors / N.I. Grishina, V.A. Nam // Saratov Journal of Medical Scientific Research. – 2021. – Vol. 17, No. 3. – P. 632–635.
Slutsky JB, Barr JM, Femia AN, Marghoob AA. Large congenital melanocytic nevi: associated risks and management considerations. Semin Cutan Med Surg. 2010 Jun;29(2):79-84. doi: 10.1016/j.sder.2010.04.007. PMID: 20579596.
Actis AG, Actis G, De Sanctis U, Fea A, Rolle T, Grignolo FM. Eyelid benign and malignant tumors: issues in classification, excision and reconstruction. Minerva Chir. 2013 Dec;68(6 Suppl 1):11-25.
Herwig-Carl, M., & Löffler, K. (2018). Lidtumoren: Klinische Aspekte der Ophthalmopathologie. Klinische Monatsblätter Für Augenheilkunde, 235(07), 776–781. doi:10.1055/a-0633-3120.
Junejo MS, Rebecca, Memon MN, Shaikh SP. Role of topical beta blockers in regression of infantile capillary hemangioma. Pak J Med Sci. 2021 Nov-Dec;37(7):1935-1938. doi: 10.12669/pjms.37.7.4317. PMID: 34912421; PMCID: PMC8613063.
Berezhnova S.G. Combined treatment of orbital hemangiomas using short-focus X-ray therapy and systemic hormone therapy / S.G. Berezhnova, V.V. Valsky // Diagnostic and Interventional Radiology. – 2011. – Vol. 5, No. 2 (Suppl.). – P. 57–59.
Berezhnova S.G. Main directions in the treatment of orbital and periorbital hemangiomas in children / S.G. Berezhnova // Russian Ophthalmological Journal. – 2013. – Vol. 6, No. 1. – P. 96–102.
Trubilin V.N., Polunina E.G., Kurenkov V.M. Applications of ultrasound biomicroscopy in assessing the condition of the eyelids and conjunctiva // Ophthalmology. – 2015. – Vol. 11. – No. 4. – P. 32–40.
Saakyan S.V., Zhiltsova M.G., Borodin Yu.I., Tsygankov A.Yu. Comprehensive clinical and cytological diagnosis of epithelial tumors of the ocular accessory apparatus. Russian Ophthalmological Journal. 2024;17(2):68-73. https://doi.org/10.21516/2072-0076-2024-17-2-68-73
Yarovoy A.A., Golubeva O.V., Kleyankina S.S., Yanchenko T.V. Juvenile xanthogranuloma of the visual organ. Vestnik Oftalmologii. 2018;134(1):89–96.
Brovkina A.F., Zhiltsova M.G., Kaplina A.V. Fine-needle aspiration biopsy in the diagnosis of visual organ tumors: a guide for physicians. Moscow: 2000; p. 16.
Tsyplakova M.S., Usoltseva A.S., Stepanova Yu.V. Giant congenital melanocytic nevus of the face // Pediatric Traumatology, Orthopaedics and Reconstructive Surgery. – 2015. – Vol. 3. – No. 2. – P. 56–60.
Balaeva R.N., Kasimov E.M. Conjunctival nevi as a risk factor for melanoma development. Vestnik Oftalmologii. 2016;132(3):21–25.
Amosov V.I., Speranskaya A.A., Lukina O.V. The use of multislice computed tomography (MSCT) in ophthalmology // Ophthalmological Vedomosti. – 2008. – Vol. 1. – No. 3. – P. 54–59.
Saakyan S.V., Ivanova O.A. Melanocytic lesions of the conjunctiva // Russian Pediatric Ophthalmology. – 2014. – No. 2. – P. 22–24.
Luo S. et al. Refractive characteristics and related factors of amblyopia after lamellar keratoscleroplasty in children with limbal dermoids // Journal of Clinical Medicine. – 2022. – Vol. 11. – No. 14. – P. 4176.
American Academy of Ophthalmology. Summary Benchmarks for Preferred Practice Pattern Guidelines. – American Academy of Ophthalmology, 2008.
Churganova M.V., Luzyanina V.V. The role of photobiomicroscopy in the clinical practice of an ophthalmologist // Pacific Medical Journal. 2017. No. 2.
Cui Y., Yin S., Yin X., Liu Y., Zhao B. Removal of a congenital corneal dermoid through tumor excision and lamellar keratoplasty in a young child: A case report. Medicine. 2021;100:e27981. doi: 10.1097.
