STATE EDUCATIONAL INSTITUTION
HIGHER PROFESSIONAL EDUCATION
"PERM STATE MEDICAL ACADEMY
named after Academician E.A. Wagner of the FEDERAL AGENCY FOR HEALTH AND SOCIAL DEVELOPMENT"
DEPARTMENT OF PATHOLOGICAL ANATOMY WITH A SECTIONAL COURSE
PRIVATE
PATHOLOGICAL
ANATOMY
Tutorial for students
medical schools
prof. G.G. Freund, Assoc. L.F. Dorofeeva, Assoc. A.N. Kryuchkov, Assoc. A.A. Galactions, Assoc. T.B. Ponomarev, Assoc. F. Shilov, senior lecturer S.P. Laptev
H Private pathological anatomy: Study guide for students medical schools/ G.G. Freind, L.F. Dorofeeva, A.N. Kryuchkov and others; GOU VPO PGMA them. acad. E.A. Wagner Roszdrav. - Perm, 2009. - 300 p.
The manual includes material on topics of private pathological anatomy and is intended for students of medical, pediatric and medical-prophylactic faculties of medical universities.
Reviewers:
Head department pathological physiology GOU VPO PGMA Roszdrav,
prof. I.D. Elkin;
Head Department of Pathological Anatomy, Ural State
medical academy prof. L.M. Greenberg
Printed by decision of the Academic Council of the State Educational Institution of Higher Professional Education of the PSMA of Roszdrav
© GOU VPO PGMA im. acad. E.A. Wagner Roszdrav, 2009
FOREWORD
The textbook, created by the staff of the Department of Pathological Anatomy of the Perm Medical Academy, is intended primarily for students of the foreign department of medical and dental faculties. In accordance with the curriculum, the main general pathological processes are outlined: metabolic disorders (dystrophy), necrosis, blood and lymph circulation disorders, inflammation, immunopathological processes, adaptation and compensation, tumor growth.
Pathological anatomy is one of the main fundamental medical disciplines. For a long time, she used the knowledge gained from autopsy, but modern pathology is more focused on the needs of clinical practice: methods of pathological anatomy, primarily histological examination, are used for in vivo diagnosis of various pathological processes. The morphological diagnosis is great importance in the choice of treatment tactics, determining the prognosis of the disease, primarily in oncology.
Head Department of Pathological Anatomy with a sectional course
Perm State Medical Academy,
doctor of medical sciences, professor G.G. Freund
tumors of childhood
Assoc. A.N. Kryuchkov
In children, a variety of benign and malignant neoplasms are detected, developing from various tissues, including embryonic ones. In some cases, it is found congenital tumors, which are formed already in the prenatal period, for example, congenital liver cancer against the background of intrauterine viral hepatitis B. As in adults, along with tumors, tumor-like processes are traditionally considered in pediatric oncology, many of which belong to the teratoma group.
Peculiarities of childhood tumors(according to T.E. Ivanovskaya) :
1. The main tumors of childhood are dysontogenetic tumors (teratoblastomas).
2. Malignant tumors in children are less common than in adults.
3. Not epithelial tumors at children prevail over epithelial.
4. In childhood, there are immature tumors capable of maturation (reversion).
General classification of childhood tumors(according to T.E. Ivanovskaya) :
1. Teratomas
2. Embryonic tumors
3. Tumors of the adult type.
Teratoma
Definition. Teratoma- tumors and tumor-like lesions arising from tissue malformations and remnants of embryonic structures. Teratomas, which are true tumors, are called teratoblastoma(dysontogenetic tumors). The term "teratoma" comes from the Greek word teras- a miracle and a term element - oma- tumor. Literally translated, "wonderful (amazing) tumor." There are two types of tissue malformations (not to be confused with malformations of organs!) - hamartia And choristers. This classification was proposed by the German pathologist Eigen Albrecht in 1904 ( Eugen Albrecht, 1872-1908). Hamartia(from Greek. hamartia- error) - an overdeveloped normal component of the organ (for example, hemangiomas, melanocytic nevi). Choristia(from Greek. choristos- split off) - the appearance of tissue that is uncharacteristic for a given organ (for example, a dermoid cyst or ovarian struma). Choristias are also called heterotopias.
Classification of teratomas. Teratomas are classified according to three main principles:
I. Depending on the origin:
1. Runs
3. Choristoms.
Runomes- tumors from the remains of embryonic structures (for example, the notochord or the pituitary gland). All progonomas are true tumors (teratoblastomas). Hamartomas- hamartia in the form of a nodule or node. Hamartomas as true tumors are called hamartoblastomas. Choristomas- choristia in the form of a nodule, node or cyst. Choristomas, which are true tumors, are called choristoblastoma.
II. According to the degree of maturity of teratoma (clinical and morphological classification):
1. Mature teratoma
2. Immature teratomas.
Mature teratoma- teratomas formed by differentiated (mature) elements. Mature teratomas are usually benign. Immature teratoma- teratomas represented by oligodifferentiated and/or undifferentiated (immature) elements. Immature teratomas are malignant neoplasms.
III. According to the number of tissue components:
1. Histioid teratomas
2. Organoid teratomas
3. Organismoid teratomas.
Histioid teratomas- teratomas, represented by one type of tissue (for example, angiomas, melanocytic nevi, chondromatous hamartoma of the lung). Organoid teratomas- teratomas formed by tissues characteristic of one organ (for example, a dermoid cyst or ovarian struma). Organismoid teratomas- teratomas built from different tissues, typical of two or more organs (for example, most sacrococcygeal teratomas).
Previously, teratomas were classified into mono-, di- and tridermomas, depending on their origin from one, two or three germ layers. Currently, this principle of classification of teratomas is practically not used.
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When classifying tumors in children, it is not always possible to apply the histogenetic principle adopted for adult tumors, since dysontogenetic tumors can consist of elements from different germ layers.
Depending on the origin, the following types of tumors in children are distinguished:
dysontogenetic;
Tumors from cambial embryonic tissues;
Tumors of the type of adult tumors.
Tumor-like conditions should be distinguished from tumors.
Heterotopia (choristoma) - microscopically normal cells or tissues located in another organ or in the area of the same organ where they should not be. For example, in the wall of the colon or stomach, foci of pancreatic tissue are found, in the lungs, kidneys, and ovaries - cells of the adrenal glands, etc. Heterotopias, as a rule, have no clinical significance and can be mistaken for neoplasms.
Hamartoma is a tumor-like local growth of tissues characteristic of a given organ. Hamartomas are borderline formations between malformations and tumors, the border between them is indistinct. So, some researchers consider hemangiomas, lymphangiomas, heart rhabdomyomas, liver adenomas to be hamartomas, others are true tumors.
benign tumors
The most common benign tumors in children are hemangiomas, lymphangiomas, fibromas. Their morphology is described in detail in other sections, this chapter describes the features of these tumors in children.
Hemangioma- the most common benign tumor childhood age. Most often, children have capillary and cavernous hemangiomas, or a combination of both. Localization - the skin of the head, neck, torso, less often - internal organs. Capillary hemangiomas can increase in size, especially rapid growth is observed in the first months of life. At the age of 1–3 years, the growth of the tumor stops, and by the age of 5 years, it usually spontaneously regresses. The tumor has infiltrating growth, and therefore relapses are possible. Giant hemangioma of the extremities and trunk in young infants can cause the development of thrombocytopenic purpura due to widespread thrombosis of the vessels of the hemangioma (Kasabakh-Merritt syndrome). Hemangiomas are one of the manifestations of the hereditary Hippel–Lindau syndrome.
Lymphangioma usually occurs in children under 3 years of age. The most clinically significant lymphangiomas are localized in the deep areas of the neck, armpit, mediastinum, retroperitoneal space. Despite the absence of cellular atypism, lymphangiomas have a locally destructive growth and increase in size after birth, sometimes damaging vital organs (eg, mediastinum) or nerve trunks. Lymphangiomas (hamartomas or true tumors) must be distinguished from lymphangiectasias, abnormally enlarged preexisting lymphatic vessels. Lymphangiectasias are manifested by diffuse edema of a limb or part of it, causing deformity. Unlike lymphangiomas, lymphangiectasias do not progress, but can cause serious cosmetic problems.
