Actinic Keratosis
Actinic keratosis is one of the most common skin lesions.
Appearance
Actinic keratoses are superficial skin lesions that can appear spontaneously. They may appear as small red or brown patches, and sometimes as scaly or horn-like growths. They feel rough to the touch.
Location
Actinic keratosis usually develops in areas that have had chronic sun exposure over many years. The areas where it is seen are generally the face, chest, backs of the hands, ears and scalp.
Development
Actinic keratoses are defined as precancerous lesions. They should be treated before they turn into squamous cell carcinoma.
Single lesions are usually frozen with liquid nitrogen to destroy the abnormal cells. If there are multiple lesions, they can be treated locally with a cream, or with a number of other medical treatments that act on the local immune response, make the cancerous cells sensitive to light, or use chemotherapy drugs.
What Is Leukoplakia?
Leukoplakia is the formation of white patches on the body. It is an uncommon condition, but it can turn into cancer. The white patches characteristic of leukoplakia appear in various places, but mostly in the mouth (and sometimes around the genitals), usually as well-defined, often thickened, raised areas. The condition is seen mostly in men between the ages of 40 and 70.
Leukoplakia, known to be precancerous – that is, able to turn into cancer – can in fact be treated even if diagnosed late. Nevertheless, because it causes few problems in its early stages and can easily be overlooked, care should be taken regarding leukoplakia.
Causes
Leukoplakia may have no specific cause, but it can also be linked to long-term irritation. Doctors suggest that leukoplakia can develop in the following situations: smoking, syphilis, sepsis (severe infection), alcohol, spices and decayed teeth. The harmful effects of heavy drinking and smoking are well known, but the mechanisms by which they act are not understood.
Some spices can be irritating. Chewing gum and biting the insides of the cheeks can also lead to leukoplakia. Syphilis, which is now treated with antibacterial medicines (that kill germs), i.e. antibiotics, is now a rare cause.
Symptoms
When leukoplakia occurs in the mouth, white patches appear on the insides of the cheeks, on the tongue, in the lower parts of the throat and in the larynx. Around the genitals, it can occur on the inner part of the foreskin and around the labia.
The absence of pain, and the fact that in the early stage of leukoplakia there may be no sign other than paleness and slight thickening of the skin in the area, mean that the disease can easily be overlooked. Later, however, the skin becomes markedly thickened and hardened. Leukoplakia can cause sensitivity to hot food and itching. Later still there may be pain and bleeding from cracks that form. Cancer usually develops at this stage. Genital leukoplakia is most often located in the vagina. The main symptom is itching.
Treatment
The first step in treatment is to remove the irritant and then to monitor the patches. If necessary, the patches can be removed by heat or freezing, and in more advanced cases surgery is used.
Actinic Cheilitis
Cheilitis is chronic inflammation of the lips. It has various clinical features and different aetiological factors causing it. In newborns, drooling often causes cheilitis. In young people and adults, those with deep lines at the corners of the mouth are at high risk. Deficiency of certain vitamins and minerals, the use of dentures, infectious agents such as Candida albicans, staphylococci and streptococci, alcohol use, excessive sun exposure, inflammation of the salivary glands and contact with chemical agents are among the causes of cheilitis. Medicines can also cause cheilitis.
First, the factor causing the cheilitis should be identified, and then appropriate treatment directed at this aetiological agent should be started. Commonly used medicines are topical, intralesional or systemic corticosteroids, topical moisturisers, topical or systemic antibiotics and antifungals. In actinic cheilitis, lip balms containing sunscreen are recommended, although in some patients it is advised not to use them as they can cause contact cheilitis. In some cases, electrosurgery, laser or surgical excision is needed. Topical 5-fluorouracil, cryotherapy and photodynamic therapy can also be used. Medicines used to treat leprosy, metronidazole, hydroxychloroquine and dapsone are among the other treatment options. Recently, successful results have been obtained with topically applied tacrolimus and imiquimod.
Bowen's Disease
Bowen's disease is the early stage of SCC, called in situ, containing atypical cells confined to the epidermis, the outermost layer of the skin; it is seen especially in patients aged 60 and over.
Factors such as arsenic, sunlight, HPV, ionising radiation, suppression of the immune system and PUVA play a role in the development of the disease.
Clinical Features of Bowen's Disease
Although it is generally located on sun-exposed areas of the body, it can also be seen on the palms, soles and genital area.
Clinically, the lesions are characterised by slowly growing, red plaques and patches with sharp, irregular borders and scaling on the surface. Their diameter can vary from a few mm to cm. This scaly appearance can cause it to be confused with psoriasis or eczema. It progresses slowly. Areas of slight healing may be seen in parts of a large Bowen's lesion.
