International Veterinary Center for Reproduction and Artificial Insemination of Small Animals. Melanoma in dogs. Interview with an oncologist

MELANOMA IN DOGS. INTERVIEW WITH AN ONCOLOGIST. One of the malignant tumors that owners sometimes encounter in their pets is melanoma. Anna Leonidovna Kuznetsova, a veterinary oncologist at the Biocontrol clinic and Candidate of Biological Sciences, spoke about what this tumor is and about modern methods of treating it. - What is “melanoma”? - Melanoma is a malignant tumor that develops from pigment cells: melanocytes. - In which animals does it occur most often and at what age? - This disease is more common in dogs. Cats rarely get melanoma. According to statistics, males get sick approximately 1.5 times more often than females. Typically, melanoma occurs in dogs over 10 years of age. The pathology is more common in dogs small breeds, especially in cocker spaniels, poodles, Scotch terriers, dachshunds, can also be observed in large animals such as black terriers, giant schnauzers, labradors and other breeds with strong pigmentation of the mucous membrane oral cavity and skin. - What are the causes of melanoma? - The etiology of melanocytic tumors in animals has not been sufficiently studied. Because melanoma occurs primarily on skin covered coat, or in the oral cavity, many authors claim that solar radiation is not a leading factor in the development of tumors in dogs. While a person ultraviolet irradiation serves as one of the main predisposing factors. - What are the prognosis for this tumor? - The prognosis for melanoma is generally unfavorable and depends on a number of factors: the size of the tumor, the depth of its germination, the form of growth, localization, and the presence of metastases. Ulceration and bleeding surface of the tumor are unfavorable signs. It is important to diagnose the disease in the early stages in order to prevent the development of a tumor and prescribe adequate treatment in a timely manner. - Melanoma can be pigmented or non-pigmented. What is their difference? - Indeed, there are non-pigmented (achromatic) tumors. Basic distinctive feature Such tumors are characterized by the absence of a specific coloration, which may lead the doctor to think about melanoma. The course and treatment of achromatic melanoma does not differ from the course and treatment of pigmented tumors. - What stages of diagnosis does an oncologist perform? - Correct assessment is of great importance clinical symptoms. At the appointment, the doctor determines the linear dimensions of the primary tumor in three projections, the macroscopic form of growth, the color of the tumor, the uniformity of coloring, the nature of the edges of the tumor at the border with healthy tissue. Palpation of the soft tissues around the tumor in the area of ​​expected lymphatic drainage towards the regional lymph nodes allows us to identify transit metastases localized in the skin and subcutaneous tissue; They also resort to palpation of all accessible groups of superficial lymph nodes. Diagnosis and stage oncological process set based on the results comprehensive examination which includes a chest x-ray and ultrasound abdominal cavity. An examination of the oral cavity is often required. general anesthesia with immediate collection of material for morphological research. Morphological diagnostic methods include cytological and histological examination. - Is there a treatment for melanoma? - Eat! Depending on the location and stage of the oncological process, the following can be used for treatment: wide surgical excision, radiation therapy, neutron capture therapy, immunotherapy, cryodestruction, etc. These methods can be combined. - Is surgical treatment effective? - Surgical intervention in the treatment of primary melanoma remains the method of choice in both humane and veterinary medicine. It is advisable to combine surgical methods treatment with immunotherapy. - How high is the likelihood of metastases? - Melanoma is characterized by rapid and early metastasis. The two main routes of its metastasis are lymphogenous and hematogenous. Regional areas are affected by the lymphogenous route The lymph nodes, less often distant. Skin metastases are common. Hematogenous metastases can occur in any organ, but the lungs, liver, spleen and bones are most often affected. - What happens if melanoma is not treated? - As a rule, melanoma has an aggressive biological behavior, characterized by rapid growth and early metastasis. Without treatment, the quality of life of animals quickly deteriorates. There is an unpleasant odor from the oral cavity, purulent or hemorrhagic discharge, bleeding, pain syndrome. Generalization of the process is usually observed 3-4 months after diagnosis. - There is a vaccine against melanoma. When should it be done and for which animals? - Yes, indeed, a therapeutic vaccine against melanoma has been developed. It is advisable to use it after extensive surgical intervention, i.e. when the main source is removed tumor cells. Vaccine therapy in combination with ablastic surgery, according to the literature, can significantly increase the patient’s life expectancy. Unfortunately, the drug is not certified in the Russian Federation, so it is extremely difficult to purchase. - Is it possible to somehow prevent this disease? - It is impossible to prevent melanoma. Timely referral is extremely important.

Melanocytic tumors are widespread in the animal world, which is convincing evidence of their general biological nature. Hippocrates first wrote about malignant (fatal) pigment formations in the 5th century BC. We also find data on the existence of malignant pigmented neoplasms in documents from ancient times.

Slide 1. Clinical and morphological parallels of melanoma in dogs

Hippocrates first wrote about malignant (fatal) pigment formations in the 5th century BC. We also find data on the existence of malignant pigmented neoplasms in documents from ancient times.

Excavations in Peru indicate that the ancient Incas suffered from this tumor more than 4,000 years ago. Radioactive analysis shows that mummies from this era have changes indicating melanoma metastases in the bones of the limbs and skull.

Slide 2. Clinical and morphological parallels of melanoma in dogs

Phylogenetically, the cellular system that produces melanin pigments appears for the first time in fish, so true melanomas can already be found in them. Melanomas have been found in more than 30 species of fish. They are most often found in colorful viviparous fish such as guppies, especially in inbreeding. But the record holders for the frequency of melanomas in fish are some swordtail hybrids. Fish melanoma arises from neural tube cells and is located mainly on the scalp, body and fins.

