Cutaneous horn: clinical guidelines

List of Abbreviations

ICD – International Classification of Diseases

UVR – ultraviolet radiation

UV – ultraviolet

WHO – World Health Organization

HPV – human papillomavirus

US – ultrasound examination

CT – computed tomography

Terms and Definitions

Cutaneous horn (cornu cutaneum, horn keratoma, Unna fibrokeratoma) is a dense epithelial formation on the surface of the skin or mucous membranes, conical or cylindrical in shape, consisting of dense horny masses, originating from keratinocytes and resulting from pronounced hyperkeratosis.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Cutaneous horn (cornu cutaneum, horn keratoma, Unna fibrokeratoma) is a dense epithelial formation on the surface of the skin or mucous membranes, conical or cylindrical in shape, consisting of dense horny masses, originating from keratinocytes and resulting from pronounced hyperkeratosis.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Cutaneous horn is formed as a result of epidermal damage, which can be:

– benign;

– precancerous;

– malignant.

The formation of the characteristic appearance of the lesion element, its external similarity to animal horns, is explained by the high adhesive capacity of the horny substance.

Cutaneous horn can be located on the skin, vermilion border of the lips, and oral mucosa [1].

Cutaneous horn can occur on unchanged skin and be primary in nature (true cutaneous horn), but usually cutaneous horn is a clinical manifestation (symptom) of a number of etiologically different diseases [1, 2], such as:

– basal cell papilloma;

– viral warts;

– molluscum contagiosum;

– trichilemmal cysts;

– epidermal nevi;

– actinic keratosis;

– keratoacanthoma;

– Bowen's disease;

– other forms of squamous cell carcinoma;

– basal cell carcinoma;

– sebaceous gland carcinoma;

– carcinoma originating from hair follicle elements;

– angiokeratoma;

– Kaposi sarcoma [3–6].

– Table: Etiology of cutaneous horn (according to the histopathology of the underlying base)

Cutaneous horn as a symptom is less important than the underlying disease that caused its development [7, 8].

60% of all registered cases of cutaneous horn are initially benign [9].

The risk of malignant transformation of a cutaneous horn ranges from 12% to 20% [10].

The most common precancerous skin lesion leading to the formation of a cutaneous horn is actinic keratosis [2].

Cutaneous horn associated with a malignant tumor is most commonly linked to squamous cell carcinoma; less commonly to basal cell carcinoma, sebaceous gland carcinoma, and hair follicle carcinoma [11, 12].

In patients with a history of malignant neoplasms or precancerous conditions, the appearance of a cutaneous horn is usually associated with new foci of malignant growth or precancerosis [13]. Unlike lesions localized on the skin, a mucosal horn of the oral cavity is more often a symptom of a malignant neoplasm than a benign condition [10, 14].

The pathogenesis of cutaneous horn is unknown. It is hypothesized that cellular senescence, photodamage, and subsequent epithelial cell dysfunction contribute to its manifestation [15]. The leading role of photodamage to the skin and integumentary epithelium of the vermilion border in the pathogenesis of cutaneous horn is confirmed by the fact that, regardless of whether its formation is the result of a benign, precancerous, or malignant condition, the lesion is predominantly localized in areas most vulnerable to ultraviolet radiation, such as the head, neck, and upper extremities [7, 8].

Changes in keratinocytes caused by viruses and other infectious agents can also lead to the formation of a cutaneous horn. Human papillomavirus and molluscum contagiosum virus are most frequently mentioned in this regard.

The etiology of oral mucosal horn differs from that of cutaneous horn. In this case, UV radiation plays no role, but poor oral hygiene, mucosal HPV infection, smoking, and other bad habits are of great importance.

1.3 Epidemiology of the Disease or Condition

The exact prevalence of cutaneous horn is currently unknown. It is considered a relatively rare pathology [16, 17].

Cutaneous horn occurs in patients of both sexes, but lip cutaneous horn is more common in men and across all age groups. Cutaneous horn can develop in childhood, but the majority of patients are individuals aged 60 to 80 years [18–20].

The probability of a cutaneous horn being associated with a malignant neoplasm increases with the patient's age. Precancerous skin diseases and malignant neoplasms presenting as a cutaneous horn are observed more frequently in men than in women [7].

Fair-skinned individuals, especially those with Fitzpatrick skin phototypes, are more susceptible to this disease [21]. However, isolated cases of cutaneous horn have also been reported in patients with dark and pigmented skin, including individuals of African descent [22, 23].

1.4 Features of Coding the Disease or Condition

Code according to the International Classification of Diseases ICD-10 —

L85.8 – Cutaneous horn

1.5 Classification of the disease or condition

There is no generally accepted classification of cutaneous horn.

1.6 Clinical presentation of the disease or condition

The clinical manifestations of cutaneous horn vary; the main feature of this lesion is the presence of an exophytic white, gray, yellow, or brown outgrowth on the skin surface consisting of dense keratin masses, resembling an animal horn in appearance: the thickness of the horny outgrowth gradually decreases from the base to the apex. The lesion may curve and twist into a spiral along its length. In most cases, the lesion is solitary [24].