Eyelid and conjunctival tumors: a comprehensive guide for ophthalmologists Olivier GALATOIRE / Christine LEVY-GABRIEL / Mathieu ZMUDA , 1 July 2019.
Vasović D.D. et al. Two Decades of Insights: Comprehensive Histopathological and Epidemiological Analysis of Conjunctival Tumors // Life. – 2024. – Vol. 14. – No. 11. – P. 1381.
Lerner M.Yu., Steshenko O.N. Malignant eyelid skin tumors in Moscow: epidemiology and medical follow-up of patients // Russian Ophthalmological Journal. – 2022. – Vol. 15. – No. 4. – P. 38–44.
Luzyanina V.V. Diagnosis and treatment of visual organ neoplasms at the Primorye Eye Microsurgery Center // Pacific Medical Journal. – 2017. – No. 2. – P. 21–25.
Vozzhennikov A.Yu., Midlenko T.A. Methodological guidelines for independent work of residents on the organization of practical training and state final certification in the residency training program 31.08.59 «Ophthalmology». – 2019.
Appendix A1. Working Group Composition
Alikhanova V.R., Cand. of Med. Sci., LLC «Association of Ophthalmologists».
Amiryan A.G., Dr. of Med. Sci., Chief Researcher, LLC «Association of Ophthalmologists».
Borodin Yu.I., Cand. of Med. Sci., LLC «Association of Ophthalmologists».
Ivanova O.A., Cand. of Med. Sci., LLC «Association of Ophthalmologists».
Katargina L.A., Professor, Dr. of Med. Sci., Honored Doctor of the Russian Federation, Chief freelance pediatric ophthalmologist of the Russian Ministry of Health, Chief Researcher and Head of the Department of Eye Pathology in Children, LLC «Association of Ophthalmologists».
Myakoshina E.B., Dr. of Med. Sci., LLC «Association of Ophthalmologists».
Panteleeva O.G., Dr. of Med. Sci., Leading Researcher, LLC «Association of Ophthalmologists».
Parmon Ya.V., Cand. of Med. Sci., LLC «Association of Ophthalmologists».
Saakyan S.V., Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Ophthalmic Oncology and Radiology, LLC «Association of Ophthalmologists».
Sklyarova N.V., Cand. of Med. Sci., LLC «Association of Ophthalmologists».
Tatskov R.A., Cand. of Med. Sci., LLC «Association of Ophthalmologists».
Tsygankov A.Yu., Cand. of Med. Sci., LLC «Association of Ophthalmologists».
Conflict of interest: none.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
Oncologists;
Surgeons;
Radiologists;
Medical geneticists;
Dermatovenereologists;
Pathologists;
Ophthalmologists;
Medical students, residents, and postgraduate students.
Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)
LoE | Definition |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)
LoE | Definition |
|---|---|
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 3. Scale for evaluating the levels of убедительности рекомендаций (LoR) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Procedure for updating clinical guidelines.
The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.
Appendix A3. Reference Materials
Order of the Russian Ministry of Health No. 804n dated October 13, 2017 (as amended on September 24, 2020, with rev. dated October 26, 2022) "On Approval of the Nomenclature of Medical Services".
Federal Law No. 323-FZ dated November 21, 2011 (as amended on December 29, 2025) "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation" (with amendments and addenda, effective April 1, 2026).
Order of the Russian Ministry of Health No. 633n dated October 24, 2025 "On Approval of the Procedure for Providing Medical Care to the Adult Population in the Field of Ophthalmology" (Registered with the Ministry of Justice of Russia on November 25, 2025, No. 84259).
Order of the Russian Ministry of Health No. 205n dated May 2, 2023 (as amended on June 3, 2025) "On Approval of the Nomenclature of Positions of Medical Workers and Pharmaceutical Workers".
Order of the Russian Ministry of Health No. 168n dated March 15, 2022 (as amended on February 28, 2024) "On Approval of the Procedure for Dispenser Observation (Clinical Surveillance) of Adults".
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Benign formations of the eyelids and conjunctiva with signs of progression require surgical treatment.
Before surgical intervention, a general ophthalmological examination is necessary, assessing both local and general status.
Morphological examination is mandatory after surgical removal of the pathological focus.
All patients require clinical surveillance for 1 year after treatment.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Not used.