The color of the tumor is gray to black. The process begins with melanosis, then the tumor grows, infiltrates surrounding tissues and metastasizes; fish melanoma cells can be cultured and transplanted. Fish can also have eye melanomas. One of the most interesting and attractive features of fish melanoma is its genetic causation and control. This can be clearly seen after the hybridization of some species of swordtails.

IN natural conditions in warm pools South America different types Swordtails do not interbreed. But this easily occurs in the laboratory, producing a viable but highly variable generation that often develops melanomas.

Among amphibians, melanoma has been described in the axolotl, and laboratory strains have been created from these melanomas. Among reptiles, melanomas often develop in adult snakes; they are located on the skin and are malignant. Melanoma is very rare in birds, with the exception of some colored breeds of pigeons.

Slide 3. The spread of melanoma in animals

There is no doubt that melanocytic tumors are most common in mammals. In wild animals, they are described in brown bears, antelopes, deer, monkeys and many others.
At the large cattle melanoma accounts for 4% of all tumors and has a sarcomatous morphological appearance, proceeds benignly and does not recur after removal.

Slides 4.5.

In gray horses, melanoma is the most common tumor, developing in almost every adult animal. The tumor has a typical location - at the root of the tail, near the anus, vulva, perineum and on the mammary glands, it is usually benign, but if it metastasizes, it is very early dates– to the lymph nodes, liver, spleen, which speaks in favor of hematogenous dissemination of the tumor.

Slide 6.Spread of melanoma in animals

Melanoma is very rare in pigs and cats; rabbits are affected more often, especially colored ones.

Slide 7.Experimental melanoma

In golden hamsters, spontaneous melanomas are quite rare, but when a tumor is induced they occur in 100% of cases.
From the 1960s to the present day, golden hamsters have been the model for inducing melanomas. A single application of 0.8 mg of the polycyclic hydrocarbon 9,10-dimethyl,1,2-benzanthracene caused skin melanomas in all treated animals.

This phenomenon reveals a lot about the etiology of this tumor in humans and animals; the ability of melanocytes to increase proliferation under the influence of certain chemical factors explains the increased incidence of melanomas in gas station workers.

“Press reviews of the Arkhangelsk region”(Published 16:42 12/22/2005)

Message from October 20 From Purnema fishermen from the farm “40 years of October” in the Arkhangelsk regionA horse misadventure. The “Octobers” decided to sell seven horses, which were still grazed by savages and eaten up by food. They took me to Onega to a meat processing plant. Externally, the horses seemed healthy to the veterinarians. But when they opened the brown ones... All the internal organs turned out to be engulfed by a tumor of unknown origin.
The meat was urgently sent to Arkhangelsk laboratories. The regional veterinary office issued a verdict: melanoma. It was even found in a four-month-old foal! After this, the meat in Onega was defrosted, examined again and came to the conclusion: it would not be possible to cut “healthy” pieces from the carcasses for sausage, the damage was too deep. All the horse meat will have to be disposed of. Veterinarians and collective farmers suggest that what happened was the result of a fuel oil spill off the coast of Purnema. In 2003, the Volgotanker vessel “fed” the Onega coast of the White Sea with oil products. And all these years the horses grazed right on the shore...
The oil version has indirect evidence. As the head of the agricultural department of the Onega administration said Yuri Baturin, the fishing collective farm named after Lenin (it is located 40 km from Purnema and was almost not damaged by the fuel oil spill) also recently handed over horses to the plant. “Lenin’s” meat turned out to be completely healthy!

Slide 8. Melanomas in dogs

This is the most common tumor in dogs.

Depending on the breed, its frequency ranges from 1.5 to 9% of all tumors in these animals. On mucous membranes, tumors most often occur in Rottweilers, Dobermans, and poodles dark colors, and of these - in males over 5 years old.

Slide 9.Melanomas in dogs. Statistics

Most often they develop melanoma of the skin, followed by mucosal melanoma and very rarely eye melanoma.

Slide 10.Melanomas in dogs. Statistics

Skin melanoma, in decreasing order of frequency, occurs on the fingers, foot, head, and scrotum.

Slide 11.Melanomas in dogs. Statistics
( Melanoma of the mucous membranes of the lips, gums, cheeks, palate and genitals)

Slide 12.Melanomas in dogs. Statistics

When localized on the limbs and trunk, the course is predominantly benign and does not require excessive radicalism. That is, if you find melanoma on a small limb, you should not amputate the entire limb, otherwise you’ve heard enough that melanoma is terribly malignant, and let’s cut it. In fact, in this case it is enough to amputate only the finger.

In our clinic, we performed amputation of a finger on an 8-year-old Doberman male who was 9 months old. melanoma was treated with antibiotics, ASD, creolin, peroxide, Vishnevsky ointment and other magic drugs, unfortunately, it did not help. Seriously speaking, at least 5 specialists took on the treatment of the animal before us, while the antibacterial therapy regimens were changed and conservative treatment continued.

When localized on the mucous membranes and membranes of the eye, the course is predominantly malignant.

When localized in the genital area and perineum, the course is often benign, but a tumor in this localization can metastasize over a long period of time.

Slide 13. Melanocytes

The source of all melanomas are melanocytes that have undergone bast transformation. Melanocytes are specialized dendritic cells in which melanin is synthesized.

Slide 14. Histogenesis of melanocytes

What kind of tumors does melanoma belong to?

In oncology there is a division of all malignant tumors into:

• carcinoma (cancer) – tumors from epithelial tissues and
• sarcoma is a tumor of connective tissue.