The diameter and size of the lesions themselves can range from thin (filiform cutaneous horn) to large in both diameter and height.

Lesions exceeding 1 cm in height are termed giant, and literature descriptions include giant cutaneous horns reaching up to 25 cm [8, 25].

In most described clinical observations, the diameter of the horn base did not exceed 1 cm, but this value can also reach much larger dimensions.

The base of the horny outgrowth is usually tightly fixed to the skin and can be located either on a visually unchanged background or against a background of erythema. A pedestal-like tissue base of the horny outgrowth may be present. Along with erythema on the skin at the base of the horny masses, horn scales of various sizes unrelated to the horn tissue itself may be present.

In cases where the horn formation is caused by a tumor lesion, the cutaneous horn may have an underlying tumor tissue typical of the symptoms of the tumor that caused its growth.

The presence of erythema at the base of the cutaneous horn is a criterion of a malignant process in 77% of cases.

A benign nature of the cutaneous horn is indicated by the presence of a "tiered morphology" of the lesion elements, determined by dermatoscopy. The "tiered morphology" sign represents an ordered structural dermatoscopic pattern with histopathology of orthohyperkeratosis consisting of horizontal parallel keratin lamellae [21].

Horny outgrowths whose height exceeds the base diameter one to two times have a higher malignant potential than a horn with a lower height-to-base diameter ratio.

Among subjective symptoms in the presence of a cutaneous horn, everyday discomfort associated with frequent mechanical irritation of the lesion (by clothing, comb, towel, etc.) should be noted. The presence of a cutaneous horn may be accompanied by pain, which, like erythema in the skin surrounding the base of the growth, should be considered an indirect sign of malignancy of the process [21].

The occurrence of cutaneous horn on mucous membranes and transition zones is rare. A cutaneous horn developing in transition zones is mostly a lesion localized on the vermilion border of the lips. The lower lip is most susceptible to such a lesion (60.9% of cases), followed by the vermilion border of the upper lip and the labial commissures. The clinical manifestations of cutaneous horn on the lips and oral angles are virtually identical to the symptoms of cutaneous horn forming on other areas of the skin [14].

A horn arising on the dorsum of the tongue and its lateral surfaces may consist exclusively of horny masses located on a visually healthy mucous membrane. Such a horn is usually not associated with tumor pathology, is small in size, and forms as a consequence of benign changes in the filiform papillae [26].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnosis of cutaneous horn is based on the appointment (examination, consultation) by a dermatologist, analysis of medical history and clinical picture. The criteria for establishing the diagnosis are the features of the typical clinical picture: a dense epithelial lesion on the surface of the skin or mucous membranes, conical or cylindrical in shape, consisting of dense horny masses.

2.1 Complaints and Anamnesis

Patients complain of a dense horny growth on the skin or lips, aesthetic defect and everyday discomfort associated with it: the formation interferes with wearing clothing, when localized on the skin of the nose and in the periorbital areas, it prevents wearing glasses, etc. Patients with a horn on the oral mucosa may be bothered by both the presence of the lesion itself and a foreign body sensation on the tongue. Symptoms of a horn arising as a manifestation of oral mucosal cancer are usually secondary to the manifestations of tumor symptoms.

A cutaneous horn may not cause subjective sensations in the patient, but in some cases, patients note soreness of the cutaneous horn, especially with its mechanical irritation. In case of trauma to the base of the lesion, phenomena of inflammation in the underlying skin may be observed.

If left untreated, cutaneous horn in elderly patients, presenting without subjective symptoms, can persist for a long time (years). In cases where the formation of the horny outgrowth is due to a malignant lesion, tumor symptoms (infiltration, ulceration, bleeding, pain, etc.) may prevail over the symptoms of the cutaneous horn itself, and it is precisely these symptoms that prompt the patient to seek medical care.

2.2 Physical Examination

For objective clinical manifestations of the disease identified during physical examination, see the "Clinical Presentation" section.

2.3 Laboratory Diagnostics

Comments: Excisional skin biopsy is preferred, as it can serve as both a diagnostic and therapeutic procedure, allowing for the radical removal of both the cutaneous horn itself and the primary malignant tumor or other lesion that caused the formation of the horny outgrowth.

If an excisional skin biopsy is not feasible, an incisional skin biopsy (of tissue at the base of the cutaneous horn) may be performed.

2.4 Instrumental Diagnostics

2.5 Other Procedures

Not applicable.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative Treatment

Not applicable.

3.2 Surgical Treatment

Comments: Surgical intervention is important for determining the etiology of the lesion. Skin biopsy is not only a diagnostic but also a therapeutic procedure, as it allows for the radical removal of both the cutaneous horn itself and the lesion that caused the formation of the horny outgrowth. The procedure is performed under local anesthesia.

3.3 Other Treatment

Carried out according to clinical guidelines depending on the identified process underlying the formation of the cutaneous horn [38–42].