Fibrous tumors in children are varied, often their degree of malignancy is unclear. Fibromatoses in children are often characterized by hypercellularity, rapid infiltrating growth, which makes it difficult to distinguish them from adult fibrosarcomas. Observe cases of spontaneous regression.
Infantile myofibromatosis - the presence of small dense nodules in the dermis, subcutaneous tissue, muscles, internal organs. Nodes can be single and multiple (more than 50). With solitary tumors, the prognosis is favorable, with multiple tumors, children die in the first year of life.
Juvenile angiofibroma of the nasopharynx usually occurs in boys older than 8 years. Microscopically, the tumor consists of fields of fibrous tissue with few fibroblasts and thin-walled blood vessels. It has infiltrating growth and sometimes sprouts the bones of the skull. The localization of the tumor and the nature of its growth make it difficult to radically remove it. If the tumor is damaged or attempted to be removed, profuse bleeding is possible. The tumor is histologically benign and does not metastasize. May spontaneously regress.
Teratoma - a tumor from embryonic undifferentiated germ cells that occurs when their migration is disturbed during the morphogenesis of the gonads of the embryo. Teratoma is represented by tissues of three germ layers, however, the main part is usually tissues of ectodermal origin. In a mature teratoma, the epidermis with all derivatives (hair, glands), glial tissue, clusters of ganglion cells, adipose, muscle tissue, cartilage, and less often other tissues, elements of the trophoblast are found.
Typical localization of teratomas - ovaries, testicles, sacrococcygeal region, mediastinum, retroperitoneal space, oropharynx and skull base. In newborns and children of the first two years of life, sacrococcygeal teratomas predominate; from the age of 15–16, the frequency of ovarian teratomas increases. Most testicular teratomas appear between the ages of 20 and 49 years.
Sacrococcygeal teratoma is the main type of teratoma in newborns and young children. This tumor is diagnosed in girls 3 times more often than in boys. Often combined with non-immune dropsy of the fetus, polyhydramnios, there may be difficulties in delivery. Most sacrococcygeal teratomas are mature. Histologically, such a tumor consists of mature tissues, often with organoid differentiation. Malignant teratomas (teratoblastomas) contain elements of a large cell carcinoma that forms papillary structures or grows solidly. Teratoblastomas are characterized by the presence of tumor elements of the endodermal sinus. These tumors have a very poor prognosis.
Malignant tumors
Most often, malignant tumors in children develop in the hematopoietic system, nervous tissue, soft tissues, bones, kidneys. The distribution of tumors in organs differs sharply from adults, they have the most frequent localization tumors - skin, lungs, mammary glands, prostate gland, large intestine. The frequency of occurrence of various malignant tumors strongly depends on the age of the child. Malignant tumors in children are most often dysontogenetic. Microscopically, they mostly have signs specific to the organ where the tumor has developed. Such tumors are often referred to as blastoma: nephroblastoma, neuroblastoma, retinoblastoma (see disc).
Neuroblastoma
Neuroblastoma is the most common childhood solid tumor that develops outside the CNS. The frequency of neuroblastoma is 6-8 cases per million children. Among all neoplasms in children, it is 14%. In 85-90% of neuroblastomas are found in children younger than 5 years. In girls, neuroblastoma is somewhat less common and has a better prognosis than in boys (see ³).
Neuroblastoma develops from neural crest cells. The most common (up to 40%) localization is the adrenal medulla and paraspinal ganglia, less often the pelvis, neck, and chest. In adults, neuroblastomas are occasionally found in the head, neck, and legs.
Macroscopically, neuroblastoma has the appearance of a node, its size can vary significantly. Some neuroblastomas are clearly delimited from the surrounding tissues and may have a thin capsule, others have a pronounced infiltrating growth and quickly grow into the surrounding tissues (kidneys, renal and inferior vena cava, aorta). On section, the tumor is represented by soft gray tissues resembling the substance of the brain. In large tumors, foci of necrosis, hemorrhages, petrificates are not uncommon. The histological picture of neuroblastoma depends on the degree of tumor differentiation.
In most cases, the tumor consists of small lymphocyte-like cells with dark nuclei and sparse cytoplasm, located in solid layers (Fig. 24-7). More differentiated tumor cells have eosinophilic neurofibrillary processes and are located in the fibrillar stroma. Sometimes in tumors, the formation of pseudorosettes in the form of a corolla of cells surrounding eosinophilic accumulations of neurofibrils is observed. Electron microscopy of tumor cells shows neurosecretory granules and nerve processes with microtubules. Further differentiation leads to the formation of cells of the ganglion type - large cells with a wide rim of eosinophilic cytoplasm, a large bubble-shaped nucleus with well-defined nucleoli, and the amount of fibrillar stroma in the tumor tissue is increased. A tumor with complete differentiation is represented by mature ganglion cells surrounded by bundles of connective tissue, nerve fibers, and Schwann cells. Such tumors are called ganglioneuromas. The tumor can have areas with different differentiation, so the diagnosis of ganglioneuroma is established only by analyzing many sections from different parts of the tumor. A number of neuroblastomas undergo differentiation and mature into ganglioneuromas or spontaneously regress. Regression occurs more often with small tumor sizes. Metastases are observed in 50% of cases of neuroblastoma in children under 1 year of age and in 70% of cases at an older age. The most common metastases are to the lymph nodes, Bone marrow, bones, liver, subcutaneous tissue.
The prognosis for neuroblastoma depends on many factors. There are markers that help determine the prognosis of a tumor (see ³).
Retinoblastoma
Retinoblastoma is diagnosed in one in 20,000 newborns and accounts for 2.5–4.5% of all malignant tumors in children. It can be unilateral or bilateral, unilateral or multifocal, and often congenital. Spontaneous regression of retinoblastoma is possible, as well as other tumors in children.
Familial and sporadic cases of retinoblastoma have been described. Non-hereditary cases of retinoblastoma are always unilateral and unifocal. Family (hereditary) cases account for about 50%, while the tumor is usually bilateral, often multifocal. Patients with genetic forms of retinoblastoma have a predisposition to develop other types malignant neoplasms. Retinoblastomas most often occur before the age of 4 years.
The development of retinoblastoma is associated with a gene mutation Rb located on chromosome 13q14. This gene encodes a nuclear protein that blocks the exit of the cell from the G 1 phase of the cell cycle and is involved in cell differentiation. In genetically determined cases, children are born with one normal and one defective gene. Rb(inherited from one of the parents or the result of a new mutation in the germ cells). The mutation of the second gene is somatic, it occurs in the retina. In non-hereditary (sporadic) cases, both mutations are somatic. Thus, two somatic mutations must occur in a retinal cell giving rise to non-hereditary retinoblastoma. Because the level of somatic mutations is low, patients with sporadic cases have only a single tumor site.
Patients with familial retinoblastoma have an increased risk of developing osteosarcomas and other soft tissue tumors. Gene inactivation Rb also found in small cell carcinoma lung, cancer Bladder, mammary and prostate glands.
Retinoblastoma develops from cells of neuroepithelial origin. The tumor is located in the posterior chamber of the eye as a single or multiple papillary formation of a pinkish-white color, with foci of necrosis and petrifications. Histologically, the tumor is represented by small
Rice. 24-7. Neuroblastoma. The tumor consists of small lymphocyte-like cells with dark nuclei and sparse cytoplasm. Cells are arranged in solid layers. Staining with hematoxylin and eosin (´350)
rounded cells with hyperchromic nuclei and sparse cytoplasm, sometimes forming ribbon-like structures. More differentiated forms of the tumor contain cuboidal or low prismatic cells that form true Flexner-Wintersteiner rosettes (Fig. 24-8). Such cells contain formations resembling photoreceptors. Initially, the tumor is located within the retina, as it grows, it destroys the vitreous plate, spreading to the choroid and vitreous body, can fill the entire cavity eyeball destroy the bony walls of the orbit. Along the course of the optic nerve, the tumor can grow into the cranial cavity. Retinoblastoma metastasizes lymphogenously and hematogenously. The most common localization of lymphogenous metastases is parotid, submandibular, cervical lymph nodes, hematogenous - skull bones and tubular bones of the extremities, liver. Spontaneous regression of the tumor with calcification and a pronounced inflammatory reaction is possible.