For a long time, there was debate among oncologists about what type of tumors melanomas should be classified as sarcomas or cancers. And only at the end of the 20th century, with the help of monoclonal antibodies, it was established that melanocytes, the cells from which melanomas develop, express on their surface markers common to cells of nervous origin (neurocytes, Schwann cells, cells of the adrenal medulla).

In the embryo at the stage of histogenesis, the ectoderm along the midline of the back differentiates and thickens, forming a neural plate, the lateral edges of which rise, forming neural folds, and a neural groove is formed between the folds.

The anterior end of the neural plate expands, later forming the brain. The lateral margins continue to ascend and grow medially until they meet and merge at the midline into the neural tube, which separates from the overlying epidermal ectoderm. The neural tube cavity persists in adults as the ventricular system of the brain and the central canal of the spinal cord.

Some cells of the neural plate are not part of either the neural tube or the epidermal ectoderm, but form clusters on the sides of the neural tube, which merge into a loose cord located between the neural tube and the epidermal ectoderm - this is the neural crest (or ganglion plate).

Macroglia of the central nervous system are subsequently formed from the neural tube. The neural crest gives rise to neurons of the sensory and autonomic ganglia, cells of the pia mater and arachnoid membranes of the brain, and some types of glia: neurolemmocytes (Schwann cells), satellite cells of the ganglia. Cells of the adrenal medulla, melanocytes of the skin, some cells of the APUD system, and sensory cells of the carotid bodies also develop from the neural crest.

Slide 15. Localization of melanocytes

Most malenocytes:

• in the skin (hair follicles, dermis and dermoepidermal joints)
• in mucous membranes
• V nervous system(soft arachnoid - far lining of the brain)
• in the eyes (vascular tract eyeball, retinal pigment epithelium)
• in the inner ear (cochlea, vestibular system).

Slide 16. Factors contributing to the occurrence of melanomas

Location

• Periungual ridge
• Lips and oral cavity
• Other localization

Slide 17. Diagnosis

The doctor will ask you about the symptoms of the disease and risk factors, when the skin lesion first appeared and whether it has changed in size and appearance.

• anamnesis

You may be asked about exposure to known substances, causing cancer skin, as well as cases of skin cancer in your family.

During the examination, the doctor will determine the size, shape, color and condition of the tissues around the skin lesion. In addition, he will find out if there is any weeping or bleeding from the suspicious formation. A full body examination will look for any spots or moles that may be related to skin cancer. The lymph nodes in the inguinal and axillary areas, on the neck and especially near a suspicious lesion. Enlarged lymph nodes may indicate that they are affected by a malignant tumor.

• inspection
• palpation

Factors causing the occurrence of melanomas

• increased insolation

Ultraviolet radiation can damage DNA. Most melanomas have abnormalities in the chromosomes, where the DNA is located. This damage makes the DNA less able to control cell growth and division. In some situations, this leads to the onset of cancer development.

Most of ultraviolet radiation comes from sunlight, but some of it comes from artificial sources, for example, ultraviolet cabins. Some such exposures may occur several years before cancer occurs. However, the tumor develops as a result of exposures that occurred many years ago. Children and young adults often receive multiple intense sun exposures that may not become apparent for years or even decades.

The mechanism of the carcinogenic effect of UV radiation may involve the formation of highly active free chemical radicals in normal cells. The occurrence of a tumor is based on the processes of damage to cell DNA by these radicals and disruption of its normal repair. The sequence of processes for the occurrence of skin melanoma under the influence of UV radiation can be schematically represented as follows:

• • • UV radiation
    • melanoblasts,
    • melanocytes or nevus cells
    • cell DNA damage
    • hyporesponsiveness

Probably, this mechanism of carcinogenesis of skin melanomas is the shortest in time, since in in this case there is no long-term proliferation normal cells and fabrics. Clinical confirmation of the possibility of “switching on” this mechanism of carcinogenesis is the fact of a more frequent occurrence of melanomas after a single and intense exposure to UV radiation (sunburn).

• various types of injuries

On the contrary, the mechanism of the carcinogenic effect of trauma to pre-existing pigmented nevi involves the proliferation of tissues in response to damage, but the injury itself does not lead to the development of a tumor. It has been proven that cells in a state of proliferation have hypersensitivity to carcinogenic effects and are especially vulnerable when in the mitotic cycle phase. Therefore, intensive reproduction (proliferation) of cells can lead to their neoplastic transformation.

The sequence of processes in the occurrence of skin melanomas as a result of trauma to pre-existing pigmented nevi can be schematically represented as follows:

• • • damage
    • nevus cells
    • inflammation and proliferation of damaged tissue
    • long-term proliferation + exposure to endogenous carcinogenic factors (immunological, endocrine, neurogenic, etc.)
    • disruption of cell DNA structure
    • cell differentiation disorder
    • change in the protein structure of the cell with the emergence of new membrane antigens
    • hyporesponsiveness
    • infinitely long reproduction (tumor growth).

• carcinogens

Some cyclic hydrocarbons contained in oil and petroleum products can cause changes in the DNA of myelocytes, followed by their blast transformation.

• Endocrine shifts
  

The process of formation of melanin in animals is associated with the activity endocrine glands. In a number of hormonal disorders (Adison's disease, chronic hyperthyroidism, hypopituitarism, etc.), as well as during pregnancy, pigmentation disorders of the skin, hair, etc. are observed. It has been established that the formation of melanin is controlled mainly by pituitary hormones (alpha and beta melanocyte-stimulating hormones), as well as thyroid gland, steroid and sex hormones.

The mechanism of hormonal control is not clear. Apparently, the main role belongs to melanin-stimulating hormones, the activity of which can be stimulated by other hormones (progesterone) or suppressed (adrenaline or norepinephrine).