The lesion surface is sometimes verrucous, and rarely the lesions may be pigmented. In the differential diagnosis of pigmented Bowen's disease, superficial basal cell carcinoma, seborrhoeic keratosis and malignant melanoma should be considered. Dermoscopy is a method widely used in the differential diagnosis of pigmented lesions.
SCC can develop in Bowen's disease, and it has a worse course than SCC developing from actinic keratosis.
Treatment of Bowen's Disease
- Topical 5-FU
- Imiquimod 5% cream
- Photodynamic therapy
- Curettage
- Surgical excision
- Cryotherapy
- Electrosurgery
- Laser can be used.
Cutaneous Horn
Cornu cutaneum, or cutaneous horn, is a well-defined conical hyperkeratotic lesion on the skin surface resembling an animal's horn. Most are yellowish-white and of various shapes and sizes, often straight or curved and twisted, and from a few millimetres to a few centimetres long. The first case of cutaneous horn was described by Thomas Bartholin. It can be flat, nodular or crateriform. Cutaneous horns, seen in older people, can occur in various parts of the body, but 30% are found on sun-exposed areas such as the face and scalp. Less often seen on the hands, chest, neck, shoulders and areas such as the penis, cutaneous horns are usually single but can be multiple.
Chronic Radiodermatitis
It results from chronic (long-term) exposure to ionising radiation over a long period at doses that do not cause redness. After a period ranging from a few months to 10-30 years, varying degrees of damage occur in the skin and subcutaneous tissue. In the past, this type of radiation reaction occurred in radiologists and radiographers who were continuously exposed to ionising radiation. It can also result from excessive treatment of various skin diseases with ionising radiation and from excessive use of diagnostic X-rays.
Dilated blood vessels and lightening of the skin colour together with increased pigment deposits (freckling) may be seen. The skin looks dry, thin, smooth and shiny. 6-12 months after radiotherapy, thickening under the skin and tethering of the superficial layers to the deeper tissues can produce tender, red patches. The nails may become ridged, brittle and break. The ability to heal wounds is reduced. Ulcers form after minor trauma. The hair is fragile and sparse. In very severe cases, cancer may follow these chronic changes.
Treatment: Protect yourself from the sun and from extreme heat and cold. Clean the affected area gently with lukewarm water and soap. Apply creams and ointments as recommended by your doctor. Corticosteroid ointments may sometimes be needed. Also have regular medical check-ups so that any malignant change in your skin can be detected early.
Keratoacanthoma
Keratoacanthoma is a benign tumour of the surface epidermis that can heal spontaneously and is clinically and histologically very similar to SCC. There are two types of keratoacanthoma: solitary and multiple.
Solitary Keratoacanthoma
A firm nodule 1-2 cm in diameter with a central crater filled with horny material. It mostly occurs as a single lesion in older people, but sometimes there is more than one, or new lesions may develop one after another. 95% of solitary keratoacanthomas appear on sun-exposed areas. However, they can occur on any area of skin where hair follicles are present. To date, they have not been reported on the palms, soles or mucous membranes. A keratoacanthoma reaches its maximum size in 6-8 weeks and usually shrinks and disappears on its own in less than 6 months. Healing ends with a slightly depressed scar. Some keratoacanthomas, especially those located on the vermilion border of the lip, tend to keep growing for more than 2 months, can reach 4-5 cm in size, and may take 12 months or even longer to heal. This type of keratoacanthoma, which also tends to recur after treatment, is harder to distinguish histologically from epidermoid carcinoma than the usual type. In 2% of cases, skin destruction and growth continue without spontaneous healing. The frequency of keratoacanthoma is increased in patients on immunosuppressive treatment.
Solitary or few keratoacanthomas have 3 rare clinical variants. Giant keratoacanthomas reach a size of over 5 cm in a short time and, although they may heal spontaneously after months, they cause destruction of the underlying tissues. They are most often located on the nose and eyelids. In keratoacanthoma centrifugum marginatum, the tumour can reach a diameter of 20 cm2. These tumours, which do not heal spontaneously, tend to grow outwards while atrophy develops in the centre. They are most often located on the backs of the hands and on the legs. The third variant of solitary keratoacanthoma, subungual keratoacanthoma, is a destructive, crateriform, painful tumour located under the distal part of the fingernails. It does not regress spontaneously and can cause pressure erosion of the terminal phalanx.
Multiple Keratoacanthomas
There are 2 variants: multiple self-healing epitheliomas of the skin and eruptive keratoacanthomas. Both variants are very rare.