The success of treatment largely depends on the age of the child. In children under 1 year of age, the mortality rate is 7%, in older children it is about 20%. With this tumor, limited to the limits of the eyeball, the chance of recovery is greatest compared to other malignant tumors. Early diagnosis significantly improves the prognosis, while organ-preserving operations with vision preservation are possible. With the spread of retinoblastoma outside the eyeball, the prognosis is much worse. Patients with retinoblastoma usually die from metastases. Cases of the development of osteosarcoma of the orbit after radiotherapy retinoblastoma.
Wilms tumor
Wilms tumor (nephroblastoma). The frequency of nephroblastoma is 7.8 cases per 1 million children aged 1 to 14 years. The tumor rarely occurs in children under 6 months and after 5 years. The highest frequency is observed at the age of 2–3 years.
Wilms' tumor exists in sporadic, familial, and syndrome-associated forms. Most patients with a tumor have a normal karyotype, but in some cases there is an association with a deletion of 11p13, where the tumor-associated WT-1 gene is located.
WT-1 is a tumor suppressor gene, its product is a regulator of a transcription factor that binds to DNA. The WT-1 protein is expressed by the kidneys and gonads of the fetus. Transgenic mice lacking both copies of the WT-1 locus have renal agenesis. Other anomalies were also found in Wilms' tumor: a mutation of the WT-2 gene located in the short arm of the chromosome
Rice. 24-8. Retinoblastoma. Tumor cells form a true rosette with a well-defined inner membrane. Staining with hematoxylin and eosin (´400)
we 11 distal to the WT-1 gene locus, loss of heterozygosity of the long arm of the chromosome 16. Often a combination of Wilms tumor with congenital malformations (see ³).
Macroscopically, nephroblastoma is usually a large single node, clearly demarcated from the kidney tissue. On the section, the tumor is soft, grayish-pink, with foci of necrosis, hemorrhages and cysts. Multifocal and bilateral lesions occur in 10% of cases.
Microscopically, Wilms' tumor is represented by derivatives of nephrogenic tissue at different stages of differentiation. The tumor is characterized by a combination of blastema, epithelial and stromal components.
The blastema component is rounded small cells with hyperchromic nuclei and a narrow rim of the cytoplasm.
The epithelial component is tubules of various types, reflecting the stages of nephron differentiation, less often glomeruli (Fig. 24-9).
Stromal (mesenchymal) component - loose immature connective tissue (Fig. 24-10), in it - areas of smooth and striated muscles, adipose tissue, cartilage and bones.
The presence of differentiated tissues in the tumor does not affect the prognosis. The only histological sign indicative of poor forecast, the presence in an anaplastic tumor. In relation to Wilms' tumor, the concept of anaplasia means the appearance of cells with enlarged hyperchromic polymorphic nuclei and pathological mitoses. The tumor metastasizes both lymphogenously and hematogenously. Lymphogenic metastases - to the lymph nodes of the kidney gate and para-aortic, then to the lymph nodes of the liver gate and mesenteric. Hematogenous metastases are predominantly in the lungs. Bone metastases are not common, unlike other kidney tumors. In the tissue of metastases, as a rule, non-epithelial components of the tumor predominate.
In many cases, Wilms tumors, as well as in congenital and hereditary anomalies in the kidneys, find foci of primitive, undifferentiated cells that form tubular metanephrogenic structures. Unlike Wilms tumor, stromal and epithelial structures are not found in them, mitoses are very rare. These lesions are called nephroblastomatosis. In kidneys removed for Wilms tumor, such foci are found in 20–44% of cases. They are considered precursors of Wilms tumor, but it is known that in most cases persistent blastoma foci in the kidneys do not lead to tumor development.
In children with a unilateral tumor that does not invade the capsule, the recovery rate exceeds 90%, in patients with distant lymphogenous or hematogenous metastases, about 60%. In children with a bilateral tumor, the prognosis, contrary to expectations, is quite favorable.
Hepatoblastoma
The frequency of hepatoblastoma is 1 case per 100 thousand children under 15 years of age. Among tumors of childhood, it is no more than 5%. Boys get sick 1.5 times more often than girls. More than half of the cases of tumor detection occur before the age of 2 years.
In children with hepatoblastomas, a number of chromosomal abnormalities are described that are less permanent than those with neuroblastoma (see ³). Familial cases of hepatoblastoma have been described. A combination of a tumor with a number of diseases and conditions is possible: hemihypertrophy, familial colon polyposis, Meckel's diverticulum. No connection was found between the tumor and the intake of hepatotoxic substances (alcohol, nitrosamines, estrogens) by the mother during pregnancy, as well as with hepatitis during pregnancy. At the same time, there are indications of a connection between hepatoblastoma and fetal alcohol syndrome (see ³).
Usually hepatoblastoma develops in the right lobe of the liver, sometimes in both lobes. The tumor has the appearance of a dense multinodular formation of a yellowish-brown color, may be surrounded by a capsule. Often there are foci of necrosis with the formation of cystic cavities and hemorrhages.
The microscopic picture depends on the degree of maturity tumor cells, the ratio of epithelial and mesenchymal components of the tumor. The epithelial component of the tumor may be represented by large light cells with a round nucleus, resembling normal fetal hepatocytes. Cells form columns, such areas can be difficult to distinguish from normal liver fetus. In less mature tumors, cells with
Rice. 24-9. Wilms tumor, epithelial component. Epithelial cells form tubules, resembling the various stages of neuron differentiation. Staining with hematoxylin and eosin (´150)
Rice. 24-10. Wilms tumor, mesenchymal component. Loose immature connective tissue. Staining with hematoxylin and eosin (´150)
a smaller rim of the cytoplasm often form tubular structures; mitoses are frequent in such tumors. Anaplastic forms of hepatoblastoma can be large- and small-celled.
Immunohistochemically, a-fetoprotein is detected in hepatoblastomas, in some cases, transferrin receptors. A possible marker is a liver protein that binds fatty acids.
With a combination of surgical treatment and combined chemotherapy, the 18-month survival rate reaches 80%. Prognosis is affected by ploidy (diploid tumors have a better prognosis than hyperploid ones). Probably, as with other embryonic tumors, the prognosis is better in young children (see ³).
Chapter 25
Skin diseases
Skin pathology is diagnosed in 20–25% of the population. Skin changes can be a manifestation of both diseases of the skin itself, and various internal diseases, and therefore are very numerous (see ³).
Skin pigmentation disorders
This pathology is manifested by a decrease or increase in the amount of melanin. In addition, melanocytes can become a source of a malignant tumor - melanoma (see ³).
Albinism (leucoderma) is a disease with an autosomal recessive type of inheritance, in which melanin synthesis in melanoblasts does not occur due to the absence of tyrosinase. Albinos have blonde hair pale skin and pink eyes.
· Vitiligo is a violation of pigmentation with the appearance of milky-white depigmented macules on the skin. Vitiligo lesions are characterized by the loss of melanocytes. Probable reasons for this: autoimmune destruction or the formation of toxic intermediates of melanogenesis that destroy melanocytes, skin inflammation (in leprosy, syphilis), burns, etc.
Freckles are small (1–10 mm) reddish or light brown maculae that first appear in early childhood after sun exposure. Hyperpigmentation is caused by an increased amount of melanin in the keratinocytes of the basal layer of the epidermis.
Chloasma (melasma, melasma, melanosis of the skin) - excessive deposition of melanin in the skin, usually in the form of symmetrical maculae on the face, more pronounced than in the elements of freckles. Melasma is associated with an increased amount of melanin in the cells of the basal layer of the epidermis or the accumulation of macrophages in the papillary dermis. The latter phagocytize melanin from the epidermis (this process is called melanin incontinence).
Lentigo - hyperplasia of melanocytes, possible at any age, often contributes to its development ultraviolet irradiation. The disease can affect both the mucous membranes and the skin. Its manifestation is small (5–10 mm) oval brown maculae. The main histological sign is linear hyperplasia of melanocytes along the basement membrane of the epidermis.