• Genetic causes

In dogs and other domestic animals, the influence of genetic factors on the occurrence of melanoma has not been studied. But hybrids of swordtails with high probability the occurrence of this tumor, and in these hybrids there are genes responsible for high tyrogenase activity.

Slide 18. Clinical characteristics of melanomas

TOclinical characteristics of melanoma

• dark color
• shiny surface
• disintegration tendency
• pigment accumulation
• damage to the epidermal layer
• fragility of the neoplasm

Slide 19. Clinical forms melanoma

Malignant melanoma has a different macroscopic shape. This difference is due to the unequal growth rate of the tumor, the presence or absence of pigment, and the onset of development.

The above described clinical options Malignant melanoma can be grouped into the following groups:

• superficial intraepidermal lentiginous melanoma
• nodular melanoma
• verucous melanoma
• fungos melanoma

Slide 20

Slide 21. Intraepidermal form of melanoma

Superficial intraepidermal lentiginous malignant melanoma. In this case, we are talking about intraepidermal malignancy of normally proliferating melanocytes collected in macular (lentiginous) formations. It is a dark-colored plaque, slightly protruding above the surface of the skin and sharply limited.

In essence, it is lentigo maligna or superficial intraepidermal melanoma. This form of melanoma can be observed in any part of the body, but most often on the limbs and torso. Despite the fact that this form is relatively benign, both regional metastases and massive hematogenous deposits in the skin and internal organs are possible.

Slide 22

Most common classic shape melanoma. In most cases, melanoma, once fully developed, appears as a nodule. Both the primary tumor and their lentigo can occur. It is a smooth black nodule protruding above the surface of the skin, which at the base of the nodule can be hyperemic and even depigmented.

Such a nodule tends to infiltratively grow deeper, has a moderately dense elastic consistency, and the localization of such a tumor is widespread.

Slide 23. Nodular malignant melanoma

The surface of verrucous nodular melanoma is uneven, lumpy, with deep fissures that contain infected necrotic mass. The tumor may emit a foul odor. Based on these signs, especially in dark-colored dogs, when the difference in color between the tumor and the surrounding skin is not noticeable, a purulent-infiltrative lesion is often diagnosed and antibiotic treatment is prescribed.

Slides 24, 25. Fungal form of melanoma

The fungal form is a large node consisting of a massive exophytic growth on a wide base. Despite the fact that the fungal form looks the most frightening, it metastasizes late and can be completely cured with radical surgical intervention. Early forms of the tumor are a slowly growing, pigmented, slightly protruding plaque or nodule. The degree of pigmentation can vary widely. During development, the tumor may become fungous or ulcerate.

Slide 26. Melanoma is characterized by rapid and early metastasis

Slides 27, 28. Hematogenous metastasis

Slide 29. Melanoma of the eye

Often pigmented tumors in dogs do not have macroscopic signs of malignancy, while the tumor has already metastasized. There are cases where metastases have already appeared, but the primary tumor has not been detected.

Slide 30. Melanoma of the eye

Aspiration biopsy for suspected melanoma is strictly prohibited, as is excisional biopsy, therefore exfoliative cytology is the only method for diagnosing melanomas available in veterinary medicine.

Slide 31. Metastasis.

Metastasis:

• regional lymph nodes
• skin metastases
• hematogenous metastases

Slides 32,33,34,35,36. Epithelial-like type of melanoma

The epithelial-like type of melanoma is characterized by the predominance in smears of tumor cells of a round, irregularly rounded or oval shape, located scatteredly or in the form of loose clusters and resembling epithelial cells. In some cases, tumor cells are quite homogeneous, but more often there is significant polymorphism; they differ from each other in size and shape, color intensity, number of nuclei and nucleoli, and chromatin structure.

There are individual tumor cells with very large, intensely stained nuclei, binucleate and multinucleate cells. The nuclei of many cells are lobed, bean-shaped, have uneven contours, sometimes budding of nuclei and their fragmentation are observed, and figures of mitotic division are found. The structure of the chromatin of the nuclei is relatively uniform, fine-grained or looped; in many cells the nuclei have 1-2, and sometimes more hypertrophied, irregular shape nucleoli.

The cytoplasm of cells is sometimes more or less abundant, with smooth or scalloped contours. In some cases it is stained sharply basophilic, in others it is weaker, and sometimes it is transparent and almost merges with the background of the preparation. The amount of melanin in tumor cells can vary; in some cases there is a lot of it, in others it is difficult to determine. Cells of apigmented epithelial melanoma are often very similar to glandular cancer cells. Unlike melanoma cells, glandular cancer cells are usually located in groups and complexes closely related friend with each other cells and are stained more intensely.

Slide 37. Melanoma metastases in the lungs

In spindle cell melanoma, the tumor cells have an elongated spindle-shaped shape and are located scattered, in clusters, intertwined with processes of the cytoplasm, and also in the form of bundles and strands. The nuclei are round and oval, in some cells they have an elongated elongated shape.

The cytoplasm is stained basophilically and has processes different lengths, sometimes extending over a considerable distance. The dust-like granules of melanin are most concentrated in the processes of the cytoplasm, which gives them a granular appearance. The presence of pigment in the cells makes it possible to differentiate the spindle cell type of melanoma from other connective tissue tumors (sarcoma, neuroma).

Slides 38,39

Slide 40. Final diagnosis

• smear-imprint
• Histological examination
• Histochemistry and immunohistochemistry

With mixed cell melanoma, smears contain tumor cells of various sizes and shapes, and it is difficult to identify any predominant cell type. Tumor cells of round, oval, spindle-shaped and polygonal process form are equally common. Definition cell type melanoma with cytological examination is possible only if there is a sufficient amount of informative material in the smears.