Medical Nutrition Therapy

Not applicable.

Pain management

Pain management is performed as needed.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Not applicable.

5. Prevention and Dispensary Observation

Dispensary follow-up (Active surveillance)

Not required.

6. Organization of Medical Care

Patients with a well-founded suspicion of a malignant nature of the lesion, or with a confirmed malignant neoplasm presenting with cutaneous horn symptoms based on examination data, should be referred for examination and treatment to an oncological specialist/pediatric oncologist/pediatric hemato-oncologist. Referral of patients must be carried out in accordance with the established referral procedure, with the execution of all necessary referral documentation and recording of this information in the patient's primary medical records.

Hospitalization in a medical organization is not required.

7. Additional Information

No additional information available.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Nikolay N. Potekaev – Doctor of Medical Sciences, Professor, President of the National Alliance of Dermatovenerologists and Cosmetologists, Member of the International Union against Sexually Transmitted Infections (IUSTI/WHO), Honorary President of the Euro-Asian Association of Dermatovenerologists (EAAD), Member of the Board of Directors of the European Academy of Dermatology and Venereology (EADV), Corresponding Member of the German Dermatological Society (DDG), Honored Doctor of the Russian Federation, Chief freelance specialist in dermatovenerology and cosmetology of the Russian Ministry of Health, Chief freelance specialist in dermatovenerology and cosmetology of the Moscow Healthcare Department, Director of the Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology, Head of the Department of Skin Diseases and Cosmetology at the Faculty of Additional Professional Education of the Pirogov Russian National Research Medical University of the Ministry of Health of Russia.

2. Sergeeva Irina Gennadyevna – Doctor of Medical Sciences, Professor at the Department of Fundamental Medicine, Novosibirsk National Research State University, member of the National Alliance of Dermatovenereologists and Cosmetologists, dermatovenereologist, oncologist.

3. Getman Alexey Dmitrievich – Candidate of Medical Sciences, Highest Category Oncologist, Head of the Oncology Department at Neo-Clinic LLC (Tyumen).

4. Yakushenko Sergey Sergeevich – member of the National Alliance of Dermatovenereologists and Cosmetologists, dermatovenereologist, oncologist, cosmetologist, pathomorphologist at the Lipetsk Regional Clinical Dermatovenereology Dispensary.

5. Kusaya Natalya Valeryevna – Candidate of Medical Sciences, Associate Professor at the Department of Normal and Pathological Physiology, Pacific State Medical University of the Russian Ministry of Health, dermatovenereologist, oncologist, cosmetologist.

6. Baranov Alexander Alexandrovich – Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Chief freelance specialist in pediatrics of the Russian Ministry of Health, member of the Union of Pediatricians of Russia.

7. Namazova-Baranova Leila Seymurovna – Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, President of the Union of Pediatricians of Russia; Past-President of EPA/UNEPSA; Head of the Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery (NC2), Head of the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Chief freelance pediatric specialist in preventive medicine of the Russian Ministry of Health.

8. Murashkin Nikolay Nikolaevich – Doctor of Medical Sciences, Head of the Dermatology Department with a Laser Surgery Group, National Medical Research Center for Children's Health of the Russian Ministry of Health, Doctor of Medical Sciences, Professor at the Department of Dermatovenereology and Cosmetology, Central State Medical Academy of the Directorate of the President of the Russian Federation, Professor at the Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University).

9. Ambarchyan Eduard Tigranovich – Candidate of Medical Sciences, Leading Researcher, Head of the Pediatric Dermatology Department, Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery (NC2) of the Ministry of Science and Higher Education of the Russian Federation, member of the Union of Pediatricians of Russia.

Conflict of Interest: The authors declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Specialist physicians: dermatovenereologists, cosmetologists, oncologists, pediatric oncologists, pediatric hematologist-oncologists, pediatrician.

2. Residents and trainees of continuing professional education programs in the specified specialties.

Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2.  Scale for evaluating levels of evidence (LE) for methods of prevention, treatment, and rehabilitation, including those based on natural therapeutic factors (preventive, therapeutic, rehabilitation interventions)

Table 3. Grade of Recommendation (GoR) scale for methods of prevention, diagnosis, treatment, and rehabilitation, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The clinical guidelines update mechanism provides for their systematic revision—at least once every three years, as well as upon the emergence of new evidence-based data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines were developed taking into account the following regulatory legal documents:

1. Procedure for the provision of medical care in the profile «dermatovenereology», approved by Order of the Ministry of Health of the Russian Federation No. 924n dated November 15, 2012.

2. Order of the Ministry of Labor and Social Protection of the Russian Federation No. 142n "On approval of the professional standard 'Dermatovenereologist'" dated March 14, 2018.

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

1. Due to the potential malignant nature of the process, diagnosis of the lesion must be performed as early as possible.

2. Self-removal of the lesion is not permitted, as this may alter the clinical presentation and hinder diagnosis.

3. Self-examination of the skin is indicated for the timely detection of new lesions.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

There is no universally accepted rating scale.