Pigmented nevus
Pigmented nevus (non-cellular, melanocytic) is a common benign skin lesion. The name "non-cellular nevus" is used in relation to any congenital or acquired tumor of melanocytes. Nevi are made up of three types cells: nevus, epidermal and dermal melanocytes.
The nuclei of nevus cells are rounded, relatively monomorphic, and contain inconspicuous nucleoli. Their mitotic activity is insignificant. Macroscopically, nevi may look like flat spots, protruding above the surface of the skin of the macula, exophytic formations - dome-shaped or papillomatous tumors on the leg. Exists a large number of clinical and histological types of non-cellular nevus (see ³).
Against the background of nevi may occur tumor - malignant melanoma. More than others, a dysplastic nevus is prone to malignancy (see ³).
Melanoma
Melanoma (gr. melanos- dark, black) - a malignant tumor growing from melanoblasts located in the basal layer of the epidermis, on the border of the epidermis and dermis. This term was proposed in 1838 by Carswell. For the first time as an independent tumor, melanoma was identified in 1864 by R. Virkhov. Skin melanoma accounts for 1–10% of all malignant skin tumors and 0.3–0.9% of all human malignancies.
Melanomagenic factors:
the presence of a nevus (especially dysplastic);
exposure to carcinogens.
A large number of gene and molecular anomalies have been found in human melanoma.
Clinical signs of melanoma are asymmetry, uneven contour, uneven pigmentation, diameter more than 6 mm. Pigmentation appears in all sorts of shades of black, brown, red and gray, there are areas of hypopigmentation. One of the varieties malignant melanoma- amelanotic (pigmentless) variant.
The morphogenesis of malignant melanoma includes the stages of radial and vertical growth.
Radial growth occurs long time. It is manifested by the horizontal spread of tumor cells in the epidermis and superficial layers of the dermis. Melanoma cells are not yet capable of metastasizing.
· Vertical growth. The tumor grows into the deeper layers of the dermis. Atypical melanocytes are located in the epidermis and dermis. During this period, clones of tumor cells with metastatic potential arise.
At microscopic examination melanoma cells are much larger than the elements of the nevus. These cells have large nuclei with irregular contours and marginal (under the nuclear membrane) arrangement of chromatin, as well as clearly visible eosinophilic nucleoli.
The main types of malignant melanoma are: malignant lentigo, acral lentigial melanoma, melanoma with superficial (radial) spread, nodular melanoma (with vertical growth) (see ³).
The likelihood of metastasis can be predicted by measuring the thickness of the tumor (in millimeters Breslow). In 2002, the American Joint Committee on Cancer Research developed new criteria for assessing the stage and prognosis of melanoma (see disc). Along with the known criteria (tumor thickness according to Breslow and germination depth Clark) assess the presence of ulceration, involvement of the lymph nodes and internal organs. In metastases, including distant ones, the synthesis of melanin is preserved.
The disease was formerly almost always regarded as fatal, but timely diagnosis And surgery provide a favorable prognosis.
Epithelial tumors
Benign epithelial tumors
and tumor-like processes
These processes are widespread in the skin. They can arise from stratified squamous keratinizing epithelium, keratinocytes of hair follicles, lining of ducts of skin appendages. Histological examination of biopsy specimens is necessary to establish the diagnosis.
seborrheic keratosis- a common disease, it is characterized by numerous round flat epidermal pigmented surface plaques with a diameter of several millimeters to several centimeters. Plaques often appear in middle or old age on the skin of the trunk, extremities, head and neck. Formations in seborrheic keratosis are built from complexes of small cells similar to the cells of the basal layer of normal epidermis and containing various amounts of melanin in the cytoplasm. Characterized by hyperkeratosis, small, keratin-filled cysts (horny cysts), and signs of keratin intrusion into the bulk of the neoplasm (pseudo-horny cysts).
Black acanthosis (acanthosis nigricans) - thickening and hyperpigmentation of the skin of the neck, armpits, vulva, perineum, anus and inguinal-femoral folds. It is believed that acanthosis nigricans is a diagnostically valuable skin marker of combined benign and malignant neoplasms. The reason for its appearance is the abnormal production by tumors of factors that stimulate epidermal growth.
Squamous papilloma(fibroepithelial polyp) - a benign tumor of the skin, has the form of limited exophytic warty growths with a papillary surface of at least 1–2 cm in size. Microscopically, papillary outgrowths of stratified squamous epithelium are detected with preservation of differentiation of the layers, intercellular bridges are well expressed. Tumor stroma - connective tissue strands with blood vessels.
Keratoacanthoma- a rapidly growing neoplasm, a benign epidermal tumor of the hair follicles in the form of a flesh-colored nodule, having a domed shape, with a depression in the central part. The diameter of the neoplasm is from 1 cm to several centimeters. Histologically, the presence of a crater filled with keratin and surrounded by proliferating epithelial cells forming solid structures is characteristic. The latter, like a collar, cover the crater and sink into the dermis in the form of uneven tongues. Epitheliocytes are relatively large, have mild signs of atypia and eosinophilic cytoplasm. Malignancy occurs in about 60% of cases.
The influence of age on tumor growth is manifested in some features of tumors in children compared with those in adults. Mainly distinguish 4 peculiarities:
The first feature tumors in children is their frequent occurrence from embryonic tissues as a result of violations of the formation of organs and tissues during fetal development. Therefore, the vast majority of tumors in children develops from tissues delayed in their development at the embryonic level , often located out of place - dystopian . Tumors from embryonic tissues are called dysontogenetic, or teratoid.
Teratoma (from the Greek. teratos - freak) - a tumor of embryonic undifferentiated germ cells that occurs when their migration is disturbed during the morphogenesis of the sex glands of the embryo. Violation of the morphogenesis of the tissue germ at any stage of the development of the embryo, the loss of its connection with the surrounding growing tissues leads to the fact that this germ is deprived of humoral and reflex influences, which normally regulate coordinated growth and proportional development of tissues. As a result of this exclusion of regulatory influences, the displaced tissue germ acquires a certain autonomy. The latter is probably a prerequisite for the occurrence of true tumor growth. In adults, teratoid dysontogenetic tumors are rare; in children, this is the main type of tumor.
The second feature tumors in children is high frequency of occurrence of benign tumors in them and the relative rarity of malignant while malignant tumors are more common in adults. The most common benign tumors in children are tumors skin -angiomas and nevi .
The third feature tumors in children are prevalence of sarcomas among malignant tumors and the rarity of cancer, while the opposite is observed in adults. Among sarcomas in childhood, predominate lymphoma and osteosarcoma. Cancer occurs mainly in organs that are not in contact with the external environment, endocrine glands- Thyroid, adrenal glands, gonads. Gastric cancer is observed as an exception in children aged 10-11 years. It has been suggested that carcinogenic substances obtained by the fetus transplacentally from the mother, circulating in the blood, come into contact primarily with the tissues of the internal environment of mesenchymal origin - the vascular bed and stroma of organs, as well as with the endocrine glands, the brain, and internal organs.
The fourth feature tumors in children is the peculiarity of the course of some malignant tumors in them compared to those in adults. Thus, malignant tumors of internal organs (embryonic nephroma and hepatoma) in children retain the expansive growth pattern characteristic of benign tumors for a long time and do not metastasize for a long time. Along with this, some benign tumors in children have infiltrating growth, such as angiomas. In children, there is a surprising phenomenon of the transition of malignant tumors (for example, neuroblastomas) to benign ones (ganglioneuromas), which is not observed in adults, this phenomenon is called tumor reversion. Malignant tumors are predominantly found in children from neonatal period to 6 years of age . More often they occur at the age of 3-5 years, which indicates the importance of intrauterine carcinogenic influences, probably coming from the mother.
Note:
Tumors that are most common in children and almost never occur in adults (nephroblastoma, neuroblastoma, retinoblastoma);
Tumors, which in adults occupy a significant place in the structure of morbidity, are extremely rare in children (cancer of the stomach, intestines);
In children, hemoblastosis ranks first in terms of incidence, followed by tumors of the central nervous system, kidneys, bones, soft tissues, etc.;
There are two age peaks of incidence: up to 4-6 years and at 11-12 years. In young children, leukemia, nephroblastoma, neurogenic tumors are more often diagnosed; in adolescence - bone neoplasms, Hodgkin's disease;
Unlike adults, childhood tumors are generally not associated with lifestyle risk factors such as smoking, alcohol consumption, malnutrition and insufficient physical activity;
Despite the rarity of tumors in children and impressive treatment successes, malignant tumors remain the leading cause of death in children under 15 years of age, second only to accidents in most age groups.