Slide 41. Melanomas of the mucous membranes

Histological classification of melanomas

The most significant clinical significance has a classification of melanomas according to the degree of vertical spread of the process.

1. Melanoma type lentigo maligna, lentigo-melanoma.
2. Superficial spreading melanoma.
3. Nodular melanoma.

During a long-term study of these types of melanoma, it was shown that each of them has its own clinical features, which largely determine the biological behavior of the tumor.

Malignant melanoma. This type accounts for about 10% of all primary skin melanomas. More than 90% of all cases are localized in the head, neck and dorsum of the hand. In addition to localization on open areas of the body, isolated lesions are observed on the skin of the back, thighs and legs.

Melanoma of the lentigo maligna type is 2 times more common in women and is the most favorable form of the disease. There are two phases in the development of this type of melanoma. The radial growth phase is very long - up to 10-20 years.

The vertical growth phase can develop over a number of years (and not months in case of superficially spreading melanoma). In the lesion, cellular polymorphism and associated changes of the type of intrafocal transformation are rarely observed. The risk of metastases with this type of melanoma is not high.

Slide 42. Cytological diagnosis

The cytological method found wide application in the diagnosis of skin melanomas. If melanoma is suspected, a biopsy is contraindicated due to the risk of stimulating tumor growth and dissemination, therefore, during the examination of the patient, cytological examination is essentially the only morphological method for verifying the clinical diagnosis.

The objects of cytological examination for melanoma are smears and scrapings from the weeping, ulcerated or macerated surface of the skin tumor, punctures of the tumor and lymph nodes suspicious for metastatic lesion. Simply applying a glass slide to an ulcerated surface does not always provide sufficiently informative material.

The best results are obtained by scraping the affected surface with a wooden spatula or the sharp edge of a surgical instrument, after first removing the purulent plaque using a gauze swab moistened saline solution. For dry crusts that do not come off with a light touch, you can apply a napkin with indifferent antiseptic or methyluracil ointment to the tumor for 3-4 hours, after which the crusts are easily removed, and prints or a light scraping are made from the surface of the tumor. If melanoma is suspected, tumor puncture is performed with a thin needle immediately before surgery.

Less commonly, the object of cytological examination for melanoma can be punctures of metastatic lymph nodes, when the primary focus of melanoma is not identified and clinical diagnosis unclear or incorrect. The preferred method of staining smears for the cytological diagnosis of melanomas of the skin is staining with asureosin, which makes it possible to more clearly identify dust-like melanin granules in the cytoplasm of tumor cells; this is especially important for diagnosis in cases where there is little melanin in the tumor.

The presence of melanin pigment in the cytoplasm of tumor cells is a very significant sign of melanomas. When stained with asureosin, melanin appears in the form of granules or drops of various sizes, less often - in the form of dust-like granularity from gray to black (when stained with hematoxylin and eosin - from brown to black).

The amount of pigment in tumor cells varies. Sometimes it completely fills the cytoplasm of the cell, and therefore it is impossible to examine the nucleus and other structural details. The pigment can also be located extracellularly in the form of granules various shapes and magnitude.

In other cases, melanin is present in small quantities only in individual cells or is absent. In cases of so-called In non-pigmented melanomas, when diagnostic difficulties arise, the DOPA reaction can be useful, which helps identify the colorless precursor of melanin - the tyrosine pigment in the form of brown or black granules or dusty granularity.

However, the most informative for making a cytological diagnosis of melanoma are the cytomorphological features of the tumor cells themselves. Depending on the predominance of tumor cells in smears with certain cytomorphological features, 4 main types of melanomas are distinguished: epithelial-like, spindle cell, nevus-like and mixed cell. The same 4 main cell types are determined by histological examination.

Determining the cell type of skin melanomas by cytological examination is clinically justified, because Various types melanomas have different tendencies towards local spread and regional metastasis, and information about the type of tumor guides the surgeon when planning surgical intervention on primary focus. However, the depth of invasive growth, which can only be determined histologically, is of key importance in determining the prognosis of melanomas.

The most common type is superficial spreading melanoma (SPM). It accounts for about 63-70% of diseases. It predominates among people of the European race. The peak incidence occurs in the 5th decade. The incidence of the tumor is almost the same for both sexes. However, the tumor occurs approximately 2 times more often in men on the scalp, neck, torso, and approximately 3 times more often in women - on the thighs and legs. PRM usually develops over several years. There is a two-phase development of this tumor.
The horizontal growth phase, characterized by its spread within the epithelial layer

Slide 43

The second phase is the vertical growth phase, characterized by invasion of tumor cells into the reticular and subcutaneous fat layer. There is indirect evidence that the horizontal growth phase lasts a long time. The biological potential of malignancy in the horizontal growth phase is extremely low, since tumor growth corresponds to the second level of invasion according to Clark. The horizontal growth phase with PRM is accompanied by relapses and metastases in less than 5% of patients, while with the vertical growth phase the development of metastases can be expected in 35-70%.

Slide 44. Cytological diagnosis. Epithelial-like type of melanoma.

In the vertical growth phase, rapid growth of the formation occurs with the development of the exophytic component.

Slides 45, 46. Cytological diagnosis. Epithelial-like type of melanoma.

Superficial spreading melanoma.

Slide 47. Cytological diagnosis. Epithelial-like type of melanoma.

The second type belongs primarily nodular melanoma. It accounts for 12-15% of all cases. The average age at the time of histological diagnosis is 50 years. Nodular melanoma is twice as common in men as in women, in locations such as the back, head and neck. From a prognostic point of view, this is the most unfavorable form of melanoma, in which there is no radial growth phase. In its evolution, nodular melanoma undergoes only a phase of vertical growth, starting from the early stages of development.