In multiple self-healing epitheliomas of the skin, new lesions continually form anywhere on the skin, including the palms and soles, particularly on the face, arms and legs. The lesions start as papules, turn into nodules with a central crater filled with horny material, and heal after a few months leaving a depressed scar. In some cases the disease is hereditary. It can develop at sites of tattoos and trauma.
In eruptive keratoacanthoma, which appears in adults, there are hundreds of tumours, most of them follicular papules 2-3 mm in diameter. The lesions can also be located on the mucous membranes and larynx. The cause of keratoacanthoma is unknown.
Treatment of Keratoacanthoma
Although keratoacanthomas can heal spontaneously, there are important reasons for treating them early. It is extremely difficult to distinguish keratoacanthoma clinically from epidermoid carcinoma. In addition, it is impossible to predict how large a keratoacanthoma will become and, accordingly, how much damage it will do to the underlying tissues. Moreover, the linear scar left after surgical removal is more aesthetic than the scar resulting from spontaneous healing. Curettage and electrocautery are used for lesions smaller than 1.5 cm, and for larger lesions there are ionising radiation, intralesional triamcinolone acetonide and 5-FU injections, and etretinate treatment. Medicines such as methotrexate and bleomycin are used to treat multiple keratoacanthomas. Imiquimod and podophyllin are also used.
Paget's Disease
Paget's disease of bone (osteitis deformans) is a focal disease of bone metabolism. The rate of bone remodelling is increased, and in the affected areas there is excessive bone growth and impaired bone integrity. Many patients are asymptomatic. The diagnosis is made incidentally during routine tests, through a rise in serum alkaline phosphatase of bone origin or on plain X-ray.
In symptomatic patients, the main clinical features are pain and skeletal deformities due to overgrowth of the affected bone.
The prevalence of the disease is difficult to estimate because most cases are asymptomatic. In studies based on randomly selected plain X-rays of hospitalised patients or on autopsy findings, Paget's disease was found in 3-3.7% of patients over 40. Prevalence increases with age, and the female-to-male ratio is equal.
I. Aetiology
Although the cause is unknown, family and pathological studies suggest that genetic factors and/or viral infection play a pathogenetic role.
Genetic Factors:
The disease is seen in 14-25% of family members of patients with Paget's disease. First-degree relatives of patients have a 7-10 times higher risk of developing Paget's disease. In families with autosomal dominant Paget's disease, four suspected loci (on chromosomes 5, 6 and 18) have been identified. Various mutations have been found in the SQSTM1 gene, which encodes the p62 protein.
Viral Infection:
Viral particles have been found in the osteoclast nuclei and cytoplasm of patients, and it has been suggested that these may belong to the paramyxovirus family. Canine distemper virus and measles virus have also been implicated in the pathogenesis.
Although unproven, the above findings suggest that latent viral infection of osteoclasts in genetically predisposed individuals may cause Paget's disease. After remaining silent for years, osteoclast activation may occur for an unknown reason, eventually leading to the increase in bone remodelling characteristic of Paget's disease.
The disease is common where people of Anglo-Saxon origin live. It is rare in Asia, India and Scandinavia. Juvenile Paget's disease, also known as idiopathic hyperphosphatasia, is a rare disease characterised by fragile and deformed bones.
II. Histology
The characteristic histopathological feature is abnormal lamellar bone. Initially, the rate of bone resorption increases in localised areas with numerous osteoclasts. Radiologically, the localised areas of osteolysis are seen as advancing wedge-shaped lytic lesions in the long bones, or as a radiolucent area in the skull called "osteoporosis circumscripta". The development of osteolysis is followed by a compensatory increase in bone formation by osteoblasts migrating to the area. Lamellar bone is deposited rapidly and in a haphazard, irregular way. This intense cellular activity produces a chaotic, irregular pattern (mosaic pattern) in trabecular bone instead of the normal linear lamellar structure. The resorbed bone and bone marrow are replaced by fibrous connective tissue rich in blood vessels, and the bone becomes hypervascular. Eventually the hypercellularity decreases and gives way to sclerotic bone.
III. Clinical Features
Many patients are asymptomatic. The diagnosis is made incidentally when a raised serum alkaline phosphatase is found or a plain X-ray is taken. The signs and symptoms of Paget's disease depend on the site and extent of bone involvement and on the relationship of the pagetic bone to neighbouring tissues. Any part of the skeleton can be involved, but the pelvis, spine, skull and long bones (proximal and distal parts) are most often affected.
The two main clinical features of Paget's disease are pain and deformities in the affected areas. In addition, fractures, bone tumours, neurological disease, heart disease and disturbances of calcium-phosphate balance may be seen. Because of increased vascularity, heavy bleeding may occur during orthopaedic surgery.