Classification.
The extreme variety of clinical and morphological variants of O., differing in tissue origin, histological structure, clinical course, prognosis, and sensitivity to antitumor therapy, led to the need to systematize them and create a unified nomenclature (basic names and synonyms) of O. and generally accepted working classifications.
WHO international expert groups have created O. classification schemes of various organs and systems, which were based on histopathological (histogenetic) principle. Each classification has the following headings: benign ABOUT., malignant O. and tumor-like processes . An attempt is made within each heading to adhere to the histogenetic (origin of O. from a specific type of cells) or structural (according to the tendency to form certain tissue structures) principle.
Depending on the characteristics of growth, they are macroscopically distinguished knotty And diffuse O. In relation to the lumen of hollow organs, O.'s growth can be exophytic (O. protrudes into the lumen of the hollow organ) and endophytic (O. spreads mainly in the thickness of the wall of the organ).
International system of clinical classification of malignant tumors ( TNM) provides for the characterization of the tumor process according to three main criteria: the size of the primary tumor, the presence of metastases in regional lymph nodes and the appearance of distant metastases.
Depending on the degree of spread of the tumor process (this applies mainly to cancer of various organs), 4 clinical stages of the disease :
first- a tumor of small size, without metastases in regional lymph nodes;
second- a tumor of a larger size, but within the affected organ, or the same as in the first stage, but with single metastases in the regional lymph nodes;
third- the tumor spreads to neighboring organs and tissues, there are multiple metastases in the regional lymph nodes;
fourth- the tumor spreads to neighboring organs, there are metastases in regional lymph nodes and distant organs. Establishment in each patient of the morphological type of tumor and the clinical stage of the disease forms the basis of diagnosis, which, in turn, determines the nature and extent medical measures and, in some cases, the prognosis of the disease.
Dysontogenetic nature of most tumors in children makes it difficult creation of their classification. On the one hand, in children in the same tumor, tissues of different histogenesis can occur, on the other hand, the embryonic nature of many tumors prevents the identification of their tissue affiliation. Therefore, it is not always possible to classify tumors in children according to the histogenetic principle, as adult tumors are classified.
If proceed from the principles of ontogenetic development, then all tumors in children can be divided into threemain type:
To tumors 1 type relate teratomas, or keratoid, dysontogenetic, tumors. The occurrence of teratomas is currently explained by a violation of the migration of germinal germ cells during the formation of the caudal end of the urogenital ridge. Separation of part of the undifferentiated germ cells of the caudal end of this ridge and their persistence lead to the development of teratomas. By histological structure distinguish between histioid, organoid and organismoid teratomas. There are also teratomas that develop from the elements of the embryoblast - embryonic teratomas and that develop from the elements of the trophoblast - extraembryonic teratomas. There are mature embryonic and extraembryonic teratomas and immature - teratoblastomas. The tissues of a mature teratoma mature synchronously with the tissues of their carrier. For example, in a fetus, they consist of tissue elements corresponding to the age of the fetus, and lose their undifferentiated character by the time of his birth. Therefore, they do not have complete autonomy, they lack the ability for progressive growth. In this, mature teratomas differ from true benign tumors. Teratoblastoma contains immature undifferentiated tissues, more often extraembryonic, capable of progressive growth, gives metastases and is a true malignant tumor. Histioid teratomas are otherwise called hamartomas, with a malignant variant - hamartomas. Hamartoma (from Greek hamarta - error) - a tumor from embryonic tissue, delayed in its differentiation compared to the tissues of the tumor carrier, developing from excessively disproportionately developed tissue complexes, for example, from excessively developed vessels. Hamartomas in children include angiomas, nevi, embryonic tumors of internal organs, embryonic tumors of mesodermal and mesenchymal histogenesis (benign and malignant). The group of hamartomas also includes tumors that develop on the basis of a run - the remains of organs of the embryonic period that have not undergone timely involution, for example, tumors from the remains of the dorsal chord, gill arches, pituitary tract, etc.
To tumors 2 types are those that arise from embryonic cambial tissues preserved in the CNS, in the sympathetic ganglia and adrenal glands during normal development. So, in a child under the age of 1 year, such immature cambial anlages remain under the ependyma of the brain ventricles and gradually disappear by the end of the first year after birth. immature cellular elements of embryonic nature in the form of sympathogonia with wide potential for growth and differentiation remain in the adrenal medulla up to 10-11 years. A feature of type 2 tumors are certain age periods within which, as a rule, these tumors are observed. However, it is not possible to accurately distinguish them from hamartomas, and the isolation of this type of tumor is somewhat arbitrary. Type 2 tumors include medulloblastoma, retinoblastoma, and neuroblastoma.
To tumors 3 types include tumors that are of the type of adult tumors. In children, the vast majority of these tumors have mesenchymal histogenesis; hemoblastoses, osteogenic tumors, and mesenchymal soft tissue tumors are most common. Epithelial benign tumors - papillomas and polyps - occur relatively often in children. Epithelial malignant tumors (cancer) are rare in children; cancer of the endocrine glands and genital organs is predominant.
RISK FACTORS FOR MALIGNANT TUMORS IN CHILDREN
Many malignant tumors in children occur at a very early age. Some of them are the result of a family predisposition due to genetic (hereditary) factors. Exposure to radiation can explain the development of some types of childhood tumors. The cause of most malignant tumors in children remains unknown.
Early diagnosis of malignant tumors in children is very difficult. For these purposes, regular medical examinations and examinations can be recommended. It is important to pay attention to the appearance of unusual signs and symptoms in time, which may include the presence of swelling or tumor formation, pale skin and increased fatigue, unexplained bruising, pain or limping, prolonged fever, frequent headaches with vomiting, sudden deterioration in vision, rapid weight loss.
The main forms of malignant tumors in children:
Leukemia It is represented mainly by acute lymphoblastic leukemia (ALL), which makes up 33% of the total number of neoplastic diseases in children and ranks first in frequency.
Tumors of the brain and spinal cord occupy the second place in frequency and develop mainly in the cerebellum and brain stem. In adults, unlike children, tumors occur in different parts of the brain, but most often in the hemispheres. Neoplasms of the spinal cord in children and adults are much less common.
Nephroblastoma (Wilms tumor) affects the kidneys, and the tumor can be unilateral or bilateral. It occurs most often at the age of 2-3 years.
Neuroblastoma is the most common extracranial tumor that occurs predominantly in the abdomen in children of the first year of life.
Retinoblastoma- a malignant tumor of the eye, which is rare, but is the cause of blindness in 5% of patients.
Rhabdomyosarcoma is the most common soft tissue tumor in children.
Osteogenic sarcoma is the most common primary bone tumor in children and young adults.
Ewing's sarcoma It is somewhat less common and usually occurs in children and adolescents.
Hodgkin's disease(Hodgkin's lymphoma, lymphogranulomatosis) develops from lymphatic tissue (lymph nodes and organs of the immune system) in both children and adults, most often in two age groups: from 15 to 40 years and after 55 years. In children under 5 years of age, Hodgkin's disease is diagnosed very rarely. 10-15% of tumors are detected at the age of 16 years or less.
Non-Hodgkin's lymphoma (lymphosarcoma) ranks third in frequency and, similarly to Hodgkin's disease, arises from the lymphatic tissue.
Treatment. In benign tumors, in most cases, surgical treatment is used - excision within healthy tissues. Surgical treatment is also highly effective in early stages of cancer (cancer in situ, TiN0M0). With widespread malignant tumors, in the late stages of the disease in the presence of massive regional or distant metastases, as well as malignant systemic lesions (leukemia, hematosarcoma), surgical treatment is ineffective, and sometimes simply not applicable. In these cases, radiation therapy is prescribed using external and incorporated sources of ionizing radiation, as well as special applicators injected directly into the tumor, and chemotherapy.