However, nodular melanoma is special shape melanoma, which is spoken of when only the vertical growth phase is detected in a histological specimen - a tumor node with an intact epidermis and papillary layer of the dermis. It is assumed that nodular melanoma arises de novo in this way, and there is currently no evidence of the pre-existence of a rapid horizontal phase with subsequent regression of the intraepidermal component in nodular melanoma.

Slide 48. Cytological diagnosis. Spindle cell type of melanoma.

The histological picture of malignant melanoma, despite its extremely wide variety, does not create difficulties for the pathologist if it contains all the signs of malignancy: atypia of cells and tissue structure, infiltrative growth and melanin.

The structure of the tumor has two main variants: nested (resembles cancer) and diffuse (resembles sarcoma). With a nested structure, cells are grouped into cells, cords or columns of various sizes and shapes.

Slide 49

With a diffuse structure, mixing bundles are observed, giving a picture resembling an undifferentiated sarcoma.

Slide 50. Cytological diagnosis. Mixed type of melanoma.

Cytologically, melanoma consists of two main types of cells: epithelioid and spindle-shaped. Epithelioid cells have different sizes, shapes, protoplasm and nucleus. In one case, epithelioid cells differ large sizes, sometimes the cells can be smaller, oval or polygonal in shape. If the nests consist of a small number of cells, the picture resembles glandular structure, and in the absence of pigment, melanoma can be confused with glandular cancer.

Melanoma, composed of cells of the epithelioid type, has great pleomorphism and mitotic activity, and very often contains giant multinucleated cells.

Slides 51,52. Classification of melanomas: malignant & benign

The spindle cells of malignant melanoma are similar to fibroblasts and fibrocytes. In some cases, the sizes are large, with a plentiful amount of cytoplasm, in others they are much smaller, and their nuclei are more hyperchromic compared to cells of the epithelioid type. Pleomorphism is less pronounced.

A common feature of all malignant melanomas, regardless of their cytological and structural features, is the absence of close contact between cells. They are located at a certain distance from each other, and this is due to a violation of the adhesive properties of the cells, and not to edema or degenerative phenomena. As is known, this explains the greater ability of melanoma cells to migrate and penetrate lymphatic and blood vessels.

Melanin production is expressed differently not only in different tumors, but also in different areas one tumor. However, pigment deposition is the most important sign for the pathologist, on the basis of which he makes a diagnosis of malignant melanoma.
The absence of pigment is observed in approximately 20% of cases, then melanoma is called apigmental.

The pigment is deposited in the form of large, coarse granules that can completely obscure the cell, but sometimes it is present in the form of delicate, diffusely scattered granules. And in some cases it can be found in melanophages - histiocytic elements.

For objective assessment mitotic activity of the cell, it is necessary to examine the mitotic index. Depending on this activity, a schematic division of melanoma into several degrees is justified, but it is most important for the prognosis to identify this mitotic activity in general. Unlike cutaneous histioma, where mitotic activity is not an indicator of malignancy, the higher the mitotic activity of melanoma, the higher its malignancy.

If the epidermal infiltration does not have of great importance From the point of view of metastasis and prognosis, determining the degree of invasion into underlying tissues plays an important role. In these cases, the pathologist must determine whether the infiltration occupies only the upper layers of the dermis (as seen in superficial melanoma), the papillary layer, the reticular region, or has penetrated deep into the subcutaneous fat.

Slide 52-55.Phases of melanoma development.

The diversity of the morphological picture and large deviations in the clinical course of malignant melanoma are a significant objective obstacle when trying to create a morphological and biological parallel.

To compare the morphological (macro- and microscopic) signs of melanoma with its biological qualities, various criteria are used.

Comparison of tumor size with patient survival in the study of melanoma did not produce strict parallelisms between tumor size and animal survival for 6 months.

Very often, melanomas consist of different morphological types of cells, which makes it difficult to compare the morphology of melanoma (its specific histological type) with clinical course tumors.
At the same time, those melanomas that consist of a variety of cell types, giant, irregular and ugly, metastasize more often.

Topographical features influence the morphology and, consequently, the prognosis of the tumor. As mentioned above, tumors on the extremities often consist of more or less monomorphic cells of the epithelioid type; such tumors are usually not malignant.

Tumors composed of spindle-shaped and highly pigmented cells metastasize to almost all organs, including the pancreas and thyroid gland. Metastasis of low-pigmented melanomas is more frequent. Thus, melanomas, like all tumors, with increasing differentiation (i.e., pigment formation) reduce the malignancy of the tumor.

Slide 56. Melanoma in situ

Treatment of melanoma depending on stage

Stage I

Treatment involves surgical excision of the melanoma within healthy tissue. Amount removed healthy skin depends on the depth of melanoma penetration. Routine removal of lymph nodes located near melanoma does not improve survival in patients with stage I melanoma.

Stage II

If there is a suspicion of damage to the sentinel lymph nodes (located near the tumor), it is necessary to perform a biopsy of one of them, and if it is affected, removal of all remaining lymph nodes in this area is indicated.

At this stage of melanoma, it is possible to prescribe additional treatment, for example, interferon alpha or other drugs that can reduce the likelihood of a relapse (return) of the disease.

Stage III

At this stage of melanoma, in addition to excision of the primary tumor, all nearby lymph nodes are removed. In some cases, the administration of immunotherapy with interferon can delay the relapse of melanoma.

If a patient has several melanomas, they should all be removed. If this is not possible, the BCG vaccine or interferon is prescribed, injected directly into the tumor. Optimal treatment for this category of patients has not yet been developed. Possible use radiation therapy on the affected area, as well as chemotherapy or immunotherapy, and these methods can be combined.