Pain:
Pain arises directly from the pagetic lesion or, more often, from degenerative arthritis, nerve compression or osteosarcoma. Bone pain increases with weight-bearing. The cause of the pain is not clear, but it is thought to be due to stretching of the periosteum caused by abnormal bone enlargement, together with hyperaemia or microfractures in weight-bearing bones. It is distinguished from osteoarthritic pain by its good response to treatments specific to Paget's disease.
Skeletal deformities:
These are most marked in the long bones, skull and clavicles. Deformities of the long bones appear as widening and bowing of the bone. Postural disorders and mechanical stress lead to back and joint pain. Increased blood flow may cause a feeling of warmth. Involvement of the skull begins with osteoporosis circumscripta, with radiolucent areas appearing radiologically. Years later, the skull enlarges, especially in the frontal and occipital regions, and a "cotton wool" appearance develops as a result of disruption of the normal bone structure.
Fractures:
The most common complications of pagetic lesions are traumatic and pathological fractures. Fractures most often occur in the femur below the lesser trochanter, transversely, and may be complete or incomplete (fissure fractures).
Bone Tumours:
Bone tumours are seen in 0.7-1% of cases. These tumours present with increasing pain and/or an enlarging mass in the pagetic area. Osteosarcomas are the most common tumours. They can be seen in the pelvis, femur, humerus, skull and facial bones. The prognosis is poor, with a 5-year survival rate of 10-20%. Death is due to local spread or lung metastases. Benign giant cell tumours and extraskeletal osteoclastomas may be seen.
Neurological Complications:
These result from compression of nerves or blood vessels by the enlarging bone. In the skull, compression of the 8th cranial nerve can cause hearing loss, and compression of the 2nd, 5th and 7th nerves can cause visual disturbance and facial palsy. With early treatment, cranial nerve disorders can improve. Involvement of the skull base can lead to invagination of the skull by the cervical vertebrae (basilar invagination) and hydrocephalus, and involvement of the vertebrae can lead to nerve compression, ischaemia and vascular steal syndrome.
Cardiac Complications:
Heart complications are seen in severe Paget's disease. High-output heart failure, calcific aortic stenosis, complete and incomplete atrioventricular block and bundle branch blocks may be seen.
Calcium and Phosphate Metabolism:
Serum Ca and P concentrations are normal in most patients. Hypercalcaemia and hypercalciuria may be seen due to immobility or an unavoidable increase in bone resorption. Hypocalcaemia due to low intake during periods of high bone formation, or hypocalcaemia and secondary hyperparathyroidism resulting from suppression of bone resorption during bisphosphonate treatment while bone formation continues, may develop.
Biochemical Markers:
Increases in urinary hydroxyproline (an indicator of increased bone resorption) and serum alkaline phosphatase (an indicator of increased bone formation) are useful findings showing the activity, extent and severity of the disease and the effectiveness of treatment. They return to normal levels with successful treatment.
Pyridinoline Cross-links:
Measurement of urinary pyridinoline cross-links is useful in assessing the response to bisphosphonate treatment. Pyridinoline and deoxypyridinoline cross-links stabilise collagen in the extracellular matrix. Pyridinoline is present in bone and cartilage collagen, while deoxypyridinoline is present only in bone collagen. They are released from osteoclasts during bone resorption and excreted in the urine in free and peptide-bound forms. Urinary pyridinoline cross-links rise in Paget's disease and fall with bisphosphonate treatment. The new generation of nitrogen-containing bisphosphonates are potent inhibitors of osteoclastic bone resorption. Before deciding on treatment, the presence of symptoms of active disease, the distribution of pagetic lesions in the skeleton, the metabolic activity of the pagetic lesions and the potential consequences of bone growth in the affected areas should be assessed.
IV. Diagnosis
In patients suspected of having Paget's disease, a good history, physical examination and serum Ca and alkaline phosphatase levels should be obtained. Most patients are asymptomatic. In a healthy older person, raised serum alkaline phosphatase, a normal Ca level and the absence of hepatobiliary disease should suggest Paget's disease. A normal serum 25-hydroxyvitamin D level rules out osteomalacia.
Bone scintigraphy is the most sensitive method for identifying pagetic bone lesions; the lesions appear as focal areas and hot spots. Plain X-rays of suspicious sites show fissure fractures and lytic areas. It can be difficult to distinguish them from metastatic bone lesions. If laboratory and radiological tests a year earlier were normal, it is not Paget's disease. When new radiological findings appear, a bone biopsy should be considered.