Chemotherapy involves a selective effect on various links in the metabolism of tumor cells in order to destroy them while maintaining vital activity. healthy cells and body tissues. For this, antitumor agents are used, which are divided into hormonal and chemotherapeutic antitumor drugs proper. The latter include cytostatics - substances that have a detrimental effect on tumor cells. The following groups of cytostatics are most common: alkylating drugs that disrupt DNA synthesis (embiquine, chlorbutine, sarcolysin, cyclophosphamide, etc.); antimetabolites that disrupt cell growth and DNA and RNA metabolism (methotrexate); antitumor antibiotics (dactinomycin, mitomycin-C, olivomycin, rubomycin, adriamycin); alkaloids (vinblastine, vincristine), etc.
Immunotherapy is intensively developing, aimed at increasing the body's natural defenses. For this purpose, immunomodulators such as interferon, interleukin-2 and other drugs are used. In the later stages of the disease, a combination of surgical treatment with radiation and (or) drug therapy (before or after surgery) is often required, so combined methods occupy the main place.
Tumors in children are much less common than in adults. Malignant neoplasms of childhood make up only 2% of all human malignant tumors. However, among the causes of death in children, they occupy one of the leading places. In economically developed countries the death rate of children from malignant neoplasms ranks second after accidents and is 10%. Childhood tumors have a number of features that significantly distinguish them from adult tumors. Often they arise from the remnants of embryonic tissues as a result of a violation of the formation of organs and tissues in the period of intrauterine development. Such tumors are called dysontogenetic. In adults, dysontogenetic neoplasms are rare, while in children it is the predominant type of tumor. Up to 85% of malignant tumors in children under the age of 1 year are represented by dysontogenetic tumors. Quite often, a connection is found between tumor growth (oncogenesis) and malformations (teratogenesis). Thus, Wilms' tumor and hepatoblastoma are often combined with hemihypertrophy (an increase in the size of one half of the trunk, limbs or face). Tumors of the central nervous system are combined with malformations of the brain, tumors of the gonads often occur simultaneously with malformations of the genital organs. In total, 30% of children with tumors various etiologies diagnosing malformations.
The great role of genetic factors in the development of childhood tumors is noted. More than 100 hereditary syndromes are known that predispose to the development of a tumor in childhood [according to Cotran R.S., Kumar V., Collins T., 1998]. It has been proven that genetic factors play a major role in the etiology of a number of congenital tumors. hereditary nature established for retinoblastoma, nephroblastoma, neuroblastoma.
Benign tumors are much more common in children than malignant ones. They account for more than 80% of neoplasms in children under 14 years of age. Among malignant tumors, tumors of the hematopoietic tissue, the central nervous system and sarcomas predominate.
Cancer is relatively rare (no more than 6% of cases), while in adults, carcinomas are very common. The criteria adopted in pathology for the characterization of malignant and benign tumors (see Chapter 7) are not always applicable to childhood neoplasms. Thus, pronounced cellular atypism and polymorphism can be observed in children with some benign tumors of the adrenal glands. Many benign neoplasms in young children can grow very quickly (eg, nevi, hemangiomas). In such cases, despite the benign structure of the node, a large number of mitotic figures can be found. At the same time, infiltrating growth is typical for juvenile fibroma, capillary hemangioma, and lymphangioma. On the contrary, some malignant tumors grow very slowly in the first years of a child's life. Nephroblastoma and neuroblastoma usually have a thin capsule and grow within it for some time. The unique ability of some neoplasms in children to "ripen" was noted: neuroblastoma can turn into ganglioneuroma, malignant hepatoblastoma into benign adenoma, teratoblastoma into teratoma. This quite unusual phenomenon, inconsistent with the progression of malignant tumors (see Chapter 7), is not fully explained. It is observed in those neoplasms that arise either from embryonic tissues that are delayed in development compared to other tissues of the child, or from stem undifferentiated (cambial) cells.
Tumors in children have features of metastasis. Soft tissue sarcomas in children in 30 or 50% of cases metastasize to the lymphatic vessels. This is also not consistent with the concept of predominantly hematogenous metastasis of sarcomas. In contrast, embryonic hepatoblastomas, i.e. epithelial tumors, give the first metastases not to the regional lymph nodes, but to the lungs. Most neoplasms of the central nervous system do not metastasize beyond the skull at all. In general, the prognosis for malignant tumors in children is usually more favorable than in adults. All this makes it necessary to pay more attention to the reduction adverse effects and long-term effects of chemotherapy and radiotherapy in surviving children (including the development of secondary tumors and genetic consequences).
When categorizing tumors in children, it is not always possible to apply the histogenetic principle adopted for neoplasms in adults, since dysontogenetic tumors can consist of elements from different germ layers. Depending on the origin of tumors in children, they are divided into three types: dysontogenetic, growing from cambial embryonic tissues, and developing according to the type of adult tumors.
Tumor-like conditions - teratomas, hamartomas and choristomas - should be distinguished from true neoplasms (see Chapter 7).
benign tumors. The most common benign tumors in children are hemangiomas, lymphangiomas, fibromas, and teratomas. The structure of these tumors is described in detail in other chapters; here we present the features of these tumors in children.
Hemangioma. It is the most common benign tumor in childhood. Typically, children have capillary and cavernous forms (see Chapter 11) or a combination of both. Hemangioma is localized mainly in the skin of the head, neck or trunk, less often in the internal organs. Capillary hemangiomas can increase in size, especially rapid growth is observed in the first months of life. When the child is 1-3 years old, the growth of the tumor stops, and by the age of 5, it usually undergoes spontaneous regression. Sometimes hemangioma has infiltrating growth, and therefore relapses are possible. Giant hemangioma of the limbs and trunk in infants may be accompanied by the development of thrombocytopenic purpura due to widespread thrombosis of the vessels of the hemangioma (Kasabah-Merritt syndrome, H.H.Kasabach, K.K.Merritt). Hemangiomas are one of the manifestations of the hereditary Hippel-Lindau syndrome (E. von Hippel, A. Lindau).
Lymphangioma. It usually occurs in children under 3 years of age. The tumor has the greatest clinical significance when localized in the deep regions of the neck, axilla, mediastinum, and retroperitoneum. Despite the absence of cellular atypism, lymphangiomas have locally destructive growth and increase in size after birth. In this regard, they can damage vital organs (for example, in the mediastinum) or nerve trunks. Lymphangiomas should be distinguished from lymphangiectasias, which are abnormally dilated preexisting lymphatic vessels. Lymphangiectasias are accompanied by diffuse edema of a limb or part of it, causing its deformation. Unlike lymphangiomas, lymphangiectasias do not progress, but can cause serious cosmetic problems.
fibrous tumors. In children, they are diverse and often cause great difficulty in determining the degree of malignancy. Fibromatoses occurring in children are often characterized by hypercellularity and rapid infiltrating growth, making them difficult to distinguish from adult fibrosarcomas. There are cases of spontaneous regression. Of the many fibrous tumors, here are just a few examples. Infantile myofibromatosis is characterized by the presence of small dense nodules in the dermis, subcutaneous tissue, muscles, and internal organs. Nodules can be single and multiple (more than 50). With single tumors, the prognosis is favorable, with multiple tumors, children die in the 1st year of life. Juvenile angiofibroma of the nasopharynx usually occurs in boys older than 8 years. Microscopically, the tumor consists of fields of fibrous tissue with few fibroblasts and thin-walled blood vessels. It has infiltrating growth and sometimes sprouts the bones of the skull. The localization of the tumor and the nature of its growth make radical removal difficult. If damaged or attempted to be removed, profuse bleeding may develop. The tumor is histologically benign and does not metastasize. May undergo spontaneous regression.