Stage IV

It is impossible to completely cure patients with this stage of melanoma. With surgery, you can remove large tumor nodes that cause unpleasant symptoms. Sometimes metastases are removed from internal organs, however, this depends on their location and symptoms. A number of patients are treated with radiation and chemotherapy for palliative purposes.

Chemotherapy has very limited opportunities in patients with stage IV melanoma. Chemotherapy can shrink the tumor, but this effect is short-lived and usually lasts 3-6 months.

Immunotherapy using interferon or interleukin-2 can prolong the life of some patients with this stage. A number of doctors recommend using chemotherapy in combination with immunotherapy.

Despite the poor prognosis of most patients with stage IV melanoma, some live for several years after treatment.

doctor biological sciences, Professor
Kartashov S.N.

Text of the article and photos 1-6 from the SMALL ANIMAL DERMATOLOGY A COLOR ATLAS AND THERAPEUTIC GUIDE 2017

Translation from English: veterinarian Vasiliev AB

Peculiarities

This condition is characterized by benign (melanocytoma) or malignant (melanoma) proliferation of melanocytes. Most cases (85%) are benign. Since melanocytomas and melanomas in dogs occur on hairy skin or in the oral cavity, sun exposure is not considered causative factor. Breed and familial prevalence in domestic animals suggests that there may be genetic predisposition to this pathology.

Changes in oncogenes, tumor suppressor genes and immunological surveillance are also involved in the development of this pathology. These tumors are common in older dogs and rare in older cats. Among the dogs predisposed breeds include Scotch Terriers, Airedale Terriers, Doberman Pinschers, Cocker Spaniels, Poodles, Irish setters and schnauzers.

Melanocytomas are usually solitary, well demarcated, dome-shaped, firm, cinnamon or black, hairless, pedunculated or verrucous in shape, and vary in size from 0.5 to 10 cm in diameter. Plaque-shaped tumors may also occur. Malignant melanomas may be pigmented or nonpigmented (amelanotic), may be ulcerated, and tend to be larger and grow more rapidly than benign melanocytomas.

Malignant tumors tend to metastasize first to regional lymph nodes and then into the lungs. Lesions can be located on any part of the body, but in dogs they are most common on the head, trunk and fingers. In cats, lesions are most often found on the head.

Diagnosis

1 Cytology: round, oval, stellate or spindle-shaped cells with moderate amount cytoplasm containing granules of brown to greenish-black pigment. Malignant melanomas may have less pigment and exhibit greater pleiomorphism, but malignancy cannot be reliably determined cytologically.

2 Dermatohistopathology: accumulation of neoplastic melanocytes, which may be spindle-shaped, epithelial or round in shape with various degrees pigmentation. The cells may be grouped into clusters, cords, or whorls, similar to nerves. Infiltration by pigmented macrophages is often observed. Benign tumors are delimited and have low nuclear variability and low mitotic rates.

Malignant melanomas may show greater invasiveness, more extensive cellular pleiomorphism, and an increased number of mitotic figures (including atypical mitotic figures). The mitotic index is the most reliable way to predict biological behavior (mitotic rate<3 митозов/10 высокомощный полей обычно ассоциирован с доброкачественностью); однако,10% гистологически доброкачественных меланоцитом ведут себя как злокачественная опухоль.

3 In animals with malignant melanomas, regional lymph nodes and the chest and abdomen should be examined to identify metastases.

Treatment and prognosis

1 The treatment of choice is radical surgical excision because benign melonocytomas cannot be clinically differentiated from malignant melanomas.

2 If surgical excision is incomplete, additional treatment options include radiation therapy and local hyperthermia.

3 Chemotherapy (carboplatin, piroxicam and dacarbazine) can prolong survival in some cases of cancer, but in general the response to chemotherapy is poor.
4 Although it was primarily evaluated in canine oral malignant melanoma, Merial's xenogeneic DNA melanoma vaccine may be useful in controlling systemic metastases from cutaneous malignant melanocytomas.
5 Tomotherapy, an advanced form of radiation therapy that uses the precision of CT scanning technology, may in the future provide better outcomes than currently available treatments.
6 The prognosis is good for benign melanocytomas. The prognosis is poor for malignant melanomas, especially if the tumor is large, there is recurrence after surgery and metastasis. Tumor location is predictive: most oral and mucocutaneous melanomas (excluding eyelid tumors) and 50% of melanomas involving the claw beds are malignant. The breed is also prognostic: more than 75% of melanocytic tumors in Doberman Pinschers and Miniature Schnauzers are benign in behavior, and 85% of these tumors in Miniature Poodles are malignant in behavior.

Photo 1. Melanocytoma and melanoma of the skin of dogs and cats. A pigmented nodule near the nasal planum in an adult dog.

Photo 2. Melanocytoma and melanoma of the skin of dogs and cats. Focal pigmented nodule on the head of an adult dog.

Photo 3. Melanocytoma and melanoma of the skin of dogs and cats. Multilobulated hairless hyperpigmented melanoma on the head of an adult schnauzer.

Photo 4. Melanocytoma and melanoma of the skin of dogs and cats. Focal pigmented nodule.

A malignant formation on the skin is called melanoma. Fortunately, in the vast majority of cases, the tumor on the skin of an animal is benign in nature, then it is called melanocytoma.

Melanoma develops from melanocytes – pigment cells. Therefore, the cancerous formation has a dark color, although colorless (amelanotic) tumors are also found.

Visually, melanoma is distinguished from melanocytoma by the shape of the tumor and its location. Typically, melanocytomas have sharper edges, a dome-like shape, and do not tend to grow. Melanoma grows very quickly, has an uneven outline and is larger in size. In addition, melanoma more often affects the mucous membranes of the mouth and eyes.