Teratoma. This tumor from embryonic undifferentiated germ cells occurs when their migration is disturbed during the morphogenesis of the gonads of the embryo (see Chapter 7). Teratoma is represented by tissues of three germ layers, however, the main part is usually tissues of ectodermal origin. The epidermis with all derivatives (hair, glands), glial tissue, accumulations of ganglion cells, adipose and muscle tissue, cartilage, less often - other tissues in the most different combinations. There may also be elements of the trophoblast. Teratomas have the following most typical localization: ovaries and testicles, sacrococcygeal region, mediastinum, retroperitoneal space, pharynx, base of the skull. In newborns and children of the first 2 years of life, sacrococcygeal teratomas predominate; from the age of 15-16, the frequency of scapular teratomas increases. The first part of testicular teratomas appears at the age of 20-49 years. Sacrococcygeal teratoma is the main type of teratoma in newborns and young children. In girls, it occurs 3 times more often than in boys, often combined with non-immune dropsy of the fetus, polyhydramnios. May cause difficulty in childbirth. Basically, sacrococcygeal teratomas consist of mature tissues, often with organoid differentiation. Malignant teratomas (teratoblastomas) contain elements of a large cell carcinoma that forms papillary structures or grows solidly. Teratoblastomas are characterized by the presence of tumor elements of the endodermal sinus. These tumors have a very poor prognosis.
Malignant tumors. Most often, malignant tumors in children develop in the hematopoietic system and nervous tissue, soft tissues, bones, and kidneys. The frequency of distribution of tumors in organs contrasts sharply with that in adults. In the latter, the lungs, mammary gland, skin, prostate gland, and colon are more often affected (see Chapter 7). The incidence of malignant tumors varies greatly depending on the age of the child.
Malignant tumors in children are, as a rule, of dysontogenetic origin. Under the microscope, more primitive (embryonic) than pleomorphic-anaplastic features are revealed, which often resembles organogenesis specific to the organ in which the tumor has developed. Such neoplasms are often designated using the suffix "blastoma": nephroblastoma, neuroblastoma, retinoblastoma.
Neuroblastoma. It is the most common childhood solid tumor that develops outside the central nervous system. It affects the adrenal glands, sympathetic ganglia and accounts for 14% of all neoplasms in children (see Chapter 26).
The frequency of neuroblastoma, according to various estimates, ranges from 6 to 8 cases per 1 million children. Average age sick for 2 years; 85-90% of sick children are younger than 5 years. In girls, neuroblastoma is somewhat less common and has a better prognosis than in boys. A hereditary predisposition to the development of neuroblastoma has been found (probably in the form of inherited mutations in germ cells that cause individual susceptibility to secondary somatic damage). The incidence of this tumor is increased in twins and siblings, as well as in Wiedemann-Beckwith syndrome and neurofibromatosis [Beckwith-Wiedemann syndrome (J.B. Beckwith, N.-R. Wiedemann) - complex congenital anomalies: hyperplasia of the kidneys, pancreas, testicles, adrenal glands, big mass body, etc.].
Neuroblastoma develops from neural crest cells. The most common (up to 40%) localization is the adrenal medulla and paraspinal ganglia. Less commonly, the tumor is located in the pelvis, neck, chest. In adults, neuroblastoma is localized in the head, neck, and legs. A node is determined macroscopically, the dimensions of which can vary significantly. Some neuroblastomas are clearly demarcated from the surrounding tissues and may have a thin capsule, while others have a pronounced infiltrating growth and quickly grow into the surrounding tissues (kidneys, renal vein, inferior vena cava, aorta). On section, the tumor appears as a soft, grayish tissue resembling brain matter. In nodes of large sizes, foci of necrosis, hemorrhage, and calcification are not uncommon.
The histological picture of neuroblastoma depends on the degree of tumor differentiation. In most cases, the tumor consists of small lymphocyte-like cells with dark nuclei and scanty cytoplasm, forming solid layers (Fig. 22.14, A). More differentiated tumor cells have eosinophilic neurofibrillary processes and are located in the fibrillar stroma. In some tumors, the formation of pseudorosettes in the form of a corolla of cells can be observed surrounding eosinophilic accumulations of neurofibrils. Electron microscopic examination of tumor cells reveals neurosecretory granules and processes with microtubules. Further differentiation leads to the formation of elements of the ganglion type - large cells with a wide rim of eosinophilic cytoplasm, a large vesicle-shaped nucleus and well-defined nucleoli (Fig. 22.14, B) (see Chapter 26). The amount of fibrillar stroma increases in the tumor tissue. A tumor with completed differentiation is represented by mature ganglion cells surrounded by bundles of connective tissue, nerve fibers and lemmocytes (Schwann cells). Such tumors are called ganglioneuromas. The tumor may contain areas with different differentiation, so the diagnosis of ganglioneuroma can only be made by analyzing many sections from different parts of the tumor. Some neuroblastomas are
Rice. 22.14.
Neuroblastoma
.A - the tumor consists of monomorphic cells with dark nuclei and sparse cytoplasm, between the cells there is a small amount of delicate fibrillar material; B - neuroblastoma with signs of differentiation, cells with a wide rim of the cytoplasm, bubble-like nuclei and well-defined nucleoli are visible.
They undergo differentiation and mature to ganglioneuromas or spontaneously regress. Regression is more often observed with small tumor sizes. Metastases occur in 50% of neuroblastoma cases in children under the age of 1 year and in 70% of cases in older children. Metastases are most often found in the lymph nodes, bone marrow, bones, liver, subcutaneous tissue.
The international classification of the growth stages of neuroblastoma is as follows.
Stage Characteristics of the tumor
1 A tumor that does not extend beyond the organ in which it developed. Metastases are absent. The neoplasm has been completely removed.
2a Unilateral tumor that extends beyond the organ in which it developed, but does not cross the midline. Removed most of tumors. No metastases
2b Unilateral tumor of any size, completely or partially removed, with metastases to regional lymph nodes
3 Tumor that cannot be completely resected and extends through the midline regardless of the involvement of the lymph nodes in the process; unilateral tumor with metastases to the lymph nodes of the opposite side of the body; midline tumor with bilateral lymph node metastases
4 Tumor with metastases to distant lymph nodes and hematogenous metastases
4S Tumor corresponding to stages 1 and 2 with hematogenous metastases to the skin, liver, bone marrow in children younger than 1 year
In young children, a neoplasm is usually detected by chance during palpation of the abdomen or during x-ray examination about any other disease. In older children, in most cases, the tumor is diagnosed only when distant metastases appear. Diagnosis of neuroblastoma is based on clinical and morphological data. The results of biochemical and cytogenetic studies can help in the diagnosis, but they are not specific enough. In the blood of 90% of patients, the concentration of catecholamines is increased, respectively, their excretion in the urine is increased. IN clinical practice use the definition of daily excretion of vanillylmandelic and homovanillic acids.
The prognosis for neuroblastoma is ambiguous, it depends on many factors. There are a number of parameters and markers that can help determine tumor prognosis. The prognosis is largely influenced by indicators such as the age of the child and the stage of tumor growth. Children under 1 year of age have the best prognosis, regardless of the stage of the disease. In total, their survival rate is 85-90%, and in children with stage 1-2 neuroblastoma (one-sided tumor without metastases), it reaches 98%. In children older than 1 year, the prognosis is much worse. In the presence of lymphogenous and hematogenous metastases, survival does not exceed 10%.
Prognostically important markers include a deletion of the short arm of chromosome 1 distal to p32. It leads to the loss of the neuroblastoma suppressor gene and significantly affects the prognosis. This is the most typical cytogenetic anomaly in neuroblastoma, however, it also occurs in other malignant tumors. Cases of loss of heterozygosity of the long arm of chromosomes 13 and 14 have also been described. The significance of such genetic heterogeneity remains unclear. Amplification of the N-myc and N-ras oncogenes also indicates an unfavorable prognosis. Multiple copies of N-myc (up to 300 in some cases) are found during tumor dissemination. For tumors with a benign course, amplification of N-myc is uncharacteristic. However, in some cases with a single copy, a rapidly progressive course is observed. Thus, it is not just the increase in the number of copies that matters, but the level of gene expression. The ploidy of tumor cells also affects prognosis. Hyperdiploidy is associated with a poor prognosis, while aneuploidy is associated with a favorable one. It has also been shown that survival increases at a high level of Trk gene expression. Differentiation of neuroblasts into more mature ganglion cells is partly due to the action of nerve growth factor, the receptor of which is encoded by the proto-oncogene Trk. Finally, there are several serum markers whose elevated levels indicate a poor prognosis. These are neuron-specific enolase, ferritin, lactate dehydrogenase. An increased serum ferritin concentration is observed in 50% of patients with stages 3 and 4 of the disease.
Retinoblastoma. This is a malignant tumor of the eye, occurs with a frequency of 1 in 20,000 newborns and accounts for 2.5-4.5% of all malignant tumors in children. Retinoblastoma can be unilateral or bilateral, unifocal or multifocal. It is often congenital. Retinoblastoma, like some other tumors in children, can undergo spontaneous regression. Familial and sporadic cases of retinoblastoma have been described. Non-hereditary retinoblastomas are always unilateral and unifocal. Family (hereditary) cases account for about 50%. The tumor is usually bilateral, often multifocal. Patients with genetic forms of retinoblastoma have a predisposition to the development of other types of malignant neoplasms. Greater number observations of retinoblastoma falls on the age of up to 4 years.
The development of retinoblastoma is associated with a mutation of the Rb gene located on chromosome 13 (13ql4). This gene encodes a nuclear protein that blocks the exit of the cell from the Gl phase of the cell cycle, and also plays a role in cell differentiation. In genetically determined cases, children are born with one normal and one defective Rb gene, which is inherited from one of the parents (familial cases) or is the result of a new mutation in the germ cells (genetic sporadic cases). The mutation of the second gene is somatic, it occurs in the retina. In non-hereditary sporadic retinoblastomas, both mutations are somatic. Thus, in a retinal cell giving rise to non-hereditary retinoblastoma, two somatic mutations should occur. Since the level of somatic mutations is low, patients with sporadic retinoblastomas have only a single tumor focus. Patients with familial retinoblastoma also have an increased risk of developing osteosarcomas and other soft tissue tumors. Inactivation of the Rb gene was also found in small cell lung cancer, bladder cancer, breast cancer, and prostate cancer.
Retinoblastoma develops from cells of neuroepithelial origin (see Chapter 26). The tumor is located in the posterior chamber of the eye as a single or multiple papillary formation of a pinkish-white color with foci of necrosis and petrifications. Histologically, the tumor is represented by small rounded cells with hyperchromic nuclei and poor cytoplasm; sometimes such cells form ribbon-like structures. More differentiated forms of retinoblastoma contain cuboidal or low prismatic cells that form true rosettes. Such cells contain formations resembling photoreceptors. Initially, the tumor is located within the retina, but as it grows, it destroys the vitreous plate, spreading to the choroid and vitreous body and can fill the entire cavity of the eyeball, destroy the bone walls of the orbit. Along the course of the optic nerve, the tumor can grow into the cranial cavity. Retinoblastoma metastasizes lymphogenously and hematogenously. The most common localization of lymphogenous metastases is the parotid, submandibular, cervical lymph nodes, hematogenous metastases are the bones of the skull, tubular bones of the extremities and the liver. There is a spontaneous regression of the tumor, accompanied by calcification and a pronounced inflammatory reaction.
The manifestations of retinoblastoma are varied. First Clinical signs diseases are expressed in a whitish glow of the pupil, pupil dilation, weakening of its reaction to light and strabismus. Patients have reduced visual acuity. With the germination of the choroid, pain in the eye, swelling of the cornea appear. Often develops inflammatory process(iridocyclitis, uveitis). Due to swelling of the orbital tissue, exophthalmos may occur. When retinoblastoma spreads into the cranial cavity, brain symptoms. The success of treatment largely depends on the age of the child. In children under 1 year of age, the mortality rate is 70%, in older children - about 20%. If retinoblastoma is limited to the outside of the eye, then there are the greatest chances of recovery compared to those with other malignant tumors. Early diagnosis significantly improves the prognosis, while organ-preserving operations with vision preservation are possible. With the spread of retinoblastoma outside the eyeball, the prognosis worsens dramatically. Patients with retinoblastoma usually die from metastases. Cases of the development of osteosarcoma of the orbit after radiation therapy of retinoblastoma are described.
Tumor Wilms (M.Wilms; nephroblastoma). It is the most common primary kidney tumor in childhood. It is 7.8 cases per 1 million children aged 1-14 years. Among all malignant neoplasms in children, nephroblastoma accounts for 6-7%. The tumor is rare in children under the age of 6 months and after 5 years. The highest incidence is observed at the age of 2-3 years.
Wilms' tumor can occur in sporadic, familial, and syndrome-associated forms. Most patients have a normal karyotype, but sometimes there is an association with a deletion of 11p13, where the tumor-associated WT-1 gene is located. The WT-1 gene is a suppressor gene; its product is a regulator of a DNA-binding transcription factor. The WT-1 protein is expressed in the kidneys and fetal gonads (transgenic mice lacking both copies of the WT-1 locus have renal agenesis). Some patients with Wilms tumor have a mutation in the WT-2 gene located in the short arm of chromosome 11 distal to the WT-1 gene locus, as well as loss of heterozygosity of the long arm of chromosome 16.
Wilms tumor is often associated with birth defects development. Most often this combination is observed in three syndromes. WAGR syndrome (Wilms "tumour, aniridia, genital anomalies, mental retardation) includes, as the name implies, aniridia (absence of the iris or part of it), genital anomalies and mental retardation. The risk of developing Wilms' tumor in such patients is 33%. In WAGR syndrome, a mutation of the autosomal dominant gene with localization 11p13 was detected.Proximal to it, also in the p13 region, the WT-1 gene is located.In many cases, patients with WAGR syndrome have a sporadic deletion of genetic material in the lip 13 region, including both of these locus.
Denis-Drash syndrome (P.Denys, A.Drash) is characterized by gonadal dysgenesis (male pseudohermaphroditism) and nephropathy, leading to kidney failure. Most of these patients develop Wilms tumor; the genetic anomaly is also localized in lip 13, however, it is represented not by a deletion, but by a negative dominant mutation of the WT-1 gene.
Wiedemann-Beckwith syndrome (J.B. Beckwith, H.R. Wiedemann) is characterized by an increase in the size of internal organs (visceromegaly), hemihypertrophy, cysts of the adrenal medulla, abnormally large cells of the adrenal cortex and high risk development of Wilms tumor. In these patients, the 11p15.5 locus, located distal to the WT-1 gene locus and called the WT-2 gene, is damaged. The function of the WT-2 gene remains unclear. In patients with sporadic cases of Wiedemann-Beckwith syndrome, a loss of maternal alleles was found in combination with paternal disomy at the lip75.5 locus, which indicates the role of genomic imprinting in tumor genesis. In patients with Wiedemann-Beckwith syndrome, in addition, the incidence of hepatoblastoma, adrenal cortex cancer, rhabdomyosarcoma, and pancreatic tumors is increased.
Macroscopically, nephroblastoma, as a rule, is represented by a large single node, clearly delimited from the kidney tissue. It has a soft texture, grayish-pink, with foci of necrosis, hemorrhages and cysts. Multifocal and bilateral lesions occur in 10% of cases. Microscopically, Wilms' tumor is represented by derivatives of nephrogenic tissue at different stages of differentiation. A tumor is characterized by a combination of three components: blastema, epithelial and stromal (Fig. 22.15). The blastem component is represented by rounded small cells with hyperchromic nuclei and a narrow rim of the cytoplasm. The epithelial component of the tumor is made up of various types of tubules, reflecting different stages nephron differentiation, less often - glomeruli. The mesenchymal component is represented by loose, immature connective tissue, which may contain areas of smooth and striated muscles, adipose tissue, cartilage, and bones. The presence of differentiated tissues in the tumor does not affect the prognosis. The only histological sign indicating a poor prognosis is the presence of anaplasia in the tumor. In relation to Wilms' tumor, the concept of anaplasia means the appearance of cells with enlarged hyperchromic, polymorphic nuclei and pathological mitoses. The tumor metastasizes both lymphogenously and hematogenously. Lymphogenic metastases are directed to the regional collectors of the hilum of the kidney, para-aortic lymph nodes, then to the collectors of the hilum of the liver and mesentery. Hematogenous metastases are found predominantly in the lungs. Bone metastases are uncommon (unlike other kidney tumors). In metastases, as a rule, non-epithelial components of the tumor predominate.