Causes of melanoma

Among the reasons for the development of a malignant skin tumor, one can only name a genetic predisposition. Otherwise, there is no accurate data on the origin of the disease in animals. Unlike humans, in animals the areas affected by melanoma are usually located in places inaccessible to sunlight: the paws, in the mouth, on the retina of the eyes, or in areas covered with fur. This fact suggests that there is no effect of solar radiation on the disease.
According to statistics, cats rarely get melanoma, and in dogs, males are more susceptible to the disease than females. Most people visit the veterinarian with older pets.

More often than others, small dog breeds suffer from melanoma, such as: poodle, Scotch terrier, schnauzer, cocker spaniel, dachshund, setter and other breeds with pigmented skin.

Clinical symptoms of melanoma

The following symptoms should alert you:

• the appearance on the surface of the skin or mucous membrane of one or more dark spots with a vague outline;
• when localized in the oral cavity - salivation, bad breath, loose teeth;
• if the formation is on the toes - lameness, loss of claws;
• loss of appetite and weight loss;
• decreased activity.

Melanoma is dangerous because it grows very quickly and metastasizes. As with any other malignant tumor, early treatment can prevent metastasis to nearby organs and tissues and save the animal's life.

Treatment and diagnosis of melanoma

The first thing the veterinarian pays attention to during examination is the size, shape and number of tumors. The affected area is palpated, as well as the lymph nodes. If melanoma is located in the oral cavity, the examination is performed under anesthesia.

It is necessary to collect material for histological and cytological examination to determine the type of tumor.
To find out whether there are metastases, they resort to X-ray irradiation and ultrasound.

To treat melanoma, surgical excision of the tumor and nearby tissues is used. At the initial stage of the lesion, this may be enough. If melanoma cannot be completely removed, chemotherapy, radiation therapy and immunotherapy are used.

When an animal's limb is severely damaged, it may be amputated to save the life of its four-legged friend. But if vital organs are involved, the surgical method is unacceptable and we can only talk about prolonging the pet’s life with the help of chemotherapy.
If the tumor is in the oral cavity, it may be necessary to remove it along with part of the jaw. When a defect obtained in this way can prevent the animal from feeding independently, the possibility of its plastic correction is considered.

Some countries use a specially developed melanoma vaccine. But it is not used to prevent the disease, but to prevent recurrent diseases after removal of the detected formation. In our country, this vaccine is not produced or used, as it has not been certified.
Unfortunately, veterinarians do not give good prognosis for recovery from melanoma. Only if you do not miss the very beginning of the disease is a cure possible. In other cases, we can only talk about extending life by several years, and sometimes months.

Melanoma in veterinary practice is considered a malignant tumor that develops from melanocytes - pigment cells that produce melanin. Melanoma in animals is a dark-colored spot or growth, usually round in shape with jagged edges. A characteristic feature of melanoma is its dark color, shiny surface and tendency to decay.

Melanoma in dogs is most often localized in the oral cavity, on its mucous membrane. Almost half of all cases of treatment at the DobroVet EC regarding melanoma were registered by specialists in the mouth. Melanoma is least common on the retina, mucous membranes of the reproductive organs and rectum.

Melanoma in cats and dogs has not been studied enough. Since melanoma is localized mainly in areas hidden from sunlight, under fur, many researchers argue that solar radiation does not matter here.

Melanoma most often occurs in males. As a rule, it develops in individuals over 10 years of age, and small breed dogs are prone to this pathology, especially cocker spaniels, poodles, Scotch terriers, and dachshunds. In short, those who have strong pigmentation of the oral mucosa and skin.

Melanoma is characterized by abundant and early metastasis - through the hematogenous and lymphogenous route. Most often, lesions affect regional lymph nodes and skin. Clinically, this manifests itself in the form of multiple, small, slightly protruding black and brown rashes.

Melanoma in dogs and cats is diagnosed comprehensively, with a correct assessment of clinical symptoms, which include a visual assessment of the tumor, physical examination, and morphological analysis. Some additional methods are also used. Morphologically, cytological and histological examination is used.

In veterinary practice, tumors can be of four histological types: epithelioid cell, spindle cell, mixed cell and nevus-like. Melanomas can be pigmented or non-pigmented.

There are pigmented and non-pigmented versions of melanomas.

Treatment of melanomas in animals

In veterinary medicine, surgery is the first choice. The tumor is excised in compliance with the rules of zonation and casing; in other words, not only the tumor itself is removed, but also the healthy tissue adjacent to it in order to prevent its further spread.

Surgery is contraindicated when the tumor is localized in vital organs, as this can be fatal.

When deciding on excision, it is important to consider the possibility of plastic rehabilitation of the defect. Unlike humans, animals are more adapted to life after segmental hemimandibulectomy, maxillectomy, etc. The operation allows you to relieve the animal of possible bleeding, unpleasant odor, as well as prolong the pet’s life and improve its quality.

Cryosurgery, or freezing of malignant tumors, is characterized by a number of undeniable advantages:

Destroys the tumor completely;

Low-traumatic, bloodless and low-painful;

Combines well with other treatment methods;

Does not form rough scar formations;

Repeated cycles of exposure are possible.

There are some other methods of treating melanoma, in particular radiation therapy, chemotherapy, immunotherapy, and neutron capture therapy.

The prognosis for melanoma in cats and dogs is most often unfavorable, depending on various factors - its size, depth of germination, localization and presence of metastases. If melanoma begins to bleed and its surface is ulcerated, these are unfavorable signs. If melanoma is diagnosed in the early stages, then its development can be prevented in time and adequate treatment can be prescribed.

You can read more about dog tumors

Veterinary center "DobroVet"